Advanced searchCitation search
Skip main navigation
Close Drawer MenuOpen Drawer Menu
Clinical GuidelinesNovember 18, 2008

Comparative Benefits and Harms of Second-Generation Antidepressants: Background Paper for the American College of Physicians

FREE
    Author, Article, and Disclosure Information
    https://doi.org/10.7326/0003-4819-149-10-200811180-00008

    Abstract

    Background:

    Second-generation antidepressants dominate the management of major depressive disorder, dysthymia, and subsyndromal depression. Evidence on the comparative benefits and harms is still accruing.

    Purpose:

    To compare the benefits and harms of second-generation antidepressants (bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine) for the treatment of depressive disorders in adults.

    Data Sources:

    MEDLINE, EMBASE, PsychLit, Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts from 1980 to April 2007, limited to English-language articles. Reference lists of pertinent review articles were manually searched and the Center for Drug Evaluation and Research database was explored to identify unpublished research.

    Study Selection:

    Abstracts and full-text articles were independently reviewed by 2 persons. Six previous good- or fair-quality systematic reviews or meta-analyses were included, as were 155 good- or fair-quality double-blind, placebo-controlled, or head-to-head randomized, controlled trials of at least 6 weeks' duration. For harms, 35 observational studies with at least 100 participants and follow-up of at least 12 weeks were also included.

    Data Extraction:

    Using a standard protocol, investigators abstracted data on study design and quality-related details, funding, settings, patients, and outcomes.

    Data Synthesis:

    If data were sufficient, meta-analyses of head-to-head trials were conducted to determine the relative benefit of response to treatment and the weighted mean differences on specific depression rating scales. If sufficient evidence was not available, adjusted indirect comparisons were conducted by using meta-regressions and network meta-analyses. Second-generation antidepressants did not substantially differ in efficacy or effectiveness for the treatment of major depressive disorder on the basis of 203 studies; however, the incidence of specific adverse events and the onset of action differed. The evidence is insufficient to draw conclusions about the comparative efficacy, effectiveness, or harms of these agents for the treatment of dysthymia and subsyndromal depression.

    Limitation:

    Adjusted indirect comparisons have methodological limitations and cannot conclusively rule out differences in efficacy.

    Conclusion:

    Current evidence does not warrant the choice of one second-generation antidepressant over another on the basis of differences in efficacy and effectiveness. Other differences with respect to onset of action and adverse events may be relevant for the choice of a medication.

    Major depressive disorder (MDD) is the most prevalent axis I disorder, affecting more than 16% of U.S. adults during their lifetime (1). In 2000, the economic burden of depressive disorders was an estimated $83.1 billion (2), more than 30% of which was attributable to direct medical expenses.

    Pharmacotherapy dominates the medical management of MDD. Since the mid-1980s, second-generation antidepressants have gradually replaced tricyclic antidepressants and monoamine oxidase inhibitors as first-line medications, primarily because of their lower toxicity in overdose and similar general efficacy (3). These newer treatments include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors, and other second-generation drugs (Table 1).

    Table 1. Second-Generation Antidepressants Approved for Use in the United States

    To date, only 2 systematic reviews have assessed the comparative efficacy and harms of second-generation antidepressants (3, 4). These studies reported no substantial differences in efficacy or harms among agents. However, because of a lack of direct head-to-head comparisons, assessments in both studies were primarily qualitative. Consequently, uncertainties persist about the differences among the drugs for which sufficient head-to-head evidence is lacking.

    We systematically assessed evidence on the comparative benefits and harms of second-generation antidepressants for the acute, continuation, and maintenance phases of treatment of MDD; subsyndromal depression; and dysthymia and the comparative efficacy and effectiveness for such accompanying symptoms as anxiety, insomnia, or neurovegetative symptoms. We also sought to determine whether efficacy, effectiveness, and harms differed among subgroups of patients on the basis of age, sex, race or ethnicity, or comorbid conditions.

    To our knowledge, this is the first meta-analysis of second-generation antidepressants to assess quantitatively all possible comparisons among drugs in this class. We update findings of an earlier report on these pharmaceuticals (5) for the Agency for Healthcare Research and Quality.

    Methods

    An open process (described at www.effectivehealthcare.ahrq.gov) involving the public, the Agency for Healthcare Research and Quality's Scientific Resource Center for Effective Health Care program, and various stakeholder groups produced key questions. We followed a standardized protocol for all review steps (5).

    Data Sources

    We searched MEDLINE, EMBASE, PsychLit, Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts from 1980 to April 2007. We used Medical Subject Heading terms when available and keywords when appropriate. We combined terms for depressive disorders with a list of 12 specific second-generation antidepressantsbupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxineand their specific trade names. We limited electronic searches to adult 19 + years, human, and English language.

    We manually searched reference lists of pertinent review articles and letters to the editor and used the Center for Drug Evaluation and Research database (up to April 2007) to identify unpublished research submitted to the U.S. Food and Drug Administration. The Scientific Resource Center invited pharmaceutical manufacturers to submit dossiers on completed research for each drug. We received dossiers from 3 pharmaceutical companies (Eli Lilly and Company, Indianapolis, Indiana; GlaxoSmithKline, Philadelphia, Pennsylvania; and Wyeth, Madison, New Jersey).

    Study Selection

    Two persons independently reviewed abstracts and relevant full-text articles. To assess efficacy or effectiveness regarding response, speed of onset, remission, maintenance of remission, and quality of life, we included head-to-head controlled trials of at least 6 weeks' duration that compared 1 drug with another. Because head-to-head evidence was lacking for many comparisons, we included placebo-controlled trials for indirect comparison models. To assess harms (specific adverse events, rates of adverse events, and discontinuations attributable to adverse events), we also examined data from observational studies with at least 100 participants and follow-up of at least 12 weeks. To assess differences of benefits and harms in subgroups and patients with accompanying symptoms, we reviewed both head-to-head and placebo-controlled trials. We included meta-analyses if we found them to be relevant for a key question and of good or fair methodological quality (6).

    If both reviewers agreed that a study did not meet eligibility criteria, we excluded it. We also excluded studies that met eligibility criteria but were reported only as an abstract. Investigators resolved disagreements about inclusion or exclusion by consensus or by involving a third reviewer.

    Data Extraction and Quality Assessment

    We used a structured, Web-based data abstraction form (SRS 4.0, TrialStat, Ottawa, Ontario, Canada) onto which trained reviewers abstracted data from each study and assigned an initial quality rating. A senior reviewer read each abstracted article, evaluated completeness of data abstraction, and confirmed the quality rating. Investigators resolved disagreements by discussion and consensus or by consulting an independent party.

    We assessed the internal validity (quality) of trials on the basis of predefined criteria and applied ratings of good, fair, or poor (5, 7, 8). Primary elements of quality assessment included randomization and allocation concealment, similarity of compared groups at baseline, blinding, use of intention-to-treat analysis, and overall and differential loss to follow-up. To assess observational studies, we used criteria involving selection of case patients or cohorts and control participants, adjustment for confounders, methods of outcomes assessment, length of follow-up, and statistical analysis (9). We rated studies with a fatal flaw in 1 or more categories as poor quality (Appendix Table 1) and did not include them in our analyses for this review unless no other head-to-head evidence was available. To identify effectiveness studies, we used a tool that distinguishes efficacy trials from effectiveness studies on the basis of certain elements of study design (10). Such studies have greater generalizability of results than efficacy trials because they enroll less selected study populations, use treatment modalities that mimic clinical practice, and assess health outcomes along with adverse events.

    Lacking clear definitions about the equivalence of dosages among second-generation antidepressants in the published literature, we developed a roster of low, medium, and high dosages for each drug based on the interquartile dosing range (5). We used this roster, which does not indicate dosing equivalence, to detect gross inequalities in dosing that could affect comparative efficacy and effectiveness.

    Appendix Table 1. Characteristics of Studies with Poor Internal Validity
    Data Synthesis

    If data were sufficient, we conducted meta-analyses of head-to-head comparisons. Efficacy outcomes included the relative benefit of achieving response (more than 50% improvement from baseline), which reflects the ratio of benefits in one treatment group to benefits in another, and the weighted mean difference of changes on the Hamilton Depression Rating Scale or the Montgomery-Asberg Depression Rating Scale.

    For each meta-analysis, we conducted a test of heterogeneity (I2 index) and applied both random- and fixed-effects models. We report the random-effects results because the results from both models were very similar in all meta-analyses. We assessed publication bias by using funnel plots and the Begg adjusted rank correlation test (11) based on the Kendall coefficient.

    Because no head-to-head evidence was available for the majority of drug comparisons, we conducted adjusted indirect comparisons (5). We employed meta-regressions of placebo-controlled trials by using individual drugs as covariates. When the number of trials was insufficient for meta-regressions, we used modified network meta-analysis (12). Evidence suggests that indirect comparisons agree with head-to-head trials if component studies are similar and treatment effects are expected to be consistent in patients included in different trials (13), although these assumptions are usually not verifiable.

    All statistical analyses used StatsDirect Statistical Software program, version 2.3.8 (StatsDirect, Sale, United Kingdom); Stata, version 9.1 (StataCorp, College Station, Texas); and SAS, version 9.1 (SAS Institute, Cary, North Carolina).

    Rating the Strength of Evidence

    We rated the strength of the available evidence for specific key questions and outcomes in a 3-part hierarchy (high, moderate, and low) (5) by using a modified GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach (14, 15) that incorporates 4 key elements: study design, study quality, consistency of results, and directness (availability of data on outcomes or populations of interest).

    Role of Funding Source

    The Agency for Healthcare Research and Quality participated in formulating the key questions and reviewed and commented on planned methods and data analysis. The Agency had no role in study selection, quality ratings, or interpretation and synthesis of the evidence, although staff reviewed interim and final evidence reports and distributed them for external peer review by outside experts.

    Results

    We identified 2318 citations from searches and reviews of reference lists (Figure 1). Of the 203 included studies (Appendix Tables 2 to 11), 140 (69.0%) were financially supported by pharmaceutical companies and 19 (9.3%) by governmental agencies or independent funds. For 44 (21.7%) studies, we could not determine the funding source.

    Figure 1. Study flow diagram.

    The number of included articles differs from the number of included studies because some studies have multiple publications.

    Appendix Table 2. Comparative Efficacy and Effectiveness Studies on Therapy for Major Depressive Disorder
    Appendix Table 3. Comparative Efficacy and Effectiveness Studies on Therapy for Dysthymia
    Appendix Table 4. Comparative Efficacy and Effectiveness Studies on Therapy for Subsyndromal Depressive Disorders
    Appendix Table 5. Comparative Efficacy and Effectiveness Studies on Maintaining Remission and Preventing Relapse
    Appendix Table 6. Comparative Efficacy and Effectiveness Studies on Therapy for Recurrent and Treatment-Resistant Depression
    Appendix Table 7. Placebo-Controlled Studies of Relapse and Recurrence
    Appendix Table 8. Comparative Efficacy and Effectiveness Studies of Treatment in Adults with Major Depressive Disorder and Accompanying Symptoms
    Appendix Table 9. Studies of Comparative Risk for Harms in Adults with Major Depressive Disorder
    Appendix Table 10. Comparative Efficacy and Effectiveness Studies in Subgroups
    Appendix Table 11. Randomized, Placebo-Controlled Trials Included for Indirect Comparisons
    Major Depressive Disorder

    Overall, we found no substantial differences in comparative efficacy and effectiveness of second-generation antidepressants for treatment of MDD (Tables 2, 3, and 4 and Figures 2, 3, and 4). This finding pertains to the acute, continuation, and maintenance phases of treatment; to patients with accompanying symptom clusters; and to subgroups defined by age, race or ethnicity, sex, or comorbid conditions (we found only sparse evidence for subgroups). Nevertheless, second-generation antidepressants are not identical drugs. They differ somewhat with respect to onset of action and frequency of some adverse events. Generally, effectiveness studies with less stringent eligibility criteria provided results similar to those of efficacy trials, indicating good generalizability of our findings to primary care populations.

    Table 2. Summary of Findings on General Effectiveness
    Table 3. Summary of Findings on Adverse Events: Comparative Risk for Harms
    Table 4. Summary of Findings on Effectiveness in Subgroups
    Figure 2. Relative benefit of response comparing selective serotonin reuptake inhibitors (

    SSRIs) with other SSRIs.

    All estimates are based on network meta-analyses except for those marked with an asterisk or a dagger.

    * Based on meta-analysis of head-to-head trials.

    Based on indirect comparisons with meta-regression.

    Figure 3. Relative benefit of response comparing selective serotonin reuptake inhibitors (

    SSRIs) with selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) and SSRIs with serotonin and norepinephrine reuptake inhibitors (SNRIs).

    All estimates are based on network meta-analyses except for those marked with an asterisk or a dagger.

    * Based on meta-analysis of head-to-head trials.

    Based on indirect comparisons with meta-regression.

    Figure 4. Relative benefit of response comparing selective serotonin reuptake inhibitors (

    SSRIs), selective serotonin and norepinephrine reuptake inhibitors (SSNRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and other second-generation antidepressants (ADs) with other second-generation ADs.

    All estimates are based on network meta-analyses except for those marked with an asterisk.* Based on meta-analysis of head-to-head trials.

    Comparative Efficacy for Acute-Phase Treatment of MDD

    Eighty good- or fair-quality head-to-head, randomized, controlled trials (RCTs), comprising more than 17000 patients, compared efficacy or effectiveness for acute-phase MDD treatment. These studies provided direct evidence for 36 of 66 possible comparisons among these drugs. Only 5 trials directly compared any second-generation nonselective serotonin reuptake inhibitor with another; of these, only 1 comparison was evaluated in more than 1 trial.

    For the 62 comparisons of 1 drug with another for which data were available, we conducted indirect evaluations of response rates, incorporating an additional 34 placebo-controlled trials of good or fair quality comprising 26349 patients (Appendix Table 11).

    For almost all comparisons, no statistically significant differences in response rates were apparent (Figures 2, 3, and 4). For some indirect comparisons, however, the precision of estimates was low and confidence intervals encompassed differences that would be clinically significant.

    Findings from some meta-analyses yielded statistically significant differences among treatments, but the modest effect sizes of the differences are probably not clinically significant (5). For example, the meta-analytic comparison of response rates to citalopram versus escitalopram (1620) yielded a statistically significant additional treatment effect for escitalopram (relative benefit favoring escitalopram, 1.14 [95% CI, 1.04 to 1.26]) (5). Pooled differences of points on the Montgomery-Asberg Depression Rating Scale presented a mean additional treatment effect (weighted mean difference) of a 1.13-point reduction (CI, 0.18 to 2.09) for escitalopram (5). A 1.13-point change on the Montgomery-Asberg Depression Rating Scale represents about one fifth to one quarter of a standard deviation, so the clinical significance of this finding may be questionable. Methods research suggests that half a standard deviation constitutes a minimally important difference for health-related quality-of-life outcomes (21).

    Meta-analyses yielded significantly lower response rates for fluoxetine than for sertraline (2225) or venlafaxine (2633). The small effect sizes of the differences are probably not clinically relevant.

    Eighteen trials (18, 23, 3348), mostly of fair quality, included health-related quality of life or functional capacity as secondary outcome measures. We found no differences among second-generation antidepressants for these outcomes.

    Comparative Effectiveness for Acute-Phase Treatment of MDD

    Three studies (23, 49, 50) can be considered effectiveness rather than efficacy trials. Their findings were consistent with those of the efficacy trials. Two fair-quality effectiveness trials indicated that improvement of health-related quality of life (work, social and physical functioning, concentration and memory, and sexual functioning) was similar for fluoxetine, paroxetine, and sertraline (23, 50).

    Speed of Response

    Seven fair-quality studies (39, 40, 45, 5155) reported that mirtazapine had a significantly faster onset of action than citalopram, fluoxetine, paroxetine, or sertraline after 1 or 2 weeks of treatment. All studies were supported by the manufacturer of mirtazapine. After 4 weeks of treatment, most response rates were similar. The extent to which the faster onset of mirtazapine can be extrapolated to other second-generation antidepressants is unclear. Mirtazapine and venlafaxine did not differ in speed of action (42).

    Response to a Second Agent after Initial Treatment Failure

    Overall, 38% of patients did not achieve a treatment response during 6 to 12 weeks of treatment with second-generation antidepressants; 54% did not achieve remission. The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) trial (56) provides the best evidence for assessing alternative medications among those for whom initial therapy failed. About 1 in 4 of the 727 people who participated in the switch of medications became symptom-free; this did not differ significantly among those who received sustained-release bupropion, sertraline, or extended-release venlafaxine. One open-label study (57) and a smaller efficacy study (58) reported significantly greater response rates for venlafaxine than for other second-generation drugs. Given the STAR*D findings, the clinical significance of this difference is questionable.

    Maintaining Response or Remission after Treatment Success

    Findings from 4 fair-quality head-to-head RCTs assessing relapse or recurrence prevention (5963) were similar for the comparisons of fluoxetine and sertraline, fluvoxamine and sertraline, duloxetine and paroxetine, and trazodone and venlafaxine. In 1 trial (59), among 105 patients who demonstrated a response at 8 weeks, 5 (10%) of 49 sertraline-treated patients and 7 (13%) of 56 of fluoxetine-treated patients had relapse over 24 weeks of continuation-phase treatment.

    Efficacy or Effectiveness for Depression or Accompanying Symptoms

    Clinicians may use symptom clusters that accompany depression (such as anxiety or insomnia) to guide antidepressant selection. This might improve outcomes for the depressive episode, the symptom cluster, or both. We reviewed available evidence for clinically relevant symptom clusters to address each possibility.

    Treatment of Depression in Patients with Accompanying Symptom Clusters
    Anxiety

    Six fair-quality head-to-head trials (31, 35, 6468) suggest that antidepressants have similar antidepressive efficacy for patients with MDD and anxiety symptoms. These studies compared either fluoxetine or paroxetine with sertraline (259 patients with accompanying anxiety) (64, 65); sertraline with bupropion (972 patients; number with anxiety not provided) (6668); and sertraline with venlafaxine (20 patients with anxiety) (35). One fair-quality, 12-week trial (31) of 146 patients reported significantly greater response (75.0% vs. 49.3%) and remission rates (59.4% vs. 40.3%) with venlafaxine than with fluoxetine.

    Insomnia

    Two fair-quality head-to-head trials (441 patients with insomnia) (24, 69) provide limited evidence for similar efficacy of fluoxetine, nefazodone, paroxetine, or sertraline for treating depression in patients with accompanying insomnia. A pooled analysis of 3 RCTs (447 patients) (70) reported that the reduction on the Montgomery-Asberg Depression Rating Scale total score was significantly greater for patients receiving escitalopram than for those receiving citalopram (16.5 vs. 14.0); however, the clinical significance of this difference remains uncertain.

    Melancholia

    Two fair-quality head-to-head trials (286 patients) (28, 65) and 1 poor-quality head-to-head trial (68 patients) (71) assessed the effects of medications for treating depression in patients with melancholia. Although 2 studies reported greater response rates for sertraline than for fluoxetine (59% vs. 44%) (65) and for venlafaxine than for fluoxetine (70% vs. 50%) (71), the small sample sizes (87 and 68 patients) and high attrition rate (71) limit confidence in these findings.

    Pain

    We found no head-to-head evidence. Two placebo-controlled trials reported similar response rates for patients with MDD and pain who received duloxetine (72) or paroxetine (73) compared with those who received placebo.

    Psychomotor Changes

    The evidence is limited to subgroup analyses from 1 fair-quality head-to-head trial (65). Fluoxetine and sertraline had similar antidepressive efficacy among 47 patients with psychomotor retardation, but sertraline had higher efficacy among 78 patients with psychomotor agitation (65). Results should be interpreted cautiously because small sample sizes and multiple testing can lead to erroneous results in such subgroup analyses.

    Treatment of Symptom Clusters in Patients with Accompanying Depression
    Anxiety

    Ten fair-quality head-to-head trials (31, 35, 40, 64, 66, 68, 7477) provide evidence that antidepressant medications do not differ substantially in efficacy for treatment of anxiety associated with MDD. Improvement of anxiety did not differ substantially among fluoxetine, paroxetine, and sertraline (549 patients) (64, 7577); sertraline and bupropion (243 patients) (66, 68); sertraline and venlafaxine (120 patients) (35); citalopram and mirtazapine (270 patients) (40); or paroxetine and nefazodone (206 patients) (74). One trial (146 patients) (31) reported significantly greater reductions in Covi Anxiety Scale scores of patients receiving venlafaxine than those receiving fluoxetine (5.7 vs. 3.9). The clinical significance of this difference remains uncertain.

    Insomnia

    Five fair-quality head-to-head trials (24, 37, 45, 62, 69) and a pooled analysis of 3 RCTs (70) involving 1540 patients provide limited evidence about the comparative effects of antidepressants on insomnia in patients with depression. Individual trials favored escitalopram over citalopram (70), nefazodone over fluoxetine (69), and trazodone over fluoxetine (37) and venlafaxine (62) in improving sleep scores. The comparisons were limited to single studies, and it is difficult to assess the clinical significance of these findings.

    Pain

    Three fair-quality head-to-head trials (63, 78, 79) and 1 poor-quality trial (80) compared duloxetine with paroxetine. These trials (1466 patients) found no substantial difference in pain relief between duloxetine and paroxetine.

    Somatization

    A fair-quality, 9-month open-label effectiveness trial reported similar improvement of somatization among 573 patients receiving fluoxetine, paroxetine, or sertraline (50).

    Risk for Harms

    We analyzed adverse events data from 80 head-to-head efficacy studies and 42 additional studies of both experimental and observational designs. Methods of adverse events assessment in efficacy trials differed greatly. Few studies used objective scales. Determining whether assessment methods were unbiased and adequate was often difficult.

    Adverse Events Profiles

    Constipation, diarrhea, dizziness, headache, insomnia, nausea, sexual adverse events, and somnolence were commonly and consistently reported adverse events. On average, 61% of patients in efficacy trials experienced at least 1 adverse event. Nausea and vomiting were the most common reasons for discontinuation in efficacy studies.

    Overall, second-generation antidepressants had similar adverse events profiles. Table 5 summarizes some differences in the incidence of specific adverse events.

    Table 5. Main Differences in Specific Adverse Events
    Sexual Dysfunction

    A fair-quality prospective observational study (1022 patients) from Spain reported that 59% of patients treated with second-generation antidepressants experienced sexual dysfunction (81). On the basis of 5 RCTs (1489 patients), bupropion led to a significantly lower rate of sexual adverse events than fluoxetine and sertraline (8286). Paroxetine frequently led to higher rates of sexual dysfunction than did fluoxetine, fluvoxamine, nefazodone, or sertraline (16% vs. 6%) (24, 76, 87, 88). Underreporting of absolute rates of sexual dysfunction is likely in these studies.

    Suicidality

    Eleven studies (8999) assessed the risk for suicidality (suicidal thinking or behavior) in patients treated with second-generation antidepressants; comparative data are sparse. No particular drug has an excess risk compared with any other drug in this class (94, 98). These findings are based primarily on retrospective cohort studies (91, 93, 94, 98). Confounding by indication (patients at higher risk for suicide being prescribed certain medications rather than others) may have led to erroneous conclusions.

    The United Kingdom's Committee on Safety of Medicines conducted the largest attempt to determine whether second-generation antidepressants increase the risk for suicidality in 2004 (89). A good meta-analysis of placebo-controlled trials of selective serotonin reuptake inhibitors, comprising more than 40000 adults, yielded no evidence that these agents increase the risk for suicide (odds ratio, 0.85 [CI, 0.20 to 3.40]) but did reveal an increased risk for nonfatal suicide attempts (odds ratio, 1.57 [CI, 0.99 to 2.55]) (92).

    Another good meta-analysis of published trial data (90), comprising more than 87000 patients, reported a significantly higher risk for suicide attempts among patients receiving selective serotonin reuptake inhibitors than among those receiving placebo (odds ratio, 2.25 [CI, 1.14 to 4.55]). This study estimated the overall rate of suicide attempts as 3.9 (CI, 3.3 to 4.6) per 1000 patients treated with these drugs, with an incidence of 18.2 suicide attempts per 1000 patient-years.

    Other Severe Adverse Events

    Evidence on the comparative risk for rare but severe adverse events, such as seizures, cardiovascular events (events relating to systolic and diastolic blood pressure and pulse or heart rate), hyponatremia, hepatotoxicity, and the serotonin syndrome, is insufficient to draw firm conclusions. Clinicians should keep in mind the risk for such harms when treating patients with a second-generation antidepressant.

    Treatment of MDD in Subgroups

    No study directly compared efficacy, effectiveness, and harms of second-generation antidepressants between subgroups and the general population for treatment of depression syndromes. Numerous studies, however, conducted subgroup analyses or used subgroups as the study population.

    Age

    Multiple head-to-head trials (22, 44, 48, 50, 54, 100107) and 2 fair-quality meta-analyses (108, 109) indicated that the efficacy of second-generation antidepressants does not differ in elderly patients (65 to 80 years of age) or very elderly patients (>80 years of age) compared with younger patients. These findings are consistent with placebo-controlled trials (110116) conducted in elderly or very elderly patients, which reported effect sizes similar to those from trials in younger patients.

    Sex

    Efficacy trials did not show differences between men and women (108, 109, 117). Observational evidence supports this conclusion (118).

    Race or Ethnicity

    One trial that evaluated efficacy differences in racial subgroups (119) did not show any differences, but this trial was rated poor quality because it lacked an intention-to-treat analysis.

    Comorbid Conditions

    No study directly compared efficacy, effectiveness, and harms of second-generation antidepressants between depressed patients with comorbid conditions and the general population.

    One poor-quality head-to-head study did not detect differences in efficacy and tolerability among fluoxetine, paroxetine, or sertraline in depressed individuals with HIV or AIDS (120).

    Seventeen placebo-controlled trials of varying quality (119, 121136) and 1 fair-quality systematic review (137) evaluated second-generation antidepressants in patients with various comorbid conditions. Some studies suggested that these drugs may not be efficacious for depressed patients with such comorbid conditions as HIV or AIDS (119, 121, 122), alcohol abuse (123125), Alzheimer disease (127), stroke (133, 134), or substance abuse (135, 136). Many of the studies were not powered to detect a meaningful difference between active treatment and placebo.

    Dysthymia

    Dysthymia is a chronic depressive disorder that is characterized by depressed mood for more days than not for at least 2 years (138). We found no head-to-head trial that studied patients with dysthymia. One good-quality trial (38) and 4 fair-quality placebo-controlled trials (36, 43, 139142) provide mixed evidence on the general efficacy and effectiveness of fluoxetine, paroxetine, and sertraline for the treatment of dysthymia.

    Subsyndromal Depression

    Subsyndromal depression (also called minor depression) is a mood disturbance of at least 2 weeks' duration with fewer symptoms of depression than MDD (138). One nonrandomized, open-label trial (100) compared citalopram with sertraline but found no difference in efficacy. Findings from 2 placebo-controlled trials (141143) were insufficient to draw any conclusions about comparative efficacy and effectiveness of second-generation antidepressants for the treatment of subsyndromal depression.

    Discussion

    In this systematic review of data from 203 studies, direct and indirect comparisons yielded no substantial differences in efficacy for the treatment of MDD. Statistically significant results were small and are unlikely to have clinical significance.

    Existing evidence on efficacy does not warrant the choice of one second-generation antidepressant over another, although we could not conclusively establish equivalence in efficacy for many comparisons. No differences in efficacy were apparent for patients with accompanying symptoms or subgroups based on age, sex, race or ethnicity, or comorbid conditions, although evidence within subgroups was limited.

    Nevertheless, second-generation antidepressants cannot be considered identical drugs. Moderate-strength evidence supports some differences among individual drugs with respect to speed of onset of response and incidence of some adverse events. For example, consistent evidence from multiple trials demonstrated that mirtazapine has a faster onset of action than citalopram, fluoxetine, paroxetine, or sertraline (39, 45, 5255) and that bupropion has fewer sexual adverse events than fluoxetine, paroxetine, or sertraline (82, 86, 144). These differences may be clinically significant and may influence medication choice for a given patient.

    Across all efficacy trials, more than 50% of patients treated with second-generation antidepressants for acute-phase depression did not achieve remission, the primary goal of depression treatment. Almost 40% did not achieve response, a less rigorous outcome. Current evidence is insufficient to identify patient factors that can reliably predict response or nonresponse to an individual drug. Although limited evidence indicates that the efficacy of second-generation antidepressants is similar among patients for whom treatment with a first-line agent failed, a substantial proportion of these patients do not achieve response or remission with second-line treatment (56). Multiple treatment options are required for patients who do not respond to first- or second-line treatment.

    Our statistical comparisons confirm the results of previous systematic reviews (3, 4, 145), although our interpretation of findings differs from that of Cipriani and colleagues (145) in their recent meta-analysis comparing fluoxetine with other antidepressants. Their pooled estimates of response rates for fluoxetine compared with sertraline and venlafaxine were slightly larger than our results. These differences might be attributable to their inclusion of open-label trials or their use of odds ratios, which overestimate differences when event rates are high. As in our study, the effect size meta-analysis by Cipriani and colleagues did not reach statistical significance, but they interpreted these differences as clinically significant.

    Our review has several limitations. First, most of the studies were efficacy trials conducted in highly selected populations. The applicability of their results to the average patient with acute MDD might be limited. However, the fact that the effectiveness trial results (23, 49, 50) were consistent with the efficacy study results strengthens our findings.

    Indirect comparisons have methodological limitations, most notably a lack of power that resulted in wide confidence intervals, which can encompass clinically significant differences between treatments. Nevertheless, we believe that the consistent similarity of treatment effects across all comparisons supports our conclusion that no substantial differences exist.

    Publication bias is a concern for all systematic reviews. Selective availability of studies with positive results can seriously bias conclusions, particularly when a pharmaceutical company compares 2 of its own drugs (as in the case of citalopram and escitalopram). Selective reporting is conceivable; however, we found no evidence to prove publication bias. The validity of statistical methods to explore publication bias, such as funnel plots, is limited because of the small number of studies for individual comparisons.

    Although our review included more than 200 studies, many questions remain. More evidence is needed on the most appropriate duration of antidepressant treatment for maintaining response and remission. Future studies should evaluate whether different formulations (for example, controlled release vs. immediate release) lead to differences in adherence and subsequent relapse or recurrence. In addition, although most trials maintained the dose used in acute-phase treatment throughout the continuation and maintenance phases of treatment, little is known about how drug dose affects the risk for relapse or recurrence. Future research is also needed to reliably establish the general efficacy of second-generation antidepressants for the treatment of dysthymia and subsyndromal depression.

    How do our findingsthat pharmacologic differences between second-generation antidepressants do not translate into substantial clinical differences, although tolerability may differinform the practicing clinician? Given the difficulty in predicting what medication will be both efficacious for and tolerated by an individual patient, familiarity with a broad spectrum of antidepressants is prudent. An emphasis on providing treatment trials of adequate dose and duration, with recent evidence providing support for maximum but tolerable doses for at least 8 weeks (146), seems at least as important as the choice of specific drug.

    References

    • 1. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, and Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:593-602. [PMID: 15939837] CrossrefMedlineGoogle Scholar
    • 2. Greenberg PE, Kessler RC, Birnbaum HG, Leong SA, Lowe SW, and Berglund PA; The economic burden of depression in the United States: how did it change between 1990 and 2000? J Clin Psychiatry. 2003;64:1465-75. [PMID: 14728109] CrossrefMedlineGoogle Scholar
    • 3. Williams JW, Mulrow CD, Chiquette E, Nol PH, Aguilar C, and Cornell J. A systematic review of newer pharmacotherapies for depression in adults: evidence report summary. Ann Intern Med. 2000;132:743-56 LinkGoogle Scholar
    • 4. Hansen RA, Gartlehner G, Lohr KN, Gaynes BN, and Carey TS. Efficacy and safety of second-generation antidepressants in the treatment of major depressive disorder. Ann Intern Med. 2005;143:415-26 LinkGoogle Scholar
    • 5. Gartlehner G, Hansen RA, Thieda P, DeVeaugh-Geiss AM, Gaynes BN, Krebs EE, et al. Comparative Effectiveness of Second-generation Antidepressants in the Pharmacologic Treatment of Adult Depression. Comparative Effectiveness Review No. 7-EHC007-EF. Rockville, MD: Agency for Healthcare Research and Quality; 2007. Accessed at www.effectivehealthcare.ahrq.gov/reports/final.cfm on 30 September 2008. Google Scholar
    • 6. Balk EM, Lau J, and Bonis PA. Reading and critically appraising systematic reviews and meta-analyses: a short primer with a focus on hepatology. J Hepatol. 2005;43:729-36. [PMID: 16120472] CrossrefMedlineGoogle Scholar
    • 7. Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, and Teutsch SM; Methods Work Group. Third US Preventive Services Task Force. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med. 2001;20:21-35. [PMID: 11306229] CrossrefMedlineGoogle Scholar
    • 8. Centre for Reviews and Dissemination. Undertaking systematic reviews of research on effectiveness: CRD's guidance for those carrying out or commissioning reviews. CRD Report Number 4. 2nd ed. York, United Kingdom: Univ of York; 2001. Accessed at www.york.ac.uk/inst/crd/report4.htm on 3 October 2008. Google Scholar
    • 9. Deeks JJ, Dinnes J, D'Amico R, Sowden AJ, Sakarovitch C, and Song F; International Stroke Trial Collaborative Group. Evaluating non-randomised intervention studies. Health Technol Assess. 2003;7:iii-x, 1-173. [PMID: 14499048] CrossrefMedlineGoogle Scholar
    • 10. Gartlehner G, Hansen RA, Nissman D, Lohr KN, and Carey TS. A simple and valid tool distinguished efficacy from effectiveness studies. J Clin Epidemiol. 2006;59:1040-8. [PMID: 16980143] CrossrefMedlineGoogle Scholar
    • 11. Begg CB and Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088-101. [PMID: 7786990] CrossrefMedlineGoogle Scholar
    • 12. Lumley T. Network meta-analysis for indirect treatment comparisons. Stat Med. 2002;21:2313-24. [PMID: 12210616] CrossrefMedlineGoogle Scholar
    • 13. Glenny AM, Altman DG, Song F, Sakarovitch C, Deeks JJ, and D'Amico R; International Stroke Trial Collaborative Group. Indirect comparisons of competing interventions. Health Technol Assess. 2005;9:1-134, iii-iv. [PMID: 16014203] CrossrefMedlineGoogle Scholar
    • 14. Atkins D, Eccles M, Flottorp S, Guyatt GH, Henry D, and Hill S; GRADE Working Group. Systems for grading the quality of evidence and the strength of recommendations I: critical appraisal of existing approaches The GRADE Working Group. BMC Health Serv Res. 2004;4:38. [PMID: 15615589] CrossrefMedlineGoogle Scholar
    • 15. Guyatt G, Gutterman D, Baumann MH, Addrizzo-Harris D, Hylek EM, and Phillips B; Grading strength of recommendations and quality of evidence in clinical guidelines: report from an American College of Chest Physicians task force. Chest. 2006;129:174-81. [PMID: 16424429] CrossrefMedlineGoogle Scholar
    • 16. Lepola UM, Loft H, and Reines EH. Escitalopram (10-20 mg/day) is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol. 2003;18:211-7. [PMID: 12817155] CrossrefMedlineGoogle Scholar
    • 17. Colonna L, Andersen HF, and Reines EH. A randomized, double-blind, 24-week study of escitalopram (10 mg/day) versus citalopram (20 mg/day) in primary care patients with major depressive disorder. Curr Med Res Opin. 2005;21:1659-68. [PMID: 16238906] CrossrefMedlineGoogle Scholar
    • 18. Burke WJ, Gergel I, and Bose A. Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry. 2002;63:331-6. [PMID: 12000207] CrossrefMedlineGoogle Scholar
    • 19. Moore N, Verdoux H, and Fantino B. Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder. Int Clin Psychopharmacol. 2005;20:131-7. [PMID: 15812262] CrossrefMedlineGoogle Scholar
    • 20. FDA Center for Drug Evaluation and Research. Statistical Review of NDA 21-323 (Escitalopram Oxalate). Rockville, MD: U.S. Food and Drug Administration; 2001. Accessed at www.fda.gov/cder/foi/nda/2002/21-323.pdf_Lexapro_Statr.pdf on 3 October 2008. Google Scholar
    • 21. Norman GR, Sloan JA, and Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care. 2003;41:582-92. [PMID: 12719681] CrossrefMedlineGoogle Scholar
    • 22. Newhouse PA, Krishnan KR, Doraiswamy PM, Richter EM, Batzar ED, and Clary CM. A double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients. J Clin Psychiatry. 2000;61:559-68. [PMID: 10982198] CrossrefMedlineGoogle Scholar
    • 23. Sechter D, Troy S, Paternetti S, and Boyer P. A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients. Eur Psychiatry. 1999;14:41-8. [PMID: 10572324] CrossrefMedlineGoogle Scholar
    • 24. Fava M, Hoog SL, Judge RA, Kopp JB, Nilsson ME, and Gonzales JS. Acute efficacy of fluoxetine versus sertraline and paroxetine in major depressive disorder including effects of baseline insomnia. J Clin Psychopharmacol. 2002;22:137-47. [PMID: 11910258] CrossrefMedlineGoogle Scholar
    • 25. Bennie EH, Mullin JM, and Martindale JJ. A double-blind multicenter trial comparing sertraline and fluoxetine in outpatients with major depression. J Clin Psychiatry. 1995;56:229-37. [PMID: 7775364] MedlineGoogle Scholar
    • 26. Costa e Silva J. Randomized, double-blind comparison of venlafaxine and fluoxetine in outpatients with major depression. J Clin Psychiatry. 1998;59:352-7. [PMID: 9714263] CrossrefMedlineGoogle Scholar
    • 27. Alves C, Cachola I, and Brandao J. Efficacy and tolerability of venlafaxine and fluoxetine in outpatients with major depression. Primary Care Psychiatry. 1999;5:57-63. Google Scholar
    • 28. Tzanakaki M, Guazzelli M, Nimatoudis I, Zissis NP, Smeraldi E, and Rizzo F. Increased remission rates with venlafaxine compared with fluoxetine in hospitalized patients with major depression and melancholia. Int Clin Psychopharmacol. 2000;15:29-34. [PMID: 10836283] CrossrefMedlineGoogle Scholar
    • 29. Tylee A, Beaumont G, Bowden MW, and Reynolds A. A double-blind, randomized, 12-week comparison study of the safety and efficacy of venlafaxine and fluoxetine in moderate to severe major depression in general practice. Primary Care Psychiatry. 1997;3:51-8. Google Scholar
    • 30. Rudolph RL and Feiger AD. A double-blind, randomized, placebo-controlled trial of once-daily venlafaxine extended release (XR) and fluoxetine for the treatment of depression. J Affect Disord. 1999;56:171-81. [PMID: 10701474] CrossrefMedlineGoogle Scholar
    • 31. De Nayer A, Geerts S, Ruelens L, Schittecatte M, De Bleeker E, and Van Eeckhoutte I; Venlafaxine compared with fluoxetine in outpatients with depression and concomitant anxiety. Int J Neuropsychopharmacol. 2002;5:115-20. [PMID: 12135535] CrossrefMedlineGoogle Scholar
    • 32. Dierick M, Ravizza L, Realini R, and Martin A. A double-blind comparison of venlafaxine and fluoxetine for treatment of major depression in outpatients. Prog Neuropsychopharmacol Biol Psychiatry. 1996;20:57-71. [PMID: 8861177] CrossrefMedlineGoogle Scholar
    • 33. Nemeroff CB and Thase ME; EPIC 014 Study Group. A double-blind, placebo-controlled comparison of venlafaxine and fluoxetine treatment in depressed outpatients. J Psychiatr Res. 2007;41:351-9. [PMID: 16165158] CrossrefMedlineGoogle Scholar
    • 34. Aberg-Wistedt A, Agren H, Ekselius L, Bengtsson F, and Akerblad AC. Sertraline versus paroxetine in major depression: clinical outcome after six months of continuous therapy. J Clin Psychopharmacol. 2000;20:645-52. [PMID: 11106136] CrossrefMedlineGoogle Scholar
    • 35. Sir A, D'Souza RF, Uguz S, George T, Vahip S, and Hopwood M; Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms. J Clin Psychiatry. 2005;66:1312-20. [PMID: 16259546] CrossrefMedlineGoogle Scholar
    • 36. Ravindran AV, Guelfi JD, Lane RM, and Cassano GB. Treatment of dysthymia with sertraline: a double-blind, placebo-controlled trial in dysthymic patients without major depression. J Clin Psychiatry. 2000;61:821-7. [PMID: 11105734] CrossrefMedlineGoogle Scholar
    • 37. Beasley CM, Dornseif BE, Pultz JA, Bosomworth JC, and Sayler ME. Fluoxetine versus trazodone: efficacy and activating-sedating effects. J Clin Psychiatry. 1991;52:294-9. [PMID: 2071559] MedlineGoogle Scholar
    • 38. Devanand DP, Nobler MS, Cheng J, Turret N, Pelton GH, and Roose SP; Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder. Am J Geriatr Psychiatry. 2005;13:59-68. [PMID: 15653941] CrossrefMedlineGoogle Scholar
    • 39. Wheatley DP, van Moffaert M, Timmerman L, and Kremer CM. Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine-Fluoxetine Study Group. J Clin Psychiatry. 1998;59:306-12. [PMID: 9671343] CrossrefMedlineGoogle Scholar
    • 40. Leinonen E, Skarstein J, Behnke K, Agren H, and Helsdingen JT. Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group. Int Clin Psychopharmacol. 1999;14:329-37. [PMID: 10565799] CrossrefMedlineGoogle Scholar
    • 41. McPartlin GM, Reynolds A, Anderson C, and Casoy J. A comparison of once-daily venlafaxine XR and paroxetine in depressed outpatients treated in general practice. Primary Care Psychiatry. 1998;:127-32. Google Scholar
    • 42. Guelfi JD, Ansseau M, Timmerman L, and Krsgaard S; Mirtazapine-Venlafaxine Study Group. Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features. J Clin Psychopharmacol. 2001;21:425-31. [PMID: 11476127] CrossrefMedlineGoogle Scholar
    • 43. Vanelle JM, Attar-Levy D, Poirier MF, Bouhassira M, Blin P, and Oli JP. Controlled efficacy study of fluoxetine in dysthymia. Br J Psychiatry. 1997;170:345-50. [PMID: 9246253] CrossrefMedlineGoogle Scholar
    • 44. Weihs KL, Settle EC, Batey SR, Houser TL, Donahue RM, and Ascher JA. Bupropion sustained release versus paroxetine for the treatment of depression in the elderly. J Clin Psychiatry. 2000;61:196-202. [PMID: 10817105] CrossrefMedlineGoogle Scholar
    • 45. Versiani M, Moreno R, Ramakers-van Moorsel CJ, and Schutte AJ; Comparative Efficacy Antidepressants Study Group. Comparison of the effects of mirtazapine and fluoxetine in severely depressed patients. CNS Drugs. 2005;19:137-46. [PMID: 15697327] CrossrefMedlineGoogle Scholar
    • 46. Boyer P, Danion JM, Bisserbe JC, Hotton JM, and Troy S. Clinical and economic comparison of sertraline and fluoxetine in the treatment of depression. A 6-month double-blind study in a primary-care setting in France. Pharmacoeconomics. 1998;13:157-69. [PMID: 10184835] CrossrefMedlineGoogle Scholar
    • 47. Bielski RJ, Ventura D, and Chang CC. A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder. J Clin Psychiatry. 2004;65:1190-6. [PMID: 15367045] CrossrefMedlineGoogle Scholar
    • 48. Finkel SI, Richter EM, Clary CM, and Batzar E. Comparative efficacy of sertraline vs. fluoxetine in patients age 70 or over with major depression. Am J Geriatr Psychiatry. 1999;7:221-7. [PMID: 10438693] CrossrefMedlineGoogle Scholar
    • 49. Ekselius L, von Knorring L, and Eberhard G. A double-blind multicenter trial comparing sertraline and citalopram in patients with major depression treated in general practice. Int Clin Psychopharmacol. 1997;12:323-31. [PMID: 9547134] CrossrefMedlineGoogle Scholar
    • 50. Kroenke K, West SL, Swindle R, Gilsenan A, Eckert GJ, and Dolor R; Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. JAMA. 2001;286:2947-55. [PMID: 11743835] CrossrefMedlineGoogle Scholar
    • 51. Hong CJ, Hu WH, Chen CC, Hsiao CC, Tsai SJ, and Ruwe FJ. A double-blind, randomized, group-comparative study of the tolerability and efficacy of 6 weeks' treatment with mirtazapine or fluoxetine in depressed Chinese patients. J Clin Psychiatry. 2003;64:921-6. [PMID: 12927007] CrossrefMedlineGoogle Scholar
    • 52. Benkert O, Szegedi A, and Kohnen R. Mirtazapine compared with paroxetine in major depression. J Clin Psychiatry. 2000;61:656-63. [PMID: 11030486] CrossrefMedlineGoogle Scholar
    • 53. Szegedi A, Mller MJ, Anghelescu I, Klawe C, Kohnen R, and Benkert O. Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression. J Clin Psychiatry. 2003;64:413-20. [PMID: 12716243] CrossrefMedlineGoogle Scholar
    • 54. Schatzberg AF, Kremer C, Rodrigues HE, and Murphy GM; Mirtazapine vs. Paroxetine Study Group. Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients. Am J Geriatr Psychiatry. 2002;10:541-50. [PMID: 12213688] CrossrefMedlineGoogle Scholar
    • 55. Behnke K, Sgaard J, Martin S, Buml J, Ravindran AV, and Agren H; Mirtazapine orally disintegrating tablet versus sertraline: a prospective onset of action study. J Clin Psychopharmacol. 2003;23:358-64. [PMID: 12920411] CrossrefMedlineGoogle Scholar
    • 56. Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, and Thase ME; STAR*D Study Team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006;354:1231-42. [PMID: 16554525] CrossrefMedlineGoogle Scholar
    • 57. Baldomero EB, Ubago JG, Cercs CL, Ruiloba JV, Calvo CG, and Lpez RP. Venlafaxine extended release versus conventional antidepressants in the remission of depressive disorders after previous antidepressant failure: ARGOS study. Depress Anxiety. 2005;22:68-76. [PMID: 16094658] CrossrefMedlineGoogle Scholar
    • 58. Poirier MF and Boyer P. Venlafaxine and paroxetine in treatment-resistant depression. Double-blind, randomised comparison. Br J Psychiatry. 1999;175:12-6. [PMID: 10621762] CrossrefMedlineGoogle Scholar
    • 59. van Moffaert M, Bartholome F, Cosyns P, and De Nayer AR. A controlled comparison of sertraline and fluoxetine in acute and continuation treatment of major depression. Hum Psychopharmacol. 1995;10:393-405. CrossrefGoogle Scholar
    • 60. Franchini L, Gasperini M, Perez J, Smeraldi E, and Zanardi R. A double-blind study of long-term treatment with sertraline or fluvoxamine for prevention of highly recurrent unipolar depression. J Clin Psychiatry. 1997;58:104-7. [PMID: 9108811] CrossrefMedlineGoogle Scholar
    • 61. Franchini L, Gasperini M, Zanardi R, and Smeraldi E. Four-year follow-up study of sertraline and fluvoxamine in long-term treatment of unipolar subjects with high recurrence rate. J Affect Disord. 2000;58:233-6. [PMID: 10802132] CrossrefMedlineGoogle Scholar
    • 62. Cunningham LA, Borison RL, Carman JS, Chouinard G, Crowder JE, and Diamond BI; A comparison of venlafaxine, trazodone, and placebo in major depression. J Clin Psychopharmacol. 1994;14:99-106. [PMID: 8195464] CrossrefMedlineGoogle Scholar
    • 63. Perahia DG, Wang F, Mallinckrodt CH, Walker DJ, and Detke MJ. Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Psychiatry. 2006;21:367-78. [PMID: 16697153] CrossrefMedlineGoogle Scholar
    • 64. Fava M, Rosenbaum JF, Hoog SL, Tepner RG, Kopp JB, and Nilsson ME. Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression. J Affect Disord. 2000;59:119-26. [PMID: 10837880] CrossrefMedlineGoogle Scholar
    • 65. Flament MF, Lane RM, Zhu R, and Ying Z. Predictors of an acute antidepressant response to fluoxetine and sertraline. Int Clin Psychopharmacol. 1999;14:259-75. [PMID: 10529069] CrossrefMedlineGoogle Scholar
    • 66. Rush AJ, Trivedi MH, Carmody TJ, Donahue RM, Houser TL, and Bolden-Watson C; Response in relation to baseline anxiety levels in major depressive disorder treated with bupropion sustained release or sertraline. Neuropsychopharmacology. 2001;25:131-8. [PMID: 11377926] CrossrefMedlineGoogle Scholar
    • 67. Rush AJ, Batey SR, Donahue RM, Ascher JA, Carmody TJ, and Metz A. Does pretreatment anxiety predict response to either bupropion SR or sertraline? J Affect Disord. 2001;64:81-7. [PMID: 11292522] CrossrefMedlineGoogle Scholar
    • 68. Trivedi MH, Rush AJ, Carmody TJ, Donahue RM, Bolden-Watson C, and Houser TL; Do bupropion SR and sertraline differ in their effects on anxiety in depressed patients? J Clin Psychiatry. 2001;62:776-81. [PMID: 11816866] CrossrefMedlineGoogle Scholar
    • 69. Rush AJ, Armitage R, Gillin JC, Yonkers KA, Winokur A, and Moldofsky H; Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder. Biol Psychiatry. 1998;44:3-14. [PMID: 9646878] CrossrefMedlineGoogle Scholar
    • 70. Lader M, Andersen HF, and Baekdal T. The effect of escitalopram on sleep problems in depressed patients. Hum Psychopharmacol. 2005;20:349-54. [PMID: 15912558] CrossrefMedlineGoogle Scholar
    • 71. Clerc GE, Ruimy P, and Verdeau-Palls J. A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. The Venlafaxine French Inpatient Study Group. Int Clin Psychopharmacol. 1994;9:139-43. [PMID: 7814822] CrossrefMedlineGoogle Scholar
    • 72. Brannan SK, Mallinckrodt CH, Brown EB, Wohlreich MM, Watkin JG, and Schatzberg AF. Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder. J Psychiatr Res. 2005;39:43-53. [PMID: 15504423] CrossrefMedlineGoogle Scholar
    • 73. Dickens C, Jayson M, Sutton C, and Creed F. The relationship between pain and depression in a trial using paroxetine in sufferers of chronic low back pain. Psychosomatics. 2000;41:490-9. [PMID: 11110112] CrossrefMedlineGoogle Scholar
    • 74. Baldwin DS, Hawley CJ, Abed RT, Maragakis BP, Cox J, and Buckingham SA; A multicenter double-blind comparison of nefazodone and paroxetine in the treatment of outpatients with moderate-to-severe depression. J Clin Psychiatry. 1996;57: 46-52. [PMID: 8626363] MedlineGoogle Scholar
    • 75. Chouinard G, Saxena B, Blanger MC, Ravindran A, Bakish D, and Beauclair L; A Canadian multicenter, double-blind study of paroxetine and fluoxetine in major depressive disorder. J Affect Disord. 1999;54:39-48. [PMID: 10403145] CrossrefMedlineGoogle Scholar
    • 76. Fava M, Amsterdam JD, Deltito JA, Salzman C, Schwaller M, and Dunner DL. A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression. Ann Clin Psychiatry. 1998;10:145-50. [PMID: 9988054] CrossrefMedlineGoogle Scholar
    • 77. Gagiano CA. A double blind comparison of paroxetine and fluoxetine in patients with major depression. Br J Clin Res. 1993;4:145-52. Google Scholar
    • 78. Detke MJ, Wiltse CG, Mallinckrodt CH, McNamara RK, Demitrack MA, and Bitter I. Duloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Neuropsychopharmacol. 2004;14:457-70. [PMID: 15589385] CrossrefMedlineGoogle Scholar
    • 79. Clinical Study Summary: Study F1J-MC-HMAT Study Group A. Indianapolis, IN: Eli Lilly; 2004. Accessed at www.clinicalstudyresults.org/drugdetails/?unique_id=4091a&sort=c.company_name&page=1&drug_id=170 on 30 September 2008. Google Scholar
    • 80. Goldstein DJ, Lu Y, Detke MJ, Wiltse C, Mallinckrodt C, and Demitrack MA. Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol. 2004;24:389-99. [PMID: 15232330] CrossrefMedlineGoogle Scholar
    • 81. Montejo AL, Llorca G, Izquierdo JA, and Rico-Villademoros F. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. J Clin Psychiatry. 2001;62: 10-21. [PMID: 11229449] MedlineGoogle Scholar
    • 82. Coleman CC, King BR, Bolden-Watson C, Book MJ, Segraves RT, and Richard N; A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained release and fluoxetine. Clin Ther. 2001;23:1040-58. [PMID: 11519769] CrossrefMedlineGoogle Scholar
    • 83. Segraves RT, Kavoussi R, Hughes AR, Batey SR, Johnston JA, and Donahue R; Evaluation of sexual functioning in depressed outpatients: a double-blind comparison of sustained-release bupropion and sertraline treatment. J Clin Psychopharmacol. 2000;20:122-8. [PMID: 10770448] CrossrefMedlineGoogle Scholar
    • 84. Coleman CC, Cunningham LA, Foster VJ, Batey SR, Donahue RM, and Houser TL; Sexual dysfunction associated with the treatment of depression: a placebo-controlled comparison of bupropion sustained release and sertraline treatment. Ann Clin Psychiatry. 1999;11:205-15. [PMID: 10596735] CrossrefMedlineGoogle Scholar
    • 85. Croft H, Settle E, Houser T, Batey SR, Donahue RM, and Ascher JA. A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Clin Ther. 1999;21:643-58. [PMID: 10363731] CrossrefMedlineGoogle Scholar
    • 86. Feighner JP, Gardner EA, Johnston JA, Batey SR, Khayrallah MA, and Ascher JA; Double-blind comparison of bupropion and fluoxetine in depressed outpatients. J Clin Psychiatry. 1991;52:329-35. [PMID: 1907963] MedlineGoogle Scholar
    • 87. Hicks JA, Argyropoulos SV, Rich AS, Nash JR, Bell CJ, and Edwards C; Randomised controlled study of sleep after nefazodone or paroxetine treatment in out-patients with depression. Br J Psychiatry. 2002;180:528-35. [PMID: 12042232] CrossrefMedlineGoogle Scholar
    • 88. Kiev A and Feiger A. A double-blind comparison of fluvoxamine and paroxetine in the treatment of depressed outpatients. J Clin Psychiatry. 1997;58:146-52. [PMID: 9164424] CrossrefMedlineGoogle Scholar
    • 89. Committee on Safety of Medicines. Report of the CSM expert working group on the safety of selective serotonin reuptake inhibitor antidepressants. London: Medicines and Healthcare products Regulatory Agency; 2004. Accessed at www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con019472.pdf on 2 December 2008. Google Scholar
    • 90. Fergusson D, Doucette S, Glass KC, Shapiro S, Healy D, and Hebert P; Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ. 2005;330:396. [PMID: 15718539] CrossrefMedlineGoogle Scholar
    • 91. Martinez C, Rietbrock S, Wise L, Ashby D, Chick J, and Moseley J; Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case–control study. BMJ. 2005;330:389. [PMID: 15718538] CrossrefMedlineGoogle Scholar
    • 92. Gunnell D, Saperia J, and Ashby D. Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review. BMJ. 2005;330:385. [PMID: 15718537] CrossrefMedlineGoogle Scholar
    • 93. Didham RC, McConnell DW, Blair HJ, and Reith DM. Suicide and self-harm following prescription of SSRIs and other antidepressants: confounding by indication. Br J Clin Pharmacol. 2005;60:519-25. [PMID: 16236042] CrossrefMedlineGoogle Scholar
    • 94. Jick H, Kaye JA, and Jick SS. Antidepressants and the risk of suicidal behaviors. JAMA. 2004;292:338-43. [PMID: 15265848] CrossrefMedlineGoogle Scholar
    • 95. Jick SS, Dean AD, and Jick H. Antidepressants and suicide. BMJ. 1995;310:215-8. [PMID: 7677826] CrossrefMedlineGoogle Scholar
    • 96. Jick H, Ulcickas M, and Dean A. Comparison of frequencies of suicidal tendencies among patients receiving fluoxetine, lofepramine, mianserin, or trazodone. Pharmacotherapy. 1992;12:451-4. [PMID: 1492009] MedlineGoogle Scholar
    • 97. Aursnes I, Tvete IF, Gaasemyr J, and Natvig B. Suicide attempts in clinical trials with paroxetine randomised against placebo. BMC Med. 2005;3:14. [PMID: 16115311] CrossrefMedlineGoogle Scholar
    • 98. Khan A, Khan S, Kolts R, and Brown WA. Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. Am J Psychiatry. 2003;160:790-2. [PMID: 12668373] CrossrefMedlineGoogle Scholar
    • 99. Lopez-Iibor . Reduced suicidality with paroxetine. Eur Psychiatry. 1993;8: 17S-19S. CrossrefGoogle Scholar
    • 100. Rocca P, Calvarese P, Faggiano F, Marchiaro L, Mathis F, and Rivoira E; Citalopram versus sertraline in late-life nonmajor clinically significant depression: a 1-year follow-up clinical trial. J Clin Psychiatry. 2005;66:360-9. [PMID: 15766303] CrossrefMedlineGoogle Scholar
    • 101. Kasper S, de Swart H, and Friis Andersen H. Escitalopram in the treatment of depressed elderly patients. Am J Geriatr Psychiatry. 2005;13:884-91. [PMID: 16223967] CrossrefMedlineGoogle Scholar
    • 102. Schne W and Ludwig M. A double-blind study of paroxetine compared with fluoxetine in geriatric patients with major depression. J Clin Psychopharmacol. 1993;13:34S-39S. [PMID: 8106654] MedlineGoogle Scholar
    • 103. Geretsegger C, Bhmer F, and Ludwig M. Paroxetine in the elderly depressed patient: randomized comparison with fluoxetine of efficacy, cognitive and behavioural effects. Int Clin Psychopharmacol. 1994;9:25-9. [PMID: 8195578] CrossrefMedlineGoogle Scholar
    • 104. Cassano GB, Puca F, Scapicchio PL, and Trabucchi M; Italian Study Group on Depression in Elderly Patients. Paroxetine and fluoxetine effects on mood and cognitive functions in depressed nondemented elderly patients. J Clin Psychiatry. 2002;63:396-402. [PMID: 12019663] CrossrefMedlineGoogle Scholar
    • 105. Rossini D, Serretti A, Franchini L, Mandelli L, Smeraldi E, and De Ronchi D; Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial. J Clin Psychopharmacol. 2005;25:471-5. [PMID: 16160624] CrossrefMedlineGoogle Scholar
    • 106. Allard P, Gram L, Timdahl K, Behnke K, Hanson M, and Sgaard J. Efficacy and tolerability of venlafaxine in geriatric outpatients with major depression: a double-blind, randomised 6-month comparative trial with citalopram. Int J Geriatr Psychiatry. 2004;19:1123-30. [PMID: 15526307] CrossrefMedlineGoogle Scholar
    • 107. Oslin DW, Ten Have TR, Streim JE, Datto CJ, Weintraub D, and DiFilippo S; Probing the safety of medications in the frail elderly: evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents. J Clin Psychiatry. 2003;64:875-82. [PMID: 12927001] CrossrefMedlineGoogle Scholar
    • 108. Thase ME, Entsuah R, Cantillon M, and Kornstein SG. Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions. J Womens Health (Larchmt). 2005;14:609-16. [PMID: 16181017] CrossrefMedlineGoogle Scholar
    • 109. Entsuah AR, Huang H, and Thase ME. Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry. 2001;62:869-77. [PMID: 11775046] CrossrefMedlineGoogle Scholar
    • 110. Rapaport MH, Schneider LS, Dunner DL, Davies JT, and Pitts CD. Efficacy of controlled-release paroxetine in the treatment of late-life depression. J Clin Psychiatry. 2003;64:1065-74. [PMID: 14628982] CrossrefMedlineGoogle Scholar
    • 111. Tollefson GD, Bosomworth JC, Heiligenstein JH, Potvin JH, and Holman S. A double-blind, placebo-controlled clinical trial of fluoxetine in geriatric patients with major depression. The Fluoxetine Collaborative Study Group. Int Psychogeriatr. 1995;7:89-104. [PMID: 7579025] CrossrefMedlineGoogle Scholar
    • 112. Tollefson GD and Holman SL. Analysis of the Hamilton Depression Rating Scale factors from a double-blind, placebo-controlled trial of fluoxetine in geriatric major depression. Int Clin Psychopharmacol. 1993;8:253-9. [PMID: 8277144] CrossrefMedlineGoogle Scholar
    • 113. Small GW, Birkett M, Meyers BS, Koran LM, Bystritsky A, and Nemeroff CB. Impact of physical illness on quality of life and antidepressant response in geriatric major depression. Fluoxetine Collaborative Study Group. J Am Geriatr Soc. 1996;44:1220-5. [PMID: 8856002] CrossrefMedlineGoogle Scholar
    • 114. Schneider LS, Nelson JC, Clary CM, Newhouse P, Krishnan KR, and Shiovitz T; Sertraline Elderly Depression Study Group. An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression. Am J Psychiatry. 2003;160:1277-85. [PMID: 12832242] CrossrefMedlineGoogle Scholar
    • 115. Sheikh JI, Cassidy EL, Doraiswamy PM, Salomon RM, Hornig M, and Holland PJ; Efficacy, safety, and tolerability of sertraline in patients with late-life depression and comorbid medical illness. J Am Geriatr Soc. 2004;52:86-92. [PMID: 14687320] CrossrefMedlineGoogle Scholar
    • 116. Roose SP, Sackeim HA, Krishnan KR, Pollock BG, Alexopoulos G, and Lavretsky H; Old-Old Depression Study Group. Antidepressant pharmacotherapy in the treatment of depression in the very old: a randomized, placebo-controlled trial. Am J Psychiatry. 2004;161:2050-9. [PMID: 15514406] CrossrefMedlineGoogle Scholar
    • 117. Kennedy SH, Eisfeld BS, Dickens SE, Bacchiochi JR, and Bagby RM. Antidepressant-induced sexual dysfunction during treatment with moclobemide, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry. 2000;61:276-81. [PMID: 10830148] CrossrefMedlineGoogle Scholar
    • 118. Morishita S and Arita S. Differential effects of milnacipran, fluvoxamine and paroxetine for depression, especially in gender. Eur Psychiatry. 2003;18:418-20. [PMID: 14680720] CrossrefMedlineGoogle Scholar
    • 119. Wagner GJ, Maguen S, and Rabkin JG. Ethnic differences in response to fluoxetine in a controlled trial with depressed HIV-positive patients. Psychiatr Serv. 1998;49:239-40. [PMID: 9575014] CrossrefMedlineGoogle Scholar
    • 120. Ferrando SJ, Goldman JD, and Charness WE. Selective serotonin reuptake inhibitor treatment of depression in symptomatic HIV infection and AIDS. Improvements in affective and somatic symptoms. Gen Hosp Psychiatry. 1997;19:89-97. [PMID: 9097063] CrossrefMedlineGoogle Scholar
    • 121. Rabkin JG, Wagner GJ, McElhiney MC, Rabkin R, and Lin SH. Testosterone versus fluoxetine for depression and fatigue in HIV/AIDS: a placebo-controlled trial. J Clin Psychopharmacol. 2004;24:379-85. [PMID: 15232328] CrossrefMedlineGoogle Scholar
    • 122. Rabkin JG, Wagner GJ, and Rabkin R. Fluoxetine treatment for depression in patients with HIV and AIDS: a randomized, placebo-controlled trial. Am J Psychiatry. 1999;156:101-7. [PMID: 9892304] CrossrefMedlineGoogle Scholar
    • 123. Gual A, Balcells M, Torres M, Madrigal M, Diez T, and Serrano L. Sertraline for the prevention of relapse in detoxicated alcohol dependent patients with a comorbid depressive disorder: a randomized, controlled trial. Alcohol Alcohol. 2003;38:619-25. [PMID: 14633652] CrossrefMedlineGoogle Scholar
    • 124. Hernandez-Avila CA, Modesto-Lowe V, Feinn R, and Kranzler HR. Nefazodone treatment of comorbid alcohol dependence and major depression. Alcohol Clin Exp Res. 2004;28:433-40. [PMID: 15084901] CrossrefMedlineGoogle Scholar
    • 125. Moak DH, Anton RF, Latham PK, Voronin KE, Waid RL, and Durazo-Arvizu R. Sertraline and cognitive behavioral therapy for depressed alcoholics: results of a placebo-controlled trial. J Clin Psychopharmacol. 2003;23:553-62. [PMID: 14624185] CrossrefMedlineGoogle Scholar
    • 126. Lyketsos CG, DelCampo L, Steinberg M, Miles Q, Steele CD, and Munro C; Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS. Arch Gen Psychiatry. 2003;60:737-46. [PMID: 12860778] CrossrefMedlineGoogle Scholar
    • 127. Magai C, Kennedy G, Cohen CI, and Gomberg D. A controlled clinical trial of sertraline in the treatment of depression in nursing home patients with late-stage Alzheimer's disease. Am J Geriatr Psychiatry. 2000;8:66-74. [PMID: 10648297] CrossrefMedlineGoogle Scholar
    • 128. Nyth AL, Gottfries CG, Lyby K, Smedegaard-Andersen L, Gylding-Sabroe J, and Kristensen M; A controlled multicenter clinical study of citalopram and placebo in elderly depressed patients with and without concomitant dementia. Acta Psychiatr Scand. 1992;86:138-45. [PMID: 1529737] CrossrefMedlineGoogle Scholar
    • 129. Roscoe JA, Morrow GR, Hickok JT, Mustian KM, Griggs JJ, and Matteson SE; Effect of paroxetine hydrochloride (Paxil) on fatigue and depression in breast cancer patients receiving chemotherapy. Breast Cancer Res Treat. 2005;89:243-9. [PMID: 15754122] CrossrefMedlineGoogle Scholar
    • 130. Glassman AH, O'Connor CM, Califf RM, Swedberg K, Schwartz P, and Bigger JT; Sertraline Antidepressant Heart Attack Randomized Trial (SADHEART) Group. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA. 2002;288:701-9. [PMID: 12169073] CrossrefMedlineGoogle Scholar
    • 131. Krishnan KR, Doraiswamy PM, and Clary CM. Clinical and treatment response characteristics of late-life depression associated with vascular disease: a pooled analysis of two multicenter trials with sertraline. Prog Neuropsychopharmacol Biol Psychiatry. 2001;25:347-61. [PMID: 11294481] CrossrefMedlineGoogle Scholar
    • 132. Strik JJ, Honig A, Lousberg R, Lousberg AH, Cheriex EC, and Tuynman-Qua HG; Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-blind, placebo-controlled trial. Psychosom Med. 2000;62:783-9. [PMID: 11138997] CrossrefMedlineGoogle Scholar
    • 133. Andersen G, Vestergaard K, and Lauritzen L. Effective treatment of poststroke depression with the selective serotonin reuptake inhibitor citalopram. Stroke. 1994;25:1099-104. [PMID: 8202964] CrossrefMedlineGoogle Scholar
    • 134. Murray V, von Arbin M, Bartfai A, Berggren AL, Landtblom AM, and Lundmark J; Double-blind comparison of sertraline and placebo in stroke patients with minor depression and less severe major depression. J Clin Psychiatry. 2005;66:708-16. [PMID: 15960563] CrossrefMedlineGoogle Scholar
    • 135. Schmitz JM, Averill P, Stotts AL, Moeller FG, Rhoades HM, and Grabowski J. Fluoxetine treatment of cocaine-dependent patients with major depressive disorder. Drug Alcohol Depend. 2001;63:207-14. [PMID: 11418225] CrossrefMedlineGoogle Scholar
    • 136. Petrakis I, Carroll KM, Nich C, Gordon L, Kosten T, and Rounsaville B. Fluoxetine treatment of depressive disorders in methadone-maintained opioid addicts. Drug Alcohol Depend. 1998;50:221-6. [PMID: 9649975] CrossrefMedlineGoogle Scholar
    • 137. Bush DE, Ziegelstein RC, Patel UV, Thombs BD, Ford DE, and Fauerbach JA; Post-myocardial infarction depression. Evid Rep Technol Assess (Summ). 2005;:1-8. [PMID: 15989376] MedlineGoogle Scholar
    • 138. . Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC American Psychiatric Assoc 2000. Google Scholar
    • 139. Kocsis JH, Zisook S, Davidson J, Shelton R, Yonkers K, and Hellerstein DJ; Double-blind comparison of sertraline, imipramine, and placebo in the treatment of dysthymia: psychosocial outcomes. Am J Psychiatry. 1997;154:390-5. [PMID: 9054788] CrossrefMedlineGoogle Scholar
    • 140. Thase ME, Fava M, Halbreich U, Kocsis JH, Koran L, and Davidson J; A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia. Arch Gen Psychiatry. 1996;53:777-84. [PMID: 8792754] CrossrefMedlineGoogle Scholar
    • 141. Williams JW, Barrett J, Oxman T, Frank E, Katon W, and Sullivan M; Treatment of dysthymia and minor depression in primary care: A randomized, controlled trial in older adults. JAMA. 2000;284:1519-26. [PMID: 11000645] CrossrefMedlineGoogle Scholar
    • 142. Barrett JE, Williams JW, Oxman TE, Frank E, Katon W, and Sullivan M; Treatment of dysthymia and minor depression in primary care: a randomized trial in patients aged 18 to 59 years. J Fam Pract. 2001;50:405-12. [PMID: 11350703] MedlineGoogle Scholar
    • 143. Judd LL, Rapaport MH, Yonkers KA, Rush AJ, Frank E, and Thase ME; Randomized, placebo-controlled trial of fluoxetine for acute treatment of minor depressive disorder. Am J Psychiatry. 2004;161:1864-71. [PMID: 15465984] CrossrefMedlineGoogle Scholar
    • 144. Kavoussi RJ, Segraves RT, Hughes AR, Ascher JA, and Johnston JA. Double-blind comparison of bupropion sustained release and sertraline in depressed outpatients. J Clin Psychiatry. 1997;58:532-7. [PMID: 9448656] CrossrefMedlineGoogle Scholar
    • 145. Cipriani A, Barbui C, Brambilla P, Furukawa TA, Hotopf M, and Geddes JR. Are all antidepressants really the same? The case of fluoxetine: a systematic review. J Clin Psychiatry. 2006;67:850-64. [PMID: 16848644] CrossrefMedlineGoogle Scholar
    • 146. Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, and Warden D; Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163:1905-17. [PMID: 17074942] CrossrefMedlineGoogle Scholar
    • 147. Aguglia E, Casacchia M, Cassano GB, Faravelli C, Ferrari G, and Giordano P; Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression. Int Clin Psychopharmacol. 1993;8:197-202. [PMID: 8263318] CrossrefMedlineGoogle Scholar
    • 148. Amini H, Aghayan S, Jalili SA, Akhondzadeh S, Yahyazadeh O, and Pakravan-Nejad M. Comparison of mirtazapine and fluoxetine in the treatment of major depressive disorder: a double-blind, randomized trial. J Clin Pharm Ther. 2005;30:133-8. [PMID: 15811165] CrossrefMedlineGoogle Scholar
    • 149. Brown ES, Vigil L, Khan DA, Liggin JD, Carmody TJ, and Rush AJ. A randomized trial of citalopram versus placebo in outpatients with asthma and major depressive disorder: a proof of concept study. Biol Psychiatry. 2005;58:865-70. [PMID: 15993860] CrossrefMedlineGoogle Scholar
    • 150. Byerley WF, Reimherr FW, Wood DR, and Grosser BI. Fluoxetine, a selective serotonin uptake inhibitor, for the treatment of outpatients with major depression. J Clin Psychopharmacol. 1988;8:112-5. [PMID: 3286684] CrossrefMedlineGoogle Scholar
    • 151. Claghorn JL and Lesem MD. A double-blind placebo-controlled study of Org 3770 in depressed outpatients. J Affect Disord. 1995;34:165-71. [PMID: 7560544] CrossrefMedlineGoogle Scholar
    • 152. Claghorn JL, Earl CQ, Walczak DD, Stoner KA, Wong LF, and Kanter D; Fluvoxamine maleate in the treatment of depression: a single-center, double-blind, placebo-controlled comparison with imipramine in outpatients. J Clin Psychopharmacol. 1996;16:113-20. [PMID: 8690826] CrossrefMedlineGoogle Scholar
    • 153. Claghorn JL. The safety and efficacy of paroxetine compared with placebo in a double-blind trial of depressed outpatients. J Clin Psychiatry. 1992;53: 33-5. [PMID: 1531821] MedlineGoogle Scholar
    • 154. Cohn JB, Crowder JE, Wilcox CS, and Ryan PJ. A placebo- and imipramine-controlled study of paroxetine. Psychopharmacol Bull. 1990;26:185-9. [PMID: 2146697] MedlineGoogle Scholar
    • 155. Cohn JB and Wilcox CS. Paroxetine in major depression: a double-blind trial with imipramine and placebo. J Clin Psychiatry. 1992;53: 52-6. [PMID: 1531826] MedlineGoogle Scholar
    • 156. Corrigan MH, Denahan AQ, Wright CE, Ragual RJ, and Evans DL. Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Depress Anxiety. 2000;11:58-65. [PMID: 10812530] CrossrefMedlineGoogle Scholar
    • 157. Croft H, Houser TL, Jamerson BD, Leadbetter R, Bolden-Watson C, and Donahue R; Effect on body weight of bupropion sustained-release in patients with major depression treated for 52 weeks. Clin Ther. 2002;24:662-72. [PMID: 12017410] CrossrefMedlineGoogle Scholar
    • 158. Dunbar GC, Cohn JB, Fabre LF, Feighner JP, Fieve RR, and Mendels J; A comparison of paroxetine, imipramine and placebo in depressed out-patients. Br J Psychiatry. 1991;159:394-8. [PMID: 1835664] CrossrefMedlineGoogle Scholar
    • 159. Dunbar GC, Claghorn JL, Kiev A, Rickels K, and Smith WT. A comparison of paroxetine and placebo in depressed outpatients. Acta Psychiatr Scand. 1993;87:302-5. [PMID: 8517168] CrossrefMedlineGoogle Scholar
    • 160. Elliott AJ, Uldall KK, Bergam K, Russo J, Claypoole K, and Roy-Byrne PP. Randomized, placebo-controlled trial of paroxetine versus imipramine in depressed HIV-positive outpatients. Am J Psychiatry. 1998;155:367-72. [PMID: 9501747] MedlineGoogle Scholar
    • 161. Evans M, Hammond M, Wilson K, Lye M, and Copeland J. Placebo-controlled treatment trial of depression in elderly physically ill patients. Int J Geriatr Psychiatry. 1997;12:817-24. [PMID: 9283926] CrossrefMedlineGoogle Scholar
    • 162. Fabre L, Birkhimer LJ, Zaborny BA, Wong LF, and Kapik BM. Fluvoxamine versus imipramine and placebo: a double-blind comparison in depressed patients. Int Clin Psychopharmacol. 1996;11:119-27. [PMID: 8803649] MedlineGoogle Scholar
    • 163. Fabre LF, Abuzzahab FS, Amin M, Claghorn JL, Mendels J, and Petrie WM; Sertraline safety and efficacy in major depression: a double-blind fixed-dose comparison with placebo. Biol Psychiatry. 1995;38:592-602. [PMID: 8573661] CrossrefMedlineGoogle Scholar
    • 164. Fabre LF. A 6-week, double-blind trial of paroxetine, imipramine, and placebo in depressed outpatients. J Clin Psychiatry. 1992;53: 40-3. [PMID: 1531823] MedlineGoogle Scholar
    • 165. Fabre LF and Putman HP. A fixed-dose clinical trial of fluoxetine in outpatients with major depression. J Clin Psychiatry. 1987;48:406-8. [PMID: 3312176] MedlineGoogle Scholar
    • 166. Falk WE, Rosenbaum JF, Otto MW, Zusky PM, Weilburg JB, and Nixon RA. Fluoxetine versus trazodone in depressed geriatric patients. J Geriatr Psychiatry Neurol. 1989;2:208-14. [PMID: 2699556] MedlineGoogle Scholar
    • 167. Fava M, Alpert J, Nierenberg AA, Mischoulon D, Otto MW, and Zajecka J; A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. J Clin Psychopharmacol. 2005;25:441-7. [PMID: 16160619] CrossrefMedlineGoogle Scholar
    • 168. Fava M, Mulroy R, Alpert J, Nierenberg AA, and Rosenbaum JF. Emergence of adverse events following discontinuation of treatment with extended-release venlafaxine. Am J Psychiatry. 1997;154:1760-2. [PMID: 9396960] CrossrefMedlineGoogle Scholar
    • 169. Feighner JP. A double-blind comparison of paroxetine, imipramine and placebo in depressed outpatients. Int Clin Psychopharmacol. 1992;6: 31-5. [PMID: 1431008] CrossrefMedlineGoogle Scholar
    • 170. Feighner JP and Boyer WF. Paroxetine in the treatment of depression: a comparison with imipramine and placebo. J Clin Psychiatry. 1992;53: 44-7. [PMID: 1531824] MedlineGoogle Scholar
    • 171. Feighner JP, Cohn JB, Fabre LF, Fieve RR, Mendels J, and Shrivastava RK; A study comparing paroxetine placebo and imipramine in depressed patients. J Affect Disord. 1993;28:71-9. [PMID: 8354771] CrossrefMedlineGoogle Scholar
    • 172. Feighner J, Targum SD, Bennett ME, Roberts DL, Kensler TT, and D'Amico MF; A double-blind, placebo-controlled trial of nefazodone in the treatment of patients hospitalized for major depression. J Clin Psychiatry. 1998;59:246-53. [PMID: 9632036] CrossrefMedlineGoogle Scholar
    • 173. Flament MF and Lane R. Acute antidepressant response to fluoxetine and sertraline in psychiatric outpatients with psychomotor agitation. Int J Psychiatry Clin Pract. 2001;5:103-9. CrossrefMedlineGoogle Scholar
    • 174. Gilaberte I, Montejo AL, de la Gandara J, Perez-Sola V, Bernardo M, and Massana J; Fluoxetine Long-Term Study Group. Fluoxetine in the prevention of depressive recurrences: a double-blind study. J Clin Psychopharmacol. 2001;21:417-24. [PMID: 11476126] CrossrefMedlineGoogle Scholar
    • 175. Grigoriadis S, Kennedy SH, and Bagby RM. A comparison of antidepressant response in younger and older women. J Clin Psychopharmacol. 2003;23:405-7. [PMID: 12920418] CrossrefMedlineGoogle Scholar
    • 176. Glseren L, Glseren S, Hekimsoy Z, and Mete L. Comparison of fluoxetine and paroxetine in type II diabetes mellitus patients. Arch Med Res. 2005;36:159-65. [PMID: 15847950] CrossrefMedlineGoogle Scholar
    • 177. Kennedy SH, Fulton KA, Bagby RM, Greene AL, Cohen NL, and Rafi-Tari S. Sexual function during bupropion or paroxetine treatment of major depressive disorder. Can J Psychiatry. 2006;51:234-42. [PMID: 16629348] CrossrefMedlineGoogle Scholar
    • 178. Lapierre YD, Browne M, Horn E, Oyewumi LK, Sarantidis D, and Roberts N; Treatment of major affective disorder with fluvoxamine. J Clin Psychiatry. 1987;48:65-8. [PMID: 3100510] MedlineGoogle Scholar
    • 179. March JS, Kobak KA, Jefferson JW, Mazza J, and Greist JH. A double-blind, placebo-controlled trial of fluvoxamine versus imipramine in outpatients with major depression. J Clin Psychiatry. 1990;51:200-2. [PMID: 2110560] MedlineGoogle Scholar
    • 180. McGrath PJ, Stewart JW, Janal MN, Petkova E, Quitkin FM, and Klein DF. A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression. Am J Psychiatry. 2000;157:344-50. [PMID: 10698808] CrossrefMedlineGoogle Scholar
    • 181. Mesters P, Cosyns P, Dejaiffe G, Fanielle J, Gilles C, and Godderis J; Assessment of quality of life in the treatment of major depressive disorder with fluoxetine, 20 mg, in ambulatory patients aged over 60 years. Int Clin Psychopharmacol. 1993;8:337-40. [PMID: 8277160] CrossrefMedlineGoogle Scholar
    • 182. Montgomery SA, Rasmussen JG, Lyby K, Connor P, and Tanghj P. Dose response relationship of citalopram 20 mg, citalopram 40 mg and placebo in the treatment of moderate and severe depression. Int Clin Psychopharmacol. 1992;6: 65-70. [PMID: 1431024] CrossrefMedlineGoogle Scholar
    • 183. Muijen M, Roy D, Silverstone T, Mehmet A, and Christie M. A comparative clinical trial of fluoxetine, mianserin and placebo in depressed outpatients. Acta Psychiatr Scand. 1988;78:384-90. [PMID: 3057817] CrossrefMedlineGoogle Scholar
    • 184. Petracca GM, Chemerinski E, and Starkstein SE. A double-blind, placebo-controlled study of fluoxetine in depressed patients with Alzheimer's disease. Int Psychogeriatr. 2001;13:233-40. [PMID: 11495397] CrossrefMedlineGoogle Scholar
    • 185. Ravindran AV, Teehan MD, and Bakish D; The impact of sertraline, desipramine, and placebo on psychomotor functioning in depression. Hum Psychopharmacol. 1995;10:4 273-281. CrossrefGoogle Scholar
    • 186. Reimherr FW, Cunningham LA, Batey SR, Johnston JA, and Ascher JA. A multicenter evaluation of the efficacy and safety of 150 and 300 mg/d sustained-release bupropion tablets versus placebo in depressed outpatients. Clin Ther. 1998;20:505-16. [PMID: 9663366] CrossrefMedlineGoogle Scholar
    • 187. Rickels K, Schweizer E, Clary C, Fox I, and Weise C. Nefazodone and imipramine in major depression: a placebo-controlled trial. Br J Psychiatry. 1994;164:802-5. [PMID: 7952987] CrossrefMedlineGoogle Scholar
    • 188. Rickels K and Case WG. Trazodone in depressed outpatients. Am J Psychiatry. 1982;139:803-6. [PMID: 7044154] CrossrefMedlineGoogle Scholar
    • 189. Rickels K, Amsterdam J, Clary C, Fox I, Schweizer E, and Weise C. The efficacy and safety of paroxetine compared with placebo in outpatients with major depression. J Clin Psychiatry. 1992;53: 30-2. [PMID: 1531820] MedlineGoogle Scholar
    • 190. Rosenbaum JF, Fava M, Hoog SL, Ascroft RC, and Krebs WB. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry. 1998;44:77-87. [PMID: 9646889] CrossrefMedlineGoogle Scholar
    • 191. Roth D, Mattes J, Sheehan KH, and Sheehan DV. A double-blind comparison of fluvoxamine, desipramine and placebo in outpatients with depression. Prog Neuropsychopharmacol Biol Psychiatry. 1990;14:929-39. [PMID: 2126144] CrossrefMedlineGoogle Scholar
    • 192. Roy-Byrne PP, Pages KP, Russo JE, Jaffe C, Blume AW, and Kingsley E; Nefazodone treatment of major depression in alcohol-dependent patients: a double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2000;20:129-36. [PMID: 10770449] CrossrefMedlineGoogle Scholar
    • 193. Rudolph RL, Fabre LF, Feighner JP, Rickels K, Entsuah R, and Derivan AT. A randomized, placebo-controlled, dose-response trial of venlafaxine hydrochloride in the treatment of major depression. J Clin Psychiatry. 1998;59:116-22. [PMID: 9541154] CrossrefMedlineGoogle Scholar
    • 194. Schweizer E, Weise C, Clary C, Fox I, and Rickels K. Placebo-controlled trial of venlafaxine for the treatment of major depression. J Clin Psychopharmacol. 1991;11:233-6. [PMID: 1918421] CrossrefMedlineGoogle Scholar
    • 195. Smith WT, Glaudin V, Panagides J, and Gilvary E. Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. Psychopharmacol Bull. 1990;26:191-6. [PMID: 2236455] MedlineGoogle Scholar
    • 196. Smith WT and Glaudin V. A placebo-controlled trial of paroxetine in the treatment of major depression. J Clin Psychiatry. 1992;53: 36-9. [PMID: 1531822] MedlineGoogle Scholar
    • 197. Stahl SM. Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline. Biol Psychiatry. 2000;48:894-901. [PMID: 11074227] CrossrefMedlineGoogle Scholar
    • 198. Thase ME, Entsuah AR, and Rudolph RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry. 2001;178:234-41. [PMID: 11230034] CrossrefMedlineGoogle Scholar
    • 199. Tollefson GD, Rampey AH, Beasley CM, Enas GG, and Potvin JH. Absence of a relationship between adverse events and suicidality during pharmacotherapy for depression. J Clin Psychopharmacol. 1994;14:163-9. [PMID: 8027412] CrossrefMedlineGoogle Scholar
    • 200. Beasley CM, Dornseif BE, Bosomworth JC, Sayler ME, Rampey AH, and Heiligenstein JH; Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression. BMJ. 1991;303:685-92. [PMID: 1833012] CrossrefMedlineGoogle Scholar
    • 201. Vartiainen H and Leinonen E. Double-blind study of mirtazapine and placebo in hospitalized patients with major depression. Eur Neuropsychopharmacol. 1994;4:145-50. [PMID: 7919944] CrossrefMedlineGoogle Scholar
    • 202. Wade A, Crawford GM, Angus M, Wilson R, and Hamilton L. A randomized, double-blind, 24-week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care. Int Clin Psychopharmacol. 2003;18:133-41. [PMID: 12702891] MedlineGoogle Scholar
    • 203. Wernicke JF, Dunlop SR, Dornseif BE, and Zerbe RL. Fixed-dose fluoxetine therapy for depression. Psychopharmacol Bull. 1987;23:164-8. [PMID: 3496625] MedlineGoogle Scholar
    • 204. Winokur A, DeMartinis NA, McNally DP, Gary EM, Cormier JL, and Gary KA. Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia. J Clin Psychiatry. 2003;64:1224-9. [PMID: 14658972] CrossrefMedlineGoogle Scholar
    • 205. Zanardi R, Franchini L, Gasperini M, Perez J, and Smeraldi E. Double-blind controlled trial of sertraline versus paroxetine in the treatment of delusional depression. Am J Psychiatry. 1996;153:1631-3. [PMID: 8942464] CrossrefMedlineGoogle Scholar
    • 206. Baldwin DS, Cooper JA, Huusom AK, and Hindmarch I. A double-blind, randomized, parallel-group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment discontinuation with escitalopram and paroxetine in patients with major depressive disorder. Int Clin Psychopharmacol. 2006;21:159-69. [PMID: 16528138] CrossrefMedlineGoogle Scholar
    • 207. Boulenger JP, Huusom AK, Florea I, Baekdal T, and Sarchiapone M. A comparative study of the efficacy of long-term treatment with escitalopram and paroxetine in severely depressed patients. Curr Med Res Opin. 2006;22:1331-41. [PMID: 16834832] CrossrefMedlineGoogle Scholar
    • 208. Dalery J and Honig A. Fluvoxamine versus fluoxetine in major depressive episode: a double-blind randomised comparison. Hum Psychopharmacol. 2003;18:379-84. [PMID: 12858325] CrossrefMedlineGoogle Scholar
    • 209. De Wilde J, Spiers R, Mertens C, Bartholom F, Schotte G, and Leyman S. A double-blind, comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients. Acta Psychiatr Scand. 1993;87:141-5. [PMID: 8447241] CrossrefMedlineGoogle Scholar
    • 210. Ekselius L and von Knorring L. Effect on sexual function of long-term treatment with selective serotonin reuptake inhibitors in depressed patients treated in primary care. J Clin Psychopharmacol. 2001;21:154-60. [PMID: 11270911] CrossrefMedlineGoogle Scholar
    • 211. Fava M, Judge R, Hoog SL, Nilsson ME, and Koke SC. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. J Clin Psychiatry. 2000;61:863-7. [PMID: 11105740] CrossrefMedlineGoogle Scholar
    • 212. Haffmans PM, Timmerman L, and Hoogduin CA. Efficacy and tolerability of citalopram in comparison with fluvoxamine in depressed outpatients: a double-blind, multicentre study. The LUCIFER Group. Int Clin Psychopharmacol. 1996;11:157-64. [PMID: 8923094] CrossrefMedlineGoogle Scholar
    • 213. Nemeroff CB, Ninan PT, Ballenger J, Lydiard RB, Feighner J, and Patterson WM; Double-blind multicenter comparison of fluvoxamine versus sertraline in the treatment of depressed outpatients. Depression. 1995;3:163-9. CrossrefGoogle Scholar
    • 214. Patris M, Bouchard JM, Bougerol T, Charbonnier JF, Chevalier JF, and Clerc G; Citalopram versus fluoxetine: a double-blind, controlled, multicentre, phase III trial in patients with unipolar major depression treated in general practice. Int Clin Psychopharmacol. 1996;11:129-36. [PMID: 8803650] MedlineGoogle Scholar
    • 215. Rapaport M, Coccaro E, Sheline Y, Perse T, Holland P, and Fabre L; A comparison of fluvoxamine and fluoxetine in the treatment of major depression. J Clin Psychopharmacol. 1996;16:373-8. [PMID: 8889909] CrossrefMedlineGoogle Scholar
    • 216. Tignol J. A double-blind, randomized, fluoxetine-controlled, multicenter study of paroxetine in the treatment of depression. J Clin Psychopharmacol. 1993;13:18S-22S. [PMID: 8106650] CrossrefMedlineGoogle Scholar
    • 217. Ventura D, Armstrong EP, Skrepnek GH, and Haim Erder M. Escitalopram versus sertraline in the treatment of major depressive disorder: a randomized clinical trial. Curr Med Res Opin. 2007;23:245-50. [PMID: 17288677] CrossrefMedlineGoogle Scholar
    • 218. Balls C, Quiros G, De Flores T, de la Torre J, Palao D, and Rojo L; The efficacy and tolerability of venlafaxine and paroxetine in outpatients with depressive disorder or dysthymia. Int Clin Psychopharmacol. 2000;15:43-8. [PMID: 10836286] CrossrefMedlineGoogle Scholar
    • 219. Goldstein DJ, Mallinckrodt C, Lu Y, and Demitrack MA. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. J Clin Psychiatry. 2002;63:225-31. [PMID: 11926722] CrossrefMedlineGoogle Scholar
    • 220. Mehtonen OP, Sgaard J, Roponen P, and Behnke K. Randomized, double-blind comparison of venlafaxine and sertraline in outpatients with major depressive disorder. Venlafaxine 631 Study Group. J Clin Psychiatry. 2000;61:95-100. [PMID: 10732656] CrossrefMedlineGoogle Scholar
    • 221. Montgomery SA, Huusom AK, and Bothmer J. A randomised study comparing escitalopram with venlafaxine XR in primary care patients with major depressive disorder. Neuropsychobiology. 2004;50:57-64. [PMID: 15179022] CrossrefMedlineGoogle Scholar
    • 222. Nierenberg AA, Greist JH, Mallinckrodt CH, Prakash A, Sambunaris A, and Tollefson GD; Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study. Curr Med Res Opin. 2007;23:401-16. [PMID: 17288694] CrossrefMedlineGoogle Scholar
    • 223. Schatzberg A and Roose S. A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression. Am J Geriatr Psychiatry. 2006;14:361-70. [PMID: 16582045] CrossrefMedlineGoogle Scholar
    • 224. Shelton RC, Haman KL, Rapaport MH, Kiev A, Smith WT, and Hirschfeld RM; A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder. J Clin Psychiatry. 2006;67:1674-81. [PMID: 17196045] CrossrefMedlineGoogle Scholar
    • 225. Silverstone PH and Ravindran A. Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. Venlafaxine XR 360 Study Group. J Clin Psychiatry. 1999;60:22-8. [PMID: 10074873] CrossrefMedlineGoogle Scholar
    • 226. Feiger A, Kiev A, Shrivastava RK, Wisselink PG, and Wilcox CS. Nefazodone versus sertraline in outpatients with major depression: focus on efficacy, tolerability, and effects on sexual function and satisfaction. J Clin Psychiatry. 1996;57: 53-62. [PMID: 8626364] MedlineGoogle Scholar
    • 227. Kasper S, Olivieri L, Di Loreto G, and Dionisio P. A comparative, randomised, double-blind study of trazodone prolonged-release and paroxetine in the treatment of patients with major depressive disorder. Curr Med Res Opin. 2005;21:1139-46. [PMID: 16083521] CrossrefMedlineGoogle Scholar
    • 228. Munizza C, Olivieri L, Di Loreto G, and Dionisio P. A comparative, randomized, double-blind study of trazodone prolonged-release and sertraline in the treatment of major depressive disorder. Curr Med Res Opin. 2006;22:1703-13. [PMID: 16968574] CrossrefMedlineGoogle Scholar
    • 229. Perry PJ, Garvey MJ, Kelly MW, Cook BL, Dunner FJ, and Winokur G. A comparative trial of fluoxetine versus trazodone in outpatients with major depression. J Clin Psychiatry. 1989;50:290-4. [PMID: 2668259] MedlineGoogle Scholar
    • 230. Halikas JA. Org 3770 (mirtazapine) versus trazodone: A placebo controlled trial in depressed elderly patients. Hum Psychopharmacol. 1995;10: S125-33. CrossrefGoogle Scholar
    • 231. van Moffaert M, de Wilde J, Vereecken A, Dierick M, Evrard JL, and Wilmotte J; Mirtazapine is more effective than trazodone: a double-blind controlled study in hospitalized patients with major depression. Int Clin Psychopharmacol. 1995;10:3-9. [PMID: 7622801] CrossrefMedlineGoogle Scholar
    • 232. Weisler RH, Johnston JA, Lineberry CG, Samara B, Branconnier RJ, and Billow AA. Comparison of bupropion and trazodone for the treatment of major depression. J Clin Psychopharmacol. 1994;14:170-9. [PMID: 8027413] CrossrefMedlineGoogle Scholar
    • 233. Weihs KL, Houser TL, Batey SR, Ascher JA, Bolden-Watson C, and Donahue RM; Continuation phase treatment with bupropion SR effectively decreases the risk for relapse of depression. Biol Psychiatry. 2002;51:753-61. [PMID: 11983189] CrossrefMedlineGoogle Scholar
    • 234. Hochstrasser B, Isaksen PM, Koponen H, Lauritzen L, Mahnert FA, and Rouillon F; Prophylactic effect of citalopram in unipolar, recurrent depression: placebo-controlled study of maintenance therapy. Br J Psychiatry. 2001;178:304-10. [PMID: 11282808] CrossrefMedlineGoogle Scholar
    • 235. Klysner R, Bent-Hansen J, Hansen HL, Lunde M, Pleidrup E, and Poulsen DL; Efficacy of citalopram in the prevention of recurrent depression in elderly patients: placebo-controlled study of maintenance therapy. Br J Psychiatry. 2002;181:29-35. [PMID: 12091260] CrossrefMedlineGoogle Scholar
    • 236. Kornstein SG, Bose A, Li D, Saikali KG, and Gandhi C. Escitalopram maintenance treatment for prevention of recurrent depression: a randomized, placebo-controlled trial. J Clin Psychiatry. 2006;67:1767-75. [PMID: 17196058] CrossrefMedlineGoogle Scholar
    • 237. Montgomery SA and Rasmussen JG. Citalopram 20 mg, citalopram 40 mg and placebo in the prevention of relapse of major depression. Int Clin Psychopharmacol. 1992;6: 71-3. [PMID: 1431025] CrossrefMedlineGoogle Scholar
    • 238. Robert P and Montgomery SA. Citalopram in doses of 20-60 mg is effective in depression relapse prevention: a placebo-controlled 6 month study. Int Clin Psychopharmacol. 1995;10: 29-35. [PMID: 7622809] CrossrefMedlineGoogle Scholar
    • 239. Rapaport MH, Bose A, and Zheng H. Escitalopram continuation treatment prevents relapse of depressive episodes. J Clin Psychiatry. 2004;65:44-9. [PMID: 14744167] CrossrefMedlineGoogle Scholar
    • 240. Schmidt ME, Fava M, Robinson JM, and Judge R. The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder. J Clin Psychiatry. 2000;61:851-7. [PMID: 11105738] CrossrefMedlineGoogle Scholar
    • 241. Dinan TG. Efficacy and safety of weekly treatment with enteric-coated fluoxetine in patients with major depressive disorder. J Clin Psychiatry. 2001;62: 48-52. [PMID: 11599649] MedlineGoogle Scholar
    • 242. Reimherr FW, Amsterdam JD, Quitkin FM, Rosenbaum JF, Fava M, and Zajecka J; Optimal length of continuation therapy in depression: a prospective assessment during long-term fluoxetine treatment. Am J Psychiatry. 1998;155:1247-53. [PMID: 9734550] CrossrefMedlineGoogle Scholar
    • 243. Michelson D, Amsterdam JD, Quitkin FM, Reimherr FW, Rosenbaum JF, and Zajecka J; Changes in weight during a 1-year trial of fluoxetine. Am J Psychiatry. 1999;156:1170-6. [PMID: 10450256] MedlineGoogle Scholar
    • 244. Terra JL and Montgomery SA. Fluvoxamine prevents recurrence of depression: results of a long-term, double-blind, placebo-controlled study. Int Clin Psychopharmacol. 1998;13:55-62. [PMID: 9669185] CrossrefMedlineGoogle Scholar
    • 245. Thase ME, Nierenberg AA, Keller MB, and Panagides J; Relapse Prevention Study Group. Efficacy of mirtazapine for prevention of depressive relapse: a placebo-controlled double-blind trial of recently remitted high-risk patients. J Clin Psychiatry. 2001;62:782-8. [PMID: 11816867] CrossrefMedlineGoogle Scholar
    • 246. Gelenberg AJ, Trivedi MH, Rush AJ, Thase ME, Howland R, and Klein DN; Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression. Biol Psychiatry. 2003;54:806-17. [PMID: 14550680] CrossrefMedlineGoogle Scholar
    • 247. Feiger AD, Bielski RJ, Bremner J, Heiser JF, Trivedi M, and Wilcox CS; Double-blind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression. Int Clin Psychopharmacol. 1999;14:19-28. [PMID: 10221638] CrossrefMedlineGoogle Scholar
    • 248. Claghorn JL and Feighner JP. A double-blind comparison of paroxetine with imipramine in the long-term treatment of depression. J Clin Psychopharmacol. 1993;13:23S-27S. [PMID: 8106652] CrossrefMedlineGoogle Scholar
    • 249. Montgomery SA and Dunbar G. Paroxetine is better than placebo in relapse prevention and the prophylaxis of recurrent depression. Int Clin Psychopharmacol. 1993;8:189-95. [PMID: 8263317] CrossrefMedlineGoogle Scholar
    • 250. Reynolds CF, Dew MA, Pollock BG, Mulsant BH, Frank E, and Miller MD; Maintenance treatment of major depression in old age. N Engl J Med. 2006;354:1130-8. [PMID: 16540613] CrossrefMedlineGoogle Scholar
    • 251. Lpine JP, Caillard V, Bisserbe JC, Troy S, Hotton JM, and Boyer P. A randomized, placebo-controlled trial of sertraline for prophylactic treatment of highly recurrent major depressive disorder. Am J Psychiatry. 2004;161:836-42. [PMID: 15121648] CrossrefMedlineGoogle Scholar
    • 252. Doogan DP and Caillard V. Sertraline in the prevention of depression. Br J Psychiatry. 1992;160:217-22. [PMID: 1540762] CrossrefMedlineGoogle Scholar
    • 253. Keller MB, Kocsis JH, Thase ME, Gelenberg AJ, Rush AJ, and Koran L; Maintenance phase efficacy of sertraline for chronic depression: a randomized, controlled trial. JAMA. 1998;280:1665-72. [PMID: 9831997] CrossrefMedlineGoogle Scholar
    • 254. Kocsis JH, Schatzberg A, Rush AJ, Klein DN, Howland R, and Gniwesch L; Psychosocial outcomes following long-term, double-blind treatment of chronic depression with sertraline vs placebo. Arch Gen Psychiatry. 2002;59:723-8. [PMID: 12150648] CrossrefMedlineGoogle Scholar
    • 255. Lustman PJ, Clouse RE, Nix BD, Freedland KE, Rubin EH, and McGill JB; Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2006;63:521-9. [PMID: 16651509] CrossrefMedlineGoogle Scholar
    • 256. Wilson KC, Mottram PG, Ashworth L, and Abou-Saleh MT. Older community residents with depression: long-term treatment with sertraline. Randomised, double-blind, placebo-controlled study. Br J Psychiatry. 2003;182:492-7. [PMID: 12777339] CrossrefMedlineGoogle Scholar
    • 257. Venlafaxine 335 Study Group. Venlafaxine versus placebo in the preventive treatment of recurrent major depression. J Clin Psychiatry. 2004;65:328-36. [PMID: 15096071] CrossrefMedlineGoogle Scholar
    • 258. Simon JS, Aguiar LM, Kunz NR, and Lei D. Extended-release venlafaxine in relapse prevention for patients with major depressive disorder. J Psychiatr Res. 2004;38:249-57. [PMID: 15003430] CrossrefMedlineGoogle Scholar
    • 259. Joliat MJ, Schmidt ME, Fava M, Zhang S, Michelson D, and Trapp NJ; Long-term treatment outcomes of depression with associated anxiety: efficacy of continuation treatment with fluoxetine. J Clin Psychiatry. 2004;65:373-8. [PMID: 15096077] CrossrefMedlineGoogle Scholar
    • 260. Khan A, Upton GV, Rudolph RL, Entsuah R, and Leventer SM. The use of venlafaxine in the treatment of major depression and major depression associated with anxiety: a dose-response study. Venlafaxine Investigator Study Group. J Clin Psychopharmacol. 1998;18:19-25. [PMID: 9472838] CrossrefMedlineGoogle Scholar
    • 261. Gillin JC, Rapaport M, Erman MK, Winokur A, and Albala BJ. A comparison of nefazodone and fluoxetine on mood and on objective, subjective, and clinician-rated measures of sleep in depressed patients: a double-blind, 8-week clinical trial. J Clin Psychiatry. 1997;58:185-92. [PMID: 9184611] CrossrefMedlineGoogle Scholar
    • 262. Mallinckrodt CH, Watkin JG, Liu C, Wohlreich MM, and Raskin J. Duloxetine in the treatment of Major Depressive Disorder: a comparison of efficacy in patients with and without melancholic features. BMC Psychiatry. 2005;5:1. [PMID: 15631624] CrossrefMedlineGoogle Scholar
    • 263. Detke MJ, Lu Y, Goldstein DJ, Hayes JR, and Demitrack MA. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry. 2002;63:308-15. [PMID: 12000204] CrossrefMedlineGoogle Scholar
    • 264. Detke MJ, Lu Y, Goldstein DJ, McNamara RK, and Demitrack MA. Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression. J Psychiatr Res. 2002;36:383-90. [PMID: 12393307] CrossrefMedlineGoogle Scholar
    • 265. Brambilla P, Cipriani A, Hotopf M, and Barbui C. Side-effect profile of fluoxetine in comparison with other SSRIs, tricyclic and newer antidepressants: a meta-analysis of clinical trial data. Pharmacopsychiatry. 2005;38:69-77. [PMID: 15744630] CrossrefMedlineGoogle Scholar
    • 266. Greist J, McNamara RK, Mallinckrodt CH, Rayamajhi JN, and Raskin J. Incidence and duration of antidepressant-induced nausea: duloxetine compared with paroxetine and fluoxetine. Clin Ther. 2004;26:1446-55. [PMID: 15531007] CrossrefMedlineGoogle Scholar
    • 267. Mackay FJ, Dunn NR, Wilton LV, Pearce GL, Freemantle SN, and Mann RD. A comparison of fluvoxamine, fluoxetine, sertraline and paroxetine examined by observational cohort studies. Pharmacoepidemiol Drug Saf. 1997;6:235-46. [PMID: 15073774] CrossrefMedlineGoogle Scholar
    • 268. Mackay FR, Dunn NR, Martin RM, Pearce GL, Freemantle SN, and Mann RD. Newer antidepressants: a comparison of tolerability in general practice. Br J Gen Pract. 1999;49:892-6. [PMID: 10818655] MedlineGoogle Scholar
    • 269. Mackay FJ, Dunn NR, and Mann RD. Antidepressants and the serotonin syndrome in general practice. Br J Gen Pract. 1999;49:871-4. [PMID: 10818650] MedlineGoogle Scholar
    • 270. Meijer WE, Heerdink ER, van Eijk JT, and Leufkens HG. Adverse events in users of sertraline: results from an observational study in psychiatric practice in The Netherlands. Pharmacoepidemiol Drug Saf. 2002;11:655-62. [PMID: 12512241] CrossrefMedlineGoogle Scholar
    • 271. Goldstein DJ, Hamilton SH, Masica DN, and Beasley CM. Fluoxetine in medically stable, depressed geriatric patients: effects on weight. J Clin Psychopharmacol. 1997;17:365-9. [PMID: 9315987] CrossrefMedlineGoogle Scholar
    • 272. Harto NE, Spera KF, and Branconnier RJ. Fluoxetine-induced reduction of body mass in patients with major depressive disorder. Psychopharmacol Bull. 1988;24:220-3. [PMID: 3264922] MedlineGoogle Scholar
    • 273. Judge R, Parry MG, Quail D, and Jacobson JG. Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment. Int Clin Psychopharmacol. 2002;17:217-25. [PMID: 12177584] CrossrefMedlineGoogle Scholar
    • 274. Perahia DG, Kajdasz DK, Desaiah D, and Haddad PM. Symptoms following abrupt discontinuation of duloxetine treatment in patients with major depressive disorder. J Affect Disord. 2005;89:207-12. [PMID: 16266753] CrossrefMedlineGoogle Scholar
    • 275. Zajecka J, Fawcett J, Amsterdam J, Quitkin F, Reimherr F, and Rosenbaum J; Safety of abrupt discontinuation of fluoxetine: a randomized, placebo-controlled study. J Clin Psychopharmacol. 1998;18:193-7. [PMID: 9617977] CrossrefMedlineGoogle Scholar
    • 276. Pedersen AG. Escitalopram and suicidality in adult depression and anxiety. Int Clin Psychopharmacol. 2005;20:139-43. [PMID: 15812263] CrossrefMedlineGoogle Scholar
    • 277. Clayton AH, Pradko JF, Croft HA, Montano CB, Leadbetter RA, and Bolden-Watson C; Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry. 2002;63:357-66. [PMID: 12000211] CrossrefMedlineGoogle Scholar
    • 278. Clayton AH, Croft HA, Horrigan JP, Wightman DS, Krishen A, and Richard NE; Bupropion extended release compared with escitalopram: effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies. J Clin Psychiatry. 2006;67:736-46. [PMID: 16841623] CrossrefMedlineGoogle Scholar
    • 279. Delgado PL, Brannan SK, Mallinckrodt CH, Tran PV, McNamara RK, and Wang F; Sexual functioning assessed in 4 double-blind placebo- and paroxetine-controlled trials of duloxetine for major depressive disorder. J Clin Psychiatry. 2005;66:686-92. [PMID: 15960560] CrossrefMedlineGoogle Scholar
    • 280. Ferguson JM, Shrivastava RK, Stahl SM, Hartford JT, Borian F, and Ieni J; Reemergence of sexual dysfunction in patients with major depressive disorder: double-blind comparison of nefazodone and sertraline. J Clin Psychiatry. 2001;62:24-9. [PMID: 11235924] CrossrefMedlineGoogle Scholar
    • 281. Landn M, Hgberg P, and Thase ME. Incidence of sexual side effects in refractory depression during treatment with citalopram or paroxetine. J Clin Psychiatry. 2005;66:100-6. [PMID: 15669895] CrossrefMedlineGoogle Scholar
    • 282. Nieuwstraten CE and Dolovich LR. Bupropion versus selective serotonin-reuptake inhibitors for treatment of depression. Ann Pharmacother. 2001;35:1608-13. [PMID: 11793630] CrossrefMedlineGoogle Scholar
    • 283. Philipp M, Tiller JW, Baier D, and Kohnen R. Comparison of moclobemide with selective serotonin reuptake inhibitors (SSRIs) on sexual function in depressed adults. The Australian and German Study Groups. Eur Neuropsychopharmacol. 2000;10:305-14. [PMID: 10974600] CrossrefMedlineGoogle Scholar
    • 284. Dunner DL, Zisook S, Billow AA, Batey SR, Johnston JA, and Ascher JA. A prospective safety surveillance study for bupropion sustained-release in the treatment of depression. J Clin Psychiatry. 1998;59:366-73. [PMID: 9714265] CrossrefMedlineGoogle Scholar
    • 285. Johnston JA, Lineberry CG, Ascher JA, Davidson J, Khayrallah MA, and Feighner JP; A 102-center prospective study of seizure in association with bupropion. J Clin Psychiatry. 1991;52:450-6. [PMID: 1744061] MedlineGoogle Scholar
    • 286. Whyte IM, Dawson AH, and Buckley NA. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. QJM. 2003;96:369-74. [PMID: 12702786] CrossrefMedlineGoogle Scholar
    • 287. Thase ME. Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients. J Clin Psychiatry. 1998;59:502-8. [PMID: 9818630] CrossrefMedlineGoogle Scholar
    • 288. Thase ME, Tran PV, Wiltse C, Pangallo BA, Mallinckrodt C, and Detke MJ. Cardiovascular profile of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine. J Clin Psychopharmacol. 2005;25:132-40. [PMID: 15738744] CrossrefMedlineGoogle Scholar
    • 289. Buckley NA and McManus PR. Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. BMJ. 2002;325:1332-3. [PMID: 12468481] CrossrefMedlineGoogle Scholar
    • 290. Coogan PF, Palmer JR, Strom BL, and Rosenberg L. Use of selective serotonin reuptake inhibitors and the risk of breast cancer. Am J Epidemiol. 2005;162:835-8. [PMID: 16177141] CrossrefMedlineGoogle Scholar
    • 291. Kirby D, Harrigan S, and Ames D. Hyponatraemia in elderly psychiatric patients treated with selective serotonin reuptake inhibitors and venlafaxine: a retrospective controlled study in an inpatient unit. Int J Geriatr Psychiatry. 2002;17:231-7. [PMID: 11921151] CrossrefMedlineGoogle Scholar
    • 292. Thapa PB, Gideon P, Cost TW, Milam AB, and Ray WA. Antidepressants and the risk of falls among nursing home residents. N Engl J Med. 1998;339:875-82. [PMID: 9744971] CrossrefMedlineGoogle Scholar
    • 293. Burt VK, Wohlreich MM, Mallinckrodt CH, Detke MJ, Watkin JG, and Stewart DE. Duloxetine for the treatment of major depressive disorder in women ages 40 to 55 years. Psychosomatics. 2005;46:345-54. [PMID: 16000678] CrossrefMedlineGoogle Scholar
    • 294. Kranzler HR, Mueller T, Cornelius J, Pettinati HM, Moak D, and Martin PR; Sertraline treatment of co-occurring alcohol dependence and major depression. J Clin Psychopharmacol. 2006;26:13-20. [PMID: 16415699] CrossrefMedlineGoogle Scholar
    • 295. Addington D, Addington J, Patten S, Remington G, Moamai J, and Labelle A; Double-blind, placebo-controlled comparison of the efficacy of sertraline as treatment for a major depressive episode in patients with remitted schizophrenia. J Clin Psychopharmacol. 2002;22:20-5. [PMID: 11799338] CrossrefMedlineGoogle Scholar
    • 296. Burke WJ and McArthur-Miller DA. Exploring treatment alternatives: weekly dosing of fluoxetine for the continuation phase of major depressive disorder. J Clin Psychiatry. 2001;62: 38-42. [PMID: 11599647] MedlineGoogle Scholar
    • 297. Claghorn J. A double-blind comparison of paroxetine and placebo in the treatment of depressed outpatients. Int Clin Psychopharmacol. 1992;6: 25-30. [PMID: 1431007] CrossrefMedlineGoogle Scholar
    • 298. Claghorn JL, Kiev A, Rickels K, Smith WT, and Dunbar GC. Paroxetine versus placebo: a double-blind comparison in depressed patients. J Clin Psychiatry. 1992;53:434-8. [PMID: 1487471] MedlineGoogle Scholar
    • 299. Cohn CK, Robinson DS, Roberts DL, Schwiderski UE, O'Brien K, and Ieni JR. Responders to antidepressant drug treatment: a study comparing nefazodone, imipramine, and placebo in patients with major depression. J Clin Psychiatry. 1996;57: 15-8. [PMID: 8626358] MedlineGoogle Scholar
    • 300. Cunningham LA. Once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression. Venlafaxine XR 208 Study Group. Ann Clin Psychiatry. 1997;9:157-64. [PMID: 9339881] CrossrefMedlineGoogle Scholar
    • 301. Feighner JP and Over K. Multicenter, placebo-controlled, fixed-dose study of citalopram in moderate-to-severe depression. J Clin Psychiatry. 1999;60:824-30. [PMID: 10665628] CrossrefMedlineGoogle Scholar
    • 302. Fontaine R, Ontiveros A, Elie R, Kensler TT, Roberts DL, and Kaplita S; A double-blind comparison of nefazodone, imipramine, and placebo in major depression. J Clin Psychiatry. 1994;55:234-41. [PMID: 8071277] MedlineGoogle Scholar
    • 303. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized, controlled trial. JAMA. 2002;287:1807-14. [PMID: 11939866] CrossrefMedlineGoogle Scholar
    • 304. Khan A, Fabre LF, and Rudolph R. Venlafaxine in depressed outpatients. Psychopharmacol Bull. 1991;27:141-4. [PMID: 1924660] MedlineGoogle Scholar
    • 305. Lineberry CG, Johnston JA, Raymond RN, Samara B, Feighner JP, and Harto NE; A fixed-dose (300 mg) efficacy study of bupropion and placebo in depressed outpatients. J Clin Psychiatry. 1990;51:194-9. [PMID: 2110559] MedlineGoogle Scholar
    • 306. Lydiard RB, Laird LK, Morton WA, Steele TE, Kellner C, and Laraia MT; Fluvoxamine, imipramine, and placebo in the treatment of depressed outpatients: effects on depression. Psychopharmacol Bull. 1989;25:68-70. [PMID: 2505304] MedlineGoogle Scholar
    • 307. Lydiard RB, Stahl SM, Hertzman M, and Harrison WM. A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression. J Clin Psychiatry. 1997;58:484-91. [PMID: 9413414] CrossrefMedlineGoogle Scholar
    • 308. Mendels J, Johnston R, Mattes J, and Riesenberg R. Efficacy and safety of b.i.d. doses of venlafaxine in a dose-response study. Psychopharmacol Bull. 1993;29:169-74. [PMID: 8290661] MedlineGoogle Scholar
    • 309. Mendels J, Reimherr F, Marcus RN, Roberts DL, Francis RJ, and Anton SF. A double-blind, placebo-controlled trial of two dose ranges of nefazodone in the treatment of depressed outpatients. J Clin Psychiatry. 1995;56: 30-6. [PMID: 7649971] MedlineGoogle Scholar
    • 310. Olie JP, Gunn KP, and Katz E. A double-blind placebo-controlled multicentre study of sertraline in the acute and continuation treatment of major depression. Eur Psychiatry. 1997;12:34-41. CrossrefMedlineGoogle Scholar
    • 311. Reimherr FW, Chouinard G, Cohn CK, Cole JO, Itil TM, and LaPierre YD; Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression. J Clin Psychiatry. 1990;51: 18-27. [PMID: 2258378] MedlineGoogle Scholar
    • 312. Reimherr FW, Byerley WF, Ward MF, Lebegue BJ, and Wender PH. Sertraline, a selective inhibitor of serotonin uptake, for the treatment of outpatients with major depressive disorder. Psychopharmacol Bull. 1988;24:200-5. [PMID: 3290941] MedlineGoogle Scholar
    • 313. Rickels K, Amsterdam J, Clary C, Fox I, Schweizer E, and Weise C. A placebo-controlled, double-blind, clinical trial of paroxetine in depressed outpatients. Acta Psychiatr Scand Suppl. 1989;350:117-23. [PMID: 2530761] CrossrefMedlineGoogle Scholar
    • 314. Shrivastava RK, Shrivastava SH, Overweg N, and Blumhardt CL. A double-blind comparison of paroxetine, imipramine, and placebo in major depression. J Clin Psychiatry. 1992;53: 48-51. [PMID: 1531825] MedlineGoogle Scholar
    • 315. Thase ME. Efficacy and tolerability of once-daily venlafaxine extended release (XR) in outpatients with major depression. The Venlafaxine XR 209 Study Group. J Clin Psychiatry. 1997;58:393-8. [PMID: 9378690] CrossrefMedlineGoogle Scholar
    • 316. Heiligenstein JH, Ware JE, Beusterien KM, Roback PJ, Andrejasich C, and Tollefson GD. Acute effects of fluoxetine versus placebo on functional health and well-being in late-life depression. Int Psychogeriatr. 1995;7: 125-37. [PMID: 8580388] CrossrefMedlineGoogle Scholar
    • 317. Trivedi MH, Pigotti TA, Perera P, Dillingham KE, Carfagno ML, and Pitts CD. Effectiveness of low doses of paroxetine controlled release in the treatment of major depressive disorder. J Clin Psychiatry. 2004;65:1356-64. [PMID: 15491239] CrossrefMedlineGoogle Scholar
    • 318. Wade A, Michael Lemming O, and Bang Hedegaard K. Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol. 2002;17:95-102. [PMID: 11981349] CrossrefMedlineGoogle Scholar
    • 319. Walczak DD, Apter JT, Halikas JA, Borison RL, Carman JS, and Post GL; The oral dose-effect relationship for fluvoxamine: a fixed-dose comparison against placebo in depressed outpatients. Ann Clin Psychiatry. 1996;8:139-51. [PMID: 8899132] CrossrefMedlineGoogle Scholar

    Comments

    0 Comments
    Sign In to Submit A Comment
    Thomas E. Finucane5 December 2008
    Comparative Benefits and Harms of Second-Generation Antidepressants

    Dr. Gartlehner and colleague's Background Paper on the comparative benefits and harms of second-generation antidepressants (SGAs) finds "no substantial differences in efficacy among these drugs," but notes that "other differences" may be relevant in choosing a drug (1). They also note that 69% of the studies were supported by the pharmaceutical industry, and for 21% of the studies, source of funding could not be determined. Drug company funding has a strong impact on the published literature. Companies naturally tend to seek publication of results favorable to their products (2).

    Seven fair quality studies are cited, all showing that mirtazapine leads to higher weight gain than other SGAs; not shown is that all seven studies are sponsored by mirtazapine's vendor, Organon, and that three of the seven have at least one author who is a drug company employee. Without any good evidence, a market niche for mirtazapine has been created: depressed patients who are losing weight.

    Writers of systematic reviews must decide how to weigh vendor-sponsored evidence, especially when most or all of the available evidence is vendor-sponsored. Here is a modest suggestion. In bibliographies, why not make the first initial of the first author scarlet if the paper is sponsored by the vendor? This would make it easy to see where the influence of industry might be suspected.

    References

    1. Gartlehner G, Gaynes BN, Hansen RA, Thieda P, DeVeaugh-Geiss A, Krebs EE, Moore CG, et al. Comparative benefits and harms of second-generation antidepressants: Background paper for the American College of Physicians. Ann Intern Med. 2008; 149: 734-750.

    2. Rising K, Bacchetti P, Bero L. Reporting bias in drug trials submitted to the Food and Drug Administration: A review of publication and presentation. PLoS Med 2008; 5(11): e217: 0001-10.

    Conflict of Interest:

    None declared

    Previous
    Next

    Submit a Comment

    Contributors must reveal any conflict of interest. Comments are moderated. Please see our information for authorsregarding comments on an Annals publication.
    *All comments submitted after October 1, 2021 and selected for publication will be published online only.
    Cancel