Comparative Benefits and Harms of Second-Generation Antidepressants for Treating Major Depressive Disorder

Danube University, Krems, Austria.
Annals of internal medicine (Impact Factor: 17.81). 12/2011; 155(11):772-85. DOI: 10.1059/0003-4819-155-11-201112060-00009
Source: PubMed


Second-generation antidepressants dominate the management of major depressive disorder (MDD), but evidence on the comparative benefits and harms of these agents is contradictory.
To compare the benefits and harms of second-generation antidepressants for treating MDD in adults.
English-language studies from PubMed, Embase, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to August 2011 and reference lists of pertinent review articles and gray literature.
2 independent reviewers identified randomized trials of at least 6 weeks' duration to evaluate efficacy and observational studies with at least 1000 participants to assess harm.
Reviewers abstracted data about study design and conduct, participants, and interventions and outcomes and rated study quality. A senior reviewer checked and confirmed extracted data and quality ratings.
Meta-analyses and mixed-treatment comparisons of response to treatment and weighted mean differences were conducted on specific scales to rate depression. On the basis of 234 studies, no clinically relevant differences in efficacy or effectiveness were detected for the treatment of acute, continuation, and maintenance phases of MDD. No differences in efficacy were seen in patients with accompanying symptoms or in subgroups based on age, sex, ethnicity, or comorbid conditions. Individual drugs differed in onset of action, adverse events, and some measures of health-related quality of life.
Most trials were conducted in highly selected populations. Publication bias might affect the estimates of some comparisons. Mixed-treatment comparisons cannot conclusively exclude differences in efficacy. Evidence within subgroups was limited.
Current evidence does not warrant recommending a particular second-generation antidepressant on the basis of differences in efficacy. Differences in onset of action and adverse events may be considered when choosing a medication.
Agency for Healthcare Research and Quality.

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    • "2. Even though TCAs carry a heavier side-effect burden and risk of serious toxicity than do the SRIs (Anderson et al., 2008), the newer drugs are not without their problems , including: drug-drug interactions, bleeding risk, sexual dysfunction, weight gain and discontinuation syndrome (Baldwin et al., 2007; Gartlehner et al., 2011; Muscatello et al., 2012). Taken together with their modest effect on sleep enhancement, it is clear that the SRI drugs have their shortcomings in treating PTSD and that they are far from being adequate replacements for older generation drugs. "
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    ABSTRACT: Serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitors (SSRI) are the first-line recommended drug treatments for post-traumatic stress disorder (PTSD); but despite their benefits, much residual pathology remains and no new drugs have yet emerged with a clearly demonstrated benefit for treating the disorder. A case is made that tricyclic drugs deserve a closer look, based on their ability to affect several of the main neurotransmitters that are relevant to PTSD. Their promising efficacy, which was shown 30 years ago, had not been followed up, until a recent trial of desipramine found advantages over a SSRI in PTSD with comorbid alcohol dependence. Opportunities exist for studying newer and purportedly safer tricyclic formulations, as well as further the work with older, established compounds. A reappraisal of their risk:benefit ratio seems in order, when treating PTSD. © The Author(s) 2015.
    Journal of Psychopharmacology 01/2015; 29(3). DOI:10.1177/0269881114565143 · 3.59 Impact Factor
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    • "Accordingly, two SSRIS drugs of fluoxetine and sertraline were associated with more impairment in sexual dysfunction items in under treated patients, while trazodone was associated with improvement in these items. SSRI-induced sexual dysfunction has been reported in previous studies [6] [7] [8] [9] [10] [11]. "
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    ABSTRACT: Background: Selective serotonin reuptake inhibitors (SSRIs) are common treatments for patients with major depressive disorder (MDD). However, adverse effects of SSRIs on sexual function are common in the treatment of patients with MDD. There is a discrepancy in the reported frequency of SSRI-induced sexual dysfunction. On the other hand, there is also less evidence about sexual dysfunction with serotonin receptor antagonists and reuptake inhibitors (SARIs). Therefore, we aimed to assess sexual dysfunction in MDD patients who received fluoxetine, sertraline and trazodone. Method: In a single-blind, randomized, controlled trial in Kermanshah, Iran, during 2009-2010, 195 patients who met the DSMIV-IR criteria for MDD were enrolled. The patients completed the Hamilton Depression Rating Scale (HAM-D) and the sexual function questionnaire (SFQ). Eligible patients were allocated in three treatment groups (receiving fluoxetine, sertraline or trazodone) for 14 weeks randomly. Measurement of HAMD was repeated in 4-week interval. Analysis for comparing sexual dysfunction among three groups and men and women was performed. Results: There were 102 men and 93 women in the three groups receiving fluoxetine (n=64), sertraline (n=67) and trazodone (n=64). There was no significant difference in the sexual dysfunction of the patients in the three groups at baseline (P>.05). After treatment, both men and women who had received fluoxetine had the most impairment in desire/drive items (43%-51% and 44%-50%, respectively), while patients receiving trazodone had the least impairment in these items (12%-18% and 23%-24%, respectively). Trazodone was also induced with a lower rate of impairment in arousal/orgasm items in men (9%-15%) compared with the other two drugs. Compared with fluoxetine and trazodone, sertraline was associated with intermediate impairment in sexual function (39%-42% in desire/drive items and 32%-39% in arousal/orgasm items) that was lower than that with fluoxetine and more than that with trazodone. Conclusion: There were different rates of sexual dysfunction with different antidepressants drugs in under treated patients. Compared with fluoxetine, and sertraline, trazodone was associated with the fewest sexual dysfunction. Fluoxetine was also associated with more sexual dysfunction than sertraline. Further research to better identify the differences among antidepressant drugs is recommended.
    General Hospital Psychiatry 10/2014; 37(1). DOI:10.1016/j.genhosppsych.2014.10.010 · 2.61 Impact Factor
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    • "Different adverse effects were experienced by Chinese patients treated with acupuncture (needling pain, transient dizziness, and nausea) and with SSRI (headache, insomnia, and tiredness). There were no significant differences in effectiveness between different SSRIs, which confirmed the findings of Gartlehner et al. [33]. "
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    ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) have become the most frequently used antidepressants in China in recent decades. This systematic review and meta-analysis examined the efficacy and tolerability of SSRIs in Chinese studies and the quality of Chinese randomized controlled trials. Major Western and Chinese electronic databases were searched for double-blind, parallel group randomised controlled trials (RCTs) comparing SSRIs (fluoxetine, citalopram, escitalopram, fluvoxamine, paroxetine, or sertraline) with other antidepressants such as SSRI, Selective Noradrenaline Reuptake Inhibitor (SNRI), tricyclic antidepressant (TCA), Traditional Chinese Medicine (TCM) and/or placebo. Response, remission, and dropout rates due to side effects were defined as primary outcomes. Mean total Hamilton Rating Scale of Depression (HAMD) scores at endpoint, overall dropout rates and total Treatment Emergent Symptom Scale (TESS) scores were defined as secondary outcomes. Data were combined with random effects models. Risk of bias was assessed by the Cochrane evaluation tool. Quality of reports was assessed by the fulfilment of Consolidated Standards of Reporting Trial (CONSORT) items. A total of 71 studies were included. Only one study was listed in both Chinese and Western databases. SSRIs were found to be more effective than TCAs. No significant differences were observed regarding dropout rates due to side effects. Using the Cochrane risk of bias tool, adequate methods of sequence generation were described in 16 (23%) studies. All authors failed to report trial registration. Informed consent, sources of funding, email address, protocol, and limitations were also not mentioned in most studies. However, reporting quality improved steadily between 1996 and 2013. In light of the low trial quality, the findings of a significant advantage of SSRI over TCA in terms of response rate and remission rate should be replicated by large high-quality Chinese studies.
    BMC Psychiatry 08/2014; 14(1):245. DOI:10.1186/s12888-014-0245-4 · 2.21 Impact Factor
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