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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    • "Given the prevalence and severity of major depressive disorder , it is not surprising that antidepressants are the most frequently prescribed medication in the USA for 18-to 44- year-olds, with one in ten people over the age of 12 using these drugs (Pratt et al. 2011). For adults, there is a large and diverse group of effective medications available for the treatment of depression (Gartlehner et al. 2011;Hirschfeld 2012), although the selective serotonin reuptake inhibitors (SSRIs) have become predominate over the last few decades (Pratt et al. 2011). The popularity of SSRIs stems from their safety and side-effect profiles, as well as their effectiveness at reducing symptoms of depression and anxiety (Cipriani et al. 2009). "
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    ABSTRACT: The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine. In experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In experiment 2, rats were injected with paroxetine (2.5, 5, or 10 mg/kg), fluoxetine (5, 10, or 20 mg/kg), or vehicle during the same time frame as experiment 1, and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle. Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration. These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors.
    Preview · Article · Jul 2015 · Psychopharmacology
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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.
    Full-text · Article · Jan 2015 · Journal of Psychopharmacology
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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.
    Full-text · Article · Oct 2014 · General Hospital Psychiatry
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