Antidepressant Medications: 66 Recent Meta-Analyses

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Antidepressant Medications: 66 Meta-Analytic Studies Published in 2013-2016

Kenneth S. Pope, Ph.D., APBB

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This site includes 3 related pages of meta-analytic resources:

For each brand name and generic antidepressant medication, I searched out meta-analytic studies on its uses, effectiveness, risks, side effects, differential effects on different populations, etc.--to help clinicians, expert witnesses, researchers, and others to stay abreast of the evolving research in this area. I focused on studies published in 2013-16, and included both the citation and a brief excerpt for each study.

  1. Anglin, R., et al. (2014). "Risk of Upper Gastrointestinal Bleeding With Selective Serotonin Reuptake Inhibitors With or Without Concurrent NonSteroidal Anti-Inflammatory Use: A Systematic Review and Meta-Analysis." Am J Gastroenterol, pp. 811-819.

    EXCERPT: SSRI medications are associated with a modest increase in the risk of upper GI bleeding....  This risk is significantly elevated when SSRI medications are used in combination with NSAIDs, and physicians prescribing these medications together should exercise caution and discuss this risk with patients.".

  2. Bhattacharjee, S., et al. (2013). "Antidepressant use and new-onset diabetes: a systematic review and meta-analysis." Diabetes Metab Res Rev 29(4): 273-284.

    EXCERPT: "Among adults, antidepressant use was associated with higher chances of new-onset diabetes. However, because a cause-and-effect relationship cannot be established by observational studies, future randomized controlled studies are needed to confirm this association."

  3. Bushe, C. J. and N. C. Savill (2013). "Suicide related events and attention deficit hyperactivity disorder treatments in children and adolescents: a meta-analysis of atomoxetine and methylphenidate comparator clinical trials." Child Adolesc Psychiatry Ment Health 7(1): 19.

    EXCERPT: "Meta-analysis finds no difference of a difference in risk between ATX and MPH with a Mantel-Haenszel risk ratio of 0.52 (95% CI; 0.06, 4.54)."

  4. Bushe, C. J. and N. C. Savill (2013). "Systematic review of atomoxetine data in childhood and adolescent attention-deficit hyperactivity disorder 2009-2011: Focus on clinical efficacy and safety." J Psychopharmacol.

    EXCERPT: "Atomoxetine has an onset of action within 4 weeks (possibly within 1 week in subsequent responders) but requires at least 12 weeks for full response to be demonstrated. Treatment-naive cohorts (6-12 weeks) report effect sizes of 0.6-1.3. Using minimum 6-week clinical trial criteria, atomoxetine may demonstrate similar efficacy to methylphenidate comparing reduction in core ADHD symptoms in meta-analysis, although the diversity of the data makes interpretation complex."

  5. Chan, Y.-Y., et al. (2015). "The benefit of combined acupuncture and antidepressant medication for depression: A systematic review and meta-analysis." Journal of Affective Disorders 176: 106-117.

    EXCERPT: "This systematic review and meta-analysis suggest that acupuncture combined with antidepressant medication is effective, has an early onset of action, safe and well-tolerated over the first 6-week treatment period. Moreover, this treatment combination appears to result in greater therapeutic efficacy than SSRI therapy alone."

  6. Chao, G. Q. and S. Zhang (2013). "A meta-analysis of the therapeutic effects of amitriptyline for treating irritable bowel syndrome." Intern Med 52(4): 419-424.

    EXCERPT: "The pooled relative risk for clinical improvement with amitriptyline therapy was 4.18 (95% CI: 2.00 to 8.77, p=0.0001).... It was thus concluded that amitriptyline exhibits a clinically and statistically significant control of IBS symptoms."

  7. Coyle, C. M. and K. R. Laws (2015). "The use of ketamine as an antidepressant: a systematic review and meta-analysis." Hum Psychopharmacol 30(3): 152-163.

    EXCERPT: "Effect sizes were significantly larger for repeat than single infusion at 4 h, 24 h and 7 days. For single infusion studies, effect sizes were large and significant at 4 h, 24 h and 7 days. The percentage of males was a predictor of antidepressant response at 7 days. Effect sizes for open-label and participant-blind infusions were not significantly different at any time point.... Single ketamine infusions elicit a significant antidepressant effect from 4 h to 7 days; the small number of studies at 12-14 days post infusion failed to reach significance. Results suggest a discrepancy in peak response time depending upon primary diagnosis - 24 h for MDD and 7 days for BD."

  8. Cuijpers, P., et al. (2014). "Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta-analysis." World Psychiatry 13(1): 56-67.

    EXCERPT: "The overall difference between pharmacotherapy and combined treatment was Hedges' g = 0.43 (95% CI: 0.31-0.56), indicating a moderately large effect and clinically meaningful difference in favor of combined treatment....  There was sufficient evidence that combined treatment is superior for major depression, panic disorder, and obsessive-compulsive disorder (OCD). The effects of combined treatment compared with placebo only were about twice as large as those of pharmacotherapy compared with placebo only, underscoring the clinical advantage of combined treatment. The results also suggest that the effects of pharmacotherapy and those of psychotherapy are largely independent from each other, with both contributing about equally to the effects of combined treatment. We conclude that combined treatment appears to be more effective than treatment with antidepressant medication alone in major depression, panic disorder, and OCD. These effects remain strong and significant up to two years after treatment. Monotherapy with psychotropic medication may not constitute optimal care for common mental disorders."

  9. Cunill, R., et al. (2013). "Atomoxetine for attention deficit hyperactivity disorder in the adulthood: a meta-analysis and meta-regression." Pharmacoepidemiol Drug Saf 22(9): 961-969.

    EXCERPT: "Treatment discontinuation was larger with atomoxetine than with placebo.... No co-variable was found to modify the effect of atomoxetine over treatment discontinuation. Atomoxetine showed modest efficacy in reducing ADHD symptoms irrespective of the assessor: patient...; clinician.... The rate of adverse events-induced discontinuation was higher with atomoxetine than with placebo.... This study suggests that atomoxetine has a poor benefit-risk balance for the treatment of adults with ADHD. The recommendation of atomoxetine use in this population is weak." Gorwood, P., et al. (2013). "Is it worth assessing progress as early as week 2 to adapt antidepressive treatment strategy? Results from a study on agomelatine and a global meta-analysis." Eur Psychiatry 28(6): 362-371.

  10. Ehret, M. and D. M. Sobieraj (2014). "Prevention of interferon-alpha-associated depression with antidepressant medications in patients with hepatitis C virus: a systematic review and meta-analysis." Int J Clin Pract 68(2): 255-261.

    EXCERPT: "SSRIs prevent depression in patients with HCV treated with INF-alpha therapy. The impact of SSRIs on completion of antiviral therapy or on the development of adverse events is less clear."

  11. Fu, J. and Y. Chen (2014). "The efficacy and safety of 5 mg/d Vortioxetine compared to placebo for major depressive disorder: A meta-analysis." Psychopharmacology, in press.

    EXCERPT: "For the treatment of major depressive disorder, our results show that a dose of 5 mg/day vortioxetine was more effective, but more easily induced nausea, compared to placebo."

  12. Galling, B., et al. (2015). "Safety and tolerability of antidepressant co-treatment in acute major depressive disorder: results from a systematic review and exploratory meta-analysis." Expert Opin Drug Saf: 1-22.

    EXCERPT: "AD + AD co-treatment was associated with significantly greater burden regarding 4/25 AEs (tremor: RR = 1.55, 95% CI = 1.01 - 2.38; sweating: RR = 1.95, 95% CI = 1.13 -3.38, >/= 7% weight gain: RR = 3.15, 95% CI = 1.34 - 7.41; weight gain = 2.17, 95% CI = 0.71 - 3.63 kg), but not more CNS, gastrointestinal, sexual or alertness-related AEs. However, 11/25 AEs (44.0%) were reported in only 1 - 2 studies. Adding noradrenergic and specific serotonergic antidepressants (NaSSA) or tricyclic antidepressants (TCA) to selective serotonin reuptake inhibitors (SSRIs) was specifically associated with more AEs.... The potential for increased AEs with AD + AD co-treatment needs to be considered vis-a-vis unclear efficacy benefits of this strategy. In particular, NaSSAs and TCAs should be added to SSRIs with caution."

  13. GENDEP Investigators; MARS Investigators; STAR*D Investigators. (2013). "Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies." Am J Psychiatry 170(2): 207-217.

    EXCERPT: "No individual association met a genome-wide threshold for statistical significance in the primary analyses. A polygenic score derived from a meta-analysis of GENDEP and MARS participants accounted for up to approximately 1.2% of the variance in outcomes in STAR*D, suggesting a weakly concordant signal distributed over many polymorphisms. An analysis restricted to 1,354 individuals treated with citalopram (STAR*D) or escitalopram (GENDEP) identified an intergenic region on chromosome 5 associated with early improvement after 2 weeks of treatment.... Despite increased statistical power accorded by meta-analysis, the authors identified no reliable predictors of antidepressant treatment outcome, although they did identify modest, direct evidence that common genetic variation contributes to individual differences in antidepressant response."

  14. Gorwood, P., et al. (2013). "Is it worth assessing progress as early as week 2 to adapt antidepressive treatment strategy? Results from a study on agomelatine and a global meta-analysis." Eur Psychiatry 28(6): 362-371.

    EXCERPT: "The meta-analysis of all studies also detected a large effect size of early improvement, stressing how rating week 2 severity could be beneficial in clinical practice.... Previous reports stressing the interest of an assessment at week 2 were reinforced by the present results, which also defined more accurately what could be the most appropriate cut-offs, and how combining these early results could be more effective."

  15. Grigoriadis, S., et al. (2013). "Antidepressant exposure during pregnancy and congenital malformations: Is there an association? A systematic review and meta-analysis of the best evidence." Journal of Clinical Psychiatry 74(4): e293-e308.

    EXCERPT: "Overall, antidepressants do not appear to be associated with an increased risk of congenital malformations, but statistical significance was found for cardiovascular malformations. Results were robust in several sensitivity analyses."

  16. Grigoriadis, S., et al. (2013). "The effect of prenatal antidepressant exposure on neonatal adaptation: A systematic review and meta-analysis." Journal of Clinical Psychiatry 74(4): e309-e320.

    EXCERPT: "Twelve studies were retrieved that examined PNAS or the signs of respiratory distress and tremors in the infant. There was a significant association between exposure to antidepressants during pregnancy and overall occurrence of PNAS.... Respiratory distress...and tremors...were also significantly associated with antidepressant exposure.... Neonatologists need to be prepared and updated in their management, and clinicians must inform their patients of this risk."

  17. Grigoriadis, S., et al. (2014). "Prenatal exposure to antidepressants and persistent pulmonary hypertension of the newborn: systematic review and meta-analysis." BMJ 348: f6932.

    EXCERPT: "The risk of persistent pulmonary hypertension of the newborn seems to be increased for infants exposed to SSRIs in late pregnancy, independent of the potential moderator variables examined. A significant relation for exposure to SSRIs in early pregnancy was not evident. Although the statistical association was significant, clinically the absolute risk of persistent pulmonary hypertension of the newborn remained low even in the context of late exposure to SSRIs."

  18. Huang, K. L., et al. (2014). "Comparison of agomelatine and selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors in major depressive disorder: A meta-analysis of head-to-head randomized clinical trials." Aust N Z J Psychiatry.

    EXCERPT: "In the acute phase, agomelatine had higher response rates...compared to SSRIs and SNRIs. In the remission analysis, only acute remission rates...significantly differed. The action of agomelatine was superior on the Leeds Sleep Evaluation Questionnaire-Quality of Sleep score.... Discontinuation due to inefficacy did not differ between agomelatine and SSRIs/SNRIs... Compared to SSRIs and SNRIs, however, agomelatine revealed a lower rate of discontinuation due to side effects.... Agomelatine has significantly higher efficacy and potential acceptability compared to SSRIs and SNRIs when treating MDD. However, the difference in efficacy is not considered clinically relevant. Because of its unique chronobiotic effects, agomelatine may be useful for the management of some MDD patients with circadian disturbance."

  19. Huybrechts, K. F., et al. (2014). "Preterm birth and antidepressant medication use during pregnancy: a systematic review and meta-analysis." PLoS One 9(3): e92778.

    EXCERPT: "There was no increased studies that identified patients based on 1st trimester exposure. Sensitivity analyses demonstrated unmeasured confounding would have to be strong to account for the observed association.... Published evidence is consistent with an increased risk of preterm birth in women taking antidepressants during the 2nd and 3rd trimesters, although the possibility of residual confounding cannot be completely ruled out."

  20. Jakubovski, E., Varigonda, A. L., Freemantle, N., Taylor, M. J., & Bloch, M. H. (2016). Systematic review and meta-analysis: dose-response relationship of selective serotonin reuptake inhibitors in major depressive disorder. American Journal of Psychiatry, pp. 174-184.

    EXCERPT: "Higher doses of SSRIs appear slightly more effective in major depressive disorder. This benefit appears to plateau at around 250 mg of imipramine equivalents (50 mg of fluoxetine). The slightly increased benefits of SSRIs at higher doses are somewhat offset by decreased tolerability at high doses."

  21. Jiang, H. Y., et al. (2015). "Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding: a systematic review and meta-analysis." Clin Gastroenterol Hepatol 13(1): 42-50 e43.

    EXCERPT: "SSRI use was associated with an almost 2-fold increase in the risk of developing UGIB, especially among patients at high risk for GI bleeding (concurrent use of nonsteroidal anti-inflammatory or antiplatelet drugs). This risk might be reduced significantly by concomitant use of acid-suppressing drugs."

  22. Kasper, S., et al. (2013). "Antidepressant efficacy of agomelatine versus SSRI/SNRI: results from a pooled analysis of head-to-head studies without a placebo control." Int Clin Psychopharmacol 28(1): 12-19.

    EXCERPT: "Agomelatine was associated with better tolerability than SSRI/SNRI. Agomelatine has favourable efficacy and tolerability versus a range of SSRIs and SNRIs - including agents considered to have superior efficacy - and may deserve benefit-risk analysis as a first-line treatment of major depressive disorder."

  23. Kasper, S. and G. Hajak (2013). "The efficacy of agomelatine in previously-treated depressed patients." Eur Neuropsychopharmacol 23(8): 814-821.

    EXCERPT: "Data from the subset of previously treated depressed patients, who can be considered more difficult to treat, indicate that agomelatine, due to its different mode of action, demonstrated antidepressant efficacy, and favorable side effect profile-with proven benefits in first-line treatment-is also an effective candidate for patients with major depressive disorder previously treated with other antidepressants."

  24. Kishi, T. and N. Iwata (2014). "Meta-analysis of noradrenergic and specific serotonergic antidepressant use in schizophrenia." Int J Neuropsychopharmacol, 17(2): 343-354.

    EXCERPT: "Our results indicate that NaSSA (especially mirtazapine) augmentation therapy improved overall and negative symptoms in patients with schizophrenia."

  25. Kloiber, S., et al. (2013). "Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels." Eur Neuropsychopharmacol 23(7): 653-662.

    EXCERPT: "Unfavorable treatment outcome was accompanied with decreased leptin mRNA and leptin serum levels. Our results suggest an involvement of leptin in antidepressant action and cognitive function in depression with genetic polymorphisms in the leptin gene, decreased leptin gene expression and leptin deficiency in serum being risk factors for resistance to antidepressant therapy in depressed patients."

  26. Koesters, M., et al. (2013). "Agomelatine efficacy and acceptability revisited: systematic review and meta-analysis of published and unpublished randomised trials." Br J Psychiatry 203: 179-187.

    EXCERPT: "Acute treatment with agomelatine was associated with a statistically significant superiority over placebo.... Data extracted from three relapse prevention studies failed to show significant effects of agomelatine over placebo.... Secondary efficacy analyses showed a significant advantage of agomelatine over placebo in terms of response (with no effect for remission).... None of the negative trials were published and conflicting results between published and unpublished studies were observed.... We found evidence suggesting that a clinically important difference between agomelatine and placebo in patients with unipolar major depression is unlikely. There was evidence of substantial publication bias."

  27. Köhler, O., Benros, M. E., Nordentoft, M., Farkouh, M. E., Iyengar, R. L., Mors, O., & Krogh, J. (2014). Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA psychiatry, 71(12), 1381-1391.

    EXCERPT: "Our analysis suggests that anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increased risks of adverse effects. However, a high risk of bias and high heterogeneity made the mean estimate uncertain."

  28. Li, J., et al. (2013). "The role of duloxetine in stress urinary incontinence: a systematic review and meta-analysis." Int Urol Nephrol 45(3): 679-686.

    EXCERPT: "Our meta-analysis showed that significant efficacy can be found in women treated with a certain dose of duloxetine. The adverse events like nausea, constipation, dry mouth, fatigue etc. are common."

  29. Liu, Y., et al. (2015). "Is pindolol augmentation effective in depressed patients resistant to selective serotonin reuptake inhibitors? A systematic review and meta-analysis." Human Psychopharmacology: Clinical and Experimental 30(3): 132-142.

    EXCERPT: "Pindolol augmentation may not be suitable for treatment-resistant depression patients with SSRI-resistant depression. However, once-daily high-dose pindolol (7.5 mg qd) appears to show a promising benefit in these patients."

  30. Ma, Y. (2015). Neuropsychological mechanism underlying antidepressant effect: a systematic meta-analysis. Molecular psychiatry, 20(3), 311-319.

    EXCERPT: "For both patients and healthy volunteers, the medial prefrontal and core limbic parts of the emotional network (for example, anterior cingulate, amygdala and thalamus) were increased in response to positive emotions but decreased to negative emotions by repeated antidepressant administration. Moreover, selective antidepressant effects were uncovered in patients and healthy volunteers, respectively. Antidepressants increased activity in the dorsolateral prefrontal (dlPFC), a key region mediating emotion regulation, during both negative and positive emotions in patients. Repeated antidepressant administration decreased brain responses to positive emotions in the nucleus accumbens, putamen, medial prefrontal and midbrain in healthy volunteers. Antidepressants act to normalize abnormal neural responses in depressed patients by increasing brain activity to positive stimuli and decreasing activity to negative stimuli in the emotional network, and increasing engagement of the regulatory mechanism in dlPFC."

  31. Ma, D., et al. (2014). "Comparative efficacy, acceptability, and safety of medicinal, cognitive-behavioral therapy, and placebo treatments for acute major depressive disorder in children and adolescents: A multiple-treatments meta-analysis." Current Medical Research and Opinion 30(6): 971-995.

    EXCERT: "Combined fluoxetine/CBT exhibited the highest efficacy, with fluoxetine alone superior to CBT, paroxetine, sertraline, citalopram, escitalopram, and placebo treatment. Sertraline, paroxetine, escitalopram, and venlafaxine showed superior acceptability to fluoxetine and combined fluoxetine/CBT. Combined fluoxetine/CBT combination was less safe, though CBT was safer than fluoxetine alone. Combined fluoxetine/CBT, fluoxetine, and mirtazapine exhibited the highest efficacy; sertraline, escitalopram, venlafaxine, and paroxetine were the best tolerated; and mirtazapine and venlafaxine were the safest.... Sertraline and mirtazapine exhibited optimally balanced efficacy, acceptability, and safety for first-line acute treatment of child and adolescent MDD."

  32. Meeker, A. S., et al. (2015). "The safety and efficacy of vortioxetine for acute treatment of major depressive disorder: a systematic review and meta-analysis." Systematic Review Registraction: Prospero CRD42013006198 4: 21.

    EXCERPT: "Vortioxetine was significantly more effective than placebo for acute treatment of major depressive disorder (MDD). Although treatment effect estimates varied substantially between studies, a dose effect was not observed. Vortioxetine does not appear to be more effective, and is potentially less effective, than an SNRI."

  33. Morgan, L. C., Gartlehner, G., Nussbaumer, B., Reichenpfader, U., Gaynes, B. N., Boland, E., & Bann, C. M. (2015). Comparative Benefits and Harms of Second-generation Antidepressants in the Pharmacologic Treatment of Depression in Older Adults: Systematic Revview and Network Meta-analysis. European Psychiatry, 30, 774.

    EXCERPT: "Evidence on older adults compared with adults of any age is sparse. In older adults, evidence indicates that efficacy does not differ substantially among second-generation antidepressants; however, there may be some differences in adverse events. Our meta-regression found a trend toward lesser efficacy of SGAs in older adults than adults of any age."

  34. Na, K. S., et al. (2014). "Efficacy of adjunctive celecoxib treatment for patients with major depressive disorder: a meta-analysis." Prog Neuropsychopharmacol Biol Psychiatry 48: 79-85.

    EXCERPT: "Of the 654 retrieved entries, we identified four relevant studies with a total of 150 patients (75 NSAID patients and 75 placebo patients) with depressive episodes. All four studies used celecoxib as the NSAID. The patients receiving adjunctive celecoxib had significantly higher mean changes in the Hamilton Rating Scale for Depression scores between baseline and endpoint measurements compared with those receiving placebo.... The adjunctive celecoxib group also showed better remission...and response rates...than the placebo group.... Adjunctive treatment with NSAIDs, particularly celecoxib, can be a promising strategy for patients with depressive disorder."

  35. Niitsu, T., et al. (2013). "Pharmacogenetics in major depression: A comprehensive meta-analysis." Progress in Neuro-Psychopharmacology & Biological Psychiatry 45: 183-194.

    EXCERPT: "In conclusion, our findings suggested the BDNF Val66Met as the best single candidate involved in AD response, with a selective effect on SSRI treatment. Our overall results supported no major effect of any single gene variant on AD efficacy."

  36. Nussbaumer, B., et al. (2014). "Comparative Efficacy and Risk of Harms of Immediate- versus Extended-Release Second-Generation Antidepressants: A Systematic Review with Network Meta-Analysis." CNS Drugs, in press.

    EXCERPT: "Available evidence currently shows no clear differences between the two formulations and therefore we cannot recommend a first choice. However, if adherence or compliance with one medication is an issue, then clinicians and patients should consider the alternative medication. If adherence or costs are a problem with one formulation, consideration of the other formulation to provide an adequate treatment trial is reasonable."

  37. Oakes, T. M., et al. (2013). "Safety and tolerability of duloxetine in elderly patients with major depressive disorder: a pooled analysis of two placebo-controlled studies." Int Clin Psychopharmacol 28(1): 1-11.

    EXCERPT: "Treatment-emergent adverse events for duloxetine of at least 5% and twice the rate of placebo were dry mouth, constipation, nausea, diarrhea, dizziness, and fatigue. Abnormal changes in vital signs and weight were not significantly different at any time between duloxetine and placebo. The mean changes in platelet count, alkaline phosphatase, potassium, random glucose, uric acid, and cholesterol were significantly different between duloxetine and placebo..., but none of these differences were considered clinically relevant. The incidence of abnormal low sodium levels was not significantly different between treatments."

  38. Oh, S. W., et al. (2014). "Antidepressant Use and Risk of Coronary Heart Disease: Meta-Analysis of Observational Studies." Br J Clin Pharmacol., in press.

    EXCERPT: "There was no association between SSRI use and the risk of CHD overall...or in subgroup meta-analysis of case-control studies ...and cohort studies.... The use of TCA antidepressant was associated with an increased risk of CHD overall..., but it was observed only in case-control studies...and low quality the subgroup meta-analyses....This meta-analysis of observational studies in subjects with no history of CHD suggests that neither SSRI nor TCA use is associated with an increased risk of CHD."

  39. Pimontel, M. A., et al. (2016). "A Meta-Analysis of Executive Dysfunction and Antidepressant Treatment Response in Late-Life Depression." Am J Geriatr Psychiatry, pp. 31-41

    EXCERPT: "The domain of planning and organization is meaningfully associated with poor antidepressant treatment response in late-life depression. These findings suggest that therapies that focus on planning and organization may provide effective augmentation strategies for antidepressant nonresponders with late-life depression."

  40. Reichenpfader, U., et al. (2014). "Sexual dysfunction associated with second-generation antidepressants in patients with major depressive disorder: results from a systematic review with network meta-analysis." Drug Saf 37(1): 19-31.

    EXCERPT: "Because of the indirect nature of the comparisons, the often wide credible intervals, and the high variation in magnitude of outcome, we rated the overall strength of evidence with respect to our findings as low. The current degree of evidence does not allow a precise estimate of comparative risk of SD associated with a specific antidepressant. In the absence of such evidence, clinicians need to be aware of SD as a common adverse event and should discuss patients' preferences before initiating antidepressant therapy."

  41. Riblet, N., et al. (2014). "Reevaluating the role of antidepressants in cancer-related depression: A systematic review and meta-analysis." General Hospital Psychiatry 36(5): 466-473.

    EXCERPT: "Trials of mianserin found a robust reduction in depression scores at 4 or more weeks of treatment.... Similar, but less robust, results were observed with paroxetine...and fluoxetine.... Conversely, there was no advantage with amitriptyline or desipramine. Compared to placebo, the odds of dropping out due to side effect were higher with fluoxetine and paroxetine and lower with mianserin.... Paroxetine, fluoxetine and mianserin improve cancer-related depression but may vary in efficacy and tolerability.

  42. Riggin, L., et al. (2013). "The fetal safety of fluoxetine: a systematic review and meta-analysis." J Obstet Gynaecol Can 35(4): 362-369.

    EXCERPT: "Overall, women who are treated with fluoxetine during the first trimester of pregnancy do not appear to have an increased risk of major fetal malformations."

  43. Romeo, B., Choucha, W., Fossati, P., & Rotge, J. Y. (2015). Meta-analysis of short-and mid-term efficacy of ketamine in unipolar and bipolar depression. Psychiatry research, 230(2), 682-688.

    EXCERPT: "Ketamine showed an overall antidepressive efficacy from day 1 to day 7. However, the maintenance of its efficacy over time failed to reach significance in bipolar depression after day 3–4. Significant SMDs were not explained by demographic or clinical characteristics of included samples. The present meta-analysis provides a high level of evidence that ketamine has a rapid antidepressive action during one week, especially in unipolar disorder."

  44. Rosenblat, J. D., Kakar, R., Berk, M., Kessing, L. V., Vinberg, M., Baune, B. T., & McIntyre, R. S. (2016). Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis. Bipolar Disorders, 18(2), 89-101.

    Excerpt: "Overall, a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis."

  45. Ross, L. E., et al. (2013). "Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis." JAMA Psychiatry 70(4): 436-443.

    EXCERPT: "There was no significant association between antidepressant medication exposure and spontaneous abortion.... Antidepressant exposure during pregnancy was significantly associated with lower birth weight...; when this comparison group was limited to depressed mothers without antidepressant exposure, there was no longer a significant association. Antidepressant exposure was significantly associated with lower Apgar scores at 1 and 5 minutes, regardless of whether the comparison group was all mothers or only those who were depressed during pregnancy but not exposed to antidepressants.... Treatment decisions must weigh the effect of untreated maternal depression against the potential adverse effects of antidepressant exposure."

  46. Sarkar, S. and M. Schaefer (2014). "Antidepressant Pretreatment for the Prevention of Interferon Alfa-Associated Depression: A Systematic Review and Meta-Analysis." Psychosomatics, 55(3): 221-234.

    EXCERPT: "Antidepressant pretreatment with selective serotonin reuptake inhibitors lowers the incidence and severity of IFN-associated depression in patients with chronic hepatitis C infection or malignant melanoma."

  47. Selle, V., et al. (2014). "Treatments for acute bipolar depression: Meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics." Pharmacopsychiatry 47(2): 43-52.

    EXCERT: "Overall, pooled drugover-placebo responder-rate superiority (RR) was moderate (29 % [CI: 19–40 %]), and NNT was 8.2 (CI: 6.4–11). By SMD, apparent efficacy ranked: olanzapine + fluoxetine ≥ valproate > quetiapine > lurasidone > olanzapine, aripiprazole, and carbamazepine; ziprasidone was ineffective, and lithium remains inadequately studied. Notably, drugs were superior to placebo in only 11/24 trials (5/5 with quetiapine, 2/4 with valproate), and only lamotrigine, quetiapine and valproate had > 2 trials. Treatment-associated mania-like reactions were uncommon (drugs: 3.7 %; placebo: 4.7 %)."

  48. Shams, T., et al. (2014). "SSRIs for hot flashes: a systematic review and meta-analysis of randomized trials." J Gen Intern Med 29(1): 204-213.

    EXCERPT: "SSRI use is associated with modest improvement in the severity and frequency of hot flashes but can also be associated with the typical profile of SSRI adverse effects."

  49. Shin, D., et al. (2014). "Use of selective serotonin reuptake inhibitors and risk of stroke: a systematic review and meta-analysis." J Neurol 261(4): 686-695.

    EXCERPT: "In our meta-analyses, the use of SSRIs was associated with an increased risk of all types of stroke..., ischemic stroke..., and hemorrhagic stroke.... Between the two subtypes of hemorrhagic stroke, that is, intracerebral and subarachnoid, the increased risk of intracerebral hemorrhage was associated with the use of SSRIs..."

  50. Silva, M. T., et al. (2013). "Olanzapine plus fluoxetine for bipolar disorder: a systematic review and meta-analysis." J Affect Disord 146(3): 310-318.

    EXCERPT: "OFC improved the response compared to olanzapine...and to placebo...but not to lamotrigine (low-quality evidence). Similar results were found for remission and relapse rates. No differences were identified for levels of depression and mania symptoms (low-quality evidence) and incidence of mania (moderate-quality evidence). Adverse effects were more common in patients treated with OFC than in those treated with lamotrigine..., but no difference was found relative to the patients treated with olanzapine (low-quality evidence)."

  51. Singh, I., et al. (2014). "Influence of pre-operative use of serotonergic antidepressants (SADs) on the risk of bleeding in patients undergoing different surgical interventions: a meta-analysis." Pharmacoepidemiol Drug Saf., in press.

    EXCERPT: "Preoperative SADs use is associated with increased bleeding risk with respect to requirement of transfusion; nevertheless, the results should not be generalized to all surgical groups."

  52. Singh, N. and J. Reece (2014). "Psychotherapy, pharmacotherapy, and their combination for adolescents with major depressive disorder: A meta-analysis." The Australian Educational and Developmental Psychologist 31(1): 47-65.

    EXCERPT: "Although all three treatment strategies were found to be effective, analysis revealed no significant difference in treatment outcome among CBT, SSRI, and combination therapy. An investigation of moderator variables revealed months to follow-up to significantly influence the relationship between treatment type and treatment outcome. Given that CBT has no side effects, is more cost effective, and is equally as effective as SSRI therapy and combination therapy, the current study makes a strong case for CBT as a first-line treatment strategy for adolescents with MDD."

  53. Strawn, J. R., Welge, J. A., Wehry, A. M., Keeshin, B., & Rynn, M. A. (2015). Efficacy and Tolerability of Antidepressants in Pediatric Anxiety Disordersa Systematic Review and Meta-Analysis. Depression and anxiety, 32(3), 149-157.

    EXCERPT: "Data for nine SSRI/SSNRIs suggest superiority of antidepressants relative to placebo for the treatment of pediatric anxiety disorders with a moderate effect size."

  54. Sun, Z., et al. (2013). "Efficacy and safety of desvenlafaxine treatment for hot flashes associated with menopause: a meta-analysis of randomized controlled trials." Gynecol Obstet Invest 75(4): 255-262.

    EXCERPT: "The meta-analysis suggests that treatment with desvenlafaxine 100 mg/day is associated with a significant reduction of moderate to severe hot flashes in postmenopausal women. Desvenlafaxine appears both safe and effective for treating hot flushes for up to 12 months."

  55. Tanaka, Y., et al. (2013). "A meta-analysis of the consistency of atomoxetine treatment effects in pediatric patients with attention-deficit/hyperactivity disorder from 15 clinical trials across four geographic regions." J Child Adolesc Psychopharmacol 23(4): 262-270.

    EXCERPT: "Patient demographics were generally similar across regions. More patients from Asia met diagnostic criteria for ADHD inattentive subtype and fewer for combined subtype compared with patients from Europe, North America, or Russia. Asian patients had a lower mean baseline ADHD total score and mean hyperactivity/impulsivity subscore. Treatment effects showed marginal inconsistency and moderate heterogeneity among the regions.... Inconsistency was observed primarily in Asia versus the other regions. Completion rates with atomoxetine were higher in Asia and Russia (94.4% and 94.3%, respectively) than in Europe (84.3%) or North America (80.4%).... Atomoxetine was demonstrated as an effective treatment for ADHD in 15 clinical trials from four global regions. The current meta-analysis has revealed a degree of heterogeneity in treatment efficacy across regions, most notably in the comparison of Asian patients relative to those from the other regions."

  56. Taylor, D., et al. (2014). "Antidepressant efficacy of agomelatine: meta-analysis of published and unpublished studies." BMJ 348: g1888.

    EXCERPT: "Compared with other antidepressants, agomelatine showed equal efficacy...."

  57. Turner, P., et al. (2014). "A systematic review and meta-analysis of the evidence base for add-on treatment for patients with major depressive disorder who have not responded to antidepressant treatment: a European perspective." J Psychopharmacol 28(2): 85-98.

    EXCERPT: "Comparison of the different drug classes indicated that most interventions had similar efficacy. The likelihood of response was significantly greater with SAMe versus placebo and lithium and with quetiapine XR versus placebo. Most add-on interventions demonstrated comparable efficacy in patients with MDD and an inadequate response to initial antidepressants.".

  58. Varigonda, A. L., et al. (2015). "Systematic review and meta-analysis: Early treatment responses of selective serotonin reuptake inhibitors in pediatric major depressive disorder." Journal of the American Academy of Child & Adolescent Psychiatry 54(7): 557-564.

    EXCERPT: "Treatment gains in pediatric MDD are greatest early in treatment and are, on average, minimal after 4 weeks of SSRI pharmacotherapy in pediatric MDD."

  59. Vázquez, G. H., et al. (2013). "Overview of antidepressant treatment of bipolar depression." International Journal of Neuropsychopharmacology 16(7): 1673-1685.

    EXCERPT: The "meta-analysis indicated that overall efficacy was significantly greater with antidepressants than with placebo-treatment and not less than was found in trials for unipolar major depression. Moreover, risks of non-spontaneous mood-switching specifically associated with antidepressant treatment are less than appears to be widely believed....Many therapeutic trials considered were small, varied in design, often involved co-treatments, or lacked adequate controls."

  60. Vidal, C., et al. (2013). "Meta-Analysis of Efficacy of Mirtazapine as an Adjunctive Treatment of Negative Symptoms in Schizophrenia." Clin Schizophr Relat Psychoses: 1-24.

    EXCERPT: "This meta-analysis supports the hypothesis that adding mirtazapine to treatment with antipsychotics can improve negative symptoms in schizophrenia."

  61. von Wolff, A., et al. (2013). "Selective serotonin reuptake inhibitors and tricyclic antidepressants in the acute treatment of chronic depression and dysthymia: a systematic review and meta-analysis." J Affect Disord 144(1-2): 7-15.

    EXCERPT: "Both SSRIs and TCAs are efficacious in terms of response rates when compared to placebo... and no statistically significant differences between the active drugs and placebo in terms of dropout rates could be found. No differences in effectiveness were found between SSRIs and TCAs in terms of response rates..., yet, SSRIs showed statistically better acceptability in terms of dropout rates than TCAs ....This systematic review provides evidence for the efficacy of both SSRIs and TCAs in the treatment of chronic depression and showed a better acceptability of SSRIs."

  62. Wang, S., et al. (2015). "Selective Serotonin Reuptake Inhibitors (SSRIs) and the Risk of Congenital Heart Defects: A Meta-Analysis of Prospective Cohort Studies." J Am Heart Assoc 4(5).

    Excerpts: "SSRIs during the first trimester in pregnant women were not associated with increased risks for newborn heart defects."

  63. Wielage, R. C., et al. (2013). "The cost-effectiveness of duloxetine in chronic low back pain: a US private payer perspective." Value Health 16(2): 334-344.

    EXCERPT: "Duloxetine appears to be a cost-effective post-first-line treatment for CLBP compared with all but generic NSAIDs. In subpopulations at risk of NSAID-related AEs, it is particularly cost-effective."

  64. Wu, Q., et al. (2013). "Tricyclic antidepressant use and risk of fractures: a meta-analysis of cohort and case-control studies." J Bone Miner Res 28(4): 753-763.

    EXCERPT: "Findings of this meta-analysis indicate that treatment with TCAs may convey an increased risk of fracture, independent of depression and bone mineral density."

  65. Yeung, W. F., et al. (2014). "A meta-analysis of the efficacy and safety of traditional Chinese medicine formula Ganmai Dazao decoction for depression." J Ethnopharmacol 153(2): 309-317.

    EXCERPT: "The overall results suggest that GMDZ has few side effects and the potential as an antidepressant. Adding GMDZ to antidepressants reduces side effects and enhances efficacy of antidepressants."

  66. Yoon, J. M., et al. (2013). "Antidepressant use and diabetes mellitus risk: a meta-analysis." Korean J Fam Med 34(4): 228-240.

    EXCERPT: "Our results suggest that the use of antidepressants is associated with an increased risk of DM."



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