Antidepressant Medications: 68 Recent Meta-Analyses

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Antidepressant Medications: 68 Meta-Analytic Studies Published in 2014-2019

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 2014-19, 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. Beyer, C., et al. (2017). "Meta-analysis: Risk of hyperhidrosis with second-generation antidepressants." Depression and Anxiety.

    EXCERPT: "Risk of hyperhidrosis was significantly increased with most antidepressant medications but was associated with dopamine transporter affinity."

  3. 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."

  4. Ciprianim A., et al. (2018). "Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis." The Lancet 391(10128): 1357-1366

    EXCERPT: "We found that all antidepressants included in the meta-analysis were more efficacious than placebo in adults with major depressive disorder and the summary effect sizes were mostly modest. Some antidepressants, such as escitalopram, mirtazapine, paroxetine, agomelatine, and sertraline had a relatively higher response and lower dropout rate than the other antidepressants. By contrast, reboxetine, trazodone, and fluvoxamine were associated with generally inferior efficacy and acceptability profiles compared with the other antidepressants, making them less favourable options. To make our results as relevant and robust as possible to inform clinical practice, we decided to focus on head-to-head studies and at the same time emphasise the certainty of the retrieved evidence. Our assessment overall found few differences between antidepressants when all data were considered, while there was more diversity in the range of efficacy and dropout patterns seen across the head-to-head comparisons than the meta-analysis of antidepressants versus placebo. The present findings in adults contrast with the efficacy of antidepressants in children and adolescents, for which fluoxetine is probably the only antidepressant that might reduce depressive symptoms.21 This differential efficacy across age groups might reflect heterogeneous mechanisms and causes of depression,22 smaller number of studies in young people, or different methodological issues affecting adult and paediatric trials.23 The effect sizes were also smaller in more recent and larger placebo-controlled trials than in older and smaller ones, which might be an indicator of bias."

  5. Cipriani, A., et al. (2016). "Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: A network meta-analysis." The Lancet 388(10047): 881-890.

    EXCERPT: "For efficacy, only fluoxetine was statistically significantly more effective than placebo…. In terms of tolerability, fluoxetine was also better than duloxetine…and imipramine…. Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo…. When considering the risk–benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated."

  6. Colle, R., et al. (2016). "Pioglitazone could induce remission in major depression: A meta-analysis." Neuropsychiatric Disease and Treatment 13.

    EXCERPT: "Pioglitazone, either alone or as add-on therapy to conventional treatments, could induce remission of MDE, suggesting that drugs with PPAR-Y agonist properties may be true and clinically relevant antidepressants, even in patients without metabolic comorbidities."

  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. 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."

  10. Fornaro, M., et al. (2018). "Incidence, prevalence and clinical correlates of antidepressant-emergent mania in bipolar depression: A systematic review and meta-analysis." Bipolar Disorders.

    EXCERPT: "Overall, concurrent lithium therapy predicted the lowest TEM rates. Inconsistent operational definitions of TEM were recorded, and the lack of information about age, sex, co-occurring anxiety, and other clinically relevant moderators precluded further stratification of the results....  Rates of TEM vary primarily depending on study setting, which is concordant with the high degree of heterogeneity of the included records."

  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. Furukawa, T. A., et al. (2018). "Initial severity of major depression and efficacy of new generation antidepressants: Individual participant data meta-analysis." Acta Psychiatrica Scandinavicas (Online in advance of print publication)

    EXCERPT: The best-fitting model revealed that the interaction between baseline severity and treatment was not statistically significant.... Several sensitivity analyses confirmed the robustness of the findings.... We may expect as much benefit from antidepressant treatments for mild, moderate or severe major depression. Clinical practice guidelines will need to take these findings into consideration.

  13. 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."

  14. Gebhardt, S., et al. (2016). "Pain relief in depressive disorders: A meta-analysis of the effects of antidepressants." Journal of Clinical Psychopharmacology 36(6): 658-668.

    EXCERPT: "The analgesic effects of SSNRIs and SSRIs in patients with primary depressive disorders can be interpreted as largely equivalent. Because of a lack of placebo-controlled TCA studies, the results for TCAs would be comparable only to those of SSRIs and SSNRIs, if non?placebo-controlled TCA studies were included. The positive correlation found indicates a close relationship of pain relief and antidepressant treatment effects. These results refer merely to patients with primary depressive disorders, not to patients with primary pain disorders."

  15. Giacobbe, P., et al. (2018). "Efficacy and tolerability of lisdexamfetamine as an antidepressant augmentation strategy: A meta-analysis of randomized controlled trials." Journal of Affective Disorders 226: 294-300.

    EXCERPT: "LDX did not demonstrate superiority in efficacy relative to placebo as indicated by a Hedges' g score of 0.126 (95% CI −0.040–0.291; p = 0.136) for mean change in Montgomery-Asberg Depression Rating Scale. Odds ratios of 1.206 (95% CI 0.745–1.954; p = 0.446) and 1.244 (95% CI 0.959–1.614; p = 0.1) were found for remission and response rates respectively. Risk differences of −0.1 (95% CI −0.155–(−0.045); p < 0.001) indicated a 10% increase chance of developing treatment-emergent adverse events (TEAE) in the LDX group. There was no significant difference in risk for developing serious or severe TEAE and discontinuing treatment due to TEAE."

  16. 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."

  17. Han, Y., et al. (2016). "Efficacy of ketamine in the rapid treatment of major depressive disorder: A meta-analysis of randomized, double-blind, placebo-controlled studies." Neuropsychiatric Disease and Treatment 12.

    EXCERPT: "These results indicated that ketamine could yield a good efficacy in the rapid treatment of MDD."

  18. He, H., et al. (2018). "Efficacy and tolerability of different doses of three new antidepressants for treating major depressive disorder: A PRISMA-compliant meta-analysis." Journal of Psychiatric Research 96: 247-259.

    EXCERPT: "The changes in the MADRS total score were significantly higher for vortioxetine at 5, 10, 20, and 10–20 mg/day than for placebo. The tolerability was significantly worse for 20 mg/day vortioxetine than for placebo (RR = 1.84, 95% confidence interval = 1.13 to 3.02). In addition, increasing the dosage improved the efficacy of vortioxetine but worsened the tolerability. Levomilnacipran and vilazodone at any dosage produced a significantly higher mean change from baseline in the MADRS total score and a worse tolerability than for placebo.... Considering both efficacy and tolerability, 10 mg/day vortioxetine might be optimal for the treatment of MDD."

  19. Hofmann, S. G., et al. (2017). "Effect of treatments for depression on quality of life: A meta-analysis." Cognitive Behaviour Therapy 46(4): 265-286

    EXCERPT: "Moderate improvements in QOL from pre to post-treatment were observed in both CBT (Hedges' g = .63) and SSRI (Hedges' g = .79) treatments. The effect size remained stable over the course of the follow-up period for CBT. No data were available to examine follow-ups in the SSRI group. QOL effect sizes decreased linearly with publication year, and greater improvements in depression were significantly associated with greater improvements in QOL for CBT, but not for SSRIs. CBT and SSRIs for depression were both associated with moderate improvements in QOL, but are possibly caused by different mechanisms."

  20. 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."

  21. 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."

  22. 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."

  23. Jiang, H.-y., et al. (2016). "Antidepressant use during pregnancy and risk of postpartum hemorrhage: A systematic review and meta-analysis." Journal of Psychiatric Research 83: 160-167.

    EXCERPT: "The findings of this meta-analysis support an increased risk of PPH in women exposure to antidepressant during late gestation."

  24. 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."

  25. 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."

  26. 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."

  27. Liu, B., et al. (2017). "Efficacy and safety of long-term antidepressant treatment for bipolar disorders—A meta-analysis of randomized controlled trials." Journal of Affective Disorders 223: 41-48.

    EXCERPT: "Antidepressants were superior to placebo in reducing new depressive episodes in bipolar disorders without increasing risk of new manic/hypomanic episodes either used as monotherapy or in combination with MS. Subgroup analyses revealed that greater benefit and lower risk may be achieved in BD II than in BD I. However, compared with MS monotherapy, AD monotherapy significantly increased the risk of affective switch with no improvement in prophylaxis of new depressive episodes.... Reduced new depressive episodes may be achieved by long-term AD treatment with no significantly increased risk of new manic/hypomanic episodes in BD, particularly in BD II. The elevated risk of affective switch of AD monotherapy compared with MS monotherapy may be contributed to the protective effect of MS in diminishing manic/hypomanic episodes."

  28. 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."

  29. 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."

  30. 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."

  31. Man, K. K. C., et al. (2018). "Prenatal antidepressant exposure and the risk of attention-deficit hyperactivity disorder in children: A systematic review and meta-analysis." Neuroscience and Biobehavioral Reviews 86: 1-11.

    EXCERPT: "These data suggest that the observed association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained by confounding by indication because the results from sibling-matched analyses do not support an increased risk of ADHD in discordant exposed siblings."

  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. Mills, K. A., et al. (2018). "Efficacy and tolerability of antidepressants in Parkinson's disease: A systematic review and network meta-analysis." International Journal of Geriatric Psychiatry 33(4): 642-651.

    EXCERPT: "Pairwise meta-analysis suggested that type B-selective monoamine oxidase inhibitors (SMD = −1.28, CI = −1.68, −0.88), selective serotonin reuptake inhibitors (SMD = −0.49, CI = −0.93, −0.05), and tricyclics (SMD = −0.83, CI = −1.53, −0.13) are effective antidepressants in PD. Network meta-analysis showed that monoamine oxidase inhibitors had the largest effect on depression in PD (SMD (vs selective serotonin reuptake inhibitors) = −0.78, CI = −1.55, −0.01), but these might not be considered traditional antidepressants given their type B selectivity. Conclusions: Although limited by few data, this review suggests that multiple antidepressant classes are potentially efficacious in the treatment of depression in PD, but that further comparative efficacy and tolerability research is needed."

  34. Monden, R., et al. (2018). "The comparative evidence basis for the efficacy of second-generation antidepressants in the treatment of depression in the US: A Bayesian meta-analysis of Food and Drug Administration reviews." Journal of Affective Disorders 235: 393-398.

    EXCERPT: "The resulted Bayes factors showed that the evidence load for efficacy varied strongly across antidepressants. However, all tested drugs except for bupropion and vilazodone showed strong evidence for their efficacy. The posterior effect-size distributions showed variation across antidepressants, with the highest pooled estimated effect size for venlafaxine followed by paroxetine, and the lowest for bupropion and vilazodone.... The results illustrate the importance of considering both the effect size and the evidence-load when judging the efficacy of a treatment. In doing so, the currently employed Bayesian approach provided clear insights on top of those gained with traditional approaches."

  35. 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."

  36. 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."

  37. Ng, Q. X., et al. (2017). "Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis." Journal of Affective Disorders 210: 211-221.

    EXCERPT: "For patients with mild-to-moderate depression, St John's wort has comparable efficacy and safety when compared to SSRIs."

  38. 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."

  39. 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."

  40. Olgiati, P., et al. (2018). "Early improvement and response to antidepressant medications in adults with major depressive disorder. Meta-analysis and study of a sample with treatment-resistant depression." Journal of Affective Disorders 227: 777-786.

    EXCERPT: "Our meta-analysis (9 studies; N = 6185) showed significant associations between early improvement, response (OR: 3.28 95% C.I: 2.06–5.20) and remission (OR: 2.10 95% C.I: 1.53–2.87). 24.6% of TRD sample remitted. VEI was a poor outcome predictor: sensitivity = 0.52 (0.40–0.63); specificity=0.82 (0.76–0.86); AUC = 0.67 (0.62–0.71). EI had a moderate predictive power: sensitivity = 0.87 (0.77–0.93); specificity = 0.71 (0.66–0.77); AUC = 0.76 (0.71–0.80). The best treatment scenario was Algorithm C (switch after 4 weeks) in which remission rate was marginally increased (35.1% vs 33.7% of Algorithm A). Algorithm B (switch after 2 weeks) led to a 4.3% decrease in remission compared to Algorithm A.... Although literature data suggest a correlation between an initial improvement of depressive symptoms and later response and remission during AD treatment, our analysis shows that such an early improvement is not a reliable outcome predictor in TRD. The nature of TRD is complex and different biological mechanisms and treatments might be necessary for TRD patients."

  41. Orgeta, V., et al. (2017). "Efficacy of antidepressants for depression in Alzheimer's disease: Systematic review and meta-analysis." Journal of Alzheimer's Disease 58(3): 725-733.

    EXCERPT: "In terms of response to treatment (6 studies, 297 patients treated with antidepressants and 223 with placebo), no statistically significant difference between antidepressants and placebo was found (odds ratio (OR) 1.95, 95% CI 0.97-3.92). We found no significant drugplacebo difference for depressive symptoms (5 studies, 311 patients, SMD -0.13; 95% CI -0.49 to 0.24). Overall quality of the evidence was moderate because of methodological limitations in studies and the small number of trials…. Despite the importance of depression in people with AD, few RCTs are available on efficacy of antidepressants, limiting clear conclusions of their potential role."

  42. 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."

  43. Prado, C. E., et al. (2018). "A meta-analysis of the effects of antidepressants on cognitive functioning in depressed and non-depressed samples." Neuropsychology Review.

    EXCERPT: "Results revealed that overall, antidepressants have a modest, positive effect on divided attention, executive function, immediate memory, processing speed, recent memory and sustained attention for depressed participants. Selective serotonin reuptake inhibitors (SSRI's) were found to have the greatest positive effect on cognition for depressed participants, as compared to the other classes of antidepressants analysed. Antidepressants did not significantly affect cognitive function in non-depressed participants."

  44. 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."

  45. 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.

  46. Ricken, R., et al. (2017). "Tranylcypromine in mind (Part II): Review of clinical pharmacology and meta-analysis of controlled studies in depression." European Neuropsychopharmacology 27(8): 714-731.

    EXCERPT: "Controlled studies revealed that TCP might provide a special advantage in the treatment of atypical depression, which was supported by a recent PET study of MAO-A activity in brain. However, TCP treatment remains beset with the need for a mandatory tyramine-restricted diet and is therefore limited to use as a third-line antidepressant according to recent treatment algorithms and guidelines for depression treatment. On the other hand, the effort needed to maintain a tyramine-restricted diet may have been overestimated in the perception of both doctors and patients, which may have led to relative underuse of TCP. Interaction with serotonergic drugs bears the risk of severe serotonin toxicity (SST) and combination with indirect sympathomimetic drugs may result in hypertensive crisis which both adds to the risks of TCP. At the same time, TCP has low to no risks of central anticholinergic, sedative, cardiac conduction, body weight, hemostatic effects, or pharmacokinetic drug interactions. Neuroprotection by MAO inhibitors due to reduced oxidative stress is becoming increasingly studied. Taken together, TCP is being increasingly recognized as an important option in systematic treatment approaches for patients suffering from severe courses of depression, such as TRD and atypical depression, by offering a MAO-related pathophysiological rationale."

  47. 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."

  48. 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."

  49. Salagre, E., et al. (2016). "Statins for the treatment of depression: A meta-analysis of randomized, double-blind, placebo-controlled trials." Journal of Affective Disorders 200: 235-242.

    EXCERPT: "All studies were double-blind RCTs, with a follow-up of 6?12 weeks. The statin agents evaluated were lovastatin, atorvastatin, and simvastatin. When compared to placebo, statins, as add-on to treatment as usual, largely improved depressive symptoms as assessed by the HDRS. No serious adverse effects were reported.... Our results suggest that adjunctive treatment with statins could be useful for the treatment of depressive symptoms."

  50. Salter, K. L., et al. (2016). "Pharmacotherapy for depression posttraumatic brain injury: A meta-analysis." The Journal of Head Trauma Rehabilitation 31(4): E21-E32.

    EXCERPT: "Pharmacotherapy after TBI may be associated with a reduction in depressive symptomatology."

  51. 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."

  52. 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.

    EXCERPT: "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 %)."

  53. 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."

  54. 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..."

  55. 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."

  56. 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."

  57. 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."

  58. Thase, M. E., et al. (2016). "A meta-analysis of randomized, placebo-controlled trials of vortioxetine for the treatment of major depressive disorder in adults." European Neuropsychopharmacology 26(6): 979-993.

    EXCERPT: "This meta-analysis of vortioxetine (5?20 mg/day) in adults with MDD supports the efficacy demonstrated in the individual studies, with treatment effect increasing with dose."

  59. 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...."

  60. Telang, S., et al. (2018). "Meta-analysis: Second generation antidepressants and headache." Journal of Affective Disorders 236: 60-68.

    EXCERPT: "SSRIs were associated with a significantly increased risk of headache (RR = 1.06, 95%CI = 1.00–1.13, z = 2.0, p = 0.045) when compared to placebo. There was no significant difference (test for subgroup differences χ² = 2.2, df = 1, p = 0.14) in the risk of headache between SSRIs and SNRIs (RR = 0.97, 95%CI = 0.88–1.06, p = 0.63). There was no significant difference in the relative risk of headache with second generation antidepressants based on diagnostic indication, pharmacological properties and dosage of medications. The only antidepressants that were found to be significantly associated with increased risk of headache compared to placebo were bupropion (RR = 1.22, 95%CI = 1.06–1.41, z = 2.73, p = 0.006) and escitalopram (RR = 1.18, 95%CI = 1.01–1.37, z = 2.11, p = 0.04).... Headaches reported after the initiation of second generation antidepressant medications are more likely to be coincidental than a treatment-emergent side effect of these medications.

  61. Tolin, D. F. (2017). "Can cognitive-behavioral therapy for anxiety and depression be improved with pharmacotherapy? A meta-analysis." Psychiatric Clinics of North America [published online ahead of print]

    EXCERPT: "The additive effect of medications was small for both anxiety and depressive disorders at posttreatment, and there was no additive benefit after medications were discontinued. A small body of evidence suggested that antidepressant medications are an efficacious second-line treatment for patients failing to respond to CBT alone. In anxiety disorders, novel agents thought to potentiate the biological mechanisms of CBT showed small effects at posttreatment; after discontinuation, some of these agents were associated with an increasing effect."

  62. 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.".

  63. 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."

  64. Wang, H. R., et al. (2016). "Ineffectiveness of nicotinic acetylcholine receptor antagonists for treatment-resistant depression: A meta-analysis." International Clinical Psychopharmacology 31(5): 241-248.

    EXCERPT: "Nicotinic acetylcholine receptor antagonists failed to show superior efficacy compared with placebo in terms of the mean change.... This meta-analysis failed to confirm preliminary positive evidence for the efficacy of nicotinic acetylcholine receptor antagonists in treatment-resistant depression."

  65. 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."

  66. 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."

  67. Zhao, X., et al. (2018). "A meta-analysis of selective serotonin reuptake inhibitors (SSRIs) use during prenatal depression and risk of low birth weight and small for gestational age." Journal of Affective Disorders 241: 563-570

    EXCERPT: "Fifteen articles involved 1,977,446 subjects were identified that tested the relationship between the SSRIs use, LBW and SGA outcomes. Statistical analyses revealed a significant association between SSRIs use and suboptimal fetal growth (RR = 1.45, 95% CI = 1.18 − 1.76, Z = 3.62, p = 0.00 for SGA; RR = 1.38, 95% CI = 1.13 − 1.69, Z = 3.14, p = 0.00 for LBW).... Our findings suggested that SSRIs use for prenatal depression is associated with suboptimal fetal growth."

  68. Zheng, W., et al. (2019). "Adjunctive ketamine and electroconvulsive therapy for major depressive disorder: A meta-analysis of randomized controlled trials." Journal of Affective Disorders 250: 123-131.

    EXCERPT: "Eleven RCTs testing the effects of ketamine on neurocognitive functions with various test batteries found mixed results. Ketamine alone significantly increased blood pressure more than other anesthetic drugs in MDD treated with ECT.... Compared to other anesthetic agents, ketamine alone does not appear to improve the efficacy of ECT. However, ketamine+other anesthetic combinations may confer a short-term advantage in improving depressive symptom at the early stages of ECT."


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