Antidepressant Medications: 46 Recent Meta-Analyses

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Antidepressant Medications: 46 Meta-Analytic Studies Published in 2016-2021

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 2016-2021, and included both the citation and a brief excerpt for each study.

  1. Beyer, C., et al. (2017). "Meta-analysis: Risk of hyperhidrosis with second-generation antidepressants." Depression and Anxiety, 34(12), 1134-1146.

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

  2. Biffi, A., et al. (2020). "Use of antidepressants during pregnancy and neonatal outcomes: An umbrella review of meta-analyses of observational studies." Journal of Psychiatric Research 124: 99-108.

    EXCERPT: " Our review included 22 meta-analyses investigating 69 associations. However, none were supported by convincing evidence. Highly suggestive evidence regarded the associations between (i) any time AD exposure and the risk of preterm birth (relative risk, 1.68; 95% confidence interval 1.52, 1.86), (ii) any time exposure to selective serotonin reuptake inhibitors (SSRIs) and the risk of preterm birth (1.43; 1.22, 1.37) and (iii) respiratory distress (1.33; 1.14, 1.55), and (iv) SSRI exposure during the first trimester of pregnancy and the risk of cardiovascular malformations (1.25; 1.13, 1.39). Suggestive evidence was obtained for any time AD exposure on 1-min low Apgar score (absolute average difference, −0.34; −0.53, −0.14).... Overall, the effects of AD exposure during pregnancy on neonatal outcomes have been extensively studied, but few of the associations are graded as high quality evidence. More prospective studies and large collaborations with comprehensive standardised reporting of analyses are needed."

  3. Boschloo, L., et al. (2019). "The symptom-specific efficacy of antidepressant medication vs. cognitive behavioral therapy in the treatment of depression: Results from an individual patient data meta-analysis." World Psychiatry 18(2): 183-191.

    EXCERPT: "Five symptoms (i.e., “depressed mood” , “feelings of guilt” , “suicidal thoughts” , “psychic anxiety” and “general somatic symptoms”) showed larger improvements in the medication compared to the CBT condition (effect sizes ranging from .13 to .16), whereas no differences were found for the twelve other symptoms. In addition, network estimation techniques revealed that all effects, except that on “depressed mood” , were direct and could not be explained by any of the other direct or indirect treatment effects. Exploratory analyses showed that information about the symptom-specific efficacy could help in identifying those patients who, based on their pre-treatment symptomatology, are likely to benefit more from antidepressant medication than from CBT (effect size of .30) versus those for whom both treatments are likely to be equally efficacious. Overall, our symptom-oriented approach results in a more thorough evaluation of the efficacy of antidepressant medication over CBT and shows potential in 'precision psychiatry'"

  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. Dinoff, A., et al. (2020). "A meta-analysis of the potential antidepressant effects of buprenorphine versus placebo as an adjunctive pharmacotherapy for treatment-resistant depression." J Affect Disord 271: 91-99.

    EXCERPT: "This meta-analysis did not reveal a significant reduction in depression symptom severity in individuals with TRD after an adjunctive intervention with buprenorphine when compared to placebo."

  8. 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."

  9. 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.
  10. 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."

  11. Geoffroy, P. A., et al. (2019). "Efficacy of light therapy versus antidepressant drugs, and of the combination versus monotherapy, in major depressive episodes: A systematic review and meta-analysis." Sleep Medicine Reviews 48.

    EXCERPT: " No differences were observed between LT and AD, with a clear superiority of the combination, thus both LT monotherapy and combination may be proposed as a first line treatment in seasonal and non-seasonal depression."

  12. 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."

  13. 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."

  14. 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."

  15. 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."

  16. Holper, L. and M. P. Hengartner (2020). "Comparative efficacy of placebos in short-term antidepressant trials for major depression: A secondary meta-analysis of placebo-controlled trials." BMC Psychiatry 20.

    EXCERPT: "The present exploratory NMA indicates that distinguishable side effects of older drugs may unblind outcome-assessors thus resulting in overestimation of the average drug-placebo difference and underrating bias in placebo-arms, particularly for the older antidepressant drugs amitriptyline and trazodone. If confirmed in prospective studies, these findings suggest that efficacy rankings for antidepressants are susceptible to bias and should be considered unreliable or misleading."

  17. 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."

  18. 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."

  19. Kato, M., et al. (2021). "Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: A systematic review and meta-analysis." Molecular Psychiatry 26(1): 118-133.

    EXCERPT: " To prevent relapse and treatment failure, maintenance therapy, and careful attention for at least 6 months after remission is recommended. SSRIs are well-balanced agents, and flexible dose adjustments are more effective for relapse prevention."

  20. Kreitzer, N., et al. (2019). "The effect of antidepressants on depression after traumatic brain injury: A meta-analysis." The Journal of Head Trauma Rehabilitation 34(3): E47-E54.

    EXCERPT: " This meta-analysis found no significant benefit of antidepressant over placebo in the treatment of MDD following TBI. Pooled estimates showed a high degree of bias and heterogeneity. Prospective studies on the impact of antidepressants in well-defined cohorts of TBI patients are warranted."

  21. Li, X. and C. Zhang (2020). "Comparative efficacy of nine antidepressants in treating Chinese patients with post-stroke depression: A network meta-analysis." J Affect Disord 266: 540-548.

    EXCERPT: "Escitalopram was associated with a quicker relief of depression, but mirtazapine was probably the best option when it comes to the efficacy of 8-week treatment duration. Amitriptyline and doxepin were nearly the worst choice regardless of the duration (2, 4 or 8 weeks)."

  22. 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."

  23. 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."

  24. 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."

  25. 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."

  26. 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."

  27. Nord, C. L., et al. (2021). "Neural effects of antidepressant medication and psychological treatments: A quantitative synthesis across three meta-analyses." The British Journal of Psychiatry: publ;ishjed online in advance of print publication.

    EXCERPT: Neural changes from psychotherapy and antidepressant medication did not significantly converge on any region. Antidepressants evoked neural changes in the amygdala, whereas psychotherapy evoked anatomically distinct changes in the medial prefrontal cortex. Both psychotherapy- and antidepressant-related changes separately converged on regions of the affect network.... This supports the notion of treatment-specific brain effects of antidepressants and psychotherapy. Both treatments induce changes in the affect network, but our results suggest that their effects on affect processing occur via distinct proximal neurocognitive mechanisms of action."

  28. 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."

  29. 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."

  30. Ostuzzi, G., et al. (2019). "Efficacy and acceptability of antidepressants in people with ischemic heart disease: A systematic review and meta-analysis." International Clinical Psychopharmacology 34(2): 65-75.

    EXCERPT: "Antidepressants appeared to be more effective than placebo in reducing depressive symptoms (11 comparisons; 1685 participants; standardized mean difference, −0.71; 95% confidence interval, −1.11 to −0.30; GRADE quality, moderate). This result was confirmed in the subgroup of serotonin selective reuptake inhibitors, and for the single drugs sertraline and citalopram, with a greater magnitude of effect and a higher quality of evidence for the former. No differences between antidepressants and placebo emerged in terms of acceptability and tolerability, quality of life, mortality, and cardiovascular events. Only two small head-to-head studies were identified. Sertraline is a reasonable first-line choice in patients with ischemic heart disease and depression, while the role of citalopram as first-line agent should be reconsidered."

  31. 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."

  32. 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."

  33. 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."

  34. 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."

  35. 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."

  36. 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."

  37. 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."

  38. 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.

  39. 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."

  40. Ulrich, S., et al. (2020). "Efficacy and adverse effects of tranylcypromine and tricyclic antidepressants in the treatment of depression: A systematic review and comprehensive meta-analysis." Journal of Clinical Psychopharmacology 40(1): 63-74.

    EXCERPT: "Tranylcypromine and TCAs have an equal antidepressant effect in a mean sample of depressed patients with mixed psychomotor symptoms. Tranylcypromine might be superior to TCAs in depression with predominant psychomotor retardation."

  41. 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."

  42. Wang, Y.-C., et al. (2018). "Increased risk of dementia in patients with antidepressants: A meta-analysis of observational studies." Behavioural Neurology 2018.

    EXCERPT: "Our findings indicate that antidepressant use is significantly associated with an increased risk of developing dementia. Therefore, we suggest physicians to carefully prescribe antidepressants, especially in elder patients. Additionally, treatment should be stopped if any symptoms related to dementia are to be noticed."

  43. Watanabe, N., et al. (2020). "Predicting antidepressant response through early improvement of individual symptoms of depression incorporating baseline characteristics of patients: An individual patient data meta-analysis." Journal of Psychiatric Research 125: 85-90.

    EXCERPT: "Primary and secondary outcomes were response and remission at week 6, respectively. We compared models that only included improvement in the overall depression severity at week 2 with models that also included improvement in individual symptoms and baseline characteristics, by conducting an individual patient data meta-analysis. We obtained data from three trials comprising 997 participants. For the response outcome, the model incorporating individual symptoms and baseline characteristics demonstrated better predictive values than those in the model including early improvement in overall depression only. However, the area under the receiver operating characteristic curve, and positive and negative predictive values were 0.65, 0.70, and 0.64, respectively, suggesting that 30% and 36% of the participants still had false-negative and false-positive predictions, respectively. For the remission outcome, the corresponding values in the latter model were 0.72, 0.62, and 0.68, respectively. We suggest that clinical judgement on early discontinuation of antidepressant from non-early improvement at week 2 should be carefully made."

  44. 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."

  45. 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."

  46. Zhou, X., et al. (2020). "Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: A systematic review and network meta-analysis." The Lancet Psychiatry 7(7): 581-601.

    EXCERPT: "Despite the scarcity of high-quality evidence, fluoxetine (alone or in combination with CBT) seems to be the best choice for the acute treatment of moderate-to-severe depressive disorder in children and adolescents. However, the effects of these interventions might vary between individuals, so patients, carers, and clinicians should carefully balance the risk-benefit profile of efficacy, acceptability, and suicide risk of all active interventions in young patients with depression on a case-by-case basis. "


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