Depression is a significant global mental health challenge, impacting diverse populations across various stages of life. Recent research highlights critical findings in understanding and addressing depression through various lenses. The first study, by Pearce et al. (2022), systematically reviews the association between physical activity and depression, revealing that even moderate physical activity significantly reduces the risk of depression, encouraging health practitioners to promote physical activity at any level. The second study, by Nuñez et al. (2022), focuses on treatment-resistant depression (TRD), comparing the efficacy and discontinuation rates of various augmentation agents. Their findings emphasize the potential of certain atypical antipsychotics, thyroid hormones, and stimulants in managing TRD, although acceptability varies. Lastly, the study by Shorey et al. (2022) examines the global prevalence of depression among adolescents, identifying a high and rising prevalence of depressive symptoms, especially in the Middle East, Africa, and Asia, and among female adolescents. This comprehensive review underscores the importance of targeted, culturally relevant interventions and the need for ongoing research to mitigate the impact of depression across different demographics.

Pearce M, Garcia L, Abbas A, Strain T, Schuch FB, Golubic R, Kelly P, Khan S, Utukuri M, Laird Y, Mok A, Smith A, Tainio M, Brage S, Woodcock J. Association Between Physical Activity and Risk of Depression: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2022 Jun 1;79(6):550-559. doi: 10.1001/jamapsychiatry.2022.0609. PMID: 35416941; PMCID: PMC9008579.

Importance: Depression is the leading cause of mental health-related disease burden and may be reduced by physical activity, but the dose-response relationship between activity and depression is uncertain.

Objective: To systematically review and meta-analyze the dose-response association between physical activity and incident depression from published prospective studies of adults.

Results: Fifteen studies comprising 191 130 participants and 2 110 588 person-years were included. An inverse curvilinear dose-response association between physical activity and depression was observed, with steeper association gradients at lower activity volumes; heterogeneity was large and significant (I2 = 74%; P < .001). Relative to adults not reporting any activity, those accumulating half the recommended volume of physical activity (4.4 marginal metabolic equivalent task hours per week [mMET-h/wk]) had 18% (95% CI, 13%-23%) lower risk of depression. Adults accumulating the recommended volume of 8.8 mMET hours per week had 25% (95% CI, 18%-32%) lower risk with diminishing potential benefits and higher uncertainty observed beyond that exposure level. There were diminishing additional potential benefits and greater uncertainty at higher volumes of physical activity. Based on an estimate of exposure prevalences among included cohorts, if less active adults had achieved the current physical activity recommendations, 11.5% (95% CI, 7.7%-15.4%) of depression cases could have been prevented.

Conclusions and relevance: This systematic review and meta-analysis of associations between physical activity and depression suggests significant mental health benefits from being physically active, even at levels below the public health recommendations. Health practitioners should therefore encourage any increase in physical activity to improve mental health.

Nuñez NA, Joseph B, Pahwa M, Kumar R, Resendez MG, Prokop LJ, Veldic M, Seshadri A, Biernacka JM, Frye MA, Wang Z, Singh B. Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis. J Affect Disord. 2022 Apr 1;302:385-400. doi: 10.1016/j.jad.2021.12.134. Epub 2022 Jan 2. PMID: 34986373; PMCID: PMC9328668.

Objective: To compare the efficacy and discontinuation of augmentation agents in adult patients with treatment-resistant depression (TRD). We conducted a systematic review and network meta-analyses (NMA) to combine direct and indirect comparisons of augmentation agents.

Methods: We included randomized controlled trials comparing one active drug with another or with placebo following a treatment course up to 24 weeks. Nineteen agents were included: stimulants, atypical antipsychotics, thyroid hormones, antidepressants, and mood stabilizers. Data for response/remission and all-cause discontinuation rates were analyzed. We estimated effect-size by relative risk using pairwise and NMA with random-effects model.

Conclusions: This NMA suggests a superiority of the regulatory approved adjunctive atypical antipsychotics, thyroid hormones, dopamine compounds (modafinil and lisdexamfetamine) and lithium. Acceptability was lower with ziprasidone, mirtazapine, and cariprazine. Further research and head-to-head studies should be considered to strengthen the best available options for TRD.

Shorey S, Ng ED, Wong CHJ. Global prevalence of depression and elevated depressive symptoms among adolescents: A systematic review and meta-analysis. Br J Clin Psychol. 2022 Jun;61(2):287-305. doi: 10.1111/bjc.12333. Epub 2021 Sep 26. PMID: 34569066.

Objective: Adolescence is a formative and turbulent phase where physiological, psychosocial, and cognitive changes leave adolescents vulnerable to psychological disorders. Given the lack of reviews that consolidate and compare worldwide prevalence of depression among adolescents, this review aims to examine the global prevalence of major depressive disorders, dysthymia, and elevated depressive symptoms among adolescents.

Methods: A systematic review and meta-analysis was conducted. Six databases were searched for studies published from 2001 to December 2020. Seventy-two studies were included. Subgroup analysis were performed for year of publication, geographical region, gender, and assessment tools used.

Results: The global point prevalence rate of elevated self-reported depressive symptoms from 2001 to 2020 was 34% (95% CI: 0.30-0.38). Point prevalence for major depressive disorder (MDD) and dysthymia was 8% (95% CI: 0.02-0.13) and 4% (95% CI: 0.01-0.07), respectively. The pooled one-year prevalence and lifetime prevalence for MDD were 8% (95% CI: 0.05-0.12) and 19% (95% CI: 0.12-0.26). Point prevalence of elevated depressive symptoms among adolescents increased from 24% (95% CI: 0.19-0.28) between 2001 and 2010 to 37% (95% CI: 0.32-0.42) between 2011 and 2020. The Middle East, Africa, and Asia have the highest prevalence of elevated depressive symptoms, and female adolescents were reported to have a higher prevalence of elevated depressive symptoms than male adolescents.

Conclusion: Besides targeting those with existing clinical depression, research and policies should also focus on educational and supportive mitigation efforts to curb depressive symptoms among adolescents before escalation. The findings encourage future research to develop more gender-specific and culturally relevant intervention programmes.

Practitioner points: 34% of adolescents globally, aged 10-19 years, are at risk of developing clinical depression, which exceeds the reported estimates of individuals aged 18 to 25 years. Practitioners are highly encouraged to prioritize depression screening and intervention implementation for individuals in this age group. Female adolescents and adolescents from Middle East, Africa, and Asia have the highest risk of developing depression. This urges practitioners and researchers to develop more gender-specific and culturally relevant intervention programmes.

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