Evolving Issues in the Treatment of Depression

Köhler‐Forsberg, Ole; Cusin, Cristina; Nierenberg, Andrew A.

doi:10.1001/jama.2019.4990

Cited by 18 publications

(23 citation statements)

References 11 publications

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“…55 Implementing regular exercise is difficult for most people and is even more challenging for those with major depression because of their symptoms of low energy and motivation. 56 From our study we can say that encouraging or prescribing regular exercise could be useful for the reduction of depressive symptoms in people without clinical depression; although, due to the low quality of the evidence, the strength of this recommendation initially would be weak. However, balance between desirable and adverse effects, values and preferences of patients and providers, and costs-effectiveness analyses 33 were not included as outcomes in our systematic review, so any attempt to establish the strength of the recommendation would have high uncertainty.…”

Section: Discussionmentioning

confidence: 80%

Effectiveness of exercise-based interventions in reducing depressive symptoms in people without clinical depression: systematic review and meta-analysis of randomised controlled trials

et al. 2021

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Background In most trials and systematic reviews that evaluate exercise-based interventions in reducing depressive symptoms, it is difficult to separate treatment from prevention. Aims To evaluate the effectiveness of exercise-based interventions in reducing depressive symptoms in people without clinical depression. Method We searched PubMed, PsycINFO, Embase, WOS, SPORTDiscus, CENTRAL, OpenGrey and other sources up to 25 May 2020. We selected randomised controlled trials (RCTs) that compared exclusively exercise-based interventions with control groups, enrolling participants without clinical depression, as measured using validated instruments, and whose outcome was reduction of depressive symptoms and/or incidence of new cases of people with depression. Pooled standardised mean differences (SMDs) were calculated using random-effect models (registration at PROSPERO: CRD42017055726). Results A total of 14 RCTs (18 comparisons) evaluated 1737 adults without clinical depression from eight countries and four continents. The pooled SMD was −0.34 (95% CI −0.51 to −0.17; P < 0.001) and sensitivity analyses confirmed the robustness of this result. We found no statistical evidence of publication bias and heterogeneity was moderate (I2 = 54%; 95% CI 22–73%). Only two RCTs had an overall low risk of bias and three had long-term follow-up. Multivariate meta-regression found that a larger sample size, country (Asia) and selective prevention (i.e. people exposed to risk factors for depression) were associated with lower effectiveness, although only sample size remained significant when adjustment for multiple tests was considered. According to the Grading of Recommendations Assessment, Development and Evaluation tool, the quality of evidence was low. Conclusions Exercise-based interventions have a small effect on the reduction of depressive symptoms in people without clinical depression. It could be an alternative to or complement psychological programmes, although further higher-quality trials with larger samples and long-term follow-up are needed.

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Section: Discussionmentioning

confidence: 80%

Effectiveness of exercise-based interventions in reducing depressive symptoms in people without clinical depression: systematic review and meta-analysis of randomised controlled trials

et al. 2021

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“…Depression is a common, recurring and debilitating mental illness that often requires treatment (Otte et al, 2016). However, despite treatment with relevant antidepressants in adequate dosages, adjunctive psychotherapy and/or pharmacotherapy, remission rates for patients suffering from depression are quite modest, with 20-30% having treatment-resistant depression, emphasizing the need for alternative treatment strategies (Kohler-Forsberg et al, 2019;McIntyre et al, 2014;Nierenberg, 2013;Trevino et al, 2014;Trivedi et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

The use of stimulants in depression: Results from a self-controlled register study

Rohde

Brink

Østergaard

et al. 2020

Aust N Z J Psychiatry

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Objective: To investigate the effectiveness of stimulants in patients with depression, by using naturalistic outcome measures, such as psychiatric admissions, psychiatric bed-days and incidents of intentional self-harm or suicide attempts. Methods: Via linkage of the Danish nationwide health registers, we identified all patients with a diagnosis of depression initiating stimulants, including methylphenidate, modafinil, amphetamine, dexamphetamine or lisdexamphetamine, from 1995 to 2012. We used a mirror-image model to test whether redemption of a stimulant prescription was associated with a reduction in psychiatric admissions, inpatient days and incidents of intentional self-harm or suicide attempts. Specifically, the number of these outcomes in the 2 years leading up to redemption of a stimulant prescription was compared to the two subsequent years. Similar outcomes were used in a reverse mirror-image model to investigate the effect of stimulant termination. Results: A total of 3354, 935 and 105 patients diagnosed with depression redeemed prescriptions for methylphenidate, modafinil or amphetamine/dexamphetamine/lisdexamphetamine, respectively. Initiation of methylphenidate was not associated with a significant change in psychiatric admissions (mean: −0.02 admissions, p = 0.11) or inpatient days (mean: 0.13 days, p = 0.74). Similar findings were made for modafinil and the amphetamines. In addition, no clinically relevant change in psychiatric admissions or inpatient days was found after termination of a stimulant. After initiation of methylphenidate, the incidents of self-harm or suicide attempts were reduced by 54%, from 68 to 31 events ( p = 0.004). No significant change in incidents of self-harm or suicide attempts were found for modafinil or the amphetamines. Conclusion: This nationwide study, using naturalistic outcomes, does not support the use of stimulants in patients with depression. However, the use of methylphenidate was associated with a 54% reduction in incidents of self-harm or suicide attempts, indicating that methylphenidate may potentially be useful in patients with depression with suicidal- or self-harming behaviour. However, further studies are needed, before any firm conclusions can be made.

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“…It is a major contributor to the overall global burden of disease 9 and in the U.S. alone accounts for more than $200 billion in health care costs 10 . While many conventional treatments are available for depression, nearly one-third of patients are treatment-resistant 11 . A significant number of depressed patients do not respond to first-line medications even after multiple treatment trials 12 .…”

Section: Main Textmentioning

confidence: 99%

Decoding Depression Severity from Intracranial Neural Activity

Xiao

Provenza

Asfouri

et al. 2022

Preprint

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Disorders of mood and cognition are prevalent, disabling, and notoriously difficult to treat. Fueling this challenge in treatment is a significant gap in our understanding of their neurophysiological basis. Here, we used intracranial neural recordings in three patients with severe depression to investigate the neural substrates of this disorder. Across prefrontal regions, we found that reduced depression severity is associated with decreased low-frequency neural activity and increased high-frequency activity. When constraining our model to decode using a single region, spectral changes in the anterior cingulate cortex best predicted depression severity in all three subjects. Relaxing this constraint revealed unique, individual-specific sets of spatio-spectral features predictive of symptom severity, reflecting the heterogeneous nature of depression. The ability to decode depression severity from neural activity increases our fundamental understanding of how depression manifests in the human brain and provides a target neural signature for personalized neuromodulation therapies.

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Evolving Issues in the Treatment of Depression

Cited by 18 publications

References 11 publications

Effectiveness of exercise-based interventions in reducing depressive symptoms in people without clinical depression: systematic review and meta-analysis of randomised controlled trials

Effectiveness of exercise-based interventions in reducing depressive symptoms in people without clinical depression: systematic review and meta-analysis of randomised controlled trials

The use of stimulants in depression: Results from a self-controlled register study

Decoding Depression Severity from Intracranial Neural Activity

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