The impact of pharmacological and non-pharmacological interventions on physical health outcomes in people with mood disorders across the lifespan: an umbrella review of the evidence from randomised controlled trials
Open accessAbstract
Objective People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical health in this population. Methods Umbrella review of meta-analyses of randomised controlled trials (RCTs) on pharmacological/non-pharmacological interventions for physical health outcomes/intolerability-related discontinuation in mood disorders (any age). Results Ninety-seven meta-analyses were included. Among youths, against placebo, in depression, antidepressants/antipsychotics had higher discontinuation rates; in bipolar depression, olanzapine+fluoxetine worsened total cholesterol (TC)/triglycerides/weight gain (WG) (large ES). In adults with bipolar disorder, olanzapine worsened HbA1c/TC/WG (moderate/large ES); asenapine increased fasting glucose (small ES); quetiapine/cariprazine/risperidone induced WG (small/moderate ES). In bipolar depression, lurasidone was metabolically neutral. In depression, psychological interventions improved physical health-related quality of life (PHQoL) (small ES), fasting glucose/HbA1c (medium/large ES); SSRIs improved fasting glucose/HbA1c, readmission for coronary disease, pain (small ES); quetiapine/aripiprazole/olanzapine induced WG (small to large ES). Exercise improved cardiorespiratory fitness (moderate ES). In the elderly, fluoxetine yielded more detrimental cardiovascular effects than sertraline/escitalopram (large ES); antidepressants were neutral on exercise tolerance and PHQoL. In mixed age groups, in bipolar disorder aripiprazole was metabolically neutral; in depression, SSRIs lowered blood pressure versus placebo and serotonin-noradrenaline reuptake inhibitors (small ES); brexpiprazole augmentation caused WG and was less tolerated (small ES); exercise improved PHQoL (moderate ES). Conclusions Some interventions (psychological therapies, exercise and SSRIs) improve certain physical health outcomes in mood disorders, few are neutral, but various pharmacological interventions are associated with negative effects. Evidence from this umbrella review has limitations, should consider evidence from other disorders and should be integrated with recent evidence from individual RCTs, and observational evidence. Effective treatments with either beneficial or physically neutral profiles should be prioritized.
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The mean increases in msec compared to placebo were very small, in line with a recent review.
“The mean increases in msec compared to placebo were very small, in line with a recent review.36”
From Comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression in adults: a systematic review and network meta-analysis (2023) · cites this paper as [36]
The Cardiovascular and respiratory system section (page unavailable) reports no difference in QTc change when antipsychotics were added to mood stabilizers in adults with bipolar disorder. The Results table (page unavailable) gives a nonsignificant standardized difference for that comparison, but the review does not report small mean increases in milliseconds versus placebo. (LLM, conf=0.78)
Experimental — accuracy not yet measuredAn umbrella review including bipolar depression pointed out that most antipsychotics have an unfavourable risk profile.
“An umbrella review including bipolar depression also pointed out that most antipsychotics have an unfavourable risk profile.36”
From Comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression in adults: a systematic review and network meta-analysis (2023) · cites this paper as [36]
The mean weight gain results are in line with those in schizophrenia.
“The mean weight gain results are in line with those in schizophrenia.36,38”
From Comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression in adults: a systematic review and network meta-analysis (2023) · cites this paper as [36]
The Body weight and body mass index section reports weight gain in people with mood disorders, but does not compare mean weight gain with results in schizophrenia. Searches for schizophrenia and comparable weight gain found no passage making that comparison in our copy. (LLM, conf=0.72)
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- Authors
- Croatto, G., Vancampfort, D., Miola, A., Olivola, M., Fiedorowicz, J. G., Firth, J., Alexinschi, O., Gaina, M. A., Makkai, V., Soares, F. C., Cavaliere, L., Vianello, G., Stubbs, B., Fusar-Poli, P., Carvalho, A. F., Vieta, E., Cortese, S., Shin, J. I., Correll, C. U., & Solmi, M.
- Affiliations
- KU Leuven (BE)
- University of Padua (IT)
- University of Pavia (IT)
- University of Ottawa (CA)
- Manchester Academic Health Science Centre (GB)
- Universidade de Pernambuco (BR)
- King's College London (GB)
- Barwon Health (AU)
- Centro de Investigación Biomédica en Red de Salud Mental (ES)
- University of Nottingham (GB)
- Yonsei University (KR)
- Northwell Health (US)
- Corresponding author
- Solmi, Marco
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2022-09-22
- Volume
- 28
- Issue
- 1
- Pages
- 369-390
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC9493151
- OpenAlex
- W4296619482
- Semantic Scholar
- 8bfbeda862e68c7aec6304dd3ecf6c8f8dc002fa
- Cited by
- 66
- References
- 50
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 16 · 2023: 9 · 2022: 3
- FWCI
- 2.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Lirias (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- UK Research and Innovation (P123958, MR/T021780/1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- mood disorders, bipolar disorder, depression, physical health, antidepressants, antipsychotic drugs, weight gain, metabolic side effects, cardiovascular risk, psychological intervention, physical activity, physical health-related quality of life, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, brexpiprazole, bipolar depression, comorbidities
- MeSH terms
- Aripiprazole, Quetiapine Fumarate, Olanzapine, Adolescent, Adult, Aged, Antidepressive Agents, Bipolar Disorder, Fluoxetine, Glycated Hemoglobin, Humans, Longevity, Antipsychotic Agents, Randomized Controlled Trials as Topic, Outcome Assessment, Health Care, Selective Serotonin Reuptake Inhibitors
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