by Josephine Machado
Graphic design by Vicky Lin
What’s one to do when a medication that is set out to help their mind mounts an unprecedented attack on their relationship with their body? While psychiatric medications can be an essential tool in improving quality of life, weight gain continues to be a particularly distressing side effect for those who rely on them. This remains a relevant concern given that the use of these medications is on the rise. Many individuals with mental health concerns face lengthy wait times to receive sustained government-funded support; therefore, relative to other treatments, psychotropic medications can provide timely and cost-effective relief for what can constitute debilitating symptoms. As a result, between 2019 and 2023, the prevalence of individuals who received antidepressants from community pharmacies in Canada increased from 15.4% to 16.4%, with over 6.6 million Canadians reporting antidepressant use in 2023 alone.1 The use of antipsychotic medications, used to treat conditions such as schizophrenia, has also increased in recent years, with over 1.5 million individuals reporting use of antipsychotic medications in 2022.1
This places additional burden on the stigma that comes with receiving treatment for depression, as weight gain is a well-established side-effect of almost all psychotropic medications.2, Antidepressants are commonly prescribed for major depressive disorder and anxiety; however, long-term use is similarly associated with weight gain, affecting up to 55–65% of patients.3 While antidepressant-related weight gain remains modest to mild in comparison to antipsychotic-related weight gain, selective serotonin reuptake inhibitors (SSRIs) such as paroxetine have been associated with weight gain of up to 2.7 kg.2 A particularly challenging aspect of prescribing psychotropic medication is that there are no tools available to definitively identify patients with a greater susceptibility to weight gain,4 making monitoring weight an imperative component of medication management.
How Do Psychotropic Medications Cause Weight Gain?
Several biological mechanisms have been proposed to facilitate antidepressant-induced weight gain, especially in cases of long-term use. Antidepressants generally act by increasing the availability of neurotransmitters in the brain, such as serotonin and dopamine. Given that serotonergic and dopaminergic pathways play a role in regulating both mood and appetite, mechanisms that improve mental health may also have an influence on body weight.3 Long-term use of SSRIs is thought to downregulate and desensitize serotonin receptors, reducing the activity of neurons that supress appetite.3 Moreover, dopamine pathways are essential for feeding behaviours, with medication-induced alterations including inhibition of dopamine pathways in the brain’s reward centres. This can blunt sensitivity to pleasure and trigger food-seeking behaviour—where a person eats more, craving carbohydrates specifically—to feel satisfied.3
Antipsychotics, however, cause weight gain by blocking histamine and serotonin receptors in the hypothalamus, where appetite is controlled, thus stimulating appetite and delaying satiety signals, leading to increased food intake.2,5 Antipsychotics can also block muscarinic receptors on cells in the pancreas that produce insulin, which interferes with insulin secretion and increases susceptibility to diabetes signals.2,5 Finally, these drugs can also alter the gene expression, promote the creation and storage of fat, and disrupt hormones such as leptin and ghrelin signals.5
Medication-related weight gain is a common deterrent to psychiatric treatment, often prompting an unwillingness to begin medication as well as increasing treatment nonadherence.4 Medication hesitancy poses a clinical concern in that it can increase the risk of relapse or worsen depressive symptoms.3 Psychotropic medication-induced weight gain can also exacerbate comorbid conditions such as obesity, diabetes, and cardiovascular disease. Obesity is the second most common cause of preventable death after smoking; thus, the need to monitor medication-induced weight gain is crucial.3
Managing Psychotropic-Medication Induced Weight Gain
Lifestyle- or behavioural-based management is one avenue of management, with methods such as alterations to diet, regular physical activity, and even switching psychotropic medications serving as common approaches for managing weight gain. Cognitive and behavioral strategies under the guidance of a licensed mental health professional may also be helpful in assisting adhering to lifestyle changes.6 Early weight gain can act as a predictor of future weight gain;7 thus, monitoring metabolic health during follow-up visits is important to help identify signs of weight gain and allow for both lifestyle-based and pharmacological interventions.
Adjunctive medications for weight-management have been utilized to mitigate antidepressant-induced weight gain. Several options exist, but the most commonly used and efficacious treatment is metformin, acting as an insulin sensitizer with moderate strength in mitigating antidepressant-related weight gain.3 However, recent years have seen a rise in the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of medication used to treat type 2 diabetes and obesity.8 GLP-1RAs induce appetite suppression and have been shown to be highly effective in mitigating the effects of medication-induced weight gain. A 2024 systematic review of six studies where participants utilized GLP-1RAs while on psychotropic drugs found that the majority reported significant and clinically meaningful effects on GLP-1RAs on metabolism and body weight, with one study reporting an average reduction of 3.7 kg compared to 0 kg in the placebo group.9 As an added bonus, although the evidence is still in its early stages, GLP-1RAs may also reduce symptoms of depression themselves, giving them the potential of alleviating the primary issue of the mental health concern that led to medication use in the first place.10
Looking Forward: Weight Conscious Care
While antidepressants and antipsychotics can profoundly improve functionality and quality of life, the metabolic consequences of such treatment modalities—particularly weight gain—remains an important clinical consideration. Weight gain has been shown to have significant impacts on treatment adherence thus affecting mental health outcomes. Part of breaking the stigma around mental health involves not only covering and accepting the collateral effects of mental health treatments, such as weight gain, but also acknowledging that the unintended consequences can also have significant impacts on both one’s self-confidence and quality of life. Overall, it is indisputable that psychotropic medication use in Canada is on the rise, not only as a result of a growing prevalence in mental health concerns, but the rather significant restraints that have been placed on access to care in a timely and effective manner. Thus, continuing to research and explore methods for mitigating the side-effects of such medications—such as psychotherapy, adjunctive medications, and lifestyle changes—is an important aspect of mental health research. The pursuit of essential mental healthcare should remain a priority by ensuring that treatment is not avoided due to side effects, but that those side effects are managed well enough for individuals to feel empowered to seek necessary care.
References
1. Medication Treatments for Mental Health Disorders in Canada An independent IQVIA report on drug utilization data, 2020-2024. Canada: IQVIA.
2. Mazereel V, Detraux J, Vancampfort D, et al. Impact of Psychotropic Medication Effects on Obesity and the Metabolic Syndrome in People With Serious Mental Illness. Front Endocrinol. 2020 Oct 9;11:573479. doi:10.3389/fendo.2020.573479
3. Mouawad M, Nabipur L, Agrawal DK. Impact of Antidepressants on Weight Gain: Underlying Mechanisms and Mitigation Strategies. Arch Clin Biomed Res. 2025;9(3):183–95. PubMed PMID: 40444017; PubMed Central PMCID: PMC12121960.
4. McIntyre RS, Kwan ATH, Rosenblat JD, et al. Psychotropic Drug–Related Weight Gain and Its Treatment. AJP. 2024 Jan 1;181(1):26–38. doi:10.1176/appi.ajp.20230922
5. Dayabandara M, Hanwella R, Ratnatunga S, et al. Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. Neuropsychiatr Dis Treat. 2017;13:2231–41. doi:10.2147/NDT.S113099 PubMed PMID: 28883731; PubMed Central PMCID: PMC5574691.
6. MPH CA MD. Harvard Health [Internet]. 2022 [cited 2026 Mar 14]. Managing weight gain from psychiatric medications. Available from: https://www.health.harvard.edu/blog/managing-weight-gain-from-psychiatric-medications-202207182781
7. Vandenberghe F, Gholam-Rezaee M, Saigí-Morgui N, et al. Importance of Early Weight Changes to Predict Long-Term Weight Gain During Psychotropic Drug Treatment. J Clin Psychiatry. 2015 Nov 25;76(11):e1417–23. doi:10.4088/JCP.14m09358
8. Collins L, Costello RA. Glucagon-Like Peptide-1 Receptor Agonists. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 [cited 2026 Mar 14]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK551568/ PubMed PMID: 31855395.
9. Menon T, Lee S, Gong XY, et al. A systematic review on the efficacy of GLP-1 receptor agonists in mitigating psychotropic drug-related weight gain. CNS Spectr. 2024 Oct;29(5):347–53. doi:10.1017/S1092852924000531
10. Chen X, Zhao P, Wang W, et al. The Antidepressant Effects of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis. The American Journal of Geriatric Psychiatry. 2024 Jan;32(1):117–27. doi:10.1016/j.jagp.2023.08.010
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