MHM Magazine

18 | MENTAL HEALTH MATTERS | 2025 | Issue 2 MHM anxiety have all been shown to be associated with significant weight gain. While it’s essential that medication efficacy be the first priority when treating patients with SMI, it’s also essential to consider tolerability of these drugs. Weight gain secondary to medication use is a common reason for discontinuation of these agents. In fact, a study published in European Psychiatry reported an average weight gain of 9 kg after a first episode of psychosis and an increase in BMI of 3 kg/ m2. It’s therefore vital that health care providers (HCPs) prescribing these drugs are aware of the side effect profile associated with different medications and consider both their efficacy and tolerability when prescribing long-term pharmacotherapy. Although the link is clear, the aetiology of weight gain with these agents is not yet fully elucidated. Psychotropic weight gain may be mediated by: • Gender: women have a greater risk of antipsychotic-induced weight gain • Increased appetite and food intake • Decreased satiety signaling • Decreased caloric expenditure • Cognitive distortions related to weight • Cytokines, including TNF-alpha • Genetic susceptibility The culprits that are responsible for significant weight gain (>10kg on average) are the following: • Antidepressants: 1. Tricyclics: amitryptilline 2. Selective serotonin reuptake inhibitors (SSRIS): citalopram, fluoxetine • Anticonvulsants: 1. Valproic acid 2. Carbamazepine 3. Gabapentin The following drugs are associated with a 5 – 10kg increase in weight, although in clinical practice, we often see significantly more: • Antidepressants: 1. SSRIs: paroxetine, escitalopram, lithium • Most first and second generation antispychotics: haloperidol, clozapine, chlorpromazine, olanzapine, quetiapine The following drugs are said to be weight neutral and some may even cause weight loss: • Antidepressants: bupropion, duloxetine, venlafaxine, desvenlafaxine, trazadone, vortioxetine • Antipsychotics: ziprasidone, aripiprazole • Anticonvulsants: topiramate, lamotrigine The effects of these drugs are so profound that in a cross-sectional Canadian population study (n = 36, 984) antidepressants and antipsychotics accounted for 86% of the relationship between mood disorders and obesity and 32% of the relationship between anxiety disorders and obesity. How do we help our patients manage psychotropic-induced weight gain? 1. Lifestyle interventions: In 2019, a metanalysis of 41 randomised controlled trials (RCTs) examining the impact of lifestyle interventions for weight management in people with SMI reported a statistically significant but clinically insignificant mean effect of individualised lifestyle interventions for weight reduction in people with SMI (mean difference in BMI was -0.6 kg/m2). Therefore, lifestyle intervention alone should not be the only strategy employed to help these patients manage their weight. 2. Switching strategies: it may be beneficial to switch patients to less metabolically active second-generation antipsychotics but this as a single intervention has limited success (switching to aripiprazole or quetiapine to olanzepine led to a mean weight reduction of 1.94kg). The decision to change treatment must be considered on a case-by-case basis in context of efficacy, tolerability and patient choice. 3. Metformin: across several published meta-analyses of RCTs in patients with schizophrenia spectrum disorders, metformin consistently emerged as an effective and safe intervention resulting in modest weight loss as compared to placebo (average of 3.5kg), as well as improvements in lipids and insulin sensitivity parameters. A meta-analysis which looked at patients with mood disorders on mood stabilisers found similar beneficial effects of metformin over placebo. The effect of metformin may be greater in first-episode patients, so this is a drug best initiated early on when starting psychotropic medications. Metformin should be started at 500mg twice daily with meals and dose increasing every one to two weeks to target a dose of 2000mg per day. 4. Glucagon like peptide 1 receptor agonists (GLP-1RAs): whilst these have been a game-changer in the world of obesity management, data in patients with SMI is still limited. Three studies looking at older GLP-1Ras (exenatide and liraglutide) suggested a body weight loss of 3.71kg after 16 weeks of treatment with an improvement in metabolic parameters. The drugs were generally well tolerated. However, newer agents such as semaglutide and tirzepatide (not yet registered in South Africa for obesity management) are being used in these patients in clinical practice and will most likely offer significant benefit in terms of sustained weight reduction. Understanding the association between mental illness and obesity is not simply an academic exercise. Patients with mental illness have increased morbidity and mortality, in some cases with a risk of premature death of up to 15 years. The increased mortality is directly linked to weight gain. It is a challenge for clinicians to address both the physical and mental needs of these patients but given the interaction between the two conditions it should be considered standard of care, both at an individual and health systems level. References available on request. MHM | 2025 | Volume 12 | Issue 2 | Obesity in the psychiatrist’s office H