How can weight gain associated with antipsychotic (anti-psychotic) medication be mitigated?

Strategies to Mitigate Antipsychotic-Associated Weight Gain

Metformin should be offered concomitantly with antipsychotics that have poor cardiometabolic profiles (particularly olanzapine and clozapine) to attenuate potential weight gain. 1

First-Line Pharmacological Interventions

• Metformin is the best-evidenced medication for counteracting antipsychotic-induced weight gain, with a recommended starting dose of 500 mg once daily, gradually increasing to 1g twice daily as tolerated 1
• Modified-release metformin preparations should be used when available to minimize gastrointestinal side effects 1
• Before starting metformin, assess renal function, as it should be avoided in patients with renal failure 1
• Ongoing monitoring should include annual liver function, HbA1c, renal function, and vitamin B12 1

Antipsychotic Selection and Switching

• Choose antipsychotics with lower weight gain liability when clinically appropriate:
  • Lurasidone and ziprasidone appear to be the most weight-neutral options 1
  • Aripiprazole generally demonstrates a lower risk for weight gain 1, 2
  • Olanzapine, clozapine, quetiapine, and risperidone are consistently associated with significant weight gain 1, 3
• Consider switching from higher-risk to lower-risk antipsychotics when clinically appropriate:
  • Studies demonstrate that patients may lose weight and develop improved glucose tolerance when switched from olanzapine to ziprasidone 1
  • Ziprasidone shows minimal weight gain in clinical trials, with a median weight gain of only 0.5 kg compared to no median weight change in placebo patients 4

Non-Pharmacological Interventions

• Lifestyle interventions should be implemented for all patients on antipsychotics:
  • Provide dietary counseling and promote physical activity 1, 5
  • Implement cognitive-behavioral strategies to address eating behaviors 5, 6
  • Regular weight monitoring is essential - check BMI, waist circumference, and blood pressure weekly for the first 6 weeks after starting or switching antipsychotics 1

Additional Pharmacological Options

• Bupropion is the only antidepressant consistently shown to promote weight loss through appetite suppression and may be considered as an adjunctive treatment when clinically appropriate 1
• Topiramate has been associated with weight loss and could be considered as an adjunctive treatment 1, 7
• GLP-1 receptor agonists may be considered for cognitive remediation treatment strategies 1

Special Considerations

• Weight gain typically occurs rapidly in the initial period after starting antipsychotics, making early intervention crucial 5, 3
• Individual responses to antipsychotics vary significantly - some patients gain weight, some maintain weight, and some lose weight even on the same medication 3, 8
• Predictors of significant weight gain include lower baseline BMI, increased appetite, and rapid initial weight increase 3
• First-episode patients are at higher risk for weight gain due to lack of prior antipsychotic exposure 3
• Improvement in negative symptoms may contribute to better weight management through increased motivation for diet and exercise 6

Monitoring Protocol

• Before starting antipsychotic treatment, obtain baseline measurements of BMI, waist circumference, blood pressure, HbA1c, glucose, lipids, prolactin, liver function tests, urea and electrolytes, full blood count, and electrocardiogram 1
• Recheck fasting glucose 4 weeks after initiation 1
• Monitor BMI, waist circumference, and blood pressure weekly for the first 6 weeks 1
• Repeat all baseline measurements after 3 months of treatment and annually thereafter 1