Updates and Advances in Antipsychotic Induced Metabolic Adverse Events

Krissy Reinstatler, PharmD, BCPP, MBA
CPNP Programming Committee Member

People with schizophrenia have a life expectancy 20 years less than the general population¹, with more than a third of these deaths attributable to cardiovascular disease (CVD) and type 2 diabetes². The increased risk of cardiometabolic disease is multifactorial and contributing causes include glucose dysregulation and weight gain associated with antipsychotic medications.² The prevalence of obesity among people with psychotic disorders is 41–50%, which is substantially higher than the 20–27% prevalence in the general population.³ Many antipsychotics are associated with weight gain and other metabolic complications.⁴ In fact, studies suggest 50% of patients treated with antipsychotics develop metabolic syndrome⁵ and the prevalence of metabolic syndrome is higher in patients treated with antipsychotics than in drug naive patients with schizophrenia⁴.

Identification and treatment of metabolic syndrome are imperative to prevent possible progression to diabetes or CVD and improve an individual’s overall health. Studies have examined a variety of approaches, including off-label uses of medications for weight-management and adjunctive antipsychotics with a more metabolically neutral side effect profile. A 2014 meta-analysis found 19 distinct interventions for antipsychotic-induced weight gain.⁶ The British Association for Psychopharmacology has recently created guidelines to address aspects of monitoring and management of risk factors for diabetes and CVD in adults over the age of 18 years with psychosis. The main interventions recommended in these guidelines are lifestyle interventions, antipsychotic switching, adjunctive aripiprazole, and adjunctive metformin.¹ One of the antipsychotics known to have some of the most deleterious effects on cardiometabolic health is olanzapine. A combination of olanzapine and the opioid modulator samidorphin to reduce weight gain and metabolic impact is currently in clinical trials.⁷

To assist clinicians in navigating treatment options for antipsychotic-induced metabolic events, Christopher Correll, MD, will be speaking at the 2020 CPNP annual meeting in Dallas, Texas.

Specific objects for Dr. Correll’s talk include:

1. Define metabolic disorder and the criteria needed for diagnosis
2. Explain the mechanism/pathophysiology behind antipsychotic-induced metabolic syndrome
3. Interpret a medication regimen and objective patient data (e.g., labs) to evaluate risk of metabolic syndrome
4. Create a treatment plan to treat metabolic syndrome and/or reduce the risk of metabolic syndrome occurring

Dr. Correll is a professor at the Center for Psychiatric Neuroscience of the Feinstein Institutes for Medical Research, the Medical Director of the Recognition and Prevention (RAP) Program in the Department of Psychiatry at Zucker Hillside Hospital, and a professor of psychiatry and molecular medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell. Dr. Correll’s research and clinical work focus on the identification, characterization and psychopharmacological management of adults and youth with severe psychiatric disorders. His areas of expertise include schizophrenia, bipolar disorder, major depression and other psychotic, mood and autism/disruptive behavior spectrum disorders. His work focuses on the risk-benefit evaluation of psychotropic medications, including the interface between psychiatry and medicine and investigations of the extent and mechanisms of cardiometabolic adverse effects.

References

1. Cooper SJ, et al. BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment. Journal of Psychopharmacology. 2016;30(8):717–748.
2. Siskind D, et al. CoMET: a protocol for a randomized controlled trial of co-commencement of METformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia newly commenced on clozapine. BMJ Open 2018;8:e021000.
3. Bruins J, et al. The Effects of Lifestyle Interventions on (Long-Term) Weight Management, Cardiometabolic Risk and Depressive Symptoms in People with Psychotic Disorders: A Meta-Analysis. PLOS One. 2014;9(12):e112276.
4. de Silva VA et al. Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis. BMC Psychiatry. 2016;16:341.
5. MacKenzie NE, et al. Antipsychotics, metabolic adverse effects, and cognitive function in schizophrenia. Front Psychiatry. 2018;9(622):1-12.
6. Mizuno Y, et al. Pharmacological Strategies to Counteract Antipsychotic-Induced Weight Gain and Metabolic Adverse Effects in Schizophrenia: A Systematic Review and Meta-analysis. Schizophrenia Bulletin. 2014;40(6):1385-1403.
7. Martin WF, et al. Mitigation of Olanzapine-Induced Weight Gain With Samidorphan, an Opioid Antagonist: A Randomized Double-Blind Phase 2 Study in Patients With Schizophrenia. Am J Psychiatry. 2019;176(6):457-467.