Metabolic Side Effects of Antipsychotics Vary, Meta-Analysis Finds

When it comes to the risk of metabolic side effects, not all antipsychotics are equal, suggests a meta-analysis published in World Psychiatry. The analysis revealed that patients with schizophrenia who took chlorpromazine or clozapine for more than 13 weeks experienced the most weight gain on average compared with those taking placebo.

Angelika Burschinski, M.D., of the Technical University of Munich and colleagues compiled data from 137 clinical trials that compared outcomes of patients who had schizophrenia, schizophreniform disorder, or schizoaffective disorder and took antipsychotics or placebo for more than 13 weeks. The combined sample included 35,007 participants who had taken 31 different antipsychotics (both oral and injectable) that are available in the United States and/or Europe. The researchers compared the effects of these medications on body weight as well as fasting glucose, cholesterol, and triglyceride levels.

The median age of the participants in the analysis was 39 years, and the median length of follow-up was 45 weeks. The researchers found that five antipsychotics contributed to significant average weight gain relative to placebo:

• chlorpromazine (5.13 kg, or over 11.3 lbs)
• clozapine (4.21 kg, or over 9.3 lbs)
• zotepine (3.87 kg, or 8.5 lbs)
• oral olanzapine (3.82 kg, or 8.4 lbs)
• long-acting injectable olanzapine (3.60 kg, or 7.9 lbs)

Seven other antipsychotics, including risperidone and quetiapine, were associated with average weight gains of 1 to 2 kg (2 to 4.5 lbs) over the study period.

The medications associated with the highest weight gain in participants were also associated with greater changes in glucose, cholesterol, and triglyceride levels. Olanzapine was associated with the greatest effects on glucose, total cholesterol, and LDL cholesterol; amisulpride (which led to an average weight gain of 1.43 kg, or over 3 lbs), was associated with the greatest effects on HDL cholesterol and triglycerides.

“[M]etabolic side effects of antipsychotics are likely to contribute to the average 14.5 years reduced lifespan of individuals with schizophrenia. Furthermore, weight gain is associated with decreased quality of life and treatment nonadherence, the latter resulting in poor treatment outcome and psychotic relapses,” Burschinski and colleagues wrote. “As antipsychotic drugs are often taken for long periods of time, our results represent more valuable clinical information on these health consequences than previous analyses based on short-term studies, which on average only lasted 6 weeks.”

To read more on this topic, see the Psychiatric News article “What Antipsychotic Dose Is Most Effective?”

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Adjunctive Liraglutide Found to Reduce Weight Gain, Metabolic Effects From Clozapine, Olanzapine

Patients with schizophrenia who experience weight gain and metabolic disturbances while taking clozapine or olanzapine may benefit from once-daily adjunctive treatment with the anti-diabetic medication liraglutide, reports a study published June 10 in JAMA Psychiatry.

“In overweight or obese patients with schizophrenia spectrum disorders and prediabetes, 16 weeks of liraglutide as an adjunctive treatment to stable treatment with clozapine or olanzapine significantly improved glucose tolerance and glycemic control. At the end of the trial, the placebo-subtracted body weight loss was 5.3 kg,” wrote Anders Fink-Jensen, D.M.Sc., of the University of Copenhagen and colleagues. Liraglutide is a glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes and obesity. 

These findings are encouraging for patients taking these antipsychotics, which are among the most effective for treating schizophrenia but also have the greatest risk of cardiovascular and metabolic side effects, according to the authors.

The study included 103 adults aged 18 to 65 who were diagnosed with a schizophrenia spectrum disorder (schizoaffective disorder excluded) and were receiving stable treatment with clozapine or olanzapine. The participants, who all had prediabetes and a body mass index of 27 or greater, were randomly assigned to 16 weeks of once-daily treatment with subcutaneously injected liraglutide (up to 1.8 mg) or placebo provided in prefilled pen injectors. Every four weeks, participants had blood samples obtained; body weight, waist circumference, and blood pressure measured; and adverse events and alcohol consumption recorded. 

After 16 weeks, patients taking liraglutide had a 23% larger reduction in their two-hour plasma glucose level compared with the placebo group. In the liraglutide group, 30 patients (63.8%) changed status from prediabetes to normal glucose tolerance compared with eight (16.0%) in the placebo group.

Additional benefits observed in the liraglutide group included decreased waist circumference, systolic blood pressure, and low-density lipoprotein cholesterol levels.

Patients in the liraglutide group experienced significantly higher rates of nausea (31 of 50 [62%] vs. 16 of 50 [32%]), but these differences diminished over time, the authors noted.

“Altogether, the liraglutide group experienced significantly fewer serious adverse events, with exacerbation of patients’ psychiatric disease being the most common cause, and no differences in quality of life, daily functioning, or psychiatric disease severity were found,” the authors added.

For related information, see the Psychiatric News article “Aripiprazole May Reduce Some Side Effects of Antipsychotics in Women.” 

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