Can changing antipsychotic medication improve side effects like increases in weight, blood sugar and cholesterol?

Weight gain is common among people with schizophrenia. The medication commonly used to treat schizophrenia may cause substantial weight gain. This weight gain could be treated through lifestyle interventions that increase physical activity or change diet; or through using other forms of medication that might help with weight loss. However, an easier alternative might be changing the antipsychotic medication to one that causes less weight gain. This review examines evidence for this possibility. Switching antipsychotic medication did show some reduction in weight and also contributed broader health benefits such as reducing fasting blood glucose. Notably, there were no significant difference in outcomes of mental state, global state and adverse events between groups which switched medications and those that remained on previous medication.

Authors' conclusions: 

Evidence from this review suggests that switching antipsychotic medication to one with lesser potential for causing weight gain or metabolic problems could be an effective way to manage these side effects, but the data were weak due to the limited number of trials in this area and small sample sizes. Poor reporting of data also hindered using some trials and outcomes. There was no difference in mental state, global state and other treatment related adverse events between switching to another medication and continuing on the previous one. When the three switching strategies were compared none of them had an advantage over the others in their effects on the primary outcomes considered in this review. Better designed trials with adequate power would provide more convincing evidence for using medication switching as an intervention strategy.

Note: the 167 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.

Read the full abstract...

Weight gain is common for people with schizophrenia and this has serious implications for a patient's health and well being. Switching strategies have been recommended as a management option.


To determine the effects of antipsychotic medication switching as a strategy for reducing or preventing weight gain and metabolic problems in people with schizophrenia.

Search strategy: 

We searched key databases and the Cochrane Schizophrenia Group's trials register (January 2005 and June 2007), reference sections within relevant papers and contacted the first author of each relevant study and other experts to collect further information.

We updated this search November 2012 and added 167 new trials to the awaiting classification section.

Selection criteria: 

All clinical randomised controlled trials comparing switching of antipsychotic medication as an intervention for antipsychotic induced weight gain and metabolic problems with continuation of medication and/or other weight loss treatments (pharmacological and non pharmacological) in people with schizophrenia or schizophrenia-like illnesses.

Data collection and analysis: 

Studies were reliably selected, quality assessed and data extracted. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. The primary outcome measures were weight loss, metabolic syndrome, relapse and general mental state.

Main results: 

We included four studies for the review with a total of 636 participants. All except one study had a duration of 26 weeks or less. There was a mean weight loss of 1.94 kg (2 RCT, n = 287, CI -3.9 to 0.08) when switched to aripiprazole or quetiapine from olanzapine. BMI also decreased when switched to quetiapine (1 RCT, n = 129, MD -0.52 CI -1.26 to 0.22) and aripiprazole (1 RCT, n = 173, RR 0.28 CI 0.13 to 0.57) from olanzapine.

Fasting blood glucose showed a significant decrease when switched to aripiprazole or quetiapine from olanzapine. (2 RCT, MD -2.53 n = 280 CI -2.94 to -2.11). One RCT also showed a favourable lipid profile when switched to aripiprazole but these measures were reported as percentage changes, rather than means with standard deviation.

People are less likely to leave the study early if they remain on olanzapine compared to switching to quetiapine or aripiprazole.

There was no significant difference in outcomes of mental state, global state, and adverse events between groups which switched medications and those that remained on previous medication. Three different switching strategies were compared and no strategy was found to be superior to the others for outcomes of weight gain, mental state and global state.