From the Guidelines
Ziprasidone is generally considered weight neutral and may even be associated with modest weight loss in some patients. Among atypical antipsychotics, ziprasidone has one of the most favorable metabolic profiles, as noted in a study published in 2017 1. Typical dosing ranges from 40-160 mg twice daily, with a total daily dose of 80-320 mg. When switching patients from other antipsychotics associated with weight gain (like olanzapine or quetiapine) to ziprasidone, some patients experience weight loss, as studies have demonstrated that patients may lose weight and develop improved glucose tolerance when switched from olanzapine to ziprasidone 1.
Some key points to consider when prescribing ziprasidone include:
- Its unique receptor binding profile, particularly its minimal effect on histamine H1 receptors and its lack of significant antagonism at 5-HT2C receptors, both of which are associated with increased appetite and weight gain when blocked 1.
- Its minimal impact on insulin sensitivity compared to other antipsychotics, making it a favorable option for patients with metabolic concerns 1.
- The importance of taking ziprasidone with food (at least 500 calories) to maximize absorption.
- The need for regular monitoring of weight and metabolic parameters during treatment, despite its favorable weight profile.
Overall, ziprasidone's weight-neutral profile makes it a valuable option for patients who are concerned about weight gain or who have experienced weight gain with other antipsychotics.
From the FDA Drug Label
Weight Gain Weight gain has been observed with atypical antipsychotic use. Monitoring of weight is recommended. In long-term (at least 1 year), placebo-controlled, flexible-dose studies in schizophrenia, the mean change from baseline weight for ziprasidone 20 to 40 mg BID was -2.3 kg (N=124); for ziprasidone 60 to 80 mg BID was +2. 5 kg (N=10); and for placebo was -2.9 kg (N=72). In the same long-term studies, the proportion of subjects with ≥7% increase in weight from baseline for ziprasidone 20 to 40 mg BID was 5.6% (N=124); for ziprasidone 60 to 80 mg BID was 20.0% (N=10), and for placebo was 5. 6% (N=72). In a long-term (at least 1 year), placebo-controlled, fixed-dose study in schizophrenia, the mean change from baseline weight for ziprasidone 20 mg BID was -2.6 kg (N=72); for ziprasidone 40 mg BID was -3.3 kg (N=69); for ziprasidone 80 mg BID was -2.8 kg (N=70) and for placebo was -3. 8 kg (N=70).
Ziprasidone is associated with weight loss in some cases, as evidenced by the mean weight change from baseline in long-term studies. However, weight gain is also possible, particularly in patients with low baseline BMI. The proportion of patients with a ≥7% increase in weight from baseline varied across studies, but overall, ziprasidone appears to be relatively weight neutral. 2
From the Research
Ziprasidone and Weight Effects
- Ziprasidone is generally considered to be weight neutral or associated with weight loss, as opposed to other antipsychotic medications that can cause significant weight gain 3, 4, 5, 6, 7.
- A study comparing ziprasidone to olanzapine found that ziprasidone-treated patients showed no significant weight gain, whereas olanzapine-treated patients experienced significant weight gain 3.
- Another study analyzing data from ziprasidone clinical trials found that ziprasidone was associated with a minimal change in weight, with a mean weight change of 0.64 kg in short-term trials and -0.96 kg in long-term trials 4.
- A study in female rats found that ziprasidone treatment resulted in significant weight gain reduction, increased resting energy expenditure, and improved thermogenesis 5.
- A study in patients with mental retardation found that ziprasidone treatment was associated with significant weight loss and improvements in lipid profiles 6.
- Ziprasidone is considered to have a neutral effect on weight and metabolism, making it a preferable option for patients at risk of metabolic syndrome 7.