Do antipsychotics differ in weight gain during first episode treatment? Early Inter Psy.2015.Epub, June, 2015


Obesity contributes significantly to poor cardiac health among individuals with psychosis. Cardiovascular risk doubles in first year of treatment with antipsychotics.  Antipsychotics (AP) contribute heavily to this weight gain. Prevention of rapid weight gain during the early period of psychosis should be a major aim.

Meta analysis suggest that anti histaminic antipsychotics (clozapine, olanazapine, chlorpromazine, quetiapine) and 5HT2C blockers ( risperidone, paliperidone) are more likely to cause weight gain compared to pure D2 blockers like haloperidol. Contributing factors/ mechanisms involved in weight gain chronic schizophrenia while on AP may be different  from first episode cases.

Tel C et al conducted a meta-analysis of all AP studies in first- episode patients looking at weight changes during  short-term (≤12 weeks) and long-term (>12 weeks) treatment. Studies on first episode psychosis patients ( minimum age of 15, less than 16 weeks AP treatment in life time or AP naive at entry, treatment provided in OP settings) were included. Short term AP treatment was defined as less than 12 weeks, long term was defined as  13-52 weeks. Since there is no placebo controlled study in first episode patients, study sample with prodromal patients were used to calculate placebo controlled group outcomes.


From 3059 studies identifies initially, 28 studies that met all inclusion criteria were analysed.  Majority (22) of these were open label studies.

Mean weight gain difference was 3.22 kg in AP group compared to placebo.  The mean weight difference was significantly higher in Western countries (4.17 kg, CI = 3.38–4.96) than in Asian countries (1.36 kg, CI = −0.25 to 2.99).

Long term effect on weight : 5.30 kg  mean gain difference  between AP medications and placebo ( CI = 2.87–7.74, P < 0.001)

Olanzapine (n = 6, 9.34 kg (CI = 5.55– 13.12), P < 0.001) and clozapine (n = 2, 7.19 kg (CI = 0.28–14.09), P = 0.041) were the interventions associated with the highest weight gain compared to placebo. The only one intervention with perphenazine reported weight loss (−0.41 kg)

Ziprasidone maintains weight benefit effect in first episode samples. (This is already shown in chronic schizophrenia samples). This might be down to  noradrenaline re uptake blocking effects. Individual risk even with  Ziprasidone is not negligible. Ziprasidone registration studies showed that 7-16% participants gained significant weight. Olanzapine and  Clozapine consistently show increase in weight irrespective of stage of illness.

Haloperidol, unlike in studies of chronic schizophrenia patients, was associated with both short- and long-term weight gains in this analysis. Aripiprazole’s advantage shown in previous studies was not observed in this. Long term studies of aripiprazole on weight are lacking.

There seems to be no advantage in selecting Olanzapine as first or second agent in first episode patients, though studies still show that this medication continue to be  the commonly used antipsychotic.

Medication studies need to ensure that baseline weight, BMI and percentage increase  as well as dose -weight relationship are reported  routinely.

Comment: Weight gain need to be monitored closely and choice of AP should consider this effect. This is more so important during early stage of AP treatment.

Summary of article:

Antipsychotic-induced weight gain in first-episode psychosis patients: a meta-analysis of differential effects ofantipsychotic medications.

Tek C, Kucukgoncu S, Guloksuz S, Woods SW, Srihari VH, Annamalai A.

Early Interv Psychiatry. 2015 May 12. doi: 10.1111/eip.12251. [Epub ahead of print]

2 thoughts on “Do antipsychotics differ in weight gain during first episode treatment? Early Inter Psy.2015.Epub, June, 2015

  1. Is pherphenazine available in India? What about thioridazine (ridazin) which is a typical agent with less EPs? Thoiridazine is available in India but is not popular among new generation practitioners.

  2. Perphenazine is available in UK. But is not a preferred antipsychotic, I understand situation is different in many European countries..
    Novartis stopped thioridazine in 2005 ( cardiac arrhythmia).Generic forms are still available in many countries. It is not prescribed at all in UK.

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