Medications that cause weight gain
Antipsychotics are used to treat mood disorders such as schizophrenia, bipolar disorder, depression, and personality disorders. First generation antipsychotics include chlorpromazine (Thorazine), loxapine (Loxitane), perphenazine (Etrafon, Trilafon), thioridazine (Mellaril), thiothixene (Navane), and trifluoperazine (Stelazine). Amongst the first generation antipsychotics, thioridazine (Mellaril) is associated with the highest risk for weight gain. Patients treated with thioridazine have reported average weight gain of 3.2 kg (7.05 pounds).
Second generation or atypical antipsychotics include clozapine (Clozaril), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), and risperidone (Risperdal). Atypical antipsychotics are associated with more weight gain than first generation antipsychotics. Among the second generation antipsychotics, clozapine and olanzapine are associated with the most weight gain. Patients may gain more than 4 kg while taking clozapine or olanzapine. Clozapine treatment has the most significant impact on weight gain. Studies have shown that weight gain from clozapine occurs in 4 to 31% of patients and the results of one study reported that 50% of patients treated gained 20% or more of their initial body weight. Olanzapine is second to clozapine in causing significant weight gain. Clinical trials have shown that 5 to 40% of all patients treated with clozapine report weight gain.
Risperidone has an intermediate effect on body weight. It can increase weight by about 2 kg. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study compared the effectiveness of the first and second generation antipsychotics. Results of the CATIE study showed that weight gain is significantly different between antipsychotic drugs. The percentage of patients who gained >7% of their body weight was 30% (olanzapine), 16% (quetiapine), 14% (risperidone), 12% (perphenazine), and 7% for ziprasidone.
All though they may also cause weight gain in some patients, aripiprazole and ziprasidone have the least impact on weight gain. Results from the CATIE trial show that ziprasidone treatment was associated with an average weight loss of 1.6 kg. Long-term treatment (26 weeks or more) with aripiprazole resulted in average weight loss of 0.9 to 1.37 kg. Therefore, ziprasidone and aripiprazole are preferred antipsychotics in patients who have experienced weight gain from other antipsychotics or those who are at high for weight gain.
Although the exact cause of weight gain from antipsychotic use is unknown, an increase in appetite is thought to be the main cause of weight gain. Also, the various antipsychotics have different effects on receptors in the brain and this is also thought to play a major role in their risk for weight gain. All antipsychotics block the dopamine-2 receptors in the brain which seems to contribute to antipsychotic-induced weight gain. Additionally, antipsychotics which block the histamine-1 and serotonin-2C receptors the most are more likely to increase weight. Clozapine and olanzapine block these receptors the most and are associated with the most weight gain. Quetiapine is highly effective in blocking the histamine-1 receptors but only weakly blocks the dopamine-2 and serotonin-2C receptors and is associated with moderate weight gain.