Can fluvoxamine, quetiapine (Seroquel), or valproate (Depakote) contribute to weight gain?

From the Guidelines

Yes, fluvoxamine, Seroquel (quetiapine), and Depakote (valproate) can all contribute to weight gain, though to varying degrees, with Seroquel typically causing the most significant weight gain. According to a recent review on obesity management in adults 1, many commonly used medications, including antipsychotics like quetiapine, are associated with weight gain. The weight gain effect of these medications can increase the risk of weight-related complications, including cardiovascular disease, diabetes, and hepatic steatosis.

Weight Gain Effects of Each Medication

• Seroquel (quetiapine) can cause significant weight gain, with patients potentially gaining 2-7 pounds within the first few weeks of treatment and up to 10-20 pounds over longer periods, as weight gain often begins within the first 4-8 weeks of therapy.
• Depakote (valproate) commonly causes moderate weight gain of approximately 5-15 pounds, typically beginning within the first 3 months of treatment.
• Fluvoxamine, an SSRI, is less likely to cause significant weight gain compared to the other two medications, with most patients experiencing minimal changes (0-5 pounds) or no weight change at all.

Mechanisms and Recommendations

The mechanisms behind this weight gain include increased appetite, altered metabolism, fluid retention, and changes in glucose regulation, as noted in the review 1. Patients with pre-existing risk factors such as a history of obesity or metabolic disorders may be more susceptible to medication-induced weight gain. Regular monitoring of weight, especially during the initial months of treatment, is recommended, and lifestyle modifications including diet and exercise can help mitigate these effects. If weight gain becomes problematic, discussing medication alternatives with your healthcare provider is advisable, as abruptly stopping these medications can lead to withdrawal symptoms or recurrence of the condition being treated. Additionally, medications like metformin and topiramate can be considered as adjunctive therapy to counteract the effects of weight gain-promoting agents, particularly antipsychotics, as they have been shown to result in a mean difference of −3.27 kg and −3.76 kg, respectively, in weight gain compared to placebo 1.

From the FDA Drug Label

Weight Gain Increases in weight have been observed in clinical trials Patients receiving quetiapine should receive regular monitoring of weight. Adults: In clinical trials with quetiapine the following increases in weight have been reported Table 6: Proportion of Patients with Weight Gain ≥ 7% of Body Weight (Adults) Vital Sign Indication Treatment Arm N Patients n (%)

• up to 6 weeks duration † up to 12 weeks duration ‡ up to 3 weeks duration § up to 8 weeks duration Weight Gain ≥7% of Body Weight Schizophrenia * Quetiapine 391 89 (23%) Placebo 206 11 (6%) Bipolar Mania (monotherapy) † Quetiapine 209 44 (21%) Placebo 198 13 (7%) Bipolar Mania (adjunct therapy) ‡ Quetiapine 196 25 (13%) Placebo 203 8 (4%) Bipolar Depression § Quetiapine 554 47 (8%) Placebo 295 7 (2%) Children and Adolescents: In two clinical trials with quetiapine, one in bipolar mania and one in schizophrenia, reported increases in weight are included in Table 7 Table 7: Proportion of Patients with Weight Gain ≥7% of Body Weight (Children and Adolescents) Vital Sign Indication Treatment Arm N Patients n (%)
• : 6 weeks duration † : 3 weeks duration Weight Gain ≥7% of Body Weight Schizophrenia * Quetiapine 111 23 (21%) Placebo 44 3 (7%) Bipolar Mania † Quetiapine 157 18 (12%) Placebo 68 0 (0%) The mean change in body weight in the schizophrenia trial was 2. 0 kg in the quetiapine group and -0.4 kg in the placebo group and in the bipolar mania trial, it was 1.7 kg in the quetiapine group and 0.4 kg in the placebo group. In an open-label study that enrolled patients from the above two pediatric trials, 63% of patients (241/380) completed 26 weeks of therapy with quetiapine. After 26 weeks of treatment, the mean increase in body weight was 4. 4 kg. Forty-five percent of the patients gained ≥ 7% of their body weight, not adjusted for normal growth. In order to adjust for normal growth over 26 weeks, an increase of at least 0.5 standard deviation from baseline in BMI was used as a measure of a clinically significant change; 18. 3% of patients on quetiapine met this criterion after 26 weeks of treatment.

Weight Gain with Quetiapine (Seroquel):

• Weight gain is a common side effect of quetiapine, with 23% of adult patients experiencing a weight gain of ≥7% of body weight in clinical trials for schizophrenia, and 21% in clinical trials for bipolar mania (monotherapy) 2.
• The mean change in body weight was 2.0 kg in the quetiapine group and -0.4 kg in the placebo group in a schizophrenia trial, and 1.7 kg in the quetiapine group and 0.4 kg in the placebo group in a bipolar mania trial.
• In an open-label study, the mean increase in body weight was 4.4 kg after 26 weeks of treatment with quetiapine.
• Weight gain can occur as early as 6 weeks into therapy.
• Fluvoxamine and Depakote: There is no information in the provided drug labels about fluvoxamine and Depakote, therefore, no conclusion can be drawn about their potential to contribute to weight gain.
• Patients receiving quetiapine should receive regular monitoring of weight.
• When treating pediatric patients with quetiapine, weight gain should be assessed against that expected for normal growth.

From the Research

Weight Gain Associated with Fluvoxamine, Seroquel, and Depakote

• Fluvoxamine: There is no direct evidence in the provided studies that fluvoxamine is associated with significant weight gain 3, 4, 5.
• Seroquel (Quetiapine): Weight gain is associated with the use of quetiapine, with an average weight gain of 1.1 kg 6.
• Depakote: There is no direct evidence in the provided studies that Depakote is associated with weight gain 6, 7. However, it is known that some anticonvulsants and mood stabilizers can cause weight gain.

Timing and Amount of Weight Gain

• The amount of weight gain varies among different drugs, with some studies reporting up to 10 kg at 52 weeks 7.
• The timing of weight gain also varies, but it can start as early as a few weeks into therapy 6, 7.
• It's essential to note that individual results may vary, and the likelihood of weight gain depends on various factors, including dosage, patient population, and duration of treatment 6, 7.

Comparison of Weight Gain Among Different Drugs

• A systematic review and meta-analysis found that weight gain was associated with several drugs, including quetiapine, but not fluvoxamine 6.
• Another study found that weight gain was a common side effect of many drugs, including some anticonvulsants and mood stabilizers, but the evidence for Depakote was not directly mentioned 7.