What medications cause weight gain and to what extent?

From the Guidelines

Medications such as antipsychotics, antidepressants, antihistamines, and beta-blockers can cause significant weight gain, with antipsychotics like olanzapine and clozapine often causing the most substantial weight gain, typically 5-10 pounds within the first few months, potentially increasing to 20+ pounds over time 1.

Medication-Induced Weight Gain

The weight gain effect of common medications is a significant concern, as it can increase the risk of weight-related complications, including cardiovascular disease, diabetes, and hepatic steatosis 1.

• Antihypertensive agents, such as beta-blockers, can promote weight gain and prevent weight loss, with selective beta-blockers like carvedilol and nebivolol being recommended when beta-blockers are required 1.
• Antidepressants, particularly tricyclics and mirtazapine, can lead to 5-15 pounds of weight gain, while SSRIs like paroxetine may cause modest increases of 3-5 pounds 1.
• Antipsychotics, such as olanzapine, clozapine, quetiapine, and risperidone, are consistently associated with weight gain, with lurasidone and ziprasidone being more weight-neutral options 1.
• Antihistamines, particularly first-generation ones, may cause 2-6 pounds of weight gain, with alternatives like decongestants being available 1.

Management of Medication-Induced Weight Gain

When initiating medications, clinicians should select therapies least likely to cause weight gain among options with similar efficacy 1.

• Clinicians should counsel patients on the risk of weight gain, discuss lifestyle modifications, and monitor weight trajectory 1.
• Metformin and topiramate can be considered as adjunctive therapy to counteract the effects of some weight gain-promoting agents, particularly antipsychotics 1.

Key Considerations

• Weight gain varies significantly between individuals based on dosage, duration, genetics, diet, and activity level 1.
• The choice of agent must be guided by best practice for the individual patient’s circumstance, taking into account the potential for weight gain and other adverse effects 1.

From the FDA Drug Label

Weight gain has occurred with the use of antipsychotics, including clozapine Monitor weight during treatment with clozapine. Table 7 summarizes the data on weight gain by the duration of exposure pooled from 11 studies with clozapine and active comparators. Table 7 Mean Change in Body Weight (kg) by Duration of Exposure from Studies in Adult Subjects with Schizophrenia Metabolic parameter Exposure duration Clozapine (N=669) Olanzapine (N=442) Chlorpromazine (N=155) n Mean n Mean n Mean Weight change from baseline 2 weeks (Day 11 to 17) 6 +0.9 3 +0.7 2 -0.5 4 weeks (Day 21 to 35) 23 +0.7 8 +0.8 17 +0.6 8 weeks (Day 49 to 63) 12 +1.9 13 +1.8 16 +0. 9 12 weeks (Day 70 to 98) 17 +2.8 5 +3.1 0 0 24 weeks (Day 154 to 182) 42 -0.6 12 +5.7 0 0 48 weeks (Day 322 to 350) 3 +3.7 3 +13. 7 0 0 Table 8 summarizes pooled data from 11 studies in adult subjects with schizophrenia demonstrating weight gain ≥7% of body weight relative to baseline. Table 8 Proportion of Adult Subjects in Schizophrenia Studies with Weight Gain ≥7% Relative to Baseline Body Weight Weight change Clozapine Olanzapine Chlorpromazine N 669 442 155 ≥7% (inclusive) 236 (35%) 203 (46%) 13 (8%)

The medications that cause weight gain are:

• Clozapine: with a mean weight change of +0.9 to +3.7 kg, and 35% of patients experiencing weight gain ≥7% of body weight
• Olanzapine: with a mean weight change of +0.7 to +13.7 kg, and 46% of patients experiencing weight gain ≥7% of body weight
• Chlorpromazine: with a mean weight change of -0.5 to +0.9 kg, and 8% of patients experiencing weight gain ≥7% of body weight 2

From the Research

Medications that Cause Weight Gain

The following medications are known to cause weight gain:

• Insulin, insulin secretagogues, and thiazolidinedione therapy, which can lead to improved glycemic control but also result in weight gain 3, 4
• Atypical antipsychotic drugs, such as clozapine, olanzapine, risperidone, and quetiapine, which can cause marked weight gain 3, 4, 5, 6, 7
• Antidepressants, including:
  • Tricyclic antidepressants (TCAs), such as amitriptyline, which can induce significant weight gain 3, 4, 5, 6
  • Selective serotonin reuptake inhibitors (SSRIs), which may decrease body weight initially but can lead to weight gain over time 5
  • Monoamine oxidase (MAO) inhibitors, which can also cause weight gain 6
• Mood stabilizers, such as lithium, valproic acid, and carbamazepine, which can induce weight gain in a considerable number of patients 3, 4, 5, 6
• Antiepileptic drugs (AEDs), including:
  • Valproate, carbamazepine, and gabapentin, which can promote weight gain 3, 4
  • Lamotrigine, which is weight-neutral 3, 4
  • Topiramate and zonisamide, which may induce weight loss 3, 4
• Corticosteroids, which can cause dose-dependent weight gain 6
• Sulfonylurea derivatives, antineoplastic agents used for breast cancer treatment, and certain drugs used in migraine prophylaxis, which may also lead to weight gain 6

Extent of Weight Gain

The extent of weight gain varies depending on the medication and individual factors. Some medications, such as clozapine and olanzapine, can cause substantial weight gain, while others may lead to more moderate weight gain 5, 7. Factors such as dosage, duration of treatment, and individual genetic predisposition can influence the degree of weight gain 5, 6.