Does Hydroxyzine Cause Weight Gain?
Yes, hydroxyzine can cause weight gain, though the evidence suggests this occurs in a minority of patients (approximately 12%) and appears comparable to placebo rates (10%), making it a relatively weight-neutral antihistamine compared to more sedating first-generation alternatives. 1
Evidence Quality and Context
The most direct evidence comes from a 4-week randomized controlled trial specifically examining hydroxyzine 50 mg/day versus placebo in patients with generalized anxiety disorder. 1 This study provides the clearest data on hydroxyzine's weight effects, though the short duration limits conclusions about long-term use.
Key Findings from Clinical Trials
Weight gain occurred in 12% of hydroxyzine-treated patients versus 10% of placebo patients in a controlled 4-week trial, suggesting the weight gain risk is minimal and not substantially different from placebo. 1
The trial duration was only 4 weeks, which limits our ability to assess long-term weight effects, as many medication-induced weight changes become more apparent with chronic use. 1
Mechanistic Considerations from Antihistamine Class
First-generation antihistamines that cross the blood-brain barrier and antagonize central H1 receptors carry higher weight gain risk than peripheral-acting agents. 2
Antihistamine Weight Gain Hierarchy
The more potent the antihistamine's central H1 receptor antagonism, the greater the potential for weight gain, based on evidence from antipsychotic medications that induce weight gain partly through hypothalamic H1 receptor blockade. 2
Sedating (first-generation) antihistamines that act centrally are more likely to promote weight gain than second- and third-generation non-sedating antihistamines that don't cross the blood-brain barrier. 2
Hydroxyzine is a first-generation sedating antihistamine, placing it in the higher-risk category theoretically, though clinical trial data suggest the actual risk is modest. 2, 1
Clinical Context: Comparison to Other Medications
When considering hydroxyzine's weight effects, it's helpful to contextualize this against medications with well-established weight gain profiles:
Medications with Substantial Weight Gain Risk (to avoid in weight-concerned patients)
Antipsychotics: Olanzapine and clozapine cause the most significant weight gain, while risperidone and quetiapine also consistently promote weight gain. 2
Antidepressants: Paroxetine (highest SSRI risk), amitriptyline (highest tricyclic risk), mirtazapine, lithium, and MAO inhibitors are closely associated with significant weight gain. 2, 3
Anticonvulsants: Gabapentin, pregabalin, and valproic acid consistently cause weight gain. 2, 4, 5
Other agents: Beta-blockers (especially non-selective), alpha-blockers like doxazosin, oral glucocorticoids, and injectable progestins. 2
Clinical Recommendations
For patients with obesity or significant weight concerns requiring antihistamine therapy, consider non-sedating second- or third-generation antihistamines first, or use decongestants like pseudoephedrine as alternatives. 2
Monitoring Approach
Baseline weight documentation is essential before initiating hydroxyzine, particularly in patients with pre-existing obesity or metabolic concerns. 2
Monitor weight at 3-month intervals during continued treatment, as this timeframe allows detection of clinically significant weight changes (≥5% body weight). 2
If weight gain exceeds 5% of baseline weight, consider switching to a non-sedating antihistamine or alternative therapeutic approach. 2
Important Caveats
The 12% weight gain rate in the hydroxyzine trial was barely above the 10% placebo rate, suggesting that anxiety disorder treatment itself, or other factors, may contribute to weight changes independent of medication. 1
Limited quality evidence exists for antihistamine-induced weight gain, especially for long-term use, as most trials examining antihistamines are of short duration. 2
Individual patient factors matter significantly: patients with pre-existing obesity, metabolic syndrome, or diabetes warrant closer monitoring and may benefit from alternative agents. 2