Hydroxyzine for generalised anxiety disorder

Hydroxyzine is an anti-histamine medication that has been studied in anxiety disorders. This review shows that hydroxyzine is better than placebo in terms of anxiety symptoms in individuals with generalised anxiety disorder (GAD). Too few data were available to be able to draw any conclusions about the efficacy and tolerability of hydroxyzine compared with benzodiazepines and buspirone. Given the robust evidence for the efficacy of antidepressants for GAD, these findings suggest that hydroxyzine should not be recommended as first-line treatment GAD.

Authors' conclusions: 

The included studies did not report on all the outcomes that were pre-specified in the protocol for this review. Even though more effective than placebo, due to the high risk of bias of the included studies, the small number of studies and the overall small sample size, it is not possible to recommend hydroxyzine as a reliable first-line treatment in GAD.

Read the full abstract...

Generalised anxiety disorder (GAD) is a common chronic long-term psychiatric disorder, particularly frequent in primary care. There are several treatment options available, both non-pharmacological (i.e. cognitive behavioral therapy) and pharmacological. Among the pharmacological interventions, antidepressants, buspirone and benzodiazepines (BDZs) have been studied in GAD. Hydroxyzine is an anti-histamine medication which has been used in the treatment of anxiety.


1. To determine the efficacy of hydroxyzine in comparison with placebo or any other active agent in alleviating the acute symptoms of GAD.
2. To review acceptability of treatment with hydroxyzine in comparison with placebo or any other active agent.
3. To investigate the adverse effects of hydroxyzine in comparison with other active agents.

Search strategy: 

The Cochrane Depression, Anxiety and Neurosis Group's controlled trial registers (CCDANCTR-Studies and CCDANCTR-References) were searched on 1 March 2010. The author team ran complementary searches on MEDLINE, CINAHL and PsycINFO and checked reference lists of included studies, previous systematic reviews and major textbooks of anxiety disorders. Personal communication with pharmaceutical companies and experts in the field was also undertaken.

Selection criteria: 

Randomised controlled trials allocating patients with GAD to hydroxyzine versus placebo and/or any other anxiolytic agent.

Data collection and analysis: 

Two authors independently extracted data. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (such as the number of patients who responded to treatment or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side effect profile).

Main results: 

The search yielded 39 studies. We included five studies in the review with a total of 884 participants. We excluded 31 studies and designated three as awaiting assessment. The data from the included studies provide some evidence that hydroxyzine is more effective than placebo for GAD (odds ratio (OR) 0.30, 95% CI 0.15 to 0.58) and that it is also acceptable/tolerable (OR 1.00, 95% CI 0.63 to 1.58) (OR 1.49, 95% CI 0.92 to 2.40). Compared to other anxiolytic agents (benzodiazepines and buspirone), hydroxyzine was equivalent in terms of efficacy, acceptability and tolerability (hydroxyzine vs chloridiazepoxide: OR 0.75, 95% CI 0.35 to 1.62; hydroxyzine vs buspirone efficacy OR 0.76, 95% CI 0.40 to 1.42). In terms of side effects, hydroxyzine was associated with a higher rate of sleepiness/drowsiness than the active comparators (OR 1.74, 95% CI 0.86 to 3.53). There was, however, a high risk of bias in the included studies.