A multicentre double-blind comparison of hydroxyzine, buspirone and placebo in patients with generalized anxiety disorder

Abstract

The efficacy of hydroxyzine and buspirone, controlled by placebo, was investigated in a double-blind, parallel group, multicentre study conducted in France and the UK. A total of 244 patients with generalised anxiety disorder in primary care was allocated randomly to treatments with hydroxyzine (12.5 mg morning and mid-day, 25 mg evening), buspirone (5 mg morning and mid-day, 10 mg evening) or placebo (three capsules/day) for 4 weeks, preceded by a 1-week single-blind placebo run-in and followed by 1-week single-blind placebo administration. Rating scales were applied on days -7,0,7,14, 12,28 and 35. Seventy percent of the patients were female, the average age was 41 +/- 11 years, and the mean Hamilton Anxiety Score at day 0 was 26.5 +/- 4.2. Only 31 of the 244 patients dropped out, but equally in the three groups. Intention-to-treat LOCF analyses on the primary variable showed a significant difference only between hydroxyzine and placebo with respect to improvement on the Hamilton Anxiety Scale (10.75 versus 7.23 points, respectively). Secondary variables such as CGI and self-ratings (HAD scale) showed both hydroxyzine and buspirone to be more efficacious than placebo. Thus, hydroxyzine is a useful treatment for GAD.

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

“…In particular, comparisons between standard drugs for GAD and psychotherapy are lacking. One study found no gains in combining buspirone and CBT (Lader and Scotto 1998); however, the statistical power of this study may have been too low. In another study, the combination of CBT and diazepam was more effective than diazepam alone (Power et al 1990).…”

“…Efficacy of the antihistamine hydroxyzine was established in a DBPC study (Ferreri et al 1994). In a comparator study, hydroxyzine, but not buspirone, was superior to placebo (Lader and Scotto 1998). In another threearm study, hydroxyzine was compared to placebo and the benzodiazepine bromazepam (Llorca et al 2002).…”

“…Buspirone was superior to placebo in some studies (Davidson et al 1999;Enkelmann 1991;Pollack et al 1997) and as effective as benzodiazepines (Feighner et al 1982;Jacobson et al 1985;Rickels et al 1982;Ross and Matas 1987;Strand et al 1990). However, it was less effective than venlafaxine (Davidson et al 1999) or hydroxyzine (Lader and Scotto 1998). Experience in long-term treatment was gained in a 24-week comparison of buspirone with abecarnil, a drug that has not been marketed due to its side-effect profile …”

A single dose of mirtazapine modulates neural responses to emotional faces in healthy people

“…An anxiolytic action can be linked with 5-HT 2A/2C receptor blockade, but H1 receptor antagonism and 5-HT 3 receptor blockade may also be relevant, as both are implicated in anxiolytic effects (Lader and Scotto 1998;Olivier et al 2000;Harmer et al 2006). The increased response to happy facial expressions seems more likely to be linked to antidepressant effects, and here, changes in noradrenergic neurotransmission, perhaps arising from blockade of presynaptic α 2 -adrenoceptors (Davis and Wilde 1996), might be relevant.…”

Treatment-Resistant Generalized Anxiety Disorder

“…(Llorca& Spadone, 2002;Lader &Scotto, 1998).The antihistamine hydroxyzine appears to have higher anxiolytic efficacy than placebo in controlled studies. Because of the side effects (sedation, anticholinergic effects) , slow onset of action, and lack of efficacy for comorbid disorders, hydroxyzine was not recommended to be used as first-line therapy in some guidelines.…”