Acute anxiolytic effects of quetiapine during virtual reality exposure--a double-blind placebo-controlled trial in patients with specific phobia

Eur Neuropsychopharmacol. 2013 Nov;23(11):1551-60. doi: 10.1016/j.euroneuro.2013.01.001. Epub 2013 Jan 30.

Abstract

Anxiety disorders are among the most frequent psychiatric disorders. With regard to pharmacological treatment, antidepressants, the calcium modulator pregabalin and benzodiazepines are recommended according to current treatment guidelines. With regard to acute states of anxiety, so far practically only benzodiazepines provide an immediate anxiolytic effect. However, the risk of tolerance and dependency limits the use of this class of medication. Therefore, there is still a need for alternative pharmacologic strategies. Increasing evidence points towards anxiety-reducing properties of atypical antipsychotics, particularly quetiapine. Therefore, we aimed to evaluate the putative acute anxiolytic effects of this compound, choosing the induction of acute anxiety in patients with specific phobia as a model for the evaluation of ad-hoc anxiolytic properties in a proof-of-concept approach. In a randomized, double-blind, placebo-controlled study, 58 patients with arachnophobia were treated with a single dose of quetiapine XR or placebo prior to a virtual reality spider challenge procedure. Treatment effects were monitored using rating scales for acute anxiety as well as measurements of heart rate and skin conductance. Overall, quetiapine showed significant anxiolytic effects compared to placebo. However, effects were not seen on the primary outcome measure (VAS Anxiety), but were limited to somatic anxiety symptoms. Additionally, a significant reduction of skin conductance was observed. Further exploratory analyses hint towards a mediating role of the (COMT) val158met genotype on treatment response. The present results thus suggest a possible suitability of quetiapine in the acute treatment of anxiety, particularly with regard to somatic symptoms.

Keywords: Anxiety disorders; COMT; Challenge; Psychophysiology; Quetiapine; Virtual reality.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Anti-Anxiety Agents / administration & dosage
  • Anti-Anxiety Agents / adverse effects
  • Anti-Anxiety Agents / pharmacology*
  • Anti-Anxiety Agents / therapeutic use
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Anxiety / drug therapy
  • Catechol O-Methyltransferase / genetics
  • Delayed-Action Preparations / administration & dosage
  • Dibenzothiazepines / administration & dosage
  • Dibenzothiazepines / adverse effects
  • Dibenzothiazepines / therapeutic use*
  • Double-Blind Method
  • Female
  • Galvanic Skin Response / drug effects
  • Genetic Predisposition to Disease / genetics
  • Heart Rate / drug effects
  • Humans
  • Male
  • Phobic Disorders / drug therapy*
  • Phobic Disorders / genetics
  • Polymorphism, Single Nucleotide
  • Psychiatric Status Rating Scales
  • Quetiapine Fumarate
  • Spiders
  • Symptom Assessment
  • User-Computer Interface*

Substances

  • Anti-Anxiety Agents
  • Antipsychotic Agents
  • Delayed-Action Preparations
  • Dibenzothiazepines
  • Quetiapine Fumarate
  • COMT protein, human
  • Catechol O-Methyltransferase