Quetiapine monotherapy helps people with generalised anxiety disorder, but side effects may limit its use

Future research needs to shed light on psilocybin-assisted treatment among people with treatment-resistant depression and experiences and side effects.

People with generalised anxiety disorder (GAD) often fail to achieve remission (recovering fully from their disease) despite standard treatments.

This systematic review examines the efficacy and tolerability of second-generation antipsychotics (SGAs) for generalised anxiety disorder as either:

  • augmentation therapy, i.e. using it alongside other treatments
  • monotherapy, i.e. using it as a stand-alone treatment

The reviewers searched a range of sources for randomised controlled trials (RCT) and found 17 eligible studies in 2,459 individuals, of which 10 were double-blind RCTs and 7 were open label studies without comparators.

Here’s what they found:

  • Five augmentation studies containing 912 adults with refractory generalised anxiety disorder indicated that:
    • second-generation antipsychotics augmentation was not more likely to produce clinical response or remission than placebo
    • and was associated with an increased risk of all-cause discontinuation (relative risk [RR] = 1.43; 95% confidence interval [CI], 1.04-1.96)
    • there was no difference in the Hamilton Anxiety Rating Scale on change from baseline or weight gain between groups
  • Four second-generation antipsychotic monotherapy studies containing 1383 patients with generalised anxiety disorder indicated that:
    • treatment with 150 mg of quetiapine was more likely to lead to a clinical response (RR = 1.31; 95% CI, 1.20-1.44), remission (RR = 1.44; 95% CI, 1.23-1.68), and a greater decrease in the Hamilton Anxiety Rating Scale score (-3.66; 95% CI, -5.13 to -2.19) than placebo
    • however, an increased risk of all-cause discontinuation (RR = 1.30; 95% CI, 1.09-1.54) and weight gain (2.2 lb; 95% CI, 1.16-3.24) was observed.

The reviewers concluded:

Existing data suggest that second-generation antipsychotics are not superior to placebo as augmentation for refractory generalised anxiety disorder.

Quetiapine monotherapy is more efficacious than placebo for uncomplicated generalised anxiety disorder, but issues with adverse effects and tolerability may limit its use.

LaLonde CD, Van Lieshout RJ. Treating generalized anxiety disorder with second generation antipsychotics: a systematic review and meta-analysis. J Clin Psychopharmacol. 2011 Jun;31(3):326-33. [PubMed abstract]

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Andre Tomlin

André Tomlin is an Information Scientist with 20 years experience working in evidence-based healthcare. He's worked in the NHS, for Oxford University and since 2002 as Managing Director of Minervation Ltd, a consultancy company who do clever digital stuff for charities, universities and the public sector. Most recently André has been the driving force behind the Mental Elf and the National Elf Service; an innovative digital platform that helps professionals keep up to date with simple, clear and engaging summaries of evidence-based research. André is a Trustee at the Centre for Mental Health and an Honorary Research Fellow at University College London Division of Psychiatry. He lives in Bristol, surrounded by dogs, elflings and lots of woodland!

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