Evidence-Based Reviews

Is quetiapine effective for anxiety?

Current Psychiatry. 2012 August;11(8):E4-E5

References

1. Alexander GC, Gallagher SA, Mascola A, et al. Increasing off-label use of antipsychotic medications in the United States, 1995-2008. Pharmacoepidemiol Drug Saf. 2011;20(2):177-184.

2. Drug Topics. 2010 Top 200 branded drugs by total prescriptions. http://drugtopics.modernmedicine.com/drugtopics/data/articlestandard/drugtopics/252011/727256/article.pdf. Published June 2011. Accessed June 26 2012.

3. Seroquel [package insert]. Wilmington DE: AstraZeneca; 2012.

4. Seroquel XR [package insert]. Wilmington DE: AstraZeneca; 2012.

5. Merideth C, Cutler A, Neijber A, et al. Efficacy and tolerability of extended release quetiapine fumarate monotherapy in the treatment of GAD. Eur Neuropsychopharmacol. 2008;18(suppl 4):S499-S500.

6. Bandelow B, Chouinard G, Bobes J, et al. Extended-release quetiapine fumarate (quetiapine XR): a once-daily monotherapy effective in generalized anxiety disorder. Data from a randomized, double-blind, placebo- and active-controlled study. Int J Neuropsychopharmacol. 2010;13(3):305-320.

7. Katzman MA, Brawman-Mintzer O, Reyes EB, et al. Extended release quetiapine fumarate (quetiapine XR) monotherapy as maintenance treatment for generalized anxiety disorder: a long-term, randomized, placebo-controlled trial. Int Clin Psychopharmacol. 2011;26(1):11-24.

8. Maglione M, Ruelaz Maher A, Hu J, et al. Agency for Healthcare Research and Quality. Off-label use of atypical antipsychotics: an update. http://www.effectivehealthcare.ahrq.gov/ehc/products/150/786/CER43_Off-LabelAntipsychotics_execsumm_20110928.pdf. Published September 2011. Accessed June 26 2012.

9. Maher AR, Maglione M, Bagley S, et al. Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults: a systematic review and meta-analysis. JAMA. 2011;306(12):1359-1369.

10. U.S. Food and Drug Administration. Psychopharmacologic Drugs Advisory Committee meeting announcement. http://www.fda.gov/AdvisoryCommittees/Calendar/ucm136250.htm. Updated June 18, 2009. Accessed June 26, 2012.

11. FDA advisory committee recommendation on Seroquel XR supplemental new drug applications [news release]. Wilmington DE: AstraZeneca; April 9, 2009. http://www.astrazeneca.com/Media/Press-releases/Article/20090409—FDA-Advisory-Committee-Recommendation-on-Seroquel-XR-. Accessed June 26, 2012.

12. Meyer JM, Koro CE. The effects of antipsychotic therapy on serum lipids: a comprehensive review. Schizophr Res. 2004;70(1):1-17.

13. Newcomer JW. Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J Clin Psychiatry. 2007;68(suppl 1):20-27.

14. Chen WY, Chen CC, Hung GC. Hyperglycemic hyperosmolar state associated with low-dose quetiapine treatment in a patient with bipolar disorder. Curr Drug Saf. 2011;6(3):207-208.

15. Williams SG, Alinejad NA, Williams JA, et al. Statistically significant increase in weight caused by low-dose quetiapine. Pharmacotherapy. 2010;30(10):1011-1015.

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The rate of off-label prescribing of second-generation antipsychotics (SGAs) is estimated to have doubled in the past decade.^1,2 In 2010, quetiapine was the most commonly used SGA in the United States with >10 million prescriptions dispensed.² Clinical experience and reports from patients indicate quetiapine may be useful for treating anxiety. When making medication choices, it can be useful to combine anecdotal evidence with the facts (or lack thereof). Does evidence support or contradict the use of quetiapine for anxiety?

What the research shows

Quetiapine is FDA-approved for treating:

adults and adolescents with schizophrenia
adults, children, and adolescents with acute manic episodes associated with bipolar I disorder (BDI) as monotherapy or as an adjunct to lithium or divalproex
adults with an acute depressive episode associated with bipolar disorder
adjunctive treatment of major depressive disorder (MDD) in adults
maintenance treatment of BDI as an adjunct to lithium or divalproex in adults.³

In addition, quetiapine extended-release (XR) is approved as an adjunctive treatment for MDD in adults.⁴

Neither the immediate-release or XR formulation is indicated for treating anxiety, but quetiapine has been studied as a treatment for several anxiety disorders, including posttraumatic stress disorder, social phobia, obsessive-compulsive disorder, and anxiety secondary to mood disorders. It has been most extensively studied as treatment for generalized anxiety disorder (GAD).

Three trials that involved >2,100 patients found quetiapine XR monotherapy is effective for GAD in doses of 50 to 300 mg/d.^5-7 In 2 of the studies, quetiapine XR was as effective as paroxetine and escitalopram for GAD.^5,6 Reviews of off-label SGA use have found that compared with placebo, quetiapine XR monotherapy is effective for GAD (number needed to treat=8).^8,9 Side effects reported in clinical trials of quetiapine included headache, somnolence, sedation, fatigue, dizziness, dry mouth, weight gain, hyperlipidemia, and elevated glucose levels.

Clinical Point

Quetiapine is effective for GAD but side effects limit its use as a first-line agent for treating anxiety

What did the FDA say?

In April 2009, the FDA’s Psychopharmacologic Drugs Advisory Committee reviewed whether evidence supported quetiapine XR for treating MDD and GAD.¹⁰ Although the committee found that quetiapine XR monotherapy effectively treated GAD, it concluded it was not acceptably safe.¹¹ The committee expressed concerns over exposing a greatly expanded population to a drug with substantial metabolic side effects, including weight gain (incidence 3% to 23%), increased cholesterol (incidence 7% to 18%), and hyperglycemia.^12-14 Weight gain and metabolic effects have been reported even when quetiapine is prescribed at low doses (≤100 mg/d).^15,16 The FDA did not approve expanding the indication of quetiapine XR to include treatment of GAD.

Our opinion

Quetiapine XR is effective for treating GAD. However, even at low doses, it is associated with substantial side effects and should be reserved for patients with poor response or contraindications (eg, mania) to traditional GAD treatments such as selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Published studies assessed quetiapine XR only when used on a scheduled basis, and did not address use of quetiapine immediate release or XR on an as-needed basis for GAD.

Related Resources

AstraZeneca. Seroquel prescribing information. www1.astrazeneca-us.com/pi/seroquel.pdf.
AstraZeneca. Seroquel XR prescribing information. www1.astrazeneca-us.com/pi/seroquelxr.pdf.

Drug Brand Names

Divalproex • Depakote
Paroxetine • Paxil
Escitalopram • Lexapro
Quetiapine • Seroquel
Lithium • Eskalith, Lithobid

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.