Advertisement

Drugs

, Volume 67, Issue 7, pp 1077–1094 | Cite as

Quetiapine

A Review of its Use in the Treatment of Bipolar Depression
  • Gillian M. KeatingEmail author
  • Dean M. Robinson
Adis Drug Evaluation

Summary

Abstract

Quetiapine (Seroquel®) is the only atypical antipsychotic approved in the US for use as monotherapy in both bipolar mania and depression, offering potential compliance advantages. Monotherapy with oral quetiapine 300 mg/day is effective in the treatment of patients with bipolar I or II depression. Rapid and sustained improvements in depressive and anxiety symptoms are seen with quetiapine, as well as improvements in health-related quality of life (HR-QOL). Quetiapine is generally well tolerated in bipolar depression and is not associated with an increased risk of treatment-emergent mania. Thus, despite the current lack of data from active comparator trials, quetiapine monotherapy should be considered a first-line option for the acute treatment of bipolar depression.

Pharmacological Properties

The precise mechanism of action of quetiapine in bipolar depression is unknown, although it has been suggested that its antidepressant activity may be linked to its higher affinity for serotonergic than dopaminergic receptors. Quetiapine is not associated with elevation of prolactin levels and has a low propensity to induce extrapyramidal symptoms, most likely reflecting its relatively low affinity for, and its rapid dissociation from, dopamine D2 receptors.

Oral quetiapine is rapidly absorbed and undergoes extensive hepatic metabolism, meaning that dosage adjustment may be needed in patients with hepatic impairment. Caution is recommended when quetiapine is co-administered with cytochrome P450 (CYP) 3A4 inhibitors such as ketoconazole, erythromycin, itraconazole and fluconazole. In addition, higher maintenance dosages of quetiapine may be needed in patients receiving concomitant CYP3A4 inducers (e.g. phenytoin, carbamazepine).

Clinical Efficacy

The efficacy of monotherapy with oral quetiapine 300 or 600 mg/day in adults with bipolar I or II disorder and a major depressive episode was demonstrated in two well designed 8-week trials (the BOLDER I and II trials) [n = 511 and 467]. In both BOLDER I and II, Montgomery-Åsberg Depression Rating Scale (MADRS) total scores at week 8 were reduced from baseline to a significantly greater extent with quetiapine than with placebo (the change from baseline in MADRS total scores was the primary endpoint). In addition, the proportion of patients who had responded or were in remission at week 8 was significantly higher with quetiapine than with placebo. No additional benefit was seen in patients receiving quetiapine 600 mg/day compared with those receiving quetiapine 300 mg/day.

Improvements in Hamilton Depression Rating Scale (HAM-D) total and HAM-D item 1 (depressed mood) scores were significantly greater with quetiapine than with placebo, as were improvements on the Clinical Global Impression-Severity of Illness scale. In terms of anxiety symptoms, improvements from baseline in Hamilton Anxiety Rating Scale total scores were significantly greater with quetiapine than with placebo.

In both the BOLDER I and II trials, HR-QOL was improved to a significantly greater extent with quetiapine 300 mg/day than with placebo, as shown by the change from baseline in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form scores. A significantly greater improvement in the quality of sleep occurred with quetiapine 300 or 600 mg/day than with placebo, as shown by the change from baseline in Pittsburgh Sleep Quality Index scores (assessed only in BOLDER I). Sheehan Disability Scale (SDS) scores (assessing functional improvement) were improved to a significantly greater extent with quetiapine 600 mg/day than with placebo, although no significant difference was seen between quetiapine 300 mg/day and placebo recipients (SDS scores were assessed only in BOLDER II).

Apost hoc pooled analysis of the BOLDER I and II trials revealed significantly greater reductions in mean MADRS item 10 (suicidal thoughts) and HAM-D item 3 (suicide) scores in patients receiving quetiapine than in those receiving placebo. Among quetiapine recipients, the incidence of treatment-emergent suicidal ideation or suicide attempt was low and similar to that seen in placebo recipients.

Exploratory subgroup analyses revealed that quetiapine was effective in reducing MADRS total scores in patients with bipolar I depression and patients with rapid-cycling bipolar disorder. In patients with bipolar II depression, quetiapine was significantly more effective than placebo in a combined analysis of the BOLDER I and II trials, and in BOLDER II alone, but not in BOLDER I alone (the separate BOLDER trials were not powered to detect between-treatment differences in subgroups of patients).

Tolerability

Quetiapine was generally well tolerated in patients with bipolar depression, according to the results of the BOLDER I and II trials. In BOLDER I, the incidence of dry mouth, sedation, somnolence, dizziness and constipation was significantly higher in patients receiving quetiapine 300 or 600 mg/day than in patients receiving placebo. Changes in scores on the Simpson-Angus Rating Scale and the Barnes Akathisia Rating Scale did not differ between quetiapine and placebo recipients. Compared with placebo, quetiapine was not associated with an increased risk of treatment-emergent mania in either trial. Only modest weight gain was seen in quetiapine recipients in these short-term studies and there were no significant differences between quetiapine and placebo recipients in terms of fasting serum glucose levels.

Keywords

Quetiapine Bipolar Depression Pittsburgh Sleep Quality Index Score MADRS Total Score Fasting Serum Glucose Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Ketter TA, Nasrallah HA, Fagiolini A. Mood stabilizers and atypical antipsychotics: bimodal treatments for bipolar disorder. Psychopharmacol Bull 2006 Winter; 39 (1): 120–46PubMedGoogle Scholar
  2. 2.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington DC: American Psychiatric Association, 1994Google Scholar
  3. 3.
    Yatham LN, Kennedy SH, O’Donovan C, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: consensus and controversies. Bipolar Disord 2005; 7 Suppl. 3: 5-69Google Scholar
  4. 4.
    Suppes T, Kelly DI, Perla JM. Challenges in the management of bipolar depression. J Clin Psychiatry 2005; 66 Suppl. 5: 11-6Google Scholar
  5. 5.
    Altshuler LL, Gitlin MJ, Mintz J, et al. Subsyndromal depression is associated with functional impairment in patients with bipolar disorder. J Clin Psychiatry 2002 Sep; 63 (9): 807–11PubMedCrossRefGoogle Scholar
  6. 6.
    Calabrese JR, Hirschfeld RMA, Reed M, et al. Impact of bipolar disorder on a US community sample. J Clin Psychiatry 2003 Apr; 64 (4): 425–32PubMedCrossRefGoogle Scholar
  7. 7.
    Mclntyre RS, Katzman M. The role of atypical antipsychotics in bipolar depression and anxiety disorders. Bipolar Disord 2003; 5 (2): 20–35CrossRefGoogle Scholar
  8. 8.
    Simpson SG, Jamison KR. The risk of suicide in patients with bipolar disorders. J Clin Psychiatry 1999; 60 Suppl. 2: 53-6Google Scholar
  9. 9.
    Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002 Jun; 59: 530–7PubMedCrossRefGoogle Scholar
  10. 10.
    Judd LL, Akiskal HS, Schettler PJ, et al. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry 2003 Mar; 60: 261–9PubMedCrossRefGoogle Scholar
  11. 11.
    Calabrese JR, Elhaj O, Gajwani P, et al. Clinical highlights in bipolar depression: focus on atypical antipsychotics. J Clin Psychiatry 2005; 66 Suppl. 5: 26-33Google Scholar
  12. 12.
    AstraZeneca. Seroquel® (quetiapine fumarate) tablets: prescribing information [online]. Available from URL: http://www.seroquel.com [Accessed 2007 Feb 5]
  13. 13.
    Yatham LN, Goldstein JM, Vieta E, et al. Atypical antipsychotics in bipolar depression: potential mechanisms of action. J Clin Psychiatry 2005; 66 Suppl. 5: 40-8Google Scholar
  14. 14.
    Goldstein JM. Preclinical profile of Seroquel (quetiapine): an atypical antipsychotic with clozapine-like pharmacology. In: Holliday SG, Ancill RJ, MacEwan GW, editors. Schizophrenia: breaking down the barriers. Chichester: John Wiley & Sons Ltd, 1996: 177–208Google Scholar
  15. 15.
    Gefvert O, Bergström M, Långström B. Time course of central nervous dopamine-D2 and 5-HT2 receptor blockade and plasma drug concentrations after discontinuation of quetiapine (Seroquel®) in patients with schizophrenia. Psychopharmacology (Berl) 1998; 135: 119–26CrossRefGoogle Scholar
  16. 16.
    Gefvert O, Lundberg T, Wieselgren I-M, et al. D2 and 5HT2A receptor occupancy of different doses of quetiapine in schizophrenia: a PET study. Eur Neuropsychopharmacol 2001; 11: 105–10PubMedCrossRefGoogle Scholar
  17. 17.
    Tarazi FI, Zhang K, Baldessarini RJ, et al. Long-term effects of olanzapine, risperidone, and quetiapine on serotonin 1A, 2A and 2C receptors in rat forebrain regions. Psychopharmacology (Berl) 2002; 161: 263–70CrossRefGoogle Scholar
  18. 18.
    Ichikawa J, Li Z, Dai J, et al. Atypical antipsychotic drugs, quetiapine, iloperidone, and melperone, preferentially increase dopamine and acetylcholine release in rat medial prefrontal cortex: role of 5-HT1a receptor agonism. Brain Res 2002; 956: 349–57PubMedCrossRefGoogle Scholar
  19. 19.
    Vieta E. Mood stabilization in the treatment of bipolar disorder: focus on quetiapine. Hum Psychopharmacol 2005; 20 (4): 225–36PubMedCrossRefGoogle Scholar
  20. 20.
    Kapur S, Seeman P. Does fast dissociation from the dopamine D2 receptor explain the action of atypical antipsychotics? A new hypothesis. Am J Psychiatry 2001 Mar; 158 (3): 360–9PubMedCrossRefGoogle Scholar
  21. 21.
    De Vane CL, Nemeroff CB. Clinical pharmacokinetics of quetiapine: an atypical antipsychotic. Clin Pharmacokinet 2001; 40 (7): 509–22CrossRefGoogle Scholar
  22. 22.
    Grimm SW, Richtand NM, Winter HR, et al. Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics. Br J Clin Pharmacol 2006 Jan; 61 (1): 58–69PubMedCrossRefGoogle Scholar
  23. 23.
    Aichhorn W, Marksteiner J, Walch T, et al. Influence of age, gender, body weight and valproate comedication on quetiapine plasma concentrations. Int Clin Psychopharmacol 2006 Mar; 21 (2): 81–5PubMedCrossRefGoogle Scholar
  24. 24.
    Jaskiw GE, Thyrum PT, Fuller MA, et al. Pharmacokinetics of quetiapine in elderly patients with selected psychotic disorders. Clin Pharmacokinet 2004; 43 (14): 1025–35PubMedCrossRefGoogle Scholar
  25. 25.
    Thyrum PT, Wong YW, Yeh C. Single-dose pharmacokinetics of quetiapine in subjects with renal or hepatic impairment. Prog Neuropsychopharmacol Biol Psychiatry 2000 May; 24 (4): 521–33PubMedCrossRefGoogle Scholar
  26. 26.
    Wong YW, Yeh C, Thyrum PT. The effects of concomitant phenytoin administration on the steady-state pharmacokinetics of quetiapine. J Clin Psychopharmacol 2001 Feb; 21 (1): 89–93PubMedCrossRefGoogle Scholar
  27. 27.
    Potkin SG, Thyrum PT, Alva G, et al. The safety and pharmacokinetics of quetiapine when coadministered with haloperidol, risperidone, or thioridazine. J Clin Psychopharmacol 2002 Apr; 22 (2): 121–30PubMedCrossRefGoogle Scholar
  28. 28.
    Potkin SG, Thyrum PT, Bera R, et al. Open-label study of the effect of combination quetiapine/lithium therapy on lithium pharmacokinetics and tolerability. Clin Ther 2002 Nov; 24 (11): 1809–23PubMedCrossRefGoogle Scholar
  29. 29.
    De Vane CL, Winter H, Smith MA. Open-label pharmacokinetic study of quetiapine plus divalproex in patients with schizophrenic/schizoaffective disorders or bipolar disorder [abstract no. P17]. Acta Psychiatr Scand 2004; 110 Suppl. 423: 18–9Google Scholar
  30. 30.
    Potkin SG, Thyrum PT, Alva G, et al. Effect of fluoxetine and imipramine on the pharmacokinetics and tolerability of the antipsychotic quetiapine. J Clin Psychopharmacol 2002 Apr; 22 (2): 174–82PubMedCrossRefGoogle Scholar
  31. 31.
    Keck PE Jr, Calabrese JR, Macfadden W, et al. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 2005 Jul; 162 (7): 1351–60PubMedCrossRefGoogle Scholar
  32. 32.
    Thase ME, Macfadden W, Weisler RH, et al. Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study). J Clin Psychopharmacol 2006 Dec; 26 (6): 600–9PubMedCrossRefGoogle Scholar
  33. 33.
    Cookson J, Keck PE Jr, Ketter TA, et al. Number needed to treat and time to response/remission for quetiapine monotherapy efficacy in acute bipolar depression: evidence from a large, randomized, placebo-controlled study. Int Clin Psychopharmacol 2007 Mar; 22 (2): 93–100PubMedCrossRefGoogle Scholar
  34. 34.
    Hirschfeld RM, Calabrese JR, Spong E, et al. Characterization of the antidepressant effects of quetiapine in bipolar depression [poster]. 19th European College of Neuropsychopharmacology; 2006 Sep 16–20; ParisGoogle Scholar
  35. 35.
    Hirschfeld RMA, Weisler RH, Raines SR, et al. Quetiapine in the treatment of anxiety in patients with bipolar I or II depres-sion: a secondary analysis from a randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2006 Mar; 67 (3): 355–62PubMedCrossRefGoogle Scholar
  36. 36.
    Lydiard RB, Raines S, Macfadden W, et al. Improvement in anxiety symptoms in bipolar depression with quetiapine monotherapy: results from two placebo-controlled studies [abstract no. NR691 plus poster]. 159th Annual Meeting of the American Psychiatric Association; 2006 May 20–25; Toron-to (ON)Google Scholar
  37. 37.
    Endicott J, Rajagopalan K, Minkwitz M, et al. A randomized, double-blind, placebo-controlled study of quetiapine in the treatment of bipolar I and II depression: improvements in quality of life. Int Clin Psychopharmacol 2007; 22 (1): 29–37PubMedCrossRefGoogle Scholar
  38. 38.
    Macfadden W, Minkwitz M, Spong E. Quetiapine monotherapy demonstrates efficacy in reducing suicidality in bipolar depres-sion [abstract no. NR248 plus poster]. 159th Annual Meeting of the American Psychiatric Assocation; 2006 May 20–25; Toronto (ON)Google Scholar
  39. 39.
    Weisler RH, Arvekvist R, Stening G, et al. Efficacy of quetiapine monotherapy in bipolar I depression: combined results from two double-blind, placebo-controlled studies [abstract no. NR298 plus poster]. 159th Annual Meeting of the American Psychiatric Association; 2006 May 20–25; Toronto (ON)Google Scholar
  40. 40.
    Hirschfeld R, Suppes T, Vieta E, et al. Quetiapine monotherapy for bipolar II depression: pooled results from two placebo-controlled studies [abstract no. NR227 plus poster no. NR277]. 159th Annual Meeting of the American Psychiatric Association; 2006 May 20–25; Toronto (ON)Google Scholar
  41. 41.
    Thase ME. Pharmacotherapy of bipolar depression: an update. Curr Psychiatry Rep 2006 Dec; 8 (6): 478–88PubMedCrossRefGoogle Scholar
  42. 42.
    American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002 Apr; 159 (4 Suppl.): 1–50Google Scholar
  43. 43.
    GM Goodwin, for the Consensus Group of the British Association for Psychopharmacology. Evidence-based guidelines for treating bipolar disorder: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2003; 17 (2): 149–73CrossRefGoogle Scholar
  44. 44.
    Keck PE Jr, Perlis RH, Otto MW, et al. The expert consensus guidelines series: treatment of bipolar disorder 2004 [online]. Available from URL: http://psychguides.com [Accessed 2007 Feb 14]
  45. 45.
    Grunze H, Kasper S, Goodwin G, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of bipolar disorders. Part I: treatment of bipolar depression. World J Biol Psychiatry 2002 Jul; 3 (3): 115–24Google Scholar
  46. 46.
    Suppes T, Dennehy EB, Swann AC, et al. Report of the Texas Consensus Conference Panel on medication treatment of bipo-lar disorder 2000. J Clin Psychiatry 2002 Apr; 63 (4): 288–99PubMedCrossRefGoogle Scholar
  47. 47.
    Eli Lilly and Company. Symbyax® (olanzapine and fluoxetine HCl capsules): prescribing information [online]. Available from URL: http://www.symbyax.com [Accessed 2007 Feb 14]
  48. 48.
    Yatham LN, Kennedy SH, O’Donovan C, et al. Canadian Net-work for Mood and Anxiety Treatments (CANMAT) guide-lines for the management of patients with bipolar disorder: up-date 2007. Bipolar Disord 2006 Dec; 8 (6): 721–39PubMedCrossRefGoogle Scholar
  49. 49.
    Dando TM, Keating GM. Quetiapine: a review of its use in acute mania and depression associated with bipolar disorder. Drugs 2005; 65 (17): 2533–51PubMedCrossRefGoogle Scholar
  50. 50.
    Calabrese JR, Rapport DJ. Mood stabilizers and the evolution of maintenance study designs in bipolar I disorder. J Clin Psychiatry 1999; 60 Suppl. 5: 5-13Google Scholar
  51. 51.
    US National Institutes of Health. ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2007 Feb 16]
  52. 52.
    Milev R, Abraham G, Zaheer J. Add-on quetiapine for bipolar depression: a 12-month open-label trial. Can J Psychiatry 2006 Jul; 51 (8): 523–30PubMedGoogle Scholar
  53. 53.
    Hardoy MC, Garofano A, Mellino G, et al. Quetiapine as add-on treatment for bipolar I disorder: efficacy in preventing relapse of depressive episodes [abstract no. NR226 plus poster]. 159th Annual Meeting of the American Psychiatric Association; 2006 May 20–25; Toronto (ON)Google Scholar
  54. 54.
    Tohen M, Vieta E, Calabrese J, et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipo-lar I depression. Arch Gen Psychiatry 2003 Nov; 60: 1079–88PubMedCrossRefGoogle Scholar
  55. 55.
    American Diabetes Association, American Psychatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. J Clin Psychiatry 2004 Feb; 65 (2): 267–72CrossRefGoogle Scholar
  56. 56.
    Guo JJ, Keck PE Jr, Corey-Lisle PK, et al. Risk of diabetesmellitus associated with atypical antipsychotics use among Medicaid patients with bipolar disorder: a nested case-control study. Pharmacotherapy 2007; 27 (1): 27–35PubMedCrossRefGoogle Scholar
  57. 57.
    Koller EA, Weber J, Doraiswamy PM, et al. A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus. J Clin Psychiatry 2004 Jun; 65 (6): 857–63PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  1. 1.Wolters Kluwer Health / AdisMairangi Bay, North Shore, AucklandNew Zealand
  2. 2.Wolters Kluwer HealthConshohockenUSA

Personalised recommendations