Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-22T07:24:08.643Z Has data issue: false hasContentIssue false
  • English
  • Français

Sexual functioning in patients with major depressive disorder in randomized placebo-controlled studies of extended release quetiapine fumarate

Published online by Cambridge University Press:  25 September 2013

Anita H. Clayton ,
Julie C. Locklear ,
Henrik Svedsäter  and
Roger S. McIntyre
Anita H. Clayton*
Affiliation:
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia, USA
Julie C. Locklear
Affiliation:
Formerly AstraZeneca Pharmaceuticals, Wilmington, Delaware, USA
Henrik Svedsäter
Affiliation:
Formerly AstraZeneca R&D, Mölndal, Sweden
Roger S. McIntyre
Affiliation:
Department of Psychiatry, University Health Network, University of Toronto, Toronto, Ontario, Canada
*
*Address for correspondence: Anita H. Clayton, MD, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 2955 Ivy Road, Northridge Suite 210, Charlottesville, VA 22903, USA. Email [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

We evaluated sexual functioning from 6 acute, randomized, placebo-controlled studies (6–10 weeks) of once-daily extended release quetiapine fumarate (quetiapine XR) 50, 150, or 300 mg/day as monotherapy (Studies 1–4) or adjunct therapy (Studies 6–7) in major depressive disorder (MDD).

Methods

We present a pre-planned, non-inferiority analysis of quetiapine XR monotherapy versus placebo using Changes in Sexual Functioning Questionnaire (CSFQ) total score change (Studies 1–4). Post hoc analyses evaluated CSFQ total and domain scores for fixed-dose monotherapy (Studies 1–2), modified fixed-dose (Studies 3–4), and adjunct therapy studies (Studies 6–7). CSFQ data for active comparators (duloxetine [Study 2], escitalopram [Study 4]) are reported.

Results

Quetiapine XR monotherapy was non-inferior to placebo for sexual functioning (least squares mean [LSM] difference in CSFQ score change versus placebo, 0.16 [95% confidence interval: −0.59, 0.92]); LSM change in CSFQ score: 1.90, quetiapine XR (all doses) and 1.73, placebo. LSM differences versus placebo (95% confidence interval): 0.18 (−1.40, 1.75), duloxetine (Study 2); 0.16 (−1.77, 2.10), escitalopram (Study 4). LSM differences with adjunct quetiapine XR 150 mg/day (0.52; p = 0.338) or 300 mg/day (0.22; p = 0.679) were comparable with placebo plus antidepressants. Post hoc all-patient and gender-specific analyses were comparable for CSFQ total scores versus placebo with quetiapine XR 50, 150, or 300 mg/day, duloxetine, and escitalopram.

Discussion

Lack of negative effects on sexual functioning in patients with MDD may improve treatment acceptability.

Conclusion

Quetiapine XR (monotherapy or adjunct therapy) had an impact on sexual function that was comparable with placebo.

Keywords

Adjunct therapyextended release quetiapine fumaratemajor depressive disordermonotherapynon-inferiority analysissexual dysfunction
Type
Original Research
Information
CNS Spectrums , Volume 19 , Issue 2 , April 2014 , pp. 182 - 196
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Kennedy, SH, Dickens, SE, Eisfeld, BS, etal. Sexual dysfunction before antidepressant therapy in major depression. J Affect Disord. 1999; 56(2–3): 201–208.CrossRefGoogle ScholarPubMed
2. Williams, K, Reynolds, MF. Sexual dysfunction in major depression. CNS Spectr. 2006; 11(8 suppl 9): 19–23.Google Scholar
3. Clayton, A, Keller, A, McGarvey, EL. Burden of phase-specific sexual dysfunction with SSRIs. J Affect Disord. 2006; 91(1): 27–32.CrossRefGoogle ScholarPubMed
4. Ashton, AK, Jamerson, BD, Weinstein, WL, etal. Antidepressant-related adverse effects impacting treatment compliance: results of a patient survey. Current Therapeutic Research. 2005; 66(2): 96–106.Google Scholar
5. Montejo, AL, Llorca, G, Izquierdo, JA, etal. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. J Clin Psychiatry. 2001; 62(suppl 3): 10–21.Google Scholar
6. Clayton, A, Kornstein, S, Prakash, A, etal. Changes in sexual functioning associated with duloxetine, escitalopram, and placebo in the treatment of patients with major depressive disorder. J Sex Med. 2007; 4(4 Pt 1): 917–929.CrossRefGoogle ScholarPubMed
7. Clayton, AH, Pradko, JF, Croft, HA, etal. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry. 2002; 63(4): 357–366.Google Scholar
8. AstraZeneca. Seroquel XR (quetiapine fumarate) extended-release tablets—US prescribing information [Web site]. July 2013. Available at: http://www1.astrazeneca-us.com/pi/seroquelxr.pdf. Accessed September 6, 2013.Google Scholar
9. AstraZeneca UK Limited. Seroquel XL Summary of Product Characteristics (UK) [Web site]. April 26, 2012. Available at: http://www.medicines.org.uk/emc/medicine/21175. Accessed November 16, 2012.Google Scholar
10. Weisler, R, Joyce, M, McGill, L, etal. Extended release quetiapine fumarate monotherapy for major depressive disorder: results of a double-blind, randomized, placebo-controlled study. CNS Spectr. 2009; 14(6): 299–313.Google Scholar
11. Cutler, AJ, Montgomery, SA, Feifel, D, etal. Extended release quetiapine fumarate monotherapy in major depressive disorder: a placebo- and duloxetine-controlled study. J Clin Psychiatry. 2009; 70(4): 526–539.Google Scholar
12. Bortnick, B, El-Khalili, N, Banov, M, etal. Efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in major depressive disorder: a placebo-controlled, randomized study. J Affect Disord. 2011; 128(1–2): 83–94.Google Scholar
13. Earley, W, McIntyre, A, Wang, G, etal. Double-blind study of the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD) [Abstract]. Int J Psychiatry Clin Pract. 2008; 12: 332.Google Scholar
14 El-Khalili, N, Joyce, M, Atkinson, S, etal. Extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in major depressive disorder (MDD) in patients with an inadequate response to ongoing antidepressant treatment: a multicentre, randomized, double-blind, placebo-controlled study. Int J Neuropsychopharmacol. 2010; 13(7): 917–932.Google Scholar
15. Bauer, M, Pretorius, HW, Constant, EL, etal. Extended-release quetiapine as adjunct to an antidepressant in patients with major depressive disorder: results of a randomized, placebo-controlled, double-blind study. J Clin Psychiatry. 2009; 70(4): 540–549.Google Scholar
16. Katila, H, Mezhebovsky, I, Mulroy, A, etal. Randomized, double-blind study of the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder. Am J Geriatr Psychiatry. 2013; 21(8): 1769–1784.Google Scholar
17. Liebowitz, M, Lam, RW, Lepola, U, etal. Efficacy and tolerability of extended release quetiapine fumarate monotherapy as maintenance treatment of major depressive disorder: a randomized, placebo-controlled trial. Depress Anxiety. 2010; 27(10): 964–976.CrossRefGoogle ScholarPubMed
18. Hu, XH, Bull, SA, Hunkeler, EM, etal. Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate. J Clin Psychiatry. 2004; 65(7): 959–965.Google Scholar
19. Williams, VS, Baldwin, DS, Hogue, SL, etal. Estimating the prevalence and impact of antidepressant-induced sexual dysfunction in 2 European countries: a cross-sectional patient survey. J Clin Psychiatry. 2006; 67(2): 204–210.Google Scholar
20. Sheehan, DV, Lecrubier, Y, Sheehan, KH, etal. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998; 59(suppl 20): 22–33.Google ScholarPubMed
21. Hamilton, M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960; 23: 56–62.CrossRefGoogle ScholarPubMed
22. Keller, A, McGarvey, EL, Clayton, AH. Reliability and construct validity of the Changes in Sexual Functioning Questionnaire short-form (CSFQ-14). J Sex Marital Ther. 2006; 32(1): 43–52.CrossRefGoogle ScholarPubMed
23. Kennedy, SH. Core symptoms of major depressive disorder: relevance to diagnosis and treatment. Dialogues Clin Neurosci. 2008; 10(3): 271–277.Google Scholar
24. Zimmerman, M, Posternak, M, Friedman, M, etal. Which factors influence psychiatrists’ selection of antidepressants? Am J Psychiatry. 2004; 161(7): 1285–1289.Google Scholar
25. Montejo-Gonzalez, AL, Llorca, G, Izquierdo, JA, etal. SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther. 1997; 23(3): 176–194.Google Scholar
26. Maguire, GA. Prolactin elevation with antipsychotic medications: mechanisms of action and clinical consequences. J Clin Psychiatry. 2002; 63(suppl 4): 56–62.Google Scholar
27. Kelly, DL, Conley, RR. A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia. Psychoneuroendocrinology. 2006; 31(3): 340–346.Google Scholar
28. Fava, M, Dording, CM, Baker, RA, etal. Effects of adjunctive aripiprazole on sexual functioning in patients with major depressive disorder and an inadequate response to standard antidepressant monotherapy: a post hoc analysis of 3 randomized, double-blind, placebo-controlled studies. Prim Care Companion CNS Disord. 2011; 13(1). DOI: 10.4088/PCC.10m00994gre.Google Scholar
29. Montejo, AL, Perahia, DG, Spann, ME, etal. Sexual function during long-term duloxetine treatment in patients with recurrent major depressive disorder. J Sex Med. 2011; 8(3): 773–782.Google Scholar
30. Kennedy, SH, Eisfeld, BS, Dickens, SE, etal. Antidepressant-induced sexual dysfunction during treatment with moclobemide, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry. 2000; 61(4): 276–281.CrossRefGoogle ScholarPubMed
31. Nurnberg, HG. Managing treatment-emergent sexual dysfunction associated with serotonergic antidepressants: before and after sildenafil. J Psychiatr Pract. 2001; 7: 92–108.Google Scholar
32. Segraves, RT. Antidepressant-induced sexual dysfunction. J Clin Psychiatry. 1998; 59(suppl 4): 48–54.Google Scholar
33. Clayton, AH, Croft, HA, Horrigan, JP, etal. Bupropion extended release compared with escitalopram: effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies. J Clin Psychiatry. 2006; 67(5): 736–746.Google Scholar
34. Perlis, RH, Laje, G, Smoller, JW, etal. Genetic and clinical predictors of sexual dysfunction in citalopram-treated depressed patients. Neuropsychopharmacology. 2009; 34(7): 1819–1828.Google Scholar
35. Bishop, JR, Moline, J, Ellingrod, VL, etal. Serotonin 2A -1438 G/A and G-protein Beta3 subunit C825 T polymorphisms in patients with depression and SSRI-associated sexual side-effects. Neuropsychopharmacology. 2006; 31(10): 2281–2288.Google Scholar
36. Cipriani, A, Furukawa, TA, Salanti, G, etal. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet. 2009; 373(9665): 746–758.Google Scholar