Sexual Functioning in Adolescents With Major Depressive Disorder: A Prospective Study

Emira Deumic Shultz, MD; James A. Mills, MS; Vicki L. Ellingrod, PharmD, FCCP; Jeffrey R. Bishop, PharmD, MS, BCPP, FCCP; Chadi A. Calarge, MD

J Clin Psychiatry 2021;82(6):21m13892

ABSTRACT

Objective: To examine the association between sexual functioning, depression and anxiety severity, and selective serotonin reuptake inhibitor (SSRI) use in adolescents.

Methods: From September 2010 to December 2014, 15- to 20-year-old participants, either unmedicated or within a month of beginning SSRI treatment, completed the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and Changes in Sexual Functioning Questionnaire (CSFQ) at baseline and every 4 months for up to 2 years. The DSM-IV–TR was used to determine presence of psychiatric disorders. Data regarding use of medications and hormonal contraception were collected. Polymorphisms of the HTR2A and ABCB1 genes were genotyped. Linear mixed-effects regression models examined the association between depression and anxiety symptom severity, SSRI use, and sexual functioning, accounting for relevant covariates.

Results: A total of 263 participants (59% female, mean ± SD age = 18.9 ± 1.6 years, 70% with major depressive disorder) contributed to this analysis. After adjusting for age, sex, and duration in the study, depression severity, but not anxiety severity, was associated with lower CSFQ total scores (β = −0.13, P < .0001) and lower arousal, orgasm, and pleasure subscale scores (all β = −0.03, P < .003). Higher SSRI doses were associated with lower orgasm subscale scores (β = −0.30, P < .03). Hormonal contraceptive use was associated with higher CSFQ total scores (β = 0.97, P < .003) and higher arousal (β = 0.25, P < .009), desire (β = 0.24, P < .001), orgasm (β = 0.27, P < .02), and pleasure (β = 0.15, P < .004) subscale scores. No significant genetic moderating effect was found.

Conclusions: In adolescents, depression is associated with lower sexual functioning while SSRI use impairs orgasm.

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References (56)

Scharko AM. Selective serotonin reuptake inhibitor-induced sexual dysfunction in adolescents: a review. J Am Acad Child Adolesc Psychiatry. 2004;43(9):1071–1079. PubMed CrossRef
Moreau C, Kågesten AE, Blum RW. Sexual dysfunction among youth: an overlooked sexual health concern. BMC Public Health. 2016;16(1):1170. PubMed CrossRef
O’Sullivan LF, Byers ES, Brotto LA, et al. A longitudinal study of problems in sexual functioning and related sexual distress among middle to late adolescents. J Adolesc Health. 2016;59(3):318–324. PubMed CrossRef
Anderson RM. Positive sexuality and its impact on overall well-being. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2013;56(2):208–214. PubMed CrossRef
Kennedy SH, Rizvi S. Sexual dysfunction, depression, and the impact of antidepressants. J Clin Psychopharmacol. 2009;29(2):157–164. PubMed CrossRef
Baldwin DS. Depression and sexual dysfunction. Br Med Bull. 2001;57(1):81–99. PubMed CrossRef
Kalmbach DA, Kingsberg SA, Ciesla JA. How changes in depression and anxiety symptoms correspond to variations in female sexual response in a nonclinical sample of young women: a daily diary study. J Sex Med. 2014;11(12):2915–2927. PubMed CrossRef
Deumic E, Butcher BD, Clayton AD, et al. Sexual functioning in adolescents with major depressive disorder. J Clin Psychiatry. 2016;77(7):957–962. PubMed CrossRef
Kronstein PD, Ishida E, Khin NA, et al. Summary of findings from the FDA regulatory science forum on measuring sexual dysfunction in depression trials. J Clin Psychiatry. 2015;76(8):1050–1059. PubMed CrossRef
Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. J Clin Psychopharmacol. 2009;29(3):259–266. PubMed CrossRef
Anderson HD, Pace WD, Libby AM, et al. Rates of 5 common antidepressant side effects among new adult and adolescent cases of depression: a retrospective US claims study. Clin Ther. 2012;34(1):113–123. PubMed CrossRef
Masand PS. Tolerability and adherence issues in antidepressant therapy. Clin Ther. 2003;25(8):2289–2304. PubMed CrossRef
Rothschild AJ. New directions in the treatment of antidepressant-induced sexual dysfunction. Clin Ther. 2000;22(suppl A):A42–A57, discussion A58–A61. PubMed CrossRef
O’Brien FE, Dinan TG, Griffin BT, et al. Interactions between antidepressants and P-glycoprotein at the blood-brain barrier: clinical significance of in vitro and in vivo findings. Br J Pharmacol. 2012;165(2):289–312. PubMed CrossRef
Uhr M, Tontsch A, Namendorf C, et al. Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron. 2008;57(2):203–209. PubMed CrossRef
Fung KL, Pan J, Ohnuma S, et al. MDR1 synonymous polymorphisms alter transporter specificity and protein stability in a stable epithelial monolayer. Cancer Res. 2014;74(2):598–608. PubMed CrossRef
Bly MJ, Bishop JR, Thomas KL, et al. P-glycoprotein (PGP) polymorphisms and sexual dysfunction in female patients with depression and SSRI-associated sexual side effects. J Sex Marital Ther. 2013;39(3):280–288. PubMed CrossRef
Bishop JR, Moline J, Ellingrod VL, et al. Serotonin 2A -1438 G/A and G-protein Beta3 subunit C825T polymorphisms in patients with depression and SSRI-associated sexual side-effects. Neuropsychopharmacology. 2006;31(10):2281–2288. PubMed CrossRef
Giuliano F, Clément P. Physiology of ejaculation: emphasis on serotonergic control. Eur Urol. 2005;48(3):408–417. PubMed CrossRef
Williams VS, Edin HM, Hogue SL, et al. Prevalence and impact of antidepressant-associated sexual dysfunction in three European countries: replication in a cross-sectional patient survey. J Psychopharmacol. 2010;24(4):489–496. PubMed CrossRef
Rosenberg KP, Bleiberg KL, Koscis J, et al. A survey of sexual side effects among severely mentally ill patients taking psychotropic medications: impact on compliance. J Sex Marital Ther. 2003;29(4):289–296. PubMed CrossRef
Calarge CA, Mills JA, Janz KF, et al. Body composition in adolescents during treatment with selective serotonin reuptake inhibitors. Pediatrics. 2017;140(1):e20163943. PubMed CrossRef
Calarge CA, Mills JA, Janz KF, et al. The effect of depression, generalized anxiety, and selective serotonin reuptake inhibitors on change in bone metabolism in adolescents and emerging adults. J Bone Miner Res. 2017;32(12):2367–2374. PubMed CrossRef
Rush AJ, Gullion CM, Basco MR, et al. The Inventory of Depressive Symptomatology (IDS): psychometric properties. Psychol Med. 1996;26(3):477–486. PubMed CrossRef
Beck AT. Depression: Clinical, Experimental, and Theoretical Aspects. New York, NY: Harper & Row; 1967.
American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.
Keller MB, Lavori PW, Friedman B, et al. The Longitudinal Interval Follow-up Evaluation: a comprehensive method for assessing outcome in prospective longitudinal studies. Arch Gen Psychiatry. 1987;44(6):540–548. PubMed CrossRef
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. PubMed CrossRef
Verbeke G, Molenberghs G. Linear Mixed Models for Longitudinal Data. Vol. XXII. 1st ed. New York: Springer-Verlag New York; 2000.
Morrell CH, Brant LJ, Ferrucci L. Model choice can obscure results in longitudinal studies. J Gerontol A Biol Sci Med Sci. 2009;64(2):215–222. PubMed CrossRef
Little RJA, Rubin DB. Statistical Analysis With Missing Data. 2nd ed.
Skovlund CW, Mørch LS, Kessing LV, et al. Association of hormonal contraception with depression. JAMA Psychiatry. 2016;73(11):1154–1162. PubMed CrossRef
Lee JMLL. L. L.; Ang, S. B. Oral contraception and female sexual dysfunction in reproductive women. Sex Med Rev. 2017;5(1):31–44. CrossRef
Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A. 2000;97(7):3473–3478. PubMed CrossRef
Kulma I, Boonprasert K, Na-Bangchang K. Polymorphisms of genes encoding drug transporters or cytochrome P450 enzymes and association with clinical response in cancer patients: a systematic review. Cancer Chemother Pharmacol. 2019;84(5):959–975. PubMed CrossRef
Garcia JR, Reiber C. Hook-up behavior: a biopsychosocial perspective. J Soc Evol Cult Psychol. 2008;2(4):192–208. CrossRef
Althof SE, McMahon CG, Waldinger MD, et al. An update of the International Society of Sexual Medicine’s guidelines for the diagnosis and treatment of premature ejaculation (PE). Sex Med. 2014;2(2):60–90. PubMed CrossRef
Osis L, Bishop JR. Pharmacogenetics of SSRIs and sexual dysfunction. J Pharm (Cairo). 2010;3(12):3614–3628.
Farmer M, Yoon H, Goldstein I. Future targets for female sexual dysfunction. J Sex Med. 2016;13(8):1147–1165. PubMed CrossRef
McCabe MP, Connaughton C. Psychosocial factors associated with male sexual difficulties. J Sex Res. 2014;51(1):31–42. PubMed CrossRef
Barlow DH. Causes of sexual dysfunction: the role of anxiety and cognitive interference. J Consult Clin Psychol. 1986;54(2):140–148. PubMed CrossRef
Kempeneers PBV. Les apports de la pléthysmographie et de la psychologie cognitive dans la compréhension des relations entre l’anxiété et l’excitation sexuelle. J Ther Comport Cogn. 2008;18(4):161–165. CrossRef
Ott MA, Shew ML, Ofner S, et al. The influence of hormonal contraception on mood and sexual interest among adolescents. Arch Sex Behav. 2008;37(4):605–613. PubMed CrossRef
Smith NK, Jozkowski KN, Sanders SA. Hormonal contraception and female pain, orgasm and sexual pleasure. J Sex Med. 2014;11(2):462–470. PubMed CrossRef
Bancroft J, Sherwin BB, Alexander GM, et al. Oral contraceptives, androgens, and the sexuality of young women, II: the role of androgens. Arch Sex Behav. 1991;20(2):121–135. PubMed CrossRef
Wehry AM, Ramsey L, Dulemba SE, et al. Pharmacogenomic testing in child and adolescent psychiatry: an evidence-based Review. Curr Probl Pediatr Adolesc Health Care. 2018;48(2):40–49. PubMed CrossRef
Hockings JK, Pasternak AL, Erwin AL, et al. Pharmacogenomics: an evolving clinical tool for precision medicine. Cleve Clin J Med. 2020;87(2):91–99. PubMed CrossRef
Zhu J, Klein-Fedyshin M, Stevenson JM. Serotonin transporter gene polymorphisms and selective serotonin reuptake inhibitor tolerability: review of pharmacogenetic evidence. Pharmacotherapy. 2017;37(9):1089–1104. PubMed CrossRef
Stevenson JM, Bishop JR. Genetic determinants of selective serotonin reuptake inhibitor related sexual dysfunction. Pharmacogenomics. 2014;15(14):1791–1806. PubMed CrossRef
Kato M, Serretti A. Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Mol Psychiatry. 2010;15(5):473–500. PubMed CrossRef
Lewis MA, Atkins DC, Blayney JA, et al. What is hooking up? examining definitions of hooking up in relation to behavior and normative perceptions. J Sex Res. 2013;50(8):757–766. PubMed CrossRef
Freidl EK, Stroeh OM, Elkins RM, et al. Assessment and treatment of anxiety among children and adolescents. Focus Am Psychiatr Publ. 2017;15(2):144–156. PubMed CrossRef
Cavazos-Rehg PA, Krauss MJ, Spitznagel EL, et al. Age of sexual debut among US adolescents. Contraception. 2009;80(2):158–162. PubMed CrossRef
Upchurch DM, Levy-Storms L, Sucoff CA, et al. Gender and ethnic differences in the timing of first sexual intercourse. Fam Plann Perspect. 1998;30(3):121–127. PubMed CrossRef
Hicks JK, Bishop JR, Sangkuhl K, et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015;98(2):127–134. PubMed CrossRef
Levine A, McGlinchey E. Assessing sexual symptoms and side effects in adolescents. Pediatrics. 2015;135(4):e815–e817. PubMed CrossRef