Generic placeholder image

Current Drug Targets

Author(s): Maszaidi Zainol, Hatta Sidi*, Jaya Kumar, Srijit Das, Shaiful Bahari Ismail, Muhammad Hizri Hatta, Najwa Baharuddin and Arun Ravindran

DOI: 10.2174/1389450118666170315110902

DownloadDownload PDF Flyer Cite As
Co-Morbid Erectile Dysfunction (ED) and Antidepressant Treatment in a Patient – A Management Challenge?

Page: [182 - 191] Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Throughout the world, antidepressants (AD) and phosphodiesterase-5 inhibitors (PDE-5i) are the commonly prescribed psychopharmacological agents for treating patients with co-morbid mental health problem and sexual dysfunction (SD). The serotonergic and noradrenergic ADs, although effective, are not without any SD adverse-effects, especially erectile dysfunction (ED). ED is a failure to obtain a satisfactory erection for rewarding sexual coitus during the phases of male’s sexual arousal. It is recognized as an important reason why non-adherence to treatment was observed in patients who were on AD. AD intervention caused remission to some of the pre- treatment psychopathology of ED. However, in many patients, AD potentially magnified the unwanted sexual sideeffects. This made the situation challenging for the mental health professional. These challenges are based on the complexity of ED, its etiology and the associated risk factors, which further add to its AD side-effect. The neuro-psychopharmacological basis for AD treatment selection was deliberated. Bio-psycho-social interventions are recommended at two pivotal stages. Firstly, a step should be taken for proper assessment (e.g. detailed history, psychosocial and laboratory investigations); and identify few modifiable risk factors for ED and associated mental health issues. Secondly, with guidance of an algorithm pathway, a practical intervention should include strategies such as dose reduction, augmentation or changing to an AD with lesser or no sexual adverse-effects. It is recommended that bupropion and mirtazepine to be prescribed when patients develop adverse sexual effects with serotonin selective reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI) and tricyclic antidepressant (TCA). Few suggestions which may be borne in mind are revising sexual scripts and improving sexual techniques, life-style modifications, psychotherapy and other nonpharmacological approaches which may be beneficial to both patients and their partners.

Keywords: Antidepressants, phosphodiesterase type 5 inhibitors (PDE-5), erectile dysfunction (ED).

Graphical Abstract

[1]
Saba Moussavi SC. Emese Verdes, Ajay Tandon, Vikram Patel, Bedirhan Ustun. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 2007; 370: 851-8.
[2]
Depression: A Global Crisis, World mental health day report. October 2012.
[3]
de Heer EW, Gerrits MM, Beekman AT, et al. The Association of Depression and Anxiety with Pain: A Study from NESDA. PLoS One 2014; 9(10): e106907.
[4]
Hirschfeld RM. The comorbidity of major depression and anxiety disorders: recognition and management in primary care. Prim Care Companion J Clin Psychiatry 2001; 3(6): 244-54.
[5]
Chen J, Chen S, Landry PF. Urbanization and mental health in china: Linking the 2010 population census with a cross-sectional survey. Int J Environ Res Public Health 2015; 12(8): 9012-24.
[6]
Hakulinen C, Elovainio M, Pulkki-Raback L, et al. Personality and depressive symptoms: Individual participant meta-analysis of 10 cohort studies. Depress Anxiety 2015; 32(7): 461-70.
[7]
Taylor RJ, Chae DH, Lincoln KD, Chatters LM. Extended family and friendship support networks are both protective and risk factors for major depressive disorder and depressive symptoms among African-Americans and black Caribbeans. J Nerv Ment Dis 2015; 203(2): 132-40.
[8]
Hoven H, Wahrendorf M, Siegrist J. Occupational position, work stress and depressive symptoms: a pathway analysis of longitudinal SHARE data. J Epidemiol Community Health 2015; 69(5): 447-52.
[9]
World Bank Group/IMF Spring Meeting April 2016, Washington D.C. http: //wwwworldbankorg/en/about.April
[10]
Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Applications. 4th ed. Cambridge University Press: New York 2013.
[11]
Stahl SM. The psychopharmacology of sex, Part 1: Neurotransmitters and the 3 phases of the human sexual response. J Clin Psychiatry 2001; 62(2): 80-1.
[12]
Rajkumar RP, Kumaran AK. Depression and anxiety in men with sexual dysfunction: a retrospective study. Compr Psychiatry 2015; 60: 114-8.
[13]
Jackson G. Prevention of cardiovascular disease by the early identification of erectile dysfunction. Int J Impot Res 2008; 20(Suppl. 2): S9-S14.
[14]
Basu J, Sharma S. Erectile dysfunction heralds onset of cardiovascular diseasePractitioner 2016; 260(1794): 21-3, 3
[15]
Nehra A. Erectile dysfunction and cardiovascular disease: efficacy and safety of phosphodiesterase type 5 inhibitors in men with both conditions. Mayo Clin Proc 2009; 84(2): 139-48.
[16]
Montorsi P, Montorsi F, Schulman CC. Is erectile dysfunction the “tip of the iceberg” of a systemic vascular disorder? Eur Urol 2003; 44(3): 352-4.
[17]
Engel GL. The need for a new medical model: A challenge for biomedicine. Science 1977; 196(4286): 129-36.
[18]
Engel GL. The clinical application of the bio-psycho-social model. Am J Psychiatry 1980; 137(5): 535-44.
[19]
Boolell M, Allen MJ, Ballard SA, et al. Sildenafil: An orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 1996; 8(2): 47-52.
[20]
Ballard SA, Gingell CJ, Tang K, et al. Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 1998; 159(6): 2164-71.
[21]
Jeremy JY, Ballard SA, Naylor AM, Miller MA, Angelini GD. Effects of sildenafil, a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum in vitro. Br J Urol 1997; 79(6): 958-63.
[22]
Gresser U, Gleiter CH. Erectile dysfunction: Comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil--review of the literature. Eur J Med Res 2002; 7(10): 435-46.
[23]
Burnett AL. Nitric oxide in the penis: Physiology and pathology. J Urol 1997; 157(1): 320-4.
[24]
Gupta M, Kovar A, Meibohm B. The clinical pharmacokinetics of phosphodiesterase-5 inhibitors for erectile dysfunction. J Clin Pharmacol 2005; 45(9): 987-1003.
[25]
Nichols DJ, Muirhead GJ, Harness JA. Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: Absolute bioavailability, food effects and dose proportionality. Br J Clin Pharmacol 2002; 53(Suppl. 1): 5S-12S.
[26]
Corbin JD, Francis SH. Pharmacology of phosphodiesterase-5 inhibitors. Int J Clin Pract 2002; 56(6): 453-9.
[27]
Eichelbaum M, Burk O. CYP3A genetics in drug metabolism. Nat Med 2001; 7(3): 285-7.
[28]
Sajjad A, Weng CY. Vision Loss in a Patient with Primary Pulmonary Hypertension and Long-Term Use of Sildenafil. Retinal cases & brief reports 2016.
[29]
Yajima T, Yajima Y, Koppiker N, Grunwald JE, Laties AM. No clinically important effects on intraocular pressure after short-term administration of sildenafil citrate (Viagra). Am J Ophthalmol 2000; 129(5): 675-6.
[30]
Gur S, Yurdaarmagan B, Bayatli N, Sikka SC. Effect of short- and long-term sildenafil treatment on erectile dysfunction in rats with partial bladder outlet obstruction. Neurourol Urodyn 2016; 35(1): 108-14.
[31]
Seftel AD, Farber J, Fletcher J, et al. A three-part study to investigate the incidence and potential etiologies of tadalafil-associated back pain or myalgia. Int J Impot Res 2005; 17(5): 455-61.
[32]
Huang SA, Lie JD. Phosphodiesterase-5 (PDE5) Inhibitors In the Management of Erectile Dysfunction. P&T 2013; 38(7): 407-19.
[33]
Rodriguez JJ, Al Dashti R, Schwarz ER. Linking erectile dysfunction and coronary artery disease. Int J Impot Res 2005; 17(Suppl. 1): S12-8.
[34]
Andrews NP, Husain M, Dakak N, Quyyumi AA. Platelet inhibitory effect of nitric oxide in the human coronary circulation: impact of endothelial dysfunction. J Am Coll Cardiol 2001; 37(2): 510-6.
[35]
Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S. Endothelial dysfunction as a target for prevention of cardiovascular disease. Diabetes Care 2009; 32(Suppl. 2): S314-21.
[36]
Shabsigh R, Stone B. Understanding the needs and objectives of erectile dysfunction patients. World J Urol 2006; 24(6): 618-22.
[37]
Araujo AB, Durante R, Feldman HA, Goldstein I, McKinlay JB. The relationship between depressive symptoms and male erectile dysfunction: Cross-sectional results from the massachusetts male aging study. Psychosom Med 1998; 60(4): 458-65.
[38]
Jeong JY, Lee SK, Kang YW, Jang SN, Choi YJ, Kim DH. Relationship between ED and depression among middle-aged and elderly men in Korea: Hallym aging study. Int J Impot Res 2011; 23(5): 227-34.
[39]
Brigitta B. Pathophysiology of depression and mechanisms of treatment. Dialogues Clin Neurosci 2002; 4(1): 7-20.
[40]
Schechter LE, Ring RH, Beyer CE, et al. Innovative approaches for the development of antidepressant drugs: Current and future strategies. NeuroRx 2005; 2(4): 590-611.
[41]
Hull EM, Muschamp JW, Sato S. Dopamine and serotonin: Influences on male sexual behavior. Physiol Behav 2004; 83(2): 291-307.
[42]
Trindade E, Menon D, Topfer LA, Coloma C. Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: A meta-analysis. CMAJ 1998; 159(10): 1245-52.
[43]
Gartlehner G, Hansen RA, Reichenpfader U, et al. Drug class review: second-generation antidepressants: Final update 5 report. Drug Class Reviews: Portland, OR 2011.
[44]
De Long NE, Stepita RA, Taylor VH, Holloway AC. Major depressive disorder and diabetes: Does serotonin bridge the gap? Curr Diabetes Rev 2015; 11(2): 71-8.
[45]
Howland RH. Critical appraisal and update on the clinical utility of agomelatine, a melatonergic agonist, for the treatment of major depressive disease in adults. Neuropsychiatr Dis Treat 2009; 5: 563-76.
[46]
Manikandan S. Agomelatine: A novel melatonergic antidepressant. J Pharmacol Pharmacother 2010; 1(2): 122-3.
[47]
Sansone RA, Sansone LA. Agomelatine: A novel antidepressant. Innov Clin Neurosci 2011; 8(11): 10-4.
[48]
Howland RH. Agomelatine: a novel atypical antidepressant. J Psychosoc Nurs Ment Health Serv 2007; 45(12): 13-7.
[49]
Stahl SM, Pradko JF, Haight BR, Modell JG, Rockett CB, Learned-Coughlin S. A review of the neuropharmacology of bupropion, a dual norepinephrine and dopamine reuptake inhibitor. Prim Care Companion J Clin Psychiatry 2004; 6(4): 159-66.
[50]
Nutt DJ. The role of dopamine and norepinephrine in depression and antidepressant treatment. J Clin Psychiatry 2006; 67(Suppl. 6): 3-8.
[51]
Grunebaum MF, Keilp JG, Ellis SP, et al. SSRI versus bupropion effects on symptom clusters in suicidal depression: post hoc analysis of a randomized clinical trial. J Clin Psychiatry 2013; 74(9): 872-9.
[52]
Clayton AH, Alkis AR, Parikh NB, Votta JG. Sexual dysfunction due to psychotropic medications. Psychiatr Clin North Am 2016; 39(3): 427-63.
[53]
de Boer T. The effects of mirtazapine on central noradrenergic and serotonergic neurotransmission. Int Clin Psychopharmacol 1995; 10(Suppl. 4): 19-23.
[54]
Watanabe N, Omori IM, Nakagawa A, et al. Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev 2011; (12): CD006528.
[55]
Simopoulos EF, Trinidad AC. Male erectile dysfunction: Integrating psychopharmacology and psychotherapy. Gen Hosp Psychiatry 2013; 35(1): 33-8.
[56]
Viera AJ, Clenney TL, Shenenberger DW, Green GF. Newer pharmacologic alternatives for erectile dysfunction. Am Fam Physician 1999; 60(4) 1159-66, 69, 72.
[57]
Barada JH. Optimizing outcomes of oral therapy for patients with erectile dysfunction. Rev Urol 2003; 5(Suppl. 7): S28-34.
[58]
Taylor MJ, Rudkin L, Bullemor‐Day P, Lubin J, Chukwujekwu C, Hawton K. Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database Syst Rev 2013; (5): CD003382.
[59]
Clayton AH, Croft HA, Handiwala L. Antidepressants and sexual dysfunction: Mechanisms and clinical implications. Postgrad Med 2014; 126(2): 91-9.
[60]
Outhoff K. Antidepressant-induced sexual dysfunction. S Afr Fam Pract 2009; 51(4): 298-302.