Hostname: page-component-7c8c6479df-nwzlb Total loading time: 0 Render date: 2024-03-27T05:28:46.870Z Has data issue: false hasContentIssue false

Lamotrigine-induced sexual dysfunction and non-adherence: case analysis with literature review

Published online by Cambridge University Press:  02 January 2018

Kenneth R. Kaufman*
Affiliation:
Departments of Psychiatry, Neurology and Anesthesiology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
Melissa Coluccio
Affiliation:
Department of Psychiatry, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
Kartik Sivaraaman
Affiliation:
Department of Neurology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
Miriam Campeas
Affiliation:
Department of Psychiatry, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
*
Kenneth R. Kaufman, Departments of Psychiatry, Neurology and Anesthesiology, Rutgers Robert Wood Johnson Medical School, 125 Paterson Street, Suite #2200, New Brunswick, NJ 08901, USA. E-mail:kaufmakr@rwjms.rutgers.edu
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Background

Optimal anti-epileptic drug (AED) treatment maximises therapeutic response and minimises adverse effects (AEs). Key to therapeutic AED treatment is adherence. Non-adherence is often related to severity of AEs. Frequently, patients do not spontaneously report, and clinicians do not specifically query, critical AEs that lead to non-adherence, including sexual dysfunction. Sexual dysfunction prevalence in patients with epilepsy ranges from 40 to 70%, often related to AEDs, epilepsy or mood states. This case reports lamotrigine-induced sexual dysfunction leading to periodic non-adherence.

Aims

To report lamotrigine-induced sexual dysfunction leading to periodic lamotrigine non-adherence in the context of multiple comorbidities and concurrent antidepressant and antihypertensive pharmacotherapy.

Method

Case analysis with PubMed literature review.

Results

A 56-year-old male patient with major depression, panic disorder without agoraphobia and post-traumatic stress disorder was well-controlled with escitalopram 20 mg bid, mirtazapine 22.5 mg qhs and alprazolam 1 mg tid prn. Comorbid conditions included complex partial seizures, psychogenic non-epileptic seizures (PNES), hypertension, gastroesophageal reflux disease and hydrocephalus with patent ventriculoperitoneal shunt that were effectively treated with lamotrigine 100 mg tid, enalapril 20 mg qam and lansoprazole 30 mg qam. He acknowledged non-adherence with lamotrigine secondary to sexual dysfunction. With lamotrigine 300 mg total daily dose, he described no libido with impotence/anejaculation/anorgasmia. When off lamotrigine for 48 h, he described becoming libidinous with decreased erectile dysfunction but persistent anejaculation/anorgasmia. When off lamotrigine for 72 h to maximise sexual functioning, he developed auras. Family confirmed patient's consistent monthly non-adherence for 2–3 days during the past year.

Conclusions

Sexual dysfunction is a key AE leading to AED non-adherence. This case describes dose-dependent lamotrigine-induced sexual dysfunction with episodic non-adherence for 12 months. Patient/clinician education regarding AED-induced sexual dysfunction is warranted as are routine sexual histories to ensure adherence.

Type
Short report
Copyright
Copyright © The Royal College of Psychiatrists 2017

Footnotes

Presented in part at the 19th Annual Conference of the International Society of Bipolar Disorders, Washington DC, 4–7 May 2017.

Declaration of interest

No financial interests. K.R.K. is Editor of BJPsych Open; he took no part in the peer-review of this work.

References

1 Boon, P, Engelborghs, S, Hauman, H, Jansen, A, Lagae, L, Legros, B, et al. Recommendations for the treatment of epilepsy in adult patients in general practice in Belgium: an update. Acta Neurol Belg 2012; 112: 119–31.Google Scholar
2 Ketter, TA, Miller, S, Dell’Osso, B, Calabrese, JR, Frye, MA, Citrome, L. Balancing benefits and harms of treatments for acute bipolar depression. J Affect Disord 2014; 169 (suppl 1): S2433.Google Scholar
3 Buelow, JM, Smith, MC. Medication management by the person with epilepsy: perception versus reality. Epilepsy Behav 2004; 5: 401–6.CrossRefGoogle ScholarPubMed
4 Chapman, SC, Horne, R, Chater, A, Hukins, D, Smithson, WH. Patients’ perspectives on antiepileptic medication: relationships between beliefs about medicines and adherence among patients with epilepsy in UK primary care. Epilepsy Behav 2014; 31: 312–20.Google Scholar
5 Sajatovic, M, Valenstein, M, Blow, F, Ganoczy, D, Ignacio, R. Treatment adherence with lithium and anticonvulsant medications among patients with bipolar disorder. Psychiatr Serv 2007; 58: 855–63.Google Scholar
6 Ettinger, AB, Manjunath, R, Candrilli, SD, Davis, KL. Prevalence and cost of nonadherence to antiepileptic drugs in elderly patients with epilepsy. Epilepsy Behav 2009; 14: 324–9.CrossRefGoogle ScholarPubMed
7 Olesen, J, Gustavsson, A, Svensson, M, Wittchen, HU, Jönsson, B, CDBE2010 Study Group et al. The economic cost of brain disorders in Europe. Eur J Neurol 2012; 19: 155–62.Google Scholar
8 Whiteford, HA, Ferrari, AJ, Degenhardt, L, Feigin, V, Vos, T. The global burden of mental, neurological and substance use disorders: an analysis from the Global Burden of Disease Study 2010. PLoS One 2015; 10: e0116820.Google Scholar
9 Kessler, RC, Akiskal, HS, Ames, M, Birnbaum, H, Greenberg, P, Hirschfeld, RM, et al. Prevalence and effects of mood disorders on work performance in a nationally representative sample of U.S. workers. Am J Psychiatry 2006; 163: 1561–8.CrossRefGoogle Scholar
10 Getnet, A, Woldeyohannes, SM, Bekana, L, Mekonen, T, Fekadu, W, Menberu, M, et al. Antiepileptic drug nonadherence and its predictors among people with epilepsy. Behav Neurol 2016; 2016: 3189108.CrossRefGoogle ScholarPubMed
11 Nakhutina, L, Gonzalez, JS, Margolis, SA, Spada, A, Grant, A. Adherence to antiepileptic drugs and beliefs about medication among predominantly ethnic minority patients with epilepsy. Epilepsy Behav 2011; 22: 584–6.Google Scholar
12 Baldessarini, RJ, Perry, R, Pike, J. Factors associated with treatment nonadherence among US bipolar disorder patients. Hum Psychopharmacol 2008; 23: 95105.Google Scholar
13 Leclerc, E, Mansur, RB, Brietzke, E. Determinants of adherence to treatment in bipolar disorder: a comprehensive review. J Affect Disord 2013; 149: 247–52.Google Scholar
14 Mitchell, AJ, Selmes, T. Why don't patients take their medicine? Reasons and solutions in psychiatry. Adv Psychiatr Treat 2007; 13: 336–46.CrossRefGoogle Scholar
15 Sleath, B, Rubin, RH, Huston, SA. Hispanic ethnicity, physician-patient communication, and antidepressant adherence. Compr Psychiatry 2003; 44: 198204.Google Scholar
16 Serretti, A, Chiesa, A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. J Clin Psychopharmacol 2009; 29: 259–66.Google Scholar
17 Kaufman, KR, Wong, S, Sivaraaman, K, Anim, C, Delatte, D. Epilepsy and AED-induced decreased libido – the unasked psychosocial comorbidity. Epilepsy Behav 2015; 52(Pt A): 236–8.Google Scholar
18 Henning, OJ, Nakken, KO, Træen, B, Mowinckel, P, Lossius, M. Sexual problems in people with refractory epilepsy. Epilepsy Behav 2016; 61: 174–9.Google Scholar
19 Sivaraaman, K, Mintzer, S. Hormonal consequences of epilepsy and its treatment in men. Curr Opin Endocrinol Diabetes Obes 2011; 18: 204–9.Google Scholar
20 Michael, A, O’Keane, V. Sexual dysfunction in depression. Hum Psychopharmacol 2000; 15: 337–45.Google Scholar
21 Grover, S, Ghosh, A, Sarkar, S, Chakrabarti, S, Avasthi, A. Sexual dysfunction in clinically stable patients with bipolar disorder receiving lithium. J Clin Psychopharmacol 2014; 34: 475–82.Google Scholar
22 La Torre, A, Giupponi, G, Duffy, DM, Pompili, M, Grözinger, M, Kapfhammer, HP, et al. Sexual dysfunction related to psychotropic drugs: a critical review. Part III: mood stabilizers and anxiolytic drugs. Pharmacopsychiatry 2014; 47: 16.Google ScholarPubMed
23 Kaufman, KR, Struck, PJ. Gabapentin-induced sexual dysfunction. Epilepsy Behav 2011; 21: 324–6.Google Scholar
24 Kandeel, FR, Koussa, VK, Swerdloff, RS. Male sexual function and its disorders: physiology, pathophysiology, clinical investigation, and treatment. Endocr Rev 2001; 22: 342–88.CrossRefGoogle ScholarPubMed
25 Capogrosso, P, Ventimiglia, E, Boeri, L, Capitanio, U, Gandaglia, G, Dehò, F, et al. Sexual functioning mirrors overall men's health status, even irrespective of cardiovascular risk factors. Andrology 2017; 5: 63–9.CrossRefGoogle ScholarPubMed
26 Viigimaa, M, Doumas, M, Vlachopoulos, C, Anyfanti, P, Wolf, J, Narkiewicz, K, et al. Hypertension and sexual dysfunction: time to act. J Hypertens 2011; 29: 403–7.Google Scholar
27 Francis, ME, Kusek, JW, Nyberg, LM, Eggers, PW. The contribution of common medical conditions and drug exposures to erectile dysfunction in adult males. J Urol 2007; 178: 591–6.CrossRefGoogle ScholarPubMed
28 McCabe, MP, Sharlip, ID, Lewis, R, Atalla, E, Balon, R, Fisher, AD, et al. Risk factors for sexual dysfunction among women and men: a consensus statement from the Fourth International Consultation on Sexual Medicine 2015. J Sex Med 2016; 13: 153–67.Google Scholar
29 Lehrner, A, Flory, JD, Bierer, LM, Makotkine, I, Marmar, CR, Yehuda, R. Sexual dysfunction and neuroendocrine correlates of posttraumatic stress disorder in combat veterans: preliminary findings. Psychoneuroendocrinology 2016; 63: 271–5.Google Scholar
30 Kumsar, NA, Kumsar, Ş, Dilbaz, N. Sexual dysfunction in men diagnosed as substance use disorder. Andrologia 2016; 48: 1229–35.CrossRefGoogle ScholarPubMed
31 Naranjo, CA, Shear, NH, Lanctôt, KL. Advances in the diagnosis of adverse drug reactions. J Clin Pharmacol 1992; 32: 897904.Google Scholar
32 Kennedy, SH, Dugré, H, Defoy, I. A multicenter, double-blind, placebo-controlled study of sildenafil citrate in Canadian men with erectile dysfunction and untreated symptoms of depression, in the absence of major depressive disorder. Int Clin Psychopharmacol 2011; 26: 151–8.CrossRefGoogle ScholarPubMed
33 Seidman, S. Ejaculatory dysfunction and depression: pharmacological and psychobiological interactions. Int J Impot Res 2006; 18 (suppl 1): S338.Google Scholar
34 Rajkumar, RP, Kumaran, AK. Depression and anxiety in men with sexual dysfunction: a retrospective study. Compr Psychiatry 2015; 60: 114–8.Google Scholar
35 Blumentals, WA, Gomez-Caminero, A, Brown, RR, Vannappagari, V, Russo, LJ. A case-control study of erectile dysfunction among men diagnosed with panic disorder. Int J Impot Res 2004; 16: 299302.CrossRefGoogle ScholarPubMed
36 Badour, CL, Gros, DF, Szafranski, DD, Acierno, R. Problems in sexual functioning among male OEF/OIF veterans seeking treatment for posttraumatic stress. Compr Psychiatry 2015; 58: 7481.CrossRefGoogle ScholarPubMed
37 Smaldone, M, Sukkarieh, T, Reda, A, Khan, A. Epilepsy and erectile dysfunction: a review. Seizure 2004; 13: 453–9.Google Scholar
38 Hellmis, E. Sexual problems in males with epilepsy – an interdisciplinary challenge! Seizure 2008; 17: 136–40.Google Scholar
39 Aull-Watschinger, S, Pataraia, E, Baumgartner, C. Sexual auras: predominance of epileptic activity within the mesial temporal lobe. Epilepsy Behav 2008; 12: 124–7.CrossRefGoogle ScholarPubMed
40 Suffren, S, Braun, CM, Guimond, A, Devinsky, O. Opposed hemispheric specializations for human hypersexuality and orgasm? Epilepsy Behav 2011; 21: 12–9.Google Scholar
41 Fiszman, A, Alves-Leon, SV, Nunes, RG, D’Andrea, I, Figueira, I. Traumatic events and posttraumatic stress disorder in patients with psychogenic nonepileptic seizures: a critical review. Epilepsy Behav 2004; 5: 818–25.CrossRefGoogle ScholarPubMed
42 Baslet, G, Roiko, A, Prensky, E. Heterogeneity in psychogenic nonepileptic seizures: understanding the role of psychiatric and neurological factors. Epilepsy Behav 2010; 17: 236–41.Google Scholar
43 Doumas, M, Douma, S. Sexual dysfunction in essential hypertension: myth or reality? J Clin Hypertens (Greenwich) 2006; 8: 269–74.CrossRefGoogle ScholarPubMed
44 Iovino, P, Pascariello, A, Limongelli, P, Tremolaterra, F, Consalvo, D, Sabbatini, F, et al. The prevalence of sexual behavior disorders in patients with treated and untreated gastroesophageal reflux disease. Surg Endosc 2007; 21: 1104–10.Google Scholar
45 Missori, P, Scollato, A, Formisano, R, Currà, A, Mina, C, Marianetti, M, et al. Restoration of sexual activity in patients with chronic hydrocephalus after shunt placement. Acta Neurochir (Wien) 2009; 151: 1241–4.CrossRefGoogle ScholarPubMed
46 La Torre, A, Giupponi, G, Duffy, D, Conca, A. Sexual dysfunction related to psychotropic drugs: a critical review – part I: antidepressants. Pharmacopsychiatry 2013; 46: 191–9.Google ScholarPubMed
47 Montejo, AL, Llorca, G, Izquierdo, JA, Rico-Villademoros, F. 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): 1021.Google Scholar
48 Fossey, MD, Hamner, MB. Clonazepam-related sexual dysfunction in male veterans with PTSD. Anxiety 1994–1995; 1: 233–6.CrossRefGoogle Scholar
49 Uhde, TW, Tancer, ME, Shea, CA. Sexual dysfunction related to alprazolam treatment of social phobia. Am J Psychiatry 1988; 145: 531–2.Google ScholarPubMed
50 Kaufman, KR. Antiepileptic drugs in the treatment of psychiatric disorders. Epilepsy Behav 2011; 21: 111.Google Scholar
51 Calabrò, RS, Italiano, D, Militi, D, Bramanti, P. Levetiracetam-associated loss of libido and anhedonia. Epilepsy Behav 2012; 24: 283–4.Google Scholar
52 Herzog, AG, Drislane, FW, Schomer, DL, Pennell, PB, Bromfield, EB, Dworetzky, BA, et al. Differential effects of antiepileptic drugs on sexual function and hormones in men with epilepsy. Neurology 2005; 65: 1016–20.Google Scholar
53 Gil-Nagel, A, López-Muñoz, F, Serratosa, JM, Moncada, I, García-García, P, Alamo, C. Effect of lamotrigine on sexual function in patients with epilepsy. Seizure 2006; 15: 142–9.Google Scholar
54 Svalheim, S, Taubøll, E, Luef, G, Lossius, A, Rauchenzauner, M, Sandvand, F, et al. Differential effects of levetiracetam, carbamazepine, and lamotrigine on reproductive endocrine function in adults. Epilepsy Behav 2009; 16: 281–7.CrossRefGoogle ScholarPubMed
55 Husain, AM, Carwile, ST, Miller, PP, Radtke, RA. Improved sexual function in three men taking lamotrigine for epilepsy. South Med J. 2000; 93: 335–6.Google Scholar
56 Grimm, RH Jr, Grandits, GA, Prineas, RJ, McDonald, RH, Lewis, CE, Flack, JM, et al. Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS). Hypertension 1997; 29(Pt 1): 814.CrossRefGoogle ScholarPubMed
57 La Torre, A, Giupponi, G, Duffy, D, Conca, A, Catanzariti, D. Sexual dysfunction related to drugs: a critical review. Part IV: cardiovascular drugs. Pharmacopsychiatry 2015; 48: 16.Google Scholar
58 Brixius, K, Middeke, M, Lichtenthal, A, Jahn, E, Schwinger, RH. Nitric oxide, erectile dysfunction and beta-blocker treatment (MR NOED study): benefit of nebivolol versus metoprolol in hypertensive men. Clin Exp Pharmacol Physiol 2007; 34: 327–31.Google Scholar
59 Fogari, R, Zoppi, A. Effects of antihypertensive therapy on sexual activity in hypertensive men. Curr Hypertens Rep 2002; 4: 202–10.CrossRefGoogle Scholar
60 Coulson, M, Gibson, GG, Plant, N, Hammond, T, Graham, M. Lansoprazole increases testosterone metabolism and clearance in male Sprague-Dawley rats: implications for Leydig cell carcinogenesis. Toxicol Appl Pharmacol 2003; 192: 154–63.Google Scholar
61 Lindquist, M, Edwards, IR. Endocrine adverse effects of omeprazole. BMJ 1992; 305: 451–2.Google Scholar
62 Lareb. Omeprazole and Erectile Dysfunction (http://databankws.lareb.nl/Downloads/kwb_2006_4_omep.pdf).Google Scholar
63 Cascorbi, I. Drug interactions – principles, examples and clinical consequences. Dtsch Arztebl Int 2012; 109: 546–56.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.