General Hospital Psychiatry xxx (2015) xxx–xxx

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Stuttering priapism associated with topiramate Narayana Manjunatha, M.D., D.P.M. a,⁎, Vivek Benegal, M.D., D.P.M. b a b

Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru 560029, India Centre for Addiction Medicine, Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru 560029, India

a r t i c l e

i n f o

Article history: Received 4 February 2015 Revised 10 June 2015 Accepted 10 June 2015 Available online xxxx Keywords: Topiramate Priapism Dose-dependent Alcohol dependence

a b s t r a c t Objectives: Priapism, or prolonged penile erection in the absence of sexual stimulation, may be a medical emergency. Many medications including antianxiety, antidepressants and antipsychotics have been implicated. This paper presents a case of priapism associated with topiramate use. Methods: This is a description of case report where topiramate was prescribed as anticraving medication in a patient with alcohol dependence. Episodic priapism developed soon after topiramate was prescribed. The severity of priapism reduced with reduction of dosage and disappeared with its discontinuation. Results: Reversible priapism (stuttering subtype) is associated with topiramate. Conclusions: This is the first report of priapism associated with topiramate in the scientific literature.

© 2015 Elsevier Inc. All rights reserved.

1. Introduction Priapism is a pathological condition in which the ‘erect penis does not return to its flaccid state despite the absence of both physical and psychological stimulation’ [1]. Authors report a case of dose-dependent priapism (stuttering subtype) associated with topiramate use in a patient with alcohol dependence syndrome. There are many medications that have been implicated in the development of priapism such as vasoactive erectile agents, alpha adrenergic receptor antagonists, anticoagulants, antihypertensive, antianxiety (hydroxyzine), antidepressants (trazodone, bupropion, fluoxetine, sertraline), antipsychotics (clozapine, risperidone, olanzapine, chlorpromazine, thioridazine, phenothiazines) and so on [2]. Although topiramate use has been associated with sexual side effects such as anorgasmia [3–5], ejaculatory pain [6] and erectile dysfunction [7,8], this appears to be the first report of topiramate causing priapism. Interestingly, topiramate has been successfully used in the treatment of persistent genital arousal disorder [9]. 2. Case report A 42-year-old married male with no previous history of sexual difficulty and with history of alcohol and nicotine dependence for 10 and 20 years respectively, was admitted with a diagnosis of alcohol dependence syndrome with complicated withdrawal state (delirium tremens following withdrawal seizure) (ICD 10: F10.41). He was treated with benzodiazepines for the treatment of alcohol withdrawal. Five days after the cessation of benzodiazepines, topiramate was started as anticraving medication, at a starting dose of 50 mg/day and ⁎ Corresponding author. E-mail address: [email protected] (N. Manjunatha).

gradually increased to 200 mg/day over 3 weeks. He was discharged on topiramate and multivitamins containing high doses of thiamine. On the first follow-up review, 15 days later, along with his spouse, he complained of having experienced prolonged painful erections (5 episodes of 30–45 min each, i.e., all sexual intercourse over the past fortnight) without ejaculation despite having prolonged sex. There was however spontaneous resolution of the erection each time. He also noticed multiple episodes of prolonged nocturnal penile tumescence for about 30 min. There was no history of retrograde ejaculation. External genitalia were normal. A complete hemogram and peripheral smear for morphology showed no abnormality. The onset of priapism was temporally correlated with starting of topiramate and there was no other obvious alternative cause, topiramate-induced priapism was suspected. Topiramate was reduced to 100 mg/day and tapered off within 1 week. Two weeks later during the second follow-up, the patient reported that the painful erections had stopped within 1 week after the discontinuation of topiramate and that the couple’s sexual functioning was improved with marked reduction in duration of erection for about 10 min. The patient reported that all sexual encounters were painless and ended with climax and ejaculation. Topiramate was stopped and acamprosate (1332 mg/day) was substituted. Multivitamins were continued as before. The score on the Naranjo Adverse Drug Reaction Probability (ADRP) Scale [10] was 7, indicating the “probable” likelihood of a side effect of topiramate. We conclude that topiramate may be associated with recurrent and dose-dependent priapism. 3. Discussion Priapism can be classified as ischemic, nonischemic and stuttering (recurrent or intermittent). Ischemic (veno-occlusive) priapism is the

http://dx.doi.org/10.1016/j.genhosppsych.2015.06.010 0163-8343/© 2015 Elsevier Inc. All rights reserved.

Please cite this article as: Manjunatha N., Benegal V, Stuttering priapism associated with topiramate, Gen Hosp Psychiatry (2015), http:// dx.doi.org/10.1016/j.genhosppsych.2015.06.010

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N. Manjunatha, V. Benegal / General Hospital Psychiatry xxx (2015) xxx–xxx

commonest form and it is usually painful. Ischemic priapism beyond 4 h can lead to compartment syndrome that may require an emergency medical and surgical intervention. Nonischemic (arterial) priapism is a less common form that is caused by unregulated cavernous inflow. It is usually painless and not fully rigid. This will never lead to compartment syndrome, but this requires a detailed evaluation. Stuttering priapism (SP) is a variant of the ischemic type that is characterized by repetitive, transient, painful, self-limiting episodes of priapism. SP is a poorly understood entity. The duration of the erectile episodes in SP is generally shorter than in ischaemic type. Causes of SP are sickle cell disease (commonest), idiopathic and rarely a neurological disorder. Topiramate has been employed as an anticraving medication prescribed for alcohol dependence at doses up to 300 mg/day. Our patient developed SP on topiramate 200 mg/day. When the dose was reduced to 100 mg/day, the duration of priapism reduced and disappeared subsequently with its discontinuation. The temporal relationship of onset of priapism with initiation of topiramate, reduction of duration of erection with reduction of dosage and disappearance of priapism with discontinuation of topiramate is suggestive of topiramate-induced priapism in a dose-dependent way. The concomitant use of multivitamins with high dose of thiamine is unlikely to have contributed to the SP, since the same dosage of multivitamins was maintained throughout the treatment

period. It is suggested that clinicians routinely enquire about sexual side effects in every patient receiving topiramate. Assessment of sexual side effects is recommended in all prospective clinical trials of topiramate. References [1] Berger R, Billups K, Brock G, Broderick GA, Dhabuwala CB, Goldstein I, et al. Report of the American Foundation for Urologic Disease (AFUD) Thought Leader Panel for evaluation and treatment of priapism. Int J Impot Res 2001;5:S39–43. [2] Morrison BF, Burnett AL. Stuttering priapism: insights into pathogenesis and management. Curr Urol Rep 2012;13(4):268–76. [3] Newman LC, Broner SW, Lay CL. Reversible anorgasmia with topiramate therapy for migraine. Neurology 2005;65(8):1333–4. [4] Sun C, Lay C, Broner S, Silberstein S, Tepper S, Newman L. Reversible anorgasmia with topiramate therapy for headache: a report of 7 patients. Headache 2006;46(9):1450–3. [5] Lasaosa SS, Fernández LG, del Val LJ. Anorgasmia due to topiramate. Neurologia 2008;23(8):541–2. [6] Pérez J, Arguis M, Moreno L, Sinche M. Management of ejaculation pain with topiramate: a case report. Clin J Pain 2004;20(5):368–9. [7] Civardi C, Collini A, Gontero P, Monaco F. Vasogenic erectile dysfunction topiramateinduced. Clin Neurol Neurosurg 2012;114(1):70–1. [8] Hung LC, Chow JC, Chang CY, Tsai JJ, Huang CW. Topiramate related reversible erectile dysfunction in temporal lobe epilepsy. Neurol Sci 2012;33(2):331–3. [9] Ramic M. A case of persistent genital arousal disorder successfully treated with topiramate in a physically healthy individual. J Clin Psychiatry 2013;74(7):693. [10] Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239–45.

Please cite this article as: Manjunatha N., Benegal V, Stuttering priapism associated with topiramate, Gen Hosp Psychiatry (2015), http:// dx.doi.org/10.1016/j.genhosppsych.2015.06.010

Stuttering priapism associated with topiramate.

Priapism, or prolonged penile erection in the absence of sexual stimulation, may be a medical emergency. Many medications including antianxiety, antid...
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