Altındag, Abdurrahman

Demir, Bahadır

Sancaktar, Muhammet

English

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272INTRODUCTIONModafinil is an agent used in narcolepsy and excessive daytime sleepiness (Adler et al. 2003).The mechanism of action of modafinil is still unknown, however, it appears to interact with dopaminergic, noradrenergic, glutamater-gic, GABAergic, serotoninergic, orexinergic, and histami-nergic pathways (Minzenberg et al. 2008). Modafinil in-creases brain dopamine levels by blocking the dopamine transporter (Volkow et al. 2009). In addition to narcolepsy, modafinil has been shown to be effective in diseases such as unipolar and bipolar depression, attention deficit and hyperactivity disorder, schizophrenia, obstructive sleep apnea, and multiple sclerosis . Especially studies conduct-ed on patients diagnosed with ADHD show that it seems to provide an improvement in cognitive areas such as attention and planning (Turner et al. 2004). The recom-mended dose range is 200-400mg/day. The adverse effects of modafinil include headache, ir-ritability, anxiety, psychosis, nausea and suicidal ideation (Whitmore et al. 2006). Despite its low addiction poten-tial, there are publications suggesting that it is addictive. Here we will share a case of hypersexuality associated with modafinil use.CASE REPORTA 24-year-old single male patient with a bachelor’s degree is currently unemployed and preparing for exams. The patient has complaints of unhappiness, malaise, lack of taste for life, attention deficit, increased appetite, day-time sleepiness and sexual reluctance, which started due to not being employed for about two years. The patient was diagnosed with major depressive disorder with these complaints. The patient had previously used escitalopram fluoxetine and venlafaxine but did not benefit. The patient was also started on methylphenidate for attention deficit because he was studying for an exam but could not toler-ate it. Then he started to use sertraline 200 mg and modaf-inil 200 mg, from which he did not benefit from sertraline as well. He’s only been on modafinil for the last 2 months. When he presented to our clinic, he was only on modaf-inil 400 mg/day. The patient’s complaint at presentation to our clinic was increased sexual drive after the modaf-inil dose adjustment from 200 mg to 400 mg. The patient, suffering from sexual reluctance and inability to orgasm for the last two years, had increased sexual desire, dissat-isfaction despite masturbation 6 times a day, incapability to study for exams due to these reasons, and deterioration in functionality in life after 400 mg/day modafinil dose adjustment. SCID-2 compatible with DSM was used in the diagnosis part. Young mania scale (YMRS) was ap-plied (YMRS<5). The patient did not have psychotic or manic symptoms (depressed mood, no increase in energy, no increase in speech, normal sleep and appetite, no in-crease in self-confidence) in the mental status examina-tion. Routine blood tests, biochemistry, hormone levels, and vital signs were regular. The physical examination was in good condition. Detailed history analysis revealed no such complaints in the past and showed no recent head trauma and any associated impulsivity, obsessive com-pulsive behavior, substance abuse, hyperorality, cogni-tive decline, and aphrodisiac use.Due to ongoing major depressive disorder and concen-tration problems, we started bupropion 150 mg/day and discontinued modafinil treatment. After 2 weeks he called for a follow-up. At the follow-up, sexual desire and urg-es returned to standard, and there was a decrease in de-pressive complaints. On subsequent follow-up visits, we achieved remission with bupropion 300mg/day treatment.DISCUSSIONIn a patient with major depressive disorder with sexual reluctance, hypersexuality developed as a result of increasing the dose of modafinil to 400 mg/day, and sexual desire and drive decreased as the dose decreased again, suggesting that modafinil causes hypersexuality at high doses in this case. Two cases of modafinil-related hypersexuality have been reported in the literature (Bulut Psychiatria Danubina, 2023; Vol. 35, No. 2, pp 272-273 https://doi.org/10.24869/psyd.2023.272  Case report© Medicinska naklada & Pro mente, Zagreb, CroatiaHYPERSEXUALITY ASSOCIATED WITH  MODAFINIL USEMuhammet Sancaktar1,*, Bahadır Demir1 & Abdurrahman Altındag11 Department of Psychiatry, University of Gaziantep, Şahinbey Research and Practice Hospital, Gaziantep, Turkey.* Corresponding Authorreceived: 08.12.2022;    revised: 21.02.2023;    accepted: 21.06.2023* * * * *273et al. 2015; Swapnajeet et al. 2016). The case published by Swapnajeet et al. is a case of hypersexuality resulting from increasing the dose of modafinil to 1000mg/day in a patient diagnosed with bipolar disorder (Swapnajeet et al. 2016). Unlike our case, hypersexuality, in this case, may be due to the underlying excess sexual desire related to the manic phase of bipolar disorder. Our patient was a patient with major depressive disorder with complaints of sexual anorexia. The case published by Bulut et al. is a case of hypersexuality developing upon initiation of 200 mg/day modafinil in a patient diagnosed with narcolepsy (Bulut et al. 2015). In this case, hypersexuality developed with a lower dose of modafinil and this adverse effect dis-appeared after the modafinil dose was reduced to 50mg/day. In our case, the development of higher doses may be the reason for the diagnosis of depression. In addition to hypersexuality, there are cases of spontaneous orgasm (Uca&Altaş 2014) and spontaneous ejaculation (Aras 2021)associated with modafinil use.Hypersexuality has typically been reported in Klu-ver Bucy syndrome. We excluded this diagnosis from our patient because of the absence of hypersomnia, hy-per-morality, and hyperphagia. Hypersexuality is also seen in head traumas, brain operations, frontal and tem-poral lobe lesions, dementia, stroke, Huntington’s disease, Tourette’s disease, dopaminergic agents, cocaine, and amphetamine (Kaplan &Krueger 2010) The pathophys-iology of modafinil-induced hypersexuality is unclear. The relationship between addiction and hypersexuality is known (Uca&Altaş 2014). Hypersexuality is a hyperdo-paminergic state (Swapnajeet et al. 2016). Modafinil-in-duced increase in dopamine in the mesolimbic pathway may explain the development of hypersexuality in our case.CONCLUSIONIn conclusion, clinicians should carefully increase the dose considering modafinil-induced hypersexuality may develop. Furthermore, it can be offered as an ad-junctive treatment in favorable patients presenting sex-ual anorexia.References1. Adler CH, Caviness JN, Hentz JG, Lind M, Tiede J. Ran-domized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinson’s disease. Mov Disord 2003;18:287–93 .2. Aras N. Modafinil Induced Spontaneous Ejaculation Without Orgasm: A Case Report. Clin Neuropharmacol 2021;44:27–8. 3. Bulut SD, Tulaci RG, Türkoğlu S, Bulut S, Örsel S. Hyper-sexuality after modafinil treatment: a case report. J Pharm Pharmacol. 2015;3:39–41. 4. Kaplan MS, Krueger RB. Diagnosis, assessment, and treat-ment of hypersexuality. J Sex Res 2010;47:181–98. 5. Minzenberg MJ, Watrous AJ, Yoon JH, Ursu S, Carter CS. Modafinil shifts human locus coeruleus to low-ton-ic, high-phasic activity during functional MRI. Science 2008;322:1700–2. 6. Swapnajeet S, Subodh BN, Gourav G. Modafinil dependence and hypersexuality: a case report and review of the evidence. Clin Psychopharmacol Neurosci 2016;30;14:402-404 7. Turner DC, Clark L, Dowson J, Robbins TW, Sahakian BJ. Modafinil improves cognition and response inhibition in adult attention-deficit/hyperactivity disorder. Biol Psychia-try 2004;55:1031–40. 8. Uca AU, Altaş M. Modafinil‐induced spontaneous unwel-come orgasms. Sleep Biol Rhythms. 2014;3:227–8. 9. Volkow ND, Fowler JS, Logan J, Alexoff D, Zhu W, Telang F, et al. Effects of modafinil on dopamine and dopamine transporters in the male human brain:clinical implications. JAMA 2009;301:1148–54. 10. Whitmore J, Hickey P, Doan B, Harrison R, Kisner J, Bel-tran T, et al. A double-blind placebo-controlled investiga-tion of the efficacy of Modafinil for maintaining alertness and performance in sustained military ground operations. Air Force Research Lab Brooks AFB TX Human Effective-ness DIR/Biodynamics and Protection DIV; 2006. Muhammet Sancaktar, Bahadır Demir & Abdurrahman Altındag: HYPERSEXUALITY ASSOCIATED  WITH MODAFINIL USE   Psychiatria Danubina, 2023; Vol. 35, No. 2, pp 272-273Correspondence: Muhammet Sancaktar Şahinbey Research and Application Hospital,  Üniversite Boulevard P.C. 27310,  Department of Psychiatry Gaziantep, Turkey drsancaktar@hotmail.com, +90 03423606060

HYPERSEXUALITY ASSOCIATED WITH MODAFINIL USE

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