Galore International Journal of Health Sciences and Research Vol.4; Issue: 3; July-September 2019 Website: www.gijhsr.com Case Report P-ISSN: 2456-9321

A Case Report on Modafinil Dependence

Dr. Priyanka D’Souza1, Dr. Joylin Jovita Mascarenhas2

1Post Graduate Resident, 2Assistant Professor, Dept. of Psychiatry, Father Muller Medical College, Mangalore

Corresponding Author: Dr. Joylin Jovita Mascarenhas

ABSTRACT Modafinil, adrafinil, and ampakine are categorized. Eugeroics are devoid of Modafinil is a non-amphetamine stimulant common side effects of traditional frequently prescribed for the treatment of sleep psychostimulants such as excess locomotor disorders such as narcolepsy, obstructive sleep activities, anxiety, jitteriness or interference apnea syndrome, and shift work sleep disorder. in recovery sleep. (9) Due to its Besides, literature also states that Modafinil enhances cognitive functions. Thus, its use dopaminergic activity and low abuse among healthy individuals is increasing to potential, Modafinil has also been used in enhance their alertness or to reduce fatigue. treatment of cocaine, methamphetamine Similar effects of Modafinil have also been abuse and impaired cognitive functions in described in patients with psychiatric illness for alcohol dependent individuals. (10-13) treatment of cognitive dysfunction. Clinical However, the recent reports reported the research has shown that Modafinil improves possibility of dependence in Modafinil due symptoms in patients with major depression, to its sensitivity to dopamine signalling in schizophrenia, and attention-deficit the brain. hyperactivity disorder (ADHD). In early studies, it was stated that Modafinil is a well-tolerated CASE DESCRIPTION drug with low addiction potential. This case report is one of the few case reports on A 55 year old male, presented to Modafinil dependence Psychiatry Inpatient-department with complaints of irritability, suspiciousness and Keywords: Dependence, Modafinil, Non assaultive behavior increased since 2 years. amphetamine, Stimulant On detailed evaluation, it was found that he had history of psychiatric illness since 30 INTRODUCTION years. The course of illness was gradual in Modafinil is a non-amphetamine onset and continuous characterized by stimulant used in narcolepsy, obstructive auditory hallucinations, referential, sleep apnea and also circadian rhythm infidelity and persecutory delusions leading disorder in shift workers. (1) It has also been to the progressive decline in social and tried for disease related fatigue, attention occupational functioning. He was evaluated deficit hyperactivity disorder, Alzheimer’s for the same and initially started on disease, depression and cognitive psychotropics. But patient was poorly impairment in schizophrenia. (2-6) Modafinil compliant to medications. Since 7 years, he has been commercialized as a wake also complained of lethargy and decreased promoting drug in 2003. (7) Even though the interest to work for which he was prescribed mechanism of action is not clear, its Modafinil 150 mg, along with the pharmacological profile is notably different antipsychotics by a private practitioner. He from the traditional psychostimulants, such reported improvement in symptoms. Hence, as amphetamine, cocaine or the treating psychiatrist advised to gradually methylphenidate. (8) A novel class of taper & stop Modafinil. But, patient psychostimulants is eugeroics under which continued to use Modafinil & when denied

Galore International Journal of Health Sciences and Research (www.gijhsr.com) 6 Vol.4; Issue: 3; July-September 2019 Priyanka D’Souza et.al. A Case Report on Modafinil Dependence by the doctor (as it was indispensable), dopaminergic and noradrenergic (activation patient would obtain it over the counter of alpha-1 receptors) neurotransmission. Its (OTC). He claimed to have symptoms of wakefulness and memory enhancing worsening of lethargy, multiple aches, properties are mostly due these effects anxiety and disturbances in sleep pattern on Modafinil dependence can be attributed to skipping the Modafinil dose. Since 3 years, its dopamine uptake blockade thereby patient had increased his Modafinil use upto increasing its concentration in dopaminergic 300mg/day on his own after few hours of areas of brain. (14) Modafinil promotes recurrence of symptoms. Patient would cognitive functions such as attention, spend most of his time contemplating about learning and memory. Studies have been procuring the drug rather than spending done on patients with mental disorders. One quality time with family/friends or even of the studies with schizophrenic patients going for a job. with Modafinil administration, in addition to Past history of trihexyphenidyl abuse antipsychotic treatment had promising was noted. Patient also had bronchial results suggestive of cognitive function asthma since childhood, with on and off improvement. (15) In this case, patient who medications for the same. Family history of had history of mental illness had symptoms psychosis in mother and younger sibling of increased sleep in the morning and was present. Physical examination was apathy. Modafinil was used to overcome within normal limits. ECG showed sinus these symptoms. rhythm. His investigations including There are few case reports in the literature haemogram, liver, renal& thyroid function stating that Modafinil dependence can occur test, lipid & glucose profile & neuroimaging in patients with substance abusers, ADHD were all within normal limits. and patients with organic mental disease in He was diagnosed to have Paranoid order to enhance cognitive functions. This is Schizophrenia-continuous (F20.00). Also, also supported with the fact that two of the additional diagnosis of Modafinil previously reported cases had concurrent dependence syndrome was made in view of history of alcohol and benzodiazepine evidence of craving, loss of control & dependence, and the third reported case had unsuccessful efforts to cut down, schizoaffective disorder and the other withdrawal symptoms ,tolerance & ADHD. (16-19) Similarly, in this case patient progressive neglect of alternative had history of Trihexyphenidyl abuse. pleasurables or interest &increased amount There is also a case of Modafinil of time spent on obtaining the substance(as associated psychosis and reports of per dependence criteria of ICD 10) withdrawal phenomenon. (20) Overdose of The dose of modafinil was tapered Modafinil is prone to cause insomnia, gradually. He initially reported of sleep agitation, tachycardia and rise in blood disturbance, irritability, anxiety and pressure. (1) lethargy. We started him on clonazepam for There are no controlled trials or symptomatic management & his symptoms reports available for the treatment of improved gradually. Following this, Modafinil addiction. Treatment with clonazepam was also tapered &stopped. antidepressants like Bupropion, Duloxetine Patient maintained well thereafter only on and treatment with benzodiazepines like anti-pyschotics. Clonazepam has been attempted in previously reported cases. (16-18) In this case, CASE DISCUSSION patient reported of sleep disturbances and Modafinil consists of R-enantiomer anxiety which was managed with and S-enantiomer and the waking effect of benzodiazepines. R-enantiomer has a longer duration. Modafinil is known to act via its effects on

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CONCLUSION Psychopharmacol [Internet]. 2000 Jan Studies have claimed that the abuse 1;14(1):53–60. potential of Modafinil is less & 9. Ferraro L, Antonelli T, O’Connor WT, psychoneuroimmunological approach is Tanganelli S, Rambert FA, Fuxe K. necessary to monitor its potential for abuse. Modafinil: An antinarcoleptic drug with a different neurochemical profile to d- But, this case report shows that modafinil amphetamine and dopamine uptake abuse is not uncommon & clinicians have to blockers. Biol Psychiatry. 1997 Dec bear in their mind about its abuse potential 15;42(12):1181–3. while prescribing it. In the recent years, 10. Dackis CA, Kampman KM, Lynch KG, there is an increase in modafinil use by Pettinati HM, O’Brien CP. A Double-Blind, night shift workers, high school students, Placebo-Controlled Trial of Modafinil for athletes and career oriented people to Cocaine Dependence. Neuropsycho- increase work efficiency without sleep in pharmacology. 2005; 30(1):205–11. the present competitive environment. This 11. Kampman KM, Lynch KG, Pettinati HM, could be because of its easy accessibility Spratt K, Wierzbicki MR, Dackis C, et al. A over the counter. Hence, strict regulations in double blind, placebo controlled trial of modafinil for the treatment of cocaine dispensing these medications must be dependence without co-morbid alcohol ensured. dependence. Drug Alcohol Depend. 2015 Oct 1;155:105–10. REFERENCES 12. Kalechstein AD, De La Garza 2nd R, 1. Lackey G, Alsop J, Albertson T. A 24 Newton TF. Modafinil administration month retrospective study of adult modafinil improves working memory in ingestions. Clin Toxicol. 2007;45:641. methamphetamine-dependent individuals 2. Morein-Zamir S, Turner DC, Sahakian BJ. who demonstrate baseline impairment. Am J A review of the effects of modafinil on Addict. 2010;19(4):340–4. cognition in schizophrenia. Schizophr Bull. 13. Schmaal L, Goudriaan AE, Joos L, Krüse 2007/07/18. 2007 Nov;33(6):1298–306. AM, Dom G, van den Brink W, et al. 3. Blackhall L, Petroni G, Shu J, Baum L, Modafinil Modulates Resting-State Farace E. A pilot study evaluating the safety Functional Network Connectivity and and efficacy of modafinal for cancer-related Cognitive Control in Alcohol-Dependent fatigue. J Palliat Med. 2009;12(5):433–439. Patients. Biol Psychiatry. 2013 Apr 15 4. Menza MA, Kaufman KR, Castellanos A. ;73(8):789–95. Modafinil augmentation of antidepressant 14. Volkow ND, Fowler JS, Logan J, Alexoff treatment in depression. J Clin Psychiatry. D, Zhu W, Telang F, et al. Effects of 2000;61(5):378–381. Modafinil on Dopamine and Dopamine 5. J. Wolf, U. Fiedler, I. Anghelescu, and N. Transporters in the Male Human Brain: Schwertfeger, “Manic switch in a patient Clinical Implications. JAMA. 2009 Mar with treatment-resistant bipolar depression 18;301(11):1148–54. treated with modafinil,” Journal of Clinical 15. Farrow TFD, Hunter MD, Haque R, Spence Psychiatry, vol. 67, no. 11, p. 1817, 2006. SA. Modafinil and unconstrained motor 6. Turner DC, Clark L, Dowson J, Robbins activity in schizophrenia. Br J Psychiatry. TW, Sahakian BJ. Modafinil improves 2006 Nov 2;189(5):461–2. cognition and response inhibition in adult 16. Cengiz Mete M, Şenormancı Ö, Saraçlı Ö, attention-deficit/hyperactivity disorder. Biol Atasoy N, Atik L. Compulsive modafinil Psychiatry. 2004 May 15;55(10):1031–40. use in a patient with a history of alcohol use 7. Mignot E. An update on the disorder. Gen Hosp Psychiatry. 2015 Mar pharmacotherapy of excessive daytime 1;37(2):e7–8. sleepiness and cataplexy. Sleep Med Rev. 17. Kate N, Grover S, Ghormode D. 2004 Oct 1;8(5):333–8. Dependence on supratherapeutic doses of 8. Jasinski DR. An evaluation of the abuse modafinil: a case report. Prim care potential of modafinil using companion CNS Disord. 2012/10/18. methylphenidate as a reference. J 2012;14(5):PCC.11l01333.

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18. Krishnan R, Chary KV. A rare case 20. Aytaş Ö, Dilek Yalvaç H. Modafinil- modafinil dependence. J Pharmacol Induced Psychosis: A Case Report. Noro Pharmacother. 2015;6(1):49–50. Psikiyatr Ars. 2015/03/01. 2015 Mar;52(1): 19. Alacam H, Basay O, Tumkaya S, Mart M, 99–101. Kar G. Modafinil Dependence: A Case with Attention-Deficit/Hyperactivity Disorder. How to cite this article: D’Souza P, Mascarenhas Psychiatry Investig. 2018/03/30. 2018 Apr; JJ. A case report on modafinil dependence. 15(4):424–7. Galore International Journal of Health Sciences & Research. 2019; 4(3): 6-9.

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