Year 2016, Volume 8 , Issue 1, Pages 42 - 51 2016-01-23

Use of Modafinil in Psychiatric Disorders
Psikiyatrik Bozukluklarda Modafinil Kullanımı

Mehmet Kokaçya [1] , Ümit Çöpoğlu [2] , Musa Şahpolat [3] , Mustafa Arı [4]

Modafinil, is a psychostimulant drug with neurochemical and behavourial effects, distinct from those of amphetamine. It is used to treat patients with narcolepsy and other excessive sleepiness. Modafinil has dopaminergic, noradrenergic, histaminergic, glutamergic, serotonergic and GABAergic interac-tions. It is also shown that modafinil has neuroprotective effects via antioxidative mechanisms. Besides modafinil shows initial promise for a variety of off-label indications in psychiatry, including bipolar disorder, attention-deficit/hyperactivity disorder, and schizophrenia. The aim of this article is to review the literature on clinical use of modafinil in psychiatric disorders.
Modafinil narkolepsi ve diğer gündüz uykululuğu yapan hastalıklarda kullanılan amfetaminden farklı nörokimyasal ve davranışsal özellikleri olan psikostimulan bir ilaçtır. Modafinilin dopaminerjik, histaminerjik, noradrenerjik glutamaterjik, GABAerjik ve serotoninerjik etkileşimleri vardır. Ayrıca antioksidatif mekanizmalar aracılığıyla nöroprotektif etkilerinin olduğu da gösterilmiştir. Bunun yanında modafinil; bipolar bozukluk, dikkat eksikliği hiperaktivite bozukluğu ve şizofreni gibi psikiyatrik hastalıklarda endikasyon dışı kullanımıyla ilgili gelecek vaadetmektedir. Bu derlemede modafinilin psikiyatrik hastalıklarda klinik kullanımın ele alınması amaçlanmıştır.
Modafinil, psikiyatrik hastalıklar, ekleme tedavisi
  • Aktas O, Yalvac HD (2015) Modafinil-induced psychosis: a case report. Archives of Neuropsychiatry, 52:99-101.
  • Amiri S, Mohammadi MR, Mohammadi M, Nouroozinejad GH, Kahbazi M, Akhondzadeh S (2008) Modafinil as a treatment for Attention-Deficit/Hyperactivity Disorder in children and adolescents: a double blind, randomized clinical trial. Prog Neuropsychopharmacol Biol Psychiatry, 32:145-149.
  • Andrade C, Kisely S, Monteiro I, Rao S (2015) Antipsychotic augmentation with modafinil or armodafinil for negative symptoms of schizophrenia: systematic review and meta-analysis of randomized controlled trials. J Psychiatr Res, 60:14-21.
  • Antonelli T, Ferraro L, Hillion J, Tomasini MC, Rambert FA, Fuxe K (1998) Modafinil prevents glutamate cytotoxicity in cultured cortical neurons. Neuroreport, 9:4209–4213.
  • APA (2010) Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd ed. Arlington, American Psychiatric Association.
  • Ballon JS, Feifel D (2006) A systematic review of modafinil: potential clinical uses and mechanisms of action. J Clin Psychiatry, 67:554 -566.
  • Belmaker RH (2007) Modafinil add-on in the treatment of bipolar depression. Am J Psychiatry, 164:1143-1145.
  • Biederman J, Swanson JM, Wigal SB, Kratochvil CJ, Boellner SW, Earl CQ et al. (2005) Efficacy and safety of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: results of a randomized, double-blind, placebo-controlled, flexible-dose study. Pediatrics, 116:777-784.
  • Cephalon, Inc. Provigil (modafinil) prescribing information. Cephalon, Inc, West Chester, PA. USA. 2004.
  • Conners CK, Sitarenios G, Parker JD, Epstein JN (1998) The revised Conners’ Parent Rating Scale (CPRS-R): factor structure, reliability, and criterion validity. J Abnorm Child Psychol, 26:257-268.
  • DeBattista C, Doghramji K, Menza MA,Rosenthal MH, Fieve RR (2003) Adjunct modafinil for the shortterm treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study. J Clin Psychiatry, 64:1057–1064.
  • Dell’Osso B, Dobrea C, Cremaschi L, Arici C, Altamura AC (2014) Wake-promoting pharmacotherapy for psychiatric disorders. Curr Psychiatry Rep, 16:524.
  • Edgar DM, Seidel WF (1997) Modafinil induces wakefulness without intensifying motor activity or subsequent rebound hypersomnolence in the rat. J Pharmacol Exp Ther, 283:757-769.
  • Elovic E (2000) Use of Provigil for underarousal following TBI. J Head Trauma Rehabil, 15:1068-1071.
  • Faraone SV, Biederman J, Mick E (2006). The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med, 36:159-165.
  • Fava M, Thase ME, DeBattista C, Doghramji K, Arora S, Hughes RJ (2007) Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness. Ann Clin Psychiatry, 19:153–159.
  • Fava M, Thase ME, DeBattista C (2005) A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. J Clin Psychiatry, 66:85–93.
  • Ferraro L, Antonelli T, O'Connor WT, Tanganelli S, Rambert F, Fuxe K (1997a) The antinarcoleptic drug modafinil increases glutamate release in thalamic areas and hippocampus. Neuroreport, 8:2883–2887.
  • Ferraro L, Antonelli T, O'Connor WT, Tanganelli S, Rambert FA, Fuxe K (1997b). Modafinil: an antinarcoleptic drug with a different neurochemical profile to d-amphetamine and dopamine uptake blockers. Biol Psychiatry, 42:1181–1183.
  • Ferraro L, Antonelli T, O'Connor WT, Tanganelli S, Rambert FA, Fuxe K (1998). The effects of modafinil on striatal, pallidal and nigral GABA and glutamate release in the conscious rat: evidence for a preferential inhibition of striato-pallidal GABA transmission. Neurosci Lett, 253:135–138.
  • Ferraro L, Antonelli T, Tanganelli S, O'Connor WT, Perez de la Mora M, Mendez-Franco J et al (1999). The vigilance promoting drug modafinil increases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: prevention by local GABAA receptor blockade. Neuropsychopharmacology, 20:346–356.
  • Fountoulakis KN, Siamouli M, Panagiotidis P, Magiria S, Kantartzis S, Iacovides A (2008) Ultra short manic like episodes after antidepressant augmentation with modafinil. Prog Neuropsychopharmacol Biol Psychiatry, 32:891-892.
  • Frye MA, Grunze H, Suppes T, McElroy SL, Keck PE Jr, Walden J et al. (2007) A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression. Am J Psychiatry 2007; 164:1242-1249.
  • Greenhill LL, Biederman J, Boellner SW, Rugino TA, Sangal BR, Earl CQ et al. (2006) A randomized, double-blind, placebo- controlled study of modafinil film coat coadministraed tablets in children and adolescents with attention-deficit/ hyperactivity disorder. J Am Acad Child Adolesc Psychiatry, 45:503-511.
  • Jenner P, Zeng BY, Smith LA, Pearce RK, Tel B, Chancharme L et al. (2000) Antiparkinsonian and neuroprotective effects of modafinil in the MPTP-treated common marmoset. Exp Brain Res, 133:178–88.
  • Lin JS, Hou Y, Jouvet M (1996) Potential brain neuronal targets for amphetamine-, methylphenidate-,and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat. Proc Natl Acad Sci USA, 93:14128–14133.
  • Lin JS, Roussel B, Akaoka H, Fort P, Debilly G, Jouvet M (1992) Role of catecholamines in the modafinil and amphetamine induced wakefulness, a comparative pharmacological study in the cat. Brain Res, 591:319-326.
  • Kanal MG, Ozkan C, Doganavsargil O, Eryılmaz M (2012) Late onset mania possibly related to modafinil use: A case report. Klinik Psikofarmakol Bulteni, 22:71-74.
  • Makela EH, Miller K, Cutlip WD 2nd (2003) Three case reports of modafinil use in treating sedation induced by antipsychotic medications. J Clin Psychiatry, 64:485–486.
  • Mariani JJ, Hart CL (2005) Psychosis associated with modafinil and shift work. Am J Psychiatry, 162:1983.
  • McClellan KJ, Spencer CM (1998) Modafinil: a review of its pharmacology and clinical efficacy in the management of narcolepsy. CNS Drugs, 9:311-324.
  • Mignot E, Nishino S, Guilleminault C, Dement WC (1994) Modafinil binds to the dopamine uptake carrier site with low affinity. Sleep. 17:436-437.
  • Moachon G, Kanmacher I, Clenet M, Matinier D (1996) Pharmacokinetic profile of modafinil. Medicamentos de actualidad, 32:23- 33.
  • Moss SB, Nair R, Vallarino A, Wang S (2007) Attention deficit/hyperactivity disorder in adults. Prim Care, 34:445-473.
  • Murphy KR, Barkley RA (1996) Updated adult norms for the DEHB Behavior Checklist for Adults. DEHB Report, 4:12-16.
  • Nasr S (2004) Modafinil as adjunctive therapy in depressed outpatients. Ann Clin Psychiatry, 16:133-138.
  • Nasr S, Wendt B, Steiner K (2006) Absence of mood switch with and tolerance to modafinil: a replication study from a large private practice. J Affect Disord, 95:111-114.
  • Ninan PT, Hassman HA, Glass SJ, McManus FC (2004) Adjunctive modafinil at initiation of treatment with a selective serotonin reuptake inhibitor enhances the degree and onset of therapeutic effects in patients with major depressive disorder and fatigue. J Clin Psychiatry, 65:414-420.
  • Nishino S, Mao J, Sampathkumaran R, Shelton J (1998) Increased dopaminergic transmission madiates the wake-promoting effects of CNS stimulants. Sleep Res, 1:49-61.
  • Pierard C, Satabin P, Lagarde D, Barrère B, Guezennec CY, Menu JP et al. (1995) Effects of a vigilance-enhancing drug, modafi nil, on rat brain metabolism:2D COSY 1H-NMR study. Brain Res, 693:251–256.
  • Pierre JM, Peloian JH, Wirshing DA, Wirshing WC, Marder SR (2007) A randomized, double-blind, placebo-controlled trial of modafinil for modafinil for negative symptoms in schizophrenia. J Clin Psychiatry, 65: 705-710.
  • Robertson P Jr, Hellriegel ET (2003) Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet, 42:123-137.
  • Rudhran V, Manjunatha N, John JP (2013) High-dose, self-administered modafinil–related psychosis: is it the pedal in the prodrome of psychosis? J Clin Psychopharmacol, 33:576-577.
  • Saavedra-Velez C, Yusim A, Anbarasan D, Lindenmayer JP (2009) Modafinil as an adjunctive treatment of sedation, negative symptoms, and cognition in schizophrenia: a critical review. J Clin Psychiatry, 70:104-112.
  • Sevy S, Rosenthal MH, Alvir J, Meyer S, Visweswaraiah H, Gunduz-Bruce H et al. (2005) Double-blind, placebo controlled study of modafinil for fatigue and cognition in schizophrenia patients treated with psychotropic medications. J Clin Psychiatry, 66 :839- 843.
  • Simon P, Hemet C., Ramassamy C, Constentin J (1995) Non-amphetamine mechanism of stimulant locomotor effect of modafinil in mice. Eur Neuropsychopharmacol, 5:509-514.
  • Swanson JM, Greenhill LL, Lopez FA, Sedillo A, Earl CQ, Jiang JG et al. (2006) Modafinil film coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: results of a randomized, double blind, placebo-controlled, fixed- dose study followed by abrupt discontinuation. J Clin Psychiatry, 67:137-147.
  • Tanganelli S, Perez de la Mora M, Ferraro L, Mendez-Franco J, Beani L, Rambert FA et al (1995). Modafinil and cortical gamma- aminobutyric acid outflow. Modulation by 5-hydroxytryptamine neurotoxins. Eur J Pharmacol, 273:63–71.
  • Taylor FB, Russo J (2000) Efficacy of modafinil compared to dextroamphetamine for the treatment of attention deficit hyperactivity disorder in adults. J Child Adolesc Psychopharmacol, 10:311-320.
  • Teitelman E (2001) Off-label uses of modafinil. Am J Psychiatry, 158:1341.
  • Turner DC, Clark L, Pomarol-Clotet E, McKenna P, Robbins TW, Sahakian BJ (2004) Modafinil improves cognition and attentional set shifting in patients with chronic schizophrenia. Neuropsychopharmacology, 29:1363-1373.
  • Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM (2001) Dopaminergic role in stimulant-induced wakefulness. J Neurosci, 21:1787-1794.
  • Visser SN, Lesesne CA (2005) Prevalence of diagnosis and medication treatment for attention-deficit/hyperactivity disorder: United States, 2003. MMWR Morb Mortal Wkly Rep, 54:842-847.
  • Vorspan F, Warot D, Consoli A, Cohen D, Mazet P (2005) Mania in a boy treated with modafinil for narcolepsy. Am J Psychiatry, 162:813-814.
  • Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M (2013) Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar disorders, 15:1-44.
  • Yu BP, Maguire GA, Liffick TF (2002) Modafinil for treatment of the negative symptoms of schizophrenia and antipsychotic induced sedation. Sleep, 25:A503.
  • Wu P, Jones S, Ryan CJ, Michail D, Robinson TD (2008) Modafinil-induced psychosis. Intern Med J, 38:677- 678. Mehmet Hanifi Kokaçya, Yrd.Doç.Dr., Mustafa Kemal Üniversitesi, Hatay; Ümit Sertan Çöpoğlu, Yrd.Doç.Dr., Mustafa Kemal Üniversitesi, Hatay; Musa Şahpolat, Yrd.Doç.Dr., Mustafa Kemal Üniversitesi, Hatay; Mustafa Arı, Doç.Dr., Mustafa Kemal Üniversitesi, Hatay .
Primary Language en
Journal Section Review

Author: Mehmet Kokaçya

Author: Ümit Çöpoğlu

Author: Musa Şahpolat

Author: Mustafa Arı


Acceptance Date : November 21, 2019
Publication Date : January 23, 2016

Bibtex @ { pgy133534, journal = {Psikiyatride Güncel Yaklaşımlar}, issn = {1309-0658}, eissn = {1309-0674}, address = {}, publisher = {Lut TAMAM}, year = {2016}, volume = {8}, pages = {42 - 51}, doi = {}, title = {Use of Modafinil in Psychiatric Disorders}, key = {cite}, author = {Kokaçya, Mehmet and Çöpoğlu, Ümit and Şahpolat, Musa and Arı, Mustafa} }
APA Kokaçya, M , Çöpoğlu, Ü , Şahpolat, M , Arı, M . (2016). Use of Modafinil in Psychiatric Disorders. Psikiyatride Güncel Yaklaşımlar , 8 (1) , 42-51 . Retrieved from
MLA Kokaçya, M , Çöpoğlu, Ü , Şahpolat, M , Arı, M . "Use of Modafinil in Psychiatric Disorders". Psikiyatride Güncel Yaklaşımlar 8 (2016 ): 42-51 <>
Chicago Kokaçya, M , Çöpoğlu, Ü , Şahpolat, M , Arı, M . "Use of Modafinil in Psychiatric Disorders". Psikiyatride Güncel Yaklaşımlar 8 (2016 ): 42-51
RIS TY - JOUR T1 - Use of Modafinil in Psychiatric Disorders AU - Mehmet Kokaçya , Ümit Çöpoğlu , Musa Şahpolat , Mustafa Arı Y1 - 2016 PY - 2016 N1 - DO - T2 - Psikiyatride Güncel Yaklaşımlar JF - Journal JO - JOR SP - 42 EP - 51 VL - 8 IS - 1 SN - 1309-0658-1309-0674 M3 - UR - Y2 - 2019 ER -
EndNote %0 Psikiyatride Güncel Yaklaşımlar Use of Modafinil in Psychiatric Disorders %A Mehmet Kokaçya , Ümit Çöpoğlu , Musa Şahpolat , Mustafa Arı %T Use of Modafinil in Psychiatric Disorders %D 2016 %J Psikiyatride Güncel Yaklaşımlar %P 1309-0658-1309-0674 %V 8 %N 1 %R %U
ISNAD Kokaçya, Mehmet , Çöpoğlu, Ümit , Şahpolat, Musa , Arı, Mustafa . "Use of Modafinil in Psychiatric Disorders". Psikiyatride Güncel Yaklaşımlar 8 / 1 (January 2016): 42-51 .
AMA Kokaçya M , Çöpoğlu Ü , Şahpolat M , Arı M . Use of Modafinil in Psychiatric Disorders. pgy. 2016; 8(1): 42-51.
Vancouver Kokaçya M , Çöpoğlu Ü , Şahpolat M , Arı M . Use of Modafinil in Psychiatric Disorders. Psikiyatride Güncel Yaklaşımlar. 2016; 8(1): 51-42.