Modafinil. Armodafinil. The use of eugeroics in assisting the treatment of depression, bipolar disorder, and schizophrenia. Benefits, drawbacks, and adverse effects
DOI:
https://doi.org/10.12775/JEHS.2023.43.01.020Keywords
Modafinil, Psychiatric, Depression, Bipolar, SchizophreniaAbstract
Modafinil is used to treat narcolepsy with cataplexy and is also being extensively studied to find new therapeutic uses. In recent years, there have been reports suggesting the potential benefits of modafinil in the treatment of psychiatric illnesses such as depression and bipolar depression. In the case of depression, modafinil can be used as an adjuvant or as monotherapy in patients who do not respond sufficiently to antidepressants. Studies have shown that modafinil improves symptoms of depression, reduces fatigue and improves cognitive function. There are also reports of a beneficial effect of modafinil in the treatment of seasonal depression. For bipolar depression, modafinil can be used as an adjunct therapy during the depressive phase, particularly in patients experiencing slowness, lethargy and loss of pleasure. Studies suggest that modafinil may improve depressive symptoms without inducing manic episodes. There are also data indicating modafinil's potential efficacy in treating negative symptoms and improving cognitive function in patients with schizophrenia. In conclusion, modafinil appears to be a promising drug in aiding the treatment of various psychiatric illnesses.
References
Janusz Rybakowski., Psychofarmakologia Kliniczna[Clinical Psychopharmacology], PZWL, Warszawa 2022;1,293-295,Polisch
Ishizuka T, Murotani T, Yamatodani A. Action of modafinil through histaminergic and orexinergic neurons. Vitam Horm. 2012;89:259-78. [PubMed]
Mahler SV, Hensley-Simon M, Tahsili-Fahadan P, LaLumiere RT, Thomas C, Fallon RV, Kalivas PW, Aston-Jones G. Modafinil attenuates reinstatement of cocaine seeking: role for cystine-glutamate exchange and metabotropic glutamate receptors. Addict Biol. 2014 Jan;19(1):49-60. [PMC free article] [PubMed]
Schmitt KC, Reith ME. The atypical stimulant and nootropic modafinil interacts with the dopamine transporter in a different manner than classical cocaine-like inhibitors. PLoS One. 2011;6(10):e25790. [PMC free article] [PubMed]
Malcolm R, Swayngim K, Donovan JL, DeVane CL, Elkashef A, Chiang N, Khan R, Mojsiak J, Myrick DL, Hedden S, Cochran K, Woolson RF. Modafinil and cocaine interactions. Am J Drug Alcohol Abuse. 2006;32(4):577-87. [PubMed]
Hart CL, Haney M, Vosburg SK, Rubin E, Foltin RW. Smoked cocaine self-administration is decreased by modafinil. Neuropsychopharmacology. 2008 Mar;33(4):761-8. [PubMed]
Robertson P, Hellriegel ET. Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [PubMed]
Lam JY, Freeman MK, Cates ME. Modafinil augmentation for residual symptoms of fatigue in patients with a partial response to antidepressants. Ann Pharmacother. 2007 Jun;41(6):1005-12. doi: 10.1345/aph.1H526. Epub 2007 May 22. PMID: 17519297. [PubMed]
Price CS, Taylor FB. A retrospective chart review of the effects of modafinil on depression as monotherapy and as adjunctive therapy. Depress Anxiety. 2005;21(4):149-53. doi: 10.1002/da.20075. PMID: 16035049. [Wiley Libary]
Kaufman KR, Menza MA, Fitzsimmons A. Modafinil monotherapy in depression. Eur Psychiatry. 2002 May;17(3):167-9. doi: 10.1016/s0924-9338(02)00646-6. PMID: 12052578. [PubMed]
Rostami H, Safaei G, Norouzi S, Abdi L, Malekpour N. Comparison between the Efficacies of Modafinil and Citalopram in the Treatment of Major Depression. Maedica (Bucur). 2022 Sep;17(3):607-614. doi: 10.26574/maedica.2022.17.3.607. PMID: 36540578; PMCID: PMC9720649. [NIH]
Even C, Friedman S, Dardennes R, Guelfi JD. Modafinil as an alternative to light therapy for winter depression. Eur Psychiatry. 2004 Feb;19(1):66. doi: 10.1016/j.eurpsy.2003.07.005. PMID: 14969786. [PubMed]
Fava M, Thase ME, DeBattista C. A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. J Clin Psychiatry. 2005 Jan;66(1):85-93. doi: 10.4088/jcp.v66n0112. PMID: 15669893. [PubMed]
Thase ME, Fava M, DeBattista C, Arora S, Hughes RJ. Modafinil augmentation of SSRI therapy in patients with major depressive disorder and excessive sleepiness and fatigue: a 12-week, open-label, extension study. CNS Spectr. 2006 Feb;11(2):93-102. doi: 10.1017/s1092852900010622. PMID: 16520686. [PubMed]
Ninan PT, Hassman HA, Glass SJ, McManus FC. 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. 2004 Mar;65(3):414-20. doi: 10.4088/jcp.v65n0318. PMID: 15096082. [PubMed]
Kaser M, Deakin JB, Michael A, Zapata C, Bansal R, Ryan D, Cormack F, Rowe JB, Sahakian BJ. Modafinil Improves Episodic Memory and Working Memory Cognition in Patients With Remitted Depression: A Double-Blind, Randomized, Placebo-Controlled Study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 Mar;2(2):115-122. doi: 10.1016/j.bpsc.2016.11.009. PMID: 28299368; PMCID: PMC5339412. [PubMed]
Frye MA, Grunze H, Suppes T, McElroy SL, Keck PE Jr, Walden J, Leverich GS, Altshuler LL, Nakelsky S, Hwang S, Mintz J, Post RM. A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression. Am J Psychiatry. 2007 Aug;164(8):1242-9. doi: 10.1176/appi.ajp.2007.06060981. PMID: 17671288. [PubMed]
Calabrese JR, Ketter TA, Youakim JM, Tiller JM, Yang R, Frye MA. Adjunctive armodafinil for major depressive episodes associated with bipolar I disorder: a randomized, multicenter, double-blind, placebo-controlled, proof-of-concept study. J Clin Psychiatry. 2010 Oct;71(10):1363-70. doi: 10.4088/JCP.09m05900gry. Epub 2010 Jul 27. PMID: 20673554. [PubMed]
Calabrese JR, Frye MA, Yang R, Ketter TA; Armodafinil Treatment Trial Study Network. Efficacy and safety of adjunctive armodafinil in adults with major depressive episodes associated with bipolar I disorder: a randomized, double-blind, placebo-controlled, multicenter trial. J Clin Psychiatry. 2014 Oct;75(10):1054-61. doi: 10.4088/JCP.13m08951. PMID: 25099397. [PubMed]
Ketter TA, Yang R, Frye MA. Adjunctive armodafinil for major depressive episodes associated with bipolar I disorder. J Affect Disord. 2015 Aug 1;181:87-91. doi: 10.1016/j.jad.2015.04.012. Epub 2015 Apr 15. PMID: 25933099. [PubMed]
Goss AJ, Kaser M, Costafreda SG, Sahakian BJ, Fu CH. Modafinil augmentation therapy in unipolar and bipolar depression: a systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry. 2013 Nov;74(11):1101-7. doi: 10.4088/JCP.13r08560. PMID: 24330897. [PubMed]
Grunze H. Stimulants for treating bipolar disorder: pro and con. Harv Rev Psychiatry. 2014 Nov-Dec;22(6):358-62. doi: 10.1097/HRP.0000000000000003. PMID: 25377610. [PubMed]
Perugi G, Vannucchi G, Bedani F, Favaretto E. Use of Stimulants in Bipolar Disorder. Curr Psychiatry Rep. 2017 Jan;19(1):7. doi: 10.1007/s11920-017-0758-x. PMID: 28144880. [PubMed]
Schoenknecht P, Olbrich S, Sander C, Spindler P, Hegerl U. Treatment of acute mania with modafinil monotherapy. Biol Psychiatry. 2010 Jun 1;67(11):e55-7. doi: 10.1016/j.biopsych.2009.12.021. Epub 2010 Feb 6. PMID: 20138253. [PubMed]
Saavedra-Velez C, Yusim A, Anbarasan D, Lindenmayer JP. Modafinil as an adjunctive treatment of sedation, negative symptoms, and cognition in schizophrenia: a critical review. J Clin Psychiatry. 2009 Jan;70(1):104-12. doi: 10.4088/jcp.07r03982. Epub 2008 Nov 18. PMID: 19026265. [PubMed]
Freudenreich O, Henderson DC, Macklin EA, Evins AE, Fan X, Cather C, Walsh JP, Goff DC. Modafinil for clozapine-treated schizophrenia patients: a double-blind, placebo-controlled pilot trial. J Clin Psychiatry. 2009 Dec;70(12):1674-80. doi: 10.4088/JCP.08m04683. Epub 2009 Aug 11. PMID: 19689921; PMCID: PMC5038350. [PubMed]
Arbabi M, Bagheri M, Rezaei F, Ahmadi-Abhari SA, Tabrizi M, Khalighi-Sigaroudi F, Akhondzadeh S. A placebo-controlled study of the modafinil added to risperidone in chronic schizophrenia. Psychopharmacology (Berl). 2012 Apr;220(3):591-8. doi: 10.1007/s00213-011-2513-z. Epub 2011 Sep 24. PMID: 21947320. [PubMed]
Scoriels L, Jones PB, Sahakian BJ. Modafinil effects on cognition and emotion in schizophrenia and its neurochemical modulation in the brain. Neuropharmacology. 2013 Jan;64:168-84. doi: 10.1016/j.neuropharm.2012.07.011. Epub 2012 Jul 20. PMID: 22820555. [PubMed]
Andrade C, Kisely S, Monteiro I, Rao S. Antipsychotic augmentation with modafinil or armodafinil for negative symptoms of schizophrenia: systematic review and meta-analysis of randomized controlled trials. J Psychiatr Res. 2015 Jan;60:14-21. doi: 10.1016/j.jpsychires.2014.09.013. Epub 2014 Sep 20. PMID: 25306261. [PubMed]
Kane JM, D'Souza DC, Patkar AA, Youakim JM, Tiller JM, Yang R, Keefe RS. Armodafinil as adjunctive therapy in adults with cognitive deficits associated with schizophrenia: a 4-week, double-blind, placebo-controlled study. J Clin Psychiatry. 2010 Nov;71(11):1475-81. doi: 10.4088/JCP.09m05950gry. Epub 2010 Aug 24. PMID: 20816042. [PubMed]
Kane JM, Yang R, Youakim JM. Adjunctive armodafinil for negative symptoms in adults with schizophrenia: a double-blind, placebo-controlled study. Schizophr Res. 2012 Mar;135(1-3):116-22. doi: 10.1016/j.schres.2011.11.006. Epub 2011 Dec 16. PMID: 22178084. [PubMed]
Lohr JB, Liu L, Caligiuri MP, Kash TP, May TA, Murphy JD, Ancoli-Israel S. Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in schizophrenia and schizoaffective disorder: a randomized, double-blind, placebo-controlled study. Schizophr Res. 2013 Oct;150(1):289-96. doi: 10.1016/j.schres.2013.07.039. Epub 2013 Aug 9. PMID: 23938173. [PubMed]
Bobo WV, Woodward ND, Sim MY, Jayathilake K, Meltzer HY. The effect of adjunctive armodafinil on cognitive performance and psychopathology in antipsychotic-treated patients with schizophrenia/schizoaffective disorder: a randomized, double-blind, placebo-controlled trial. Schizophr Res. 2011 Aug;130(1-3):106-13. doi: 10.1016/j.schres.2011.05.015. Epub 2011 Jun 8. PMID: 21641776. [PubMed]
Darwish M, Bond M, Yang R, Hellriegel ET, Robertson P Jr. Evaluation of Potential Pharmacokinetic Drug-Drug Interaction between Armodafinil and Aripiprazole in Healthy Adults. Pharmacopsychiatry. 2015 Jul;48(4-5):170-5. doi: 10.1055/s-0035-1554671. Epub 2015 Jul 16. PMID: 26181194. [PubMed]
Darwish M, Bond M, Yang R, Hellriegel ET, Robertson P. Evaluation of potential pharmacokinetic drug-drug interaction between armodafinil and risperidone in healthy adults. Clin Drug Investig. 2015 Nov;35(11):725-33. doi: 10.1007/s40261-015-0330-6. PMID: 26387027. [PubMed]
Darwish M, Bond M, Yang R, Hellriegel ET, Robertson P Jr. Evaluation of the potential for a pharmacokinetic drug-drug interaction between armodafinil and ziprasidone in healthy adults. Clin Drug Investig. 2014 Oct;34(10):691-9. doi: 10.1007/s40261-014-0220-3. PMID: 25047407.[PubMed]
Darwish M, Bond M, Yang R, Hellriegel ET, Robertson P Jr. Evaluation of the potential for pharmacokinetic drug-drug interaction between armodafinil and carbamazepine in healthy adults. Clin Ther. 2015 Feb 1;37(2):325-37. doi: 10.1016/j.clinthera.2014.09.014. Epub 2014 Oct 16. PMID: 25438721. [PubMed]
Wu P, Jones S, Ryan CJ, Michail D, Robinson TD. Modafinil-induced psychosis. Intern Med J. 2008 Aug;38(8):677-8. doi: 10.1111/j.1445-5994.2008.01710.x. PMID: 18808567. [Wiley Online Libary]
DiSciullo AA, English CD, Horn WT. Modafinil Induced Psychosis in a Patient with Bipolar 1 Depression. Case Rep Psychiatry. 2018 Oct 17;2018:3732958. doi: 10.1155/2018/3732958. PMID: 30416836; PMCID: PMC6207879. [PubMed]
Vorspan F, Warot D, Consoli A, Cohen D, Mazet P. Mania in a boy treated with modafinil for narcolepsy. Am J Psychiatry. 2005 Apr;162(4):813-4. doi: 10.1176/appi.ajp.162.4.813-a. PMID: 15800167. [PubMed]
Yasui-Furukori N, Kusunoki M, Kaneko S. Hallucinations associated with modafinil treatment for narcolepsy. J Clin Psychopharmacol. 2009 Aug;29(4):408. doi: 10.1097/JCP.0b013e3181accefe. PMID: 19593192. [PubMed]
Aytaş Ö, Dilek Yalvaç H. Modafinil-Induced Psychosis: A Case Report. Noro Psikiyatr Ars. 2015 Mar;52(1):99-101. doi: 10.5152/npa.2015.7160. Epub 2015 Mar 1. PMID: 28360685; PMCID: PMC5353011. [PubMed]
Swapnajeet S, Bn S, Gourav G. Modafinil Dependence and Hypersexuality: A Case Report and Review of the Evidence. Clin Psychopharmacol Neurosci. 2016 Nov 30;14(4):402-404. doi: 10.9758/cpn.2016.14.4.402. PMID: 27776397; PMCID: PMC5083941. [PubMed]
Mutlu D, Kültürsay B, Karagöz A. Modafinil-induced ventricular arrhythmia: A case report. Turk Kardiyol Dern Ars. 2022 Jan;50(1):79-82. doi: 10.5543/tkda.2022.21084. PMID: 35197237. [PubMed]
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Norbert Kandefer, Anna Jaremek, Joanna Kępa, Michał Wyszkowski, Aleksandra Grabarczyk, Anna Pawlak, Sylwia Grad, Paweł Gregorek, Małgorzata Gregorek, Laura Loryś, Klaudia Klimczak
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 2501
Number of citations: 0