Exacerbation of Obsessions With Modafinil in 2 Patients With Medication-Responsive Obsessive-Compulsive Disorder
Oguz Tan, M.D.,1 Adnan Coban, M.D.,1 Nevzat Tarhan, M.D.,1 Semra Baripoglu, M.D.,1 Funda Guducu, M.D.,1 Hasan Basri Izgi, M.D.,2 Gokben Hizli, M.D.,2 Oznur Ates, M.D.,2 and Huseyin Bulut, M.D.21Department of Psychiatry, Memory Center Neuropsychiatry Clinic 2Department of Psychiatry, Hospital of Neuropsychiatry Istanbul, Istanbul, Turkey 1,2 enhancing the increased activation demonstrated in OCD patients and leading to an exacerbation of symptoms in some. Case reports Mr. A, a 47-year-old man, had suffered from OCD for 25 years when he began to take modafinil in June 2006. His symptoms had been controlled and not clinically distressing with a regimen of paroxetine 60 mg, clomipramine 300 mg, and risperidone 3 mg daily for 2 years. Obsessions and compulsions recurred on the first day he took 100 mg of modafinil and were severely aggravated on the second day. He continued to take modafinil 100 mg daily for an additional 2 days (4 days total). Obsessive-compulsive symptoms improved abruptly on the fifth day when he stopped taking modafinil. Ms. B, a 57-year-old woman, had a 20-year history of OCD when she began to take modafinil in February 2006. Her symptoms had been under control and not clinically distressing for 1 year with a regimen of paroxetine 60 mg, trazodone 200 mg, and olanzapine 15 mg daily. Obsessions and compulsions recurred to a severe degree on the first day she took 100 mg of modafinil. She continued to take modafinil 100 mg daily for 6 additional days (i.e., she took modafinil for a total of 7 days). Obsessive-compulsive symptoms improved suddenly on the eighth day when she stopped taking modafinil. Neither of the patients experienced any distressing life event, had any medical/neurologic condition, used illicit substances and/or alcohol or any drug other than those prescribed for OCD. Both patients were given modafinil because of excessive daytime sleepiness. Wakefulness was provided during modafinil use; however, it might have been the result of the severe anxiety due to the recurring obsessions. Clinical diagnoses were made according to DSM-IV. The patients were not assessed with any clinical scale such as The Yale-Brown Obsessive Compulsive Scale or the Hamilton Rating Scale for Depression because they were undergoing routine clinical follow-up while taking modafinil. The mechanism of action of modafinil is not clear. At pharmacologically relevant doses, modafinil does not bind to receptors for norepinephrine, serotonin, dopamine, γ-aminobutyric acid, adenosine, histamine-3, melatonin, or benzodiazepines.3 There is no published report of obsessions occuring during modafinil use. However, anxiety, agitation, emotional lability, and even psychosis have been reported in modafinil users.3,4 Numerous studies have suggested that OCD patients have a hypermetabolism in the cingulate cortex,5–8 and cingulotomy remains a viable treatment option for patients with severe treatment-refractory OCD.9–11 Chronic anterior capsular electro-stimulation in OCD patients has resulted in decreased metabolic activity, especially in the subgenual anterior cingulate.12 Compared with placebo, modafinil administration has been associated with significantly greater activation in the anterior cingulate cortex using functional magnetic resonance imaging during a working memory task in chronic schizophrenic patients.1 The cingulate cortex has been activated in rats given high doses of modafinil.2 Therefore, a substance activating the cingulate may result in obsessions. Our observation suggests that modafinil causes an increase in the activity of the cingulate cortex, enhancing the increased activation demonstrated in OCD patients and leading to an exacerbation of symptoms in some.
AcknowledgmentsThe authors report no financial affiliation or other relationship relevant to the subject of this letter.
- Spence SA, Green RD, and Wilkinson ID. et al. Modafinil modulates anterior cingulate function in chronic schizophrenia. Br J Psychiatry. 2005. 187:55–61. [PubMed].
- Scammel TE, Estabrooke IV, and McCarthy MT. et al. Hypothalamic arousal regions are activated during modafinil-induced wakefulness. J Neurosci. 2000. 20:8620–8628. [PubMed].
- FDA approved labeling text for NDA 20-717/S-005&S-008, approved 23-Jan-2004. Available at:www.fda.gov/cder/foi/label/2004/20717se1-008_provigil_lbl.pdf. Accessibility verified January 17, 2008.
- Mariani JJ, Hart CL. Psychosis associated with modafinil and shift work. Am J Psychiatry. 2005;162:1983. [PubMed]
- Micallef J, Blin O. Neurobiology and clinical pharmacology of obsessive-compulsive disorder. Clin Neuropharmacol.2001;24:191–207. [PubMed]
- Szeszko PR, Ardekani BA, and Ashtari M. et al. White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study. Arch Gen Psychiatry. 2005. 62:782–790. [PubMed].
- Sumitani S, Harada M, and Kubo H. et al. Proton magnetic resonance spectroscopy reveals an abnormality in the anterior cingulate of a subgroup of obsessive-compulsive patients. Psychiatry Res. 2007. 154:85–92. [PubMed].
- Szeszko PR, MacMillan S, and McMeniman M. et al. Brain structural abnormalities in psychotropic drug-naive pediatric patients with obsessive-compulsive disorder. Am J Psychiatry. 2004. 161:1049–1056. [PubMed].
- Dougherty DD, Baer L, and Cosgrove GR. et al. Prospective long-term follow-up of 44 patients who received cingulotomy for treatment-refractory obsessive-compulsive disorder. Am J Psychiatry. 2002. 159:269–275.[PubMed].
- Kim CH, Chang JW, and Koo MS. et al. Anterior cingulotomy for refractory obsessive-compulsive disorder. Acta Psychiatr Scand. 2003. 107:283–290. [PubMed].
- Jung HH, Kim CH, and Chang JH. et al. Bilateral anterior cingulotomy for refractory obsessive-compulsive disorder: long-term follow-up results. Stereotact Funct Neurosurg. 2006. 84:184–189. [PubMed].
- Van Laere K, Nuttin B, and Gabriels L. et al. Metabolic imaging of anterior capsular stimulation in refractory obsessive-compulsive disorder: a key role for the subgenual anterior cingulate and ventral striatum. J Nucl Med. 2006. 47:740–747. [PubMed].
01 Ekim 2008 Çarşamba, 00:00
Bu yazı 4746 kez okundu