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.²

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.

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.

The authors report no financial affiliation or other relationship relevant to the subject of this letter.