Aggressive Behavior After Ingestion of a High Dose of Sildenafil

Sir: Only 1 study pertaining to the use of sildenafil in men with erectile dysfunction who are undergoing treatment with antipsychotic drugs has been performed.1 There are only 2 reports about adverse effects of high doses of sildenafil in this population.2,3 We report a case of a man, treated with different psychotropic drugs, who exhibited serious aggression after having ingested a high dose of sildenafil. Case report. Mr. A, a 50-year-old patient with a 5-year history of a psychotic disorder due to a head trauma, with delusions, and with personality change due to a head trauma, combined type (both according to DSM-IV), was admitted to a psychiatric hospital in May 2007 because of suicidal thoughts and low mood. He was complaining about his erectile dysfunction, which had begun after he had started taking antipsychotics a year before. He was convinced that erectile dysfunction was the main reason for his low mood and diminished will to live. Mr. A sometimes used vardenafil, with no success. At the time of admission, he was receiving quetiapine, mirtazapine, and valproate. After 10 days in the hospital, his suicidal thoughts decreased, and his mood improved. He went home for a 2-day holiday and came back very agitated. He shouted that he needed a woman and that he would have all the women in the world; he started harassing the nurses and took off all his clothes. He reported taking 400 mg of his father's sildenafil at home the day before. Agitation progressed into a tremendous rage, and he had an aggressive outburst during which he broke 2 chairs and a window. He had to be physically restrained and was calmed down with haloperidol (15 mg daily) and diazepam (40 mg daily) administered parenterally. This agitated condition persisted for the next 6 days, with only moderate response to continuous treatment with haloperidol and diazepam. Mr. A's mood fluctuated, he shouted obscenities, and he was aggressive toward everyone in the ward. In the next 4 days, his condition improved; however, he started feeling depressed and had paranoid ideas. Upon his discharge after 3 weeks, he was in a better mood without paranoid ideas, his agitation had subsided, and he regretted his behavior. In the U.S. Food and Drug Administration Adverse Event Reporting System, sildenafil has been implicated as a suspected cause of neurological, emotional, and psychological disturbances.2 The mechanism of those adverse events is still unknown, and different hypotheses are being tested: inhibition of phosphodiesterase type 5 in the brain, reduction in the concentration of nitric oxide in the hippocampus, accumulation of cyclic guanosine monophosphate, impact on neuronal communications, and others.3 The link between aggressive behavior and sildenafil treatment is not convincing, but, nevertheless, extra caution may be needed when sildenafil is used for the management of sexual dysfunction in patients with organic brain disorders who are undergoing treatment with psychotropic drugs. Blanka Kores Plesnicar, M.D., Ph.D. Department of Psychiatry, University Clinical Centre Maribor, Maribor, Slovenia Andrej Plesnicar, M.D., M.Sci. University College of Health Studies, Ljubljana, Slovenia