Correspondence
Ganciclovir-Induced Psychosis
N Engl J Med 1996; 335:1397October 31, 1996
- Article
To the Editor:
Several reports of ganciclovir-induced psychiatric disturbances have been reported in the medical literature.1-3 Two cases involved patients with mild renal insufficiency1,2 and one a patient who was undergoing hemodialysis.3 Since ganciclovir is primarily eliminated through the kidney as the parent compound (91 percent),4 renal failure probably contributed to these cases. We describe a case of ganciclovir-induced psychosis that was not associated with renal insufficiency.
A 43-year-old man with advanced human immunodeficiency virus disease (CD4 lymphocyte count, 17 per cubic millimeter in October 1995) was admitted because of acute changes in mental status. He was incontinent and disoriented and demonstrated inappropriate behavior and responses to commands. His speech was disjointed, nonsensical, and fixated on religion and death. Auditory and visual hallucinations were also present.
Laboratory values were generally within normal ranges, including the serum creatinine concentration (0.8 mg per deciliter). A toxicologic screen was negative, and magnetic resonance imaging demonstrated no evidence of cerebral atrophy, toxoplasmosis, or lymphomas. Cerebrospinal fluid values were within normal limits; cerebrospinal fluid was negative for cytomegalovirus and herpes simplex virus on analysis with the polymerase chain reaction; bacterial and fungal cultures of cerebrospinal fluid were also negative. Results of the Venereal Disease Research Laboratory test and staining with India ink were also negative. The patient had no history of mental illness.
Ganciclovir (300 mg intravenously every 12 hours) had been added to the patient's regimen six days before admission. Approximately two days later, the patient had experienced multiple episodes of forgetfulness, frustration, agitation, and confusion. Other medications he had received before admission included acyclovir, trimethoprim and sulfamethoxazole (co-trimoxazole, double strength), fluconazole, and ranitidine, all of which had been prescribed for various periods (one month to one year). All medications were discontinued on admission.
The patient's mental status continued to deteriorate over the next 1 1/2 days. He was agitated and continued to experience disorientation, hallucinations, and incontinence. He spoke in incoherent phrases, and his speech was slurred. He was unable to respond to simple verbal commands. The patient also had violent, screaming outbursts, which were successfully managed with lorazepam. Over an 11-hour period, he spoke in a continuous and repetitious fashion that focused on religion, death, song lyrics, and nursery rhymes.
Approximately two days after the discontinuation of all medications, there was a dramatic improvement in his condition. He became more alert and was able to converse and respond appropriately.
The patient's condition continued to improve, and ganciclovir was reinstituted on the third day after admission. Within two hours, he became agitated and his speech became incoherent. Ganciclovir was subsequently discontinued because of the continued deterioration in mental status. During the ensuing three days, the patient once again became disoriented, confused, and incontinent; he introduced himself as Jesus; and he refused to answer questions. Haloperidol and lorazepam were used to manage the psychotic episodes. Three days after the discontinuation of ganciclovir, the patient's mentation improved and eventually returned to base line.
Subsequently, foscarnet was begun and co-trimoxazole was reinstituted before he was discharged. On follow-up three weeks after discharge, the patient was tolerating both agents well and was unable to recall many of the events described above.
Various factors, such as the temporal relation between the initiation of ganciclovir and the onset of psychosis, in addition to the effects of the discontinuation and resumption of ganciclovir, are highly suggestive of ganciclovir-induced psychosis. This case illustrates that psychosis may develop in patients with normal renal function who take ganciclovir.
4 ReferencesBarbara A. Hansen, Pharm.D.
Kenneth S. Greenberg, D.O., Pharm.D.
Jason A. Richter, M.D.
Rose Medical Center, Denver, CO 802201
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Chen JL ,Brocavich JM ,Lin AY . Psychiatric disturbances associated with ganciclovir therapy. Ann Pharmacother 1992;26:193-195
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- Citing Articles (6)
Citing Articles
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Nancy Perrottet, Laurent A. Decosterd, Pascal Meylan, Manuel Pascual, Jerome Biollaz, Thierry Buclin. (2009) Valganciclovir in Adult Solid Organ Transplant Recipients. Clinical Pharmacokinetics 48:6, 399-418
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S. P. Aslam, K. A. Carroll, B. Naz, A. O. Alao. (2009) Valacyclovir-Induced Psychosis and Manic Symptoms in an Adolescent Young Woman With Genital Herpes Simplex. Psychosomatics 50:3, 293-296
CrossRef3
R Foster, D Olajide, I P Everall. (2003) Antiretroviral therapy-induced psychosis: case report and brief review of the literature. HIV Medicine 4:2, 139-144
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Mary Ross Southworth, Stephanie H. Dunlap. (2000) Psychotic Symptoms and Confusion Associated with Intravenous Ganciclovir in a Heart Transplant Recipient. Pharmacotherapy 20:4, 479-483
CrossRef5
Schiff, Harold B., . (1997) More on Ganciclovir-Induced “Psychosis”. New England Journal of Medicine 336:16, 1190-1191
Full Text6
&NA;. (1996) Ganciclovir. Reactions Weekly &NA;:626, 8
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