Association of Auditory Hallucinations and Anticonvulsant Hypersensitivity Syndrome with Carbamazepine Treatment

• Introduction
• Case report
• Discussion
• References

Carbamazepine is effective in the treatment of acute mania and in the prevention of episodes in bipolar disorder, and it may also be useful in depression, impulse-control disorder and withdrawal from alcohol and benzodiazepine dependence. A potentially life-threatening side effect is the anticonvulsant hypersensitivity syndrome. Here, we describe a patient who developed severe auditory hallucinations followed by a distinct hypersensitivity syndrome most likely induced by carbamazepine treatment.

Introduction

Carbamazepine is an iminodibenzyl drug structurally similar to imipramine and effective in the treatment of acute mania and in the prevention of both manic and depressive episodes in bipolar I disorder. Available data suggest that carbamazepine may also be useful in depression, impulse-control disorder and withdrawal from alcohol and benzodiazepine dependence, especially in patients at risk of seizures [7] [9] [11] [13]. Common dosage-related side effects include nausea, dizziness, ataxia, sedation and dysarthria. A rare (1-4.1/10 000 treated patients) but potentially life-threatening side effect is the anticonvulsant hypersensitivity syndrome, an idiosyncratic, non-dose-related adverse reaction characterized by the triad of fever, rash, and internal organ involvement usually developing 1 to 12 weeks after initiation of therapy [6]. Although the occurrence of visual hallucinations has been repeatedly described in prior studies [1] [2] [14], reports on auditory hallucinations associated with carbamazepine use are very limited. Here, we describe a patient who developed severe auditory hallucinations followed by a hypersensitivity syndrome while under treatment with carbamazepine.

Case report

A 46-year-old male patient was referred to our psychiatric clinic for the treatment of a major depressive episode and social phobia. He had a history of recurrent depressive episodes with the first manifestation at the age of 17 leading to a suicide attempt. In the course of the disorder, the patient suffered from two depressive, but no manic episodes. He had no history of psychotic symptoms and had never experienced hallucinations. Because of phobic anxiety symptoms, the patient had taken lorazepam for about six months and developed a benzodiazepine dependence syndrome. At the time of admission he was on paroxetine (40 mg/day) and lorazepam (8 mg/day) without relief of symptoms. The patient was in good physical health, all routine laboratory findings (including TPHA) were within the normal range. Magnetic resonance imaging and electroencephalography revealed no abnormalities. Ten days after the admission, paroxetine was discontinued and replaced by venlafaxine. In addition, carbamazepine was initiated to facilitate benzodiazepine withdrawal. Seven days later, the patient reported for the first time that a male voice ordered him to commit suicide. The voice occurred several times during the day and the night. At that time he was on carbamazepine 1000 mg (serum plasma concentration 9.7 μg/ml), venlafaxine 375 mg and lorazepam 5 mg. Due to the imperative and threatening character of the voice, the patient was transferred to the acute psychiatric ward. A neuroleptic medication with quetiapine (up to 500 mg/day) and haloperidol (up to 10 mg/day) was given for 14 days with no improvement of the hallucinations. On day 18 of the carbamazepine treatment, the patient developed fever, rash, toxic liver damage and pneumonia. Assuming an anticonvulsant hypersensitivity syndrome, carbamazepine was immediately stopped leading to a complete relief of auditory hallucinations within three days. The hypersensitivity syndrome was successfully treated with an initial dose of 250 mg of prednisolone, which was tapered off, followed by antibiotic medication. The neuroleptics could be discontinued without recurrence of the perceptual disturbances. A clinical follow-up examination 8 months after the event revealed no hallucinations.

Discussion

We suggest that treatment with carbamazepine induced auditory hallucinations in terms of a male voice that ordered the patient to commit suicide. The patient suffered from recurrent major depression and social phobia but he had never experienced psychotic symptoms prior to the onset of carbamazepine treatment. Due to the threatening and imperative character of the acoustic hallucination and because the patient was not able to recognize the unreality of the perceptional disturbances, we classified them as a psychotic decompensation and not as pseudohallucinations. The latter are typically characterized by the fact that the patients are aware of the experiences being hallucinations. However, pseudohallucinations may occur during psychopharmacological treatment as recently reported [4]. Nevertheless the acoustic hallucinations did not respond to neuroleptic treatment but ceased after carbamazepine discontinuation. However, no re-exposure trial has been performed to prove a causal relationship between carbamazepine and acoustic hallucinations. This was especially due to ethical reasons facing the danger of suicide and the fact that the auditory hallucinations were preceding a full-blown hypersensitivity reaction most likely caused by carbamazepine treatment.

Only a very limited number of case studies reported a possible association of auditory hallucinations and carbamazepine treatment. McKee et al. reported a 23-year-old man with generalized epilepsy medicated both with valproate (200 mg) and carbamazepine (400 mg) who heard Russian voices [8]. The symptoms started eight days after initiation of the treatment and improved three days after withdrawal of carbamazepine. Dalby reported that one patient out of 91 with dementia developed a psychosis with schizophreniform character which disappeared after carbamazepine was discontinued [3]. Franks and Richter [5] described a 23-year-old woman who experienced auditory hallucinations after administration of carbamazepine, but recovered one week after withdrawal of carbamazepine. The authors discussed that mild chronic organic brain syndrome may lead to an increased sensitivity to toxic effects of anticonvulsants [5]. Interestingly, recent case reports suggest that carbamazepine may be an effective treatment for auditory hallucinations and palinacousis secondary to temporal lobe damage or temporal lobe seizures [10] [12]. To our knowledge, this is the first report describing the occurrence of two rare adverse reactions in a patient most likely induced by carbamazepine treatment.

References

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• 13 Tariot PN, Erb R, Podgorski CA, Cox C, Patel S, Jakimovich L. et al . Efficacy and tolerability of carbamazepine for agitation and aggression in dementia.  Am J Psychiatry. 1998;  155 54-61
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Correspondence

P. A. Beitinger

Max Planck Institute of Psychiatry

Kraepelinstr. 2-10·80804 Munich·Germany

Phone: +49/89/30 62 24 04

Fax: +49/89/30 62 25 50

Email: beitinger@mpipsykl.mpg.de

References

• 1 Benatar M, Sahin M, Davis R. Antiepileptic drug-induced visual hallucinations in a child.  Pediatr Neurol. 2000;  23 439-441
  CrossrefPubMedSearch in Google Scholar
• 2 Berger H. An unusual manifestation of Tegretol (carbamazepine) toxicity.  Ann Intern Med. 1971;  74 449-450
  PubMedSearch in Google Scholar
• 3 Dalby MA. Antiepileptic and psychotropic effect of carbamazepine (Tegretol) in the treatment of psychomotor epilepsy.  Epilepsia. 1971;  12 325-334
  PubMedSearch in Google Scholar
• 4 Degner D, Kropp S, Porzig J, Grohmann R, Ruther E. Pseudohallucinations associated with moclobemide: a case report.  Pharmacopsychiatry. 2005;  38 179-181
  Thieme ConnectPubMedSearch in Google Scholar
• 5 Franks RD, Richter AJ. Schizophrenia-like psychosis associated with anticonvulsant toxicity.  Am J Psychiatry. 1979;  136 973-974
  PubMedSearch in Google Scholar
• 6 Knowles SR, Shapiro LE, Shear NH. Anticonvulsant hypersensitivity syndrome: incidence, prevention and management.  Drug Saf. 1999;  21 489-501
  CrossrefPubMedSearch in Google Scholar
• 7 Malcolm R, Myrick H, Roberts J, Wang W, Anton RF, Ballenger JC. The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial.  J Gen Intern Med. 2002;  17 349-355
  CrossrefPubMedSearch in Google Scholar
• 8 Mckee RJW, Larkin JG, Brodie MJ. Acute psychosis with carbamazepine and sodium valproate.  Lancet. 1989;  333 167
  PubMedSearch in Google Scholar
• 9 Post RM, Uhde TW, Roy-Byrne PP, Joffe RT. Antidepressant effects of carbamazepine.  Am J Psychiatry. 1986;  143 29-34
  CrossrefPubMedSearch in Google Scholar
• 10 Prueter C, Waberski TD, Norra C, Podoll K. Palinacousis leading to the diagnosis of temporal lobe seizures in a patient with schizophrenia.  Seizure. 2002;  11 198-200
  CrossrefPubMedSearch in Google Scholar
• 11 Schweizer E, Rickels K, Case WG, Greenblatt DJ. Carbamazepine treatment in patients discontinuing long-term benzodiazepine therapy. Effects on withdrawal severity and outcome.  Arch Gen Psychiatry. 1991;  48 448-452
  PubMedSearch in Google Scholar
• 12 Stewart B, Brennan DM. Auditory hallucinations after right temporal gyri resection.  J Neuropsychiatry Clin Neurosci. 2005;  17 243-245
  PubMedSearch in Google Scholar
• 13 Tariot PN, Erb R, Podgorski CA, Cox C, Patel S, Jakimovich L. et al . Efficacy and tolerability of carbamazepine for agitation and aggression in dementia.  Am J Psychiatry. 1998;  155 54-61
  PubMedSearch in Google Scholar
• 14 Weaver DF, Camfield P, Fraser A. Massive carbamazepine overdose: clinical and pharmacologic observations in five episodes.  Neurology. 1988;  38 755-759
  CrossrefPubMedSearch in Google Scholar

Correspondence

P. A. Beitinger

Max Planck Institute of Psychiatry

Kraepelinstr. 2-10·80804 Munich·Germany

Phone: +49/89/30 62 24 04

Fax: +49/89/30 62 25 50

Email: beitinger@mpipsykl.mpg.de