Psychosomatics 47:68-69, February 2006
doi: 10.1176/appi.psy.47.1.68
© 2006 Academy of Psychosomatic Medicine
Zonisamide-Induced Suicidal Ideation
Rajnish Mago, M.D.,
Steven Huege, M.D.,
Niraj Ahuja, M.D., and
Elisabeth J.S. Kunkel, M.D.
Received November 1, 2004; revised November 4, 2004; accepted December 4, 2004. From Thomas Jefferson Univ., Dept. of Psychiatry and Human Behavior, Philadelphia, PA (RM, SH, EJSK), and Newcastle, N. Tyneside and Northumberland NHS MH Trust, and the School of Neurology, Neurobiology, and Psychiatry, Univ. of Newcastle, Newcastle-upon-Tyne, UK (NA). Send correspondence and reprint requests to Rajnish Mago, M.D., Thomas Jefferson Univ., Dept. of Psychiatry and Human Behavior, 833 Chestnut St. East, Suite 210 E, Philadelphia, PA 19107. e-mail: rajnish.mago{at}jefferson.edu
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INTRODUCTION
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Various psychiatric symptoms can occur in epilepsy or be induced by antiepileptic medications. Zonisamide is an antiepileptic medication used as adjunctive therapy for partial seizures. Depression,1 mania,1,2 obsessive-compulsive disorder,3 and psychotic symptoms4,5 have been reported in patients on zonisamide. According to the Physician’s Desk Reference, the most common psychiatric adverse effects of zonisamide are agitation (9%), depression (6%), insomnia (6%), anxiety (3%), nervousness (2%), and "schizophrenic behavior" (2%). Although a greater number of patients on zonisamide (1.1%) attempted suicide than those on placebo (0.4%), it was not clarified whether this was due to the induction of depression. We present here a case of sudden suicidal impulses without any concomitant depressive symptoms in a patient on zonisamide.
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Case Report
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A 34-year-old woman with a 20-year history of complex partial seizures was admitted for presurgical evaluation of her epilepsy. She had had multiple trials on various anticonvulsant medications, including divalproex, carbamazepine, and lamotrigine. Most recently, she had been on lamotrigine, to which zonisamide was added.
The patient began feeling irritable soon after starting zonisamide. Things that normally would not upset her started to bother her. However, there were no hypomanic symptoms or symptoms of depression, including sadness, anhedonia, poor sleep, poor appetite, guilt, low energy, or impaired concentration.
The patient, well-educated and articulate, gave a clear and detailed history of sudden, intrusive suicidal thoughts occurring after being started on zonisamide. Upon returning home one day, she suddenly and unexpectedly found herself looking at her medication bottles, with a strong urge to take all the pills in the bottles to end her life. She was surprised and disturbed by these thoughts and knew it would be wrong to take her life. Fortunately, the patient was able to resist the impulses. Because of the irritability and suicidal thoughts, zonisamide was discontinued by the patient’s neurologist, and the suicidality did not recur, even though lamotrigine was continued. Upon careful questioning, the patient clearly denied feeling depressed before or around the time that she had these suicidal impulses. Although irritable at other times, at the particular time the suicidal impulses occurred, she was not either frustrated or irritable. She did not have any other psychiatric symptoms during this period. Apart from some obsessive-compulsive personality traits, there was no past history of depressive disorder, psychosis, or other psychiatric disorders.
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Discussion
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This patient developed isolated suicidal ideation in the absence of any depressive symptoms while on a trial of zonisamide for treatment of her seizure disorder. Suicidal thoughts can occur in the setting of mood and psychotic disorders, but are uncommon in their absence. Suicide, although associated with epilepsy, tends to occur with longstanding complex partial seizures and dysphoric states. The suicides are most likely to occur a short time after full control of the seizures is achieved. Suicide may occur during interictal dysphoric episodes or in a state of postictal depression.6 In this patient, there was poor control of the seizures, and the patient was not depressed.
In accordance with the recommended literature search strategy,7 MEDLINE and EMBASE were searched (last on 10/1/04), using the terms zonisamide, suicide, depression, obsess*, impuls*, compuls*, and psychiatric. The databases were also searched under the Medical Subject Heading (MeSH) terms "depressive disorders," "suicide," "mental disorders," "obsessive behavior," "compulsive behavior," and "obsessive-compulsive disorder," along with the textword "zonisamide." None of these searches produced any cases of isolated suicidal ideation in patients taking zonisamide. A search of the Food and Drug Administration’s website and communication with the manufacturer of zonisamide, Elan Pharmaceuticals, did not reveal any cases of isolated suicidal ideation, either.
Although the mechanism by which zonisamide causes its psychiatric adverse effects is not known, it has been speculated8 that they may be related to a biphasic effect of zonisamide on serotonin function. Although therapeutic plasma levels increase levels of serotonin, 5-hydroxyindoleacetic acid (the principal serotonin metabolite), and 5-hydroxytryptophan (the precursor of serotonin), supratherapeutic concentrations either decrease or do not affect these levels. A substantial literature links low levels of serotonin and 5-HIAA to suicidal ideation and suicide attempts.
Another possible explanation for this patient’s suicidal ideation is that the suicidal impulse was an obsessive symptom induced by zonisamide. It did have an ego-dystonic and intrusive quality similar to an obsession. Zonisamide has been associated with onset of obsessive-compulsive disorder in a child.3 Also, obsessive-compulsive symptoms were associated in children with psychosis induced by zonisamide.5
Thus, clinicians should monitor patients on zonisamide and other anticonvulsants for suicidal thoughts/ impulses; these can occur even in the absence of other prominent thought or mood disturbances.
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REFERENCES
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- Ozawa K, Kobayashi K, Noda S, et al: Zonisamide-induced depression and mania in patients with epilepsy. J Clin Psychopharmacol 2004; 24:110–111[CrossRef][Medline]
- Charles CL, Stoesz L, Tollefson G: Zonisamide-induced mania. Psychosomatics 1990; 31:214–217[Free Full Text]
- Hirai K, Kimiya S, Tabata K, et al: Selective mutism and obsessive compulsive disorders associated with zonisamide. Seizure 2002; 11:468–470[CrossRef][Medline]
- Hirose M, Yokoyama H, Haginoya K, et al: A five-year-old girl with epilepsy showing forced normalization due to zonisamide. No To Hattatsu. (Japanese) 2003; 35:259–263
- Miyamoto T, Kohsaka M, Koyama T: Psychotic episodes during zonisamide treatment. Seizure 2000; 9:65–70[CrossRef][Medline]
- Blumer D, Montouris G, Davies K, et al: Suicide in epilepsy: psychopathology, pathogenesis, and prevention. Epilepsy Behav 2002; 3:232–241[CrossRef][Medline]
- Mago R: Searching the medical literature for case reports. J Clin Psychiatry 2004; 65:444–445[Medline]
- Okada M, Hirano T, Kawata Y, et al: Biphasic effects of zonisamide on serotonergic system in rat hippocampus. Epilepsy Res 1999; 34(2-3):187-197
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INTRODUCTION
Case Report
