Letters to the Editor
Gabapentin-Induced Paradoxical Exacerbation of Psychosis in a Patient With Schizophrenia
Dear Editor:
Gabapentin is an anticonvulsant that is increasingly prescribed to patients with schizophrenia (1). Uses of anticonvulsants in this population have traditionally included antipsychotic augmentation and control of aggression and impulsivity (1). Gabapentin is reported to have antianxiety and hypnotic effects in patients with schizophrenia (2) and panic disorder (3). Documented behavioural side effects include hypomanic and manic mood changes, aggression, and agitation (4–6). We report a case of paradoxical worsening psychosis associated with initiation of gabapentin in a patient with schizophrenia.
Mr A, aged 23 years, was diagnosed at age 18 years with schizophrenia according to DSM-IV criteria. He has permanent, full-time employment. His medications prior to starting gabapentin included clozapine 425 mg daily, procyclidine 10 mg daily, divalproex sodium 1000 mg daily, and fluoxetine 30 mg daily. He has been maintained on divalproex sodium since his initial presentation for affective symptoms. Fluoxetine was added to alleviate medication-induced obsessive–compulsive symptoms. No recent medication changes have been made. His baseline psychotic symptomatolgy included rare paranoid ideation and rare auditory hallucinations. He presented with complaints of decreased sleep, and gabapentin therapy was initiated at 300 mg nightly. After 4 days, he noted increased paranoid ideation, increased auditory hallucinations, and racing thoughts. Although his sleep significantly improved with gabapentin, worsening psychosis necessitated 2 days off work. He stopped the medication after 4 days and noticed a gradual decrease in symptoms over the following 8 days. He denied concomitant alcohol or drug use and was compliant with medication. He was seen 2 weeks after starting gabapentin therapy and judged to be at baseline.
We propose 2 possible mechanisms to explain our observation. First, gabapentin is a structural analog of the inhibitory neurotransmitter GABA (7). Like benzodiazepines, gabapentin is a GABA-enhancing drug (7). Paradoxical worsening of psychotic symptoms has been documented in schizophrenia patients treated with benzodiazepines (8). Paradoxical aggravation of psychosis by gabapentin may occur through a similar mechanism. Alternatively, gabapentin is known to interfere with amino acid uptake across cell membranes (7). By interfering with clozapine transport across membranes, gabapentin may cause an acute decrease in cerebrospinal fluid or intracellular clozapine, leading to paradoxical psychosis. However, this effect appears rare, because gabapentin with clozapine has been given to schizophrenia patients, with therapeutic benefits (2,9).
References
1. Citrome L, Levine J, Allinghamn B. Changes in use of valproate and other mood stabilizers for patients with schizophrenia from 1994 to 1998. Psychiatr Serv 2000;51:634–8.
2. Chouinard G, Beauclair L, Belanger MC. Gabapentin: long-term antianxiety and hypnotic effects in psychiatric patients with comorbid anxiety-related disorders. Can J Psychiatry 1998;43:305.
3. Pande AC, Pollack MH, Crockatt J, Grenier M, Chouinard G, Lydiard RB, and others. Placebo-controlled study of gabapentin treatment of panic disorder. J Clin Psychopharmacol 2000;20:467–71.
4. Pinninti NR, Umdnj S, Mahajan DS. Gabapentin-associated aggression. J Neuropsychiatry Clin Neurosci 2001;13:424.
5. Trinka E, Niedermuller U, Thaler C, Doering S, Moroder T, Laudurner G, Bauer G. Gabapentin-induced mood changes with hypomanic features in adults. Seizure 2000;9:505–8.
6. Leweke FM., Bauer J, Elger CE: Manic episode due to gabapentin treatment. Br J Psychiatry 1999;175:291.
7. Taylora CP, Geed NS, Sub TZ, Kocsise JD, Weltyc DF, Brownd JP, and others. A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res 1998;29:231–46.
8. Stimmel GL. Benzodiazepines in schizophrenia. Pharmacotherapy 1996;16:148S–151S.
9. Kolivakis TT, Margolese HC, Beauclair L, Chouinard G. Clozapine for first-episode schizophrenia. Am J Psychiatry 2002;159:317.
Karin Jablonowski MD, CM
Howard C Margolese MD, CM, FRCPC
Guy Chouinard MD, MSc, FRCPC
Montreal, Quebec
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