Successful Antimanic Treatment and Mood Stabilization with Lamotrigine, Clozapine, and Valproate in a Bipolar Patient after Lithium-induced Cerebellar Deterioration

We report the case of a 56-year-old male with an 18-year history of a bipolar I affective disorder (DSM-IV criteria), who has been successfully treated with lithium for 8 years. When lithium was discontinued due to a lithium-induced persistent cerebellar syndrome at therapeutic lithium levels, the combination of valproate and clozapine was less effective to achieve mood stabilization. A re-challenge with lithium failed due to impairment of neurological symptoms. When lamotrigine at a daily dose of 50 mg was co-administered to valproate and clozapine, the patient’s condition improved rapidly and remained stable over a follow-up period of 12 months. Concomitant administration of lamotrigine increased the serum levels of both valproate and clozapine. We conclude that

1. Normal lithium levels in co-medication with classical neuroleptics and concurrent medical illness are able to induce severe neurotoxicity.

2. Lithium re-administration after lithium-induced neurotoxicity should be strictly avoided.

3. Lamotrigine is safe when applied to patients with lithium-induced neurological sequelae.

4. Lamotrigine augmentation could enhance the efficacy of valproate and clozapine therapy to achieve antimanic action and mood stabilization in patients with refractory bipolar affective disorder.

5. Concomitant administration of lamotrigine interferes with the serum levels of both valproate and clozapine, thus implying continuous drug monitoring.

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