Successful treatment of Meige's syndrome induced by risperidone and fluvoxamine with olanzapine monotherapy in schizophrenia

Meige's syndrome is a focal dystonia characterized by symmetrical blepharospasm and oromandibular dystonia.¹ Its typical feature is difficulty in opening the eyelids, resulting from involvement of the bilateral orbicularis muscle. Although the causes of this syndrome are unknown, it has been reported to be induced by dopamine agonists or antagonists, cerebellar degeneration, basal ganglia dysfunction, and brain tumors.² We now report a case of Meige's syndrome that was secondary to combined treatment with low-dose risperidone and fluvoxamine, which was successfully treated with olanzapine in first-episode schizophrenia.

A 33-year-old man came to Department of Neuropsychiatry at St Marianna University School of Medicine Hospital with a 1.5-year history of persistent persecutory delusion and auditory hallucination. His mood was not depressed, and his thought process was logical but not fluent. His medical history was uneventful, and there was no family history of movement disorders. His laboratory examination and computed tomography of the brain did not show any abnormalities. He started receiving risperidone monotherapy from 3 mg/day, increasing up to 4 mg/day thereafter. After 2 months of treatment he reported a complete reduction in his psychotic symptoms, but experienced side-effects such as decreased libido and ejaculatory deficit. Risperidone was then gradually decreased to 2 mg/day. After being at this dose for 5 months, predominant negative symptoms such as social withdrawal, avolition and lack of interest were observed. We thus added fluvoxamine 50 mg/day to risperidone. Two days after coadministration of risperidone and fluvoxamine, severe blepharospasm (excessive blinking, difficulty in seeing, facial grimacing) and tongue tremor appeared. His fluvoxamine was withdrawn and risperidone was decreased to 1 mg/day. One week later the change of medication was not satisfactory because he still complained of difficulty in opening his eyes, especially on the left side. He then decided to stop risperidone and his medication regimen was changed to olanzapine 10 mg/day monotherapy, with significant resolution of his blepharospasm in 10 days. After two months of treatment with olanzapine the improvement of blepharospasm was more evident but he complained of somnolence. We decreased olanzapine to 5 mg/day. After another couple of weeks his blepharospasm and tongue tremor were completely relieved. Olanzapine was also as effective as the previous regimen in controlling his psychotic symptoms. In addition there was a marked improvement of his negative symptoms and no other side-effects were observed. The patient gave his informed consent to permit this case report.

To our knowledge this is the first report demonstrating that Meige's syndrome is induced by combined treatment with fluvoxamine and low-dose risperidone. Risperidone administered either alone or concomitantly with other antipsychotics has been reported to induce Meige's syndrome, although there have been a few case reports of the improvement of tardive dystonia with risperidone.³ In the present case coadministering fluvoxamine, which can potently inhibit cytochrome P450 (CYP)2D6 and CYP3A4, might increase the levels of risperidone metabolized by the CYP isoenzymes. Several placebo-controlled trials have shown that adding fluvoxamine to antipsychotics can improve negative symptoms in schizophrenia. However, caution should be paid to this adjunctive strategy due to the risk of drug interactions and subsequent unpredictable adverse events, even if the antipsychotic was given at a low dose.

Meige's syndrome has been reported to improve when the offending antipsychotics were discontinued.⁴ However, antipsychotic treatment often has to be continued in those schizophrenia patients who require maintenance treatment. The present case supports the previous reports demonstrating that olanzapine may have a beneficial effect in ameliorating Meige's syndrome.⁵ The precise pharmacophysiologic basis for its effectiveness remains unknown. Further studies are necessary to examine this effect and its mechanism.