Lurasidone-induced Tardive Oromandibular Dystonia

We present the case of a 31-year-old Caucasian woman with a history of schizoaffective disorder who was treated in one of the Outpatient Units of the Department of Mental Health, Provincial Health Company of Agrigento, Italy, beginning in August 2020. She was clinically stable for ten months on the following unchanged polytherapy: olanzapine 20 mg/d, oxcarbazepine 600 mg/d, trazodone 300 mg/d, and lorazepam 2.5 mg/d. Due to a progressive weight gain of 15 kg, we gradually switched from olanzapine to aripiprazole 20 mg/d in June 2021. After two weeks, aripiprazole was discontinued due to nausea, a feeling of nervousness, myalgia, and insomnia, and lurasidone 74 mg/d was initiated with good efficacy and tolerability. Given the long half-life of aripiprazole, an abrupt switch approach was used [4]. However, four months after lurasidone therapy, in October 2021, the patient experienced an episode of tardive oromandibular dystonia, which resulted in a compromised position of the jaw with uncontrolled and sustained left lateral dystonic movements of the jaw that interfered with opening and closing the mouth, chewing, and speech (fig. 1). The patient appeared significantly distressed and anxious, with impaired activities of daily living, so lurasidone was stopped, biperiden 8 mg/d was started, and lorazepam was increased to 7.5 mg/d. Two weeks later, due to therapeutic inefficacy, tetrabenazine was added and titrated up to 75 mg/d. One year after the onset of dystonia, the symptoms remained unchanged, and the patient switched to a different outpatient mental health service.

Lurasidone is an atypical antipsychotic approved for the treatment of schizophrenia and bipolar I disorder. Lurasidone shows high affinity for the 5-hydroxytryptamine (serotonin) receptor 1A (5-HT1A), 5-HT2A2, 5-HT7, and D2 alpha 2 receptors and low affinity for the muscarinic acetylcholine M1, histamine H1, 5-HT2C, and alpha 1 adrenergic receptors [5]. Some of the most common adverse events reported with lurasidone include akathisia, parkinsonism, and insomnia; however, weight gain is less common than with olanzapine [6]. In a study of 107 patients treated for tardive dystonia, baclofen, tetrabenazine, benzodiazepines, and anticholinergic medications showed “at least some benefit” in about 50% of patients and 83% following botulinum toxin injection. The remission rate was low, related to the duration of the antipsychotic treatment, and occurred after a mean of 2.6 years from its discontinuation [2].