Asenapine-Induced Acute Dystonia in an Adolescent Male

To the Editor:

Asenapine is a sublingually absorbed newer second-generation antipsychotic that is approved for the treatment of schizophrenia and bipolar disorder in patients, with a lower propensity to cause extrapyramidal adverse effects as compared with haloperidol (Citrome 2009). The adverse effects commonly reported with asenapine with rates higher than placebo include akathisia, oral hypoesthesia, somnolence, and dizziness (Citrome 2009). Also, compared with other second-generation antipsychotics, it has a benign metabolic adverse effects profile (De Hert et al. 2012). We report an adolescent boy having schizophrenia who developed an acute dystonic reaction while being treated with asenapine.

Case Study

A 17-year-old boy presented with a history of disturbed sleep, smiling, and muttering to self, irrelevant talk, poor personal care, and decreased social interaction of 3 months duration. There was no significant past or family history. His developmental history was unremarkable. On mental status examination, he was poorly kempt, had poor eye contact, hallucinatory behavior, scant speech with formal thought disorder, and inappropriate affect. Laboratory tests including complete blood count, renal and liver function tests, and blood sugar were normal.

Considering a diagnosis of undifferentiated schizophrenia as per ICD-10 criteria, he was hospitalized and treated with tablet asenapine 10 mg sublingually and tablet lorazepam 4 mg per day in divided doses. The dose of asenapine was increased to 15 mg after 4 weeks, considering poor response. Four days later he developed a sudden onset of pain in the left perioral region, difficulty in swallowing, and inability to close his mouth along with twisting of neck muscle, suggestive of acute dystonia. Injection promethazine 50 mg was administered intravenously and the symptoms subsided within a few minutes. Subsequently, trihexyphenidyl 4 mg in divided doses was added to prevent further episodes. He was discharged after 6 weeks of hospital stay and was found to be symptom free on follow-ups till a year after discharge, without any recurrence of dystonia.

Discussion

Our subject developed acute dystonia 4 days after increasing the dosage of asenapine from 10 to 15 mg. A Naranjo adverse drug reaction probability scale score was 7, which is suggestive of probable association (Naranjo 1981). He did not have any exposure to antipsychotics in the past. No adverse effects were noted for the initial 4 weeks, which suggests that the acute dystonia could possibly be dose related, that is, occurring at higher doses. In general, acute dystonic reactions occur within 36 hours of administration or on increasing the dose of the offending drug and may persist for up to 24 hours if left untreated (Liu 1979). It is known that young males are at a higher risk for acute dystonia with antipsychotic exposure (Van Harten et al. 1999); our subject was 17-year-old with early-onset schizophrenia.

A PubMed search revealed only one published case report of dystonia with asenapine treatment (Ridout et al. 2015), although the summary of product characteristics describes it as a common adverse effect (occurring at a frequency of 1%–10%) (Sycrest 2010). Asenapine is an antipsychotic with dibenzo-oxepino pyrrole structure that acts as D₂ receptor antagonist as well as 5HT_2A, 5HT_2C, 5HT₇ receptor antagonist (Minassian and Young 2010). The exact mechanism of dystonia with asenapine is not known, although a possible imbalance between dopaminergic and serotonergic levels could be contributory. The clinicians should be aware of the possibility of asenapine to cause dystonia, specifically in adolescent patients when it is used at doses more than 10 mg per day.