Clozapine Withdrawal Related Mania in an Adolescent: Case Report

Clozapine discontinuation is known to trigger withdrawal-associated psychosis, but non-psychotic withdrawal symptoms, though clinically significant, are less frequently discussed. Proposed mechanisms include dopaminergic receptor upregulation, cholinergic rebound, and serotonergic dysregulation. No previous reports describe clozapine withdrawal-associated mania in pediatric patients, and only three cases of withdrawal-related mania have been described in adults. We describe a 16-year-old female with schizophrenia who had previously shown limited response and poor tolerability to multiple antipsychotics. Since clozapine is known to be effective in psychotic symptoms nonresponsive to other antipsychotics, it was initiated during hospitalization and titrated to 250 mg/day. It was stopped after 7 days at the target dose due to suspected myocarditis. After 4 days, the patient presented with elated mood, tachypsychia, hypersexuality, and decreased need for sleep, without psychotic symptoms. Symptoms resolved over 10 days with olanzapine. Psychotic symptoms re-emerged post-discharge, in the absence of mood features. This appears to be the first report of clozapine withdrawal-associated mania in an adolescent without a previous mood disorder. Earlier cases have only involved adults with schizoaffective disorder and long-term treatment. While schizoaffective disorder was considered in this case, the brief duration of symptoms, full remission with antipsychotic monotherapy, and close temporal link to clozapine cessation favor a withdrawal-related phenomenon. This case exposes for the first time in the literature the onset of manic symptoms following clozapine withdrawal in an adolescent with only psychotic symptoms before this trial. This report raises awareness for the importance of monitoring different effects during and after psychopharmacologic treatment, other than the reappearance of psychotic symptomatology. It also raises questions about diagnostic evolution in early-onset psychosis.