Manic episodes induced by
antidepressant withdrawal are rarely reported.
Mirtazapine is a tetracyclic, piperazinoazepine compound and is a noradrenergic,
adrenergic, serotonergic, histaminergic, and
muscarinic-antagonist antidepressant that is used for the treatment of major depression and other
psychiatric illnesses. There are several reported cases of manic/
hypomanic episodes induced by
mirtazapine withdrawal based on suspected clinical symptoms that were not confirmed by autopsy and toxicology. We present the first reported case of
mirtazapine withdrawal-induced
mania/
hypomania associated with
sudden death and confirmed by autopsy and toxicology. Our patient was a 26-year-old male who had been diagnosed with
schizophreniform disorder, borderline intellectual functioning, polysubstance abuse, mild
mental retardation, and attention deficit hyperactive disorder. He took only
mirtazapine in the final and terminal weeks of his life and stopped taking
mirtazapine 4 days before his death. He exhibited a sudden manic/
hypomanic episode and died during a physical altercation during this episode. A full autopsy with comprehensive toxicologic analysis of his body fluids and tissues was performed. Autopsy revealed that he died from blunt force
trauma of the head, neck, and trunk with extremely low and markedly subtherapeutic levels of
mirtazapine and
desmethylmirtazapine in the blood (
mirtazapine: 0.005 mg/L;
desmethylmirtazapine 0.011 mg/L). Advanced selective radioligand and neurochemical assays for density and affinity-binding parameters of
dopamine transporter and
heat shock protein 70 did not reveal any evidence of excited
delirium or autonomic hyperactivity state. We recommend that toxicologic analysis of blood for
antidepressants should become routine parts of autopsy protocols for the investigation of
sudden death following terminal manic/
hypomanic episodes for further elucidation of
mania/
hypomania induced by
antidepressant withdrawal.