title: Dysphoric mania induced by high-dose mirtazapine: a case for 'norepinephrine syndrome'?
abstract: The antidepressant mirtazapine antagonizes central presynaptic alpha2-adrenergic auto- and heteroreceptors resulting in increased central norepinephrine and serotonin activity. Histamine H2 receptors are also antagonized, as are postsynaptic serotonin 5-HT2 and 5-HT3 receptors, leading to serotonergic activity primarily via 5-HT1A receptors. Based on the case report of a patient who developed mania with higher than recommended dosage of mirtazapine, we review the literature on the atypical nature of manic symptoms with mirtazapine. Eight subjects, including those in our study, were identified as having developed mirtazapine-induced mania with atypical features, consisting of dysphoria, irritability, insomnia, psychomotor agitation and abnormal gait. Predisposing features may have included the presence of underlying brain dysfunction and certain selective serotonin reuptake inhibitor-mirtazapine combinations. Dysphoric mania with atypical features may be induced by mirtazapine, providing support for a common hypothesis such as 'central norepinephrine hyperactivity' as the basis for development of mania with mirtazapine.
authors.affiliation: Clinical Psychopharmacology Unit, Allan Memorial Institute, McGill University Health Center, McGill University, Montreal, Quebec, Canada. nadeem.bhanji@mail.mcgill.ca
authors.forename: N H
authors.initials: NH
authors.lastname: Bhanji
authors.forename: H C
authors.initials: HC
authors.lastname: Margolese
authors.forename: M
authors.initials: M
authors.lastname: Saint-Laurent
authors.forename: G
authors.initials: G
authors.lastname: Chouinard
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000139:chemically induced*; D003866:Depressive Disorder / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008803:Mianserin / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000627:therapeutic use; D000078785:Mirtazapine; D009638:Norepinephrine / Q000494:pharmacology*; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013577:Syndrome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D008803:Mianserin; D000078785:Mirtazapine; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors