Quetiapine-Induced Hypomania and its Association with Quetiapine/Norquetiapine Plasma Concentrations: A Case Series of Bipolar Type 2 Patients

Abstract

International guidelines consider quetiapine at medium doses (300–400 mg/day) as valid options for the treatment of bipolar depression for the supposed lower risk of a switch to hypomania/mania than antidepressants. Norquetiapine is an active metabolite with antidepressant action. We describe three cases of induced hypomania in bipolar type 2 subjects who received quetiapine extended-release monotherapy (300 mg/day) for a mild/moderate major depressive episode. Quetiapine and norquetiapine plasma concentrations were measured after 1 week of treatment. Hypomania appeared after 7–10 days of quetiapine extended-release monotherapy and all subjects had a quetiapine/norquetiapine plasma concentration ratio <1. We propose a ratio value <1 as a predictor of risk for a switch to hypomania in bipolar depressed subjects receiving quetiapine extended-release monotherapy. Future research should ascertain the validity of this laboratory parameter to assess the risk of quetiapine-induced hypomania in large samples of bipolar patients.

Are Hypomanic/Manic Episodes “Induced by” or “Associated with” Quetiapine Initiation?

“…Accordingly, when these patients receive an antipsychotic drug with mood-stabilizing properties, they will not benefit from its effects unless higher doses are reached [ 10 ]. Finally, as Rovera et al [ 2 ] discuss, norquetiapine, the most important active metabolite of quetiapine, has also been implicated in this induction of hypomania/mania. In fact, norquetiapine has been shown to be associated with antidepressant and anxiolytic effects in humans through its effect on dopamine release in the prefrontal cortex as well as dopamine reuptake inhibition.…”

“…In fact, norquetiapine has been shown to be associated with antidepressant and anxiolytic effects in humans through its effect on dopamine release in the prefrontal cortex as well as dopamine reuptake inhibition. Moreover, norquetiapine potentiates serotoninergic and noradrenergic transmission through its high affinity for serotoninergic receptors and through noradrenalin reuptake inhibition [ 2 ].…”

“…An increasing number of case reports are concerned with hypomanic/manic symptoms induced by some atypical antipsychotic drugs, especially quetiapine [ 1 ]. In the current volume of Drug Safety—Case Reports , the case series published by Rovera et al [ 2 ] demonstrates that quetiapine-related hypomania is an interesting event that is worth being appropriately diagnosed and managed in patients with bipolar disorder. Quetiapine is a second-generation dibenzothiazepine antipsychotic drug approved for the treatment of schizophrenia, major depression, bipolar disorder, bipolar depression, and mania.…”