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.

Context-Dependent Effects of a Single Administration of Mirtazapine on the Expression of Methamphetamine-Induced Conditioned Place Preference

“…If so, administration of mirtazapine prior to re-exposure to the Meth-paired chamber would be expected to produce a dysphoric effect to override the previous Meth-induced preference. While very high doses of mirtazapine have been reported to produce dysphoria (Bhanji et al, 2002), the mirtazapine dose used in our experiments would not be expected to produce either preference or aversion (Kang et al, 2008). Thus, it seems unlikely that this explanation is responsible for the outcomes observed in our experiments.…”

Antidepressant-associated mania: soon after switch from fluoxetine to mirtazapine in an elderly woman with mixed depressive features

“…The duration might be even longer taking into account of our patient's old age and multiple physical illnesses. Moreover, being predisposed to fluoxetine will inhibit the metabolism of mirtazapine through its effects upon cytochrome P450 isoenzymes (Bhanji, et al, 2002). Consequently, it is very likely that both agents have coexisted in our patient at higher than expected levels for more than a week and both contributed to her manic switch.…”

“…However, we should be cautious whether such an approach would put the patient on double risk to develop manic symptoms. As brain vulnerability, higher dosage and/ or longer duration of exposure to antidepressants have been proposed to increase risk of manic switch under combined antidepressant therapy (Bhanji, et al, 2002), we would like to emphasise another risk factor, mixed depressive features, because our case did not receive unusually high doses of both antidepressants and was just exposed to mirtazapine for a very short period of time.…”

SNRI‐NaSSA combination therapy for treatment‐resistant depression

“…The observation that SNRIs are more vulnerable to induce hypomanic switch suggests that this may be a syndrome of noradrenergic instability. 16 In a similar way, af fective switch is also observed when the noradrenaline reuptake inhibitor (NARI) reboxetine is added to SSRIs.…”