An 85-year-old woman developed sudden confusion and dysarthria progressing to mutism, orobuccal dyskinesias, generalized tremors worse with activity, ataxia, and rigidity with cog wheeling without high-grade fevers or dysautonomia. These findings were related temporally to the institution of mirtazapine as monotherapy for a major depressive illness with superimposed anxiety disorder. Withdrawal of the agent resulted in early notable clinical resolution with only residual hypertonia after 2 weeks. This is a rare report of serotonin syndrome induced by mirtazapine monotherapy. The hypothesized pathophysiologic mechanism in this case is overstimulation of serotonin (5-hydroxytryptamine or 5-HT) type 1A receptors (5-HT1A) in the brainstem and spinal cord in an individual with risk factors for hyperserotoninemia resulting from reduced, acquired endogenous serotonin metabolism.
Serotonin syndrome is a potentially dangerous and fatal hyperserotonergic state that occurs most commonly with the use of two or more serotonergic drugs (selective serotonin reuptake inhibitors, monoamine oxidase [MAO] inhibitors, tricyclic and tetracyclic antidepressants, dopamine serotonin receptor agonists, opioids, L-tryptophan, and amphetamine derivatives), although cases resulting from the use of a single agent have also been reported (1-6). It is characterized clinically by the sudden onset of a triad consisting of cognitive/behavioral changes (agitation, hypomania, confusion), autonomic instability (hyperthermia, diaphoresis, diarrhea, mydriasis, tachycardia), and neurologic changes (hyperreflexia, myoclonus, tremor, incoordination, rigidity) (1,2). The diagnosis requires at least three of these clinical features coincidental with the addition or increase in a known serotonergic agent to an established medical regimen, in the absence of modification in the dosage of a neuroleptic agent, and excluding other possible etiologies such as metabolic derangements, infections, or drug intoxication or withdrawal (1).
Serotonin syndrome has been described rarely in association with mirtazapine (3,7-9), and only a single case involving monotherapy (7) was reported previously. We report a case of serotonin syndrome related temporally to the institution of mirtazapine (Remeron) monotherapy with clinical resolution after drug administration was discontinued, emphasizing the need for increased awareness of this syndrome when using this agent.