Clonidine induced sexual disinhibition in a patient with treatment-resistant schizophrenia: A case report

To the Editor

We present the case report of Mr A, a 55-year-old male with treatment-resistant schizophrenia, admitted and treated in an extended care unit due to significant risks associated with wandering and disorganization. Mr A had head injury of unknown severity at 12 years of age; however, no abnormalities were detected in computed tomography (CT) scan. The illness onset was at 14 years of age with failed adequate anti-psychotic trials. His illness was characterized by positive and negative psychotic symptoms with disorganization. Clozapine was commenced 9 years ago, with good response of positive symptoms but with persisting negative symptoms and disorganization and with hyper-salivation leading to choking episodes, which did not respond to anti-cholinergic agents. Clonidine at 50 µg was trialed to control the hyper-salivation. However, within 7 days of commencement of clonidine, new-onset behavioral problems were observed, including sexual disinhibition and impulsivity in the form of repeated inappropriate touching of female co-clients that did not respond to redirection. There were no other observed changes in his mental state. Clonidine was ceased with a resolution of these behaviors within a week.

Clonidine, an alpha-2 adrenergic receptor agonist, initially used primarily as an antihypertensive medication, is currently being used to treat various psychiatric disorders notably childhood attention-deficit hyperactivity disorder as well as clozapine-induced sialorrhea (Praharaj et al., 2005). Common adverse effects of clonidine include sedation, dizziness, fatigue and rebound hypertension and less commonly anxiety, depressive symptoms, sleep disturbances and hallucinations have also been reported (Praharaj et al., 2005).

Sexual disinhibition secondary to clonidine use has not been reported and we hypothesize that this rare side effect could be secondary to an increase in dopaminergic activity. The norepinephrine transporter is a presynaptic transporter in sympathetic neurons that is important for the clearance of both synaptic norepinephrine and dopamine (Morón et al., 2002). Clonidine, via its action on post synaptic alpha-2 receptors, increases synaptic noradrenaline levels. We postulate that increased synaptic noradrenaline levels could compete with the reuptake of dopamine, theoretically increasing synaptic dopamine levels. Increased levels of synaptic dopamine may stimulate central dopaminergic projections to the nucleus accumbens, resulting in an increase in disinhibited and impulsive behaviors (Becker et al., 2001).