Acute Dystonia Induced by Adding Midodrine, a Selective Alpha 1 Agonist, to Risperidone in a Patient With Catatonic Schizophrenia

SIR: Acute dystonia is one of the well-known side effects observed in patients treated with conventional neuroleptics. Extrapyramidal symptoms reportedly are less common with risperidone, a newer atypical neuroleptic, than with conventional neuroleptics.¹ Here we offer the first report of a case of acute dystonia occurring after initiation of midodrine, a selective alpha 1 agonist, in a patient with catatonic schizophrenia treated with risperidone.

Case Report

Mrs. A., a 33-year-old woman with a 12-year history of catatonic schizophrenia, discontinued her medication because of adverse effects from typical neuroleptics, such as sedation and extrapyramidal side effects. Six months after cessation of neuroleptic treatment, she was admitted in a severe catatonic state, showing stupor, fixed posture, psychotic mutism, and negativism with a remarkably waxy flexibility. Four weeks after initiation of risperidone 6 mg/day, her catatonic symptoms had remitted completely.

The patient experienced no side effects from risperidone except for orthostatic hypotension. Her systolic blood pressure declined 20 mm Hg or more after standing, with symptoms such as dizziness and near-syncope. Midodrine 4 mg/day was added to risperidone to cope with this orthostatic hypotension. Two days after initiation of midodrine, she presented prominent acute dystonic symptoms including tongue protrusion, retrocollis, and oculogyric crisis. These dystonic reactions disappeared rapidly after intramuscular injection of anticholinergics. The use of midodrine was stopped and risperidone 6 mg/day was continued. The dystonic symptoms did not occur during 2 weeks on this medication, but the frequency of orthostatic hypotension increased. Again, midodrine 4 mg/day was added to risperidone, and the patient had an acute dystonic reaction the next day. This dystonic reaction disappeared soon after one-time injection of an anticholinergic. Midodrine was stopped and risperidone 6 mg/day was continued for the next 2 weeks. Acute dystonic reaction did not occur during this period; however, we had to reduce risperidone dose to 3 mg/day to control orthostatic hypotension. Under this medication, neither the catatonic symptoms nor the dystonic reaction has recurred for 3 months.

Comment

Acute dystonic reaction in this patient occurred twice within a few days of adding midodrine to risperidone and did not recur after discontinuation of midodrine. This pattern would suggest that addition of midodrine might have been responsible for the acute dystonia observed in this case. Risperidone is not only a serotonin-dopamine antagonist, it can also block alpha 2 adrenoceptors.² In turn, the alpha 2 antagonism can increase noradrenergic activity by inhibiting the autoreceptors.³ It has been shown that risperidone can increase noradrenergic transmission in human brain.⁴ Animal study has suggested that enhanced activity of central noradrenergic nuclei is one of the pathophysiologies of dystonia.⁵ It is likely therefore that the noradrenergic enhancement effect of risperidone was increased by the addition of midodrine, leading to an acute dystonic reaction. However, the exact nature of this interaction is difficult to characterize.

Although acute dystonia is usually reversible, this uncomfortable side effect occurs abruptly and dramatically, causing great anxiety in patients at the prospect of continuing the medication. Clinicians therefore should closely monitor for acute dystonic reaction when an alpha 1 agonist such as midodrine is necessary for controlling risperidone-induced orthostatic hypotension, especially in patients with catatonic schizophrenia.