Letters to the Editor

PROPRANOLOL IN THE TREATMENT OF NEUROLEPTIC-INDUCED AKATHISIA

Restless legs syndrome (RLS) is a movement disorder that frequently results in significant complaints of insomnia. Based on published case reports, it is commonly believed that RLS can be caused or exacerbated by antidepressant agents, thus complicating the treatment of depressed patients who are already prone to sleep disturbances. However, there are no systematic studies demonstrating an association between the clinical diagnosis of RLS and the use of antidepressant medication.

Retrospective chart review of 200 consecutive patients presenting for evaluation of sleep initiation insomnia at an accredited freestanding sleep disorders center that is part of an integrated health care system.

Mean age (±SD) of patients was 51.1±14.8 years; 60% were women. Fifty-six percent carried a diagnosis of depression, 38% were being treated with antidepressant medication at presentation and 45% met clinical diagnostic criteria for RLS. There were no statistical associations, either by χ² analysis or odds ratios, between RLS and antidepressant use or use of any specific class of antidepressant. Positive associations with RLS were found for patients receiving treatment for hypothyroidism and those taking estrogens; a significant negative association was found for patients receiving beta adrenergic antagonists.

Although there are anecdotal reports of antidepressant use causing or exacerbating RLS, systematic study of this issue fails to corroborate an association.

Neuroleptic-induced defecation in rats in a well-habituated environment has been proposed as a model of the subjective component of akathisia. In this study, we examined the effects of two lipophilic β-adrenoceptor antagonists — the non-selective drug propranolol and the relatively β₁-selective metoprolol — and one non-selective hydrophilic drug nadolol in this model. Young male Wistar rats were randomly assigned to one of eight groups (n=12 in each group) and treated with haloperidol or vehicle, with or without one of the β-antagonists. Haloperidol-treated rats had higher bolus counts than vehicle-treated rats, and this increase was significantly reversed by the lipophilic but not the hydrophilic β-antagonists. This finding is consistent with the reported anti-akathisia effects of these drugs in humans, suggesting that this effect is central in origin and achievable with relatively selective β₁-antagonism. The β-antagonist drugs significantly reduced the cataleptic effect of haloperidol and this effect warrants further examination. © 1997 Elsevier Science Ireland Ltd.

The effectiveness of β-blockers in the treatment of neuroleptic-induced akathisia (NIA) suggests that β-adrenergic overactivity is involved in the manifestation of NIA. As an approach to understanding this postulated overactivity, we investigated the β₂-receptor density on mononuclear blood cells in 21 patients suffering from NIA as well as in 12 patients without NIA. The β₂-receptor density in NIA-positive patients was significantly higer than that in NIA-negative patients (t = 2.84; p = .008). The NIA-positive patients were treated with 20 mg propranolol t.i.d. for 5 days. The β₂-receptor density in treatment responders did not differ significantly from that in non-responders. Our results indicate that β₂-receptors on mononuclear cells in patients with NIA may be of a certain degree of importance. With the prerequisites of replicability as well as correlation of this parameter with therapeutic success of β-blockers, it may be considered as a predictor for treatment response.

Although akathisia is most commonly associated with neuroleptic medication, few cases of paroxetine-induced akathisia have been reported. A review of the authors' charts (C.F.B., AX, S.N.G., and G.S.S.) was conducted to determine an estimated incidence for paroxetine-induced akathisia. Three cases of akathisia were reported in 67 patients treated with paroxetine. A case of akathisia secondary to paroxetine in an 18-year-old female is presented. Given the potential untoward effects of this syndrome, early diagnosis is essential. Clinical presentations and differential diagnoses are discussed.