Faculty Bibliography

This investigation reports pilot data on two points originally raised in the earliest reports of the efficacy of beta-blockers in akathisia: their potential utility in the akathisia of idiopathic Parkinson's disease and the possibility of determining a central vs. a peripheral site of action by comparing the time course of the effects of lipophilic and hydrophilic agents. Akathisia improved in 4 patients with idiopathic Parkinson's disease after low dose propranolol treatment. Six patients with neuroleptic-induced akathisia were treated with the hydrophilic beta-blocker nadolol. Effects on akathisia occurred, but evolved much more slowly than after treatment with lipophilic agents, such as propranolol and metoprolol, thus suggesting a central site of action

There have been several case reports of improvement in tardive dyskinesia (TD) after treatment with calcium-blocking agents. We have conducted prior single-blind (rater-blind) studies of verapamil and diltiazem and found a statistically significant improvement in TD with verapamil, and a small improvement that did not reach statistical improvement after diltiazem treatment. We now report a single-blind (rater-blind) study of a third calcium antagonist, nifedipine, in the treatment of TD. Nifedipine (30-60 mg/day) was administered to eight schizophrenic patients with TD. Mean AIMS scores on items 1-7 decreased from 12.9 +/- 2.0 (SD) at baseline to 10.8 +/- 2.7 after treatment (t = 3.66, p = 0.01). All subjects were able to tolerate the maximal dose of nifedipine without significant side effects. TD is known to be affected by drugs that affect dopamine neurotransmission. Several lines of pre-clinical and clinical evidence suggest interactions between the calcium antagonists and the CNS dopamine system and provide a possible explanation for the effects on TD seen with calcium antagonists

Recent studies have shown that the beta-blockers can be effective treatments for neuroleptic-induced akathisia. However, the relative contributions of beta-1 versus beta-2 blockade to the therapeutic effect of beta-blockers remains unclear. We treated nine patients who had neuroleptic-induced akathisia with low doses (25-100 mg/day) of the beta-blocker metoprolol. At these doses metoprolol causes selective blockade of beta-1 receptors. Seven patients improved after metoprolol; no further substantial changes were seen after subsequent treatment with propranolol. This finding suggests that neuroleptic-induced akathisia can be improved by selective beta-1 blockade

beta-Blockers, particularly propranolol, have been shown to be an effective treatment for neuroleptic-induced akathisia (NIA). To examine the relative contribution of beta-1 and beta-2 receptor blockade to the therapeutic effect of propranolol, we studied a beta-1 selective agent (low dose metoprolol) and a beta-2 specific blocker (ICI 118,551). Both agents ameliorated NIA. To further evaluate instruments for quantifying NIA we compared (a) two sets of clinical ratings during the metoprolol study and (b) clinical and electromechanical ratings of NIA during the ICI 118,551 study. The changes in clinical ratings of NIA after metoprolol were similar for most patients; however, the changes in electromechanical and clinical ratings after ICI 118,551 were similar in less than half of the patients studied

Neuroleptic-induced akathisia (NIA) is a relatively common side effect of neuroleptics, in which patients complain of a subjective sense of restlessness usually referable to the legs and have characteristic motor movements. This paper will review: 1) history of spontaneously occurring syndromes of pathologic restlessness and NIA, 2) the clinical significance of NIA, 3) issues concerning the diagnosis and quantification of NIA, 4) treatments of NIA and 5) possible future directions for research in this area. Special attention will be paid to newer treatments for this syndrome, specifically beta-blockers

To assess the role of blockade of beta-receptor subpopulations in the treatment of neuroleptic-induced akathisia (NIA), the specific beta 2-antagonist ICI 118,551 was compared to placebo in a double-blind study. After a baseline evaluation on placebo, patients were treated with ICI 118,551 or placebo. Five of six patients treated with ICI 118,551 showed improvements in NIA, while only one of four patients improved on placebo. Patients were then treated openly with propranolol, a mixed beta 1, beta 2-antagonist. Compared to ICI 118,551, no further improvement on objective measures of akathisia was seen on propranolol. Mean subjective assessments of NIA declined on propranolol, but changes were variable and not statistically significant