A Double Blind Trial of Lithium Carbonate and Haloperidol in Huntington's Chorea

Abstract

Six patients with a family history of Huntington's chorea (HC) participated in a double blind crossover trial involving four treatments--lithium carbonate, haloperidol, lithium carbonate and haloperidol, and placebo. Each treatment was administered for three weeks and, at the end of each treatment period, assessments were made of chorea and a number of psychological variables. None of the treatments significantly affected chorea measurements. With regard to the psychological variables, the levels of irritability, the frequency of angry outbursts and depression did appear to be affected in some patients by the treatment. Three patients improved on a combination of lithium carbonate and haloperidol while the remaining three did not. Haloperidol alone significantly raised depression ratings above levels for other treatments including placebo. It is suggested that lithium carbonate and haloperidol together should be seriously considered in the treatment of HC when patients are excessively irritable and impulsive.

Dysregulation of Corticostriatal Connectivity in Huntington’s Disease: A Role for Dopamine Modulation

“…Haloperidol, a typical antipsychotic, is a potent antagonist of D2-like receptors with a slow kinetic dissociation and a high affinity for D 3 receptors (0.74 nM) followed by D 2 (1.55 nM) and D 4 receptors (5–9 nM) [325–327]. Haloperidol is effective in reducing chorea [328–330] and also has been used for treating episodes of psychosis, aggression, and impulsivity [331]. Severe side effects, such as akathisia, dystonia, tardive dyskinesia, and neuroleptic malignant syndrome, have limited its use [331–333].…”

An overview of psychiatric symptoms in Huntington’s disease

“…Haloperidol and lithium [92] Double blind, placebo-controlled crossover, randomized, 6 (four treatment groups: lithium, haloperidol, lithium and haloperidol, and placebo)…”

Pharmacological Management of Huntingtons Disease: An Evidence- Based Review

“…In male patients, crime rates are significantly increased compared to first degree relatives and controls [247]. Haloperidol was useful in a level-II study (double-blind, crossover in 6 patients) in treating irritability, aggressive outbursts, and depression [13]. Two small level-III studies on olanzapine [80,81] showed a significant improvement in the UHDRS psychiatric subscores depression, anxiety, irritability, and obsessions.…”

“…We found negative level-II trials on the somatostatin-depleting agent cysteamine [171], the methionine-enkephalin analogue FK 33-824 [172] and lithium [9,13,[173][174][175][176] (for lithium also exist lower evidence papers with different results [144,[177][178][179]). Piracetam [180,181] even worsened chorea in two level II trials of 1 day, respectively.…”

“…There is evidence from three level II [7][8][9] and three level III studies [10][11][12] that it may be effective in ameliorating HD-related chorea. In detail, haloperidol (2-80 mg/d; dosage was increased until chorea was suppressed) was effective in a single-blinded (videotapes presented to blinded observer) trial of 13 patients of unclear study duration [8], but failed to reduce chorea in six patients on 15 mg/d in a double-blind, crossover comparison to lithium [13]. However, a further single-blind, cross-over study [7] of 11 patients showed an equal efficacy of haloperidol compared to tetrabenazine with less severe adverse effects in the haloperidol group, although tardive dyskinesia complicated haloperidol therapy in three of 11 patients.…”