What is the role of dopamine D2 receptor antagonist therapy in the treatment of Tourette syndrome (TS) and other tic disorders?

Updated: May 30, 2019
  • Author: William C Robertson, Jr, MD; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP  more...
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In 1959, soon after its introduction, chlorpromazine was reported to dramatically improve tic severity. [156] Since then, several allocation randomized controlled trials with various neuroleptics (eg, haloperidol, fluphenazine, pimozide) have confirmed these initial results. [157] On average, tic severity declines by approximately 50-80% with neuroleptic treatment.

Neuroleptic drugs are the current standard in terms of efficacy in the treatment of tics. They can be effective at doses far below the usual treatment dose for psychosis, and most adverse effects are manageable with pharmacologic manipulations. Unfortunately, many patients do not tolerate acute adverse effects (most commonly sedation, weight gain, depression, lethargy, and akathisia), and prolonged treatment poses a small risk of tardive dyskinesia. Therefore, other treatments have been investigated.

Risperidone, olanzapine, [158] and ziprasidone have been shown to produce at least as much clinical effect as a classic neuroleptic comparator, with fewer adverse effects. [159, 160, 161] A small study of clozapine suggested little effect. [162] Small studies of the dopamine D2R partial agonist aripiprazole show that it is effective for tic suppression. [163, 164] RCT data are not yet available, however.

Metoclopramide is a D2 receptor antagonist that is usually used for nausea. A case series [165] and an RCT [166] suggest it treats tics with good short-term tolerability. However, long-term use of metoclopramide has been associated with tardive dyskinesia.

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