Extrapyramidal

What are extrapyramidal side effects?

Extrapyramidal side effects include dyskinesias; repetitive, involuntary, and purposeless body or facial movements. Parkinsonism may occur, involving cogwheel muscle rigidity, pill-rolling tremor and reduced or slowed movements. Akathisia involves motor restlessness, especially in the legs, and dystonias are muscle contractions causing unusual twisting of parts of the body, most often in the neck. These side effects are caused by the dopamine receptor antagonist action of antipsychotics.

What is the evidence for extrapyramidal side effects?

Overall prevalence rate

Moderate quality evidence suggests the overall prevalence rate of tardive dyskinesia is around 25%, with rates highest with first generation antipsychotic use and with longer duration of illness. Rates were lowest in Asian countries.

All antipsychotics versus placebo

Moderate quality evidence shows a small effect of fewer extrapyramidal side effects with clozapine than with placebo. Small effects of increased extrapyramidal side effects were reported with ziprasidone, paliperidone, and risperidone, and medium-sized effects were reported with lurasidone, chlorpromazine, zotepine, and haloperidol. No differences in extrapyramidal side effects were reported for sertindole, olanzapine, quetiapine, aripiprazole, iloperidone, amisulpride and asenapine when compared to placebo.

First versus second generation antipsychotics

Moderate to high quality evidence suggests fewer extrapyramidal side effects with second generation antipsychotics, in particular olanzapine and risperidone, when compared to first generation antipsychotic haloperidol. Fewer extrapyramidal side effects were reported with second generation antipsychotic clozapine when compared to first generation antipsychotic chlorpromazine. Moderate quality evidence suggests clozapine, olanzapine, and risperidone produce fewer extrapyramidal side effects than low-potency first generation antipsychotics.

Second generation antipsychotics

Moderate to high quality evidence suggests risperidone may be associated with more use of antiparkinson medication than clozapine (medium-sized effect), olanzapine, quetiapine, and ziprasidone (small effects). Ziprasidone may be associated with more use of antiparkinson medication than olanzapine (small effect) and quetiapine (medium-sized effect). Olanzapine may be associated with more use of antiparkinson medication than quetiapine (medium-sized effect), and aripiprazole may be associated with more use of antiparkinson medication than olanzapine (small effect). No differences were found between amisulpride and olanzapine, risperidone, or ziprasidone. No differences were found between aripiprazole and risperidone, or between clozapine and olanzapine or ziprasidone. Low quality evidence is unable to determine if there are differences between zotepine and clozapine.

Schizophrenia versus affective disorders

Moderate quality evidence suggests people with affective disorders treated with aripiprazole may show more akathisia than people with schizophrenia treated with aripiprazole. People with schizophrenia treated with olanzapine may show more parkinsonism than people with bipolar disorder treated with olanzapine.

Ethnic differences

Moderate to low quality evidence suggests people from China, Japan and Korea who are treated with antipsychotics may show a small increase in extrapyramidal side effects compared to people from other countries treated with antipsychotics. No differences were reported between Black and White populations.

November 2019

Last updated at: 2:03 am, 27th November 2019
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