People with bipolar disorder often have increased rates of co-occurring disorders. The neurotransmitter dopamine may be dysfunctional in both disorders. Moreover, medications used to treat bipolar disorder can induce Parkinson’s symptoms including bradykinesia, resting tremor, rigidity, and postural instability.

What is the evidence for Parkinson’s disease?

Moderate quality evidence suggests a medium-sized increased risk of Parkinson’s disease in people with bipolar disorder compared to people without the disorder. The risk is higher in studies with follow-up periods of less than nine years than in studies with follow-up periods of more than nine years.

October 2021

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Catatonia was originally categorised as a subtype of schizophrenia, but it is found in people with other medical, neurological, and psychiatric disorders, including bipolar disorder. Catatonia is characterised by repetitive non-goal-directed movements or goal-directed movements that are executed in an idiosyncratic way, often affecting gait. Other forms of catatonia include immobility, mutism, staring, and rigidity. Tardive dyskinesia is a ‘hyper-kinetic’ (excessive movement) disorder, characterised by jerky, involuntary movements, usually of the face and/or limbs. Parkinsonism is another common movement disorder associated with schizophrenia and is a ‘hypo-kinetic’ (reduced movement) disorder, characterised by slowness of movement and rigidity. These movement disorders are associated with antipsychotic medications but can arise independent of medication status.

What is the evidence for movement disorders in people with bipolar disorder?

Moderate to low quality evidence finds the prevalence of abnormal involuntary movements in people with bipolar disorder is between 7% and 14%, while catatonic symptoms are found in around 20% of patients.

February 2022

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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, but can also be found in people with schizophrenia who have never taken antipsychotics and in their relatives.

What is the evidence for extrapyramidal side effects?

Overall prevalence rate

Moderate quality evidence finds the overall prevalence of extrapyramidal symptoms in people taking antipsychotics is around 37%. Parkinsonism prevalence is 20%, akathisia prevalence is 11%, and tardive dyskinesia prevalence is 7-25%. The rates of tardive dyskinesia is 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.

Please also see the treatment topic for movement disorders.

February 2022

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Movement disorders and extrapyramidal symptoms are common side effects of many antipsychotic medications. They can also be apparent in people with schizophrenia who are have never taken antipsychotic medications and in their relatives. Extrapyramidal symptoms include tardive dyskinesia, a severe and chronic condition involving repetitive, involuntary movements, most commonly occurring around the mouth and face. Akathisia is characterised by a feeling of restlessness and movements such as shuffling of the legs, pacing, rocking from foot to foot, or the inability to sit down or stand still. Dystonia involves muscular spasms and abnormal postures. Medications prescribed to treat the side effects of antipsychotic drugs increase adherence to antipsychotics, which reduces the risk of psychotic relapse.

What is the evidence for medications for movement disorders?

For tardive dyskinesia, moderate to low quality evidence finds large benefits over placebo of the hormone insulin, the antipsychotic promethazine, and pyridoxal 5 phosphate (vitamin B6). There were medium-sized benefits over placebo for the anxiolytic buspirone, the cognitive enhancer/stimulant pemoline, and the alkaloids dihydrogenated ergot alkaloid and L-Stepholidine. There were small benefits over placebo for GABA-acting medications, branched-chain amino acids, enzyme VMAT2 inhibitors, ginkgo biloba, and the antiepileptic levetiracetam. There was a medium to large benefit of the antidepressant isocarboxazid over the anticholinergic procyclidine.

There were no significant benefits for tardive dyskinesia of ceruletide, vitamin E, cholinergic medications, noradrenergic or dopaminergic medications, benzodiazepines, evening primrose oil, lithium, oestrogen, the antidepressants selegiline and ritanserin, melatonin, the antihistamine cyproheptadine, the alkaloid papaverine, the cognitive enhancer piracetam, eicosapentaenoic acid derivative, and the antiepileptic levetiracetam.

For akathisia, moderate quality evidence finds a large benefit of 5-HT2A antagonists over placebo, with no differences in sedation levels. There was no benefit of eicosapentaenoic acid derivative for akathisia. For dystonia, moderate to low quality evidence finds a small benefit of eicosapentaenoic acid derivative over placebo.

For catatonia, only one small study assessed the effects of benzodiazapines and found no benefit over placebo.

February 2022

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Catatonia was originally categorised as a subtype of schizophrenia, but it is found in people with other medical, neurological, and psychiatric disorders. Catatonia is characterised by repetitive non-goal-directed movements or goal-directed movements that are executed in an idiosyncratic way. Other forms of catatonia include immobility, mutism, staring, and rigidity. Tardive dyskinesia is a ‘hyper-kinetic’ (excessive movement) disorder, characterised by jerky, involuntary movements, usually of the face and/or limbs. Parkinsonism is another common movement disorder associated with schizophrenia and is a ‘hypo-kinetic’ (reduced movement) disorder, characterised by slowness of movement and rigidity. These movement disorders are associated with antipsychotic medications but can arise independent of medication status.

What is the evidence for movement disorders in schizophrenia?

Moderate quality evidence finds the overall prevalence of extrapyramidal symptoms in people with schizophrenia taking antipsychotics is around 37%. Parkinsonism prevalence is 20%, akathisia prevalence is 11%, catatonia prevalence is 10%, and tardive dyskinesia prevalence is 7%. Non-white ethnicity and the presence of early extrapyramidal symptoms is associated with a small to medium-sized increase in the risk of tardive dyskinesia in patients treated with antipsychotics. There were no moderating effects of age, sex, or medication dose.

Moderate to high quality evidence finds around 17% of people with schizophrenia who are antipsychotic-naïve show symptoms of parkinsonism, and 9% show symptoms of dyskinesia. This corresponds to a large increase in the risk of dyskinesia and parkinsonism when compared to controls. There was also a small increase in these symptoms in first-degree relatives of people with schizophrenia.

February 2022

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