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?

All antipsychotics versus placebo

Moderate quality evidence shows a small effect of fewer extrapyramidal side effects with clozapine than 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.

 

July 2017

Vitamin E

What is Vitamin E?

Vitamin E is a fat-soluble vitamin that plays a role as an antioxidant in the body. Vitamin E has been proposed as a treatment that may help alleviate tardive dyskinesia, a common side effect of antipsychotic medication.

What is the evidence for Vitamin E?

Moderate or moderate to low quality evidence suggests no benefit of Vitamin E for tardive dyskinesia, study retention or mental state.

 

June 2016

GABA agonists

What are GABA-acting medications?

GABA (gamma-aminobutyric acid) is a common neurotransmitter in the brain, and GABA-ergic neurons are thought to interact with antipsychotic medications, contributing to side effects such as tardive dyskinesia. GABA-acting medications, such as baclofen, progabide, or sodium valproate, may contribute to increasing the activity of GABA neurons, potentially leading to reduced medication side effects. Adjunct medications prescribed to treat side effects of antipsychotic medication may contribute to increasing adherence to these medications, and reduce the risk of psychotic relapse.

What is the evidence for GABA-acting medications?

Moderate quality evidence suggests no significant benefit of GABA-acting medications for mental state, tardive dyskinesia, or study attrition, and no differences between treatment and placebo in adverse effects.

 

June 2016

Beta blockers

What are beta blockers? 

Beta blockers can be prescribed in addition to standard antipsychotic regimes in order to target some side effects of these medications, including extrapyramidal symptoms such as akathisia (a type of restlessness, a common and early-onset side effect of many neuroleptics). Beta blockers are adrenergic beta receptor antagonists, inhibiting the action of neurotransmitters adrenaline/epinephrine and noradrenaline/norepinephrine on beta-receptors, ultimately influencing brain regions that control functions such as movement. Beta blockers have also been used to reduce the physical symptoms of anxiety in schizophrenia (for example, pounding heart, clammy hands, sweating), and have also been suggested to reduce aggression.

What is the evidence on beta blockers?

Moderate quality evidence suggests norepinephrine reuptake inhibitors atomoxetine and reboxetine may reduce depressive symptoms, but not positive or negative symptoms, in people with schizophrenia. Lower quality evidence suggests no benefit of beta blockers for improving extrapyramidal symptoms such as akathisia, or for reducing aggression.

 

 

June 2016

Cholinergic medication

What are cholinergic medications?

Cholinergic medications have been prescribed for tardive dyskinesia, which is a common side effect of antipsychotics, involving repetitive, involuntary movements most commonly occurring around the mouth and face. The cause of tardive dyskinesia is largely unknown, however some theories proposing the cause implicates brain cells that utilise the acetylcholine neurotransmitter. Older cholinergic medications (such as those included in this summary) can have adverse effects themselves, while newer compounds have less severe side effects, but they have not yet been studied in relation to tardive dyskinesia.

What is the evidence on cholinergic medications?

Moderate to low quality evidence suggests no benefit of cholinergic medications compared to placebo for tardive dyskinesia. There were also no benefits for global state, mental state, or adverse effects.

 

June 2016

Anticholinergic medications

How are anticholinergic medications used for schizophrenia?

Anticholinergics block the action of the neurotransmitter acetylcholine. Anticholinergic medications may have some utility for the treatment of side effects of antipsychotic medications, including movement disorders like akathisia (a type of restlessness, a common side effect of many neuroleptics), as well as excessive salivation. Adjunct medications prescribed to treat such side effects may contribute to increasing adherence to antipsychotic medications, and reduce the risk of psychotic relapse.

What is the evidence for anticholinergic medications?

Moderate quality evidence suggests small to medium-sized effects of greater improvement in hypersalivation with astemizole or propantheline over placebo, and no differences in adverse effects. There is moderate to low quality evidence for greater improvement in hypersalivation with propantheline over astemizole, with no differences in adverse effects.

 

July 2016

Treatments for movement disorders

What are movement disorders?

Movement disorders and extrapyramidal symptoms are common side effects of many antipsychotic medications. Extrapyramidal symptoms include tardive dyskinesia, a severe and chronic condition involving repetitive, involuntary movements, most commonly occurring around the mouth and face. Akathisia is another extrapyramidal symptom, and 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. These movements are typically bilateral and relatively symmetrical. Medications prescribed to treat the side effects of antipsychotic drugs increases adherence to antipsychotics, which reduces the risk of psychotic relapse.

What is the evidence for adjunctive therapies for movement disorders?

Moderate quality evidence suggests a large effect of 5-HT2A antagonists for improving akathisia symptoms when compared to placebo, with no differences between groups in study attrition or sedation. Moderate to low quality evidence suggests improved tardive dyskinesia with Pyridoxal 5 phosphate (Vitamin B6).

Moderate quality evidence suggests no benefit of GABA-acting medications, ceruletide or Vitamin E for tardive dyskinesia, although there may be greater deterioration of symptoms with placebo. Moderate to low quality evidence also suggests no benefit of cholinergic medications, and low quality evidence is uncertain of the benefit of other compounds such as noradrenergic or dopaminergic medications, benzodiazepines, evening primrose oil, insulin, lithium, oestrogen, or phenylalanine.

Also see the extrapyramidal side effects topic and the physical features movement disorders topic.

June 2016

Movement disorders

What are movement disorders? 

Movement disorders have been reported in people with schizophrenia, with tardive dyskinesia among the most commonly reported. This disorder is a ‘hyper-kinetic’ (excessive movement) disorder, characterised by jerky, involuntary movements, usually of the face and/or limbs. Parkinsonism is another movement disorder associated with schizophrenia, and is a ‘hypo-kinetic’ (reduced movement) disorder, characterised by slowness of movement and rigidity. Movement disorders are primarily associated with the use of antipsychotic medications, however they have also been reported in people who are antipsychotic-naïve.

What is the evidence for movement disorders in schizophrenia?

Moderate to high quality evidence suggests a large increase in the risk of dyskinesia and parkinsonism in people with schizophrenia compared to people without schizophrenia. There is also a small increase in this risk in first-degree relatives of people with schizophrenia. Moderate to high quality evidence suggests non-white ethnicity and the presence of early movement symptoms is associated with a small to medium-sized increase in the risk of tardive dyskinesia in people with schizophrenia. There was no effect of age, sex, or medication dose on this association. Moderate quality evidence suggests spontaneous movement disorder may occur in antipsychotic-naïve patients, with approximately 17% showing symptoms of parkinsonism, and 9% showing symptoms of dyskinesia.

 

March 2016

Psychomotor ability

What is psychomotor ability?

Psychomotor ability refers to a wide range of actions involving physical movement related to conscious cognitive processing. Psychomotor ability may be measured by accuracy or speed (reaction time). Examples of psychomotor tests include the Grooved Pegboard test, and the Purdue Pegboard test that measure visual-motor coordination. The Finger Tapping test requires study participants to place their dominant hand face-down and tap as quickly as possible. The task is repeated with the non-dominant hand and assesses motor speed, manual dexterity and lateralisation. The Digit Symbol Substitution test involves paired numbers and symbols. Participants are shown several numbers and asked to write the missing corresponding symbols as quickly as possible, measuring motor ability and attention. The Pursuit Rotor Motor task presents participants with a turntable with a dot in the centre that they must hold with a flexible metal wand as the turntable spins, measuring motor coordination and learning. The Star Mirror Tracing task asks participants to trace a star while only looking at their hand in the reflection of a mirror, assessing visual-motor learning.

What is the evidence for impaired psychomotor ability?

Compared to people without schizophrenia, moderate to high quality evidence suggests poor psychomotor ability in people with schizophrenia, including people with first-episode schizophrenia, or early onset schizophrenia (< 16 years old). Compared to people with affective psychoses such as bipolar disorder, moderate quality evidence suggests a small effect of poor psychomotor and mental speed in people with schizophrenia. Moderate to high quality evidence suggests a large effect of poor motor performance in people with schizophrenia and antisocial traits compared to people with antisocial traits without schizophrenia.

In general, high quality evidence suggests greater improvement in motor skills in people taking second generation antipsychotics compared to people taking first generation antipsychotics. Specifically, moderate to high quality evidence suggests people taking clozapine may show improvements in motor skills after treatment, while people taking olanzapine, quetiapine, risperidone or haloperidol show no improvements. High quality evidence suggests a small effect of better psychomotor skills in people with a psychotic disorder and a substance use disorder when compared to people with a psychotic disorder without a substance use disorder.

 

April 2016