# 132 - Extrapyramidal symptoms

# Extrapyramidal symptoms

126
The Maudsley® Prescribing Guidelines in Psychiatry
CHAPTER 1
ANTIPSYCHOTIC ADVERSE EFFECTS
Extrapyramidal symptoms
The EPS associated with antipsychotic medication can be stigmatising, distressing, 
potentially disabling and act as a disincentive to taking medication.1,2 EPS are commonly overlooked and underdiagnosed or misdiagnosed in clinical practice.3,4 These 
movement disorders tend to be dose-­related and are less likely to occur with SGAs, 
particularly clozapine, olanzapine, quetiapine and aripiprazole,2,5 compared with FGAs 
such as haloperidol. Generally it is agreed that the greater use of SGAs has led to a 
reduction in the frequency of EPS,6 although the prevalence of EPS of any description 
in community samples may exceed 30%.7 The incidence of EPS is often steeply dose-­
related for most drugs (clozapine and quetiapine are possible exceptions) and this relationship extends beyond the licensed dose range for some drugs.8
Patients who experience one type of EPS may be more vulnerable to developing 
­others.9 Substance misuse increases the risk of dystonia, akathisia and TD,10,11 and there 
is some evidence for an association between alcohol use and akathisia.12,13 Vulnerability 
to EPS may be partly genetically determined.14–16
Establishing the prevalence of antipsychotic-­induced EPS is problematic, given that similar movement disorders may be seen in never-­medicated patients with schizophrenia.17–19 
In one study of such patients at first episode, 1% had dystonia, 8% parkinsonian symptoms and 11% akathisia.19 Parkinsonian symptoms and other motor abnormalities in this 
context may be associated with cognitive impairment19,20 and poor long-­term psychosocial 
functioning.21 In another study of never-­treated patients with established psychotic illness, 
9% exhibited spontaneous dyskinesias and 17% parkinsonian symptoms.22 Table 1.28 
details the most common EPSEs.

Table 1.28  Most common extrapyramidal side effects.
Dystonia (uncontrolled
muscular spasm)
Pseudoparkinsonism
(bradykinesia, tremor, muscle rigidity, 
etc.)
Akathisia
(restlessness)23
Tardive dyskinesia (TD)
(abnormal involuntary movements)
Signs and 
symptoms24
■
■Muscle spasm in any part of the 
body, e.g.
■
■eyes rolling upwards (oculogyric 
spasm)
■
■head and neck twisted to the 
side (torticollis)
■
■The patient may be unable to 
swallow or speak clearly. In extreme 
cases, the back may arch or the jaw 
dislocate.
■
■Acute dystonia can be both painful 
and very frightening
■
■Tremor and/or rigidity
■
■Bradykinesia (decreased facial expression, 
flat monotone voice, slow body 
movements, inability to initiate 
movement)
■
■Bradyphrenia (slowed thinking)
■
■Salivation
■
■Pseudoparkinsonism can be mistaken for 
depression or negative symptoms of 
schizophrenia
■
■A subjectively unpleasant state of inner 
restlessness with a desire or compulsion to 
move23,25
■
■Foot stamping when seated
■
■Constantly crossing/uncrossing legs
■
■Rocking from foot to foot when standing
■
■Constantly pacing up and down
■
■Akathisia can be mistaken for psychotic 
agitation and has been linked with suicidal 
ideation26 and aggression towards others27
■
■A wide variety of movements can 
occur,28 such as:
■
■lip smacking or chewing
■
■tongue protrusion (‘fly catching’)
■
■choreiform hand movements 
(‘piano playing’)
■
■dystonic and choreoathetoid 
movements of the limbs
■
■Severe orofacial movements can lead 
to difficulty speaking, eating or 
breathing. Movements are worse 
when under stress.
Rating scales (see 
Martino et al. 2023)29
■
■No specific scale
■
■Small component of general EPS 
scales
■
■Simpson–Angus EPS Rating Scale30
■
■Barnes Akathisia Rating Scale3,31
■
■Abnormal Involuntary Movement 
Scale32,33
Prevalence
■
■Approximately 10%34 but more 
common:35
■
■in young males
■
■in those who are 
antipsychotic-­naïve
■
■with high-potency medications 
(e.g. haloperidol)
■
■Dystonic reactions are rare in the 
elderly
■
■Approximately 20%36 but more common 
in:
■
■elderly females
■
■those with pre-­existing neurological 
damage (head injury, stroke, etc.)
■
■Wide variation but approximately 25%37 
for acute akathisia with FGAs, lower with 
SGAs
■
■The relative liability of individual 
antipsychotic medications for akathisia is 
uncertain,2 but there is consensus that the 
incidence is lowest for olanzapine, 
quetiapine and clozapine38,39
■
■5% of patients per year of antipsychotic exposure.40 More common in 
respect to:41
■
■age
■
■affective illness
■
■schizophrenia
■
■higher doses
■
■acute EPS early in treatment
■
■Lower incidence in those on SGAs.42,43 
TD may be associated with neurocognitive deficits.44
(Continued)

Table 1.28  (Continued)
Dystonia (uncontrolled
muscular spasm)
Pseudoparkinsonism
(bradykinesia, tremor, muscle rigidity, 
etc.)
Akathisia
(restlessness)23
Tardive dyskinesia (TD)
(abnormal involuntary movements)
Time taken to 
develop
■
■Acute dystonia can occur within 
hours of starting antipsychotic 
medication (minutes if the IM or IV 
route is used)
■
■TD occurs after months to years of 
antipsychotic treatment
■
■Days to weeks after the start of 
antipsychotic medication or an increase in 
dose
■
■Acute akathisia occurs within hours to 
weeks of starting antipsychotic medication 
or increasing the dose
■
■Akathisia that has persisted for several 
months or so is called ‘chronic akathisia’. 
Tardive akathisia tends to occur later in 
treatment and may be exacerbated or 
provoked by antipsychotic dose reduction 
or withdrawal.23
■
■Months to years
■
■The proportion of cases showing 
reversibility on cessation of antipsychotic medication is unclear and may 
partly depend on age28
Treatment
■
■Anticholinergic drugs 
given orally, IM or IV 
depending on the severity of 
symptoms35
■
■Remember the patient may be 
unable to swallow
■
■Response to IV administration will 
be seen within 5 minutes
■
■Response to IM administration takes 
around 20 minutes
■
■TD may respond to ECT45,46
■
■Where severe symptoms do not 
respond to simpler measures 
including switching to an 
antipsychotic with a low propensity 
for EPS, botulinum toxin may be 
effective47,48
■
■Several options are available depending 
on the clinical circumstances:
■
■Reduce the antipsychotic dose
■
■Change to an antipsychotic medication 
with a lower propensity for pseudoparkinsonism (see section on relative 
liability of antipsychotic medications 
for adverse effects)
■
■Prescribe an anticholinergic. The 
majority of patients do not require 
long-­term anticholinergic agents. Use 
should be reviewed at least every 
3 months. Do not prescribe at night 
(symptoms usually absent during 
sleep).
■
■Reduce the antipsychotic dose
■
■Change to an antipsychotic drug with 
lower propensity for akathisia (see sections 
on akathisia and relative liability of 
antipsychotic medications for adverse 
effects)
■
■A reduction in symptoms may be seen 
with25,49,50 low-­dose propranolol, 
30–80mg/day; clonazepam (low dose); 
5HT2 antagonists such as cyproheptadine,46 mirtazapine,49 trazodone,51,52 
mianserin53 and cyproheptadine46 may 
help, as may possibly diphenhydramine54
■
■Note that all of the above medications are 
unlicensed for this indication
■
■Anticholinergics are generally unhelpful 
unless possibly if akathisia is part of a 
general EPS spectrum55,56
■
■Stop anticholinergic if prescribed
■
■Reduce dose of antipsychotic 
medication
■
■Change to an antipsychotic with lower 
propensity for TD;57–60 note that data 
are conflicting61,62
■
■Clozapine is the antipsychotic most 
likely to be associated with resolution 
of symptoms.63,64 Quetiapine may also 
be useful in this regard.65
■
■Both valbenazine66 and deutetrabenazine67–69 have a positive risk–benefit 
balance as add-­on treatments.67,70 
There is also some evidence for 
tetrabenazine and Ginkgo biloba71 as 
add-­on treatments. For other 
treatment options,72,73 see the review 
by the American Academy of 
Neurology74 and the section on 
treatment of TD in this chapter.