Extrapyramidal side effects- Management

Background

Extrapyramidal side effects (EPSE) and movement disorders can manifest as several symptoms, detailed in the tables below. It is important that staff are aware of the clinical features and treatments for the different EPSE symptoms.

All antipsychotics have the potential to cause EPSE but it is more common with first generation antipsychotics (e.g. flupentixol, haloperidol) and the effect tends to be dose related. Caution should be used in prescribing other medication likely to cause EPSE such as sodium valproate, lithium and some antidepressants and the patient should be monitored closely for additive effects.

Following initiation of an antipsychotic patients should be monitored for emergence of EPSEs on a weekly basis and for 2 weeks after target dose reached. After dose increases patients should be monitored for 2 weeks.

Akathisia

Akathisia - A state of inner restlessness, with a strong desire/compulsion to move
Clinical features	- Foot stamping when seated - Crossing/uncrossing legs - Rocking from foot to foot - Pacing up and down - Akathisia may be mistaken for psychotic agitation and has been linked with suicidal ideation and aggression towards others
Rating scales	Barnes akathisia scale (appendix 1)
Prevalence	Approximately 25%, less with second generation antipsychotics in decreasing order; aripiprazole, lurasidone, risperidone, olanzapine, quetiapine and clozapine.
Time taken to develop	Occurs within hours to weeks of starting antipsychotics or increasing the dose. Tardive akathisia can take longer to develop and persist after antipsychotics have been withdrawn
Treatment	Depending on the clinical circumstances; - Reduce antipsychotic dose - Change to an antipsychotic with a lower propensity for akathisia - Anticholinergics (e.g. procyclidine) are usually ineffective - Benzodiazepines can be used short term during initiation - The following drugs may reduce akathisia (all unlicensed for this indication- see Maudsley for dosing); o Propranolol o Clonazepam (low dose) o H₂antagonists e.g. Mirtazapine, trazodone The Maudsley- Practice guidelines for physical health conditions in psychiatry has a good flow chart showing treatment options (Athens login required)

Dystonia

Dystonia - Uncontrolled muscular spasm in any part of the body
Clinical features	- Abnormal face and body movements - Oculogyric crisis (eyes rolling upwards) - Torticollis (head and neck twisting to the side) - Inability to swallow or speak clearly - In extreme cases, back may arch or jaw dislocate
Rating scales	No specific scale
Prevalence	Approximately 10% but more common; - In young males - In neuroleptic naïve - With high potency antipsychotics Rare in the elderly
Time taken to develop	Can occur within hours of starting antipsychotics (minutes if given via IM or IV)
Treatment	Anticholinergic drugs given PO, IM or IV depending on the severity of the symptoms; - Example PO anticholinergic: procyclidine 2.5mg three times daily, increased in steps of 2.5mg-5mg daily if required, up to maximum 30mg daily in 2-4 divided doses ^[3] - For procyclidine IM dosing please consult the BNF. The maximum IM procyclidine dose is 20mg daily ^[4]but in acute crisis doses of up to 30mg can be used. - Elderly patients may be more susceptible to the anticholinergic effects of procyclidine and a reduced dosage may be required - Response to IM takes ~20 minutes - If after 3 doses of IM, symptoms have not resolved then patient should be transferred to acute care - Remember: patient may be unable to swallow Reduce dose or switch to an antipsychotic with lower propensity

Tardive dyskinesia

Tardive Dyskinesia – Abnormal movements
Clinical features	- Lip smacking or chewing - Tongue protrusion ‘fly catching’ - Pill rolling or piano playing (choreiform hand movements) - Pelvis thrusting - Severe orofacial movements can lead to difficult speaking, eating or breathing. Symptoms can worsen under stress.
Rating scales?	Abnormal Involuntary Movement Scale (AIMS) (appendix 2)
Prevalence	5% of patients per year of antipsychotic exposure. More common in; - Older age - Affective illness - Those who have had acute EPS early in treatment - Genetic predisposition - Length of exposure to antipsychotics
Time taken to develop	Months to years. Approximately 50% of cases are reversible
Treatment	Depending on the clinical circumstances; - Stop anticholinergic if prescribed - Reduce dose of antipsychotic - Change to an antipsychotic with lower propensity for tardive dyskinesia - Clozapine is the antipsychotic most likely to be associated with resolution of symptoms, quetiapine may also be useful. - Tetrabenazine is licensed for the treatment of TD, starting at 12.5mg and titrating to 25-75mg/day.

Pseudoparkinsonism

Pseudoparkinsonism
Clinical features	- ‘mask like’ face - Resting tremor - Rigidity - Cogwheeling - Bradykinesia - Bradyphenia
Rating scales	Simpson-Angus EPS Rating Scale (appendix 3)
Prevalence	Approximately 20%. More common in: - Elderly females - Those with pre-existing neurological damage
Time taken to develop	Days to weeks after initiation or dose changes
Treatment	Depending on the clinical circumstances; - Consider cautious dose reduction of causative agent - If side effects persist, consider switching to an antipsychotic with lower propensity to cause parkinsonism (aripiprazole, quetiapine, olanzapine, clozapine) - Prescribing an anticholinergic, monitoring for side effects (dry mouth, constipation, urinary retention, cognitive impairment). Review use regularly. Example agents: procyclidine 2.5mg three times daily, increased in steps of 2.5mg-5mg daily if required, up to maximum 30mg daily in 2-4 divided doses ^[3] - After 3 months should be gradually withdrawn, to prevent cholinergic rebound, and restarted if symptoms reappear ^[5]

References

[1] Taylor, D. et al.The Maudsley Prescribing Guidelines in Psychiatry 12^th Edition; 2015

[2] Taylor, D. et al. The Maudsley Practice Guidelines for Physical Health Conditions in Psychiatry. 2021.

[3] BNF

[4] Summary of Product Characteristics. Kemadrin 5mg/ml solution for injection. [Accessed 23/12/21]

[5] Psychotropic drug directory 2020/21. Stephen Bazire.