21st November 2023

Extrapyramidal Side Effects

Extrapyramidal side effects (EPSEs) are probably the most common disorders of motor control that you will see in MRCPsych Paper A questions. We’ll discuss each one in turn, but I’ll provide a general overview here.

The four EPSE’s are:

• Akathisia.
• Dystonia.
• Parkinsonism.
• Tardive dyskinesia.

In the literature, EPSEs are often attributed to the dopaminergic antagonism of antipsychotics (especially first generation) at the D2 receptors. However, it is worth noting that studies have shown that those with a diagnosis of schizophrenia who are medication naive have higher rates of EPSEs than the general populous (Rybakowski et al., 2014).

In terms of medication culprits, first generation antipsychotics (such as haloperidol) carry the highest risk. Of the second-generation agents, risperidone carries the highest risk, whereas clozapine very rarely causes EPSEs (Divac et al., 2014). EPSEs usually occur within a short time of commencing an antipsychotic (hours to weeks), other than tardive dyskinesia, which has a much more delayed onset (often years).

Akathisia

This is the feeling described by patients as ‘inner restlessness’, which is manifested by the patient through the motor system, e.g. by pacing foot stamping (Salem et al., 2017). Akathisia normally occurs within hours and weeks of commencing an antipsychotic.

To manage this, a reduction in dose or switch to an alternative antipsychotic can be trialled. Propranolol is also used to have a good effect on managing restlessness. Akathisia, however, is often recognised as the most difficult EPSE to definitively manage.

Dystonia

A dystonia is a sustained muscle contraction, which is dose-dependent, that is especially seen with the use of IM haloperidol. This increases muscle tone, which leads to an abnormal posture. It often occurs within the first 2-5 days following administration of the offending drug (Pasricha et al., 2006). Young males are especially at risk.

Common forms include:

• Torticollis  – The head turns to one side due to painful muscle spasms.
• Trismus  – Commonly known as lockjaw.
• Opisthotonus  – Arching of the back of the head and neck.
• Laryngeal dystonia  – Notoriously difficult to diagnose but can be life threatening. Look out for stridor, shortness of breath and the patient grasping their throat.
• Oculogyric crisis  – The eyes move in one direction, often upwards.

Management depends on the severity, but often, anticholinergic medication (such as procyclidine) is used; IM and IV forms act very rapidly and are used in emergency situations. Thought should be put into reducing the triggering anti-psychotic.

Parkinsonism

Symptoms of Parkinsonism include  – Akinesia, resting pill-rolling tremor, rigidity (often described as ‘lead-pipe’ or ‘cogwheel’) and bradykinesia, which is the slowing of movements (Jankovic, 2008).

Akinesia

Akinesia is often thought of as a subset of bradykinesia, and it is the absence of movement. It is often seen in patients with Parkinsonism as a loss of facial emotion with exam questions using the phrase, ‘mask like expression’ or ‘serpentine’ stare.

Tardive dyskinesia

Tardive dyskinesia is a later onset EPSE in which the patient gets involuntary movements of their body, often of the face (oro-facio-bucco lingual movements), but it can also affect the trunk and body (Caroff, 2020). Movements often include repetitive lip smacking, tongue protrusion and grimacing.

Tardive dyskinesia can be very distressing for patients, not only due to the stigma associated but also due to its painful nature. Oro-facio-bucco lingual movements may lead to issues with eating, drinking, and even speaking. Patients with long term exposure to antipsychotics are especially susceptible to tardive dyskinesia.

Management is to consider reducing/changing/stopping the offending antipsychotic if possible. Clozapine is a good alternative. Tetrabenazine, a VMAT-2 inhibitor, is licensed as an add-on for the management of tardive dyskinesia but is yet to see widespread clinical use.