Extra-Pyramidal Symptoms (EPS) refers to involuntary motor movement side effects that can result from antipsychotic use. EPS is generally less likely to occur with second generation antipsychotic medications (Risperdal, Seroquel, Abilify, Geodon, Zyprexa, Latuda) compared to first generation antipsychotic medications, especially the high potency ones (Haldol, Prolixin, Trilafon). It is important to monitor for EPS, given that it can be serious and cause significant impairment. EPS worsens with increased dose of medication and with long-term use of an antipsychotic medication.
The Abnormal Involuntary Movement Scale is a standardized tool for assessing for EPS side effects in patients. Here is a link with instructions on how to conduct the assessment (typically takes 10 minutes), how to score it and a pdf of the scale.
One useful way to distinguish the types of EPS is to remember them in the time frame that they usually present:
| Type | Description | Time | Treatment |
| Dystonia | Tongue swelling, jaw locking, oculogyric crisis, emergency situation | Minutes to hours | IM benztropine or IM diphenhydramine |
| Akathisia | Internal feeling of restlessness | Days to weeks | Propranolol, Benzodiazepines |
| Parkinsonism | Shuffling gait, cogwheeling, bradykinesia, masked facies | Weeks to months | Amantadine, diphenhydramine |
| Tardive dyskinesia | Stereo-typed movements, lip smacking | Months to years | Valbenazine
(Ingrezza) |
Propranolol (Inderal) is a beta-blocker that can be helpful for akathisia with a typical dose range of 10-40 mg bid-tid. It should be dosed bid-tid for best effect. Side effects include hypotension, dizziness, and sedation. It can also be useful as an adjunctive medication for anxiety.
Benztropine (Cogentin) is an anti-cholinergic medication that can be helpful for neuroleptic-induced parkinsonism. It should be dosed bid because it has a short half-life. Starting dose is 0.5 mg bid and can increased as needed and tolerated to 2 mg bid. Side effects to monitor for include: confusion, sedation, constipation, dry mouth, urinary retention, and blurred vision. For this reason, benztropine should be avoided with low potency neuroleptic medications, to avoid additive anti-cholinergic side effects. Another commonly used anti-cholinergic medication is trihexyphenidyl (Artane), with a typical range of 5-15 mg dosed TID. Anticholinergic medications are not typically helpful for akathisia.
Amantadine is a dopamine agonist that can be used to treat neuroleptic-induced parkinsonism. Starting dose is 100mg bid with a max of 400mg/day. It is generally well tolerated and is associated with less memory impairment than anti-cholinergic medications. Primary side effects include: nausea, dry mouth, dizziness, and tremor.
IM diphenhydramine (Benadryl) can be used to treat acute dystonia. Oral diphenhydramine 25-100 mg can be helpful for neuroleptic-induced parkinsonism. Primary side effects include sleepiness, dry mouth and decreased motor coordination. It is available over the counter.
Tardive dyskinesia (TD) can be tricky. Initially it can improve if the dose of the neuroleptic medication is increased but overall it worsens with increases in dose. If the medication is discontinued, 1/3 of patients get better, 1/3 have no real change, and 1/3 get temporarily worse. The best option is to discontinue the medication and change to a lower potency, newer antipsychotic medication. Risk factors for TD include being female, older, smoking and being African American. Approximately 15% of patients taking long-term high potency neuroleptics will develop TD.
The FDA recently approved a medication for the treatment of TD, which up until now there was no treatment for. Valbenazine (Ingrezza) is a highly selective vesicular monoamine transporter 2 inhibitor. It is dosed as 80mg once per day. Side effects include sleepiness and OT prolongation. It is therefore important to monitor an EKG on patients taking valbenazine. It allows patients to potentially continue on a medication at a dose that is helpful for their psychotic symptoms without having to change medication or reduce the dose to treat their side effects.
The goal of this brief overview is to provide some baseline information on monitoring for, differentiating, and treating EPS side effects for medications that might be used in the primary care setting.