EXTRAPYRAMIDAL SIDE EFFECTS
Damn those antipsychotics
Extrapyramidal Side Effects (EPS) are an unusual group of side effects caused by antipsychotic medications. The underlying cause is a high ratio of acetylcholine (ACh) relative to dopamine (DA) in the nigrostriatal tract. By blocking dopamine, antipsychotics let ACh become comparatively elevated. EPS only occurs after taking antipsychotics (or Metoclopramide, a dopamine blocker). There aren’t any organic illnesses that cause EPS. This is a chemical imbalance in a single location in the brain: the nigrostriatal tract. You see, the nigrostriatal tract is like a see-saw, with DA on one side and ACh on the other. Antipsychotics treat psychosis by blocking D2 receptors in the mesolimbic and mesocortical tracts. But their impact isn’t just limited to those two pathways -- they block DA all over the brain, including the nigrostriatal tract. Blocking DA there tips the chemical see-saw in favor of ACh. Treatment typically consists of anticholinergics (ones that cross the BBB) to bring the ACh levels down alongside the lowered DA levels. But keep in mind that not all antipsychotics are created equal.
The typicals block lots of dopamine (D2), but relatively little serotonin (5HT2). The atypicals block serotonin quite well, but don’t bother the dopamine as much. Therefore, typical antipsychotics cause a lot of EPS.
Among the typicals, the high-potency drugs like Haloperidol and Fluphenazine block an especially high number of D2 receptors. For that reason, Haloperidol and Fluphenazine are implicated in the majority of cases of EPS.
The low-potency drugs (Chlorpromazine) and the -DONES (Risperidone) are also capable of causing EPS.
The -PINES (Olanzapine) rarely cause EPS.
Dystonia (hours) is a sudden, but sustained, muscle contraction. Young males are especially vulnerable to Dystonia. I’ve only seen a severe case of dystonia once, and it was in a young man with torticollis. Torticollis is a type of dystonia where the neck muscles contract and twist to one side. It’s incredibly painful. Dystonia can also occur in the wrist (writer’s cramp), eye muscles (oculogyric crisis) and the eyelid muscles (blepharospasm). It can occur anywhere in the body. The most dangerous place to get dystonia is the larynx, as sustained contraction of this tube will suffocate you. Prevent that with early intubation. Treat dystonia with Benztropine or Trihexyphenidyl.
Pseudoparkinsonism (weeks) is the drug-induced onset of Parkinsonian symptoms (cogwheel rigidity, tremor, shuffling gait, stooped posture). The patient’s substantia nigra would look normal under a microscope, unlike with regular Parkinson’s. Do NOT treat this with L-DOPA, that will exacerbate the patient’s psychosis! The whole point of antipsychotics is to block DA, remember? Instead of modulating the DA, modulate their ACh with anticholinergics like Benztropine or Trihexyphenidyl.
Akathisia (weeks) is inner restlessness. One doctor told me it’s “the intense urge to run out of the room.” The patient will tap their feet and wring their hands. The pathophysiology for akathisia isn’t well understood. But treatment with Propranolol has been shown to help.
Tardive Dyskinesia (years) is a permanent side effect from taking antipsychotics for many, many years. It causes dyskinesia (duh), usually in the form of lip smacking and tongue athetosis. They look a bit like rabbits munching on food. Once considered permanent, a new promising drug called Valbenazine (a VMAT inhibitor) may have some curative properties. In addition to starting Valbenazine you should also switch antipsychotics to a less offensive class, like the -PIPs or -PINEs.
Neuroleptic Malignant Syndrome is a rare, but lethal, form of EPS. Their vital signs skyrocket, they become confused, and their muscles become rigid. The onset takes a few days (unlike the rapid Serotonin Syndrome). NMS = Not Much Shaking (tremors and hyperreflexia are seen in the similar Serotonin Syndrome). To treat, stop the Antipsychotic A$AP Rocky and give Dantrolene. See the dedicated page on induced vital sign dysregulation.
