| Extrapyramidal symptoms | |
|---|---|
| Other names | extrapyramidal manifestations; extrapyramidal side effects (EPSE) (when caused by drugs) |
| Specialty | Neurology |
Extrapyramidal symptoms (EPS) aresymptoms that arearchetypically associated with theextrapyramidal system of the brain. When such symptoms are caused bymedications or other drugs, they are also known asextrapyramidal side effects (EPSE). The symptoms can beacute (short-term) orchronic (long-term). They includemovement dysfunction such asdystonia (continuous spasms and muscle contractions),akathisia (may manifest as motor restlessness),[1]parkinsonism characteristic symptoms such asrigidity,bradykinesia (slowness of movement),tremor, andtardive dyskinesia (irregular, jerky movements).[2] Extrapyramidal symptoms are a reason why subjects drop out ofclinical trials ofantipsychotics; of the 213 (14.6%) subjects that dropped out of one of the largest clinical trials of antipsychotics (the CATIE trial [Clinical Antipsychotic Trials for Intervention Effectiveness], which included 1460 randomized subjects), 58 (27.2%) of those discontinuations were due to EPS.[3]
Extrapyramidal symptoms are most commonly caused bytypical antipsychotic drugs that antagonize dopamine D2 receptors.[2] The most commontypical antipsychotics associated with EPS arehaloperidol andfluphenazine.[4] Atypical antipsychotics have lower D2 receptor affinity or higher serotonin 5-HT2A receptor affinity which lead to lower rates of EPS.[5]
Other anti-dopaminergic drugs, like the antiemeticmetoclopramide, can also result in extrapyramidal side effects.[6] Short and long-term use of antidepressants such asselective serotonin reuptake inhibitors (SSRI),serotonin-norepinephrine reuptake inhibitors (SNRI), andnorepinephrine-dopamine reuptake inhibitors (NDRI) have also resulted in EPS.[7] Specifically,duloxetine,sertraline,escitalopram,fluoxetine, andbupropion have been linked to the induction of EPS.[7]
Other causes of extrapyramidal symptoms can include brain damage and meningitis.[8] However, the term "extrapyramidal symptoms" generally refers to medication-induced causes in the field of psychiatry.[9]
Since it is difficult to measure extrapyramidal symptoms, rating scales are commonly used to assess the severity of movement disorders. The Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), Abnormal Involuntary Movement Scale (AIMS), and Extrapyramidal Symptom Rating Scale (ESRS) are rating scales frequently used for such assessment and are not weighted for diagnostic purposes;[2] these scales can help clinicians weigh the benefit/expected benefit of a medication against the degree of distress which the side effects are causing the patient, aiding in the decision to maintain, reduce, or discontinue the causative medication(s).[citation needed]
Medications are used to reverse the symptoms of extrapyramidal side effects caused by antipsychotics or other drugs, by either directly or indirectly increasing dopaminergic neurotransmission. The treatment varies by the type of the EPS, but may involveanticholinergic agents such asprocyclidine,benztropine,diphenhydramine, andtrihexyphenidyl. Certain medications such asdopamine agonists are not used, as they may worsen psychotic symptoms to those taking neuroleptic drugs.
If the EPS are induced by anantipsychotic, EPS may be reduced by decreasing the dose of the antipsychotic or by switching from atypical antipsychotic to an (or to a different)atypical antipsychotic, such asaripiprazole,ziprasidone,quetiapine,olanzapine,risperidone, orclozapine. These medications possess an additional mode of action that is believed to mitigate their effect on thenigrostriatal pathway, which means they are associated with fewer extrapyramidal side-effects than "conventional" antipsychotics (chlorpromazine,haloperidol, etc.)[11]
Anticholinergic medications are used to reverse acute dystonia. If the symptoms are particularly severe, the anticholinergic medication may be administered byinjection into a muscle to rapidly reverse the dystonia.[9]
Certain second-generation antipsychotics, such as lurasidone and the partial D2-agonistaripiprazole, are more likely to cause akathisia compared to other second-generation antipsychotics.[12] If akathisia occurs, switching to an antipsychotic with a lower risk of akathisia may improve symptoms.[13]Beta blockers (likepropranolol) are frequently used to treat akathisia. Other medications that are sometimes used includeclonidine,mirtazapine, or evenbenzodiazepines. Anticholinergic medications are not helpful for treating akathisia.[9]
Medication interventions are generally reserved for cases in which withdrawing the medication that caused the pseudoparkinsonism is either ineffective or infeasible.Anticholinergic medications are sometimes used to treat pseudoparkinsonism, but they can be difficult to tolerate when given chronically.Amantadine is sometimes used as well. It is rare for dopamine agonists to be used for antipsychotic-induced EPS, as they may exacerbate psychosis.[9]
When other measures fail or are not feasible, medications are used to treat tardive dyskinesia. These include thevesicular monoamine transporter 2 inhibitorstetrabenazine anddeutetrabenazine.[9]
Extrapyramidal symptoms (also called extrapyramidal side effects) get their name because they are symptoms of disorders in theextrapyramidal system, which regulates posture and skeletal muscle tone. This is in contrast to symptoms originating from thepyramidal tracts.[citation needed]