Antipsychotics in the ER

Since the 1950's, antipsychotics have become effective treatment for positive and negative symptoms of psychosis. With the introduction of second generation antipsychotics there was some decrease in the extrapyramidal effects associated with these medications, however side effects, including potentially deadly, are still commonly seen in the ER. 
Antipsychotics bind and inhibit dopamine receptors, causing the varying effects of these medications. This is also the source of many of the adverse effects of the medications.     

• Major adverse reactions of antipyschotics
• QTc prolongation
• Neuroleptic Malignant Syndrome
• Movement Disorders

Prolonged QTc

First generation antipsychotics are more likely to cause prolonged QT, however second generation medications are also known to cause QT, and there is a dose relationship between the medication and QT prolongation risk. Many formulas are available to correct the QTc. Normal QTc should be <460 for females and 450 for males. Prolonged QTc can lead to Torsades de Pointes, a polymorphic ventricular tachycardia with a high risk of deterioration into ventricular fibrillation. 

Treatment is to stop any medications which may cause prolonged QT, and give magnesium regardless of current magnesium level. Potassium should also be repleated to at least 4.5. Temporary pacing may be necessary. Additionally, sodium bicarb can be used to treat intraventricular conduction delay or ventricular arrhythmias. 

Lower-risk medications for QTc prolongation is latuda, ziprasidone, and haldol. 

While antipsychotics do have risk of QT prolongation, use of benzodiazapines with antipsychotics has less risk of adverse events than either benzodiazapines alone or antipsychotics alone. Best case scenario would be to check an EKG prior to antipsychotic usage. 

Extrapyramidal Symptoms

Extrapyramidal symptoms are typically categorized into three patterns; early onset reversible, delayed-onset reversible, and irreversible syndromes. Prevalence ranges from 8-70% of patients, and although second generation antipsychotics were thought to decrease these symptoms, recent studies show there is no difference in prevalence between the generations. Symptoms can be distressing, painful, or even life-threatening. 

Early-onset symptoms typically start within hours to days of initiation of treatment, and include acute dystonia and akathisia. Acute dystonia is a hyperkinetic movement disorder with uncoordinated involuntary movements/contractions of the face, tongue, and upper extremities. Akathisia is the sensation of motor restlessness which may appear as increased agitation.  Akathisia can also present as a burning sensation in limbs. 

Delayed-onset symptoms include Parkinson-like tremors and slowed movements and Tardive Dyskinesia; choreiform movements of the face and extremities which the patient may not be aware of.  

Treatment for dystonia includes benadryl, promethazine, or benxotropine, which should be continued for 1-2 days. Propanolol or benzodiazapines can be used for akathisia. Parkinsonism symptoms can be treated with anticholinergics or amantadine. There is little data supporting any of the suggested treatments. 

Neuroleptic Malignant Syndrome

NMS typically presents as a 1-3 day progression of fever, muscular rigidity, autonomic dysfunction, and altered mental status, and is considered a gradual progression when compared to serotonin syndrome. . "Lead-pipe" or "cogwheel" rigidity is typically described, similar to parkinsonism. Commonly, patients present with elevated CK levels, leukocytosis, transaminitis, and metabolic acidosis, which sets NMS apart from serotonin syndrome (normally has no lab abnormalities). Up to 3% of patients treated with antipsychotics have an episode of NMS, and first generation antipsychotics have an increased risk, High-dose medcations, such as haldol "depot" dosing has a higher risk of NMS. 

Treatment is mostly supportive including removing restrains, cooling the patient, fluid resuscitation and symptomatic treatment. Pharmacotherapy has little proven efficacy. Benzodiazapines should be used initially and for mild to moderate symptoms. Dantrolene has been used previously, but based on theoretical pharmacology. Bromocriptine can also be given to overcome dopamine blockade, however is only an oral medication.