FDA Indications:

• It is for schizophrenia, schizoaffective, and other conditions presenting with symptoms of psychosis. Prochlorperazine can be used to treat both acute psychotic episodes and chronic mental illnesses. As a first-generation antipsychotic, the drug is better at treating positive symptoms than negative ones, including delusions, hallucinations, agitation, and disorganized speech and behavior.[1]      
• To treat nausea and vomiting (Post-chemotherapy, post-radiation therapy, pre- and post-operative setting, and other conditions). One review concluded that prochlorperazine was as equally effective as metoclopramide, ondansetron, promethazine, and droperidol in the emergency department (ED). Side effects for all the medications studied were generally mild.[2]

Non-FDA Indications

• Migraine
  • For adult migraines, the American Headache Society recommended prochlorperazine as well as metoclopramide and sumatriptan as first-line medications in the ED for treating migraines.[3]    
  • For pediatric migraine, ED physicians often prescribe a combination of a nonsteroidal anti-inflammatory drug and a dopamine antagonist.[4] One study examined three dopamine antagonists (prochlorperazine, metoclopramide, and promethazine) and compared their effectiveness with one another. Researchers found prochlorperazine to be the most effective in reducing the need for opioids and reducing pain by at least 50%.[5] The authors in another study confirmed that prochlorperazine was superior amongst dopamine antagonists but found that adding diphenhydramine (antihistamine) to a dopamine antagonist increased the chances of an ED revisit.[4]  

As a first-generation antipsychotic, prochlorperazine mainly blocks D2 dopamine receptors in the brain. It can also block histaminergic, cholinergic, and noradrenergic receptors.[1] One study also found that prochlorperazine inhibits the P2X7 receptor in human macrophages, but not in mouse cells, preventing a calcium ion influx.[6] This mechanism was independent of dopamine antagonism.  

Prochlorperazine administration can be oral, parenteral, intramuscular, and rectal.[1] All four routes can be given to control nausea and vomiting. For nausea and vomiting pre- and post-surgery, the intramuscular and parenteral routes are both viable options. For psychiatric conditions, the administration can be via both intramuscular and oral routes. For headaches, parenteral is the route used.[2]

As a first-generation antipsychotic, prochlorperazine can cause a variety of adverse effects.[1] Significant extrapyramidal symptoms, including acute dystonia, tardive dyskinesia, Parkinsonism, akathisia, and neuroleptic malignant syndrome. Anticholinergic side effects include anorexia, blurred vision, constipation, dry mucosa, and urinary retention. Antihistaminic side effects (blockage of H1 receptor) include sedation. Prochlorperazine can also lower the seizure threshold. It can also lead to prolonged QTc interval and cause other cardiac conduction abnormalities. Antiadrenergic effects (blockage of the alpha1-adrenergic receptor) can lead to orthostatic hypotension. Due to dopamine blockade in the tuberoinfundibular tract, hyperprolactinemia, amenorrhea, breast enlargement, and sexual dysfunction may also occur.[1]

Leukopenia, agranulocytosis, cholestatic jaundice, and fatty liver are other possible but rare side effects. A rare but very severe condition that can result from any antipsychotic use is the neuroleptic syndrome. Symptoms occur over 24 to 72 hours and present with elevated vitals, agitation, confusion, severe muscle rigidity, increased white blood cell count, increased creatinine phosphokinase concentrations, abnormal liver function tests, myoglobinuria, and acute renal failure.[1]

Prochlorperazine may also have a negative effect on melanocytes. In one in-vitro study, the presence of the drug correlated with decreased cell viability as well as reduced melanin content and tyrosinase activity.[7]     

Prochlorperazine may have significant adverse effects on children. One study from 2009, examining treatment modalities for pediatric nausea and vomiting, noted that side effects of prochlorperazine are high in children; therefore, patients under two years of age should not use it, and patients over two years old should consider alternatives such as ondansetron (5-HT3 receptor antagonist).[8] A review/meta-analysis from 2016 examined 49 previous studies and recorded pediatric side effects from dopamine antagonist use. Sedation and extrapyramidal symptoms were the most common, whereas serious adverse effects such as seizure, tardive dyskinesia, neuroleptic malignant syndrome, and autonomic failure were rare.[9] Therefore, healthcare providers should exercise caution when prescribing prochlorperazine to children.

It is important to note that geriatric patients with dementia have a higher risk of death when treated with an antipsychotic, including prochlorperazine.

The following lists contraindications for prochlorperazine[1][8]

• History of allergy to prochlorperazine or the phenothiazine drug class
• Concomitant use of CNS depressants (opioids, benzodiazepines, and barbiturates) leading to sedation
• Concomitant use of anticholinergic medications (scopolamine, atropine, etc.)
• Pre-existing cardiac conduction abnormalities
• History of seizure/epilepsy (prochlorperazine lowers seizure threshold)
• Narrow-angle glaucoma
• Prostatic hypertrophy
• Past or current history of tardive dyskinesia
• Patients under two years of age

It is not a recommended agent for patients who are pregnant. Antipsychotics are generally not recommended in pregnant patients.[1] Also, there is a lack of evidence to suggest that prochlorperazine is clinically effective in treating nausea and vomiting during pregnancy, nor are the side effects completely understood.[10]