Haloperidol

Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks for people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth. Haloperidol may result in movement disorders such as tardive dyskinesia, and akathisia, both of which may be permanent. Neuroleptic malignant syndrome and QT interval prolongation may occur, the latter particularly with IV administration. In older people with psychosis due to dementia it results in an increased risk of death. When taken during pregnancy it may result in problems in the infant. It should not be used by people with Parkinson's disease. Haloperidol was discovered in 1958 by the team of Paul Janssen, prepared as part of a structure-activity relationship investigation into analogs of pethidine (meperidine). It is on the World Health Organization's List of Essential Medicines. It is the most commonly used typical antipsychotic. In 2020, it was the 303rd most commonly prescribed medication in the United States, with more than 1 million prescriptions.

Medical uses Haloperidol is used in the control of the symptoms of:

Acute psychosis, such as drug-induced psychosis caused by ketamine, and phencyclidine, and psychosis associated with high fever or metabolic disease. Some evidence has found haloperidol to worsen psychosis due to psilocybin. Adjunctive treatment of alcohol and opioid withdrawal Agitation and confusion associated with cerebral sclerosis Alcohol-induced psychosis Hallucinations in alcohol withdrawal Hyperactive delirium (to control the agitation component of delirium) Hyperactivity, aggression Otherwise uncontrollable, severe behavioral disorders in children and adolescents Schizophrenia Therapeutic trial in personality disorders, such as borderline personality disorder Treatment of intractable hiccups Treatment of neurological disorders, including tic disorders such as Tourette syndrome, and chorea Treatment of severe nausea and emesis in postoperative and palliative care, especially for palliating adverse effects of radiation therapy and chemotherapy in oncology. Also used as a first line antiemetic for acute cannabinoid hyperemesis syndrome. As chemical restraint in acute care psychiatry, mainly for violent and self-harming patients (controversial use but very commonly found in movies). Haloperidol was considered indispensable for treating psychiatric emergency situations. However, the newer atypical drugs have gained a greater role in a number of situations, as outlined in a series of consensus reviews published between 2001 and 2005. In a 2013 comparison of 15 antipsychotics in schizophrenia, haloperidol demonstrated standard effectiveness. It was 13–16% more effective than ziprasidone, chlorpromazine, and asenapine, approximately as effective as quetiapine and aripiprazole, and 10% less effective than paliperidone. A 2013 systematic review compared haloperidol to placebo in schizophrenia:

In contrast to certain other antipsychotics like risperidone, haloperidol is ineffective as a hallucinogen antidote or "trip killer" in blocking the effects of serotonergic psychedelics like psilocybin and lysergic acid diethylamide (LSD).

Pregnancy and lactation Data from animal experiments indicate haloperidol is not teratogenic, but is embryotoxic in high doses. In humans, no controlled studies exist. Reports in pregnant women revealed possible damage to the fetus, although most of the women were exposed to multiple drugs during pregnancy. In addition, reports indicate neonates exposed to antipsychotic drugs are at risk for extrapyramidal and/or withdrawal symptoms following delivery, such as agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder. Following accepted general principles, haloperidol should be given during pregnancy only if the benefit to the mother clearly outweighs the potential fetal risk. Haloperidol is excreted in breast milk. A few studies have examined the impact of haloperidol exposure on breastfed infants and in most cases, there were no adverse effects on infant growth and development.

Other considerations

During long-term treatment of chronic psychiatric disorders, the daily dose should be reduced to the lowest level needed for maintenance of remission. Sometimes, it may be indicated to terminate haloperidol treatment gradually. In addition, during long-term use, routine monitoring including measurement of BMI, blood pressure, fasting blood sugar, and lipids, is recommended due to the risk of side effects. Other forms of therapy (psychotherapy, occupational therapy/ergotherapy, or social rehabilitation) should be instituted properly. PET imaging studies have suggested low doses are preferable. Clinical response was associated with at least 65% occupancy of D2 receptors, while greater than 72% was likely to cause hyperprolactinaemia and over 78% associated with extrapyramidal side effects. Doses of haloperidol greater than 5 mg increased the risk of side effects without improving efficacy. Patients responded with doses under even 2 mg in first-episode psychosis. For maintenance treatment of schizophrenia, an international consensus conference recommended a reduction dosage by about 20% every 6 months until a minimal maintenance dose is established.

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