Haloperidol

Article Author:
Sajedur Rahman
Article Editor:
Raman Marwaha
Updated:
7/31/2020 2:20:49 PM
PubMed Link:
Haloperidol

Indications

Haloperidol is a first-generation (typical) antipsychotic medication that is used widely around the world. Food and Drug Administration (FDA) approved the use of haloperidol is for schizophrenia, Tourette syndrome (control of tics and vocal utterances in adults and children), hyperactivity (which may present as impulsivity, difficulty maintaining attention, severe aggressivity, mood instability, and frustration intolerance), severe childhood behavioral problems (such as combative, explosive hyperexcitability), intractable hiccups. It is a typical antipsychotic because it works on positive symptoms of schizophrenia, such as hallucinations and delusions.[1][2][3][4][5]

Mechanism of Action

Haloperidol is a first-generation (typical antipsychotic) which exerts its antipsychotic action by blocking dopamine D2 receptors in the brain. When 72% of dopamine receptors are blocked, this drug achieves its maximal effect.[6] Haloperidol is not selective for the D2 receptor. It also has noradrenergic, cholinergic, and histaminergic blocking action. The blocking of these receptors is associated with various side effects.

Administration

Haloperidol is used widely in different countries. It is available in various forms; the oral route is the most common. For the oral administration, it is available as a tablet form and oral concentrate form. It is also available in a nasal spray formulation. Haloperidol lactate is used as a short-acting parenteral solution available for use intramuscularly and intravenously. Haloperidol decanoate is available for long-acting intramuscular preparation.[6]

Haloperidol in psychosis: In this instance, the oral and intramuscular forms can be used. For moderate symptomology: 0.5 to 2 mg 2 to 3 times a day orally. In some resistant cases, up to 30 mg/day may be necessary. For prompt control of acute agitation, an intramuscular injection can be given as a 2 to 5 mg dose every 4 to 8 hours. The maximum intramuscular dose is 20 mg/day.

Haloperidol in schizophrenia: In moderately severe patients, dosing is 0.5 to 2 mg haloperidol orally 2 to 3 times a day. It should not exceed 30 mg daily in case of severe cases. To control acute agitation in a schizophrenic patient, dosing is 2 to 5 mg haloperidol intramuscularly every 4 to 8 hours.

Haloperidol in Tourette syndrome: Dosing is 0.5 to 2 mg orally 2 to 3 times a day in the moderately symptomatic cases, and for severe cases, it can be higher: 3 to 5 mg, 2 to 3 times a day.

Pediatric Use: Safety, effectiveness, and doses of haloperidol in the pediatric population have not been established yet.

Geriatric Use: the prevalence of tardive dyskinesia is the highest among older patients, especially older women.

Usage in Pregnancy: There are no well-controlled studies for the haloperidol use in pregnant women. But there are several reports, however, of cases of limb malformations in the newborn whose mother used haloperidol, but causal relationships were not appropriately established in these cases. Since these experiences do not exclude the possibility of a fetal anomaly due to haloperidol, this drug should be used only if the benefit outweighs the potential risk to the fetus.

Adverse Effects

Due to the blockade of the dopamine pathway in the brain, typical antipsychotic medications such as haloperidol have correlations with extrapyramidal side effects.[6][1]

Extrapyramidal symptoms

  • Acute Dystonia - (Develops within hours to days of initiation. Maybe presented as muscle spasm, stiffness, oculogyric crisis)
  • Akathisia - (Develops within days to months of use of haloperidol - characterized by restlessness.)
  • Neuroleptic malignant syndrome - (NMS; infrequent but severe condition. May present as High fever, muscle rigidity)
  • Parkinsonism - (Develops after days to month use of haloperidol)
  • Tardive dyskinesia - (Develops after years. Presents as chore especially orofacial region)

Common

  • Anticholinergic effects - (Elevated temperature, dry mouth, drowsiness or sedation, constipation, urinary retention)
  • Sedation
  • Weight gain
  • Erectile dysfunction in male
  • Oligomenorrhea or amenorrhea in female

Less common

  • Orthostatic hypotension - (After IM injection of haloperidol), tachycardia, palpitation
  • Agitation, generalized anxiety, cerebral edema, new-onset depression, dizziness, euphoric mood, headache, sleeplessness, poikilothermia, restlessness, generalized weakness, confusion
  • Anorexia, constipation, dyspepsia, ileus, decreased gag reflex.
  • Lens opacities - (If used for a prolonged time)

Uncommon

  • ECG changes - (QT prolongation, torsades de pointes)[7][8][9][10]
  • Photosensitivity reaction
  • Generalized pruritus
  • Diarrhea, gastrointestinal distress
  • Blood dyscrasia
  • Ejaculatory problems

Rare

  • Seizure
  • Cholestatic jaundice
  • Priapism 

Contraindications

Haloperidol is contraindicated if there is documented hypersensitivity to this drug, in Parkinson disease, dementia with Lewy body, comatose patient, in any condition with the depressed central nervous system (CNS). Since many drugs (barbiturates, benzodiazepines, and opioids) can cause depression to CNS, concurrent use of haloperidol should be avoided or used with great caution.

Monitoring

Due to potential side effects development, patients receiving haloperidol require monitoring, especially when receiving the intramuscular form. It can be easily monitored by taking blood levels. It has a therapeutic range of 2 to 15 ng/ml in serum. Blood levels should be monitored at 12-hour or 24-hour intervals or after the last dose of haloperidol use in a patient. 

Toxicity

Toxicities are the exaggerated symptoms of known pharmacologic effects and known adverse reactions. The most prominent toxicities of haloperidol are 1) severe extrapyramidal symptoms, hypotension, sedation. The patient may appear comatose with severe respiratory depression or shock from hypotension. The extrapyramidal symptoms are muscular weakness or rigidity, a generalized or localized tremor that may be characterized by the akinetic or agitations types of movements, respectively. Haloperidol overdose is also associated with  ECG changes known as torsade de pointes, which may cause arrhythmia or cardiac arrest. 

Since there is no specific antidote, supportive treatment is the mainstay of haloperidol toxicity. If a patient develops sign symptoms of toxicities, the clinician should consider gastric lavage or induction of emesis as soon as possible, followed by the administration of activated charcoal. Maintenance of  Airway, Breathing, and circulation are the most important factors for survival.  A patent airway must be ensured by the use of an oropharyngeal airway or endotracheal tube or by tracheostomy if the patient is in a coma. Respiratory depression can be managed by artificial respiration or by mechanical respirators in severe cases or a comma. Hypotension and circulatory collapse are manageable by using intravenous fluids, concentrated albumin, and vasopressor agents ( phenylephrine or norepinephrine).

Epinephrine should not be used as it can decrease blood pressure. If the patient develops severe extrapyramidal reactions, antiparkinson medication should be considered. ECG and vital signs require monitored at regular intervals. Especially for signs of torsades de Pointes or  Q-T prolongation or dysrhythmias, cardiac monitoring should be in place until the ECG becomes normal. If the patient develops arrhythmias, which could be life-threatening, prompt management should commence with appropriate anti-arrhythmic measures.[11]

Enhancing Healthcare Team Outcomes

Haloperidol is one of the most commonly used antipsychotics in this world. Generally, the psychiatrist, nurse practitioner, primary care physician, or internist prescribes the medication. Since the drug can cause several side effects and related to several toxicities after initiation, the healthcare workers must be familiar with its pharmacology, sign symptoms of toxicity and management of adverse effects. They must monitor their side effects and toxicities. A proper history and physical examination are necessary before initiation of haloperidol in any patient.  

Interprofessional team discussion with psychiatrists, cardiologists, pharmacists is crucial; this is true for any patient but especially when considering using haloperidol in a psychotic patient. The team must monitor the signs-symptoms of toxicity at a regular interval and should be ready to initiate a prompt response if any complications occur. Besides this interprofessional teamwork, they should also educate the patients and their family members about dosing, side effects, and warning signs, which may arise in the future while using haloperidol. The patient should also receive counsel regarding when to call for help and when to come back to the hospital.


References

[1] Dold M,Samara MT,Li C,Tardy M,Leucht S, Haloperidol versus first-generation antipsychotics for the treatment of schizophrenia and other psychotic disorders. The Cochrane database of systematic reviews. 2015 Jan 16     [PubMed PMID: 25592299]
[2] Rouse S,Wodziak M, Intractable Hiccups. Current neurology and neuroscience reports. 2018 Jun 22;     [PubMed PMID: 29934880]
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[8] Beach SR,Celano CM,Noseworthy PA,Januzzi JL,Huffman JC, QTc prolongation, torsades de pointes, and psychotropic medications. Psychosomatics. 2013 Jan-Feb;     [PubMed PMID: 23295003]
[9] Hasnain M,Vieweg WV, QTc interval prolongation and torsade de pointes associated with second-generation antipsychotics and antidepressants: a comprehensive review. CNS drugs. 2014 Oct;     [PubMed PMID: 25168784]
[10] Cubeddu LX, QT prolongation and fatal arrhythmias: a review of clinical implications and effects of drugs. American journal of therapeutics. 2003 Nov-Dec;     [PubMed PMID: 14624285]
[11] Solmi M,Murru A,Pacchiarotti I,Undurraga J,Veronese N,Fornaro M,Stubbs B,Monaco F,Vieta E,Seeman MV,Correll CU,Carvalho AF, Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Therapeutics and clinical risk management. 2017;     [PubMed PMID: 28721057]