Haloperidol

Haloperidol is an older antipsychotic used in the treatment of schizophrenia and in the treatment of acute psychotic states and delirium. A long-acting decanoate ester is used as an injection given every 4 weeks to people with schizophrenia or related illnesses who have a poor compliance with medication and suffer frequent relapses of illness, or to overcome the drawbacks inherent to its orally administered counterpart that burst dosage increases risk or intensity of side effects. In some countries, injections of antipsychotics such as haloperidol can be ordered by a court at the request of a psychiatrist. Doses As directed by the physician, depends on the condition to be treated, age, and weight of patient:

Acute problems: the British National Formulary recommends a maximum daily dose of 30mg total (IM and oral) with maximum 18mg by IM route. Single doses of 1 mg to 5 mg (up to 10 mg) oral or i.m., usually repeated every 46 hours, not exceeding an oral dose of 100 mg daily. Doses used for IV injection are usually 5 to 10 mg as a single dose; not exceeding 50 mg daily.

Note that PET imaging studies by Tauscher et al (2001) suggested that low doses were ideal. They found that 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 5mg increased the risk of sideeffects without improving efficacy. Oosthuizen et al (2001) found that patients responded with doses under even 2mg in first episode psychosis.

Chronic conditions: 0.5 to 20 mg daily oral, rarely more. The lowest dose that maintains remission is employed. Experimental doses: In resistant cases of psychosis small studies with oral doses of up to 300 mg 500 mg daily have been conducted (in most cases together with an anticholinergic antiparkinsonian drug (Biperiden, Benzatropine, etc.) to avoid severe early extrapyramidal side effects. These studies showed no superior results and led to severe side effects. Also, the frequency of otherwise unusual side effects (hypotension, QT-time prolongation, and serious cardiac arrhythmias) was dramatically increased. The clinical use of haloperidol in these doses is discouraged now and it is recommended to switch the patient gradually to a different neuroleptic (e.g., clozapine, olanzapine, aripiprazole).

Depot forms are also available; these are injected deeply i.m. at regular intervals. The depot forms are not suitable for initial treatment, but are suitable for patients who have demonstrated inconsistency with oral dosages.

Adverse effects Haloperidol is noted for its strong early and late extrapyramidal side effects. The risk of the facial disfiguring tardive dyskinesia is around 4% per year in younger patients. Other predispositive factors may be female gender, preexisting affective disorder, and cerebral dysfunction. Akathisia often manifests itself with anxiety, dysphoria, and an inability to remain motionless. Other side effects include dry mouth, lethargy, restlessness of akathisia, muscle-stiffness, muscle-cramping, restlessness, tremors, Rabbit syndrome, and weight-gain; side effects like these are more likely to occur when the drug is given in high doses and/or during long-term treatment. Depression, severe enough to result in suicide, is quite often seen during long-term treatment. Care should be taken to detect and treat depression early in course. Sometimes the change from haloperidol to a mildly potent neuroleptic (e.g., chlorprothixene or chlorpromazine), together with appropriate antidepressant therapy, does help. Sedative and anticholinergic side effects occur more frequently in the elderly. The likelihood of one's experiencing one or more of these side-effects is quite high regardless of age and gender, especially with prolonged use. Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first-generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups. The potentially fatal neuroleptic malignant syndrome (NMS) is a significant possible side effect. Haloperidol and fluphenazine are the two drugs that cause NMS most often. NMS involves fever and other symptoms. Allergic and toxic side effects occur. Skin rash and photosensitivity both occur in fewer than 1% of patients. Children and adolescents are particularly sensitive to the early and late extrapyramidal side effects of haloperidol. It is not recommended to treat pediatric patients. QT prolongation with sudden death is a rarely seen but clinically significant side-effect. Likewise, the development of thromboembolic complications are also seen. Haloperidol may have a negative impact on vigilance or decrease the ability of the patient to drive or operate a machine, particularly initially. Haloperidol is not devoid of potential psychological dependence. However, due to the debilitating side effects, patients prescribed this drug have a high rate of non-compliance. The current recommendation is to pay close attention to the patient's experience, and taper or discontinue use if the patient has a high rate of dissatisfaction with treatment, as it may lead to dangerously rapid discontinuation. Haloperidol has been shown to dramatically increase dopamine activity, up to 98%, in test subjects after two weeks on a "moderate to high" dose compared to chronic schizophrenics.[24] In another study, a live survey of a patient showed that the person has 90% more dopamine

receptors, of the D2 subtype, than before treatment with haloperidol. The long term effect of this is unknown, but the first study concludes that this upregulation is positively associated with severe dyskinesias (more upregulation, more dyskinesia). Some research studies have suggested effects of haloperidol on brain tissue. In a 2005 placebo-compared study of six macaques receiving haloperidol for up to 27 months, a significant brain volume change of about 10% and weight decreases were detected. In later studies (2008) of the stored samples, the previously reported changes were attributed primarily to astrocyte and oligodendrocyte loss, with the neuron loss at about 5%, which was not statistically significant. A study in 2011 of rats given haloperidol in doses comparable to clinical use for 8 weeks found a reduction in brain cortex volume of 1012%. In other studies, the use of potent antipsychotics has been associated with cognitive decline and permanent brain damage. Contraindications

Preexisting coma, acute stroke Severe intoxication with alcohol or other central depressant drugs Known allergy against haloperidol or other butyrophenones or other drug ingredients Known heart disease; when combined will tend towards cardiac arrest Preexisting Parkinson's disease or dementia with Lewy bodies Patients at special risk for the development of QT prolongation (hypokalemia, concomitant use of other drugs causing QT prolongation) Compromised liver-function (as haloperidol is metabolized and eliminated mainly by the liver) Patients with hyperthyreosis; the action of haloperidol is intensified and side-effects are more likely. IV injections: risk of hypotension or orthostatic collapse.

Interactions

Other central depressants (alcohol, tranquilizers, and narcotics): actions and side effects of these drugs (sedation, respiratory depression) are increased. In particular, the doses of concomitantly used opioids for chronic pain can be reduced by 50%. Methyldopa: increased risk of extrapyramidal side effects and other unwanted central effects Levodopa: decreased action of levodopa Tricyclic antidepressants: metabolism and elimination of tricyclics significantly decreased, increased toxicity noted (anticholinergic and cardiovascular side effects, lowering of seizure threshold) Quinidine, buspirone, and fluoxetine: increased plasma levels of haloperidol, decrease haloperidol dose, if necessary Carbamazepine, phenobarbital, and rifampicin: plasma levels of haloperidol significantly decreased, increase haloperidol dose, if necessary lithium: rare cases of the following symptoms have been noted: encephalopathy, early and late extrapyramidal side effects, other neurologic symptoms, and coma.[32] Guanethidine: antihypertensive action antagonized Epinephrine: action antagonized, paradoxical decrease in blood pressure may result

How should you take Haloperidol? Follow your doctors directions for taking Haloperidol. Haloperidol may be taken with food or after eating. If taking Haloperidol in a liquid concentrate form, you will need to dilute it with milk or water. You should not take Haloperidol with coffee, tea, or other caffeinated beverages, or with alcohol. Haloperidol causes dry mouth. Sucking on a hard candy or ice chips may help alleviate the problem. If you miss a dose take it as soon as you remember. Take the rest of the doses for that day at equally spaced intervals. Do not take two doses at once. Store Haloperidol away from heat, light, and moisture in a tightly closed container. Do not freeze the liquid.