Haloperidol is used orally and parenterally for the symptomatic management of psychotic disorders (i.e., schizophrenia). Drug therapy is integral to the management of acute psychotic episodes in patients with schizophrenia and generally is required for long-term stabilization to improve symptoms between episodes and to minimize the risk of recurrent acute episodes. Antipsychotic agents are the principal class of drugs used for the management of all phases of schizophrenia and generally are effective in all subtypes of the disorder and subgroups of patients. Conventional antipsychotic agents, such as haloperidol, generally are considered to exhibit similar efficacy in treating acute psychotic symptoms, although they vary in their potency and adverse effect profile. Haloperidol is a high-potency antipsychotic that has been shown to be effective in the management of acute and stable phases of schizophrenia, but is frequently associated with extrapyramidal reactions such as akathisia, dystonia, or parkinsonian symptoms, even at low dosages.
Results of short-term studies indicate that oral haloperidol is more effective than placebo and equally or less effective than atypical antipsychotics in the treatment of positive (e.g., delusions, hallucinations) and negative symptoms (e.g., withdrawal from social interaction, blunted emotional expression) of schizophrenia. However, in one clinical study, haloperidol was less effective than the atypical antipsychotic agent risperidone in preventing relapse in adult outpatients with clinically active schizophrenia or schizoaffective disorders who were assigned to receive either drug for a minimum of 1 year. In this study, approximately 40% of patients in the study who received usual dosages of haloperidol had relapsed by the end of the study compared with approximately 25% of those receiving usual dosages of risperidone.
Because atypical antipsychotics appear to be at least as effective in the treatment of positive symptoms and possibly more effective in the treatment of negative symptoms of schizophrenia and have fewer extrapyramidal reactions, some clinicians prefer use of atypical antipsychotics rather than conventional antipsychotics, such as haloperidol, for the management of schizophrenia, except in stable patients who have had good response to conventional antipsychotics without major adverse effects, in patients who require IM therapy, which is not yet available for some atypical antipsychotics, and for the acute management of aggression/violence in some patients, particularly those requiring long-acting (depot) parenteral preparations. However, patient response and tolerance to antipsychotic agents are variable, and patients who do not respond to or tolerate one drug may be successfully treated with an agent from a different class or with a different adverse effect profile.
The long-acting decanoate ester of haloperidol is used parenterally principally in patients requiring prolonged antipsychotic therapy (e.g., patients with chronic schizophrenic disorder). Parenteral antipsychotic therapy with a long-acting preparation may be particularly useful in patients with a history of poor compliance. In addition, long-acting antipsychotic preparations may be useful in patients with suspected GI malabsorption or variable GI absorption of the drug. The principal disadvantage of long-acting parenteral antipsychotics is the inability to terminate the drug's action when severe adverse reactions occur. Long-acting antipsychotic preparations should not be used in the acute management of severely agitated patients. Generally, patients should be stabilized on antipsychotic medication prior to conversion to haloperidol decanoate therapy and should have previously received and tolerated a shorter-acting haloperidol preparation so that the possibility of an unexpected adverse reaction that potentially could not be readily reversed following the decanoate can be minimized. For further information on the use of antipsychotic agents in the symptomatic treatment of schizophrenia,
Haloperidol is used orally and parenterally for the control of tics and vocal utterances of Tourette's syndrome (Gilles de la Tourette's syndrome) in children and adults. Haloperidol generally has been considered the drug of choice for the management of Tourette's syndrome and pimozide has been an effective alternative in some patients who have an inadequate response to or do not tolerate haloperidol. Because limited data suggest that pimozide may be more effective than haloperidol in reducing tics and pimozide appears to be better tolerated than haloperidol, some clinicians and experts prefer the use of pimozide in patients with Tourette's syndrome.
In children with tic disorders (e.g., Tourette's syndrome) and comorbid attention deficit hyperactivity disorder (ADHD) in whom stimulants alone cannot control tics, haloperidol may be used concomitantly with a stimulant.
Antipsychotic agents, mainly haloperidol, have been used in the management of delirium.
Delirium is principally a disturbance of consciousness, attention, cognition, and perception but also may affect sleep, psychomotor activity, and emotions. It is a common psychiatric illness among medically compromised patients, particularly hospitalized patients, and may be a harbinger of substantial morbidity and mortality.
Prevalence and Course
The prevalence of delirium in hospitalized medically ill patients ranges from 10-30%; in those who are elderly, delirium ranges up to 40%. Up to 25% of hospitalized cancer patients and 30-40% of hospitalized patients with acquired immunodeficiency syndrome (AIDS) develop delirium. Up to about 50% of postoperative patients develop delirium, and up to 80% of terminally ill patients develop it near death. EEG abnormalities, mainly generalized slowing, have fairly good sensitivity for aiding in the diagnosis of delirium, but the absence of such changes does not rule out the diagnosis. Prodromal manifestations may progress to full-blown delirium over 1-3 days; the duration of delirium generally ranges from less than a week to more than 2 months, but typically does not exceed 10-12 days. Symptoms persist for up to 30 days or longer in up to 15% of patients, and frequently persist for longer than 1 month in geriatric patients. Although most patients recover fully, delirium may progress to stupor, coma, seizures, and death, particularly if untreated. Full recovery is less likely in geriatric patients and patients with AIDS, possibly because of underlying dementia in both populations.
Underlying general medical conditions associated with delirium include CNS disorders (e.g., head trauma, seizures, postictal state, vascular or degenerative disease), metabolic disorders (e.g., renal or hepatic failure, anemia, hypoxia, hypoglycemia, thiamine deficiency, endocrinopathy, fluid or electrolyte imbalance, acid-base imbalance), cardiopulmonary disorder (myocardial infarction, congestive heart failure, cardiac arrhythmia, shock, respiratory failure), and systemic illness (e.g., substance intoxication or withdrawal, infection, cancer, severe trauma, sensory deprivation, temperature dysregulation, postoperative state).
Clinicians should undertake an essential array of psychiatric management tasks designed to provide immediate interventions for urgent general medical conditions, identify and treat the etiology of delirium, ensure safety of the patient and others in contact with the patient, and improve the patient's functioning. Environmental (e.g., varying light levels in intensive care units to heighten awareness about time of day and reduce the perception of timelessness) and supportive interventions (e.g., to deal with disorientation, to assure the patient that manifestations are temporary and reversible and do not reflect a persistent psychiatric disorder) also generally are offered to patients with delirium and are designed to reduce factors that may exacerbate delirium, to reorient patients, and to provide support. Patients may have life-threatening medical conditions that require therapeutic intervention even before a specific or definitive cause of the delirium is determined. The goal of diagnosis is to identify potentially reversible causes of delirium and prevent complications through prompt treatment of these specific disorders. Psychiatric management is essential and should be undertaken for all patients with delirium. Somatic interventions principally consist of drug therapy. The choice of somatic intervention will depend on the specific features of the patient's clinical condition, the underlying etiology of the delirium, and any associated comorbid conditions.
Antipsychotic agents often are the drugs of choice for the management of delirium. Although other drugs (e.g., phenothiazines, droperidol) have been used, haloperidol generally is considered the antipsychotic of choice for most patients with delirium because of its relatively low risk of anticholinergic activity and of sedative and hypotensive effects. In addition, haloperidol has been studied most extensively, although few studies have used standardized definitions of delirium or reliable and valid delirium symptom rating measures to assess symptom severity before and after initiation of treatment. For drugs other than haloperidol, there have been no large, prospective studies that included a control. Evidence of efficacy for such alternative therapies, including second-generation antipsychotic agents (e.g., olanzapine, quetiapine, risperidone, ziprasidone), is principally from small case series, case reports, or open-label studies. In addition, interpretation of findings from many such case presentations is difficult because of use of nonstandardized delirium definitions and/or informal measures of delirium symptom severity. In general, evidence of the efficacy of antipsychotics, including haloperidol, in the management of delirium comes from numerous case reports and uncontrolled studies. However, evidence from a randomized, double-blind, comparator-drug controlled study (haloperidol, chlorpromazine, and lorazepam) in patients with AIDS that employed standardized clinical measures of delirium demonstrated clinical superiority of antipsychotic agents compared with benzodiazepines. Statistically significant improvement in the Delirium Rating Scale was evident after 2 days in patients receiving haloperidol or chlorpromazine but not in the lorazepam group (mean decreases in the score [i.e., improvement] were 8, 8.5, and 1, respectively). The symptomatic improvement in delirium occurred quickly among patients receiving antipsychotic therapy, usually before initiation of interventions directed at the medical etiologies of delirium.
Although various antipsychotic agents may be given orally, IM, or IV, IV administration is considered most effective in emergency situations or where oral access is limited. In addition, some evidence indicates that IV administration of antipsychotic agents may be associated with less severe extrapyramidal effects.
Antipsychotic agents, particularly IV haloperidol, used in the management of delirium have been associated with lengthening of the QT interval, possibly leading to atypical ventricular tachycardia (torsades de pointes), ventricular fibrillation, and sudden death. The manufacturer of Haldol and the US Food and Drug Administration (FDA) state that although injectable haloperidol is approved only for IM injection and not for IV administration, there is considerable evidence from the medical literature that IV administration of the drug is a relatively common, unlabeled (''off-label'') clinical practice, principally for the treatment of severe agitation in intensive care units, and recommend ECG monitoring in any patient receiving the drug IV. Many clinicians also recommend that baseline and periodic or continuous ECG monitoring be performed with special attention paid to the length of the QTc interval. Prolongation of the QTc interval to greater than 450 msec or to greater than 15-25% over that in previous ECGs may warrant telemetry, a cardiology consultation, and dose reduction or discontinuance. Serum concentrations of magnesium and potassium also should be monitored at baseline and periodically in critically ill patients, especially those with baseline QTc intervals of 440 msec or longer, those receiving other drugs known to increase the QT interval, and those who have electrolyte disorders. Limited evidence suggests that the incidence of torsades de pointes in patients receiving haloperidol IV is about 0.4-3.6%, but may increase to greater than 10% at relatively high IV doses (e.g., 35 mg or more over 24 hours).
(See Cautions: Cardiovascular Effectsand also see Cautions: Precautions and Contraindications.)
Disruptive Behavior Disorder and Attention Deficit Hyperactivity Disorder
Haloperidol is used orally for the treatment of severe behavioral problems in children marked by combativeness and/or explosive hyperexcitable behavior (out of proportion to immediate provocations), and for the short-term treatment of hyperactive children who exhibit excessive motor activity with accompanying conduct disorders that are manifested as impulsive behavior, difficulty sustaining attention, aggression, mood lability, and/or poor frustration tolerance. However, the possible risks of tardive dyskinesia, withdrawal dyskinesia, and other extrapyramidal reactions should be considered. Some experts currently recommend use of haloperidol only for the treatment of comorbid tics in children with attention deficit hyperactivity disorder (ADHD). Some clinicians recommend routine administration of the Abnormal Involuntary Movement Scale (AIMS) to all children receiving antipsychotic agents.
Nausea and Vomiting
Haloperidol also has been used in the prevention and control of severe nausea and vomiting (e.g., cancer chemotherapy-induced emesis). Based on limited data, haloperidol appears to be as effective as phenothiazines in the prevention of cancer chemotherapy-induced emesis. Additional studies are required to determine the efficacy of haloperidol in the prevention and control of severe nausea and vomiting.