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Optimizing haloperidol dosage
Monitoring patient compliance
Draw blood immediately before next scheduled dose.
Centrifuge and aliquot serum into plastic vial within 2 hours of collection.
Haloperidol (Haldol) is a member of the butyrophenone class of neuroleptic drugs used to treat psychotic disorders (eg, schizophrenia). It is also used to control the tics and verbal utterances associated with Tourette syndrome and in the management of intensely hyperexcitable children who fail to respond to other treatment modalities.
The daily recommended oral dose for patients with moderate symptoms is 0.5 to 2.0 mg; for patients with severe symptoms, 3 to 5 mg may be used. However, some patients will respond only at significantly higher doses.
Haloperidol is metabolized in the liver to reduced haloperidol, its major metabolite.
Use of haloperidol is associated with significant toxic side effects, the most serious of which include tardive dyskinesia, which can be irreversible, extrapyramidal reactions with Parkinson-like symptoms, and neuroleptic malignant syndrome. Less serious side effects can include hypotension, anticholinergic effects (blurred vision, dry mouth, constipation, urinary retention), and sedation. The risk of developing serious, irreversible side effects seems to increase with increasing cumulative doses over time.
Studies show a strong relationship between dose and serum concentration; however, there is a modest relationship of clinical response or risk of developing long-term side effects to either dose or serum concentration.
A therapeutic window exists for haloperidol, but some patients may respond to concentrations outside of this range. Patients who respond at serum concentrations between 5 to 16 ng/mL show no additional improvement at concentrations greater than 16 to 20 ng/mL. Some patients may respond at concentrations less than 5 ng/mL, and others may require concentrations significantly greater than 20 ng/mL before an adequate response is attained.
Because of such inter-individual variation, the serum concentration should only be used as one factor in determining the appropriate dose and must be interpreted in conjunction with the clinical status.
Although the metabolite, reduced haloperidol, has minimal pharmacologic activity, evidence has been presented suggesting that an elevated ratio of reduced haloperidol-to-haloperidol (ie, >5) is predictive of a poor clinical response. A reduced haloperidol-to-haloperidol ratio <0.5 indicates noncompliance; the metabolite does not accumulate except during steady-state conditions.