Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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's 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.(1,2)
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.(1,3)
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Studies show a strong relationship between dose and serum concentration (4); 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; patients who respond at serum concentrations between 5 to 16 ng/mL show no additional improvement at concentrations >16 to 20 ng/mL.(3,5) Some patients may respond at concentrations <5 ng/mL, and others may require concentrations significantly >20 ng/mL before an adequate response is attained.
Because of such inter-individual variation, the serum concentration should only be used as 1 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.(3,6) A reduced haloperidol-to-haloperidol ratio <0.5 indicates noncompliance; the metabolite does not accumulate except during steady-state conditions.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Potentially interfering drugs include hydroxyzine (interferes with haloperidol), tiagabine (interferes with reduced haloperidol), and quetiapine (interferes with internal standard resulting in artificially low haloperidol).
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Lawson GM: Monitoring of serum haloperidol. Mayo Clin Proc 1994;69:189-190
2. Ereshefsky L, Davis CM, Harrington CA, et al: Haloperidol and reduced haloperidol plasma levels in selected schizophrenic patients. J Clin Psychopharmacol 1984;4:138-142
3. Volavka J, Cooper TB: Review of haloperidol blood level and clinical response: looking through the window. J Clin Psycho-pharmacol 1987;7:25-30
4. Moulin MA, Davy JP, Debruyne JC, et al: Serum level monitoring and therapeutic effect of haloperidol in schizophrenic patients. Psychopharmacology 76:346-350, 1982
5. Van Putten T, Marder SR, Mintz J, Polant RE: Haloperidol plasma levels and clinical response: a therapeutic window relationship. Am J Psychiatry 1992;149:500-505
6. Shostak M, Perel JM, Stiller RL, et al: Plasma haloperidol and clinical response: a role for reduced haloperidol in antipsychotic activity? J Clin Psychopharmacol 1987;7:394-400