A case illustrating the worsening of a patient's schizophrenic symptoms following haloperidol dosage increases is presented. This case is remarkable in that few cases of psychotic exacerbation with haloperidol dosage increases have been reported in the world literature. The possibility exists that, like certain tricyclic antidepressants, neuroleptic medication may possess a “therapeutic window.” The concept of a therapeutic window and its relationship to the phenomenon of psychotic exacerbation is reviewed. In evaluating this condition, the clinician should consider other causes of psychotic exacerbation, such as akathisia and anticholinergic psychosis.
SimpsonGMVargaEHaherJ. Psychotic exacerbations produced by neuroleptics. Dis Nervous System1976; 37: 367–9.
2.
BarchasJDBergerPACiaranelloRD, eds. Psychopharmacology from theory to practice. New York: Oxford University Press, 1977: 137.
3.
ColonnaL. Effects paradoxa des neuroleptiques?Encephale1976; 2 (3): 197–200.
4.
WeintraubM. The therapeutic window: When more is much, much less. Drug Therapy1979; 4 (10): 50–2.
5.
ChaffinDS. Phenothiazine-induced acute psychotic reaction: The “psychotoxicity” of a drug. Am J Psychiatry1964; 121: 26–32.
6.
WilliamsP. An unusual response to chlorpromazine therapy. Br J Psychiatry1972; 121: 439–40.
7.
MayRH. Catatonic-like states following phenothiazine therapy. Am J Psychiatry1959; 115: 1119–20.
8.
BehrmanS. Mutism induced by phenothiazinesBr J Psychiatry1972:121: 599–604.
9.
LiptonMADimascioAKillamKF, eds. Psychopharmacology: A generation of progress. New York: Raven Press, 1978: 895, 1022.
10.
Kragh-SorensenDHansenCEBaastrupPCHuidbergEF. Self-inhibiting action of nortriptyline's antidepressive effect at high plasma levels. Psychopharmacologie1976; 45: 305–16.
11.
AsbergMCronholmBSjoqhistFTuckD. Relationship between plasma level and therapeutic effect of nortriptyline. Br Med J1971; 3: 331–4.
12.
HaaseHTJanssenPA. The action of neuroleptic drugs. Chicago: Year Book Medical Publishers, 1965.
13.
BurkiHREichenbergerESaversACWhiteTC. Clozapine and the dopamine hypothesis of schizoprenia: A critical appraisal. Pharmakopsychiatr Neuro-pharmakol1975; 8: 115–21.
14.
SchouM, The practical management of lithium treatment. Br J Hosp Med1971; 6: 53–60.
15.
AlfredssonG, Levels of chlorpromazine and its active metabolites in rat brain and the relationship to central monoamine metabolism and prolactin secretion. Psychopharmacology1977; 53: 13–18.
16.
Wode-HelgodtB, Clinical effects and drug concentrations in plasma and cerebrospinal fluid in psychotic patients treated with fixed doses of chlorpromazine. Acta Psychiatr Scand1978; 58: 149–73.
17.
Rivera-CalimlimL, Clinical response and plasma levels: Effect of dose, dosage schedules and drug interactions on plasma chlorpromazine levels. Am J Psychiatry1976; 133: 646–52.
18.
Rivera-CalimlimLCastanedaLLasagnaL. Effects of mode of management on plasma chlorpromazine in psychiatric patients. Clin Pharmacol Ther1973; 14: 978–86.
19.
CurrySHMarshallJHLDavisJM. Chlorpromazine plasma levels and effects. Arch Gen Psychiatry1970; 22: 289–96.
20.
ForsmanAOhmanR. Pharmacokinetic studies on haloperidol in man. Curr Ther Res1976; 20: 319–36.
21.
ForsmanALarssonM. Metabolism of haloperidol. Curr Ther Res1978; 24: 567–8.
22.
EricksenSEHurtSWChangS. Haloperidol dose, plasma levels, and clinical response: A double blind study. Psychopharmacol Bull1978; 14 (2): 15–16.
23.
ForsmanAOhmanR. Applied pharmacokinetics of haloperidol in man. Curr Ther Res1977; 21: 396–409.
24.
CoutselinisABohkisDKentarchouP. Haloperidol concentrations in blood in cases of acute intoxication (letter). Clin Chem1977; 23: 980.
25.
MorselliPLBianchettiGDurandG. Haloperidol plasma level monitoring in pediatric patients. In: Therapeutic drug monitoring. New York: Raven Press, 1979.
26.
MayPRVan PuttenT. Plasma levels of chlorpromazine in schizophrenia. Arch Gen Psychiatry1978; 35: 1081–7.
27.
PerryP, Anticholinergic psychosis. Am J Hosp Pharm1978; 35: 725–7.
28.
Van PuttenT. The many faces of akathisia. Compr Psychiatry1975; 16: 43–7.
29.
SnyderSGreenbergDYamamuraHI, Antischizophrenic drugs and brain cholinergic receptors. Affinity for muscarinic sites predicts extrapyramidal effects. Arch Gen Psychiatry1974; 31: 58–61.
30.
CraneGENaranjoER. Motor disorders induced by neuroleptics. Arch Gen Psychiatry1971; 24: 179–84.
