Haloperidol in schizophrenia

Zarifian E, Scatton B, Bianchetti G, Cuche H, Loo H, Morselli PL. High doses of haloperidol in schizophrenia. A clinical, biochemical, and pharmacokinetic study. Arch Gen Psychiatry 1982 39(2) 212-5. 

Copolov DL, Link CG, Kowalcyk B. A multicentre, double-blind, randomized comparison of quetiapine (ICI 204,636, Seroquel ) and haloperidol in schizophrenia. Psychol Med 2000 30(1) 95-105. 

Edgell ET, Hamilton SH, Gregor KJ (1999). Functional outcomes in schizophrenia a European comparison of olanzapine and haloperidol (abstract). Poster presented at the 12th Congress of the European College of Neuropsychopharmacology, London, 21—25 September 1999. 

Grainger DL, Hamilton SH, Genduso LA, et al (1998a). Medical resource use and work and social outcomes for olanzapine compared with haloperidol in the treatment of schizophrenia and other psychotic disorders. Poster presented at the 21st Congress of the CINP, Gla ow, July 1998. 

Rosenheck R, Cramer J, Xu W, et al (1997). A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. N Engl J Med b b7> 809-15. 

Tollefson GD, Beasley CM, Tran PV (1997). Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders results of an international collaborative trial. Am J Psychiatry 154, 457-65. 

Tran PV, Dellva MA, Tollefson GD, et al (1998). Oral olanzapine vs oral haloperidol in rhe mainrenance rrearmenr of schizophrenia. Br J... 

In 1952 reserpine, an alkaloid extract from the Indian snakewort plant, Rauwolfia serpentina, which had been used in that country to treat madness , was first tried in schizophrenia. The beneficial impact on patients and the hospital wards was dramatic, as was that a year later of chlorpromazine, a phenothiazine derivative and haloperidol, a butyrophenone. These latter two drugs and closely related derivatives remained the mainstay of therapy for almost 40 years. 

Like fluphenazine, haloperidol is available in oral, injectable, and depot forms. In schizophrenia, haloperidol is begun at doses of 5 mg daily and increased as needed. Lower doses are used for most other indications. The depot form of haloperidol is initiated by administration of a 50mg test dose. Depot haloperidol is given monthly at about 20 times the daily dose of the oral form. The maximum depot dose is 200 mg per month. Dose dumping does not seem to be a problem with depot haloperidol. 

Mr. James began haloperidol therapy for schizophrenia and within several weeks developed bradykinesia, rigidity, and tremor. Though his psychoses were well controlled, he was switched to another agent, thioridazine, which proved to be as effective as haloperidol in managing his primary condition and did not result in the undesirable symptoms. The most likely explanation for these observations is that... 

Efficacy in short-term treatment. From studies in adult schizophrenia, it is evident that clozapine treatment has at least the same or superior antipsychotic effect, compared to typical antipsychotics. In some studies, clozapine was superior with regard to symptom reduction in severe and acute schizophrenic patients. As the guidelines do not allow the use of clozapine as a first-choice drug, most patients have been treated before with at least two atypical or typical antipsychotics. Only one controlled trial has assessed the efficacy of clozapine in child and adolescent psychiatry. In this study (Kumra et ah, 1996), clozapine was found to be superior to haloperidol in all measures of psychosis, and showed a striking superiority for both positive and negative symptoms. 

Atypical neuroleptics. Because of the limited effectiveness and safety of conventional neuroleptics in TS, clinicians have turned to a new generation of neuroleptics that have been introduced for the treatment of schizophrenia. Risperidone, a member of a class of antipsychotics that blocks both DA and serotonin receptors, has been established as superior to placebo and equal, or superior, to haloperidol in the treatment of schizophrenia (Chouinard et al. 1993 Marder and Meibach 1994]. Risperidone has a more favorable side-effect profile than that of conventional neuroleptics and may have less potential for producing tardive dyskinesia. Compared with haloperidol, fewer extrapyramidal side effects are observed with risperidone in doses of 6 mg/ day or less. As encouraging reports appear in the literature (Lombroso et al. 1995 Stamenkovic et al. 1994 van der Linden et al. 1994], risperidone is currently being widely used by clinicians to treat tic disorders. 

Breier A, Meehan K, Birkett M, et al A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia. Arch Gen Psychiatry 59 441 48, 2002... 

Two dose effect studies with haloperidol allow a statement to be made regarding adequate doses, at least for this antipsychotic a double-blind comparison between daily doses of 10, 30 and 80 mg of haloperidol in 87 recently hospitalized patients with schizophrenia revealed no advantage of the two higher doses over the dose of lOmg per day (Rifkin ei al., 1991), and a study by McEvoy et cd. (1991) in 106 patients with schizophrenia and schizoaffective psychoses showed that an increase in dose above an individually optimal level (mostly less than lOmg per day in this study) produced no additional therapeutic effect but rather an increase in side effects, especially EPS. 

Bilder, R.M., Goldman, R.S., Volavka, J., et al Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder.. 4m. J. Psychiatry 159, 1018-1028, 2002. 

Pimozide is FDA-labeled for Tourette s disorder and is particularly interesting in that it is a highly specific DA antagonist that may produce fewer adverse effects than haloperidol. In open studies with adequate doses, this agent has demonstrated efficacy for acute schizophrenia. Several double-blind trials comparing pimozide with other neuroleptics also found it to be an equally effective maintenance therapy ( 34, 35, 36, 37 and 38). We consider this agent to be as effective as the other standard agents, with the same, but perhaps less severe, side effects. 

Arvanitis and Miller (129) reported a multiple fixed-dose, placebo-controlled, double-blind study of quetiapine in comparison with haloperidol and placebo in acutely exacerbated patients with chronic schizophrenia. Quetiapine was administered in five doses 75, 150, 300, 600, and 750 mg/day haloperidol was given at 12 mg/day. The study design had slightly more than 50 patients in each group. The 75-mg dose of quetiapine was clearly less efficacious than the higher doses. Doses of 150 to 750 mg/day were superior to placebo and comparable with haloperidol in reducing positive symptoms and 300 mg/day was superior to placebo and comparable with haloperidol for negative symptoms. 

Altamura AC, Mauri MC, Mantero M, et al. Clonazepam/haloperidol combination therapy in schizophrenia a double-blind study. Acta Psychiatr Scand 1987 76 702-706. 

Csernansky J, Okamoto A. Risperidone vs haloperidol for prevention of relapse in schizophrenia and schizoaffective disorder. Presented at the Annual Meeting of the American College of Neuropsychopharmacology, Acapulco, December 12-16,1999. 

Smith RC, Baumgartner R, Misra CH, et al. Haloperidol. Plasma levels and prolactin response as predictors of clinical improvement in schizophrenia. Chemical versus radioreceptor plasma level assays. Arch Gen Psychiatry 1984 41 1044-1049. 

Doddi S, Rifkin A, Karajgi B, et al. Blood levels of haloperidol and clinical outcome in schizophrenia. J Clin Psychopharmacol 1994 14 187-195. 

Kirch GG, Bigelow LB, Korpi ER, et al. Serum haloperidol concentration and clinical response in schizophrenia. Schizophr But 1988 14 283-289. 

Coryell W, Kelly M, Perry P, et al. Haloperidol plasma levels and acute clinical change in schizophrenia. J Clin Psychopharmacol 1990 10 397-402. 

Kidron R, Averbuch I, Klein E, et al. Carbamazepine-induced reduction of blood levels of haloperidol in chronic schizophrenia. Biol Psychiatry 1985 20 219-222. 

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