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Treatment of first episode schizophrenia with low-dose haloperidol : a study in the Western Cape Province of South Africa

Dissertation (PhD)--Stellenbosch University, 2003.

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Main Author: Oosthuizen, P. P. (Petrus Paulus)
Other Authors: Emsley, R. A.
Format: Thesis
Language:en_ZA
Published: Stellenbosch : Stellenbosch University 2012
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access_status_str Open Access
author Oosthuizen, P. P. (Petrus Paulus)
author2 Emsley, R. A.
author_browse Emsley, R. A.
Oosthuizen, P. P. (Petrus Paulus)
author_facet Emsley, R. A.
Oosthuizen, P. P. (Petrus Paulus)
author_sort Oosthuizen, P. P. (Petrus Paulus)
collection Thesis
dc_rights_str_mv Stellenbosch University
description Dissertation (PhD)--Stellenbosch University, 2003.
format Thesis
id oai:scholar.sun.ac.za:10019.1/49804
institution Stellenbosch University (South Africa)
language en_ZA
last_indexed 2026-06-10T12:43:29.289Z
license_str Other — see source repository
provenance_str_mv Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository
publishDate 2012
publishDateRange 2012
publishDateSort 2012
publisher Stellenbosch : Stellenbosch University
publisherStr Stellenbosch : Stellenbosch University
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source_str SUNScholar — Stellenbosch University Repository
spelling oai:scholar.sun.ac.za:10019.1/49804 Treatment of first episode schizophrenia with low-dose haloperidol : a study in the Western Cape Province of South Africa Oosthuizen, P. P. (Petrus Paulus) Emsley, R. A. Stellenbosch University. Faculty of Medicine & Health Sciences. Dept. of Psychiatry . Schizophrenia -- Chemotherapy -- South Africa -- Western Cape Antipsychotic drugs Dissertations -- Medicine Theses -- Medicine Dissertations -- Psychiatry Theses -- Psychiatry Dissertation (PhD)--Stellenbosch University, 2003. ENGLISH ABSTRACT: Although schizophrenia is traditionally viewed as an illness with a very poor prognosis, research over the last few years indicates that early intervention may substantially improve the long-term outcome of this disorder. Several studies suggest that patients with first-episode psychosis (FEP) are more sensitive to, and require lower doses of antipsychotic medications than patients with more chronic forms of illness. However, the optimal dose of first-generation anti psychotics in patients with FEP has not been explored extensively and continues to be a controversial subject. This study evaluated the efficacy and safety of low-dose haloperidol in a South African cohort with FEP. The study was conducted in two phases: Phase 1 was an open-label, naturalistic study of 57 subjects with FEP who were commenced on 1mg of haloperidol for 4 weeks, after which gradual escalation of doses were allowed, if required. Subjects who failed to respond at haloperidol 10mg per day were switched to thioridazine. Failure to respond to thioridazine 600mg per day was interpreted to indicate treatment resistance. These subjects were then commenced on clozapine. The principal finding of this phase of the study was that the majority of subjects could be stabilized and maintained on very low doses of haloperidol (1.7 ± 1.0 mg/day at 12 months and 1.3 ±0.8 mg/day at 24 months). Ratings for extra-pyramidal side-effects did not increase significantly from baseline over the duration of the study, except in the case of tardive dyskinesia (TD), where a substantial number of subjects (12.3%) developed TD within 12 months of starting treatment. Phase 2 of the study was a double-blind, randomized controlled trial of low-dose (2mg/day) versus "standard dose" (8mg Iday) haloperidol. Forty subjects were included in this phase of the study; 20 in each treatment arm. The main finding was that there were no significant differences in treatment reponse between the two treatment groups. There were, however, significant differences between the two treatment groups in extrapyramidal side effects (EPSE), with the 8mg per day group exhibiting significantly higher levels of EPSE than the 2mg per day group. This was manifested by significant differences in scores on the Extrapyramidal Symptom Rating Scale (ESRS) and the Simpson-Angus Rating Scale. Furthermore, subjects in the 8mg haloperidol per day group required significantly higher doses of anticholinergic medication and had significantly higher mean levels of prolactin at the end of the study period. This study indicates that a majority of subjects with first-episode psychosis can be treated and maintained successfully with very low doses of haloperidol. It also shows that low-dose treatment is as effective as, and better tolerated than, "standard" doses. Despite the success with the low-dose treatment, however, there was still a much higher than expected incidence of tardive dyskinesia, a serious and potentially irreversible side-effect of neuroleptic treatment. AFRIKAANSE OPSOMMING: Hoewel skisofrenie tradisioneel gesien is as 'n siekte met 'n uiters swak prognose, dui navorsing oor die afgelope jare daarop dat vroeë ingryping die langtermynuitkoms van hierdie toestand drasties mag verbeter. Resultate van verskeie studies dui daarop dat pasiënte met eerste-episode psigose (EEP) nie net meer sensitief is vir antipsigotiese middels nie, maar ook laer dosisse daarvan benodig tydens behandeling as pasiënte met meer kroniese vorms van psigotiese siekte. Desondanks is die kwessie van die korrekte dosis van eerste generasie antipsigotika in hierdie groep nog onvolledig nagevors en bly dit 'n omstrede onderwerp. Hierdie studie het ten doel gehad om die effektiwiteit en veiligheid van lae dosis haloperidol in 'n Suid-Afrikaanse populasie van pasiënte met EEP te evalueer. Die studie is uitgevoer in twee fases: Fase 1 was 'n oop, naturalistiese studie van 57 pasiënte met EEP wat aanvanklik behandel is met 1mg haloperidol per dag vir 4 weke, waarna geleidelike verhoging van dosisse toegelaat is, soos nodig. Diegene wat nie bevredigende respons getoon het op haloperidol 10mg per dag nie, is oorgeskakel na tioridasien. Ontoereikende respons teen 600mg/dag tioridasien is geïnterpreteer as 'n aanduiding van behandelingsweerstandigheid en behandeling met klosapien is begin. Die belangrikste bevinding van hierdie fase van die studie was dat die meerderheid pasiënte gestabiliseer en in stand gehou kom word op baie lae dosisse haloperidol (1.7 ± 1.0 mg/dag op 12 maande en 1.3 ±0.8 mg/dag op 24 maande). Metings van ekstra-piramidale newe-effekte (EPNE) het nie beduidend toegeneem oor die duur van die studie nie, behalwe in die geval van tardiewe diskinese (TO), waar 'n beduidende aantal pasiënte (12.3%) TO ontwikkel het binne 12 maande na aanvang van behandeling. Fase 2 van die studie was 'n dubbelblinde, ewekansig gerandomiseerde studie waarin behandeling met lae dosis haloperidol (2mg/dag) vergelyk is met "standaard" dosis haloperidol (8mg/dag). Veertig pasiënte is ingesluit in hierdie fase van die studie, 20 in elke behandelingsarm. Die hoofbevinding was dat daar geen beduidende verskille in respons op behandeling was tussen die twee groepe nie. Daar was egter beduidende verskille in EPNE, waar die 8mg/dag groep beduidend hoër vlakke van EPNE gehad het as die 2mg/dag groep. Hierdie verskil in EPNE is aangedui deur 'n statisties beduidende verskil in tellings op die Extrapyramidal Symptom Rating Scale (ESRS) en die Simpson- Angus Rating Scale. Verder het pasiënte in die 8mg/dag groep beduidend hoër dosisse antikolinerge medikasie benodig en ook hoër gemiddelde prolaktienvlakke gehad teen die einde van studie. Hierdie studie dui dus daarop dat die meerderheid van pasiënte met EEP suksesvol behandel en in stand gehou kan word met baie lae dosisse haloperidol. Die studie wys ook daarop dat behandeling met lae dosisse net so effektief is en beter verdra word as behandeling met "standaard" dosisse. Ten spyte van die suksesvolle gebruik van lae dosisse medikasie het die studie egter ook getoon dat daar "n baie hoër as verwagte insidensie was van TO, "n emstige en potensieelonomkeerbare newe-effek van neuroleptiese behandeling. Doctoral 2012-08-27T11:33:06Z 2012-08-27T11:33:06Z 2003--03 Thesis http://hdl.handle.net/10019.1/49804 en_ZA Stellenbosch University 234 p. application/pdf Stellenbosch : Stellenbosch University
spellingShingle Schizophrenia -- Chemotherapy -- South Africa -- Western Cape
Antipsychotic drugs
Dissertations -- Medicine
Theses -- Medicine
Dissertations -- Psychiatry
Theses -- Psychiatry
Oosthuizen, P. P. (Petrus Paulus)
Treatment of first episode schizophrenia with low-dose haloperidol : a study in the Western Cape Province of South Africa
title Treatment of first episode schizophrenia with low-dose haloperidol : a study in the Western Cape Province of South Africa
title_full Treatment of first episode schizophrenia with low-dose haloperidol : a study in the Western Cape Province of South Africa
title_fullStr Treatment of first episode schizophrenia with low-dose haloperidol : a study in the Western Cape Province of South Africa
title_full_unstemmed Treatment of first episode schizophrenia with low-dose haloperidol : a study in the Western Cape Province of South Africa
title_short Treatment of first episode schizophrenia with low-dose haloperidol : a study in the Western Cape Province of South Africa
title_sort treatment of first episode schizophrenia with low dose haloperidol a study in the western cape province of south africa
topic Schizophrenia -- Chemotherapy -- South Africa -- Western Cape
Antipsychotic drugs
Dissertations -- Medicine
Theses -- Medicine
Dissertations -- Psychiatry
Theses -- Psychiatry
url http://hdl.handle.net/10019.1/49804
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