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.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/49804 |
| Date | January 1900 |
| Creators | Oosthuizen, P. P. (Petrus Paulus) |
| Contributors | Emsley, R. A., Stellenbosch University. Faculty of Medicine & Health Sciences. Dept. of Psychiatry . |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | Unknown |
| Type | Thesis |
| Format | 234 p. |
| Rights | Stellenbosch University |
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