The purpose of this study was to describe family members' influence on medication adherence rates for schizophrenic clients following an educational program presented simultaneously to both client and family member. Three chronic schizophrenic clients participated in this study, two were females, and the other was male. The two family members who provided data were husbands of the two female clients. The obtained scores and responses of two questionnaires was indicative of improved medication adherence for clients and family members. The level of adherence was similarly perceived by the clients and their family members as obtained scores and responses were similar across both time periods. However, family members' attendance at the program presentation did not influence the level of reported medicated adherence behaviors of their wives as compared to the client who attended the program alone because the greatest increase in obtained scores was reported by the client who attended the program alone.

Adherence to antipsychotic medication in schizophrenia has been shown to predict symptom exacerbations; however, adherence remains poor in this population. The concept of taking medication on a maintenance regime is an example of prospective memory (PM). The current investigation is comprised of three studies in which 59 outpatients diagnosed with schizophrenia completed a comprehensive assessment including measures of PM, executive functioning, comprehension of medication instructions, insight into the need for medication, and environmental variables supporting adherence. An objective measure of medication adherence was also collected during a one-month baseline period. In study 1, medication adherence was conceptualized as a PM task and variables for predicting adherence based on PM literature were examined. Of the hypothesized variables, the interactive effect of PM ability and comprehension of medication instructions was the only predictor of adherence to antipsychotic medication. Comprehension of medication instructions alone was the only predictor of adherence to total psychotropic medication regime. Study 2 investigated the role of executive functions in the awareness of PM deficits and use of compensatory strategies. Results indicated that patients with poorer executive skills were less reliable in their report of PM ability compared to performance on PM measures. However, both fair and poor executive functioning groups reported similar use of compensatory strategies. Lastly, the third study manipulated the specificity of retrieval context for a 5-day habitual PM task intended to mimic medication-taking. The aim of this investigation was to examine the effect of retrieval context specificity and executive functioning on task performance. Results demonstrated that patients categorized as fair executive functioning completed significantly more days of the habitual task than patients categorized as poor executive functioning. There was no difference in performance between patients receiving greater retrieval context specificity versus patients receiving a general context. However, there was a trend for individuals with fair executive functioning to benefit from greater retrieval context specificity, implying that a minimum level of executive skill may be necessary for individuals to recognize the risk of a restricted retrieval interval and/or mobilize additional resources for encoding. Clinical implications are discussed. / text

Dissertation (DSc)-- Stellenbosch University, 2008. / ENGLISH ABSTRACT: The overall aim of these studies was to investigate selected aspects of psychopathology, neurobiological abnormalities and treatment in schizophrenia. The following topics were researched: 1. Psychopathology: We explored the symptom structure of schizophrenia by means of principal components and factor analysis in two separate samples. a. The first study investigated the nature of symptoms in patients with a first-episode of schizophrenia, in a large cohort of patients who were participating in a multinational clinical trial. We compared our findings with similar analyses previously conducted in multi-episode schizophrenia patients. b. We then assessed the influence of culture on the symptom structure of schizophrenia by conducting a principal components and factor analysis of the symptom ratings in a large sample of South African Xhosa patients with schizophrenia, and comparing the results with those in other parts of the world. c. We investigated the occurrence of co-morbid depressive and anxiety symptoms, and their demographic and clinical correlates. The sample for this study comprised acutely psychotic patients who were participants in clinical drug trials conducted at our centre. d. To explore the relationships between obsessive-compulsive disorder and schizophrenia, we conducted a review of the relevant literature. 2. Neurobiological abnormalities: a. We performed a series of studies to investigate disorders of water homeostasis and vasopressin secretion in schizophrenia. To test the hypothesis that acutely psychotic patients have disordered regulation of water homeostasis, we applied a dynamic suppression test - a water loading test, with assessment of excretory capacity (including arginine vasopressin assay) in acutely psychotic patients. To evaluate whether a subset of patients with schizophrenia and co-morbid disordered water homeostasis sustained cerebral damage as a consequence of water intoxication we did the following experiment: We identified a cohort of subjects with schizophrenia and disordered water homeostasis and compared them with patients with schizophrenia without disordered water homeostasis in terms of cerebral ventricular size and cognitive function. To assess the prevalence of disordered water homeostasis in a long-term inpatient sample of psychiatric patients we conducted serum sodium screening tests. Those subjects with dilutional hyponatraemia were then further investigated for dysregulation of water homeostatic mechanisms. b. We studied neurological soft signs in a sample of subjects with first-episode schizophrenia followed up over a two year period. We investigated their occurrence, relationships to psychiatric symptoms and medication effects, their temporal stability and their outcome correlates. We also investigated their potential to predict outcome in schizophrenia 3. Treatment aspects A great deal of our work has focussed on the pharmacological treatment of schizophrenia. The following aspects of treatment are included in this thesis: a. Treatment effects on psychiatric symptoms: i. To assess the effects of ethnicity on treatment outcome in schizophrenia we compared the acute response to antipsychotic treatment in 3 ethnic groups, namely blacks, coloureds and whites. We included patients in this analysis who had participated in clinical trials in our department as well as the Department of Psychiatry in the University of the Free Sate. Patients had been treated under blinded conditions over a 6-week period. ii. After discussions with the late Dr David Horrobin, who had pioneered possible applications of the omega-3 fatty acids in the treatment of various psychiatric disorders, we became interested in further investigating the potential of this group of compounds as an affordable adjunct to treating schizophrenia. We assessed the antipsychotic potential of the omega-3 fatty acid, ethyl-eicosapentaenoic-acid (e-EPA) supplementation versus placebo supplementation in a small sample of subjects with schizophrenia who had been only partially responsive to antipsychotic treatment previously. We also conducted a review of the literature to evaluate the evidence for efficacy for the omega-3 fatty acids in schizophrenia according to published studies. b. Treatment effects on neurological abnormalities: i. In a single-blinded controlled study we compared a new generation antipsychotic to a conventional antipsychotic in the treatment of tardive dyskinesia (TD). This was a long-term (1 yr) study in patients with chronic schizophrenia and established tardive dyskinesia. ii. We also assessed the effect of omega-3 fatty acid (e-EPA) supplementation in treating TD. This was conducted in a larger sample (n=84) of patients with chronic schizophrenia and established TD. The blinded, placebo-controlled phase was 12 weeks. This was followed by an open-label extension for 40 weeks. c. Conventional versus new generation antipsychotic agents. Several evidence-based literature reviews of the efficacy and tolerability of the new generation of antipsychotics compared to the conventional agents were conducted. Some multinational, randomised, controlled clinical trials in which the author was principal investigator, are included in this thesis. Also, studies addressing patients with partial treatment refractoriness are included, as well as studies of the effects of antipsychotics on depressive symptoms, body mass and glycaemic control. Finally, we have included a pharmacoeconomic study comparing a conventional antipsychotic (haloperidol) with a new generation antipsychotic (quetiapine) in partially refractory patients in a South African setting. Findings and conclusions: 1. Psychopathology: Our studies demonstrated that the factor structure for the symptoms of schizophrenia is replicable across samples, and is not greatly influenced by ethnic and cultural factors. However, changes in the factor structures do occur over time. There are symptom domains that are present in first-episode schizophrenia but disappear as a distinct entity as the illness becomes chronic. Particularly, a motor component is evident in untreated patients, but disappears after initiation of treatment. We found that depression and anxiety are common co-morbid symptoms in schizophrenia, and have important clinical and outcome correlates. Depressive symptoms in the acute psychotic phase of schizophrenia are associated with a favourable prognosis and diminish as the symptoms of psychosis improve in response to antipsychotic treatment. However, persistent depressive symptoms are associated with a poorer prognosis, and require additional therapeutic intervention. 2. Neurobiological abnormalities: We investigated the occurrence of disordered water regulation in a population of psychiatric inpatients, and conducted further investigations on those identified, in order to establish mechanisms involved. Polydipsia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) were found to occur in a subset of patients with schizophrenia, and are associated with acute psychosis, as well as with some psychotropic medications. These patients are characterised by more severe cognitive impairment and evidence of cerebral atrophy. The condition can become life-threatening in the presence of other factors impeding water excretion, particularly thiazide diuretics. Neurological soft signs were investigated in a sample of patients with a first-episode of schizophrenia. These soft signs appear to be trait-like (present early in the illness, and stable over time), except for a motor sequencing factor. Patients performing poorly on this latter group of tests have a longer duration of untreated psychosis, and are at significant risk for developing TD. 3. Treatment aspects: Our studies suggest that there are important ethnic differences in antipsychotic treatment response, but that these differences could be explained by a number of environmental and biological factors. As was found with many studies worldwide, we found that the new generation antipsychotics have important efficacy and safety advantages over their predecessors. Risperidone was as effective as haloperidol in first-episode psychosis, but with a more favourable side-effect profile in terms of reduced extrapyramidal symptoms. Quetiapine treatment in partially refractory patients resulted in more responders compared to haloperidol, and fewer extrapyramidal symptoms. However, evidence of a different side-effect profile is emerging. Of particular concern is the finding that some of the new antispychotics cause weight gain, glucose intolerance and dyslipidaemias. We found that one novel antipsychotic, quetiapine, was not associated with significantly more weight gain or disordered glucose metabolism that a conventional agent, haloperidol. The omega-3 fatty acids, particularly EPA may have a role in the treatment of various psychiatric disorders. Our studies provided mixed results – the first found a significant beneficial effect on psychotic symptoms and dyskinesia scores for EPA supplementation, while the second failed to demonstrate a beneficial effect on TD or psychotic symptoms. We explored the early treatment response in first-episode psychosis and found, unlike that reported in multi-episode patients, some patients took a long time to respond. We also found that early treatment response was a significant predictor of later remission, as was duration of untreated psychosis, educational level and baseline excitement factor scores. Finally, our pharmacoeconomic study conducted for South African circumstances in patients with a partial response to conventional antipsychotic treatment showed cost-neutrality or cost-benefits for quetiapine compared with haloperidol treatment for direct costs. / AFRIKAANSE OPSOMMING: Die oorkoepelende doel van hierdie studies was om geselekteerde aspekte van psigopatologie, neurobiologiese abnormaliteite en behandeling in skisofrenie te ondersoek. Die volgende onderwerpe is nagevors: 4. Psigopatologie: Ons het die simptoomstruktuur van skisofrenie ondersoek deur middel van hoofkomponent- en faktoranalise in twee aparte steekproewe. a. Die eerste studie het die aard van simptome in pasiënte, met ʼn eerste-episode van skisofrenie, ondersoek in ʼn groot kohort van pasiënte wat deelgeneem het aan ʼn multi-nasionale kliniese proefneming. Ons het ons bevindinge vergelyk met soortgelyke analises wat voorheen gedoen is in multi-eposode skisofrenie pasiënte. b. Hierna het ons die invloed van kultuur op die simptoom struktuur van skisofrenie geassesseer deur ʼn hoofkomponent- en faktoranalise van die simptoomtellings uit te voer in ʼn groot steekproef van Suid-Afrikaanse Xhosa pasiënte met skisofrenie en die resultate te vergelyk met bevindinge in ander dele van die wêreld. c. Ons het die voorkoms van ko-morbiede depressiewe en angssimptome ondersoek, asook hul demografiese en kliniese korrelate. Die steekproef vir hierdie studie het bestaan uit akute psigotiese pasiënte wat deelnemers was in ʼn kliniese geneesmiddel proef wat uitgevoer is by ons sentrum. d. Om die verband tussen obsessief-kompulsiewe steurnis en skisofrenie te verken, het ons ʼn oorsig van die relevante literatuur gedoen. 5. Neurobiologiese abnormaliteite: a. Ons het ʼn reeks studies uitgevoer om steurnisse in water homeostase en vasopressien sekresie in skisofrenie te ondersoek. Om die hipotese dat akute psigotiese pasiënte versteurde regulering van water homeostase het te ondersoek, het ons ʼn dinamiese onderdrukkingstoets toegepas – ʼn water ladingstoets, met assessering van ekskresiekapasiteit (insluitend arginien vasopressien essai) in akute psigotiese pasiënte. Om te evalueer of ʼn onderafdeling van skisofrenie pasiënte met ko-morbiede versteurde water homeostase serebrale skade opgedoen het as gevolg van water intoksikasie, het ons die volgende eksperiment uitgevoer: Ons het ʼn kohort deelnemers met skisofrenie en versteurde water homeostase geïdentifiseer en hulle vergelyk met skisofrenie pasiënte sonder versteurde water homeostase in terme van serebrale ventrikulêre grootte en kognitiewe funksionering. Om die voorkoms van versteurde water homeostase in ʼn langtermyn binne-pasiënt steekproef van psigiatriese pasiënte te bepaal, het ons serum natrium siftingstoetse uitgevoer. Deelnemers met hiponatremie is hierna verder ondersoek vir disregulering van water homeostatiese meganismes. b. Ons het neurologiese sagte tekens in ʼn steekproef van deelnemers met eersteepisode skisofrenie bestudeer en opgevolg oor ʼn twee jaar tydperk. Ons het hulle voorkoms, verwantskappe met psigiatriese simptome en medikasie effekte, hulle temporale stabiliteit en hul uitkoms korrelate ondersoek. Ons het ook hulle potensiaal om die uitkoms in skisofrenie te voorspel, ondersoek. 6. Behandelings aspekte ʼn Groot meerderheid van ons werk het gefokus op die farmakologiese behandeling van skisofrenie. Die volgende aspekte van behandeling is ingesluit in hierdie tesis: a. Behandelingseffekte op psigiatriese simptome: i. Om die effek van etnisiteit op behandelingsuitkoms in skisofrenie te assesseer, het ons die akute respons op anti-psigotiese behandeling in 3 etniese groepe vergelyk, naamlik swart, gekleurd, en wit. Ons het pasiënte wat deelgeneem het aan kliniese proefnemings in ons departement sowel as die Departement Psigiatrie van die Universiteit van die Vrystaan ingesluit in hierdie analise. Pasiënte is behadel onder geblinde toestande oor ʼn tydperk van 6 weke. ii. Na besprekings met wyle Dr David Horrobin, wie die moontlike toepassings van omega-3 vetsure in die behandeling van verskeie psigiatreise steurnisse gepionier het, het ons begin belangstel in verdere ondersoek na die potensiaal van hierdie groep samestellings as ʼn bekostigbare toevoeging in die behandeling van skisofrenie. Ons het die anti-psigotiese potensiaal van die omega-3 vetsuur, etieleikosapentanoësuur (e-EPA) supplementasie versus plasebo supplementasie ondersoek in ʼn klein steekproef van deelnemers met skisofrenie wat slegs gedeeltelik responsief was op anti-psigotiese behandeling in die verlede. Ons het ook ʼn literatuuroorsig gedoen om die bewyse vir die effektiwiteit vir die omega-3 vetsure in skisofrenie te evalueer volgens gepubliseerde studies. b. Behandelingseffekte op neurologiese abnormaliteite: i. In ʼn enkelblinde kontrole studie het ons ʼn nuwe generasie anti-psigotiese medikasie vergelyk met ʼn konvensionele anti-psigotiese medikasie in die behandeling van tardiewe diskinesie (TD). Hierdie was ʼn langtermyn (1- jaar) studie in pasiënte met chroniese skisofrenie en vasgestelde TD. ii. Ons het ook die effek van omega-3 vetsuur (e-EPA) suplementasie geassesseer in die behandeling van TD. Dit was gedoen in ʼn groter steekproef (n=84) van pasiënte met chroniese skisofrenie en vasgestelde TD. Die blinde, placebo kontrole fase was 12 weke. Dit is gevolg deur ʼn nie-geblinde ekstensie vir 40 weke. c. Konvensionele versus nuwe generasie anti-psigotiese agente. Verskeie bewys-gebaseerde literatuuroorsigte oor die effektiwiteit en toleransie van die nuwe generasie anti-psigotiese agente in vergelyking met die konvensionele agente, is gedoen. Sommige multi-nasionale, ewekansige, kontole kliniese proefnemings waarin die outeur die hoofnavorser was, is ingesluit in hierdie tesis. Verder, studies wat die pasiënte met gedeeltelike behandelingsweerstandigheid aanspreek, is ingesluit, sowel as studies oor die effekte van anti-psigotiese agente op depressiewe simptome, liggaamsmassa en glisemiese kontrole. Laastens, het ons a farmakoekonomiese studie ingesluit wat die konvensionele anti-psigotiese behandeling (haloperidol) met ʼn nuwe generasie anti-psigotiese behandeling (quetiapien) in gedeeltelik weerstandige pasiënte in ʼn Suid-Afrikaanse ligging vergelyk. Bevindinge en gevolgtrekkings: 4. Psigopatologie: Ons studies het gedemonstreer dat die faktor struktuur vir die simptome van skisofrenie herhaalbaar is oor steekproewe, en dat dit nie grootliks beïnvloed word deur etnisiteit en kulturele faktore nie. Veranderinge vind egter in die faktor strukture wel plaas met verloop van tyd. Daar is simptoom domeine wat teenwoordig is in eerste-episode skisofrenie, maar verdwyn as ʼn afsonderlike entiteit soos wat die toestand chronies word. Spesifiek, ʼn motoriese komponent is duidelik in onbehandelde pasiënte, maar verdwyn na die aanvang van behandeling. Ons het gevind dat depressie en angs algemene ko-morbiede simptome in skisofrenie is en het belangrike kliniese en uitkoms korrelate. Depressiewe simptome in die akute psigotiese fase van skisofrenie word geassosieer met ʼn gunstige prognose en verminder soos wat die simptome van psigose verbeter in repons op anti-psigotiese behandeling. Egter, volgehoue depressiewe simptome word geassosieer met ʼn swakker prognose en benodig addisionele terepeutiese intervensie. 5. Neurobiologiese abnormaliteite: Ons het die voorkoms van versteurde water regulering ondersoek in ʼn populasie van psigiatriese binne-pasiënte en verdere ondersoek ingestel op dié wie geïdentifiseer is, om die betrokke meganismes vas te stel. Polidipsie en en die sindroom van onvoldoende antidiuretiese hormoon sekresie (SIADH) is gevind om voor te kom in ʼn onderafdeling van pasiënte met skisofrenie, en word geassosieer met akute psigose sowel as met somige psigotropiese medikasie. Hierdie pasiënte word gekenmerk deur meer ernstige kognitiewe beperking en bewyse van serebrale atrofie. Die toestand kan lewensbedreigend raak in die teenwoordigheid van ander faktore wat water ekskresie hinder, veral tiasied diuretikums. Neurologiese sagte tekens is ondersoek in ʼn steekproef van pasiënte met eerste-episode skisofrenie. Hierdie sagte tekens blyk om kenmerkend (teenwoordig vroeg in die siekte, en stabiel oor tyd) te wees, behalwe vir ʼn motoriese volgorde faktor. Pasiënte wat swak vaar op die laasgenoemde groep toetse, het ʼn langer durasie van onbehandelde psigose, en het ʼn beduidende risko om TD te ontwikkel. 6. Behandeling aspekte: Ons studies stel voor dat daar ʼn belangrigke etniese verskil is in anti-psigotiese behandelingsrespons, maar dat hierdie verskille verduidelik kan word deur ʼn aantal omgewings- en biologiese faktore. Soos wat gevind was vir verskeie studies wêreldwyd, het ons gevind dat die nuwe generasie anti-psigotiese agente belangrike effektiwiteit- en veiligheidsvoordele het bo hulle voorgangers. Risperidoon was net so effektief as haloperidol in eerste-episode psigose, maar met ʼn meer gunstige newe-effkte profiel in terme van verminderde ekstrapirimidale simptome. Quetiapien behandeling in veral refraktêre pasiënte het gelei tot meer respondeerders vergeleke met haloperidol, en minder ekstra pirimidale simptome. Alhoewel, bewyse van ʼn verskillende newe-effekte profiel is besig om na vore te kom. Van spesifieke belang is die bevinding dat sommige van die nuwe anti-psigotiese agente gewigstoename, glukose intoleransie en dyslipidemie veroorsaak. Ons het gevind dat een nuwe anti-psigotiese agent, quetiapien, nie geassosieer was met enige beduidende meer gewigstoename of versteurde glukose metabolisme as ʼn konvensionele agent, haloperidol, nie. Die omega-3 vetsure, spesifiek EPA mag moontlik ʼn rol in die behandeling van verskeie psigiatriese versteurings hê. Ons studies het gemengde resultate voorsien – die eerste het ʼn beduidende voordelige effek op psigotiese simptome en diskinesie tellings vir EPA supplementasie gevind, terwyl die tweede nie ʼn voordelige effek op TD of psigotiese simptome gevind het nie. Ons het die vroeë behandelingsrespons ondersoek in eersteepisode pasiënte en het gevind, in teenstelling met dit wat gerapporteer word in multi-episode pasiënte, dat sommige pasiënte ʼn lang tyd geneem het om te reaggeer. Ons het ook gevind dat vroeë behandelingsrespons ʼn beduidende voorspeller was van latere remissie, so ook die durasie van onbehandelde psigose, opvoedingspeil, en basisvlak opwindings-faktor tellings. Laastens het ons farma-ekonomiese studie, wat uitgevoer is vir Suid-Afrikaanse omstandighede in pasiënte met ʼn gedeeltelike repons op konvensionele anti-psigotiese behandeling, koste-neutraliteit of koste-voordele aangetoon vir quetiapien vergeleke met haloperidol behandeling vir direkte onkostes.

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.

Physicians are often unaware of mentally disabled outpatients' symptomatic behaviors that are relevant to their medication prescriptions. Such information is available to the clients' residential care providers . The present study trained clients' residential care providers in data collection and provided these data to physicians. It was predicted that these data would improve medication treatment for these clients and consequently lead to a decrease in client's symptomatic behaviors . The results did not confirm the predictions; the data provided to physicians on clients' between- visit behaviors had no measured effect on the physicians' treatment of these clients, although the physicians reported positive attitudes about the helpfulness and utility of ·the system .

Thesis (DMed (Psychiatry))--University of Stellenbosch, 2007. / This study reports on the effect of seminar education by studying changes in knowledge, attitude and behaviour to haloperidol prescribing patterns of psychiatrists who In summary, this study demonstrated a direct relationship between seminar attendance and changes to selected minimum effective haloperidol dose and duration of treatment. However, seminar attendance did not appear to be a significant factor in changes to antipsychotic class used for treatment and changes in optimal effective haloperidol dose: rather a change in the level of “background” knowledge of participants was most likely responsible. This study also found individual participant characteristic differences in those who did change treatment duration and minimum effective dose. In conclusion, this study showed that the successful integration of international treatment recommendations into daily psychiatric practise could be facilitated by the use of appropriate educational seminars. Not all attendees benefit i.e. “learn”, but those needing to “learn” most do - i.e. those who need to change their prescribing habits most to meet internationally accepted guidelines. The peer exposure provided allows a format for informed discussion and the practise of evidence-based medicine. The judicious use of such seminars should result in better treatment options and outcomes for patients.attended evidence-based schizophrenia seminars presented by the Lundbeck Institute in Denmark. The objectives of the study were two-fold. Firstly, it set out to determine whether changes actually occurred in the post-seminar haloperidol prescribing behaviour of participants. This was done by analysing changes in choice of optimal haloperidol dose (both in acute treatment i.e. most effective dose and maintenance treatment i.e. minimum effective dose), selected duration of treatment (for first- and multi-episode schizophrenia patients) and drug-class used (conventional versus new generation antipsychotic). The study then investigated whether these changes (if they occurred) could be ascribed wholly or in part to the effect of schizophrenia seminar attendance, or whether other factors e.g. scientific progress over time in understanding schizophrenia and its treatment (“background” knowledge) and differences between participant datasets studied (only paired pre- and post-seminar data were used in this study) also played a role. Secondly, it attempted to identify factors predictive of seminar participants changing their haloperidol prescribing behaviour post-seminar i.e. what were the factors that predisposed some attendees to change their prescribing behaviour? This was done by analysing the effect that pre-seminar prescribing behaviour, participant nationality, patient caseload, work experience and workplace environment had on post-seminar behaviour. Results show that changes did occur in post-seminar haloperidol prescribing behaviour, but that they were not always due to an effect of seminar attendance. Only the changes in the minimum effective haloperidol dose and duration of treatment for first- and multi-episode schizophrenia patients could validly be ascribed to the effects of schizophrenia seminar attendance. Furthermore, multivariate analysis of the factors relating to these changes found that a participant was most likely to change their selected minimum effective haloperidol dose to be more in line with internationally accepted standards if they i) selected above the target dose pre-seminar, ii) had a relatively low caseload comprised mainly of schizophrenia patients and iii) came from either Greece, Germany, Britain, Spain, Italy or some other Eastern European country. The single most important factor related to changes in duration of treatment was found to be pre-seminar behaviour: respondents below the recommended duration of treatment increased their duration of treatment significantly.