Thesis (PhD)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Prospective, longitudinal clinical studies in first-episode schizophrenia have become relatively
commonplace over the past two decades or more and have provided a wealth of useful information
regarding the clinical presentation, treatment, course and outcome of the illness. However, there
remain several unanswered questions. The majority of the studies have been conducted in upper
income countries using often costly medication with heterogeneous samples. While the overall outcome
of patients showed some progress, there is room for improvement yet. The overall aim of the
dissertation was to study the clinical, biological and functional aspects of outcome in first episode
schizophrenia in a resource constrained setting.
We conducted a prospective, non-comparative, longitudinal study over 12 months assessing the efficacy
and tolerability of a cost effective, long-acting injectable antipsychotic (LAI; flupenthixol decanoate)
combined with an assertive monitoring program (AMP) among first-episode schizophrenia patients.
Efficacy was measured by examining rates of response, remission and relapse, as well as quality of life
and social and occupational functioning. Tolerability of our intervention was assessed by measuring
extrapyramidal symptoms, and weight and metabolic changes. We also examined the evolution of
treatment refractoriness by studying the rates of non-response, and other associated predictor and
outcome features.
We found high rates of acceptance and adherence to the LAI and AMP. Seventy percent of our patients
completed the 12 months of treatment. Treatment response was achieved by 82% of the participants and 60% achieved remission. Although 19% of our patients relapsed, the majority of the relapses were
mild and did not require hospitalisation. Patients experienced significant quality of life and social and
occupational functioning improvements. We found mild rates of extrapyramidal effects, present in only
a third of our cohort. The majority of the extrapyramidal effects were treated with anticholinergics or
propranolol. Only 3% of our patients developed transient dyskinesia over the duration of the study.
However, our cohort gained considerable weight, with statistically significant increases in BMI (p< .0001)
and waist circumference (p=0.0006). Our cohort also experienced significant deleterious changes to
their lipid profiles. Of particular concern was the increase in triglycerides (p=0.03) and a significant
decrease in high density lipoprotein (p=0.005) leading to a 91% increase in the triglyceride/high density
lipoprotein ratio.
With regards to emerging treatment refractoriness, 12% of our patients met our pre-defined criteria for
non-response. Non-responders were younger and at baseline showed more prominent disorganised
symptoms, poorer social and occupational functioning, poorer quality of life for psychological, social and
environmental domains, more prominent neurological soft signs (NSS), and lower BMI. At endpoint the
non-responders were characterised by higher levels of symptomatology in all domains; poorer
functional outcome, poorer quality of life and greater cognitive impairments. They also had more
prominent NSS and a lower BMI. The strongest predictors of non-response were prominent baseline
NSS and poor early (7 weeks) treatment response.
In conclusion, the combination of an LAI with an AMP may be an effective and safe intervention in firstepisode
schizophrenia, and may be particularly suitable for resource-constrained settings. The risk of
weight gain and metabolic syndrome associated with antipsychotic treatment in first-episode
schizophrenia are not restricted to second generation antipsychotics and low-potency first-generation
antipsychotics. Ensuring effective treatment for first episode schizophrenia patients is a global problem,
and likely to be under-recognised in LMICs. / AFRIKAANSE OPSOMMING: Oor die afgelope twee dekades het toenemend meer longitudinale kliniese studies, wat eerste episode
skisofrenie bestudeer, die lig gesien. Die studies het ‘n magdom van waardevolle inligtng oor die
kliniese voorkoms, behandeling, verloop en uitkomste van die siekte opgelewer. Die meerderheid van
die studies is egter in hoë inkomste ontwikkelde lande gedoen met pasiënte wat duur medikasie gebruik
en hoofsaaklik in heterogene steekproewe. Alhoewel dit blyk uit hierdie studies dat daar oor die
algemeen vordering gemaak word ten opsigte van die behandeling van pasiënte is daar steeds ‘n gebrek
aan voldoende inligting oor die onderwerp veral in minder gegoede, ontwikkelende lande. Die
oorhoofse doel van hierdie proefskrif is om binne ‘n hulpbron beperkte konteks die kliniese, biologiese
en funksionele aspekte van pasiënt -uitkomste in eerste episode skisofrenie te ondersoek.
Ons het ‘n longitudinale studie gedoen waarin ons die effektiwiteit en toleransie van ‘n enkele
antipsigotiese medikasie vir 12 maande nagevors het. Die medikasie wat ons ondersoek het, is
flupenthixol decanoate en word deur ‘n inspuiting gegee en die medikasie word dan geleidelik deur die
liggaam geabsorbeer. As deel van die behandeling het ons pasiënte ook streng gemonitor. Ons het die
effektiwiteit van die behandeling gemeet nagelang van hoe pasiënte reageer op die behandeling,
hoeveel pasiënte in remissie gaan en terugval, en ook pasiënte se kwaliteit van lewe en hulle sosiale en
beroepsfunksionering. Ons het toleransie gemeet nagelang van pasiënte se gewig en metaboliese
verandering sowel as die voorkoms van medikasie geïnduseerde newe-effekte. Verder het ons pasiënte
wat nie op medikasie gereageer het nie ondersoek sowel as die aspekte wat moontlik hiernee verband
hou. Ons het bevind dat die meerderheid van pasiënte hulle medikasie getrou geneem het en ook die streng
monitering aanvaar het. Sewentig persent van die pasiënte het hulle 12 maande behandeling voltooi,
82% het op die medikasie gereageer en 60% het in remissie ingegaan. Alhoewel 19% van die pasiënte
teruggeval het, was dit nie so ernstig dat ons hulle moes hospitaliseer nie. Pasiënte het beduidende
verbetering ten opsigte van hulle kwaliteit van lewe en sosiale en beroepsfunksionering getoon. Ons het
slegs ‘n gematigde mate van medikasie geïnduseerde newe-effekte opgemerk en alleenlik by ‘n derde
van die kohort. In die meerderheid van gevalle het ons die newe-effekte met anticholinergics of
propranolol behandel. Slegs 3% van die pasiënte het gedurende die verloop van 12 maande die kondisie
transient dyskinesia ontwikkel. Ongelukkig het ons kohort geweldig baie gewig opgetel en die toename
in pasiënte se BMI (p< .0001) en middellyf omtrek (p=0.0006) was statisties beduidend. Ons het ook
bevind dat veranderinge in ons kohort se lipied profiele kommerwekkend is veral as in ag geneem word dat die toename in trigliseriede (p = 0,03) en die beduidende afname in die hoë digtheid lipoproteïen (p
= 0,005) gelei het tot ‘n 91% verhoging in trigliseriede: hoë digtheid lipoproteïen verhouding.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/97904 |
| Date | 12 1900 |
| Creators | Chiliza, Bonginkosi |
| Contributors | Emsley, Robin, Stellenbosch University. Faculty of Health Sciences. Dept. of Psychiatry. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | English |
| Type | Thesis |
| Format | 83 pages |
| Rights | Stellenbosch University |
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