A prospective study of clinical, biological and functional aspects of outcome in first episode psychosis

[摘要] ENGLISH ABSTRACT: Prospective, longitudinal clinical studies in first-episode schizophrenia have become relativelycommonplace over the past two decades or more and have provided a wealth of useful informationregarding the clinical presentation, treatment, course and outcome of the illness. However, thereremain several unanswered questions. The majority of the studies have been conducted in upperincome countries using often costly medication with heterogeneous samples. While the overall outcomeof patients showed some progress, there is room for improvement yet. The overall aim of thedissertation was to study the clinical, biological and functional aspects of outcome in first episodeschizophrenia in a resource constrained setting.We conducted a prospective, non-comparative, longitudinal study over 12 months assessing the efficacyand 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 lifeand social and occupational functioning. Tolerability of our intervention was assessed by measuringextrapyramidal symptoms, and weight and metabolic changes. We also examined the evolution oftreatment refractoriness by studying the rates of non-response, and other associated predictor andoutcome features.We found high rates of acceptance and adherence to the LAI and AMP. Seventy percent of our patientscompleted 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 weremild and did not require hospitalisation. Patients experienced significant quality of life and social andoccupational functioning improvements. We found mild rates of extrapyramidal effects, present in onlya third of our cohort. The majority of the extrapyramidal effects were treated with anticholinergics orpropranolol. 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 totheir lipid profiles. Of particular concern was the increase in triglycerides (p=0.03) and a significantdecrease in high density lipoprotein (p=0.005) leading to a 91% increase in the triglyceride/high densitylipoprotein ratio.With regards to emerging treatment refractoriness, 12% of our patients met our pre-defined criteria fornon-response. Non-responders were younger and at baseline showed more prominent disorganisedsymptoms, poorer social and occupational functioning, poorer quality of life for psychological, social andenvironmental domains, more prominent neurological soft signs (NSS), and lower BMI. At endpoint thenon-responders were characterised by higher levels of symptomatology in all domains; poorerfunctional outcome, poorer quality of life and greater cognitive impairments. They also had moreprominent NSS and a lower BMI. The strongest predictors of non-response were prominent baselineNSS 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 firstepisodeschizophrenia, and may be particularly suitable for resource-constrained settings. The risk ofweight gain and metabolic syndrome associated with antipsychotic treatment in first-episodeschizophrenia are not restricted to second generation antipsychotics and low-potency first-generationantipsychotics. Ensuring effective treatment for first episode schizophrenia patients is a global problem,and likely to be under-recognised in LMICs.

[发布机构] Stellenbosch University