Thesis (PhD (Psychiatry))--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Contemporary research has confirmed the presence of cognitive deficits as a core feature of schizophrenia that has a definite and adverse impact on functional outcome. Cognitive functioning can be improved by psychopharmacological intervention, with evidence supporting the superiority of second generation antipsychotics over their first generation predecessors. Despite evidence that cognitive impairment contributes to medication non-adherence and that depot antipsychotics are able to enhance treatment compliance whilst decreasing relapse rates, depot preparations remain less frequently prescribed than their oral counterparts, especially in patients with first episode psychosis (FEP). The aims of this study were primarily to investigate cognitive deficits in patients with FEP, and to then describe the response of these impairments to treatment with a very low dose flupenthixol decanoate. This was a prospective, non-randomized, single arm, open-label, longitudinal study of 58 participants with FEP treated according to a fixed protocol over a period of 12 months. There was a wash-out phase of up to seven days during which all psychotropic medications were discontinued. There was an initial treatment period of one week with oral flupenthixol 1mg/day, after which flupenthixol decanoate was initiated at 10mg intramuscular depot injection every fortnight. Dose increases, in cases of poor or inadequate response, were allowed at 6-weekly intervals and in increments of 10mg per injection, up to a maximum of 30mg per fortnight. The principal findings of the study were as follows: The majority of participants were markedly ill, with significant cognitive impairment at baseline. There was a discrepancy between subjectively reported, and objectively measured, cognitive impairment. The majority of the participants responded to, and achieved remission, on a very low dose of flupenthixol decanoate (22.48 ± 0.47mg/month). The majority of symptomatic and cognitive improvement occurred between baseline and three months, with response leveling out at six months. Social cognition did not improve significantly over time, whereas functional outcome and quality of life did improve with treatment. Flupenthixol decanoate was well tolerated and side-effects were of a mild and transient nature. This study reconfirms that the majority of individuals with FEP experience significant cognitive impairment at baseline. It also suggests that these impairments can be successfully treated with a very low dose of flupenthixol decanoate. The use of depot flupenthixol decanoate ensures sustained treatment delivery, thereby decreasing the risk for relapse. This holds the promise of improved long-term functional outcome for those suffering with psychotic illness. / AFRIKAANSE OPSOMMING: Onlangse navorsing het kognitiewe inkorting identifiseer as een van die kern simptoomkomplekse van skisofrenie, met toenemende bewyse vir die duidelike en ongunstige impak hiervan op funksionele uitkoms. Kognitiewe funksionering kan deur psigofarmakologiese ingrepe verbeter word. Onlangse literatuur toon dat die tweede generasie antipsigotika relatief meer effektief is as hulle eerste generasie voorgangers. Ondanks bewyse vir die negatiewe impak van kognitiewe inkorting op behandelingsinskiklikheid, én data wat daarop wys dat die gebruik van langwerkende intramuskulere (depot) antipsigotika inskiklikheid verbeter en periodes van simptoom-terugval voorkom, word dié preparate steeds minder gereeld as hulle orale eweknieë voorgeskryf, veral by pasiënte met 'n eerste episode psigose (FEP). Die doel van hierdie studie was om kognitiewe probleme by pasiënte met FEP te beskryf, en ook om die respons hiervan op behandeling met 'n baie lae dosis flupentiksol dekanoaat, te ondersoek. Die studie was 'n prospektiewe, nie-ewekansige, enkel middel, oop studie van 58 deelnemers met FEP, wat oor „n tydperk van 12 maande volgens 'n spesifieke protokol behandel is. Daar was 'n uitwas periode van 7 dae, waartydens alle psigotrope medikasie gestaak is. Hierna is behandeling met orale flupentiksol 1mg/dag begin vir een week, waarna flupentiksol dekanoaat geinisieer is teen 10mg intramuskulêr elke 2de week. Dosisverhogings, in geval van onvoldoende respons, was toelaatbaar met 6-weeklikse tussenposes, in inkremente van 10mg per inspuiting, tot 'n maksimum van 30mg elke 2de week. Die vernaamste bevindinge van die studie was soos volg: Die meerderheid van die deelnemers was ernstig siek, met beduidende kognitiewe inkorting tydens basislyn evaluasie. Daar was 'n verskil tussen subjektief-gerapporteerde en objektief-meetbare kognitiewe inkorting. Die meerderheid van die deelnemers het goed reageer op behandeling en het ook remissie op 'n baie lae dosis flupentiksol dekanoaat (22.48 ± 0.47mg/maand), bereik. Die meerderheid van simptomatiese en kognitiewe verbetering het plaasgevind binne die eerste 3 maande, met afplatting in die tempo en hoeveelheid van verbetering vanaf 6 maande. Sosiale kognisie het nie beduidend gedurende die studieperiode verbeter nie. Funksionele uitkoms en lewenskwailiteit van deelnemers het ook met behandeling verbeter. Flupentiksol dekanoaat is goed verdra en die newe-effekte, indien dit teenwoordig was, was van ligte graad en verbygaande aard. Hierdie studie herbevestig dat individue met FEP beduidende kognitiewe inkorting by basislyn ervaar, maar dat hierdie inkortings effektief met 'n baie lae dosis van flupentiksol dekanoaat behandel kan word. Die gebruik van depot flupentiksol is 'n suksesvolle manier om volgehoue behandeling te verseker en sodoende die risiko vir terugvalle te verminder. Dit verstewig dus die hoop op beter langtermyn funksionering vir persone met psigotiese siektes.