Progress in Neuro-Psychopharmacology and Biological Psychiatry
Safety, effectiveness, and quality of life of olanzapine in first-episode schizophrenia: a naturalistic study
Introduction
The first episode of schizophrenia typically takes place during adolescence or early adulthood. For the majority of patients, it is a recurrent or chronic disorder accompanied by significant impairment of psychosocial functioning. Different sociodemographic and psychopathological factors, such as being male, poor premorbid adjustment, insidious onset and at an early age, absence of triggers, and a predominance of negative symptoms are associated with poor outcomes Ram et al., 1976, Strauss and Carpenter, 1977, McGlashan, 1986, Hwu et al., 1995, Bailer et al., 1996. Nevertheless, first-episode psychosis responds better to treatment than does multiepisode psychosis, and intensive, phase-specific treatment appears to result in short-term improvements in outcome and cost effectiveness (McGorry et al., 2000). There is growing evidence that early intervention with appropriate pharmacological treatment can make a positive contribution to improving the course of illness Loebel et al., 1992, Linszen et al., 1998, McGorry et al., 2002.
Intensive psychosocial rehabilitation also helps to minimize the social impairment resulting from schizophrenia, although it is of the utmost importance that it be initiated in the earliest stages of the disease (Marshall and Lockwood, 2000). Remission must be achieved as completely and as quickly as possible and relapses must be prevented for adequate psychosocial rehabilitation to be achieved. Furthermore, posterior episodes appear to be associated with progressive clinical deterioration (McGlashan, 1988) and residual symptoms (Szymanski et al., 1995), thus hindering this process even further.
Discontinuation of medication is the most important factor in calculating the possibility of symptom exacerbation and the emergence of new episodes (Robinson et al., 1999). Treatment compliance maximizes treatment response, bringing about better remission and relapse prevention rates, thereby improving patients' clinical situation and psychosocial functioning.
Although poor adherence to treatment in schizophrenia is a complex phenomenon involving multiple factors, it is principally associated with the presence of adverse cognitive and emotional effects (neuroleptic dysphoria), as well as physical ones, in particular, those due to extrapyramidal symptoms Blackwell, 1996, Kampman and Lehtinen, 1999. For this reason, the choice of an antipsychotic that offers both effectiveness and good tolerance in the first episode of schizophrenia is essential if better treatment adherence is to be attained, thereby improving the patient's quality of life (Qol).
Qol is an issue of growing interest when assessing the results of clinical trials conducted with schizophrenic patients. The treatment objective would therefore not merely be concerned with decreasing symptoms, but also with improving subjective and objective aspects related to Qol. The new, so-called atypical antipsychotics have few or no extrapyramidal effects, a low capacity for raising prolactin levels, and offer greater effectiveness in treating negative symptoms than conventional antipsychotics (CA); all these features are presumed to be associated with improved Qol for patients.
Olanzapine, a thienobenzodiazepine, is an antipsychotic drug with atypical characteristics. The effectiveness and safety of olanzapine in treating schizophrenia has been proven in several clinical trials both when compared to placebo Beasley et al., 1996a, Beasley et al., 1996b and when compared to haloperidol (Tollefson et al., 1997) and risperidone (Tran et al., 1997). In these studies, treatment with olanzapine did not induce adverse effects significantly more frequently than did placebo (Beasley et al., 1996a) and extrapyramidal symptoms appear to be less frequent in patients treated with olanzapine than in those treated with haloperidol (Tollefson et al., 1997) or even with risperidone (Tran et al., 1997); nevertheless, another study has shown that the frequency and severity of extrapyramidal symptoms were similar in olanzapine- and risperidone-treated groups when lower dosages of the latter were used (Conley and Mahmoud, 2001).
The aims of this study were to determine the safety and effectiveness of olanzapine in routine clinical conditions versus other antipsychotic drugs in treating an outpatient population with first-episode schizophrenia and to determine patients' subjective satisfaction with treatment and Qol following 6 months of treatment.
Section snippets
Study design
Participants in this study were taken from the EFESO study (Estudio Farmacoepidemiológico en la Esquizofrenia con Olanzapina). The design of this trial has been previously described Gómez et al., 2000, Sacristán et al., 2000. Briefly put, EFESO is a Phase IV, multicenter, observational, prospective, open-label, comparative pharmacoepidemiological study conducted in parallel groups, to evaluate the safety of olanzapine in comparison with other antipsychotics in the outpatient setting. It was
Results
The sociodemographic and baseline clinical data of the 182 patients that comprised the sample are given in Table 1. For the purposes of this study, three groups were established for comparison: patients who were started on olanzapine, risperidone, or CA. Most patients in the last group were started on treatment with haloperidol (67.6%). No statistically significant differences in any of the sociodemographic or baseline clinical characteristics were observed in the three groups.
The reasons for
Safety
One of the aims of the study was to evaluate the safety of olanzapine under ordinary clinical conditions of use in treating a first episode of schizophrenia. The only adverse effect that was recorded above 10% was weight gain, similar to the incidence reported in previously run clinical trials. In contrast, somnolence, the other adverse effect related to olanzapine that is also included in the European Summary of Product Characteristics (SPC) as having a frequency greater than 10%, had a lower
Conclusions
This naturalistic study addresses the issues of safety, effectiveness, and improved Qol in first-episode schizophrenia and reveals olanzapine's substantial advantages over conventional antipsychotics and even when compared to other atypical antipsychotics such as risperidone, as proven by the lower incidence of extrapyramidal symptoms which, in turn, makes for better treatment adherence and, therefore, fewer relapses.
Acknowledgements
Participating psychiatrists in the EFESO Study Group: Patricio Ruiz, César Antón, Eva Fontova, Eduardo Ortega, Alfonso Santiso, Iñaki Márquez, Óscar Taboada, Fernando Garcı́a, José Montero, Ernesto Capdevila, Cristina Hernández, Salvador Gimeno, Raúl Fernández, Antonio Arumi, José Ignacio Mendezona, Emilio González, Enrique Aragués, Montserrat Garcı́a, Carlos Carmona, Juan Luis Figuerido, José Luis Rodrı́guez, Juan Ramón Sambola, Fernando Teba, Felisa Gómez, Elena Lozano. Jehad Kamel Suleiman,
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