بهبود رفاه ذهنی بیماران مبتلا به اسکیزوفرنی تحت داروهای آنتی سایکوتیک غیر معمولی

Recent research indicates that subjective well-being is a major determinant of medication compliance in schizophrenia. However, it is yet unresolved whether atypical neuroleptics differ regarding subjective side-effects. A self-report instrument has been constructed to evaluate ‘subjective well-being under neuroleptics’ (SWN). The primary aims of the present study were to develop a short form of the SWN and to investigate the extent to which the atypical antipsychotic improves the patient's subjective well-being. The short form of the SWN was constructed following an item analysis based on data from 212 schizophrenic patients medicated with either typical or atypical antipsychotics. The short form of the SWN showed sufficient internal consistency and good construct validity. The SWN was only moderately correlated with positive and negative syndrome scale (PANSS) scores or changes in psychopathology (r=−0.20 to −0.37). SWN-ratings in patients receiving olanzapine were superior compared to those of patients medicated with either clozapine or risperidone on three of five domains of well-being. Clozapine reduced global psychiatric symptoms significantly more than risperidone. It is concluded that the assessment of subjective well-being under antipsychotic treatment provides an independent outcome measure which is relevant to compliance.

Despite significant advances in the pharmacotherapy of schizophrenia, non-compliance remains a major problem (Garavan et al., 1998 and Marder, 1998). Although estimated rates of non-compliance vary due to inconsistent definitions and heterogeneous samples, studies agree that 25–70% of all schizophrenic patients (median: 55%) are non-compliant. There is overwhelming evidence that non-compliant patients are more likely to relapse than medication compliers. On the basis of seven international studies, Fenton et al. (1998) concluded that non-compliant patients have a 3.7% greater risk of relapse than compliers (within six to 24 months). Though an individualized approach is clearly warranted to address the specific reasons for medication non-compliance, a growing literature has identified two major determinants, the quality of the doctor–patient relationship and the impact of antipsychotic drugs on subjective well-being (Awad, 1993; Naber, 1995, Van Putten, 1974 and Van Putten et al., 1981). Among drug-induced complaints and reasons for non-compliance are not only motor symptoms, but also affective blunting, cognitive slowing, avolition and loss of spontaneity (Windgassen, 1992 and Lewander, 1994). These distinct side-effects are sometimes hard to differentiate from primary negative symptoms and have been described in various ways: ‘pharmacogenic depression’, ‘akinetic depression’, ‘neuroleptic dysphoria’, ‘neuroleptic depression’, and ‘neuroleptic-induced anhedonia’ (Rifkin et al., 1975, Van Putten and May, 1978, Emerich and Sanberg, 1991, Harrow et al., 1991, Lader, 1993 and Wise, 1991). Considering the enormous use of neuroleptics over the last decades, it is surprising that the systematic evaluation of patients’ subjective complaints has received so little attention. Only a few studies have explored the clinical relevance of adverse subjective effects of neuroleptics (Van Putten and May, 1978, Liddle and Barnes, 1988, Jaeger et al., 1990, Selten et al., 1993 and Naber et al., 1999). As atypical antipsychotics such as clozapine, olanzapine, and risperidone rarely induce extrapyramidal symptoms which are among the most stigmatizing and subjectively disturbing side-effects of conventional antipsychotics, superior compliance has been inferred for these new agents (Marder, 1998). However, except for clozapine (Naber et al., 1999), a broad empirical basis has not been provided yet (Tollefson et al., 1997a and Tollefson et al., 1997b). Indirect evidence for enhanced subjective well-being and compliance during treatment with atypical antipsychotics has been obtained in a study conducted by Naber et al. (1994). Patients medicated with clozapine exhibited greater well-being at discharge than patients treated with conventional antipsychotics despite previous negative selection (treatment resistance). In another group of patients, subjective well-being at discharge significantly predicted medication compliance at follow-up while psychopathology did not discriminate between future compliers or non-compliers (Naber et al., 1994). The assessment of the subjective effects of antipsychotics is of major importance to assess both the benefits and burdens of drug therapy. Many well established objective examinations like the Simpson–Angus-Scale (Simpson and Angus, 1970) cover only a restricted range of side-effects. Particularly during long-term treatment, it is essential to thoroughly consider the patient's perspective which sometimes markedly differs from that of the psychiatrist. For that purpose, a self-rating scale assessing ‘subjective well-being under neuroleptic treatment’ (SWN) along five major dimensions was developed (Naber, 1995). SWN scores are barely related to objective psychopathology as assessed with the positive and negative syndrome scale (PANSS) and modestly to self-rated depression and quality of life. The patient is asked to endorse on a six-point scale well-being items that have been identified to be related to antipsychotic treatment. The 38 item version of this scale, translated into 12 languages, has been used in several double-blind controlled and open clinical trials (Ramaekers et al., 1999 and Tuynman-Qua et al., 1999) as well as in a recent study to assess the relationship between dopamine D2 receptor occupancy and subjective well-being (de Haan et al., 2000). Another major issue in psychopharmacology is related to the efficacy of the available antipsychotic agents to treat a broad range of schizophrenic symptoms. Although most patients are (re-)hospitalized due to the emergence of psychotic symptoms, there is growing awareness that the more persistent and socially disabling negative, depressive and cognitive symptoms are of major prognostic importance. In contrast to conventional antipsychotics which sometimes worsen negative symptomatology (Schooler, 1994), the new generation of serotonine–dopamine-antagonists, e.g. clozapine, risperidone, olanzapine and quetiapine, show beneficial effects on the treatment of primary cognitive and negative symptoms without additionally inducing secondary ones (like parkinsonian symptoms) (Chouinard et al., 1993, Marder and Meibach, 1994, Tollefson et al., 1997a, Tollefson et al., 1997b and Naber et al., 1999). In the present study, both subjective well-being and psychopathology were assessed in hospitalized patients treated with atypical antipsychotics at admission and shortly before discharge. Patients were either medicated with clozapine, olanzapine or risperidone. With the exception of clozapine, the atypical agents were utilized as the initial treatment. The present study had three major aims: 1. To improve the utility of the SWN for clinical settings, a short form was developed. It allows quick assessment of subjective side-effects. 2. To assess the (discriminant and convergent) validity of the short form, the relationship between SWN-subscores with objective psychopathology (PANSS) (Kay et al., 1989)), the UKU side-effect rating scale (Lingjaerde et al., 1987) and an unspecific self-rating on general well-being (Befindlichkeits-Skala [Well-Being-Scale] (Bf-S) (Zerssen, 1973)) was investigated. Finally, cut-off scores were computed for the exclusion of unreliable data based on mean differences between ‘negative’ and ‘positive’ items, i.e. questions with divergent item content. 3. Patients treated either with risperidone, olanzapine or clozapine were compared concerning objective psychopathology and subjective well-being prior to psychopharmacotherapy and at discharge. It was assumed that in line with recent research, atypical agents would ameliorate both positive and negative symptoms in the acute illness phase. The hypothesis that these drugs would differ in their effects upon subjective well-being was investigated.