ارتباط بین بهزیستی ذهنی و نشانه های افسردگی در اسکیزوفرنی مقاوم به درمان قبل و بعد از درمان با کلوزاپین

Abstract Background We examined the relationship between subjective well-being and depressive symptoms in patients with treatment-resistant schizophrenia before and after treatment with clozapine to contribute to the growing body of research regarding the determinants of patients' perspective of their own well-being in schizophrenia. Methods Forty patients with treatment-resistant schizophrenia were comprehensively evaluated for subjective well-being, schizophrenic symptoms, and depressive symptoms before and 8 weeks after the initiation of treatment with clozapine. Correlation analysis and Fisher's z-transformation statistics were performed. Results There were significant improvements in all Positive and Negative Syndrome Scale (PANSS) factor scores and Beck Depression Inventory (BDI) score over the treatment period (P < .05). Before clozapine administration, the subjective well-being score had significant negative correlations with the PANSS depression factor score (P < .05) and the BDI score (P < .05). After clozapine treatment, the subjective well-being score still had significant negative correlations with the PANSS depression factor score (P < .05) and the BDI score (P < .05) and no new associations emerged with treatment. Fisher's z-transformation statistics revealed that the correlations between the subjective well-being score and the depression score were not significantly different before and after clozapine treatment. Conclusions These results indicate that depressive symptoms are significantly associated with low subjective well-being in patients with treatment-resistant schizophrenia. The association was equally significant before and after treatment with clozapine, suggesting that the relationship does not change with clozapine treatment, even when depressive symptoms improve significantly, and that there may be a common pathophysiological basis for depressive symptoms and the subjective appraisal of well-being in schizophrenia.

Introduction Subjective well-being is a major component of the quality of life (QOL) of patients with schizophrenia, and it has been reported that subjective well-being has a strong impact on drug compliance and achieving remission in schizophrenia [1] and [2]. Therefore, a comprehensive evaluation of patients' perceptions of their own well-being is crucial in order to improve their treatment compliance and functional outcome. Since the concept of QOL was introduced in schizophrenia research, there have been efforts to identify clinical factors that are most likely to play a major role in determining subjective well-being [3]. With regard to psychopathology, a number of reports have shown that depressive symptoms are strongly related to subjective well-being [4], [5], [6], [7] and [8], while positive and negative symptoms are only moderately correlated with it [3], [4], [5], [6], [7], [8] and [9], suggesting that the detection and appropriate treatment of depressive symptoms in schizophrenia patients may affect the perception of their own well-being. However, previous studies of the association of depressive symptoms with subjective well-being mainly focused on the cross-sectional relationship in stable patients and the results may not be generalizable to other patient groups, such as treatment-resistant inpatients characterized by a high level of positive symptoms and poor functioning [10]. Moreover, it is unclear whether clozapine administration can change the relationship between depressive symptoms and subjective well-being in patients with treatment resistance. Hence, the purpose of the present study was to examine the relationship between subjective well-being and depressive symptoms in patients with treatment-resistant schizophrenia before and after treatment with clozapine, in order to contribute to the growing body of research regarding the determinants of patients' perspective of their own well-being in schizophrenia.

. Results The demographic and baseline clinical characteristics of the subjects are presented in Table 1. The mean PANSS total score was 94.0 ± 19.8, suggesting a marked severity of illness. Table 2 shows the intercorrelations between the SWN score and clinical variables before clozapine administration. The SWN score had no significant correlations with age, gender, duration of illness, or years of education (P > .05). The SWN score had a significant negative correlation with the PANSS only for the depression factor (r = −0.45, P < .01). There was also a significant negative correlation between the SWN score and the BDI score (r = −0.83, P < .01). The SWN score had no significant correlation with the CGI-S score (P > .05) ( Table 2). Table 1. Demographic and clinical characteristics of the subjects (n = 40). Variables Mean ± SD/Number (percentage) Age (y) 33.0 ± 8.1 Gender Male 23 (58.0%) Female 17 (42.0%) Duration of illness (y) 10.0 ± 7.2 Education (y) 13.9 ± 2.1 Marital status Single 33 (82.5%) Married 7 (17.5%) PANSS factor score Positive 31.7 ± 7.0 Negative 22.1 ± 7.9 Cognitive/disorganized 15.4 ± 5.8 Depression/anxiety 15.1 ± 4.5 Excitement 10.7 ± 3.9 Total score 94.0 ± 19.8 SD indicates standard deviation; PANSS, Positive and Negative Syndrome Scale. Table options Table 2. Correlations of subjective well-being with demographic and clinical variables before clozapine administration. Variables SWN score Age 0.06 Gender 0.05 Duration of illness −0.01 Education 0.22 Marital status −0.15 PANSS factor score Positive 0.08 Negative −0.21 Cognitive/disorganized −0.17 Depression −0.45⁎⁎ Excitement 0.15 BDI −0.83⁎⁎ CGI-S −0.07 SWN indicates Subjective Well-being under Neuroleptics Scale; PANSS, Positive and Negative Syndrome Scale; BDI, Beck Depression Inventory; CGI-S, Clinical Global Impression Scale of Severity. ⁎⁎ P < .01. Table options All patients completed an 8-week clozapine trial. Table 3 presents the changes in subjective well-being and psychopathology. Wilcoxon matched-pairs tests showed that there were significant improvements in PANSS factor scores, CGI-S score, and BDI score over the treatment period (P < .05). Subjective well-being, as measured by the SWN, also tended to improve over the course of the treatment (P = .08) ( Table 3). Table 3. Changes in psychopathology and subjective well-being from baseline and to 8 weeks of treatment. Variables Baseline Week 8 P value PANSS positive 31.7 ± 7.0 24.4 ± 5.6 <.01⁎⁎ PANSS negative 22.1 ± 7.9 20.3 ± 7.9 .04⁎ PANSS cognitive/disorganized 15.4 ± 5.8 13.2 ± 4.6 <.01⁎⁎ PANSS depression 15.1 ± 4.5 12.6 ± 4.1 <.01⁎⁎ PANSS excitement 10.7 ± 3.9 8.8 ± 2.9 <.01⁎⁎ PANSS total 94.0 ± 19.8 79.1 ± 16.8 <.01⁎⁎ CGI-S 5.7 ± 1.0 4.2 ± 1.0 <.01⁎⁎ BDI 15.6 ± 12.1 10.6 ± 10.3 .01⁎ SWN 82.3 ± 19.1 88.1 ± 16.9 .08 Values are presented as mean ± standard deviation. All P values represent the results of the Wilcoxon matched-pairs test. PANSS indicates Positive and Negative Syndrome Scale; CGI-S, Clinical Global Impression Scale of Severity; BDI, Beck Depression Inventory; SWN, Subjective Well-being under Neuroleptics Scale. ⁎ Significant effect of time (P < .05). ⁎⁎ Significant effect of time (P < .01). Table options Table 4 shows the intercorrelations between the SWN score and symptomatology after clozapine treatment. The SWN score had significant negative correlations with the PANSS depression factor score (r = −0.34, P = .03) and the BDI score (r = −0.73, P < .01). The SWN score had no significant correlation with the other PANSS factor scores or the CGI-S score (P > .05). Table 4. Correlations of subjective well-being with demographic and clinical variables after clozapine treatment. Variables SWN score PANSS factor score Positive −0.14 Negative −0.02 Cognitive/disorganized −0.09 Depression −0.34⁎ Excitement 0.21 BDI −0.73⁎⁎ CGI-S −0.09 SWN indicates Subjective Well-being under Neuroleptics Scale; PANSS, Positive and Negative Syndrome Scale; BDI, Beck Depression Inventory; CGI-S, Clinical Global Impression Scale of Severity. ⁎ P < .05. ⁎⁎ P < .01. Table options The correlation coefficients between subjective well-being and depressive symptoms before and after clozapine treatment were compared using Fisher's z-transformation statistics. The analysis revealed that the correlations between the SWN score and the PANSS depression factor score were not significantly different before and after clozapine treatment (z = −0.57, P = .57). The correlation coefficients between the SWN score and the BDI score were also not significantly different before and after clozapine treatment (z = −1.03, P = .30).