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Early Intervention in Psychiatry 2015; ••: ••–••

doi:10.1111/eip.12246

Brief Report Quality of life and functioning in first-episode psychosis Chinese patients with different antipsychotic medications Edwin H.M. Lee,1 Christy L.M. Hui,1 Jessie J.X. Lin,1 Elaine Y.N. Ching,1 W.C. Chang,1 Sherry K.W. Chan1 and Eric Y.H. Chen1,2 Abstract Aim: This study compared the quality of life and functioning of 285 firstepisode psychosis Chinese patients with different antipsychotic medications in Hong Kong.

1 Department of Psychiatry, Queen Mary Hospital, and 2State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong

Corresponding author: Dr Edwin H.M. Lee, Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Pokfulam, Hong Kong. Email: [email protected] Received 8 January 2015; accepted 12 April 2015 Author Disclosure Information Dr Lee sat on a scientific advisory board for AstraZeneca and Eli Lilly. Professor Chen sat on a scientific advisory board for Otsuka, received educational grant support from Janssen-Cilag, and research funding from AstraZeneca, Janssen-Cilag, Pfizer, Eli Lilly, Sanofi-Aventis and Otsuka.

Method: Under the Jockey Club Early Psychosis project, a total of 285 patients were recruited from all inpatient and outpatient psychiatric units in Hong Kong between 2009 and 2011. In addition to the medication information, patients were assessed with the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, the Udvalg for Kliniske Undersøgelser (UKU), Barnes Akathisia Rating Scale (BARS), the Social and Occupational Functioning Assessment Scale (SOFAS), the Role Functioning Scale, and the Medical Outcomes Study Short Form 12-Item Health Survey (SF-12) after stabilization of mental condition. Differences between individual antipsychotic medications were compared using anova and multinomial regression model.

Conclusions: The findings suggest that antipsychotics have differential associations with the quality of life and functioning in patients with firstepisode psychosis. Future prospective study is warranted to investigate if patients with first-episode psychosis will benefit specific type of antipsychotics more than the others.

Key words: antipsychotic, first-episode psychosis, functioning, quality of life.

INTRODUCTION Psychosis is a severe mental illness that can cause great burden in patient’s physical health, psychological well-being, quality of life (QoL) and functioning.1,2 Early intervention services have been developed in addition to fundamental antipsychotic medication treatment to reduce disability and maximize functional recovery.3 An optimal outcome © 2015 Wiley Publishing Asia Pty Ltd

Results: The results demonstrated significant differences between different antipsychotic medications in the mean of UKU neurological subscore, BARS total score, SOFAS score and SF-12 Mental Component Summary (MCS) score. Patients with haloperidol had higher mean UKU neurological subscore than patients with olanzapine or amisulpride. Risperidone was associated with higher mean BARS total score than olanzapine, amisulpride or sulpiride. Higher mean MCS was found in patients with amisulpride than patients with risperidone.

cannot be achieved without consideration of three closely related aspects including clinical, functional and QoL.4 Many clinical trials have shown the efficacy of antipsychotics in improvement of clinical symptoms with evidence to suggest some antipsychotics to be superior, particularly clozapine.5,6 However, their effects on functioning and QoL are relatively less commonly studied.7 1

Quality of life and functioning in FEP There were some studies that suggested the differential effects of antipsychotics on QoL and functioning in patients with psychosis. In a metaanalysis, 17 of 150 double-blind clinical trials compared QoL between first- and second-generation antipsychotics and it was found that secondgeneration antipsychotics, including amisulpride, clozapine and sertindole, were associated with better QoL than first-generation antipsychotics.8 However, in the Clinical Antipsychotic Trials of Intervention Effectiveness study9 and the Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study,10 no differences in QoL and functioning were found between patients having first- and second-generation antipsychotic treatment. Patients at different stages of psychotic disorders may have different needs.11 Patients with longer duration of illness may have increased duration of psychotic symptoms, substance abuse, and functional/social disabilities, all of which may influence drug response.12 Chinese culture has been emphasized on functioning, but QoL is still a domain that needs to be further developed.13 Limited research has examined the effect of antipsychotics on functioning and QoL in firstepisode psychosis despite their impact is crucial in this critical period.14 The current study was designed to compare the QoL and functioning in first-episode psychosis patients with different antipsychotic medications in naturalistic setting.

existing medical illness was collected. Premorbid functioning was assessed with the Premorbid Adjustment Scale.17 The positive and negative symptoms were assessed by the Scale for the Assessment of Positive Symptoms18 and the Scale for the Assessment of Negative Symptoms,19 respectively. Sideeffects of psychotropic medications were assessed by Udvalg for Kliniske Undersøgelser (UKU)20 and Barnes Akathisia Rating Scale (BARS).21 The general functioning was assessed by the Social and Occupational Functioning Assessment Scale (SOFAS).22 Specific functioning domains at work, independent living/self-care, immediate social network relationships and extended social network relationships were assessed by the Role Functioning Scale.23 Overall mental and physical health functioning was assessed by the Medical Outcomes Study Short Form 12-Item Health Survey (SF-12) which can derive Mental Component Summary (MCS) score and Physical Component Summary score.24

METHODOLOGY

Data analysis

Participants

Baseline demographics and clinical variables of patients with different antipsychotic medication were compared using anova or its non-parametric equivalent. Post-hoc analysis was done to compare the individual difference between antipsychotic medications. Significant factors will then be entered as independent variables into a multinomial regression model to explore their relationships with type of antipsychotic medication as dependent variable. The Statistical Package for the Social Sciences (SPSS for Windows, version 20) was used for statistical analysis and P-values of less than 0.05 were considered to be statistically significant.

This was a naturalistic observational study conducted under the Jockey Club Early Psychosis (JCEP) project in Hong Kong.15 JCEP is an early intervention service that targets patients aged between 25 and 55 years, who had been diagnosed as having first-episode psychotic disorders (schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, or psychotic disorder not otherwise specified according to the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-4)).16 A total of 285 patients with firstepisode psychosis, aged 25–55, were recruited from all inpatient and outpatient psychiatric units (except forensic unit) in Hong Kong from 2009 to 2011. Clinical instruments Demographic information including gender, age, education, duration of untreated psychosis and 2

Procedure The study had been approved by local research ethics committees and written informed consent was obtained from all participants. Participants were assessed upon entry into the study after stabilization of mental condition. Demographic and clinical information was collected by structure interview and case note review.

RESULTS Demographic characteristics and clinical variables of the patients are shown in Table 1. There was no significant difference between the six antipsychotic medications, except for the mean chlorpromazine equivalent dosage (P < 0.001). © 2015 Wiley Publishing Asia Pty Ltd

© 2015 Wiley Publishing Asia Pty Ltd

54.7 (24.5) 62.9 (25)

133 (81.6) 30 (18.4) 0.19 (0.18) 111 (28–409) 92 (56.4%) 149.4 (77.7)

38 (86.4) 6 (13.6) 0.17 (0.17) 62 (12–225) 30 (68.1%) 160.8 (137.4)

63.5 (25.8) 68.1 (24.6)

144 (88.3) 19 (11.7)

37 (84.1) 7 (15.9)

5.3 (9.3) 12.6 (15.9) 0.51 (0.38) 0.15 (0.19) 0.19 (0.22) 0.13 (0.13) 0.37 (0.78) 57.1 (13.3) 19.5 (4.4)

89 (54.6) 48 (29.4) 26 (16)

20 (45.5) 16 (36.4) 8 (18.2)

4.8 (8.1) 10.2 (16.4) 0.52 (0.46) 0.25 (0.26) 0.19 (0.2) 0.1 (0.13) 0.77 (1.16) 61.91 (14.1) 20.9 (4.2)

37.3 (8.3) 82 (50.3) 10.9 (4.0)

Risperidone (n = 163)

39.1 (8.7) 26 (59.1) 10.6 (3.1)

Haloperidol (n = 44)

61.5 (25.2) 73.5 (24.1)

5.6 (6.8) 7.4 (7.5) 0.33 (0.31) 0.07 (0.13) 0.12 (0.17) 0.1 (0.15) 0.15 (0.49) 57.9 (15.5) 19.9 (4.4)

16 (80) 4 (20) 0.18 (0.15) 121 (34–788) 11 (55%) 260.8 (273.3)

16 (80) 4 (20)

11 (55) 6 (30) 3 (15)

37.7 (10.6) 12 (60) 11.8 (4.9)

Olanzapine (n = 20)

71.8 (23.2) 72.3 (24.9)

2.1 (3.9) 7.5 (9.8) 0.54 (0.39) 0.16 (0.26) 0.17 (0.19) 0.15 (0.18) 0.13 (0.35) 62.6 (14) 21.9 (3.4)

11 (73.3) 4 (26.7) 0.11 (0.09) 24 (10–486) 9 (60%) 246.7 (247.8)

14 (93.3) 1 (6.7)

5 (33.3) 8 (53.3) 2 (13.4)

38.3 (9.0) 11 (73.3) 11.7 (4.5)

Quetiapine (n = 15)

73.1 (22.6) 75 (24.6)

2.9 (4.9) 4.8 (7.1) 0.39 (0.41) 0.07 (0.12) 0.1 (0.14) 0.07 (0.09) 0.2 (0.65) 63 (10) 21.2 (3.3)

17 (68) 8 (32) 0.2 (0.17) 82 (20.5–593.5) 10 (40%) 318 (209.1)

21 (84) 4 (16)

16 (64) 6 (24) 3 (12)

36.5 (8.1) 12 (48) 11.6 (3.3)

Amisulpride (n = 25)

57.6 (26.4) 58.6 (24.5)

3.7 (7.6) 5.9 (8.6) 0.45 (0.35) 0.15 (0.22) 0.25 (0.35) 0.14 (0.14) 0.06 (0.24) 64.7 (12.7) 21.3 (4.6)

14 (77.8) 4 (22.2) 0.16 (0.15) 99 (11–823.8) 12 (66.7%) 102.8 (62.4)

17 (94.4) 1 (5.6)

7 (38.9) 8 (44.4) 3 (16.7)

42.3 (8.9) 15 (83.3) 10.2 (3.2)

Sulpiride (n = 18)

F(5, 255) = 3.41, P = 0.005 NS

NS NS NS F(5, 279) = 3.63, P = 0.003 NS NS F(5, 279) = 3.70, P = 0.003 F(5, 279) = 2.38, P = 0.039 NS

NS NS NS NS NS F(5, 279) = 10.17, P < 0.001

NS NS

NS NS NS

NS NS NS

P-value

BARS, Barnes Akathisia Rating Scale; DUP, duration of untreated psychosis; IQR, interquartile range; MCS, Mental Component Summary score; NS, not significant; PAS, Premorbid Adjustment Scale; PCS, Physical Component Summary score; QoL, quality of life; RFS, Role Functioning Scale; SANS, Scale for the Assessment of Negative Symptoms; SAPS, Scale for the Assessment of Positive Symptoms; SOFAS, Social and Occupational Functioning Assessment Scale; UKU, Udvalg for Kliniske Undersøgelser.

Age, years, mean (SD) Female, n (%) Education, years, mean (SD) Marital status, n (%) Single Married Others Living condition, n (%) With others Alone Existing medical conditions, n (%) No Yes PAS, mean (SD) DUP, days, median (IQR) History of hospitalization, n (%) Chlorpromazine equivalent dosage, mg: mean (SD) SAPS, total, mean (SD) SANS, total, mean (SD) UKU psychiatric subscale, mean (SD) UKU neurologic subscale, mean (SD) UKU autonomic subscale, mean (SD) UKU others subscale, mean (SD) BARS, mean (SD) SOFAS, mean (SD) RFS total score, mean (SD) QoL MCS, mean (SD) PCS, mean (SD)

TABLE 1. Baseline characteristics

E. H. M. Lee et al.

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Quality of life and functioning in FEP Significant differences were found between different antipsychotic medications in the mean of UKU neurological subscore, BARS total score, SOFAS score and MCS score. Post-hoc analysis showed that patients with haloperidol had higher mean UKU neurological subscore than patients with olanzapine or amisulpride. Patients with risperidone had higher mean BARS total score than patients with olanzapine, amisulpride or sulpiride. Patients with amisulpride had higher mean MCS score than patients with risperidone. No significant difference was found in the mean SOFAS score between antipsychotic medications. Multinomial regression analysis showed SOFAS score and BARS total score remained to be significant factors associated with different antipsychotic medications after controlling for chlorpromazine equivalent dosage.

DISCUSSION Our findings suggested that antipsychotic medications are associated differently with QoL and functioning in patients with first-episode psychosis. Amisulpride was associated with better QoL when compared to other antipsychotics whereas haloperidol and risperidone were associated with more extrapyramidal side-effects. Our finding suggested that amisulpride was associated with better mental component of QoL when compared to risperidone. Amisulpride is a selective dopamine D2/3 antagonist which is different from many other secondgeneration antipsychotics that have no significant affinity for serotonergic (5HT2A), muscarinic, cholinergic or α-adrenergic receptors.25 Previous studies suggested that amisulpride is better in improvement of negative symptoms and it causes fewer extrapyramidal side-effects, weight gain, and specific endocrinological and sexual disorders than risperidone in patients with psychosis.26–28 The selective action at limbic cortical dopamine D2/D3 receptors that cause less severe extrapyramidal side-effects and 5-HT7A receptor antagonism underlying antidepressant actions may contribute to the difference in QoL.29 Haloperidol and risperidone have higher potency at dopamine D2 receptors than other antipsychotics and they caused more severe extrapyramidal sideeffects in patients with first-episode psychosis despite their relative moderate dosage. Risperidone and first-generation antipsychotics are commonly used in Asia due to its lower cost when compared to other second-generation antipsychotics.30 QoL 4

has been an increasing concern which patients are not willing to trade to avoid symptoms.31 The current findings have its clinical significance that extrapyramidal side-effects should be monitored carefully and patients at risk of these adverse effects may benefit from other second-generation antipsychotics. There are some limitations in our study that need to be addressed. First, the cross-sectional design cannot conclude a causal relationship and future prospective clinical trial is needed. Second, majority of patients were put on risperidone because of its availability in Hong Kong and the naturalistic design cannot exclude the effect of physicians and patients’ choices on treatment. Third, the study did not measure patients’ adherence of antipsychotic medication and whether they received other clinical interventions which may affect the effect on QoL and functioning. Fourth, generalization of the findings may need to be cautious in view of the large difference in number of patients with different antipsychotics. CONCLUSION Despite the above limitations, the current study investigated the effect of antipsychotics on QoL and functioning in patients with first-episode psychosis which can serve as a basis for future research in view of the limited number of studies in antipsychotics’ effect in this important group of patients. Future prospective study is warranted to investigate if patients with first-episode psychosis will benefit from specific type of antipsychotics more than the others. ACKNOWLEDGEMENT The study was funded by the Hong Kong Jockey Club Charities Trust. The funder had no role in the analysis of data or in the preparation of the manuscript. REFERENCES 1. Millier A, Schmidt U, Angermeyer MC et al. Humanistic burden in schizophrenia: a literature review. J Psychiatr Res 2014; 54: 85–93. 2. Rabinowitz J, Berardo CG, Bugarski-Kirola D et al. Association of prominent positive and prominent negative symptoms and functional health, well-being, healthcare-related quality of life and family burden: a CATIE analysis. Schizophr Res 2013; 150: 339–42. 3. McGorry PD, Killackey E, Yung A. Early intervention in psychosis: concepts, evidence and future directions. World Psychiatry 2008; 7: 148–56. © 2015 Wiley Publishing Asia Pty Ltd

E. H. M. Lee et al. 4. Remington G, Foussias G, Agid O. Progress in defining optimal treatment outcome in schizophrenia. CNS Drugs 2010; 24: 9–20. 5. Chakos M, Lieberman J, Hoffman E et al. Effectiveness of second-generation antipsychotics in patients with treatmentresistant schizophrenia: a review and meta-analysis of randomized trials. Am J Psychiatry 2001; 158: 518–26. 6. Leucht S, Komossa K, Rummel-Kluge C et al. A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry 2009; 166: 152–63. 7. Awad AG, Voruganti LN. Impact of atypical antipsychotics on quality of life in patients with schizophrenia. CNS Drugs 2004; 18: 877–93. 8. Leucht S, Corves C, Arbter D et al. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 2009; 373: 31–41. 9. Swartz MS, Perkins DO, Stroup TS et al. Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study. Am J Psychiatry 2007; 164: 428–36. 10. Jones PB, Barnes TR, Davies L et al. Randomized controlled trial of the effect on Quality of Life of second- vs firstgeneration antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry 2006; 63: 1079–87. 11. Francey SM, Nelson B, Thompson A et al. Who needs antipsychotic medication in the earliest stages of psychosis? A reconsideration of benefits, risks, neurobiology and ethics in the era of early intervention. Schizophr Res 2010; 119: 1–10. 12. Zhang JP, Malhotra AK. Pharmacogenetics of antipsychotics: recent progress and methodological issues. Expert Opin Drug Metab Toxicol 2013; 9: 183–91. 13. Xiang YT, Chiu HF, Ungvari GS. Quality of life and mental health in Chinese culture. Curr Opin Psychiatry 2010; 23: 43–7. 14. Leucht S, Cipriani A, Spineli L et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013; 382: 951– 62. 15. Hui CL, Chang WC, Chan SK et al. Early intervention and evaluation for adult-onset psychosis: the JCEP study rationale and design. Early Interv Psychiatry 2014; 8: 261–8. 16. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorder, 4th edn. Washington, DC: APA, 1994. 17. Cannon-Spoor HE, Potkin SG, Wyatt RJ. Measurement of premorbid adjustment in chronic schizophrenia. Schizophr Bull 1982; 8: 470–84.

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18. Andreasen N. Scale for the Assessment of Positive Symptoms (SAPS). Iowa: University of Iowa, 1984. 19. Andreasen N. Scale for the Assessment of Negative Symptoms (SANS). Iowa: University of Iowa, 1984. 20. Lingjaerde O, Ahlfors UG, Bech P et al. The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand 1987; 334: 1–100. 21. Barnes TR. The Barnes Akathisia Rating Scale – revisited. J Psychopharmacol 2003; 17: 365–70. 22. Goldman HH, Skodol AE, Lave TR. Revising axis V for DSM-IV: a review of measures of social functioning. Am J Psychiatry 1992; 149: 1148–56. 23. Goodman SH, Sewell DR, Cooley EL et al. Assessing levels of adaptive functioning: the Role Functioning Scale. Community Ment Health J 1993; 29: 119–31. 24. Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996; 34: 220–33. 25. Schoemaker H, Claustre Y, Fage D et al. Neurochemical characteristics of amisulpride, an atypical dopamine D2/D3 receptor antagonist with both presynaptic and limbic selectivity. J Pharmacol Exp Ther 1997; 280: 83–97. 26. Komossa K, Rummel-Kluge C, Hunger H et al. Amisulpride versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2010; (1): CD006624. 27. Peuskens J, Bech P, Möller HJ et al. Amisulpride vs. risperidone in the treatment of acute exacerbations of schizophrenia. Amisulpride study group. Psychiatry Res 1999; 88: 107–17. 28. Sechter D, Peuskens J, Fleurot O et al. Amisulpride vs. risperidone in chronic schizophrenia: results of a 6-month double-blind study. Neuropsychopharmacology 2002; 27: 1071–81. 29. Juruena MF, de Sena EP, de Oliveira IR. Safety and tolerability of antipsychotics: focus on amisulpride. Drug Healthc Patient Saf 2010; 2: 205–11. 30. Gallego JA, Bonetti J, Zhang J et al. Prevalence and correlates of antipsychotic polypharmacy: a systematic review and meta-regression of global and regional trends from the 1970s to 2009. Schizophr Res 2012; 138: 18–28. 31. Briggs A, Wild D, Lees M et al. Impact of schizophrenia and schizophrenia treatment-related adverse events on quality of life: direct utility elicitation. Health Qual Life Outcomes 2008; 6: 105.

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Quality of life and functioning in first-episode psychosis Chinese patients with different antipsychotic medications.

This study compared the quality of life and functioning of 285 first-episode psychosis Chinese patients with different antipsychotic medications in Ho...
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