Rajkumar A P1, Chitra C1, Bhuvaneshwari S1, Poonkuzhali B1, Kuruvilla A1, Jacob K S1. 1. Dr. Rajkumar, MD, DPM, DNB, Department of Psychiatry, Christian Medical College, Vellore, India. Center for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark. Ms. Chitra, MSW, Dr. Bhuvaneshwari, MBBS, DPM, Prof. Kuruvilla, MD, Prof. Jacob, MD, MRCPsych, PhD, Department of Psychiatry, Christian Medical College, Vellore, India. Dr. Poonkuzhali, PhD, Department of Haematology, Christian Medical College, Vellore, India.
Abstract
OBJECTIVES: Despite clozapine's superior clinical efficacy in Treatment Resistant Schizophrenia (TRS), its adverse effects, need for periodic leukocyte monitoring, cost and variable clinical outcomes make the therapeutic decision making process difficult and mandate a clinical need to predict its treatment response. Hence, we investigated various clinical variables associated with treatment responses and adverse events of clozapine in TRS. EXPERIMENTAL DESIGN: We assessed socio-demographic and clinical profiles, premorbid adjustment, traumatic life events, cognition, disability, psychopathology and serum clozapine levels of 101 patients with TRS on stable dose of clozapine using the following instruments: Brief Psychiatric Rating Scale, Abnormal Involuntary Movements Scale, Addenbrooke's Cognitive Examination-Revised, WHO Disability Assessment Scale-II, Childhood and Recent Traumatic Events Scale, and Premorbid Assessment Scale. We defined clozapine response a priori, adopted a case-control design framework and employed appropriate multivariate analyses. PRINCIPAL OBSERVATIONS: Past history of catatonia (p = 0.005), smoking more than one pack/day (p = 0.008), hyper-somnolence (p = 0.03) and cognitive dysfunction (p = 0.007) were associated with non-response to clozapine. Outcome definitions of non-response to clozapine influenced its association with clinical predictors. CONCLUSIONS: Clinical variables are useful to predict response to clozapine. Smoking can be a potentially modifiable risk factor. Future longitudinal studies, investigating clinical and pharmacogenetic variables together, are desired.
OBJECTIVES: Despite clozapine's superior clinical efficacy in Treatment Resistant Schizophrenia (TRS), its adverse effects, need for periodic leukocyte monitoring, cost and variable clinical outcomes make the therapeutic decision making process difficult and mandate a clinical need to predict its treatment response. Hence, we investigated various clinical variables associated with treatment responses and adverse events of clozapine in TRS. EXPERIMENTAL DESIGN: We assessed socio-demographic and clinical profiles, premorbid adjustment, traumatic life events, cognition, disability, psychopathology and serum clozapine levels of 101 patients with TRS on stable dose of clozapine using the following instruments: Brief Psychiatric Rating Scale, Abnormal Involuntary Movements Scale, Addenbrooke's Cognitive Examination-Revised, WHO Disability Assessment Scale-II, Childhood and Recent Traumatic Events Scale, and Premorbid Assessment Scale. We defined clozapine response a priori, adopted a case-control design framework and employed appropriate multivariate analyses. PRINCIPAL OBSERVATIONS: Past history of catatonia (p = 0.005), smoking more than one pack/day (p = 0.008), hyper-somnolence (p = 0.03) and cognitive dysfunction (p = 0.007) were associated with non-response to clozapine. Outcome definitions of non-response to clozapine influenced its association with clinical predictors. CONCLUSIONS: Clinical variables are useful to predict response to clozapine. Smoking can be a potentially modifiable risk factor. Future longitudinal studies, investigating clinical and pharmacogenetic variables together, are desired.
Authors: Rudi Hwang; Takahiro Shinkai; Vincenzo De Luca; Daniel J Müller; Xingqun Ni; Fabio Macciardi; Steven Potkin; Jeffrey A Lieberman; Herbert Y Meltzer; James L Kennedy Journal: Psychopharmacology (Berl) Date: 2005-10-15 Impact factor: 4.530
Authors: Daniel S Umbricht; William C Wirshing; Donna A Wirshing; Marjorie McMeniman; Nina R Schooler; Stephen R Marder; John M Kane Journal: J Clin Psychiatry Date: 2002-05 Impact factor: 4.384
Authors: A P Rajkumar; B Poonkuzhali; A Kuruvilla; A Srivastava; M Jacob; K S Jacob Journal: Psychopharmacology (Berl) Date: 2012-06-15 Impact factor: 4.530