A Longitudinal Study of Relation between Side-effects and Clinical Improvement in Schizophrenia: Is There a Neuro-metabolic Threshold for Second Generation Antipsychotics?
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Objective: Classical studies demonstrated Neuroleptic Induced Extrapyramidal Side-effects (NIES; Neuroleptic threshold) to correlate with the efficacy of first generation antipsychotics. Second generation antipsychotics (SGAs), in addition to the extrapyramidal side effects, are also associated with metabolic side effects. This prospective study on antipsychotic-naïve schizophrenia patients, for the first-time, examined concurrently the relationship between clinical improvement and these side-effects NIES and Neuroleptic Induced Metabolic Side-effects. Methods: Thirty six-antipsychotic-naïve schizophrenia (DSM-IV) patients were examined at baseline and after 5 weeks of treatment with antipsychotics. At baseline and follow-up, we recorded the body mass index (BMI) and assessed psychopathology using Scale for Assessment of Positive-symptoms (SAPS) and Scale for Assessment of Negative-symptoms (SANS), extrapyramidal symptoms using Simpson-Angus Extra Pyramidal Scale (SAEPS) and improvement using Clinical Global Impression Improvement (CGI). Results: After treatment, patients showed significant reduction in SAPS (baseline, 27.97±14.47; follow-up, 14.63±13.25; p＜0.001)and SANS total scores (baseline, 63.77±28.96; follow-up, 49.30±28.77; p=0.001) and a significant increase in BMI (baseline,18.5±3.37; follow-up, 19.13±3.17; p＜0.001). At follow-up CGI-Improvement score was (2.55±0.65) and SAEPS score was (0.8±1.32). CGI-Improvement score had a significant negative correlation with magnitude of increase in BMI (rs=-0.39; p=0.01)and SAEPS symptom score at follow-up (rs=-0.58; p＜0.001). In addition, magnitude of increase in BMI showed positive correlation with the magnitude of reduction in SAPS total score (rs=0.33; p=0.04). Conclusion: The study findings suggest a possible relation between clinical improvement and antipsychotic-induced neuroleptic as well as metabolic side-effects in schizophrenia. Though the mechanism of this relation is yet to be elucidated, insulin signaling pathways and lipid homeostasis are potential mechanisms in addition to the established neurotransmitter hypothesis. Theoretically findings support the novel hypothetical construct of ‘Neuro-Metabolic threshold’ in the treatment of schizophrenia.
Abstract
Objective: Classical studies demonstrated Neuroleptic Induced Extrapyramidal Side-effects (NIES; Neuroleptic threshold) to correlate with the efficacy of first generation antipsychotics. Second generation antipsychotics (SGAs), in addition to the extrapyramidal side effects, are also associated with metabolic side effects. This prospective study on antipsychotic-naïve schizophrenia patients, for the first-time, examined concurrently the relationship between clinical improvement and these side-effects NIES and Neuroleptic Induced Metabolic Side-effects. Methods: Thirty six-antipsychotic-naïve schizophrenia (DSM-IV) patients were examined at baseline and after 5 weeks of treatment with antipsychotics. At baseline and follow-up, we recorded the body mass index (BMI) and assessed psychopathology using Scale for Assessment of Positive-symptoms (SAPS) and Scale for Assessment of Negative-symptoms (SANS), extrapyramidal symptoms using Simpson-Angus Extra Pyramidal Scale (SAEPS) and improvement using Clinical Global Impression Improvement (CGI). Results: After treatment, patients showed significant reduction in SAPS (baseline, 27.97±14.47; follow-up, 14.63±13.25; p＜0.001)and SANS total scores (baseline, 63.77±28.96; follow-up, 49.30±28.77; p=0.001) and a significant increase in BMI (baseline,18.5±3.37; follow-up, 19.13±3.17; p＜0.001). At follow-up CGI-Improvement score was (2.55±0.65) and SAEPS score was (0.8±1.32). CGI-Improvement score had a significant negative correlation with magnitude of increase in BMI (rs=-0.39; p=0.01)and SAEPS symptom score at follow-up (rs=-0.58; p＜0.001). In addition, magnitude of increase in BMI showed positive correlation with the magnitude of reduction in SAPS total score (rs=0.33; p=0.04). Conclusion: The study findings suggest a possible relation between clinical improvement and antipsychotic-induced neuroleptic as well as metabolic side-effects in schizophrenia. Though the mechanism of this relation is yet to be elucidated, insulin signaling pathways and lipid homeostasis are potential mechanisms in addition to the established neurotransmitter hypothesis. Theoretically findings support the novel hypothetical construct of ‘Neuro-Metabolic threshold’ in the treatment of schizophrenia.
참고문헌 (21)
- Bitter I, "The concept of the neuroleptic threshold: an update", J Clin Psychopharmacol, 11, pp.28~33 (1991)
- McEvoy JP, "The neuroleptic threshold as a marker of minimum effective neuroleptic dose", Compr Psychiatry, 27, pp.327~335 (1986)
- Kapur S, "Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia", Am J Psychiatry, 157, pp.514~520 (2000)
- Nordstrom AL, "Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients", Biol Psychiatry, 33, pp.227~235 (1993)
- Farde L, "Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects", Arch Gen Psychiatry, 49, pp.538~544 (1992)
- Stahl SM, "Which comes first: atypical antipsychotic treatment or cardiometabolic risk?", Acta Psychiatr Scand, 119, pp.171~179 (2009)
- Bustillo JR, "Differential effect of clozapine on weight: a controlled study", Am J Psychiatry, 153, pp.817~819 (1996)
- Leadbetter R, "Clozapine-induced weight gain: prevalence and clinical relevance", Am J Psychiatry, 149, pp.68~72 (1992)
- Meltzer HY, "Clozapine-induced weight gain predicts improvement in psychopathology", Schizophr Res, 59, pp.19~27 (2003)
- Czobor P, "Antipsychotic-induced weight gain and therapeutic response: a differential association", J Clin Psychopharmacol, 22, pp.244~251 (2002)
- Gupta S, "Olanzapine: weight gain and therapeutic efficacy", J Clin Psychopharmacol, 19, pp.273~275 (1999)
- Jones B, "Weight change and atypical antipsychotic treatment in patients with schizophrenia", J Clin Psychiatry, 62(Suppl 2), pp.41~44 (2001)
- Basson BR, "Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone", J Clin Psychiatry, 62, pp.231~238 (2001)
- Sheehan DV, "The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10", J Clin Psychiatry, 59(Suppl 20), pp.22~33 (1998)
- Andreasen NC, "The Scale for the Assessment of Positive Symptoms (SAPS). Iowa City" (1984), University of Iowa
- Andreasen NC, "The Scale for the Assessment of Negative Symptoms (SANS)" (1983), University of Iowa
- Mohan V, "A simplified Indian Diabetes Risk Score for screening for undiagnosed diabetic subjects", J Assoc Physicians India, 53, pp.759~763 (2005)
- Girgis RR, "Antipsychotic drug mechanisms: links between therapeutic effects, metabolic side effects and the insulin signaling pathway", Mol Psychiatry, 13, pp.918~929 (2008)
- Ryan MC, "Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia", Am J Psychiatry, 160, pp.284~289 (2003)
- Mukherjee S, "Family history of type 2 diabetes in schizophrenic patients", Lancet, 1, pp.495~ (1989)
- Venkatasubramanian G, "Insulin and insulin-like growth factor-1 abnormalities in antipsychotic- naive schizophrenia", Am J Psychiatry, 164, pp.1557~1560 (2007)