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When do we use Clozapine when a patient presents with Schizophrenia?

When do we use Clozapine when a patient presents with Schizophrenia?. Evidence on comparing the use of various typical and atypical antipsychotics when treating schizophrenia. By Monisha Kumar. Presentation Outline. Research strategy Schizophrenia PBL case – Mrs Maria Scarlez

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When do we use Clozapine when a patient presents with Schizophrenia?

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  1. When do we use Clozapine when a patient presents with Schizophrenia? Evidence on comparing the use of various typical and atypical antipsychotics when treating schizophrenia. By Monisha Kumar

  2. Presentation Outline • Research strategy • Schizophrenia • PBL case – Mrs Maria Scarlez • Treatment – –Antipsychotics • Measurements used in studies • A study: Clozapine vs. Other Atypical • Why I Chose Clozapine • Comparing two studies – Clozapine vs. Haloperidol • Interpreting results & discussing any discrepancies • Relevance to Mrs. Scarlez • Conclusion

  3. Research Strategy • Databases searched • EBSCO host • Oxford Database • Medline • Pubmed • Pubmed Central • Search Terms • Schizophrenia treatment, antipsychotics, atypical, typical, Clozapine, haloperidol, side effects

  4. Schizophrenia • Schizophrenia is a complex brain disorder, which affects about one in a 100 or around 190,000 Australians. The illness is characterised by a breakdown of thinking and emotions, and a loss of contact with reality. (Schizophrenia, n.d.) • People diagnosed with schizophrenia usually experience a combination of positive (i.e. hallucinations, delusions, racing thoughts) and negative (i.e. apathy, lack of emotion, poor or nonexistant social functioning) symptoms • Although negative symptoms are more common

  5. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) • Characteristic symptoms: Two or more of the following, each present for much of the time during a one-month period • Delusions • Hallucinations • Disorganized speech • Grossly disorganized behaviour or catatonic behaviour • Negative symptoms: Blunted affect (lack or decline in emotional response), alogia (lack or decline in speech), or avolition (lack or decline in motivation) • If the delusions are bizarre, or hallucinations consist of hearing one or more voices, etc • only that symptom is required above. • Duration: Continuous signs of the disturbance persist for at least six months. • This six-month period must include at least one month of symptoms

  6. Mrs Maria Scarlez • 70yrs old • poorly nourished • Extensive leg ulceration • Cared for by district nurses at home • Shares home with 6 cats • Bizarre delusions - she believed her cats talked to her; • Jimbo didn’t like her taking her medication • Chelsea did let her in the kitchen to eat

  7. Treatment – Antipsychotics • Typical Antipsychotics • Also known as First Generation Antipsychotics (FGA) • Examples: Haloperidol (Haldol, Serenace), Droperidol • Atypical Antipsychotics • Also known as Second Generation Antipsychotics (SGA) • Newest class of Antipsychotics • Examples: Clozapine, risperidone, olanzapine, quetiapine

  8. Measures used to obtain results in research into Schizophrenia • Heinrichs–Carpenter Quality of Life Scale • range of possible scores, 0–126 used to evaluate social functioning & behaviour • lower scores represent poorer mental health. • PANSS – Positive and Negative Syndrome Scale • Seven point scoring system • 1 (absent) to 7 (extreme) • MMSE – Mini Mental State Exam • Tests cognition in 5 areas • Scores range from 0 (severe impairment) to 30 (normal) (Essali A et al 2010)

  9. Clozapine vs. other Atypical antipsychotics - University of Manchester; Imperial College, London; Institute of Psychiatry, London; University of Cambridge • Participants were 136 people aged 18–65 with DSM-IV schizophrenia and related disorders • whose medication was being changed because of poor clinical response to 2 or more previous antipsychotic drugs. • Participants were randomly allocated to Clozapine or to one of the class of other SGA drugs • Outcomes were assessed with blind treatment allocation. • One-year assessments were carried out in 87% of the sample (Lewis S.W. et al 2006)

  10. Results - overview • Overall higher costs associated with randomised Clozapine participants, compared to the other SGA drugs • Weight gain occurred in both groups • QLS not statistically significant • PANSS - +ve and –ve syndrome scale, showed a difference (Lewis S.W. et al 2006)

  11. Clozapine showed fewer total extrapyramidal side effects • At 12 weeks participants randomly assigned to Clozapine reported their mental health was significantly better than the reports from participants on other SGA’s (Lewis S.W. et al 2006)

  12. Why I chose Clozapine • The previous study showed patient satisfaction and greater improvement in +ve and –ve symptoms compared to other SGA drugs • Benefits • Reduced extrapyramidal SE (Lewis S.W. et al 2006) • Lower risk of neuroleptic malignant syndrome (NMS)(Buchanan 1995) • Lower risk of developing Tarditive Dyskinesia (TD) (Buchanan 1995) • Efficacy (Buchanan 1995)

  13. However there are many costs involved with using Clozapine • The greater monetary cost compared to other SGA’s and FGA’s (Lewis S.W. et al 2006) • Greater weight gain in comparison to FGA drugs ≈ 7% Clozapine, 4% FGA drugs after 2 years (N.H. Covell et al 2004) • Higher risk of developing agranulocytosis and abnormalities in bone marrow function (Buchanan 1995) • This is severe • Sedation • Look at studies comparing Clozapine and FGA drugs, also in the terms of: • Quality of life • Reduction of +ve and –ve symptoms

  14. Rational • To find out the outcome of Pharmacotherapy of Clozapine vs. FGA drugs • Quality of life • Reduction of positive and negative symptoms associated with schizophrenia • Having a greater statistical understanding when comparing the drugs • To make a more informed decision when treating a patients with schizophrenia

  15. Research Studies: • Two Studies: • Rosenheck R et al. A Comparison of Clozapine and Haloperidol in Hospitalized Patients with Refractory Schizophrenia. • New England Journal of Medicine, Vol. 337:809-815, no. 12, Sept 1997 • Evans D, Herz L, Cramer J, Xu W, Thomas J, Henderson W, Charney D. How Long to Wait for a Response to Clozapine: A Comparison of Time Course of Response to Clozapine and Conventional Antipsychotic Medication in Refractory Schizophrenia. • Schizophrenia Bulletin, vol. 25, no. 4, 1999

  16. Criteria for the two studies • Evans & Rosenheck • Both • 1 year outcome studies • Used H-C Quality of Life Scale • PANSS • Compared randomly selected groups; Clozapine (SGA) or Haloperidol (FGA) • Clozapine(100 to 900 mg per day) or Haloperidol (5 to 30 mg per day). • Criteria for study included: • history of a high level of use of inpatientservices • diagnosis of schizophrenia, as defined in the Diagnostic andStatistical Manual of Mental Disorders (third edition, revised)(DSM-III-R) • Required written consent (Rosenheck R et al, 1997) (Evans, et al, 1999)

  17. Evans • Data for this study were obtained from a prospective, double-blind study • patients were recruited over 2 years & randomly assigned to Clozapine or haloperidol and treated for 12 months. • n = 121 (Clozapine) • n = 122 (Haloperidol) • Interviews were conducted at 6wks, 3months, 6moths • Rosenheck • patients hospitalized at15 medical centres were randomly assigned toreceive Clozapine or haloperidol for 12months. • n = 202 (Clozapine) • n = 211 (Haloperidol) • Interviews were conducted at 6 wks, 3months, 6months, 9months, 1year (Rosenheck R et al, 1997) (Evans, et al, 1999)

  18. Results – 6 weeks (Rosenheck R et al, 1997) (Evans, et al, 1999)

  19. Results – 3 months (Rosenheck R et al, 1997) (Evans, et al, 1999)

  20. Results – 9 months (Rosenheck R et al, 1997) (Evans, et al, 1999)

  21. Results • Values are similar • Overall we can see that clozapine has a higher % : • PANSS improvement • H-C Quality of Life improvement • In BOTH studies • There are a few variations in the statistics • ↑ H-C QLS in Rosenheck study • Clozapine by almost 20% • Haloperidol by about 15% • Due to experimental design

  22. Validity • Descrepency in improved H-C QL could be due to • How the interview was conducted (participant-interveiwer interaction) • Evans study being 6months shorter • At Baseline measurements for both studies • When comparing PANSS & H-C QL scores • Statistically insignificant

  23. Other issues: • Evans study contained around 200 less participants • Only 1 female in Clozapine study • 7.4% Alcohol Abuse • 6.6% Drug Abuse • Only 1 female in haloperidol study • 8.1% Alcohol Abuse • 9% Drug Abuse • ≈ 70% Caucasian • Rosenheck study contained >400 participants • 99% male in Clozapine study • 70.6% Alcohol Abuse • 47.5% Drug Abuse • 96% male in haloperidol study • 61% Alcohol Abuse • 47.7% Drug Abuse • ≈ 60% Caucasian • Small Demographic

  24. Conclusion • Clozapine overall was seen to be have greater efficacy towards treating symptoms • Compared to FGA’s and other SGA’s • Quality of Life & PANSS improvement • Outcomes are patient dependant • Eg. History of drug and alcohol abuse, genetics, severity of SE’s • Mrs Scarlez has no previous antipsychotic use • Clozapine > efficacy but risk of more sever SE vs. Other SGD • FGD > Extrapyramidal SE, Cost Less than most SGD • As a health professional with prescribing rights, we have to weigh up costs to benefits of treatment • Side effects; irreversible, reversible • Cost of treatment • Quality of Life • Patients circumstance (eg. Maria may be unable to take drugs initially at home due to her delusion of Jimbo, her cat, talking.)

  25. References • Buchanan RW. Clozapine: Efficacy and Safety. Published in Schizophrenia Bulletin, vol. 21, no. 4, pp. 579-591, 1995 • Covell NH, Weissman EM, Essock SM. Weight Gain With Clozapine Compared to First Generation Antipsychotic Medications. Published in Schizophrenia Bulletin, vol. 30, no. 2, 2004 • Essali a, Hassan NAH, Li C, Rathbone J. Clozapine versus typical neuroleptic medication for schizophrenia. [Reviews] The Cochrane Database of Systematic Reviews, vol.1 2010 • Evans D, Herz L, Cramer J, Xu W, Thomas J, Henderson W, Charney D. How Long to Wait for a Response to Clozapine: A Comparison of Time Course of Response to Clozapine and Conventional Antipsychotic Medication in Refractory Schizophrenia. Published in Schizophrenia Bulletin, vol. 25, no. 4, 1999

  26. Jeste DV, Lacro JP, Glibert PL, Kline J, Kline N. Treatment of Late-Life Schizophrenia With Neuroleptics. Published in Schizophrenia Bulletin, vol. 19, no. 4, 1993 • Lewis SW, Barnes TRE, Davies L, Murray RM, Dunn G, Hayhurst KP, Markwick A, Lloyd H, Jones PB. Randomised Controlled Trial of Effect of Prescription of Clozapine Versus Other Second-Generation Antipsychotic Drugs in Resistant Schizophrenia. Published in Sichophrenia Bulletin, vol. 32, no. 4, pp. 715-723, 2006 • Robinson DG, Woerner MG, Delman HM, Kane JM. Pharmacological Treatments for First-Episode Schizophrenia. Published in Schizophrenia Bulletin, vol. 31, no.3, pp. 105-722, 2005 • Rosenheck R et al. A Comparison of Clozapine and Haloperidol in Hospitalized Patients with Refractory Schizophrenia. New England Journal of Medicine, Vol. 337:809-815, no. 12, Sept 1997 • Schizophrenia (n.d.) Better Health Channel, cited on 3/06/10 http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Schizophrenia

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