Department of Psychiatry

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EVIDENCE BASED TREATMENTS FOR SCHIZOPHRENIAA
Case-Based ApproachRohan Ganguli, M.D.

• Department of Psychiatry
• University of Pittsburgh School of Medicine
• University of Pittsburgh Medical Center

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POTENTIAL CONFLICTS OF INTEREST

• Current sources of research funding
• National Institute of Mental Health, Stanley
  Research Foundation, Bristol Myers Squibb
• Consultant to or receiving honoraria from
• Astra Zeneca, Bristol Myers Squibb, Janssen,
  Pfizer
• Investments in pharmaceutical or other
  healthcare-related industry
• NONE

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LEVELS OF EVIDENCE
Case Reports
WEAK
Expert Opinion
Clinical Experience
Non-randomized controlled clinical trials
STRONG
Randomized Controlled Clinical Trials
31
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EVIDENCE IS NOT ENOUGH TO DETERMINE TREATMENT
CHOICES

• Patients values and expectations
• Should always play a central role in determining
  whether and which interventions take place
• Were getting better at quantifying and
  integrating patient choice
• We need to do more to make sure that patients
  (and families and other caregivers) are fully
  aware of the scientific evidence for the
  available treatment choices

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EVIDENCE-BASED INTERVENTIONS IN SCHIZOPHRENIA

• Antipsychotic medications
• Assertive community treatment (ACT)
• Family psychoeducation
• Social skills training
• Supported employment
• Intensive case management
• Cognitive behavior therapy (CBT)
• For symptoms
• To improve adherence with treatment
• Personal therapy (PT)
• Cognitive enhancement/remediation

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M.K. HISTORY

• 26 year old man
• Of European Descent
• Unmarried
• College graduate, currently unemployed
• Living with parents
• Non-smoker

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M.K. HISTORY

• Diagnosed as suffering from schizophrenia
• Medication history
• Initially on haloperidol (Haldol)
• Later tried on thiothixene (Navane)
• Finally tried on risperidone
• Maximum tolerated dose was 6 mg per day
• Duration of illness 6 years
• No history of alcohol or drug abuse

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M.K. HISTORY

• Moderately good symptom response to haloperidol
  (5mg per day) on his first admission to hospital
• However, he still had some delusions when he was
  discharged and was also still experiencing
  hallucinatory voices.
• Relapsed within three months of discharge, and
  was readmitted
• Discharged on a higher dose of haloperidol (12mg
  per day)
• Had troublesome restlessness, which was only
  partially relieved by propranolol
• Two more admissions over the next two years
• Better but usually still experiencing psychotic
  symptoms at the time of discharge

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M.K. HISTORY

• Thiothixene (up to ..mg per day) was tried due to
  his persistent complaints of subjective side
  effects from haloperidol, particularly
  restlessness
• Even on 60mg per day he experienced markedly
  more severe psychotic symptoms, than when he was
  on haloperidol
• Risperidone was introduced to the US during his
  4th in patient hospitalization
• With his and his parents agreement he was
  started on this new medication
• He developed stiffness and restlessness at a dose
  of 6mg and requested that the dose not be
  increased any further
• However, he continued to have psychotic symptoms
  which preoccupied his mind and prevented him from
  engaging in any meaningful social or vocational
  activities.

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M.K. THE PROBLEM
What are the evidence-based options for MK, to
obtain relief from his delusions and
hallucinations?
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CATIE STUDY DESIGN
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CATIE Phase 2 randomization
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CATIE 2 Efficacy pathway
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CATIE-2 Efficacy Pathway results
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CATIE-2 Efficacy Pathway results
CLOZAPINE
OLANZAPINE
QUETIAPINE
RISPERIDONE
Discontinuation survival curves 0 to 18 months
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CATIE-2 Efficacy Pathway results
CHANGE IN PANSS SCORE
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CATIE-2 Efficacy Pathwaymean daily doses

• Clozapine 332.1
• Olanzapine 23.4 mg
• Risperidone 4.8 mg
• Quetiapine 642.9 mg

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N.S. HISTORY

• 48 year old African American woman
• Divorced
• On social security disability
• Living on her own in Pittsburgh
• Non-smoker
• Height 5 4
• Weight 222 lb
• BMI 38.1

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N.S. HISTORY

• Diagnosis schizoaffective disorder
• Current medications
• Quetiapine 900 mg per day
• Citalopram 20 mg per day
• Prevacid 20 mg per day
• Duration of illness 20 years
• Past history of alcohol and cocaine abuse
• Currently in full remission from both

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N.S. HISTORY

• Patient is very satisfied with current
  antipsychotic, except for the weight gain
• so she would prefer it if she didnt have to
  switch antipsychotics
• Is there evidence that this can be accomplished?

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WEIGHT LOSS IN SCHIZOPHRENIAStudies With Some
Form of Control Group
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N.S. HISTORY

• Enrolled in weight reduction study July 2004
• Had some difficulty attending in the early phases
  of the study
• Lost 2 lb in the first 7 weeks
• Lost another 6 lb in the next 7 weeks
• Over the next 2 years she has lost 32 lb

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N.S. COURSE OF RESPONSE TO TREATMENT
Week 0
Week 7
Week 14
Month 4
Month 8
Month 12
Month 16
Month 20
Month 24
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A.M. HISTORY

• 28 year old woman of European descent
• Works at a local grocery store chain
• Single
• Smokes one pack of cigarettes a day
• Weight 196lb
• Height 5 7
• BMI 30.7

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A.M. HISTORY

• Duration of illness 2 years
• Medication history
• Initially treated with quetiapine
• Switched to olanzapine because of what was felt
  to be an incomplete treatment response
• Discharged on olanzapine 25 mg per day
• Currently on olanzapine 30 mg per day

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A.M. THE PROBLEM

• A.M. is distressed that she has gained 36 lb
  since starting olanzapine
• even though she has no psychotic symptoms, she
  wants to switch to something which will reverse
  the changes
• 160 to 196 lb (BMI before starting olanzapine
  25.1)
• Is there any evidence that switching will
  accomplish what A.M. desires?

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CHANGE IN FASTING BLOOD GLUCOSE switching study
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CHANGE IN FASTING TRIGLYCERIDES switching study
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CHANGE IN LIPIDS switching study
Simpson et al. 2005 American J Psychiatry
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CHANGE IN FASTING GLUCOSE AND INSULIN switching
study
Simpson et al. 2005 American J Psychiatry
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CONCLUSIONS

• There is much good quality evidence to help guide
  responses to common clinical problems
• There are also many popular practices for which
  evidence is weak of lacking altogether
• Patients deserve to have access to the best
  quality evidence regarding treatment options
  being offered to them
• Thus research of the highest standards should be
  applied to popular practices which have not been
  adequately evaluated.