# Presentation: 727421

## Using Recent Research to Improve the Cost-Effectiveness of VA Antipsychotic Formulary Policy

- Robert Rosenheck MD
- Michael Sernyak MD
- New England MIRECC
- Yale Medical School
- VA Connecticut Health Care System

## VA Cooperative Study #455 Results(1)

- Patients assigned to olanzapine had:
- less akathisia and
- superior cognitive functioning (although not enough to affect quality of life);
- Olanzapine showed _*no*_ advantage in:
- Symptoms
- Quality of life
- Parkinsonian (EPS) side effects
- Olanzapine incurred greater weight gain and greater VA costs ($3,000 - $9,000/pt/year).

## Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS)(S Lewis et al. 2005)

- RCT conducted in the UK for the NHS Health Tecnhnology Assessment Program
- Recruited: Aug 1999 – April 2002
- Randomly assigned patients to “doctor’s choice” of any SGA other than clozpaine or FGA (n=227)
- No difference on symptoms, quality of life, side effects, health service use
- Conventional were more cost-effective

## CATIE Cost Effectiveness Analysis (CEA) Study Design

- Comparison of _***Initiation***_ Strategies
- Longer duration of treatment on olanzapine than risperidone or quetiapine: no difference from the FGA perphenazine
- Atypicals vs perphenazine:
-  Cost $3,600 – $6,000 more,
- are no more effective on symptoms, quality of life, violence, employment, neurocognition, EPS, TD, akathesia
- several incur greater weight gain

## Antipsychotic Formulary Policy Revisited

- Virtual current policy: only use SGAs
- 10x greater cost	 ($230 million for VA/year)
- 400 MHICM teams or PCTs
- 3800 Employment specialists
- No greater effectiveness
- Greater risk of weight gain/metabolic syndrome/ diabetes
- Less risk of EPS/TD _than moderate/high dose haloperidol_, but not intermediate or high potency FGAs (perphenazine, loxitane, thiothixene)
- Risperidone, least expensive SGA is off patent and will be less expensive.

## Two Aspects of Formulary Policy

- What is the most cost-effective sequence of treatments?
- How do we create incentives to follow it?
- No marketing for generics even if they are SGAs
- Apprehension about restriction of any MH treatment if cost-saving is a potential motivation.

## Preferred Sequence: Four groups of APS drugs

- Risperidone or intermediate potency FGA
- Clozapine (after 2 or 3 drug failures)
- Aripiprazole, ziprasidone or quetiapine
- Olanzapine: greatest weight gain

- Rosenheck et al., Schizophr Bull, 2008,34(2):375-380

## Incentives to Change

- Academic Detailing; Education/Information
- Monitor prescribing decision making with a structured form when NEW SGAs are prescribed
- Very weak disincentive (time burden for the form)
- Feedback information in further academic detailing
**Caveat:** Astra-Zeneca complained that we were not treating all SGAs equally as per VA agreement so we had to add risperidone to level 2

## Slide 9

## Slide 10

## Monitoring Form Data (N=1,721): Diagnosis

- Schizophrenia or BP    44%
- Schizophrenia		18.1%
- Bipolar disorder		26.6%
- Sleep			     18%
- Other Diagnoses	     38%
- Other affective		24.0%
- PTSD			          23.4%

## Monitoring Form Data (N=1,721): Reason for new medication

- Efficacy			39.3%
- Sleep			30.0%
- Patient preference		27.0%
- Less EPS		 	 12.5%
- Less TD risk		  8.9%
- Less akathisia		  4.7%
- Less sedation		  5.8%
- Treatment of TD	 	  0.8%
- Other			20.7%

## Monitoring Form Data (N=1,721): Health Status

- Age= 54.5 (±14)
- Weight=195 (±47) lbs.
- Ht = 5’9”
- BMI=28.8 (30=obese)

## Monitoring Form Data (N=1,721):Co-Morbidity

- TD 			4.3%
- EPS 			3.7%
- Akathisia		3.0%
- Diabetes		14.9%
- Hyperlipidemia	29.0% (DK-17.0%)
- Obesity		20.5% (DK-11.3%)
- Hypertension		34.0% (DK-10.2%)
- -  ASCVD		10.6% (DK-24.5%)

## Antipsychotics for Sleep (n=318 [18%])

- Medication
- Quetiapine 78.0%
- Olanzapine  9.7%
- Risperidone 8.8%
- Co-morbidities
- HTN-38.4%
- Hyperlipidemia-28.6%
- Diabetes 13.5%
- Obesity-16.7%

## Previous drug trials

- Failed previous trial (efficacy)
- Risperidone (5.0%)
- Perphenazine (0.5%)
- Haloperidol (2.4%)
- Aripiprazole (1.4%)
- Quetiapine (1.9%)
- Ziprasidone(1.5%)
- Clozapine (0.3%)
- Olanzapine (1.7%)
- Don’t know (26.6%)

- Failed  previous trial (intolerability)
- Risperidone (7.0%)
- Perphenazine (1.8%)
- Haloperidol (2.7%)
- Aripiprazole (1.2%)
- Quetiapine (3.3%)
- Ziprasidone (1.6%)
- Clozapine (0.5%)
- Olanzapine (3.3%)

## Additional Interventions

- Reviewed findings with groups
- MDs
- APRNs
- MHSLs
- No detail work force

## Slide 18

## Slide 19

## Conclusions

- SGAs are largely used for reasons without supporting evidence
- SGAs are largely used in patients who have medical conditions that these drug may worsen.
- MHSL managers have few tools to impact prescribing (?)
- Visit:
**http://vaww.nepec.mentalhealth.va.gov/AFP.htm**

## Favors FGA

- Favors SGA

- Hypothesis of 5
- point advantage
- for SGA *excluded*

**Difference in QLS scores**
**	****	****	****	****     ****Data from Table 3b**

- Equivalence

- Estimate of difference
- in QLS after imputation
- of missing data, with
- 95% c.i. of difference

- Expected

- Observed

- 0

- 1

- 2

- 3

- 4

- 5

- -1

- -2

- -3

- -4

- -5

- -6

- 6

## Treatment (N=1,721)

- Treatment proposed:
- Quetiapine		49.4%
- Olanzapine		17.7%
- Aripirazole		13.2%
- Risperidone*		12.4%
- Ziprasidone	  	  5.2%
- CONSTA		  1.4%

- *Added in Summerof 2008