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

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

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 5point advantagefor SGA excluded

Difference in QLS scores Data from Table 3b

Equivalence

Estimate of differencein QLS after imputationof missing data, with95% c.i. of difference

ExpectedObserved

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