Joe parks dd best practices 4 13 (2)

Best Practices for Best Outcomes

April 13, 2010

Psychotropic Medication Utilization

Medication Hab Center CMHC

Antipsychotic 55% 68%

Antidepressant 35% 70%

Benzodiazepine 50% 45%

Anticonvulsant/MS 52% 31%

Antipsychotic PatternsUsage Hab Center CMHC

Any 55% 68%

2 or More 22% 6.1%

3 or More 1.3% 0.5%

High Dose 15% 3%

FGA (typical) 29% 15%

With dyskinetic 36% 21%

Portion of Prescriptions Potentially Questionable

CMHC’s 6.3% - 17.5%CPS Special Housing 18.0% - 22.6% Hab Centers 16.6% - 36.3%

Outlier Prescribing and Psychiatry Time

Hab Center % Outlier Prescriptions

Annual HrsPsychiatry per Resident

SEMORS 36.3% Community

MHC 32.4% 0.1

NHC 30.2% Community

HHC 24.9% 2.1

SLDDTC 17.7% 7.0

BHC 16.6% 7.1

Causes of Polypharmacy

• Not Enough Psychiatry Coverage• Incorrect Diagnosis• Failed Tapers• Over reliance on medication as the sole

treatment• Desperation

Negative Outcomes Associated with Polypharmacy

• Drug Interactions• Increased Medication Errors• Increasing Difficulty Assessing Effect of

Individual Medications• Increased Side Effects• Increased Mortality• Additional Medications for Side Effects• Cost

Antipsychotic PolypharmacyMEDLINE search 1966-2007

• Categorized by Study Population– Treatment Resistant (15 studies)– Non-Treatment Resistant (15 studies)

• Included: – Randomized Controlled Trials, (9 trials)– Non- Randomized Controlled Trials (6 trials)– Non-Controlled Observational studies (15

studies)• Excluded:

– Series without statistical analysis – case reports

Limitations of Literature

Small sample Sizes

Short Duration

Limited Matching Characteristics

Treatment Resistant StudiesMethod Total

Studies

Outcome Poly –AP better

No Difference

Mono- APBetter

Observational 9 Symptoms 8 1 0

Side Effects

1 4 3

Non-Controlled Random Trial

0

RCT 6 Symptoms 2 3 1

Side Effects

0 2 4

Totals 15 Symptoms 10 4 1

Side Effects

1 6 7

Treatment Resistant Studies by Medications Utilized

Methodology Clozapine Augmentation

AP unavailable in USA

Not ClozapineAvailable in USA

RTC 5 1 0

Observational 8 0 1

Megna et. Al 2007

• Only Study to show superiority of Multiple Antipsychotics in Treatment Resistant Psychosis without Clozapine or Non-US AP

• Retrospective Chart Review of 26 patients• Second antipsychotic added after 4 months

on mono-therapy• Outcomes

– 26% reduction on BPRS and decreased PRN use– Increased side effects– None improved enough for discharge

Non-Treatment Resistant StudiesMethod Total

Studies

Outcome Poly –AP better

No Difference

Mono- APBetter

Observational

6 Symptoms 0 4 2

Side Effects

2 1 3

Non-Controlled Random Trial

6 Symptoms 0.5Low dose mono

5.5 0

Side Effects

0 2 4

RCT 3 Symptoms 0 3 0

Side Effects

1 0 2

Totals 15 Symptoms 0.5 12.5 2

Side Effects

3 3 9

Non-Treatment Resistant Studies by Medications Utilized

Methodology Clozapine Augmentation

AP unavailable in USA

Not ClozapineAvailable in USA

RTC 1 0 2

Non-ControlledRandom Trial

1 0 5

Observational 2 0 4

Nishikawa, et. al. 1985

• Only Study to show superiority of Multiple Antipsychotics in Non-Treatment Resistant Psychosis without Clozapine or Non-US AP

• Non-Randomized Controlled Trial• Compared pimozide/thioridazine

polypharmacy with both as mono-therapy• Outcomes

– Poly was superior to low dose mono– Poly was no better than higher dose mono– Signs of “overdose” more common with poly

Three Adjunctive Studies

• All in Non-Treatment Resistant Population

• All had Metabolic Syndrome reduction as Primary Outcome

• One Non-Controlled Observational Study– CLZ vs CLZ/quetiapine: poly did better

• Two Non-Controlled Random Studies– Mono-SGA vs poly-SGA : no difference– CLZ vs CLZ/RIS : CLZ/RIS did worse

Antipsychotic PolypharmacyMortality Studies

• Waddington, et. Al. 1998– 10 year prospective inpatient schizophrenia

study– RR associated with AP polypharmacy = 2.46– Adjusted for cumulative AP dose and years on

APs• Joukamaa, et. Al. 2006

– 17 year retrospective schizophrenia study– RR associated with AP polypharmacy = 2.50– Adjusted for age, gender, BMI, smoking,

education, and multiple other factors

Conclusions - What we know

Antipsychotic Polypharmacy improves when augmenting Clozapine in treatment Resistant Patients, but also increases side effects.

Antipsychotic Polypharmacy in Non-treatment Resistant Patients› No improvement in symptoms› More side effects› Higher Mortality

Adjunctive Antipsychotic Polypharmacy does not reduce metabolic side effects

Limitations- What We Don’t Know

Efficacy of non-Clozapine SGA Polypharmacy in treatment resistant psychosis

Efficacy of Clozapine polypharmacy in non-treatment resistant psychosis

Aripiprazole augmentation of Risperidone or Quetiapine

Correll, Kane, Goff et.al. June , 2008 Poster

16 week, double blind, placebo controlled RTC

323 patients on risperidone or quetiapine given aripiprazole or placebo

No improvement in symptoms with SGA polypharmacy

Mixed changes in side effects

Published Practice GuidelinesRegarding Antipsychotic Polypharmacy

Published Guide lines include› American Psychiatric Association› Expert Consensus Guideline Series› Texas Medication Algorithmns› PORT

All recommend use of more than one AP only:› After multiple trials of monotherapy› After trial of clozapine

Justifications for Antipsychotic Polypharmacy

Clozapine Augmentation A History of 3 or more failed Trials of

monotherapy Recommended Plan to taper to

monotherapy

§483.450(e) Standard: Drug Usage

(e)(1) The facility must not use drugs in doses that interfere with the individual client’s daily living activities.

(e)(2) Drugs used for control of inappropriate behavior must be approved by the interdisciplinary team and be used only as an integral part of the client’s individual program plan that is directed specifically towards the reduction of and eventual elimination of the behaviors for which the drugs are employed.

http://www.cms.gov/manuals/downloads/som107ap_j_intermcare.pdf accessed 4.09.10

http://www.cms.gov/manuals/downloads/som107ap_j_intermcare.pdf


(e)(3) Drugs used for control of inappropriate behavior must not be used until it can be justified that the harmful effects of the behavior clearly outweigh the potentially harmful effects of the drugs.

(e) (4)(i) Drugs used for control of inappropriate behavior must be monitored closely, in conjunction with the physician and the drug regimen review requirement for desired responses and adverse consequences by facility staff; and




(e)(4)(ii) Gradually withdrawn at least annually in a carefully monitored program conducted in conjunction with the interdisciplinary team, unless clinical evidence justifies that this is contraindicated



Spectrum of AP Side Effects

Sedation Sedation

Weight Gain Weight Gain

NMS NMS EPS EPS

WBC WBC

Diabetes/DKA Diabetes/DKA

Anticholinergic Anticholinergic Orthostasis Orthostasis

Lipids Lipids

ANTIPSYCHOTICAGENTS

Seizures Seizures

Prolactin Prolactin

NMS = Neuroleptic Malignant Syndrome

Professional Resources & Business Development

Drug EPS TD Prolactin Elevation

WeightGain

LipidIncrease

GlucoseChange

Antichol Sedation

High Potency Conventional AP

+++ +++ +++ + + + ++ ++

Low Potency Conventional AP

++ ++ ++ ++ + + +++ +++

Clozapine +/- +/- + +++ ++ ++ ++ +++Risperidone ++ + ++ + + + + +Olanzapine + + + +++ ++ ++ + ++Quetiapine + + + ++ ++ ++ ++ ++Ziprasidone + + + +/- +/- +/- +/- +/-Aripiprazole + + + +/- +/- +/- +/- +/-Paliperidone ++ + ++ + + + + +Asenapine + + + +/- +/- +/- +/- +/-

Relative Risk of Side Effects Among Agents

Mueser KT, Jeste DV. in Clinical Handbook of Schizophrenia, 2008, Fuller M, Sajatovic M, in Psychotropic Drug Information Handbook 2009, Drug PIs

+++ substantial risk, ++ moderate risk, + mild risk, +/- minimal risk or insufficient data

Meaningful Medication Tapers

Polypharmacy – 2 or more in same class› 25% dose reduction per month› Completely off in 6 – 9 months

Monotherapy – only one of that class› 10% dose reduction per month› Completely off in 12 – 18 months

But Our Patients are Sicker

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Joe parks dd best practices 4 13 (2)