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614-893-0910 or BTCarroll1@cs.com - 614-937-9427
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Refractory Psychosis
Is Schizophrenia a Single Entity? … Schizophrenia is a disease in that it is a chronic condition that leads to disability. However, the fact that there are 6 etiologies and hundreds of genetic markers points to multiple illnesses.
Schizophrenia is not a solitary illness
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Suppose the APs are Not Absorbed?
ETOH/other Meds may interfere
GI Absorption varies (e.g. Seroquel > 600 mg/dose - not all is absorbed)
Excessive 1st pass metabolism
Compliance varies (58% Adherence)
Consider Depot Antipsychotics or Meds the patient prefers
Depot APs Bypass the Obstructions
They are potent D2 Blockers, They are less effected by ETOH/drugs/metabolism, and They assist in Compliance
Augmentation of APs - “What can be measured will be measured, Part II”
Lithium and Valproic Acid (Depakote) have the best data
Carbamazepine/Oxcarbamazepine
Lamotrigine, Gabapentin, Topirimate
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Treatment Refractory Defined
Failure of 2 Novel APs or 1 - Novel and 1 – Standard or Fails Clozapine The patient still has Psychosis that leads to functional impairment
The Volavka Study, 2002
Agents Used were: Clozapine, Olanzapine, & Risperidone in a NY state hospital population. Showed some indications for use of these of each of these meds. Hematological problems lead to d/c of 3 on clozapine and 2 on risperidone. Seizures led to the d/c of 2 on clozapine.
The Buffalo Study - Novel Tx Refractory
These patients failed 2 Novel APs at high doses for at least 6 wks
Improvement on Clozapine was 6/10 (60%)
Open-Label and used Blood Levels
Dr. Carroll Says ...What Can be Measured, Will Be Measured…
Clozapine has a therapeutic serum level of at least … 350 ng/ml
It is variable in its metabolism. Its metabolite is Norclozapine
Nicotine reduces it, Prozac increases it.
There are places where Clozapine can be used, and others where it is not.
Clozapine has beneficial effects and is cost effective, but needs clinical support
There are certain augmentation strategies that can be applied to patients who show only partial response or require further treatment.
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The Gold Standard – Clozapine vs. The Alchemy of Antipsychotics
Clozapine + Quetiapine (50/50)
Clozapine + Ziprasidone (+++)
Depakote + Clozapine (prev. Sz)
SSRIs + Clozapine (> 350 ng/ml)
2 Novel Antipsychotics = “making Clozaril”
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PRIZE Study - Partial Responders International SchiZophrenia Evaluation
Trial of Prolixin (fluphenazine) with no or only Partial response after 4 wks:
Quetiapine 600 mg per day versus Haloperidol 20 mg per day
The PRIZE Study, 2000, Results:
Entered, N = 365
Randomized, N = 288 (Seroquel- 143, Haldol- 145)
Completed, N = 228 (Seroquel- 111, Haldol- 117)
Response (>20% on PANSS): 52% vs 38%
Response (< 3 on CGI): 48% vs 36%
Response (on BOTH): 40% vs 28%
Conclusion: Quetiapine effective in Partial Responders
What about High Dose Novel Antipsychotics?
Olanzapine > 20 mg/d (up to 80 mg)
Risperidone > 6 mg/d (up to 16 mg)
Quetiapine > 800 mg/d (to 1600 mg)
Ziprasidone > 200 mg/d
Aripiprazole > 30 mg/d
No Evidence-Based Studies, “You can’t get there from here.”
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What to do…Clinically?
Identify the target symptoms or subtype.
Identify the need for clinical support.
Identify the acceptance of the regimen.
Identify the need for medication treatment.
including Clozapine and ECT
“What Can Be Measured Will Be Measured”, “Trust but Verify” and “Stay the Course”.
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