1. Copyright Notice
This presentation is copyrighted by the Psychopharmacology Institute.
Subscribers can download it and use it for professional use.
The contents of the presentation may be modified, but the Psychopharmacology Institute logo must remain visible in all slides.

2. What to Do if Clozapine Augmentation is Ineffective (Node 5)
David N. Osser, MD
Associate Professor of Psychiatry
Harvard Medical School
Brockton Division of the VA Boston Healthcare System
General Editor - Psychopharmacology Algorithm Project
Harvard South Shore Residency Training Program

3. AP
Antipsychotic
Clozapine
Clozapine Augmentation
Probability of improvement is low
Unexpected positive results can happen

4. - Risperidone, lamotrigine,
topiramate, ECT
- Memantine, O3FA
Augmentation
Best next option: aripiprazole
(anecdotal data)
Switch AP

5. Aripiprazole After Clozapine
High-potency D2 APs
upregulation of D2 receptors
Clozapine
downregulation of D2 receptors

6. Aripiprazole 27% of patients ARI
response
(30% PANSS improvement)
2 or more antipsychotic trials
Perphenazine 25% of patients
PER

7. FGA + Mirtazapine Combination
Likelihood of success if clozapine has been tried
FGA
Mirtazapine
If clozapine has not been tried this combination might be considered
thought to duplicate the receptor impact of clozapine

8. Celecoxib 100 mg twice daily
SGA+ Celecoxib
Effective in patients who had been ill for less than two years
SGA
Celecoxib 100 mg twice daily
Inflammation could contribute to schizophrenia pathogenesis

9. Antipsychotic Combinations Not Involving Clozapine
No good evidence of efficacy
Strong negative evidence
Antipsychotic
Antipsychotic
AP + quetiapine
AP + risperidone

10. Key Points
After three failed antipsychotic trials the probability of improvement is low
Some selected interventions:
Stopping clozapine and trying aripiprazole
Stopping clozapine and trying a combination of FGA + mirtazapine or SGA+ celecoxib

11. End of Presentation