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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

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

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

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

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

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

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

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

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

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