Podcast: Using Antipsychotic Plasma Levels to Guide Schizophrenia Treatment With Jonathan M. Meyer, MD

In a recent episode of “Brain Trust: Conversations in Psychopharmacology,” host Joseph F. Goldberg, MD, spoke with Jonathan M. Meyer, MD, voluntary clinical professor of psychiatry at the University of California, San Diego, about therapeutic drug monitoring of antipsychotics in schizophrenia spectrum disorders.

Meyer recommended 12-hour trough levels, which track oral dose in predictable ratios. Aripiprazole levels run roughly 11 times the nightly dose, and the total risperidone active moiety roughly 7 times the dose. A level more than 50% below the expected value most often reflects nonadherence. A repeat level separates erratic adherence from ultrarapid metabolism. Before raising a dose, he suggested drawing a level on the current dose so that 2 data points are available.

Thresholds vs Therapeutic Levels

Meyer cautioned against calling a level therapeutic simply because it exceeds the response threshold, such as 350 ng/mL for clozapine. Patients with an inadequate response above the threshold may need higher levels, up to what he terms the point of futility, beyond which fewer than 5% of patients respond. He places that point at approximately 1000 ng/mL for clozapine and 18 ng/mL for haloperidol. Patients who respond below a threshold should be managed according to their clinical status rather than the number.

Most positive-symptom benefit from a given oral dose appears within 2 weeks, with little added gain after 4 weeks.

Practical Pearls

Meyer said laboratory-reported antipsychotic ranges are often unreliable, noting upper limits for fluphenazine that vary 5-fold between laboratories. An unexpectedly high result should prompt a patient assessment and a repeat level, because laboratory error and doses taken just before the draw are common. A lithium sample drawn in a tube containing lithium heparin can also produce a falsely elevated level.

He does not recommend levels for iloperidone, ziprasidone, or quetiapine. For patients with clozapine-induced tachycardia, he advised recalculating QTc with a linear formula such as Framingham rather than Bazett.

Meyer described plasma levels as more useful than pharmacogenetic testing because they capture genetics, smoking, and drug interactions in a single measurement. He recommended checking levels every 6 months in stable outpatients taking oral antipsychotics.

“Don’t guess, measure,” concluded Meyer.

Dr Goldberg is a clinical professor of psychiatry at The Icahn School of Medicine at Mount Sinai in New York, NY and the immediate-past president of the American Society of Clinical Psychopharmacology.

Dr Meyer is a voluntary clinical professor of psychiatry at the University of California, San Diego.