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Tips on Choosing an Antipsychotic for Schizophrenia

August 26, 2020

Which antipsychotics should we consider selecting as the first-line and second-line treatments, and what should we base this decision on? Dr. Aziz addresses this in a past article from The Carlat Psychiatry Report. Here’s some of his advice:

Process:

Tolerability instead of efficacy should be considered when selecting a first-line treatment. “If it’s not tolerable, switch to an option with a different side effect profile”.

Tolerability and efficacy should be the main determinants when choosing a proper second-line treatment, after 4 weeks of an inadequate response to the first-line treatment.

Move to clozapine quickly for treatment-resistant cases, defined as a failure to respond to 2 or more antipsychotics.

Antipsychotic Selection in Schizophrenia:

First-Line Treatments.

“Aripiprazole, risperidone, ziprasidone, and cariprazine are good starting places”.

Particularly, aripiprazole and, if cost is not an issue, cariprazine “stand out for their mild benefits in negative symptoms and favorable long term side effect profiles”. However, aripiprazole-treated patients are more likely to experience akathisia.

Second-Line Treatments.

“Options include an alternate second-generation antipsychotic, risperidone if not already tried, olanzapine, or a first-generation antipsychotic”.

If efficacy is the main concern, then olanzapine is a great choice, however, it may negatively impact metabolism (Osser DN et al, Harv Rev Psychiatry 2013;21(1):18–40).

Treatment-Resistant Cases.

Once a patient is considered treatment-resistant, clozapine must be started early because the chances of “responding to clozapine drops by 8%-11% with every failed antipsychotic trial”, and if it’s started 3 years after the first episode, then its potential efficacy diminishes from 82% to 32% (John AP et al, Can J Psychiatry 2018;63(8):526–531; Yoshimura B et al, Psych Res 2017;250:65–70).

While clozapine may produce some treacherous side effects including “neutropenia, seizures, cardiotoxicity, and small bowel obstruction”, a meta-analysis showed that “the mortality rate was 44% lower with clozapine than other antipsychotics” (Vermeulen JM et al, Schizophr Bull 2019;45(2):315–329).

Helpful Resources:

The Harvard South Shore Psychopharmacology Algorithm Project. A flowchart that helps guide your decision-making process.

Jonathan Meyers’ The Clozapine Handbook (2019). “A useful guide to managing clozapine’s side effects”.

CATIE trial. A study that evaluated the effectiveness of second-generation antipsychotics v.s. Each other and perphenazine (Lieberman JA and Stroup TS, Am J Psychiatry 2011;168(8):770–775).