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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:
Antipsychotic Selection in Schizophrenia:
First-Line Treatments.
Second-Line Treatments.
Treatment-Resistant Cases.
Helpful Resources:
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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).
- “Seven Clozapine Tips”. A recent podcast we did containing imperative information about clozapine treatment.
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