Chapter 4: Antipsychotics

GENERAL PRESCRIBING TIPS

Which antipsychotic should you choose? There are dozens of options and approved indications. Here are some of the factors you should weigh as you decide which antipsychotic to prescribe for a given patient:

• Efficacy

• Side effects

• Cost

Efficacy

While there’s some debate about this, most experts consider clozapine to be the only antipsychotic that is clearly more effective than the others. Unfortunately, clozapine also happens to have one of the worst side effect profiles in psychiatry. Weight gain is the most prominent: You can expect half of all patients who take clozapine to have a 20% or more weight gain over time (Umbricht DS et al, J Clin Psychiatry 1994;55(Suppl B):157–160). When you consider its other major side effects, like sedation, drooling, and life-threatening neutropenia, not to mention the necessity of monthly blood draws, it’s no wonder that clozapine is used relatively rarely. Nonetheless, it’s incredibly helpful for certain treatment-resistant patients.

Next on the list of drugs that might be more effective than others is olanzapine, another side effect overachiever. It doesn’t cause as much weight gain as clozapine, but it’s close. In the CATIE trial, 30% of patients gained at least 7% of their initial weight.

Beyond this, there’s no consensus that any of the other second-generation antipsychotics (SGAs) differ in efficacy, at least for core symptoms of psychosis. It’s possible that SGAs have a broader spectrum of efficacy, given that many are approved for various mood syndromes as well as psychosis. Some people believe that SGAs are more effective than first-generation antipsychotics (FGAs) for negative symptoms. This probably stems from the fact that FGAs are more likely to cause side effects, like extrapyramidal symptoms (EPS), which can mimic negative symptoms. It is becoming more reasonable to choose SGAs over FGAs for most patients as more of the former go generic.

Side Effects

Below are some of the key antipsychotic side effects along with our best estimates of the liabilities of specific agents. You’ll find a more detailed comparison of relative side effects in Table 4-4.

• Weight gain/hyperlipidemia/hyperglycemia:

  • - Most weight gain: Clozapine, olanzapine

  • - Moderate: Asenapine, iloperidone, olanzapine/samidorphan, paliperidone, quetiapine, risperidone

  • - Least weight gain: Aripiprazole, brexpiprazole, cariprazine, lumateperone, lurasidone, ziprasidone, most FGAs (eg, haloperidol, perphenazine)

• Sedation:

  • - Most sedating: Chlorpromazine, clozapine, olanzapine, olanzapine/samidorphan, quetiapine (note that sedation can sometimes be beneficial for agitated, anxious, or manic patients)

  • - Moderately sedating: Asenapine, iloperidone, lurasidone, risperidone, ziprasidone

  • - Least sedating: Aripiprazole, brexpiprazole, cariprazine, lumateperone, paliperidone

• Cardiac issues (primarily prolonged QT interval):

  • - Most issues: Chlorpromazine, iloperidone, thioridazine, ziprasidone

  • - Moderate: Asenapine, clozapine, haloperidol, olanzapine, olanzapine/samidorphan, paliperidone, quetiapine, risperidone

  • - Fewest issues: Aripiprazole, brexpiprazole, cariprazine, loxapine, lumateperone, lurasidone, olanzapine, risperidone

• EPS:

  • - Most EPS: Fluphenazine, haloperidol, paliperidone, risperidone

  • - Most akathisia: Aripiprazole, brexpiprazole, cariprazine

  • - Moderate: Asenapine, iloperidone, lumateperone, lurasidone, ...