What are second-generation antipsychotics similar to Fanapt (Iloperidone)?

From the Guidelines

Fanapt (iloperidone) and other second-generation antipsychotics, such as risperidone, paliperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, brexpiprazole, cariprazine, lurasidone, and asenapine, should be carefully monitored for changes in weight, glycemic control, and cholesterol levels, especially in patients with diabetes, due to the increased risk of type 2 diabetes associated with these medications 1. When considering second-generation antipsychotics similar to Fanapt, it is essential to evaluate their pharmacological profiles, side effect profiles, and FDA-approved indications.

• These medications share a similar mechanism of targeting dopamine D2 and serotonin 5-HT2A receptors, though each has a unique receptor binding profile.
• Risperidone and paliperidone are most similar to Fanapt in their receptor binding patterns.
• All these medications are FDA-approved for schizophrenia, with some also approved for bipolar disorder, depression, and other conditions.
• They generally cause fewer extrapyramidal symptoms (movement disorders) than first-generation antipsychotics, though they vary in their side effect profiles.
• Some, particularly olanzapine and quetiapine, carry higher metabolic risks (weight gain, diabetes), while others like aripiprazole and ziprasidone tend to be more metabolically neutral.
• Clinicians should consider factors including the patient's symptom profile, previous medication response, side effect tolerance, comorbid conditions, and insurance coverage when selecting an alternative to Fanapt.
• Coordinated management of diabetes or prediabetes and serious mental illness is recommended to achieve diabetes treatment targets, especially for patients taking second-generation antipsychotics 1.

From the FDA Drug Label

The mechanism of action of paliperidone in schizophrenia is unclear. However, the drug's therapeutic effect in schizophrenia could be mediated through a combination of central dopamine Type 2 (D 2) and serotonin Type 2 (5HT 2A) receptor antagonism.

Second generation antipsychotics similar to Fanapt are not explicitly mentioned in the provided drug labels. However, based on the mechanism of action described, paliperidone can be considered a second-generation antipsychotic.

• Key characteristics of paliperidone include:
  • Central dopamine Type 2 (D 2) receptor antagonism
  • Serotonin Type 2 (5HT 2A) receptor antagonism
  • Antagonism at α 1 and α 2 adrenergic receptors and H 1 histaminergic receptors
• Other second-generation antipsychotics with similar mechanisms of action may include:
  • Risperidone (parent compound of paliperidone)
  • Other atypical antipsychotics with dopamine and serotonin receptor antagonism properties 2 2

From the Research

Second Generation Antipsychotics Similar to Fanapt

• Fanapt (iloperidone) is a second-generation antipsychotic, and other similar medications include:
  • Asenapine 3
  • Lurasidone 3
  • Cariprazine 3
  • Ziprasidone 3, 4
  • Aripiprazole 3, 4, 5
• These medications are advisable for their lower propensity to cause weight gain and metabolic abnormalities compared to older second-generation antipsychotics like olanzapine or clozapine 3
• Lurasidone seems to be the best in terms of minimizing unwanted alterations in body weight and metabolic variables 3

Dose Equivalents for Second-Generation Antipsychotics

• The minimum effective doses for second-generation antipsychotics have been identified, including:
  • Iloperidone: 8 mg/day, equivalent to 1.07 mg/day of olanzapine 4
  • Asenapine: 10 mg/day, equivalent to 1.33 mg/day of olanzapine 4
  • Aripiprazole: 10 mg/day, equivalent to 1.33 mg/day of olanzapine 4
  • Ziprasidone: 40 mg/day, equivalent to 5.33 mg/day of olanzapine 4
  • Lurasidone: 40 mg/day, equivalent to 5.33 mg/day of olanzapine 4

Comparative Effectiveness of Atypical Antipsychotics

• A review of the comparative effectiveness of atypical antipsychotics found that:
  • Quetiapine was not effective in the treatment of eating disorders or personality disorder 6
  • Risperidone was associated with benefits in the treatment of OCD 6
  • Adverse events are common with atypical antipsychotics, including weight gain, fatigue, sedation, and extrapyramidal symptoms 6
• A comparison of quetiapine with other atypical antipsychotics found that:
  • Quetiapine produced slightly fewer movement disorders and less weight gain than olanzapine, but increased QTc prolongation 5
  • Quetiapine induced slightly fewer movement disorders and less prolactin increase than risperidone, but greater cholesterol increase 5

Paliperidone Palmitate

• Paliperidone palmitate is a long-acting injection formulation of paliperidone, which is the active metabolite of risperidone 7
• Paliperidone palmitate has been shown to be effective in controlling the acute symptoms of schizophrenia and delaying time to relapse, with a safety and tolerability profile comparable to risperidone long-acting injection 7