What long-acting injectables (LAIs) are FDA-approved for bipolar disorder?

FDA-Approved Long-Acting Injectable Antipsychotics for Bipolar Disorder

Currently, risperidone long-acting injectable (LAI) is the only FDA-approved long-acting injectable antipsychotic for bipolar disorder, specifically indicated for the maintenance treatment of Bipolar I Disorder as monotherapy or as adjunctive therapy to lithium or valproate. 1

Details of Risperidone LAI for Bipolar Disorder

FDA Approval and Indications

• Risperidone LAI is FDA-approved for:
  • Maintenance treatment of Bipolar I Disorder as monotherapy
  • Maintenance treatment of Bipolar I Disorder as adjunctive therapy to lithium or valproate 1

Dosing and Administration

• Recommended dose: 25 mg intramuscular every 2 weeks
• Some patients may benefit from higher doses of 37.5 mg or 50 mg
• Maximum dose should not exceed 50 mg every 2 weeks
• Dosages above 50 mg have not been studied in bipolar population 1

Administration Route

• Deep intramuscular injection via:
  • Deltoid administration: Use 1-inch needle, alternating between arms
  • Gluteal administration: Use 2-inch needle, alternating between buttocks 1

Initiation Protocol

• Establish tolerability with oral risperidone prior to initiating LAI treatment
• A lower initial dose of 12.5 mg may be appropriate when clinical factors warrant dose adjustment:
  • Patients with hepatic or renal impairment
  • Certain drug interactions that increase risperidone plasma concentrations
  • History of poor tolerability to psychotropic medications 1

Clinical Evidence for Risperidone LAI in Bipolar Disorder

Efficacy Data

• In a multicenter, double-blind, placebo-controlled study of adults with Bipolar I Disorder:

  • Time to relapse to any mood episode was significantly delayed with risperidone LAI monotherapy compared to placebo
  • Majority of relapses were due to manic rather than depressive symptoms 1

• As adjunctive therapy with lithium or valproate:

  • Time to relapse was delayed compared to placebo
  • Relapse types were approximately half depressive and half manic or mixed episodes 1, 2

• Risperidone LAI has shown better efficacy in preventing manic episodes than depressive episodes 3

Important Clinical Considerations

Patient Selection

• Best candidates for risperidone LAI include:
  • Patients with adherence problems to oral medications
  • Patients with a history of response to oral risperidone
  • Patients with predominantly manic polarity 4, 3

Monitoring Requirements

• Regular assessment of efficacy using standardized measures
• Monitoring of metabolic parameters (weight, glucose, lipids) at baseline and periodically
• Monitoring for injection site reactions, akathisia, and initial anxiety 4

Tolerability and Safety

• Generally well tolerated in patients with bipolar disorder
• Most adverse reactions are mild to moderate in severity
• Common side effects include:
  • Weight gain (>7% body weight in 12% of patients on maintenance therapy)
  • Extrapyramidal symptoms
  • Injection site reactions 1, 5

Practical Implementation

Storage Requirements

• Store in refrigerator (36° to 46°F; 2° to 8°C)
• Protect from light
• If refrigeration unavailable, can be stored at temperatures not exceeding 77°F (25°C) for no more than 7 days prior to administration 1

Missed Dose Management

• Missed LAI doses are immediately apparent to the clinical team, unlike oral medications
• This allows for prompt intervention when adherence issues arise 4

Limitations and Caveats

• Despite potential benefits, LAIs remain an underutilized option in many countries despite frequent non-adherence with oral medication and subsequent relapse 6
• While risperidone LAI is effective for preventing manic recurrences, it may be less effective for preventing depressive episodes 3
• Consider the need for regular clinic visits for administration when selecting patients for LAI treatment