What long-acting injection (LAI) can be given to a patient with a current mixed bipolar episode who is already on Seroquel (quetiapine)?

Long-Acting Injectable Antipsychotics for Mixed Bipolar Episodes

For a patient with a current mixed bipolar episode on quetiapine (Seroquel), risperidone LAI is the most strongly recommended long-acting injectable option, with aripiprazole LAI as a reasonable alternative. 1, 2

Primary Recommendation: Risperidone LAI

Risperidone LAI is the best-evidenced LAI for bipolar disorder and specifically demonstrated efficacy in patients with recent mixed episodes. 1

• The pivotal randomized controlled trial enrolled patients with "current or recent manic or mixed episodes" and demonstrated that risperidone LAI significantly delayed time to recurrence of any mood episode compared to placebo (p < 0.001). 1

• Most patients (77%) received 25 mg every 2 weeks during the maintenance phase, with dosing flexibility between 25-50 mg biweekly. 1

• A 15-month effectiveness trial showed risperidone LAI-treated bipolar patients experienced significantly fewer negative clinical events (mean 0.86 ± 0.73) compared to oral atypical antipsychotics including quetiapine (mean 1.61 ± 1.29, p = 0.028). 3

• The British Journal of Psychiatry recommends considering the oral form of the same medication when initiating LAI treatment, and since your patient is already on quetiapine, transitioning to risperidone LAI would require establishing oral risperidone tolerability first. 4

Alternative Option: Aripiprazole LAI

Aripiprazole LAI represents the only other FDA-approved LAI specifically for bipolar disorder maintenance treatment. 2

• A large double-blind, placebo-controlled trial (731 participants enrolled, 266 stabilized and randomized) demonstrated that nearly twice as many LAI aripiprazole-treated participants remained stable compared to placebo over 52 weeks. 2

• Akathisia combined with restlessness occurred in 23% of patients, which is the primary tolerability concern. 2

• This option may be particularly useful if the patient has experienced akathisia or extrapyramidal symptoms with risperidone in the past. 2

Clinical Implementation Algorithm

Step 1: Establish oral tolerability 4

• Initiate oral risperidone (or aripiprazole if choosing that alternative) while continuing quetiapine initially
• Titrate to therapeutic dose over 1-2 weeks
• Monitor for tolerability, particularly extrapyramidal symptoms and metabolic effects

Step 2: Transition to LAI 5

• Begin LAI as soon as acute symptoms improve and dosage flexibility is no longer required
• For risperidone LAI: Start with 25 mg every 2 weeks, continue oral supplementation for 3 weeks 1
• For aripiprazole LAI: Follow standard initiation protocol with oral overlap

Step 3: Taper quetiapine 1

• Once LAI is established (after 3-4 weeks), gradually taper quetiapine
• Monitor closely for symptom re-emergence during transition

Important Caveats

Weight gain requires vigilant monitoring with both agents. 1, 3

• Weight gain ≥7% occurred in 15% of risperidone LAI patients during stabilization and 12% during maintenance. 1
• In the effectiveness trial, 38% of risperidone LAI patients and 50% of oral atypical antipsychotic patients gained ≥7% baseline body weight. 3

Mixed episodes present a specific challenge. 1

• Risperidone LAI significantly delayed recurrence of elevated-mood episodes (p < 0.001) but not depressive episodes (p = 0.805). 1
• This means additional mood stabilizer coverage (lithium or valproate) may be necessary for depressive symptom prevention. 6

The evidence base strongly favors second-generation LAIs over first-generation agents due to better tolerability and fewer neurological side effects. 5, 4

Why Not Other LAIs?

• Paliperidone palmitate: Evidence limited to one observational study and one case series in bipolar disorder. 7
• Olanzapine pamoate: Only a single case report exists for bipolar disorder, despite olanzapine's established efficacy in oral form for mixed episodes. 7, 8

The systematic review of second-generation LAIs for bipolar disorder found substantial disparity in available evidence, with risperidone LAI having multiple RCTs and aripiprazole LAI having one RCT, while other agents lack adequate controlled trial data. 7