Aripiprazole modified release (Abilify Maintena) for schizophrenia

Oral aripiprazole has been available for the treatment of schizophrenia in Australia since 2003.³ It has a receptor-binding profile that allows partial agonist activity at dopamine D₂ and serotonin 5-HT_1A receptors and antagonist activity at serotonin 5-HT_2A receptors.^2-4 This mechanism of action is distinct from that of other atypical agents.^{4, 5}

Antipsychotic medicines are the mainstay of pharmacological treatment for patients with schizophrenia.⁶ Australian guidelines recommend oral second-generation (atypical) antipsychotic agents for first-line treatment in most patients, due to the lower risk of extrapyramidal symptoms (EPS) (ie, akathisia, tardive dyskinesia) compared with typical agents.^{6, 7}

Poor adherence to treatment is a recognised problem in the management of patients with schizophrenia,⁸ and is predictive of poor outcomes (relapse, aggressive behaviour, suicide, substance abuse) and increased risk of hospitalisation.^{6, 8}

Multiple factors have been identified as increasing the risk of non-adherence, including complex medicines schedules and the use of oral treatments.⁹ Long-acting formulations of typical and atypical antipsychotic medicines have the potential to improve long-term outcomes due to improved adherence.^{8, 10}

Guidelines suggest that long-acting antipsychotic medicines may be offered to people who would prefer such treatment or in cases where avoiding covert non-adherence to antipsychotic medication (either intentional or unintentional) is a clinical priority within the treatment plan.^{6, 11}

ALAI is already approved for the treatment of schizophrenia in several European countries as well as the US.^{4, 12}

Three other second-generation antipsychotic medicines are currently available on the PBS in long-acting injection formulations — risperidone, olanzapine and paliperidone (Table 1).¹³

In the double-blind active-controlled ASPIRE EU trial, adult patients with schizophrenia stabilised on oral aripiprazole (minimum of 8 weeks) were randomised 2:2:1 to maintenance treatment with:

• ALAI (400 mg once monthly, n = 265) or
• oral aripiprazole (10–30 mg/day, n = 266) or
• ALAI (50 mg once monthly, n = 131)^†

and followed out to 38 weeks.¹⁷ A double-dummy design ensured all patients, including those randomised to oral aripiprazole, received an injection.

The primary outcome was Kaplan–Meier estimated impending relapse rates at week 26. Trial results demonstrated non-inferiority for ALAI 400 mg compared with oral aripiprazole (7.12% vs 7.76%, treatment difference –0.64%, p = 0.79).¹⁷ Both treatments were superior to ALAI 50 mg (21.80%, p ≤ 0.001).

† A dose below the therapeutic threshold for assay sensitivity.

Overall findings from ASPIRE EU reported that frequency of treatment-emergent adverse events was comparable across all three groups and largely mild to moderate in severity.¹⁷

Serious treatment-emergent adverse events were also similar across treatment arms: 5.7% for ALAI 400 mg, 5.6% for oral aripiprazole and 8.4% for ALAI 50 mg.

More patients treated with ALAI 400 mg experienced treatment-emergent EPS and EPS-related adverse effects (21.9%) compared with oral aripiprazole (11.7%) and ALAI 50 mg (12.2%).

Injection-site pain was also more common in the aripiprazole 400 mg group (7.5%) than in the 50 mg (0.8%) group or the oral group receiving placebo injections (2.3%).

It has been suggested that ALAI may provide some advantage over other available atypical antipsychotic LAIs for patients in whom weight gain, adverse metabolic effects or prolactin increase are a concern.^{5, 10}

However, with no head-to-head trials directly comparing ALAI to other LAI formulations, recommendations regarding the use of one LAI over another cannot be readily made.^{10, 18}

An indirect comparison of ALAI, paliperidone LAI and olanzapine LAI, using placebo-controlled registration trial data, suggests comparable efficacy across the three agents in terms of relapse prevention.¹⁰

A comparative study of ALAI versus paliperidone LAI is currently underway (NCT01795547).¹⁹

Two dosage strengths of ALAI are listed on the PBS: 400 mg and 300 mg.²

Both doses are available as a kit containing:²

• a vial of the active ingredient (in lyophilised powder form)
• a vial of sterile water for reconstitution
• a sterile syringe and needle for reconstitution
• a sterile syringe and safety needles for injection
• a vial adaptor.

The recommended starting and maintenance dose is 400 mg once monthly, with continued treatment with oral aripiprazole (10–20 mg/day) or other oral antipsychotic for 2 weeks after the first injection.²

If there are adverse reactions with the 400 mg dose, consider reducing the dose to 300 mg once monthly.²

Dose adjustments are recommended in patients known to be CYP2D6 poor metabolisers or if strong inhibitors of CYP2D6 or CYP3A4 are being taken concomitantly for ≥ 2 weeks. The Product Information provides further details.²