Aripiprazole for treating moderate to severe manic episodes in adolescents with bipolar I disorder

Aripiprazole (Abilify, Otsuka Pharmaceuticals Europe) is an antipsychotic with partial dopamine D2 and D3 agonistic properties. It has a UK marketing authorisation 'for the treatment up to 12 weeks of moderate to severe manic episodes in bipolar I disorder in adolescents aged 13 and older'. It also has a UK marketing authorisation for the treatment of moderate to severe manic episodes in bipolar I disorder in adults, and for the prevention of a new manic episode in adults who experienced predominantly manic episodes and whose manic episodes responded to aripiprazole treatment.

Aripiprazole is administered orally. The summary of product characteristics states that the recommended dosage for aripiprazole is 10 mg per day administered once daily without regard to meals. It also states that treatment should be initiated at 2 mg (using aripiprazole oral solution 1 mg/ml) for 2 days, and titrated to 5 mg for 2 additional days to reach the recommended daily dose of 10 mg. The summary of product characteristics notes that enhanced efficacy at doses higher than a daily dose of 10 mg has not been demonstrated and that a daily dose of 30 mg is associated with a substantially higher incidence of significant undesirable effects. It states that doses higher than 10 mg/day should therefore only be used in exceptional cases and with close clinical monitoring.

The summary of product characteristics lists the following adverse reactions specific to adolescents treated with aripiprazole: very common reactions (10% or more) were somnolence (23.0%), extrapyramidal disorder (18.4%), akathisia (16.0%) and fatigue (11.8%); and common reactions (between 1% and 10%) were upper abdominal pain, increased heart rate, increased weight, increased appetite, muscle twitching and dyskinesia. The following undesirable effects had a possible dose–response relationship: extrapyramidal disorder (incidences were: 10 mg dose 9.1%, 30 mg dose 28.8%, placebo 1.7%) and akathisia (incidences were: 10 mg dose 12.1%, 30 mg dose 20.3%, placebo 1.7%). For full details of adverse reactions and contraindications, see the summary of product characteristics.

Aripiprazole is available in 5 mg, 10 mg, 15 mg and 30 mg tablets, as 10 mg and 15 mg orodispersible tablets, and as an oral solution (1 mg/ml). The acquisition cost of aripiprazole 5 mg, 10 mg and 15 mg is £95.74 for 28 tablets. For 30 mg it is £191.47 for 28 tablets, and for oral solution it is £102.57 for 150 ml. Costs exclude VAT and are from the BNF, edition 63. For people whose condition responds to aripiprazole, the expected length of a course of treatment is 12 weeks. For a course of 12 weeks (84 days), the 10 mg dose would cost £287.22. This cost would be the same for a 15 mg dose. A course of the 30 mg dose would cost £574.41. Costs may vary in different settings because of negotiated procurement discounts.