43 - Antipsychotic long acting injections in bipol

Antipsychotic long-acting injections in bipolar disorder

Bipolar disorder CHAPTER 2 Antipsychotic long-­acting injections in bipolar disorder LAIs are widely used in bipolar disorder although none is formally licensed in the UK for this indication (Abilify Maintena is approved by the FDA in the USA). Support for their use is rather limited: there have been dozens of open-­label trials or case series published, but few included more than a handful of subjects.1–­3 Retrospective cohort studies, mirror-­image studies and population-­level studies do, nonetheless, offer some support for the use of LAIs (mainly SGAs) in bipolar maintenance.1 Mirror-­image studies uniformly show a reduction in admissions and bed days when patients are switched from oral medication to LAI formulations of aripiprazole4–­6 and paliperidone,6,7 although study numbers were small. Prospective open-­label studies also support the prophylactic effect of aripiprazole LAI, both monthly and two-­monthly.8,9 There have also been seven RCTs, only five of which were sufficiently powered to produce interpretable results (the remaining two trials included only 30 subjects in total10,11). These five RCTs represent the highest level of evidence for LAIs in bipolar disorder. Their details are set out in Table 2.5. Few firm conclusions can be drawn from the controlled trials outlined in Table 2.5. Risperidone LAI is clearly effective either as the sole treatment or as an adjunct but provides protection only against manic, hypomanic and mixed-­manic episodes and Table 2.5  Randomised controlled trials (RCTs) of the use of long-­acting injections (LAIs) in bipolar affective disorder. Reference Number LAI Comparator Duration Outcome Ahlfors et al., 198112 (19/14) Flupentixol decanoate Lithium 18 months Neither treatment improved main outcome (number of mood episodes) Macfadden et al., 200913* (65/59) Risperidone (adjunct) Placebo (adjunct) 12 months Risperidone LAI reduced rate of relapse compared with placebo (relative risk 2.3) Quiroz et al., 201014* (154/149) Risperidone monotherapy Placebo monotherapy 24 months Overall relapse rate was 30% with risperidone, 56% with placebo. Risperidone did not protect against depressive relapse. Vieta et al., 201215* (132/135/131) Risperidone monotherapy Placebo or oral olanzapine monotherapy 18 months Recurrence of any mood episode: oral olanzapine 23.8%; risperidone LAI 38.9%; placebo 56.4%. Olanzapine and risperidone reduced risk of elevated mood episode but only olanzapine reduced risk of depression. Calabrese et al., 201716* (133/133) Aripiprazole monotherapy Placebo monotherapy 12 months Relapse to any mood episode 26.5% with aripiprazole; 51.1% with placebo. No clear effect on recurrence of depression. An open follow-­on study of this RCT (that also included patients newly prescribed aripiprazole) showed somewhat better levels of protection: 87–­98% of participants remained well over 12 months.17 *Trial sponsored by manufacturer.