medwireNews: The atypical antipsychotic cariprazine may be effective for the treatment of bipolar I depression, phase II study findings show.
Of three dosages studied, 1.5 mg/day presented the best balance between efficacy and tolerability, the researchers Lakshmi Yatham (University of British Columbia, Vancouver, Canada) and colleagues note in The American Journal of Psychiatry.
At this dose, 145 patients with symptomatic bipolar I depression had an average 4-point greater reduction in Montgomery–Åsberg Depression Rating Scale (MADRS) score after 6 weeks of treatment than 141 patients given placebo.
And the patients were twice as likely to respond to treatment at 6 weeks, having achieved at least a 50% reduction in MADRS score, as those given placebo, and 2.38 times more likely to go into remission (MADRS score ≤10).
The team calculates that six patients would need to be treated with cariprazine 1.5 mg/day for one patient to show a response to treatment, with a comparable number needing to be treated for one patient to go into remission.
They also note that improvements on the MADRS with cariprazine 1.5 mg/day were significant compared with placebo for most of the individual items, “suggesting potential benefit for cariprazine across a range of depression symptoms”. And improvements similar to those seen on the MADRS were also evident on the Clinical Global Impressions Severity Scale and the Hamilton Depression Rating Scale.
Cariprazine at 0.75 mg/day, trialled in 140 patients, was not significantly different to placebo in terms of change in MADRS score over the 6 weeks of treatment. The 3.0 mg/day dose, given to 145 patients, was associated with a significant 4.9-point greater reduction in MADRS score compared with placebo, but significance was lost with adjustment for multiplicity.
The researchers suggest that, despite a similar efficacy to the 1.5 mg/day dose, 3.0 mg/day may be less tolerable, finding that only 65% of patients on this dose completed the study, compared with 80% of those taking 1.5 mg/day.
Cariprazine was generally well tolerated at the 1.5 mg/day dose, however, with a lower rate of discontinuations due to adverse events than placebo.
As with other antipsychotics, akathisia and insomnia occurred more frequently with cariprazine than placebo but rates of these effects and any treatment-emergent adverse events were relatively low, at 4.8% versus 1.4%, 6.8% versus 8.3% and 62.3% versus 54.5%, respectively.
In addition, rates of treatment-emergent mania were similar between cariprazine and placebo, as were changes in metabolic parameters.
Cariprazine is a potent dopamine D3 and D2 receptor partial agonist that, unlike other atypical antipsychotics, preferentially binds to D3, which is expressed in brain regions that regulate motivation and reward-related behaviour and may therefore present a new treatment target, comments the team.
They conclude that “given the limited number of positive studies for atypical antipsychotics in bipolar I depression, future studies are warranted to extend these phase II findings.”
By Lucy Piper
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