Pimavanserin plus atomoxetine a promising treatment candidate for OSA

In the treatment of patients with obstructive sleep apnoea (OSA), using pimavanserin with atomoxetine appears to be beneficial, according to a small crossover study.

The study included 18 participants with OSA (apnoea-hypopnoea index [AHI] >15 events/h). They were randomly assigned to receive pimavanserin 34 mg plus atomoxetine or placebo for 1 week, then crossed over to the alternative treatment, with a 1-month washout in between. Atomoxetine included a 3-day run-in at 40 mg, followed by 4 days at 80 mg. Pimavanserin plus atomoxetine was taken 4 h and 30 min before bedtime.

Researchers performed follow-up polysomnography to assess outcomes. AHI was the primary outcome, while arousal index and nadir oxygen saturation (Spo₂) were the secondary outcomes. Safety, subjective sleep quality, and flow-estimated endotypes (using oronasal pneumotachograph flow) were evaluated.

Compared with placebo, atomoxetine plus pimavanserin was associated with a 42-percent (95 percent confidence interval [CI], 18–60) reduction in AHI (p<0.001). This translated to an absolute reduction of 16.9 events/h (95 percent CI, 8.1–23.6).

Nadir Spo₂ also improved by 5.0 percent (95 percent CI, 1–8) and arousal index by 10.9 events/h (95 percent CI, 2.4–18.1) on combination treatment vs placebo.

Aside from overnight heart rate increasing by 4.8 beats/min on pimavanserin plus atomoxetine, no other change in subjective sleep quality or next-morning vital signs was noted. Likewise, the combination treatment did not increase the risk of side effects compared with placebo.

On combination treatment, pharyngeal collapsibility improved by 7.9 percent of stable breathing during sleep, while loop gain was reduced by 20 percent, with no decrease in the arousal threshold.