Tablets for OSA?

Are there any new treatments on the horizon for obstructive sleep apnoea?

Well, yes … and no. One reason we follow up our patients who have significant obstructive sleep apnoea is so that we can offer them the benefit of alternative therapy if they are unhappy with CPAP therapy. While there are no particularly exciting new options available at present, occasionally a paradigm-changing treatment possibility comes along. If there were a simple treatment available in tablet form for obstructive sleep apnoea, a treatment that caused no side effects, wouldn’t that be terrific?

Now, there’s no reason to get particularly excited – but I think some cause to be interested – in the results of a trial of two tablets, Ondansetron and Fluoxetine – which was published in Sleep journal at the start of this month.

Each of these medications works on serotonin receptors. Serotonin is a neurotransmitter – a chemical messenger between nerves. It is found in many places in the body. The authors of this study commented particularly on two of these sites, and their associated effects.

Firstly, serotonin in the brainstem can promote muscle tone in the muscles that dilate the upper airway when we are awake via 5-HT2 receptors. Secondly, other serotonin receptors (5-HT3) in the ‘nodose’ ganglion (great name) promote REM-related apnoea (cessation of breathing in REM sleep). The hypothesis was that if they could stimulate the former and block the latter receptor then they might be able to effectively treat OSA.

So they randomized 44 patients to treatment with either placebo, placebo plus ondansetron (which is an anti-nausea tablet and blocks 5-HT3 receptors) or fluoxetine (5-HT2 receptor agonist/stimulator and antidepressant) and ondansetron, in two doses – lower and higher.

Interestingly they found that the treatment was very well tolerated, and that treatment with the highest dose of medications in combination led to a reduction in apnoea-hypopnoea index of 13 respiratory events per hour, or 40.5% from baseline, by day 28 of treatment. There was no change on the placebo or ondansetron alone, and a tend towards change on the low dose combination.

I think these results represent a very interesting direction in investigation, which needs to be developed much more fully. Characteristics of patients in whom such a treatment may be beneficial will need to be clearly defined, and it certainly is too early to be recommending this treatment to anyone.

Serotonin agonists are commonly used in treatment of depression, and those of us who report sleep studies consider the possibility that they might have an impact on the severity of sleep-disordered breathing we observe while reporting (as well as on sleep quality in general). I suspect, however, that within a few years we will be treating some OSA patients with tablets that have minimal side effects.

Andrew