New findings from a phase III clinical trial suggest that investigational seltorexant significantly alleviated symptoms of major depressive disorder (MDD) and insomnia in individuals who had previously shown inadequate responses to standard antidepressant therapies. This promising drug could soon provide relief where other treatments have failed.
By the sixth week of the trial, participants taking seltorexant alongside their existing antidepressant treatments exhibited a least-squares mean difference of -2.6 in the total change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS) when compared to those receiving a placebo. This statistic, with a 95% confidence interval of -4.53 to -0.74 and a two-sided P value of 0.007, indicates a clinically relevant improvement, according to Andrew Krystal, MD, from the University of California San Francisco Weill Institute for Neurosciences, and his research team.
Krystal noted, “A difference of two points on the MADRS is generally regarded as clinically significant.” This highlights the importance of even modest changes in depressive symptoms for many patients.
Additionally, as presented at the recent Psych Congress in Boston, those in the seltorexant group reported noteworthy enhancements in two essential secondary endpoints compared to placebo:
- Participants demonstrated a least-squares mean difference of -3.7 in the Patient-Reported Outcome Measurement Information System-Sleep Disturbance 8-item short form T-score, with a 95% confidence interval of -5.48 to -2.00, achieving statistical significance (two-sided P).
- Additionally, there was a least-squares mean difference of -2.0 in the MADRS score excluding the sleep item, with a 95% confidence interval of -3.75 to -0.28, and a P value of 0.023.
The trial also measured self-reported depression symptoms using the Patient Health Questionnaire-9, revealing a total score change from baseline of -2.1 points (95% CI -3.30 to -0.93). These results strengthen the argument for seltorexant’s effectiveness in this patient population.
Seltorexant stands out as a potential first-in-class medication, functioning as a potent and selective orexin-2 receptor antagonist that helps normalize hyperarousal and promotes restorative sleep. This unique mechanism positions it apart from other treatments currently available on the market.
Krystal emphasized, “Seltorexant is unique,” pointing out that it could be the first depression treatment to act by blocking orexin receptors, should it receive FDA approval. This would address a significant gap in the current pharmaceutical landscape where no other antidepressants or insomnia therapies employ such a mechanism.
“While several FDA-approved insomnia medications inhibit orexin receptors, they are classified as dual orexin receptor antagonists, impacting both OX1 and OX2 receptors. In stark contrast, seltorexant specifically targets only the OX2 receptors,” he elaborated.
Such innovations could fill a critical void in care for individuals grappling with both depression and insomnia. Krystal pointed out, “Approximately 70% of patients with depression experience insomnia, and optimal treatment should involve addressing both challenges.” He lamented the lack of FDA-approved medications specifically designed to treat depression in patients suffering from insomnia, further highlighting the potential of seltorexant.
Krystal noted that among the commonly prescribed antidepressants, the tetracyclic antidepressant mirtazapine may offer some benefits for those dealing with both depression and insomnia. However, he cautioned that its efficacy for this indication has not been thoroughly studied and that many patients are unable to tolerate it due to side effects, which commonly include daytime sedation and weight gain.
“Seltorexant represents the first agent rigorously tested in large-scale trials that has proven effective for treating the dual challenges of depression and insomnia,” Krystal stated confidently. “Consequently, it is poised to become the first FDA-approved therapy specifically tailored to address these interconnected issues.”
The clinical trial comprised 588 adults aged 18 to 74 diagnosed with MDD, who were randomized to receive either seltorexant (20 mg once daily) or a placebo. Of those receiving seltorexant, 216 also had insomnia, while 228 in the placebo group reported similar symptoms. The median participant age was 47, with a majority of 76.6% being female and 77.1% identifying as white. Notably, 69% of participants were utilizing selective serotonin reuptake inhibitors (SSRIs), while 31% were on serotonin-norepinephrine reuptake inhibitors (SNRIs).
All participants were required to have a primary DSM-5 diagnosis of MDD without psychotic features. They also needed a Hamilton Depression Rating Scale (HDRS)-17 score of 20 or higher during initial screenings. Importantly, participants had previously exhibited insufficient response to one or two SSRIs or SNRIs administered at stable doses for a duration of at least six weeks but not exceeding two years.
The mean baseline HDRS-17 score was recorded at 26.5 (with the HDRS scale ranging from 0 to 52), while the Insomnia Severity Index score averaged at 20 (0-28). The length of the current depressive episode among participants averaged 35.4 weeks, further underscoring the chronic nature of their conditions.
Overall, these compelling findings pave the way for further research and development of seltorexant as an innovative treatment option for individuals battling both MDD and insomnia, Krystal concluded. He disclosed that researchers have also embarked on a new phase III study of seltorexant in MDD patients presenting no or mild insomnia symptoms, with anticipated results forthcoming.
Disclosures
The study was funded by Janssen.
Krystal disclosed relationships with numerous pharmaceutical companies, including Janssen, Adare, and several others in the industry.
Primary Source
Psych Congress
Source Reference: Thase ME, et al “Seltorexant, adjunctive to antidepressants, in adults with MDD with insomnia symptoms: results of a double-blind, randomized, placebo-controlled study” Psych Congress 2024; Poster 124.
Please enable JavaScript to view the comments powered by Disqus.
Groundbreaking News: Seltorexant Takes Center Stage in Treating Depression with Insomnia!
Hold onto your hats, folks! Scientists have stumbled upon a potential game-changer in the management of major depressive disorder (MDD)—and it’s got a name that sounds like it could be a trendy cocktail. Enter seltorexant, which, based on a phase III trial, is proving to be quite the overachiever, helping people with MDD and insomnia, especially when existing antidepressants didn’t quite cut it. Seriously, this drug might just be the best thing since sliced bread—or at least, since the last antidepressant that promised to rescue us from our melancholic slumber.
So, what’s the magic behind seltorexant? Well, Dr. Andrew Krystal from the University of California San Francisco Weill Institute for Neurosciences has all the juicy details. According to the trial results, by the time week six rolled around, participants who were taking this wonder drug alongside their usual antidepressants experienced a significant decline in their depression scores—a nifty little number of -2.6 points on the Montgomery-Åsberg Depression Rating Scale (MADRS). And let’s not gloss over the fact that a difference of two points is enough to raise eyebrows and possibly panic the competition. If depression was a race, seltorexant just pulled ahead of the pack.
But wait, there’s more! Those lucky souls who were on seltorexant also reported a whopping improvement in their sleep disturbances—a -3.7 point drop on the Patient-Reported Outcome Measurement Information System-Sleep Disturbance scale. Imagine finally catching those sweet Z’s without wrestling with insomnia. It’s like moving from night terrors to your very own sleep sanctuary!
The Science Behind the Smiles
Now for a touch of science, and I promise it’s more fun than you think! Seltorexant isn’t just another run-of-the-mill antidepressant; it’s an orexin-2 receptor antagonist. Think of it as a bouncer at the club of your brain, kicking out overexcited neurons throwing a hyperarousal rave. In contrast to its less sophisticated cousins that block all types of orexin receptors, seltorexant stands out like a bespoke suit at a dress-down Friday. It selectively blocks only the OX2 receptors, which could be the crucial element allowing it to shine brighter than the others in the gloomy world of insomnia and depression!
Dr. Krystal confidently puts forward that this is not just another hopeful entry in the antidepressant category – it could be the first-ever therapy tailored for those battling both depression and insomnia simultaneously. He even goes so far as to declare, “We don’t have any medications FDA-approved for treating depression in those with insomnia.” So essentially, if we were to award a medal here, seltorexant would surely be up for gold!
Who’s in the Trial?
For the statistics enthusiasts out there, let’s break down the numbers. The trial involved 588 adults aged 18 to 74 suffering from MDD, with a staggering 76.6% being women – and let’s face it, they often take the brunt of insomnia while balancing the universe on their shoulders. The participants had previously been on SSRIs or SNRIs but were still feeling as low as a limbo bar at a party. The outcome? A solid mean baseline HDRS-17 score of 26.5, which is a polite way of stating these people were genuinely wrestling their inner demons.
What’s Next?
As the dust settles, the implications of this study could mean happier mornings for many. And the wonderful Dr. Krystal and his team aren’t stopping at merely “hopeful”; they’re launching another phase III study with MDD patients experiencing no or mild insomnia symptoms. It’s like they’re saying, “We dare you to dream!”
In a world saturated with antidepressants doing very little more than gathering dust on pharmacy shelves, let’s raise a metaphorical glass to seltorexant—may it bring hope and a good night’s sleep to those in need!
Commentary:
Now, wasn’t that a riveting read? Just had me glued to the screen like a sequel to my favorite sitcom! It’s like they’ve penned a script for success with this seltorexant thing. Who knew battling depression could come with a side of “let’s get a solid seven hours in”?
And speaking of breakthroughs, if I had a pound for every time new antidepressants promised the moon but delivered a crater instead, I would be… well, I wouldn’t be here, I’d be on a yacht. But let’s sincerely hope that the FDA gives this little gem the green light, because we could all use a little less insomnia and a whole lot more joy in our lives. Perhaps it could be the plot twist everyone needs—a happy ending in a dramedy where depression is the antagonist. Cheers to that!
Seltorexant MDD
To find a way to improve even further!” With continued research on seltorexant, there’s potential for this medication to redefine how we address the intersection of depression and insomnia, giving individuals a more tailored and effective option to improve both mood and sleep quality.
As the scientific community eagerly awaits the outcomes of future trials, there’s palpable excitement about the contributions seltorexant could bring to the mental health landscape. If it continues to show promise, seltorexant might indeed become a household name in the treatment of major depressive disorder, much like antidepressants have over the past few decades. For now, we can only stay tuned as we observe how this groundbreaking treatment evolves and if it can indeed become a revolutionary player in psychiatric care.
In the meantime, if you’re affected by MDD and insomnia, consult your healthcare provider about your treatment options. Staying informed and connected with your health professional is crucial as new potential therapies come into play. Here’s to hoping for better sleep and brighter days ahead, courtesy of innovations like seltorexant!
