Celine Goldberger, MD, PhD

Seltorexant Limits Weight Gain in Obese MDD Patients, With Celine Goldberger, MD, PhD

Subgroup analyses from a 26-week, double-blind, head-to-head study suggest that the metabolic benefits associated with adjunctive seltorexant for 

 may be particularly pronounced in patients with obesity.

Celine Goldberger, MD, PhD, vice president of global medical affairs at Johnson & Johnson, discussed the findings with

 following the study’s presentation at the American College of Neuropsychopharmacology (ACNP) annual meeting from January 12 – 15, 2026, in the Bahamas.

“We see that there is less weight gain with seltorexant than quetiapine, and when you look at the obese population—the patients were obese at baseline—there was actually no change on average with seltorexant, [compared with an] increase in weight with quetiapine [of] about 1.9 kilograms,” Goldberger told 

The trial compared adjunctive seltorexant, an investigational orexin-2 receptor antagonist, with adjunctive quetiapine XR in adults with major depressive disorder (MDD) and clinically significant insomnia symptoms. While the primary endpoint assessed antidepressant response, showing numerically greater response rates and fewer discontinuations due to adverse events with seltorexant, the ACNP poster focused on longer-term metabolic outcomes, including body weight and insulin resistance.

In the interview, Goldberger emphasized that insomnia is highly prevalent in MDD, affecting roughly two-thirds of patients, and that a substantial proportion continue to experience residual insomnia despite treatment with SSRIs or SNRIs. Depression with comorbid insomnia is also associated with greater rates of obesity, diabetes, and other cardiovascular risk factors, underscoring the importance of considering metabolic effects when selecting adjunctive therapies.

Goldberger noted that weight gain remains a common reason for discontinuation of psychiatric medications, especially antipsychotics used adjunctively for their sedative properties. In this context, she suggested that having an adjunctive option with a more favorable tolerability profile could support longer-term treatment continuity and help patients remain engaged in care as they work toward remission. She said the next step is assessing seltorexant in real-world settings, as well as assessing its safety profile in further studies.

“[Seltorexant] will really help patients in their quest to achieve remission of their depressive episodes,” Goldberger said. “It’s really having an additional option in the moratorium…to be able to really offer a great efficacy…with a very nice probability profile and some benefits compared to what's available.”

Goldberger has no relevant reported disclosures.

Wajs E, Trombello JM, Kelly R, et al. Metabolic profiles of participants with major depressive disorder with insomnia symptoms in a phase 3 trial of seltorexant versus quetiapine extended release as adjunctive therapy. Poster presented at American College of Neuropsychopharmacology 64th Annual Meeting 64th annual meeting; January 12-15; Bahamas. Accessed January 19, 2026.

Goldberger C. Seltorexant Shows Favorable Metabolic Profile, With Celine Goldberger, MD, PhD. HCPLive. Accessed on January 19, 2026. Published on January 19, 2026. 

https://www.hcplive.com/view/seltorexant-shows-favorable-metabolic-profile-celine-goldberger-md-phd

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In a 26-week study, adjunctive seltorexant showed no average weight gain in obese patients with MDD and insomnia unlike quetiapine, according to data presented at ACNP 2026.


Seltorexant Limits Weight Gain in Obesity, MDD, With Celine Goldberger, MD, PhD

Seltorexant Shows Favorable Metabolic Profile, With Celine Goldberger, MD, PhD

Adjunctive seltorexant was associated with less weight gain and more favorable trends in insulin sensitivity than adjunctive quetiapine XR in adults with 

symptoms, according to new metabolic analyses from a 26-week, double-blind, head-to-head study presented at the American College of Neuropsychopharmacology (ACNP) annual meeting from January 12 – 15 at the Bahamas.

The study compared adjunctive seltorexant, an investigational orexin-2 receptor antagonist, with adjunctive quetiapine XR in patients with MDD and clinically significant insomnia symptoms. While earlier results from the trial demonstrated numerically greater response rates and fewer discontinuations due to adverse events with seltorexant, the current analysis focused on metabolic outcomes, an area of particular importance given the high prevalence of cardiometabolic risk in this population.

The study found that body weight changes over 26 weeks were more limited with seltorexant than with quetiapine XR. The mean weight gain was approximately 0.5 kg with seltorexant compared with 2.1 kg with quetiapine XR, representing a 1.6 kg or 3.5 lb difference in 6 months.

“It's very meaningful to patients and can make a difference between patients continuing the drug and discontinuing the drug,” Celine Goldberger, MD, PhD, vice president of global medical affairs at Johnson & Johnson, told 

Metabolic differences extended beyond weight. In participants with baseline metabolic risk, defined by obesity, diabetes, or a homeostatic model assessment of insulin resistance (HOMA-IR) score ≥ 2.9, investigators observed improvement in HOMA-IR and fasting insulin levels with seltorexant. In contrast, quetiapine XR was associated with trends toward worsening. These shifts occurred in the absence of meaningful changes in fasting glucose or hemoglobin A1c, suggesting a potential effect on insulin sensitivity rather than glycemic control.

Furthermore, a greater proportion of patients with baseline insulin resistance transitioned to insulin sensitivity with seltorexant than with quetiapine XR over the 26 weeks. While Goldberger emphasized that these findings are exploratory and warrant further investigation, she noted that insulin resistance is a recognized marker of cardiovascular risk and may be particularly relevant when selecting long-term adjunctive therapies.

“That is [a] very relevant finding that obviously needs to be confirmed, but [a] very interesting thing,” she said.

In a 26-week head-to-head study, adjunctive seltorexant led to less weight gain and improved insulin sensitivity trends compared with quetiapine XR in MDD with insomnia.


Celine Goldberger, MD, PhD

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