2026 ECNP Congress

PS01-1102

Linking Montgomery-Åsberg Depression Rating Scale and patient health questionnaire total scores: evidence from adjunctive lumateperone trial data

John Sheehan — T.G. Rhee, S. Durgam, W.R. Earley, I. Turkoz · Johnson & Johnson Innovative Medicine, Senior Director, Raritan, United States

2026 ECNP Congress

Background

The Patient Health Questionnaire-9 (PHQ-9) is widely used in real-world practice to measure depression severity; however, it is rarely used as an outcome measure in major depressive disorder (MDD) clinical drug trials. The two pivotal 6-week Phase 3 trials of adjunctive lumateperone in MDD used the Montgomery-Asberg Depression Rating Scale (MADRS) as the primary endpoint, which may be less familiar to practicing clinicians. Estimating the PHQ-9–equivalent change from MADRS scores may help clinicians interpret trial results in real-world practice.

To translate changes in MADRS Total score into clinically interpretable, PHQ-9–equivalent change in pooled adjunctive lumateperone trials, we applied an established MADRS-to-PHQ-9 mapping model. This model was developed using esketamine data from two 4-week randomised controlled trials (RCTs) in treatment-resistant depression (NCT02417064, NCT02418585).

Methods

The esketamine-derived conversion model was used to map MADRS Total scores to PHQ-9 scores based on data from the two pooled RCTs of lumateperone + antidepressant therapy (ADT) versus placebo+ADT (NCT04985942, NCT05061706) in patients with MDD with an inadequate response to ADT using a local regression model. Outcomes included predicted PHQ-9 score by treatment over time, response (≥50% improvement from baseline in predicted PHQ-9 score), and remission (predicted PHQ-9 score <5). Changes in predicted PHQ-9 scores were analysed using a mixed-effects model for repeated measures; response and remission rates were analysed using chi-square tests and odds ratios (ORs).

Results

The conversion model was used to transform MADRS Total scores (0-60) in the pooled lumateperone+ADT trials into comparable PHQ-9 scores (1-27). Lumateperone+ADT (n=471) significantly improved predicted PHQ-9 scores versus placebo+ADT (n=479) beginning at Day 8 (least squares mean difference vs placebo+ADT [LSMD], −0.59; effect size [ES], −0.24; P<.001), with significant improvements persisting through Day 43 (LSMD, −2.29; ES, −0.56; P<.001). PHQ-9 response rates were significantly greater with lumateperone+ADT vs placebo+ADT at Day 8 (6.6% vs 2.1%; OR, 3.3; 95% CI, 1.58-6.73; P<.001) and at each visit through Day 43 (49.9% vs 28.7%; OR, 2.5; 95% CI, 1.87-3.28; P<.001). Lumateperone+ADT led to a 3.7 times greater likelihood of achieving a sustained response for ≥36 days compared with placebo+ADT (OR, 3.7; 95% CI, 1.47-9.19; P<.01). PHQ-9 remission rates were significantly greater with lumateperone+ADT vs placebo+ADT from Day 15 (5.8% vs 2.8%; OR, 2.2; 95% CI, 1.10-4.28; P<.05) through Day 43 (24.6% vs 11.6%; OR, 2.5; 95% CI, 1.73-3.59; P<.001). The likelihood of sustained remission for ≥22 days was 2.3 times greater with lumateperone+ADT than with placebo+ADT (OR, 2.3; 95% CI, 1.18-4.32; P<.05).

Conclusions

In pooled trials, lumateperone+ADT significantly improved predicted PHQ-9–equivalent scores at all visits during the studies and led to significantly greater PHQ-9 response and remission rates compared with placebo+ADT. These results demonstrate the clinically interpretable translation of MADRS outcomes to PHQ-9–equivalent improvements, suggesting earlier and sustained symptom improvement with adjunctive lumateperone in patients with MDD with an inadequate response to ADT.

References

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