Frequently Asked Questions

Yes. In this post hoc 56-week analysis, negative symptoms improved with olanzapine/samidorphan, with LS mean changes from baseline of -7.6 on the PANSS Negative Symptoms Subscale and -8.2 on the Marder Negative Factor at week 56. Improvement began during the first 4 weeks, when LS mean changes were -4.1 and -4.5, respectively, and then continued during the 52-week open-label extension.

A substantial portion of the improvement occurred after week 4. The authors reported that negative symptoms decreased over the first 4 weeks and that continued improvement during the following 52 weeks accounted for almost half of the total reduction seen at week 56. Quantitatively, PANSS Negative Symptoms Subscale change improved from -4.1 at week 4 to -7.6 at week 56, and Marder Negative Factor change improved from -4.5 to -8.2.

Yes. Among patients with prominent or high negative symptoms at baseline, defined as a Marder Negative Factor score of at least 24, LS mean change in PANSS Negative Symptoms Subscale score was -4.6 at week 4 and -8.7 at week 56, while LS mean change in Marder Negative Factor score was -5.0 at week 4 and -9.6 at week 56. This subgroup included 186 patients.

Yes. In the subgroup with predominant negative symptoms at baseline, defined by high negative symptoms plus low positive symptoms, LS mean change in Marder Negative Factor score was -4.7 (SE 0.58) at week 4 and -8.9 (SE 0.78) at week 56. The authors interpreted this pattern as suggesting that improvement in negative symptoms may be relatively independent of changes in positive symptoms.

Prominent or high negative symptoms were defined as a baseline Marder Negative Factor score of 24 or higher. Predominant negative symptoms required that same Marder Negative Factor threshold, scores of 4 or higher on 2 of 3 PANSS negative symptom items—blunted affect, passive/apathetic social withdrawal, and lack of spontaneity and flow of conversation—and a PANSS Mohr Positive Factor score of 19 or lower.

According to the discussion, yes. The authors noted that published anchor-based estimates for minimal improvement were -3.8 and -5.0 for the Marder Negative Factor and -5.0 for the PANSS Negative Symptoms Subscale, and the week 56 changes in this analysis exceeded those thresholds overall and in each subgroup. They also noted that the 8.7-point week 56 improvement on the PANSS Negative Symptoms Subscale in the prominent negative symptoms subgroup was similar to reductions previously associated with clinically relevant functional improvement.

This was a post hoc integrated analysis of patients who completed the 4-week ENLIGHTEN-1 trial and had at least 1 PANSS assessment in the 52-week open-label ENLIGHTEN-1 Extension, for a total of 281 patients followed up to 56 weeks. For this analysis, the olanzapine/samidorphan, placebo, and olanzapine groups from the initial 4-week trial were combined, and all patients then received olanzapine/samidorphan in the extension. That design allows description of long-term change in negative symptoms but limits direct attribution of early changes specifically to olanzapine/samidorphan.

• The 52-week extension had no placebo or active control group, which limits causal interpretation of long-term changes.
• Data from the olanzapine/samidorphan, placebo, and olanzapine groups during weeks 1 to 4 were pooled, so the effect of olanzapine/samidorphan during the acute phase could not be measured directly.
• The study included patients who met ENLIGHTEN-1 enrollment criteria for acute exacerbation of schizophrenia, which may limit generalizability.
• The predominant negative symptoms subgroup was relatively small at 48 patients.
• Functional outcome assessments were not included, so the clinical relevance of score changes could not be determined directly in this dataset.

The analysis included 281 adults aged 18 to 70 years with schizophrenia who had been enrolled during an acute exacerbation or relapse. Their mean age was 41.7 years, 57% were male, and 79% were White. Baseline illness severity was substantial, with a mean PANSS Total score of 101.7 and a mean Marder Negative Factor score of 25.2.

Negative symptoms were assessed with the PANSS Negative Symptoms Subscale and the Marder Negative Factor. The PANSS Negative Symptoms Subscale is the sum of 7 PANSS items, and the Marder Negative Factor is a broader 7-item factor that includes 5 PANSS negative symptom items plus Motor Retardation and Active Social Avoidance from the PANSS General Psychopathology subscale. The authors described both measures as valid and reliable for assessing negative symptoms of schizophrenia.