Life Engagement Improvement Following Initiation of Brexpiprazole Treatment in Patients with MDD: A Naturalistic, Retrospective Real-World Study

Figures & data

Figure 1 Construction of life engagement scores.

Notes: The process of creating a life engagement score involved utilizing Natural Language Processing (NLP) to transform unstructured free-text data from the patient’s electronic health records (EHR) into structured variables (NLP labels) representing symptoms, behaviors, or observable phenotypes present in the patient at the time of evaluation. Clinical experts then assigned importance weights to each NLP label based on their clinical significance. The resulting life engagement scores were calculated by combining the relevant NLP labels and quantifying variations in life engagement over time, across multiple clinical visits.

Table 1 Demographic and Clinical Characteristics at the Start of Treatment

Variables	Brexpiprazole analysis cohort (n=624)
Demographic characteristics  Female, n (%)	424 (67.9)
Age at index event (years), mean (SD)	48 (15)
White, n (%)	387 (62.0)
Other ethnicities,^a n (%)	33 (5.3)
Demographic characteristics  Female, n (%)	424 (67.9)
Clinical characteristics
Diagnosis of anxiety disorder, n (%)	291 (46.6)
Diagnosis of substance-related disorder, n (%)	98 (15.7)
Diagnosis of trauma-related disorder, n (%)	116 (18.6)
Diagnosis of neurodevelopmental disorder, n (%)	93 (14.9)
Concomitant anxiolytics, n (%)	113 (18.1)
CGI-S at index event, mean (SD)	4.4 (1.0)^b
GAF at index event, mean (SD)	50.1 (16.0)^b

Notes: ^aOthers include Black, Asians, Native American Indians, and Pacific Islanders. The remaining are of unknown ethnicities; ^b75 missing CGI-S values and 529 missing GAF values at index event for brexpiprazole analysis cohort.

Abbreviations: CGI-S, Clinical Global Impressions Scale – Severity; GAF, Global Assessment of Functioning; SD, standard deviation.

Table 2 Summary of Selected Clinical Labels for Life Engagement Score

Domain	Number of Clinical Label(s)	Example of Clinical Label(s)
Emotional	15	Negative labels: Mood – irritable/angry, Affect – labile, Impulse control – serious
		Positive labels: Mood – improved, Affect – good/improved
Physical	11	Negative labels: Low energy – present, General health – bad, Affect – blunted/constricted/inappropriate, Conscious – catatonic
		Positive labels: N/A
Social	9	Negative labels: Eye contact – bad, General behavior – bad, Dress – bad
		Positive labels: General behavior – good, Grooming/hygiene – good
Cognitive	24	Negative labels: Speech – rate issues, Language – minimally verbal, Fund of knowledge – bad/inappropriate, Thought process – general issues, Thought process – tangential, Concentration – issues - present
		Positive labels: Reasoning – concrete/improved, Executive functioning – improved

Table 3 Descriptive Statistics for Baseline, Maximum Change, and First Change in Life Engagement Score

Brexpiprazole Analysis Cohort (n=624)	Baseline Score – Non-Normalized			Maximum Change^a		First Change^a
				Non-Normalized	Normalized	Non-Normalized	Normalized
	Mean (SD)	Median (IQR)	Min-Max	Mean (SD)	Mean (SD)	Mean (SD)	Mean (SD)
All domains	−4.12 (2.45)	−4.0 (−5.0 - −2.0)	−17.0–3.0	1.21 (2.01)	0.45 (0.74)	0.21 (1.38)	0.08 (0.51)
Cognitive	−4.23 (1.39)	−5.0 (−5.0 - −3.0)	−9.0–0.0	0.11 (0.67)	0.04 (0.25)	−0.04 (0.47)	−0.01 (0.18)
Emotional	−2.87 (1.43)	−3.0 (−4.0 - −2.0)	−9.0–3.0	0.73 (1.38)	0.22 (0.41)	0.1 (0.91)	0.03 (0.27)
Physical	−0.38 (0.84)	0.0 (0.0–0.0)	−4.0–1.0	0.19 (0.65)	0.09 (0.3)	0.0 (0.47)	0.0 (0.22)
Social	−1.41 (1.36)	−1.0 (−3.0–0.0)	−6.0–2.0	0.47 (0.99)	0.18 (0.37)	0.02 (0.76)	0.01 (0.29)

Notes: ^aA positive change indicates an improvement in life engagement, whereas negative change indicates worsening of life engagement relative to the patients’ baseline score.

Abbreviations: IQR, interquartile range; SD, standard deviation.

Figure 2 Comparison of life engagement scores at index event and different follow-up time points.

Figure 3 Comparison of domain-specific life engagement scores at index event and different follow-up time points: (A) cognitive domain, (B) emotional domain, (C) physical domain, (D) social domain.

Figure 4 Survival analysis for time to life engagement score improvement among brexpiprazole patients (ordered from top to bottom): (A) Cumulative rates of patients with life engagement improvement over time. (B) Cumulative rates of patients with life engagement score improvement over time using different thresholds for life engagement score improvement indicators. (C) Cumulative rates of patients with domain-specific improvement over time.