Durability of symptomatic responses obtained with adjunctive vagus nerve stimulation in treatment-resistant depression

Figures & data

Table 1 Baseline demographic characteristics and clinical features of participants with treatment-resistant depression receiving TAU with or without adjunctive VNS + TAU (two-sided t-test P-value for continuous data and asymptotic normal test P-value for categorical data)

	VNS + TAU (N=328)		TAU (N=271)		P-value
	Mean or N	SD or %	Mean or N	SD or %
Age (years)	48.8	10.37	50.0	10.80	0.168
Number of female subjects	225	68.6	192	70.8	0.612
Number of white subjects	318	97.0	246	90.8	0.002
Age at initial onset of depression (years)	20.8	12.12	21.4	11.54	0.536
Age at initial diagnosis of depression (years)	29.0	10.90	29.7	11.67	0.451
Number of failed treatments for depression	8.0	3.04	7.4	2.93	0.014
Lifetime number of diagnosed depressive episode	15.1	24.34	11.7	24.56	0.090
Psychiatric hospitalizations within prior 5 years	2.8	4.63	1.5	2.87	<0.001
Lifetime suicide attempts	2.0	4.35	1.2	2.32	0.004
History of electroconvulsive therapy	191	58.2	107	39.5	<0.001
DSM-IV-TR primary diagnosis
Moderate recurrent major depression	40	12.2	66	24.4	<0.001
Severe recurrent major depression	133	40.5	85	31.4	0.025
Moderate single-episode major depression	12	3.7	29	10.7	0.001
Severe single-episode major depression	46	14.0	32	11.8	0.496
Bipolar I, currently moderately severe major depressive episode	19	5.8	18	6.6	0.795
Bipolar I, currently severe major depressive episode	46	14.0	10	3.7	<0.001
Bipolar II, currently depressed	32	9.8	31	11.4	0.592
Baseline scores
Montgomery–Åsberg Depression Rating Scale	33.2	7.67	29.5	6.40	<0.001
Clinical Global Impressions-Severity	5.2	0.78	4.7	0.72	<0.001
Quick Inventory of Depressive Symptomatology-Self Report	18.3	4.67	15.8	4.92	<0.001

Abbreviations: TAU, treatment as usual; VNS, vagus nerve stumulation.

Table 2 Kaplan–Meier probability estimates with 95% CI

	Probability of first response over time
	3 months	6 months	9 months	12 months
TAU	0 (0, 0.03)	0.10 (0.07, 0.15)	0.19 (0.15, 0.24)	0.24 (0.19, 0.30)
VNS + TAU	0.01 (0, 0.03)	0.22 (0.17, 0.27)	0.33 (0.28, 0.38)	0.42 (0.36, 0.47)
	Probability of retaining the first response (response durability) over time
TAU	0.75 (0.63, 0.84)	0.58 (0.45, 0.69)	0.41 (0.29, 0.53)	0.39 (0.27, 0.51)
VNS + TAU	0.85 (0.78, 0.9)	0.65 (0.57, 0.73)	0.52 (0.43, 0.6)	0.47 (0.38, 0.56)
	Probability of second response over time following relapse from the first response
TAU	0	0.13 (0.06, 0.27)	0.27 (0.16, 0.43)	0.32 (0.20, 0.48)
VNS + TAU	0.07 (0.04, 0.15)	0.26 (0.18, 0.36)	0.44 (0.35, 0.55)	0.47 (0.37, 0.58)
	Probability of retaining second response (response durability) over time
TAU	0.97 (0.79, 1)	0.82 (0.63, 0.92)	0.63 (0.42, 0.78)	0.46 (0.27, 0.64)
VNS + TAU	0.98 (0.89, 1)	0.89 (0.78, 0.95)	0.73 (0.59, 0.82)	0.66 (0.52, 0.77)

Abbreviations: TAU, treatment as usual; VNS, vagus nerve stimulation.

Figure 1 A Kaplan–Meier plot demonstrates time to first response among 328 participants in the VNS + TAU group and 271 participants in the TAU group.

Notes: Time to first response was defined as the time from baseline to the first visit with a reduction in MADRS score of ≥50% compared to baseline. Median time to the first response was 18.1 months (Q1=6.9, Q3=49.1) for VNS + TAU participants compared to 49.1 months (Q1=12.3, Q3= not estimable) for TAU participants.
Abbreviations: MADRS, Montgomery–Åsberg Depression Rating Scale; TAU, treatment as usual; VNS, vagus nerve stimulation.

Figure 2 A Kaplan–Meier plot for durability of the first response that occurred within the first year.

Notes: Duration of first response was defined as the time from first response to the first visit when reduction in MADRS score was <40% compared to baseline (ie, relapse). Median time to relapse from first response in first year was 10.1 months (Q1=4.2, Q3=31.5) for VNS + TAU and 7.3 months (Q1=3.1, Q3=17.6) for TAU.
Abbreviations: MADRS, Montgomery–Åsberg Depression Rating Scale; TAU, treatment as usual; VNS, vagus nerve stimulation.

Figure 3 A Kaplan–Meier plot for durability of first response in the first year for VNS + TAU participants by visit.

Note: The trend in the probability of retaining the first response beyond 1 year was higher in the early responders (ie, those who first responded at 3 or 6 months after VNS initiation) compared with the late responders (ie, those who first responded at 9 or 12 months after VNS initiation).
Abbreviations: TAU, treatment as usual; VNS, vagus nerve stimulation.

Figure S1 A Kaplan–Meier plot for durability of first response in the first year for VNS + TAU participants by early and late responder.

Note: The trend in the probability of retaining the first response beyond 1 year was higher in the early responder group (ie, first response at 3 or 6 months after VNS initiation) compared with the late responder group (ie, first response at 9 or 12 months after VNS initiation).

Abbreviations: TAU, treatment as usual; VNS, vagus nerve stimulation.

Figure S2 A Kaplan–Meier plot shows the chance of a second response after relapse following the first response within the first year in both VNS + TAU and TAU.

Abbreviations: TAU, treatment as usual; VNS, vagus nerve stimulation.

Figure S3 A Kaplan–Meier plot demonstrates that the second response may be more durable with VNS + TAU versus TAU.

Abbreviations: TAU, treatment as usual; VNS, vagus nerve stimulation.

Figure S4 A Kaplan–Meier plot demonstrates that there was no difference in durability of the response in either treatment group based on the polarity of the depression.

Abbreviations: TAU, treatment as usual; VNS, vagus nerve stimulation.