Daily activity level improvement with antidepressant medications predicts long-term clinical outcomes in outpatients with major depressive disorder

Figures & data

Table 1 Baseline sociodemographic and clinical characteristics of CO-MED trial participants according to baseline activity impairment

Number	Total		No or minimal impairment		Moderate impairment		Severe impairment		Chi-square (df)	P-value
	664a		140		208		316
Categorical variables	n	%	n	%	n	%	n	%
Sex									78.66 (2)	0.02
Male	213	32.1	56	40.0	71	34.1	86	27.2
Female	451	67.9	54	60.0	137	65.9	230	72.8
Race									0.80 (4)	0.94
White	425	64.0	91	65.0	128	61.5	206	65.2
Black	176	26.5	36	25.7	59	28.4	81	25.6
Other	63	9.5	13	9.3	21	10.1	29	9.2
Monthly income									6.53 (4)	0.16
<$2,000	378	62.9	67	54.9	132	68.1	179	62.8
$2,000–$4,000	128	21.3	29	23.8	35	18.0	64	22.5
>$4,000	95	15.8	26	21.3	27	13.9	42	14.7
Treatment arm									7.94 (2)	0.09
SSRI monotherapy	224	33.7	43	30.7	77	37.0	104	32.9
Bupropion plus SSRI	220	33.1	58	41.4	67	32.2	95	30.1
Venlafaxine plus mirtazapine	220	33.1	39	27.9	64	30.8	117	37.0
Education									1.11 (4)	0.89
<12 years	98	15.3	17	12.8	33	16.3	48	15.7
12–15 years	351	54.8	73	54.9	111	55.0	167	54.8
>15 years	191	29.9	43	32.3	58	28.7	90	29.5
Hispanic ethnicity	101	15.2	17	12.1	39	18.8	45	14.2	3.27 (2)	0.19
Employed at baseline	331	49.8	81	57.9	109	52.4	141	44.6	7.59 (2)	0.02
Suicidal ideations at baseline	394	59.3	78	55.7	114	54.8	202	63.9	5.29 (2)	0.07
Onset of depression before age 18	296	44.7	72	51.4	78	37.7	146	46.4	7.04 (2)	0.03
Chronic depression	368	55.6	73	52.1	128	61.8	167	53.0	4.79 (2)	0.09
Recurrent depression	516	77.9	115	82.1	151	73.0	250	79.4	4.81 (2)	0.09
Lifetime history of suicide attempt	59	9.2	14	10.4	18	8.9	27	8.9	0.29 (2)	0.87
Presence of melancholic features	227	34.2	35	25.0	61	29.3	131	41.46	14.86 (2)	<0.001
Presence of atypical features	123	18.5	27	19.3	37	17.8	59	18.7	0.13 (2)	0.94
Presence of anhedonia	318	47.9	54	38.6	86	41.4	178	56.3	17.46 (2)	<0.001
Presence of anxious features	496	74.9	95	67.9	150	72.5	251	79.7	8.18 (2)	0.02
Continuous variables	Mean	SD	Mean	SD	Mean	SD	Mean	SD	F-value (df)	P-value
Mean age (years)	42.7	13.0	41.9	13.3	43.6	13.3	42.5	12.7	0.77 (2, 661)	0.46
Weight (pounds)	194.1	59.2	195.2	54.5	195.8	59.3	192.5	61.2	0.23 (2, 660)	0.80
BMI	31.0	8.8	30.5	7.5	31.3	9.1	31.1	9.2	0.36 (2, 658)	0.70
Mean QIDS-SR	15.5	4.3	14.1	5.0	14.2	4.3	16.9	3.6	38.16 (2, 661)	<0.001
Mean WSAS	26.9	8.8	21.6	9.5	24.4	7.9	30.9	7.1	82.09 (2, 660)	<0.001
Mean QOLI	21.0	14.0	24.0	13.9	23.9	13.6	17.1	13.6	17.36 (2, 661)	<0.001
Mean CPFQ	27.6	5.9	25.7	5.9	25.9	5.4	29.6	5.5	39.74 (2, 661)	<0.001
Activity impairment	57.1	32.0	7.4	8.5	48.2	10.6	84.9	10.7	2,880.38 (2, 661)	<0.001
Number of general medical conditions	1.9	1.6	1.4	1.3	2.1	1.6	2.1	1.6	13.67 (2, 661)	<0.001
Number of comorbid psychiatric conditions	1.3	1.6	1.0	0.9	1.2	1.6	1.5	1.7	5.70 (2, 660)	0.004
Duration of current episode (weeks)	61.7	104.8	61.9	108.8	63.9	103.8	60.3	104.0	0.07 (2, 659)	0.68

Notes: No or minimal, moderate, and severe activity impairment were defined as scores of activity impairment <25.22, 25.22–62.75, and >62.75 based on the mean and standard deviation of activity impairment reported in the 2009 National Health and Wellness Survey.³¹

a Activity impairment information at baseline was missing for one participant, thus this number differs from the total number of participants (n=665) in CO-MED trial (NCT00590863).

Abbreviations: CO-MED, Combining Medications to Enhance Depression Outcomes; SSRI, selective serotonin reuptake inhibitor; SD, standard deviation; df, degrees of freedom; BMI, body mass index; QIDS-SR, Quick Inventory of Depressive Symptomatology, self-report; WSAS, Work and Social Adjustment Scale; QOLI, Quality of Life Inventory; CPFQ, Cognitive and Physical Functioning Questionnaire.

Figure 1 Impairment in ability to perform routine day-to-day activities during acute phase of CO-MED trial (NCT00590863).

Note: No or minimal, moderate, and severe activity impairment were defined as scores of activity impairment <25.22, 25.22–62.75, and >62.75 based on the mean and standard deviation of activity impairment reported in the 2009 National Health and Wellness Survey.³¹
Abbreviation: CO-MED, Combining Medications to Enhance Depression Outcomes.

Figure 2 Change in activity impairment during acute phase of CO-MED trial (NCT00590863) based on treatment arm.

Note: The three treatment arms were as follows: escitalopram plus placebo (SSRI monotherapy), sustained-release bupropion plus escitalopram (bupropion–SSRI), and extended-release venlafaxine plus mirtazapine (venlafaxine–mirtazapine).
Abbreviations: CO-MED, Combining Medications to Enhance Depression Outcomes; SSRI, selective serotonin reuptake inhibitor.

Table 2 Correlation coefficients of activity impairment and self-reported depression symptoms, functional outcomes, and side effects

	Acute phase	Continuation phase
	Coefficient	Coefficient
WSAS	0.68	0.70
CPFQ	0.51	0.56
QOLI	-0.40	-0.47
FIBSER	0.48	0.29
QIDS-SR
Total score	0.54	0.57
Sad mood	0.46	0.45
Sleep	0.31	0.30
Appetite	0.17	0.14
Concentration	0.43	0.43
View of self/guilt	0.32	0.35
Thoughts of death or suicide	0.25	0.24
General interest	0.39	0.44
Energy level	0.50	0.54
Psychomotor agitation/retardation	0.35	0.36

Notes: The nine symptom domains of QIDS-SR are consistent with the diagnostic criteria of major depressive disorder. Participation beyond acute phase (baseline to 3 months) in CO-MED trial (NCT00590863), referred to as continuation phase of an additional 4 months, was restricted to participants with clinical improvement. The correlation coefficients reported here were calculated using repeated observations for each subject during both acute and continuation phases separately.

Abbreviations: WSAS, Work and Social Adjustment Scale; CPFQ, Cognitive and Physical Functioning Questionnaire; QOLI, Quality of Life Inventory; FIBSER, Frequency, Intensity, and Burden of Side Effect Rating; QIDS-SR, Quick Inventory of Depressive Symptomatology, self-report; CO-MED, Combining Medications to Enhance Depression Outcomes.

Figure 3 Depression severity levels of depressed outpatients (n=665) in the CO-MED trial (NCT00590863) based on week 6 activity impairment category.

Notes: *Participation in continuation phase was restricted to those participants who experienced clinical improvement during acute phase. Vertical line marks week 6, which was used to define activity impairment categories. No or minimal, moderate, and severe activity impairment were defined as scores of activity impairment <25.22, 25.22–62.75, and >62.75 based on the mean and standard deviation of activity impairment reported in the 2009 National Health and Wellness Survey.³¹
Abbreviations: CO-MED, Combining Medications to Enhance Depression Outcomes; QIDS-SR, Quick Inventory of Depressive Symptomatology, self-report.

Table 3 Prediction of short- and long-term remission based on activity impairment categories at week 6

	Remission at 3 months		Remission at 7 months
	Odds ratio	95% CI	Odds ratio	95% CI
Univariate analysis
Activity impairment category at week 6
No or minimal vs moderate	2.62	1.71, 4.02	1.96	1.29, 2.98
No or minimal vs severe	5.29	3.14, 8.85	4.37	2.65, 1.79
Multivariate analysis with backwards elimination
Activity impairment category at week 6
No or minimal vs moderate	1.74	1.07, 2.84	1.61	1.002, 2.59
No or minimal vs severe	2.60	1.49, 4.83	3.25	1.77, 5.95
In remission at week 6	3.31	2.04, 5.39	2.19	1.36, 3.53
Female vs male sex	1.05	0.66, 1.66	1.22	0.79, 1.89
Treatment arm
Bupropion–SSRI vs SSRI monotherapy	1.02	0.61, 1.69	1.13	0.70, 1.84
Venlafaxine–mirtazapine vs SSRI monotherapy	1.11	0.67, 1.83	1.04	0.64, 1.69
Employed at baseline	1.41	0.92, 2.17	1.02	0.67, 1.53
Presence of suicidal ideations at baseline	0.70	0.45, 1.08	0.52	0.34, 0.79
Presence of anxious features at baseline	0.99	0.61, 1.60	1.18	0.74, 1.87
Number of comorbid medical conditions	1.01	0.87, 1.17	1.02	0.89, 1.18
Number of comorbid psychiatric disorders	0.81	0.68, 0.96	0.85	0.73, 0.995
Baseline depression severity	0.99	0.92, 1.06	1.00	0.93, 1.06
Baseline cognitive and physical function	0.96	0.92, 1.06	0.99	0.94, 1.03
Baseline psychosocial function	1.00	0.97, 1.03	1.02	0.99, 1.05
Baseline quality of life	0.99	0.98, 1.01	1.01	0.99, 1.02
Activity impairment category at baseline
No or minimal vs moderate	1.04	0.58, 1.86	0.68	0.39, 1.19
Severe vs moderate	1.42	0.84, 2.39	0.80	0.49, 1.30

Notes: Values shown in bold represent statistically significant (P<0.05) findings. Data from the CO-MED trial (NCT00590863).

Abbreviations: CI, confidence interval; CO-MED, Combining Medications to Enhance Depression Outcomes; SSRI, selective serotonin reuptake inhibitor.

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