Factors associated with failure to achieve remission and with relapse after remission in patients with major depressive disorder in the PERFORM study

Figures & data

Table 1 Variables selected for univariate analyses to identify factors associated with remission at month 2 and relapse at month 6 for patients in remission at month 2

	Remission	Relapse
Sociodemographic factors	Country Age^Citation49 Sex^Citation21,Citation22 Tobacco use^Citation21 Educational level^Citation21,Citation23 Body-mass index^Citation50 Marital status^Citation24 Employment status^Citation21,Citation23 Living area At least one important life event	Country^Citation51 Age^Citation52 Sex^Citation27 Tobacco use^Citation53 Educational level^Citation54 Body-mass index (M2)^Citation27,Citation55 Marital status (M2)^Citation54 Employment status (M2) At least one important life event (M2)
Patient history	Depressive episode before the visit^Citation56 Previous depressive episode^Citation56 Time since beginning of this depressive episode^Citation25	Previous depressive episode^Citation27,Citation28
Comorbidities	At least one other concomitant mental disorder^Citation21,Citation57 At least one chronic medical condition^Citation21,Citation22 Chronic pain or fibromyalgia^Citation22 At least one anxiety symptom/disorder^Citation21,Citation25,Citation56,Citation58	At least one concomitant mental disorder^Citation53,Citation59,Citation60 At least one chronic medical condition Chronic pain or fibromyalgia^Citation51 At least one anxiety symptom/disorder (M2)^Citation25,Citation61,Citation62
Resource use and treatment patterns	Physician specialty Current psychotherapy Sick leave within past 12 months Hospitalization for depression over past 12 weeks^Citation63 Switch of antidepressant	Physician specialty Previous or current psychotherapy Treatment stopped between baseline and M2 Sick leave (pre-M2) Hospitalization for depression (pre-M2) Switch of antidepressant (pre-M2) MMAS-4 score (M2)^Citation64 Treatment line (M2)
Disease characteristics	Prior suicide attempt^Citation23,Citation63 PHQ-9 total score^Citation25,Citation26,Citation56 CGI-S score^Citation25,Citation26 PDQ-5 total score WPAI-SHP score^Citation21,Citation65 SF-12 – PCS score^Citation21,Citation24 SF-12 – MCS score^Citation21,Citation24 Sexual dysfunctiona	Suicide attempt (pre-M2)^Citation60 PHQ-9 total score (M2)^Citation51,Citation66 CGI-S score (M2)^Citation51,Citation66 PDQ-5 total score (M2) WPAI-SHP score (M2)^Citation67 SF-12 – PCS score (M2)^Citation67 SF-12 – MCS score (M2)^Citation67 Sexual dysfunctiona (M2)

Notes:

a Patients were categorized as having sexual dysfunction if their total ASEX score was ≥19 or their score was ≥5 for one item or ≥4 for at least three items. Variables were selected based on literature review and clinical evaluation. All variables were assessed at baseline, unless otherwise indicated.

Abbreviations: ASEX, Arizona Sexual Experience Scale; CGI-S, Clinical Global Impressions–severity of illness; M2, month 2; MCS, mental component summary; MMAS-4, 4-item Morisky–Green Medication Adherence Scale; PCS, physical component summary; PDQ-5, 5-item Perceived Deficit Questionnaire; PHQ-9, 9-item Patient Health Questionnaire; Pre-M2, prior and up to M2 (any time before baseline, at baseline, or between baseline and M2); SF-12, 12-item Short-Form Health Survey; WPAI-SHP, Work Productivity and Activity Impairment–specific health problem.

Table 2 Baseline sociodemographic characteristics for subsets of patients by remission status at month 2 and by relapse status at month 6 in those who achieved remission at month 2

Characteristic	Remission status at month 2			Relapse status at month 6 in those who achieved remission at month 2
	In remission (n=330)	Not in remissiona (n=782)	Total (n=1,112)	Relapsed (n=59)	Not relapsed (n=241)	Total (n=300)
Age, mean ± SD (years)	45.3±11.9	44.1±11.9	44.4±11.9	43.9±12.1	45.7±11.7	45.3±11.8
Female (%)	72.7	73.2	73.1	67.8	74.3	73.0
Marital status (%)
Single	20.0	22.3	21.6	15.3	19.5	18.7
Married/couple	60.0	57.9	58.5	74.6	58.5	61.7
Divorced/separated	17.0	16.8	16.8	8.5	18.7	16.7
Widowed	3.0	3.1	3.1	1.7	3.3	3.0
Education (%)
No degree or diploma	2.7	4.9	4.2	1.7	2.9	2.7
Elementary school	21.2	26.6	25.0	32.2	19.5	22.0
High school	36.4	37.4	37.1	25.4	37.3	35.0
Non-university degree	14.2	12.9	13.3	13.6	14.9	14.7
University degree	25.5	18.2	20.3	27.1	25.3	25.7
Living area (%)
Rural	36.1	30.1	31.9	39.0	36.5	37.0
Urban	63.9	69.9	68.1	61.0	63.5	63.0
Work status (%)
Paid employment or self employed	67.9	66.4	66.8	67.8	68.9	68.7
Tobacco use (%)	29.4	35.7	33.8	30.5	28.6	29.0
BMI classification (%)
Normal weight	50.9	45.1	46.8	42.4	52.3	50.3
Overweight	30.3	28.7	29.2	37.3	29.5	31.0
Obese	18.8	26.2	24.0	20.3	18.3	18.7

Note:

a Information was missing for one patient for each of age, sex, tobacco use, marital status, living area, and educational level, and for four patients regarding BMI.

Abbreviation: BMI, body-mass index.

Table 3 Medical profile, functioning, and quality of life at baseline for subsets of patients by remission status at month 2 and by relapse status at month 6 in those who achieved remission at month 2

Characteristics of current depressive episode	Remission status at month 2			Relapse status at month 6 in those who achieved remission at month 2
	In remission (n=330)	Not in remission (n=782)	Total (n=1,112)	Relapsed (n=59)	Not relapsed (n=241)	Total (n=300)
Treated with antidepressant before baseline visit (%)	16.7	23.8	21.7	20.3	15.8	16.7
Time since beginning of this depressive episode (%)
<1 week	3.3	0.8	1.5	3.4	3.3	3.3
1–2 weeks	7.6	5.1	5.9	8.5	7.5	7.7
2–4 weeks	25.5	19.3	21.2	27.1	27.5	27.4
4–8 weeks	18.5	20.9	20.2	20.3	18.3	18.7
>8 weeks	45	53.9	51.3	40.7	43.3	42.8
Significant symptoms of anxiety (%)a	61.2	63.2	62.6	61.0	62.7	62.3
Symptoms treated with anxiolytics (%)	42.6	41.6	41.9	38.5	44.3	43.2
Currently receiving psychotherapy (%)	10.3	15.9	14.2	8.5	10.0	9.7
Questionnaire scores, mean ± SD
PDQ-5	9.6±4.5	12.1±4.4	11.3±4.6	11.6±4.2	8.9±4.4	9.4±4.5
PHQ-9	15.1±5.6	18.7±4.8	17.6±5.3	16.6±4.1	14.7±5.8	15.0±5.6
CGI-S	3.9±1.1	4.3±0.9	4.2±1.0	4.1±1.0	3.9±1.2	3.9±1.2
MADRS	31.8±7.4	33.0±7.1	32.7±7.2	33.3±6.2	31.6±7.7	32.0±7.4
ASEX
Total score	20.3±5.5	21.9±5.8	21.4±5.7	20.8±5.3	20.2±5.5	20.3±5.5
Sexual dysfunctionb (%)	75.4	84.4	81.8	70.8	76.5	75.3
Other current illnesses
Mental health disorders other than depression (%)
Alcohol abuse or dependence	2.7	2.3	2.4	1.7	2.9	2.7
Other abuse disorders	0.3	1.5	1.2	0.0	0.4	0.3
Somatoform disorders	6.4	8.7	8.0	6.8	6.2	6.3
Eating disorders (anorexia, bulimia)	4.8	8.7	7.6	1.7	4.6	4.0
Other	1.2	0.3	0.5	1.7	0.8	1.0
Functional syndromes (%)
Chronic pain	14.2	17.5	16.5	18.6	13.3	14.3
Chronic fatigue	11.8	17.9	16.1	15.3	11.6	12.3
Fibromyalgia	3.9	8.3	7.0	5.1	3.7	4.0
Premenstrual syndrome	2.7	3.7	3.4	5.1	2.1	2.7
Sleep disorders	22.7	30.1	27.9	22.0	24.1	23.7
Other	2.4	2.9	2.8	3.4	2.5	2.7
Chronic medical conditions (%)
Cardiovascular disease	10.9	11.3	11.2	13.6	10.8	11.3
Diabetes	4.8	4.7	4.8	0.0	5.0	4.0
Cancer	2.1	0.8	1.2	5.1	1.7	2.3
Rheumatoid arthritis	0.9	1.8	1.5	0.0	0.8	0.7
Neurologic disorders	2.4	2.9	2.8	0.0	3.3	2.7
Other	9.7	13.8	12.6	11.9	9.1	9.7
Previous depressive episodes
History of depression (%)
Previous episode	57.1	56.0	56.3	61.0	55.8	56.9
Episode within previous 12 months of previous episode	23.4	25.9	25.1	27.8	24.6	25.3
Previous suicide attempt	8.0	16.0	13.6	16.7	5.2	7.6

Notes: n refers to the total number of patients in each subgroup; as not all patients provided data for all parameters, n is not the denominator for all percentage calculations, and the actual denominator varies between parameters.

a Percentages refer to patients “probably” or “definitely” presenting clinically significant symptoms of anxiety according to physician;

b patients were categorized as having sexual dysfunction if their total ASEX score was ≥19 or their score was ≥5 for one item or ≥4 for at least three items.

Abbreviations: ASEX, Arizona Sexual Experience Scale; CGI-S, Clinical Global Impressions–severity of illness; PDQ-5, 5-item Perceived Deficit Questionnaire; PHQ-9, 9-item Patient Health Questionnaire; MADRS, Montgomery–Åsberg Depression Rating Scale.

Table 4 Multivariate logistic regression model for analysis of risk factors of failure to achieve remission at month 2 (backward selection)

Variable	Category	n/N (%)	OR (95% CI)	P-value
Countrya	France	53/158 (33.5)	1
	Spain	32/91 (35.2)	1.04 (0.57–1.88)	0.900
	UK	67/204 (32.8)	1.57 (0.93–2.62)	0.089
	Sweden	11/34 (32.4)	1.62 (0.67–3.91)	0.284
	Germany	24/101 (23.8)	0.45 (0.24–0.85)	0.013
Age	Per additional year	–	1.01 (0.99–1.02)	0.412
Sex	Female	136/430 (31.6)	1
	Male	51/158 (32.3)	0.74 (0.48–1.16)	0.187
Body-mass index	<30 kg/m^2	156/448 (34.8)	1
	≥30 kg/m^2	31/140 (22.1)	0.51 (0.31–0.84)	0.008
Time since beginning of this depressive episodeb	<4 weeks	70/165 (42.4)	1
	4–8 weeks	34/111 (30.6)	0.60 (0.34–1.05)	0.073
	>8 weeks	83/312 (26.6)	0.51 (0.33–0.81)	0.004
Current psychotherapy	No	169/494 (34.2)	1
	Yes	18/94 (19.1)	0.51 (0.28–0.93)	0.028
PHQ-9 total score	Per additional unit	–	0.87 (0.84–0.91)	<0.001
Sexual dysfunction (ASEX)	No	49/112 (43.8)	1
	Yes	138/476 (29.0)	0.62 (0.38–0.99)	0.045

Notes: n refers to the number of patients with remission in each category; N refers to the total number of patients in each category.

a Global P=0.005;

b global P=0.016.

Abbreviations: ASEX, Arizona Sexual Experience Scale; PHQ-9, 9-item Patient Health Questionnaire.

Table 5 Multivariate logistic regression model for analysis of risk factors of relapse at month 6 for patients in remission at month 2 (backward selection)

Variable	Category	n/N (%)	OR (95% CI)	P-value
Countrya	France	11/59 (18.6)	1
	Spain	5/27 (18.5)	0.79 (0.22–2.82)	0.719
	UK	15/65 (23.1)	0.97 (0.36–2.64)	0.952
	Sweden	3/9 (33.3)	2.15 (0.40–11.49)	0.371
	Germany	3/26 (11.5)	0.51 (0.12–2.22)	0.367
Age	Per additional year	–	0.99 (0.96–1.03)	0.765
Sex	Female	21/131 (16.0)	1
	Male	16/55 (29.1)	2.47 (1.05–5.8)	0.037
Marital status (M2)	Single or divorced/separated or widowed	8/66 (12.1)	1
	Married or living as a couple	29/120 (24.2)	2.73 (1.05–7.12)	0.040
PHQ-9 total score (M2)	Per additional unit	–	1.27 (1.02–1.59)	0.030
PDQ-5 total score (M2)	Per additional unit	–	1.12 (1.00–1.25)	0.042

Notes: n refers to the number of patients with relapse in each category; N refers to the total number of patients in remission at month 2 in each category.

a Global P=0.703.

Abbreviations: M2, month 2; PDQ-5, 5-item Perceived Deficit Questionnaire; PHQ-9, 9-item Patient Health Questionnaire.

Figure S1 Summary of supportive analyses of PDQ-5 effect on relapse at month 6.

Notes: ^aComputed for patients with complete values on all candidate variables (n=186); ^bcomputed for patients with complete values on all variables in the final model (n=193); ^cadditional criterion for relapse definition: minimum change in PHQ-9 total score between month 2 and month 6. Values expressed as OR (95% CI).

Abbreviations: MADRS, Montgomery–Åsberg Depression Rating Scale; PHQ-9, 9-item Public Health Questionnaire.

Figure S2 Summary of supportive analyses of PHQ-9 effect on relapse at month 6.

Notes: ^aComputed for patients with complete values on all candidate variables (n=186); ^bcomputed for patients with complete values on all variables in the final model (n=193); ^cadditional criterion for relapse definition: minimum change in PHQ-9 total score between month 2 and month 6. Values expressed as OR (95% CI).

Abbreviations: MADRS, Montgomery–Åsberg Depression Rating Scale; PHQ-9, 9-item Public Health Questionnaire.

Table S1 Details of backward-selection process for analysis of factors associated with remission at month 2

Step	Factors in model	Factor removed	OR (95% CI)	P-value	AIC	BIC
0	23	–	–	–	684.158	815.460
1	22	At least one other concomitant mental disorder	1.00 (0.52–1.92)	0.9910	682.158	809.083
2	21	Chronic pain or fibromyalgia	1.03 (0.57–1.88)	0.9185	680.169	802.717
3	20	SF-12 – mental health (MCS)	1.00 (0.97–1.04)a	0.8809	678.191	796.363
4	19	Tobacco use	1.09 (0.71–1.68)	0.6871	676.353	790.148
5	18	Sick leave within the 12 months before baseline	0.87 (0.55–1.36)	0.5348	674.740	784.158
6	17	At least one chronic medical condition	0.82 (0.50–1.34)	0.4278	673.373	778.415
7	16	Switch of antidepressant	1.24 (0.73–2.10)	0.4253	672.004	772.669
8	15	Hospitalization for depression during the 12 weeks before baseline	0.58 (0.15–2.28)	0.4336	670.671	766.959
9	14	SF-12 – physical health (PCS)	1.01 (0.99–1.03)a	0.2907	669.792	761.703
10	13	WPAI – percentage activity impairment due to problem	1.01 (1.00–1.02)a	0.1753	669.654	757.188
11	12	PDQ-5 total score	0.97 (0.91–1.02)a	0.2426	669.020	752.178
12	11	Living area	1.37 (0.89–2.12)b	0.1502	669.082	747.863
13	10	CGI-S	0.85 (0.70–1.04)a	0.1127	669.574	743.978
14	9	Educational level (4 categories)	1.67 (0.95–2.94)c	0.1277	669.435	730.709
14	9	Educational level (4 categories)	1.82 (0.92–3.59)d	–	–	–
14	9	Educational level (4 categories)	1.95 (1.09–3.48)e	–	–	–
15	8	Suicide attempt – before baseline	0.44 (0.18–1.04)	0.0624	671.406	728.304

Notes:

a Continuous factor;

b rural vs urban;

c high school vs no degree or diploma/elementary school;

d non-university degree vs no degree or diploma/elementary school;

e university degree vs no degree or diploma/elementary school.

Abbreviations: AIC, Akaike Information Criterion; BIC, Bayesian Information Criterion; CGI-S, Clinical Global Impressions–severity of illness; MCS, mental component summary; PCS, physical component summary; PDQ-5, 5-item Perceived Deficit Questionnaire; SF-12, 12-item Short-Form Health Survey; WPAI, Work Productivity and Activity Impairment.

Table S2 Details of backward-selection process for analysis of factors associated with relapse at month 6 for patients in remission at month 2

Step	Factors in model	Factor removed	OR (95% CI)	P-value	AIC	BIC
0	12	–	–	–	178.837	230.449
1	11	WPAI – percentage activity impairment due to problem (M2)	1.00 (0.97–1.03)	0.9937	176.837	225.223
2	10	Switch of antidepressant at baseline, between baseline and M2, or at M2 (up to M2)	1.48 (0.56–3.92)	0.4349	175.437	220.598
3	9	SF-12 – mental health (MCS – M2)	0.97 (0.92–1.03)	0.3213	174.428	216.362
4	8	CGI-S (M2)	1.40 (0.92–2.13)	0.1087	175.093	213.802
5	7	Suicide attempt before baseline or between baseline and M2 (up to M2)	4.61 (0.83–25.51)	0.0844	175.981	211.464
6	6	SF-12 – physical health (PCS – M2)	0.96 (0.92–1.00)	0.0667	177.333	209.591

Abbreviations: AIC, Akaike Information Criterion; BIC, Bayesian Information Criterion; CGI-S, Clinical Global Impressions–severity of illness; M2, month 2; MCS, mental component summary; PCS, physical component summary; PDQ-5, 5-item Perceived Deficit Questionnaire; SF-12, 12-item Short-Form Health Survey; WPAI, Work Productivity and Activity Impairment.

Table S3 Complementary analysis comparing factors identified as potential indicators of severity and chronicity of depression according to psychotherapy at baseline

Factor	Psychotherapy (n=158)	No psychotherapy (n=954)	P-valuea
Is the current episode the patient’s first depressive episode?
Yes	60 (38.2%)	425 (44.6%)	0.135 (χ^2)
No	97 (61.8%)	528 (55.4%)
If no:
Previous psychotherapy
Yes	67 (69.1%)	159 (30.2%)	<0.001 (χ^2)
Did your patient achieve remission after this episode?
Yes	77 (79.4%)	442 (83.7%)	0.296 (χ^2)
Has the patient been hospitalized for depression?
Yes	13 (13.4%)	42 (8.0%)	0.082 (χ^2)
Has the patient ever attempted suicide?
Yes	15 (15.5%)	70 (13.3%)	0.560 (χ^2)
Time since beginning of this depressive episode (3 categories)
<4 weeks	33 (20.9%)	284 (29.8%)	0.058 (χ^2)
4–8 weeks	38 (24.1%)	186 (19.5%)
>8 weeks	87 (55.1%)	482 (50.6%)
Patient considered “difficult to treat” or “treatment-resistant”?
Yes	33 (20.9%)	112 (11.8%)	0.002 (χ^2)
Is the current depressive episode already being treated with an antidepressant (prior to this visit)?
Yes	41 (25.9%)	200 (21.0%)	0.163 (χ^2)
At least one chronic medical condition
Yes	41 (25.9%)	254 (26.6%)	0.859 (χ^2)
At least one important life event
Yes	74 (54.8%)	386 (48.7%)	0.192 (χ^2)
PHQ-9 total score
Mean ± SD	18.1±5.2	17.5±5.4	0.311
CGI-S
Mean ± SD	4.4±1.1	4.1±1.0	0.003

Note:

a χ² test or Fisher’s exact test for categorical variables, Student’s t-test for continuous variables.

Abbreviations: CGI-S, Clinical Global Impressions–severity of illness; PHQ-9, 9-item Patient Health Questionnaire.

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