Background
Methods
Data sources, study population and cohort selection
Variables
Statistical analysis
Results
Patient demographics and treatment pattern
Variable | Alla (N = 2946) | Monotherapy | Combination therapy | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Benzodiazepine (n = 1067) | Non-benzodiazepine (n = 850) | Melatonin receptor agonist (n = 76) | Orexin receptor antagonist (n = 94) | Total (n = 2087) | 2 drugs (n = 622) | 3 drugs (n = 166) | ≥4 drugs (n = 71) | Total (n = 859) | ||
Age, years, mean ± SD | 41.6 ± 10.2 | 42.4 ± 9.9 | 42.2 ± 10.0 | 38.3 ± 11.2 | 42.5 ± 11.4 | 42.2 ± 10.1 | 40.5 ± 10.4 | 38.9 ± 10.1 | 38.9 ± 9.1 | 40.1 ± 10.2 |
< 40 years, n (%) | 1214 (41.2) | 404 (37.9) | 328 (38.6) | 37 (48.7) | 40 (42.6) | 809 (38.8) | 284 (45.7) | 84 (50.6) | 37 (52.1) | 405 (47.1) |
≥ 40 years, n (%) | 1732 (58.8) | 663 (62.1) | 522 (61.4) | 39 (51.3) | 54 (57.4) | 1278 (61.2) | 338 (54.3) | 82 (49.4) | 34 (47.9) | 454 (52.9) |
Sex, n (%) | ||||||||||
Male | 1850 (62.8) | 693 (64.9) | 507 (59.6) | 44 (57.9) | 51 (54.3) | 1295 (62.1) | 403 (64.8) | 105 (63.3) | 47 (66.2) | 555 (64.6) |
Insured or dependent, n (%) | ||||||||||
Insured | 2186 (74.2) | 805 (75.4) | 619 (72.8) | 49 (64.5) | 68 (72.3) | 1541 (73.8) | 468 (75.2) | 124 (74.7) | 53 (74.6) | 645 (75.1) |
Spouse | 567 (19.2) | 201 (18.8) | 187 (22.0) | 14 (18.4) | 25 (26.6) | 427 (20.5) | 103 (16.6) | 24 (14.5) | 13 (18.3) | 140 (16.3) |
Other family member | 193 (6.6) | 61 (5.7) | 44 (5.2) | 13 (17.1) | 1 (1.1) | 119 (5.7) | 51 (8.2) | 18 (10.8) | 5 (7.0) | 74 (8.6) |
History of psychiatric disordersb, n (%) | ||||||||||
Anxiety disorder | 489 (16.6) | 179 (16.8) | 155 (18.2) | 14 (18.4) | 16 (17.0) | 364 (17.4) | 89 (14.3) | 23 (13.9) | 13 (18.3) | 125 (14.6) |
Bipolar disorder | 14 (0.5) | 3 (0.3) | 8 (0.9) | 1 (1.3) | 0 | 12 (0.6) | 2 (0.3) | 0 (0) | 0 | 2 (0.2) |
Schizophrenia | 40 (1.4) | 18 (1.7) | 5 (0.6) | 1 (1.3) | 0 | 24 (1.1) | 10 (1.6) | 6 (3.6) | 0 | 16 (1.9) |
ADHD | 2 (0.1) | 0 | 0 | 0 | 0 | 0 | 2 (0.3) | 0 | 0 | 2 (0.2) |
Autism | 1 (0.0) | 0 | 0 | 0 | 0 | 0 | 1 (0.2) | 0 | 0 | 1 (0.1) |
Comorbid psychiatric disordersc, n (%) | ||||||||||
Anxiety disorder | 1200 (40.7) | 416 (39.0) | 343 (40.4) | 36 (47.7) | 45 (47.9) | 840 (40.2) | 263 (42.3) | 62 (37.3) | 35 (49.3) | 360 (41.9) |
Bipolar disorder | 509 (17.3) | 167 (15.7) | 78 (9.2) | 10 (13.2) | 13 (13.8) | 268 (12.8) | 166 (26.7) | 47 (28.3) | 28 (39.4) | 241 (28.1) |
Schizophrenia | 466 (15.8) | 179 (16.8) | 61 (7.2) | 6 (7.9) | 13 (13.8) | 259 (12.4) | 138 (22.2) | 47 (28.3) | 22 (31.0) | 207 (24.1) |
ADHD | 48 (1.6) | 16 (1.5) | 4 (0.5) | 2 (2.6) | 3 (3.2) | 25 (1.2) | 13 (2.1) | 9 (5.4) | 1 (1.4) | 23 (2.7) |
Autism | 2 (0.1) | 0 | 0 | 0 | 0 | 0 | 2 (0.3) | 0 | 0 | 2 (0.2) |
History of medication at baselineb, n (%) | ||||||||||
Steroid, hormonal drug | 1437 (48.8) | 501 (47.0) | 452 (53.2) | 36 (47.4) | 53 (56.4) | 1042 (49.9) | 293 (47.1) | 73 (44.0) | 29 (40.8) | 395 (46.0) |
Anxiolytics | 555 (18.8) | 201 (18.8) | 176 (20.7) | 15 (19.7) | 18 (19.1) | 410 (19.6) | 101 (16.2) | 31 (18.7) | 13 (18.3) | 145 (16.9) |
Leukotriene receptor antagonists | 276 (9.4) | 96 (9.0) | 82 (9.6) | 6 (7.9) | 9 (9.6) | 193 (9.2) | 54 (8.7) | 21 (12.7) | 8 (11.3) | 83 (9.7) |
Neurological medication, psychotropic drug | 198 (6.7) | 66 (6.2) | 60 (7.1) | 2 (2.6) | 5 (5.3) | 133 (6.4) | 43 (6.9) | 15 (9.0) | 7 (9.9) | 65 (7.6) |
Analgesic, anti-inflammatory | 187 (6.3) | 67 (6.3) | 55 (6.5) | 1 (1.3) | 8 (8.5) | 131 (6.3) | 44 (7.1) | 11 (6.6) | 1 (1.4) | 56 (6.5) |
Antibacterial and/or antifungal | 179 (6.1) | 56 (5.2) | 53 (6.2) | 5 (6.6) | 4 (4.3) | 118 (5.7) | 41 (6.6) | 15 (9.0) | 5 (7.0) | 61 (7.1) |
Antihypertensive, cardiotonic | 52 (1.8) | 14 (1.3) | 22 (2.6) | 3 (3.9) | 1 (1.1) | 40 (1.9) | 8 (1.3) | 4 (2.4) | 0 | 12 (1.4) |
Antipsychotic | 49 (1.7) | 18 (1.7) | 13 (1.5) | 1 (1.3) | 0 | 32 (1.5) | 10 (1.6) | 7 (4.2) | 0 | 17 (2.0) |
Antismoking product | 21 (0.7) | 9 (0.8) | 5 (0.6) | 0 | 0 | 14 (0.7) | 7 (1.1) | 0 | 0 | 7 (0.8) |
Antineoplastic | 7 (0.2) | 2 (0.2) | 3 (0.4) | 1 (1.3) | 1 (1.1) | 7 (0.3) | 0 | 0 | 0 | 0 |
Mood stabilizer | 2 (0.1) | 1 (0.1) | 1 (0.1) | 0 | 0 | 2 (0.1) | 0 | 0 | 0 | 0 |
Immunostimulant | 2 (0.1) | 2 (0.2) | 0 | 0 | 0 | 2 (0.1) | 0 | 0 | 0 | 0 |
Centrally-acting anti-obesity product | 1 (0) | 0 | 0 | 0 | 0 | 0 | 1 (0.2) | 0 | 0 | 1 (0.1) |
Other | 324 (11.0) | 124 (11.6) | 92 (10.8) | 9 (11.8) | 14 (14.9) | 239 (11.5) | 56 (9.0) | 19 (11.4) | 10 (14.1) | 85 (9.9) |
Concomitant medication at baselinec, n (%) | ||||||||||
Steroid, hormonal drug | 1118 (37.9) | 383 (35.9) | 353 (41.5) | 27 (35.5) | 40 (42.6) | 803 (38.5) | 229 (36.8) | 55 (33.1) | 31 (43.7) | 315 (36.7) |
Anxiolytics | 1427 (48.4) | 521 (48.8) | 361 (42.5) | 39 (51.3) | 47 (50.0) | 968 (46.4) | 319 (51.3) | 96 (57.8) | 44 (62.0) | 459 (53.4) |
Leukotriene receptor antagonists | 173 (5.9) | 60 (5.6) | 58 (6.8) | 5 (6.6) | 6 (6.4) | 129 (6.2) | 27 (4.3) | 12 (7.2) | 5 (7.0) | 44 (5.1) |
Neurological medication, psychotropic drug | 260 (8.8) | 92 (8.6) | 54 (6.4) | 7 (9.2) | 6 (6.4) | 159 (7.6) | 60 (9.6) | 24 (14.5) | 17 (23.9) | 101 (11.8) |
Analgesic, anti-inflammatory | 96 (3.3) | 36 (3.4) | 26 (3.1) | 2 (2.6) | 1 (1.1) | 65 (3.1) | 22 (3.5) | 9 (5.4) | 0 | 31 (3.6) |
Antibacterial and/or antifungal | 115 (3.9) | 34 (3.2) | 33 (3.9) | 2 (2.6) | 6 (6.4) | 75 (3.6) | 27 (4.3) | 9 (5.4) | 4 (5.6) | 40 (4.7) |
Antihypertensive, cardiotonic | 82 (2.8) | 26 (2.4) | 26 (3.1) | 2 (2.6) | 2 (2.1) | 56 (2.7) | 17 (2.7) | 7 (4.2) | 2 (2.8) | 26 (3.0) |
Antipsychotic | 607 (20.6) | 222 (20.8) | 89 (10.5) | 10 (13.2) | 16 (17.0) | 337 (16.1) | 178 (28.6) | 59 (35.5) | 33 (46.5) | 270 (31.4) |
Antismoking product | 17 (0.6) | 3 (0.6) | 4 (0.5) | 0 | 1 (1.1) | 8 (0.4) | 4 (0.6) | 4 (2.4) | 1 (1.4) | 9 (1.0) |
Antineoplastic | 12 (0.4) | 4 (0.4) | 4 (0.5) | 1 (1.3) | 1 (1.1) | 10 (0.5) | 1 (0.2) | 0 | 1 (1.4) | 2 (0.2) |
Mood stabilizer | 215 (7.3) | 63 (5.9) | 27 (3.2) | 5 (6.6) | 4 (4.3) | 99 (4.7) | 73 (11.7) | 26 (15.7) | 17 (23.9) | 116 (13.5) |
Immunostimulant | 1 (0) | 1 (0.1) | 0 | 0 | 0 | 1 (0.0) | 0 | 0 | 0 | 0 |
Centrally-acting anti-obesity product | 2 (0.1) | 0 | 0 | 0 | 0 | 0 | 1 (0.2) | 1 (0.6) | 0 | 2 (0.2) |
Other | 231 (7.8) | 80 (7.5) | 68 (8.0) | 4 (5.3) | 7 (7.4) | 159 (7.6) | 48 (7.7) | 19 (11.4) | 5 (7.0) | 72 (8.4) |
Sedative antidepressant, n (%) | 917 (31.1) | 288 (27.0) | 251 (29.5) | 26 (34.2) | 38 (40.4) | 603 (28.9) | 221 (35.5) | 65 (39.2) | 28 (39.4) | 314 (36.6) |
Mirtazapine | 600 (20.4) | 177 (16.6) | 165 (19.4) | 20 (26.3) | 26 (27.7) | 388 (18.6) | 149 (24.0) | 43 (25.9) | 20 (28.2) | 212 (24.7) |
Trazodone hydrochloride | 360 (12.2) | 122 (11.4) | 87 (10.2) | 10 (13.2) | 12 (12.8) | 231 (11.1) | 88 (14.1) | 27 (16.3) | 14 (19.7) | 129 (15.0) |
Mianserin hydrochloride | 95 (3.2) | 31 (2.9) | 19 (2.2) | 1 (1.3) | 4 (4.3) | 55 (2.6) | 28 (4.5) | 8 (4.8) | 4 (5.6) | 40 (4.7) |
Antidepressant dosage at end of treatment, n (%) | ||||||||||
< Recommended maximum dose | 2740 (93.0) | 987 (92.5) | 806 (94.8) | 70 (92.1) | 91 (96.8) | 1954 (93.6) | 570 (91.6) | 150 (90.4) | 66 (93.0) | 786 (91.5) |
≥ Recommended maximum dose | 206 (7.0) | 80 (7.5) | 44 (5.2) | 6 (7.9) | 3 (3.2) | 133 (6.4) | 52 (8.4) | 16 (9.6) | 5 (7.0) | 73 (8.5) |
Dosage of antidepressants during treatment (mg/day)d, n (%) | ||||||||||
Mean (95% CI) | 74.3 (72.3–76.3) | 73.0 (69.9–76.1) | 68.2 (64.8–71.7) | 67.3 (52.9–81.7) | 69.1 (57.9–80.4) | 70.7 (68.4–72.9) | 82.5 (77.4–87.7) | 87.7 (77.7–97.7) | 77.4 (66.6–88.3) | 83.1 (78.8–87.4) |
Median (IQR) | 64.9 (37.5, 100.0) | 65.5 (37.5, 100.0) | 58.4 (37.5, 81.2) | 46.4 (37.5, 75.0) | 60.2 (30.0. 85.7) | 61.1 (37.5, 93.5) | 71.0 (37.5, 105.1) | 75.0 (37.5, 120.1) | 75.0 (38.1, 105.0) | 73.0 (37.5, 106.8) |
< 75 mg/day | 1678 (57.0) | 605 (56.7) | 526 (61.9) | 53 (69.7) | 54 (57.4) | 1238 (59.3) | 328 (52.7) | 80 (48.2) | 32 (45.1) | 440 (51.2) |
≥ 75 and < 150 mg/day | 1005 (34.1) | 378 (35.4) | 264 (31.1) | 16 (21.1) | 32 (34.0) | 690 (33.1) | 218 (35.0) | 62 (37.3) | 35 (49.3) | 315 (36.7) |
≥ 150 mg/day | 263 (8.9) | 84 (7.9) | 60 (7.1) | 7 (9.2) | 8 (8.5) | 159 (7.6) | 76 (12.2) | 24 (14.5) | 4 (5.6) | 104 (12.1) |
Effect of hypnotic prescription pattern on MDD recurrence
Factors associated with MDD recurrence
Variable | Reference | Category | MDD recurrence at 360 days, OR (95% CI) |
---|---|---|---|
Prescription pattern | Benzodiazepine | Non-benzodiazepine | 0.84 (0.67–1.07) |
Melatonin receptor agonist | 0.87 (0.47–1.60) | ||
Orexin receptor antagonist | 0.87 (0.50–1.50) | ||
Combination therapy (2 drugs) | 1.23 (0.97–1.56) | ||
Combination therapy (3 drugs) | 0.91 (0.60–1.37) | ||
Combination therapy (≥4 drugs) | 0.97 (0.53–1.75) | ||
Gendera | Male | Female | 0.67 (0.50–0.88) |
Agea | < 40 years | ≥40 years | 0.95 (0.78–1.14) |
Insured or dependent | Insured | Spouse | 1.44 (1.03–2.02) |
Other family member | 1.46 (0.99–2.16) | ||
Prior neurological medication, psychotropic drug | Absent | Present | 1.22 (0.86–1.73) |
Prior anxiolytic medication | Absent | Present | 0.98 (0.77–1.24) |
Concomitant antipsychotic medication | Absent | Present | 1.11 (0.88–1.39) |
Sedative antidepressant | Absent | Present | 1.50 (1.24–1.82) |
Antidepressant dosage at end of treatment | <Recommended maximum dose | ≥Recommended maximum dose | 1.11 (0.77–1.60) |
Antidepressant dosage (mg/day)b | < 75 mg/day | ≥75 and < 150 mg/day | 1.06 (0.86–1.29) |
≥150 mg/day | 1.14 (0.81–1.61) |