Table 2.
Unadjusted and adjusted hazard ratios for arrhythmia by antidepressant class, dose, and duration over 5 years’ follow-up
| No of events | Person years | Unadjusted hazard ratio (95% CI) | Adjusted analysis† | ||
|---|---|---|---|---|---|
| Hazard ratio (95% CI) | P value | ||||
| Antidepressant class | |||||
| No current use | 887 | 568 365 | 1.00 | 1.00 | - |
| TCAs | 102 | 41 208 | 1.59 (1.29 to 1.96) | 1.09 (0.88 to 1.35) | 0.46 |
| SSRIs | 352 | 224 985 | 1.02 (0.89 to 1.18) | 0.84 (0.73 to 0.97) | 0.02 |
| Other antidepressants | 68 | 28 048 | 1.55 (1.23 to 1.95) | 1.21 (0.96 to 1.54) | 0.11 |
| Combined antidepressants | 10 | 4233 | 1.47 (0.75 to 2.89) | 1.07 (0.54 to 2.09) | 0.85 |
| Antidepressant class and dose categories | |||||
| No current use | 887 | 568 365 | 1.00 | 1.00 | - |
| TCAs: | |||||
| ≤0.5 DDD | 51 | 23 506 | 1.37 (1.03 to 1.82) | 0.89 (0.67 to 1.19) | 0.44 |
| >0.5 DDD/≤1.0 DDD | 26 | 8400 | 2.03 (1.39 to 2.96) | 1.35 (0.91 to 1.99) | 0.14 |
| >1.0 DDD | 14 | 5306 | 1.66 (0.98 to 2.81) | 1.32 (0.77 to 2.26) | 0.31 |
| Test for trend§ | - | - | - | - | 0.15 |
| SSRIs: | |||||
| ≤0.5 DDD | 30 | 15 995 | 1.19 (0.82 to 1.71) | 0.93 (0.64 to 1.35) | 0.71 |
| >0.5 DDD/≤1.0 DDD | 236 | 157 668 | 0.97 (0.82 to 1.14) | 0.79 (0.67 to 0.94) | 0.007 |
| >1.0 DDD | 75 | 42 566 | 1.16 (0.91 to 1.49) | 0.98 (0.76 to 1.26) | 0.88 |
| Test for trend§ | - | - | - | - | 0.55 |
| Others: | |||||
| ≤0.5 DDD | 9 | 4026 | 1.40 (0.74 to 2.64) | 0.98 (0.52 to 1.86) | 0.95 |
| >0.5 DDD/≤1.0 DDD | 31 | 13 199 | 1.52 (1.08 to 2.15) | 1.16 (0.81 to 1.65) | 0.41 |
| >1.0 DDD | 20 | 8411 | 1.49 (0.97 to 2.29) | 1.28 (0.84 to 1.97) | 0.25 |
| Test for trend§ | - | - | - | - | 0.69 |
| Antidepressant class by time since starting and stopping treatment | |||||
| No current or recent use | 804 | 510 266 | 1.00 | 1.00 | - |
| TCAs: | |||||
| First 28 days | 23 | 5482 | 2.56 (1.64 to 4.02) | 1.99 (1.27 to 3.13) | 0.003 |
| 29-84 days after starting | 12 | 5400 | 1.36 (0.77 to 2.43) | 1.04 (0.58 to 1.87) | 0.89 |
| ≥85 days after starting | 44 | 18 941 | 1.52 (1.11 to 2.07) | 0.91 (0.67 to 1.25) | 0.57 |
| 1-28 days after stopping | 11 | 3614 | 2.04 (1.15 to 3.62) | 1.57 (0.86 to 2.86) | 0.14 |
| 29-84 days after stopping | 11 | 7030 | 1.02 (0.56 to 1.88) | 0.85 (0.46 to 1.56) | 0.60 |
| 85-182 days after stopping | 15 | 10 711 | 1.00 (0.60 to 1.66) | 0.79 (0.46 to 1.35) | 0.39 |
| SSRIs: | |||||
| First 28 days | 44 | 20 639 | 1.31 (0.90 to 1.89) | 1.23 (0.85 to 1.79) | 0.28 |
| 29-84 days after starting | 44 | 27 863 | 0.95 (0.66 to 1.37) | 0.91 (0.63 to 1.32) | 0.63 |
| ≥85 days after starting | 198 | 127 197 | 1.04 (0.88 to 1.23) | 0.78 (0.66 to 0.92) | 0.004 |
| 1-28 days after stopping | 22 | 15 685 | 0.88 (0.58 to 1.36) | 0.94 (0.61 to 1.44) | 0.76 |
| 29-84 days after stopping | 41 | 30 405 | 0.94 (0.70 to 1.26) | 0.94 (0.69 to 1.27) | 0.69 |
| 85-182 days after stopping | 66 | 46 815 | 0.97 (0.75 to 1.27) | 1.01 (0.77 to 1.33) | 0.92 |
| Others: | |||||
| First 28 days | 7 | 2776 | 1.56 (0.75 to 3.23) | 1.35 (0.65 to 2.80) | 0.42 |
| 29-84 days after starting | 7 | 3504 | 1.44 (0.71 to 2.91) | 1.07 (0.50 to 2.30) | 0.85 |
| ≥85 days after starting | 41 | 16 854 | 1.52 (1.13 to 2.04) | 1.14 (0.85 to 1.54) | 0.38 |
| 1-28 days after stopping | 5 | 1573 | 2.00 (0.83 to 4.79) | 1.86 (0.78 to 4.46) | 0.16 |
| 29-84 days after stopping | 6 | 3023 | 1.29 (0.58 to 2.88) | 1.19 (0.54 to 2.65) | 0.66 |
| 85-182 days after stopping | 8 | 4537 | 1.16 (0.58 to 2.34) | 1.09 (0.54 to 2.21) | 0.80 |
DDD=defined daily dose; SSRI=selective serotonin reuptake inhibitor; TCA=tricyclic and related antidepressant.
*Based on numbers in adjusted analysis.
†Adjusted for age, sex, year of diagnosis of depression, severity of depression, deprivation, smoking status, alcohol intake, ethnic group (white/not recorded or non-white), coronary heart disease, diabetes, hypertension, cancer, epilepsy/seizures, hypothyroidism, osteoarthritis, asthma/chronic obstructive pulmonary disease, stroke/transient ischaemic attack, rheumatoid arthritis, osteoporosis, liver disease, renal disease, obsessive-compulsive disorder, statins, non-steroidal anti-inflammatory drugs, aspirin, antihypertensives, anticonvulsants, hypnotics/anxiolytics, oral contraceptives, hormone replacement therapy, antipsychotics, bisphosphonates, anticoagulants.
‡Daily doses could not be evaluated for some prescriptions.
§Test for trend uses continuous values of dose.