Table 3.
Safety Outcomes.
| Outcome | Step 1 | Step 2 | |||
|---|---|---|---|---|---|
| Aripiprazole-Augmentation Group (N = 211) | Bupropion-Augmentation Group (N = 206) | Switch-to-Bupropion Group (N = 202) | Lithium-Augmentation Group (N = 127) | Switch-to-Nortriptyline Group (N = 121) | |
| Falls * | |||||
| Rate per patient | 0.33 | 0.55 | 0.38 | 0.47 | 0.38 |
| Total no. of falls† | 70 | 114 | 77 | 60 | 46 |
| No. of injurious falls | 36 | 52 | 38 | 27 | 16 |
| Serious adverse events | |||||
| Rate per patient | 0.07 | 0.08 | 0.12 | 0.10 | 0.09 |
| Total no. of eventsद | 15 | 16 | 24 | 13 | 11 |
| Psychiatric event | 0 | 3 | 0 | 0 | 2 |
| Nonpsychiatric event | 15 | 13 | 24 | 13 | 9 |
| Death | 1‖ | 1** | 1†† | 0 | 0 |
| Relation of events to intervention — no.‡‡ | |||||
| Probably or possibly related | 1 | 7 | 3 | 5 | 4 |
| Not likely to be related | 14 | 9 | 21 | 8 | 7 |
| Adverse events | |||||
| Rate per patient | 2.82 | 2.20 | 2.55 | 2.73 | 3.12 |
| Total no. of events | 596 | 453 | 515 | 347 | 377 |
| Most common adverse events — no. | |||||
| Dizziness or impaired balance | 36 | 41 | 40 | 28 | 21 |
| Gastrointestinal distress | 27 | 35 | 37 | 20 | 20 |
| Reduced salivation | 15 | 30 | 23 | 13 | 51 |
| Tension, inner unrest, or anxiety | 30 | 20 | 29 | 8 | 9 |
| Reduced or disturbed sleep | 39 | 18 | 33 | 6 | 6 |
Falls were assessed during each trial call or visit every other week.
In step 1, the risk ratio for the aripiprazole-augmentation group as compared with the bupropion-augmentation group was 0.59 (95% CI, 0.38 to 0.92; P = 0.02), for the aripiprazole-augmentation group as compared with the switch-to-bupropion group was 0.77 (95% CI, 0.49 to 1.22; P = 0.27), and for the bupropion-augmentation group as compared with the switch-to-bupropion group was 1.32 (95% CI, 0.88 to 1.96; P = 0.17). In step 2, the risk ratio for the lithium-augmentation group as compared with the switch-to-nortriptyline group was 1.22 (95% CI, 0.62 to 2.39; P = 0.57).
In step 1, a total of 55 serious adverse events occurred in 49 patients. In the switch-to-bupropion group, 3 patients had 2 serious adverse events each and 1 patient had 3 serious adverse events. In step 2, a total of 24 serious adverse events occurred in 22 patients. In the lithium-augmentation group, 1 patient had 2 serious adverse events; in the switch-to-nortriptyline group, 1 patient had 2 serious adverse events.
I n step 1, the hazard ratios were 0.59 (95% CI, 0.31 to 1.11) in the aripiprazole-augmentation group, 0.61 (95% CI, 0.32 to 1.15) in the bupropion-augmentation group, and 1.00 (reference) in the switch-to-bupropion group. In step 2, the hazard ratios were 1.30 (95% CI, 0.58 to 2.92) in the lithium-augmentation group and 1.00 (reference) in the switch-to-nortriptyline group.
In step 1, P = 0.93 for the aripiprazole-augmentation group as compared with the bupropion-augmentation group, P = 0.10 for the aripiprazole-augmentation group as compared with the switch-to-bupropion group, and P = 0.13 for the bupropion-augmentation group as compared with the switch-to-bupropion group. In step 2, P = 0.52 for the lithium-augmentation group as compared with the switch-to-nortriptyline group.
One patient died of an unknown cause; this patient had not started randomized treatment.
One serious adverse event was a fall and resulted in death, which was deemed to be related to benzodiazepine and alcohol use.
One operation was followed by a fatal postsurgical pneumonia. This was counted as two serious adverse events. This patient was no longer taking the trial medication (bupropion) at the time of death.
The relationship of the serious adverse event to the intervention was determined by the site principal investigator.