Background
Methods
Results
Efficacy
Presenting episode: depression
Index episode and duration | Drug | Number of Patients |
---|---|---|
Depression | ||
8–12 weeks | olanzapine | 351 |
olanzapine/fluoxetine | 287 | |
quetiapine | 661 | |
risperidone + ms | 10 | |
risperidone/paroxetine + ms | 10 | |
paroxetine + ms | 10 | |
lamotrigine | 205 | |
placebo | 685 | |
Mania/Mixed | ||
<6 weeks | olanzapine | 265 |
risperidone | 449 | |
risperidone + ms | 127 | |
quetiapine | 209 | |
quetiapine + ms | 275 | |
ziprasidone | 270 | |
aripiprazole | 437 | |
divalproex | 126 | |
haloperidol | 428 | |
haloperidol + ms | 53 | |
lithium | 128 | |
placebo | 1126 | |
placebo + ms | 411 | |
6–12 weeks | olanzapine | 291 |
olanzapine + ms | 229 | |
quetiapine | 209 | |
aripiprazole | 174 | |
divalproex | 63 | |
lithium | 98 | |
haloperidol | 488 | |
placebo | 196 | |
placebo + ms | 115 | |
>12 weeks | olanzapine | 567 |
olanzapine + ms | 51 | |
aripipazole | 78 | |
divalproex | 126 | |
lithium | 214 | |
placebo | 219 | |
placebo + ms | 48 |
Events/total patients | Event rate (%) | ||||||
---|---|---|---|---|---|---|---|
Outcome | Trials | Treatment | Placebo | Treatment | Placebo | Relative Risk (95% CI) | NNT (95% CI) |
Efficacy
| |||||||
Response
| |||||||
olanzapine 2–20 mg/day | 1 | 137/351 | 108/355 | 39 | 30 | 1.3 (1.04 to 1.6) | 11.6 (6.4 to 62) |
quetiapine 300–600 mg/day | 2 | 379/648 | 313/330 | 58 | 40 | 1.5 (1.3 to 1.7) | 5.4 (4.2 to 7.7) |
Combined atypical | 3 | 516/999 | 240/685 | 52 | 35 | 1.4 (1.2 to 1.6) | 6.0 (4.8 to 7.7) |
Symptomatic remission
| |||||||
olanzapine 2–20 mg/day | 1 | 115/351 | 87/355 | 33 | 25 | 1.3 (1.06 to 1.7) | 12.1 (6.7 to 62) |
quetiapine 300–600 mg/day | 2 | 640/648 | 96/330 | 52 | 29 | 1.8 (1.5 to 2.2) | 4.3 (3.5 to 5.9) |
Combined atypical | 3 | 455/999 | 183/685 | 46 | 27 | 1.6 (1.3 to 1.9) | 5.3 (4.3 to 7.0) |
Emergence of mania
| |||||||
olanzapine 2–20 mg/day | 1 | 19/345 | 23/345 | 6 | 7 | 0.8 (0.5 to 1.5) | not calculated |
quetiapine 300–600 mg/day | 2 | 23/697 | 18/347 | 5 | 3 | 0.6 (0.4 to 1.2) | not calculated |
Combined atypical | 3 | 42/1042 | 41/692 | 4 | 6 | 0.7 (0.5 to 1.1) | not calculated |
Discontinuations
| |||||||
All cause
| |||||||
olanzapine 2–20 mg/day | 1 | 191/351 | 232/355 | 54 | 65 | 0.8 (0.7 to 0.9) |
9.1 (5.5 to 27)
|
quetiapine 300–600 mg/day | 2 | 292/702 | 132/349 | 38 | 42 | 1.1 (0.8 to 1.3) | not calculated |
Combined atypical | 3 | 483/1053 | 364/704 | 46 | 52 | 0.9 (0.8 to 1.05) |
17 (10 to 50)
|
Lack of efficacy
| |||||||
olanzapine 2–20 mg/day | 1 | 73/351 | 121/355 | 21 | 34 | 0.6 (0.5 to 0.8) |
7.5 (5.1 to 15)
|
quetiapine 300–600 mg/day | 2 | 13/702 | 37/349 | 2 | 11 | 0.2 (0.1 to 0.3) |
11 (7.7 to 20)
|
Combined atypical | 3 | 86/1053 | 158/704 | 8 | 22 | 0.5 (0.4 to 0.6) |
7.0 (5.6 to 10)
|
Adverse events
| |||||||
olanzapine 2–20 mg/day | 1 | 34/351 | 19/355 | 10 | 5 | 1.8 (1.1 to 3.1) | 23 (12 to 220) |
quetiapine 300–600 mg/day | 2 | 109/702 | 17/349 | 16 | 5 | 3.2 (2.0 to 5.2) | 9.4 (6.7 to 14) |
Combined atypical | 3 | 143/1053 | 36/704 | 14 | 5 | 2.6 (1.8 to 3.7) | 12 (10 to 14) |
Presenting episode: mania or mixed
Response
Events/total patients | Event rate (%) | ||||||
---|---|---|---|---|---|---|---|
Outcome | Trials | Treatment | Placebo | Treatment | Placebo | Relative Risk (95% CI) | NNT (95% CI) |
Less than 6 weeks [24, 26, 28, 29, 31-38, 42, 43]
| |||||||
Efficacy
| |||||||
Response
| |||||||
All mono- and adjunctive therapy | 14 | 845/1634 | 473/1467 | 52 | 32 | 1.6 (1.5 to 1.8) | 5.1 (4.4 to 6.2) |
All monotherapy only | 8 | 486/949 | 234/791 | 51 | 30 | 1.7 (1.5 to 2.0) | 4.6 (3.8 to 5.8) |
Olanzapine | 2 | 69/125 | 41/129 | 55 | 32 | 1.8 (1.3 to 2.4) | 4.3 (2.8 to 8.7) |
Risperidone | 4 | 276/502 | 157/478 | 55 | 33 | 1.7 (1.5 to 2.0) | 4.5 (3.6 to 6.2) |
Quetiapine | 4 | 247/474 | 167/469 | 52 | 36 | 1.5 (1.3 to 1.7) | 6.1 (4.4 to 9.8) |
Aripiprazole | 2 | 123/263 | 66/259 | 47 | 25 | 1.8 (1.4 to 2.3) | 4.7 (3.4 to 7.6) |
Symptomatic remission
| |||||||
All mono- and adjunctive therapy | 4 | 210/448 | 128/453 | 47 | 28 | 1.7 (1.4 to 2.0) | 5.4 (4.0 to 8.1) |
All monotherapy only | 2 | 83/182 | 44/179 | 46 | 25 | 1.9 (1.4 to 2.5) | 4.8 (3.3 to 8.8) |
Emergence of depression
| |||||||
Quetiapine, plus mood stabiliser | 2 | 33/275 | 30/285 | 12 | 11 | 1.2 (0.7 to 1.8) | not calculated |
Discontinuations
| |||||||
All cause | 13 | 513/1507 | 613/1350 | 34 | 45 | 0.7 (0.7 to 0.8) |
8.8 (6.7 to 13)
|
Lack of efficacy | 13 | 187/1507 | 306/1350 | 12 | 23 | 0.5 (0.5 to 0.6) |
9.8 (7.7 to 13)
|
Adverse events | 13 | 81/1507 | 66/1350 | 5.4 | 4.9 | 1.1 (0.8 to 1.5) | not calculated |
6 to 12 weeks [39, 42,43]
| |||||||
Efficacy
| |||||||
Response
| |||||||
All mono- and adjunctive therapy | 3 | 268/428 | 116/309 | 63 | 38 | 1.6 (1.4 to 1.9) | 4.0 (3.1 to 5.6) |
Symptomatic remission
| |||||||
All mono- and adjunctive therapy | 3 | 309/428 | 145/309 | 72 | 47 | 1.5 (1.3 to 1.7) | 4.0 (3.1 to 5.5) |
Emergence of depression
| |||||||
All mono- and adjunctive therapy | 2 | 9/208 | 17/197 | 8.6 | 4.3 | 0.5 (0.2 to 1.1) | not calculated |
Discontinuations
| |||||||
All cause | 3 | 151/438 | 154/313 | 34 | 49 | 0.8 (0.6 to 0.9) |
6.8 (4.6 to 13)
|
Lack of efficacy | 3 | 50/438 | 95/313 | 11 | 30 | 0.5 (0.3 to 0.6) |
5.3 (4.0 to 7.7)
|
Adverse events | 3 | 37/438 | 12/313 | 8.4 | 3.8 | 2.2 (1.1 to 4.4) | 22 (13 to 80) |
Events/total patients | Event rate (%) | ||||||
---|---|---|---|---|---|---|---|
Outcome | Trials | Treatment | Active control | Treatment | Active control | Relative Risk (95% CI) | NNT (95% CI) |
Less than 6 weeks [37, 42, 43]
| |||||||
Efficacy
| |||||||
All mono- and adjunctive therapy | 3 | 242/487 | 227/466 | 50 | 49 | 1.0 (0.9 to 1.2) | not calculated |
Symptomatic remission
| |||||||
All mono- and adjunctive therapy | 3 | 137/333 | 126/322 | 41 | 39 | 1.1 (0.9 to 1.3) | not calculated |
Discontinuations
| |||||||
All cause | 4 | 75/346 | 90/338 | 22 | 27 | 0.8 (0.6 to 1.1) | not calculated |
Lack of efficacy | 3 | 19/331 | 17/323 | 5.7 | 5.3 | 1.1 (0.6 to 2.1) | not calculated |
Adverse events | 4 | 21/346 | 15/338 | 6.1 | 4.4 | 1.4 (0.7 to 2.6) | not calculated |
6 to 12 weeks [40-44]
| |||||||
Efficacy
| |||||||
All mono- and adjunctive therapy | 4 | 394/616 | 353/585 | 64 | 60 | 1.1 (0.97 to 1.2) | not calculated |
Symptomatic remission
| |||||||
All mono- and adjunctive therapy | 4 | 335/616 | 280/585 | 54 | 48 | 1.1 (1.01 to 1.3) | 15 (8.2 to 110) |
Emergence of depression
| |||||||
All mono- and adjunctive therapy | 4 | 40/510 | 62/492 | 7.8 | 13 | 0.6 (0.4 to 0.9) | 21 (12 to 99) |
Discontinuations
| |||||||
All cause | 5 | 300/675 | 346/651 | 44 | 53 | 0.8 (0.8 to 0.9) |
11 (7.1 to 30)
|
Lack of efficacy | 5 | 119/675 | 94/651 | 18 | 14 | 1.2 (0.95 to 1.6) | not calculated |
Adverse events | 5 | 68/675 | 132/651 | 10 | 20 | 0.5 (0.4 to 0.7) |
9.8 (7.1 to 16)
|
Remission
Emergence of depression
Relapse in maintenance trials
Events/total patients | Event rate (%) | ||||||
---|---|---|---|---|---|---|---|
Outcome | Trials | Treatment | Active control | Treatment | Active control | Relative Risk (95% CI) | NNTp or NNH (95% CI) |
Relapse
| |||||||
Any relapse
| |||||||
All versus placebo | 3 | 135/332 | 166/257 | 41 | 65 | 0.6 (0.5 to 0.7) |
4.2 (3.1 to 6.2)
|
Olanzapine versus placebo | 2 | 116/255 | 130/174 | 45 | 75 | 0.6 (0.5 to 0.7) |
3.4 (2.6 to 4.9)
|
Olanzapine versus active | 2 | 79/250 | 96/237 | 32 | 41 | 0.8 (0.6 to 0.98) |
11 (5.7 to 250)
|
Depressive relapse
| |||||||
All versus placebo | 3 | 84/332 | 79/257 | 25 | 31 | 0.8 (0.6 to 0.98) |
18 (7.8 to 18)
|
Olanzapine versus placebo | 2 | 75/255 | 68/174 | 29 | 39 | 0.7 (0.6 to 0.97) |
10 (5.3 to 200)
|
Manic relapse
| |||||||
All versus placebo | 3 | 39/332 | 74/257 | 12 | 29 | 0.4 (0.3 to 0.6) |
5.9 (4.2 to 9.5)
|
Olanzapine versus placebo | 2 | 33/255 | 55/174 | 13 | 32 | 0.4 (0.3 to 0.6) |
5.4 (3.7 to 9.4)
|
Discontinuation
| |||||||
All cause
| |||||||
All versus placebo | 3 | 146/354 | 116/267 | 41 | 43 | 1.1 (0.9 to 1.3) | not calculated |
Olanzapine versus placebo | 2 | 107/276 | 61/184 | 39 | 33 | 1.3 (1.04 to 1.7) | 18 (6.9 to 30) |
Olanzapine versus active | 2 | 222/342 | 250/341 | 65 | 73 | 0.9 (0.8 to 0.98) |
12 (6.5 to 67)
|
Lack of efficacy
| |||||||
All versus placebo | 3 | 36/354 | 55/267 | 10 | 21 | 0.6 (0.5 to 0.9) |
9.6 (6.2 to 22)
|
Olanzapine versus placebo | 2 | 17/276 | 19/184 | 6 | 10 | 0.8 (0.4 to 1.4) | not calculated |
Olanzapine versus active | 2 | 55/342 | 62/340 | 16 | 18 | 0.9 (0.6 to 1.2) | not calculated |
Adverse events
| |||||||
All versus placebo | 3 | 27/354 | 9/267 | 8 | 4 | 2.4 (1.1 to 5.0) | 24 (13 to 160) |
Olanzapine versus placebo | 2 | 22/276 | 8/184 | 8 | 5 | 2.0 (0.9 to 4.5) | not calculated |
Olanzapine versus active | 2 | 72/342 | 80/340 | 21 | 24 | 0.9 (0.7 to 1.2) | not calculated |
Discontinuations
Adverse events
Measured adverse events
Weight gain >7% baseline
Events/total patients | Event rate (%) | ||||||
---|---|---|---|---|---|---|---|
Event | Trials | Treatment | Placebo | Treatment | Placebo | Relative Risk (95% CI) | NNH/NNTp (95% CI) |
Less than 6 weeks [24, 26, 28, 30-35 37, 38]
| |||||||
Measured weight increase >7% | 4 | 12/469 | 8/408 | 3 | 2 | 1.14 (0.5 to 2.8) | not calculated |
Treatment emergent weight gain | 2 | 20/266 | 6/272 | 8 | 2 | 3.4 (1.4 to 8.4) | 19 (11 to 59) |
Treatment emergent akathisia | 5 | 73/738 | 26/599 | 10 | 4 | 2.2 (1.4 to 3.5) | 18 (12 to 35) |
Treatment emergent extrapyramidal disorder | 5 | 115/566 | 30/477 | 20 | 6 | 3.5 (2.4 to 5.1) | 7.1 (5.6 to 10) |
Treatment emergent tremor | 5 | 46/618 | 16/529 | 7 | 3 | 2.5 (1.4 to 4.3) | 23 (14 to 53) |
Treatment emergent somnolence | 11 | 340/1293 | 96/1244 | 26 | 8 | 3.5 (2.8 to 4.3) | 5.4 (4.7 to 6.4) |
Treatment emergent depression | 2 | 10/145 | 10/144 | 7 | 7 | 1.0 (0.4 to 2.3) | not calculated |
6–12 weeks [20, 22, 39, 41-43]
| |||||||
Measured weight increase >7% | 4 | 136/1151 | 15/803 | 12 | 2 | 6.4 (3.9 to 11) | 10 (8.3 to 13) |
Treatment emergent weight gain | 2 | 76/336 | 9/212 | 23 | 4 | 4.7 (2.5 to 9.1) | 5.4 (4.2 to 7.6) |
Treatment emergent akathisia | 4 | 7/209 | 12/198 | 3 | 6 | 0.6 (0.2 to 1.4) | not calculated |
Treatment emergent extrapyramidal disorder | 3 | 79/800 | 31/448 | 10 | 7 | 1.6 (1.04 to 2.4) | 33 (16 to infinity) |
Treatment emergent tremor | 3 | 67/438 | 25/313 | 15 | 8 | 1.6 (1.1 to 2.5) | 14 (8.5 to 36) |
Treatment emergent somnolence | 6 | 450/1487 | 109/1015 | 30 | 11 | 2.7 (2.2 to 3.3) | 5.1 (4.4 to 6.1) |
Treatment emergent depression | 3 | 49/438 | 25/313 | 11 | 8 | 1.1 (0.7 to 1.7) | not calculated |
More than 12 weeks [46, 48, 49]
| |||||||
Measured weight increase >7% | 3 | 57/332 | 6/244 | 17 | 2 | 6.6 (3.0 to 15) | 6.8 (5.2 to 9.9) |
Treatment emergent weight gain | 2 | 28/276 | 5/184 | 10 | 3 | 4.2 (1.6 to 11) | 13 (9 to 32) |
Treatment emergent somnolence | 3 | 20/353 | 12/267 | 6 | 4 | 1.5 (0.7 to 3.0) | not calculated |
Events/total patients | Event rate (%) | ||||||
---|---|---|---|---|---|---|---|
Event | Trials | Treatment | Active control | Treatment | Active control | Relative Risk (95% CI) | NNTp or NNH (95% CI) |
Less than 6 weeks [27, 30, 37]
| |||||||
Treatment emergent tremor | 3 | 24/331 | 26/323 | 7 | 8 | 0.9 (0.5 to 1.5) | not calculated |
Treatment emergent somnolence | 3 | 69/331 | 47/323 | 21 | 15 | 1.5 (1.1 to 2.0) | 16 (8.3 to 210) |
6–12 weeks [21, 40, 41, 42, 43]
| |||||||
Measured weight increase >7% | 3 | 152/536 | 39/515 | 31 | 13 | 3.6 (2.6 to 5.0) | 4.8 (4.0 to 6.1) |
Treatment emergent weight gain | 3 | 62/398 | 21/380 | 16 | 6 | 2.9 (1.8 to 4.6) | 10 (7.0 to 17) |
Treatment emergent akathisia | 4 | 42/618 | 110/585 | 7 | 19 | 0.4 (0.3 to 0.5) |
8.3 (6.4 to 12)
|
Treatment emergent extrapyramidal disorder | 3 | 27/511 | 148/490 | 5 | 30 | 0.2 (0.1 to 0.3) |
4.0 (3.4 to 4.9)
|
Treatment emergent tremor | 4 | 39/618 | 122/585 | 6 | 21 | 0.3 (0.2 to 0.4) |
6.9 (5.5 to 9.3)
|
Treatment emergent somnolence | 5 | 133/705 | 72/684 | 19 | 11 | 1.8 (1.4 to 2.4) | 12 (8.3 to 22) |
More than 12 weeks [45, 47]
| |||||||
Measured weight increase >7% | 2 | 93/340 | 43/337 | 27 | 13 | 2.2 (1.6 to 3.0) | 6.9 (4.9 to 12) |
Treatment emergent weight gain | 2 | 45/342 | 25/340 | 13 | 7 | 1.8 (1.1 to 2.8) | 17 (10 to 79) |
Treatment emergent somnolence | 2 | 64/342 | 31/340 | 19 | 9 | 2.1 (1.4 to 3.0) | 10 (6.8 to 23) |
Treatment emergent depression | 2 | 88/342 | 63/340 | 26 | 19 | 1.4 (1.1 to 1.8) | 14 (7.5 to 100) |