What do systematic reviews say?

Augmentation of current antidepressant (SSRI) with ziprasidone (40 mg/d to 160 mg/d) vs augmentation of current antidepressant (SSRI) with placebo or continue on SSRI monotherapy

Augmentation of current antidepressant (SSRI) with ziprasidone (40… probably leads to higher response (≥ 50% reduction in MADRS/HAM‐D score) ‐ Any dose compared with augmentation of current antidepressant (SSRI) with placebo or… (moderate certainty).

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  RR 1.8 [1.07, 3.04]
  2 studies · 199 participants
  Moderate

Augmentation of current antidepressant (SSRI) with ziprasidone (40 mg/d to 160 mg/d) vs augmentation of current antidepressant (SSRI) with placebo or continue on SSRI monotherapy

Augmentation of current antidepressant (SSRI) with ziprasidone (40… showed no clear difference in remission (clinician‐rated) ‐ Any dose compared with augmentation of current antidepressant (SSRI) with placebo or… (moderate certainty).

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  OR 1.46 [0.75, 2.86]
  2 studies · 199 participants
  Moderate

Augmentation of current antidepressant (SSRI) with ziprasidone (40 mg/d to 160 mg/d) vs augmentation of current antidepressant (SSRI) with placebo or continue on SSRI monotherapy

The review found no eligible studies for this question.

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  no estimate extracted
  Studies not reported
  No studies found

Augmentation of current antidepressant (fluoxetine 20 mg/d) with mianserin (60 mg/d) vs placebo plus antidepressant

Augmentation of current antidepressant (fluoxetine 20 mg/d) with… showed no clear difference in dropouts compared with augmentation of current antidepressant (fluoxetine 20 mg/d) with… (low certainty).

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  RR 1.02 [0.38, 2.72]
  1 study · 70 participants
  Low

Augmentation of current antidepressant (fluoxetine 20 mg/d) with mianserin (60 mg/d) vs placebo plus antidepressant

Augmentation of current antidepressant (fluoxetine 20 mg/d) with… may leads to higher response (≥ 50% reduction in HAM‐D score) compared with augmentation of current antidepressant (fluoxetine 20 mg/d) with… (low certainty).

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  RR 1.7 [1.03, 2.78]
  1 study · 70 participants
  Low

Augmentation of current antidepressant (fluoxetine 20 mg/d) with mianserin (60 mg/d) vs placebo plus antidepressant

Augmentation of current antidepressant (fluoxetine 20 mg/d) with… may leads to higher remission (HAM‐D total score ≤ 7) compared with augmentation of current antidepressant (fluoxetine 20 mg/d) with… (low certainty).

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  RR 2.38 [1.09, 5.16]
  1 study · 70 participants
  Low

Augmentation of current antidepressant (various) with cariprazine (1 mg/d to 4.5 mg/d) vs augmentation of current antidepressant (various) with placebo

Augmentation of current antidepressant (various) with cariprazine (1… probably leads to higher dropouts ‐ any dose compared with augmentation of current antidepressant (various) with placebo (moderate certainty).

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  RR 1.68 [1.16, 2.41]
  1 study · 821 participants
  Moderate

Augmentation of current antidepressant (various) with cariprazine (1 mg/d to 4.5 mg/d) vs augmentation of current antidepressant (various) with placebo

Augmentation of current antidepressant (various) with cariprazine (1… probably leads to higher response (≥ 50% improvement in MADRS score) ‐ any dose compared with augmentation of current antidepressant (various) with placebo (moderate certainty).

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  RR 1.27 [1.07, 1.52]
  1 study · 808 participants
  Moderate

Augmentation of current antidepressant (various) with cariprazine (1 mg/d to 4.5 mg/d) vs augmentation of current antidepressant (various) with placebo

Augmentation of current antidepressant (various) with cariprazine (1… showed no clear difference in remission (MADRS total score ≤ 10) ‐ any dose compared with augmentation of current antidepressant (various) with placebo (moderate certainty).

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  RR 1.07 [0.86, 1.33]
  1 study · 808 participants
  Moderate

Augmentation of current antidepressant (various) with cariprazine (1 mg/d to 4.5 mg/d) vs augmentation of current antidepressant (various) with placebo

The review found no eligible studies for this question.

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  no estimate extracted
  Studies not reported
  No studies found

Augmentation of current antidepressant (various) with quetiapine (150 mg/d to 300 mg/d) vs augmentation of current antidepressant (various) with placebo

Augmentation of current antidepressant (various) with quetiapine… showed no clear difference in dropouts ‐ Any dose compared with augmentation of current antidepressant (various) with placebo (moderate certainty).

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  RR 1.33 [0.9, 1.95]
  3 studies · 997 participants
  Moderate

Augmentation of current antidepressant (various) with quetiapine (150 mg/d to 300 mg/d) vs augmentation of current antidepressant (various) with placebo

Augmentation of current antidepressant (various) with quetiapine… probably leads to higher response (≥ 50% reduction in MADRS or HAM‐D score) ‐ Any dose compared with augmentation of current antidepressant (various) with placebo (moderate certainty).

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  RR 1.25 [1.09, 1.44]
  3 studies · 977 participants
  Moderate

Augmentation of current antidepressant (various) with quetiapine (150 mg/d to 300 mg/d) vs augmentation of current antidepressant (various) with placebo

Augmentation of current antidepressant (various) with quetiapine… probably leads to higher remission (MADRS score ≤ 8/HAM‐D score ≤ 7) ‐ Any dose compared with augmentation of current antidepressant (various) with placebo (moderate certainty).

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  RR 1.53 [1.23, 1.9]
  3 studies · 977 participants
  Moderate

Augmentation of current antidepressant (various) with quetiapine (150 mg/d to 300 mg/d) vs augmentation of current antidepressant (various) with placebo

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  no estimate extracted
  2 studies · 884 participants
  Moderate

Augmentation of current antidepressant (fluoxetine 20 mg/d to 60 mg/d) with olanzapine (5 mg/d to 20 mg/d) vs augmentation of current antidepressant (fluoxetine 20 mg/d to 60 mg/d) with placebo

Augmentation of current antidepressant (fluoxetine 20 mg/d to 60… showed no clear difference in dropouts compared with augmentation of current antidepressant (fluoxetine 20 mg/d to 60… (low certainty).

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  RR 0.33 [0.04, 2.69]
  1 study · 20 participants
  Low

Augmentation of current antidepressant (fluoxetine 20 mg/d to 60 mg/d) with olanzapine (5 mg/d to 20 mg/d) vs augmentation of current antidepressant (fluoxetine 20 mg/d to 60 mg/d) with placebo

Augmentation of current antidepressant (fluoxetine 20 mg/d to 60… showed no clear difference in response (≥50% reduction in MADRS score) compared with augmentation of current antidepressant (fluoxetine 20 mg/d to 60… (low certainty).

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  RR 6 [0.87, 41.21]
  1 study · 20 participants
  Low

Augmentation of current antidepressant (fluoxetine 20 mg/d to 60 mg/d) with olanzapine (5 mg/d to 20 mg/d) vs augmentation of current antidepressant (fluoxetine 20 mg/d to 60 mg/d) with placebo

The review found no eligible studies for this question.

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  no estimate extracted
  Studies not reported
  No studies found

Augmentation of current antidepressant (fluoxetine 20 mg/d to 60 mg/d) with olanzapine (5 mg/d to 20 mg/d) vs augmentation of current antidepressant (fluoxetine 20 mg/d to 60 mg/d) with placebo

The review found no eligible studies for this question.

• Pharmacological interventions for treatment‐resistant depression in adults 2019 · Cochrane Headline outcomes only
  no estimate extracted
  Studies not reported
  No studies found

Brexpiprazole vs antidepressive agents

Brexpiprazole showed no clear difference in change in depressive symptoms at 8 weeks compared with antidepressive agents (high certainty).

• Brexpiprazole versus placebo or other antidepressive agents for treating depression 2023 · Cochrane Headline outcomes only
  MD 1.39
  8 studies · 3263 participants
  High

Abrupt discontinuation vs continuation of long‐term antidepressants

• Approaches for discontinuation versus continuation of long‐term antidepressant use for depressive and anxiety… 2021 · Cochrane Headline outcomes only
  no estimate extracted
  3 studies · 330 participants
  Very low