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2. Augmentation with Second-Generation Antipsychotics
Prof. Philip Cowen
Professor of Psychopharmacology
Department of Psychiatry
University of Oxford, UK

3. Placebo-controlled randomized trials Addition of SGAs
Olanzapine, quetiapine, aripiprazole, brexpiprazole
Useful in patients who failed to respond to an SSRI
Similar effects in patients taking SNRIs
No systematical studies
Placebo-controlled randomized trials
Over 3000 patients
Addition of SGAs
Augmentation strategy with best evidence base
Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC (2013). Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes. PLoS Med 10, e
Citrome L. The ABC's of dopamine receptor partial agonists–aripiprazole, brexpiprazole and cariprazine: the 15‐min challenge to sort these agents out. International journal of clinical practice Nov 1;69(11):

4. Placebo-controlled randomized trials Addition of SGAs
Olanzapine, quetiapine, aripiprazole, brexpiprazole
Useful in patients who failed to respond to an SSRI
Similar effects in patients taking SNRIs
No systematical studies
Placebo-controlled randomized trials
Over 3000 patients
Addition of SGAs
Augmentation strategy with best evidence base
Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC (2013). Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes. PLoS Med 10, e
Citrome L. The ABC's of dopamine receptor partial agonists–aripiprazole, brexpiprazole and cariprazine: the 15‐min challenge to sort these agents out. International journal of clinical practice Nov 1;69(11):

5. Placebo-controlled randomized trials Addition of SGAs
Olanzapine, quetiapine, aripiprazole, brexpiprazole
Useful in patients who failed to respond to an SSRI
Similar effects in patients taking SNRIs
No systematical studies
Placebo-controlled randomized trials
Over 3000 patients
Addition of SGAs
Augmentation strategy with best evidence base
Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC (2013). Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes. PLoS Med 10, e
Citrome L. The ABC's of dopamine receptor partial agonists–aripiprazole, brexpiprazole and cariprazine: the 15‐min challenge to sort these agents out. International journal of clinical practice Nov 1;69(11):

6. Lower doses than used to treat psychosis
SGA dosing
Lower doses than used to treat psychosis

7. Lower doses than used to treat psychosis
SGA dosing
Lower doses than used to treat psychosis
Aripiprazole: 2.5 – 10 mg
Quetiapine: 50 – 300 mg

8. SGA dosing Lower doses than used to treat psychosis
Aripiprazole: 2.5 – 10 mg
Quetiapine: 50 – 300 mg
Potential mechanism: 5-HT2 antagonism

9. Best NNT (Number Needed to Treat)
Quetiapine
Aripiprazole
Best NNT (Number Needed to Treat)
Nelson JC, Papakostas GI (2009). Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. American Journal of Psychiatry 166, 980–91.

10. Best NNT (Number Needed to Treat)
Quetiapine
Aripiprazole
Best NNT (Number Needed to Treat)
Anxiety
Sleep difficulties
Nelson JC, Papakostas GI (2009). Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. American Journal of Psychiatry 166, 980–91.

11. Best NNT (Number Needed to Treat)
Quetiapine
Aripiprazole
Best NNT (Number Needed to Treat)
Anxiety
Sleep difficulties
Lack of motivation
Anhedonia
Nelson JC, Papakostas GI (2009). Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. American Journal of Psychiatry 166, 980–91.

12. Quetiapine Aripiprazole
Best NNT (Number Needed to Treat)
Anxiety
Sleep difficulties
Lack of motivation
Anhedonia
High side effect burden
NNH (Number Needed to Harm) twice the NNT
Nelson JC, Papakostas GI (2009). Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. American Journal of Psychiatry 166, 980–91.

13. Quetiapine Aripiprazole
Best NNT (Number Needed to Treat)
Anxiety
Sleep difficulties
Lack of motivation
Anhedonia
High side effect burden
NNH (Number Needed to Harm) twice the NNT
Sedation, weight gain
Movement disorders, anxiety
Nelson JC, Papakostas GI (2009). Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. American Journal of Psychiatry 166, 980–91.

14. Augmentation Concepts
How long?
Not clear, studies suggest several months
Discontinuation may lead to relapse
Withdraw the SGA slowly
Watch out for signs of relapse
When to augment?
When a patient has shown a partial response to an antidepressant
Pae CU, Wang SM, Han C, Lee SJ, Patkar AA, Masand PS (2015). Quetiapine augmentation for depression: dosing pattern in routine practice. International Clinical Psychopharmacology 30, 54-8.

15. Augmentation Concepts
How long?
Not clear, studies suggest several months
Discontinuation may lead to relapse
Withdraw the SGA slowly
Watch out for signs of relapse
When to augment?
When a patient has shown a partial response to an antidepressant

16. Augmentation Concepts
How long?
Not clear, studies suggest several months
Discontinuation may lead to relapse
Withdraw the SGA slowly
Watch out for signs of relapse
When to augment?
When a patient has shown a partial response to an antidepressant

17. Avoid weight gain
Avoid mirtazapine
Prefer aripiprazole or bupropion

18. Next Presentation: Use of Mood Stabilizers in TRD