Copyright Notice This presentation is copyrighted by the Psychopharmacology Institute. Subscribers can download it and use it for professional use. The contents of the presentation may be modified, but the Psychopharmacology Institute logo must remain visible in all slides.

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

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, e1001403. 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. 2015 Nov 1;69(11):1211-20.

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, e1001403. 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. 2015 Nov 1;69(11):1211-20.

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, e1001403. 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. 2015 Nov 1;69(11):1211-20.

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

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

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

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.

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.

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.

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.

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.

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.

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

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

Avoid weight gain Avoid mirtazapine Prefer aripiprazole or bupropion

Next Presentation: Use of Mood Stabilizers in TRD