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Node 1 Newer SGAs: Could They Be First-Line? David N. Osser, MD Associate Professor of Psychiatry Harvard Medical School Brockton Division of the VA Boston Healthcare System General Editor - Psychopharmacology Algorithm Project Harvard South Shore Residency Training Program

I have free samples, shouldn’t I use them? Unclear role

Equivalent to ziprasidone (one study) Iloperidone (Fanapt) Initially rejected in 2008 Approved in 2009 Equivalent to ziprasidone (one study)

Equivalent to ziprasidone (one study) Iloperidone (Fanapt) Initially rejected in 2008 Approved in 2009 Equivalent to ziprasidone (one study) Marino, J., & Caballero, J. (2010). Iloperidone for the treatment of schizophrenia. Annals of Pharmacotherapy, 44(5), 863-870.

Equivalent to ziprasidone (one study) Iloperidone (Fanapt) Initially rejected in 2008 Approved in 2009 Equivalent to ziprasidone (one study) No role in algorithm

Iloperidone (Fanapt) Low incidence of EPS More weight gain than risperidone QTc prolongation Twice-daily administration

Sublingual administration Asenapine (Saphris) Approved in 2009 Sublingual administration Practicality? Only 5% absorbed if swallowed Evidence One negative and two positive published studies Unpublished negative studies

Sublingual administration Asenapine (Saphris) Approved in 2009 Sublingual administration Practicality? Only 5% absorbed if swallowed Evidence One negative and two positive published studies Unpublished negative studies Janicak, P. G., & Rado, J. T. (2009). Asenapine: a review of the data. Psychopharm Review, 44(12), 89-95.

Sublingual administration Asenapine (Saphris) Approved in 2009 Sublingual administration Practicality? Only 5% absorbed if swallowed Evidence One negative and two positive published studies Unpublished negative studies Kane, J. et at (2010). Efficacy and safety of asenapine in a placebo-and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia. Journal of clinical psychopharmacology, 30(2), 106-115. Ashih HW. Saphris and Fanapt: two new antipsychotics. Carlat Psychiatry Rep 2009;7:1Y3

Potential role in algorithm Lurasidone (Latuda) Effectiveness It may be as effective as aripiprazole, quetiapine and ziprasidone Seems less effective than olanzapine Potential role in algorithm Mild side effects profile No studies in first-onset patients Potkin, S. G., Ogasa, M., Cucchiaro, J., & Loebel, A. (2011). Double-blind comparison of the safety and efficacy of lurasidone and ziprasidone in clinically stable outpatients with schizophrenia or schizoaffective disorder. Schizophrenia research, 132(2), 101-107. Meltzer, H. Y., Cucchiaro, J., Silva, R., Ogasa, M., Phillips, D., Xu, J., ... & Loebel, A. (2011). Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo-and olanzapine-controlled study. American Journal of Psychiatry, 168(9), 957-967.

Potential role in algorithm Lurasidone (Latuda) Effectiveness It may be as effective as aripiprazole, quetiapine and ziprasidone Less effective than olanzapine Potential role in algorithm Mild side effects profile No studies in first-onset patients Potkin, S. G., Ogasa, M., Cucchiaro, J., & Loebel, A. (2011). Double-blind comparison of the safety and efficacy of lurasidone and ziprasidone in clinically stable outpatients with schizophrenia or schizoaffective disorder. Schizophrenia research, 132(2), 101-107. Meltzer, H. Y., Cucchiaro, J., Silva, R., Ogasa, M., Phillips, D., Xu, J., ... & Loebel, A. (2011). Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo-and olanzapine-controlled study. American Journal of Psychiatry, 168(9), 957-967.

Potential role in algorithm Lurasidone (Latuda) Effectiveness It may be as effective as aripiprazole, quetiapine and ziprasidone Less effective than olanzapine Potential role in algorithm Mild side effects profile No studies in first-onset patients

Brexpiprazole (Rexulti) Approved in 2015 Schizophrenia Adjunct to antidepressants for MDD Pharmacology Less intrinsic activity than aripiprazole at D2 receptors D2 partial agonist Rexulti (Brexpiprazole) [Prescribing Information] Otsuka America Pharmaceutical, Inc., Rockville, MD .

Brexpiprazole (Rexulti) Approved in 2015 Schizophrenia Adjunct to antidepressants for MDD Pharmacology Less intrinsic activity than aripiprazole at D2 receptors D2 partial agonist Citrome, L. (2015). 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, 69(11), 1211-1220.. .

Cariprazine (Vraylar) Approved in 2015 Schizophrenia Mania Pharmacology D2 partial agonist Citrome, L. (2015). 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, 69(11), 1211-1220.. .

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