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Experimental Treatments: Anti-inflammatory Agents Prof. Philip Cowen Professor of Psychopharmacology Department of Psychiatry University of Oxford, UK

Experimental treatments Focus: repurposing treatments Psychiatric research is slow

Experimental treatments Focus: repurposing treatments Psychiatric research is slow

Anti-inflammatory agents Raison CL, Miller AH (2011). Is depression an inflammatory disorder? Current Psychiatry Reports 13, 467-75.

Anti-inflammatory agents Peripheral markers of inflammation C-reactive protein (CRP) Interleukin-6 (IL-6) Tumor Necrosis Factor (TNF) Raison CL, Miller AH (2011). Is depression an inflammatory disorder? Current Psychiatry Reports 13, 467-75.

Anti-inflammatory agents Peripheral markers of inflammation C-reactive protein (CRP) Interleukin-6 (IL-6) Tumor Necrosis Factor (TNF) Raison CL, Miller AH (2011). Is depression an inflammatory disorder? Current Psychiatry Reports 13, 467-75.

Anti-inflammatory agents High risk of depressive symptoms Patients who receive interferon Udina M, Castellví P, Moreno-España J, Navinés R, Valdés M, Forns X, Langohr K, Solà R, Vieta E, Martín-Santos R (2012). Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis. Journal of Clinical Psychiatry, 73, 1128-38.

Anti-inflammatory agents Anti-inflammatory drugs Treatment-resistant patients Evidence of inflammatory markers High risk of depressive symptoms Patients who receive interferon Udina M, Castellví P, Moreno-España J, Navinés R, Valdés M, Forns X, Langohr K, Solà R, Vieta E, Martín-Santos R (2012). Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis. Journal of Clinical Psychiatry, 73, 1128-38.

Anti-inflammatory agents Anti-inflammatory drugs Treatment-resistant patients Evidence of inflammatory markers High risk of depressive symptoms Patients who receive interferon Udina M, Castellví P, Moreno-España J, Navinés R, Valdés M, Forns X, Langohr K, Solà R, Vieta E, Martín-Santos R (2012). Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis. Journal of Clinical Psychiatry, 73, 1128-38.

Antidepressant response and CRP levels Patients with MDD Escitalopram Nortriptyline No difference in outcome

Antidepressant response and CRP levels Patients with MDD Escitalopram Nortriptyline

Antidepressant response and CRP levels Patients with MDD Escitalopram Nortriptyline No difference in outcome

Antidepressant response and CRP levels Patients with MDD Baseline CRP levels > 2 mg/L < 1 mg/L

Antidepressant response and CRP levels Patients with MDD Baseline CRP levels > 2 mg/L < 1 mg/L Better response with nortriptyline Better response with escitalopram Uher R, Tansey KE, Dew T, Maier W, Mors O, Hauser J, Dernovsek MZ, Henigsberg N, Souery D, Farmer A, Peter M (2014). An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. American Journal of Psychiatry 171, 1278-86.

Antidepressant response and CRP levels Patients with MDD Baseline CRP levels > 2 mg/L < 1 mg/L Better response with nortriptyline Better response with escitalopram Uher R, Tansey KE, Dew T, Maier W, Mors O, Hauser J, Dernovsek MZ, Henigsberg N, Souery D, Farmer A, Peter M (2014). An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. American Journal of Psychiatry 171, 1278-86.

Antidepressant response and CRP levels C-reactive protein (CRP) Readily available Worthwhile measuring in patients with resistant depression

Antidepressant response and CRP levels C-reactive protein (CRP) Readily available Worthwhile measuring in patients with resistant depression Could suggest nortriptyline might be an option

Role for specific anti-inflammatory agents Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH (2013). A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry, 70, 31-41.

Role for specific anti-inflammatory agents TNF-alpha blocker: Infliximab as add-on No better than placebo Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH (2013). A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry, 70, 31-41.

Role for specific anti-inflammatory agents TNF-alpha blocker: Infliximab as add-on No better than placebo In patients with high baseline levels of CRP Infliximab was most effective Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH (2013). A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry, 70, 31-41.

Role for specific anti-inflammatory agents TNF-alpha blocker: Infliximab as add-on No better than placebo In patients with high baseline levels of CRP Infliximab was most effective Post-hoc analysis Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH (2013). A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry, 70, 31-41.

Role for specific anti-inflammatory agents Useful as adjunct to first-line treatment Meta-analysis: celecoxib Unclear evidence In clinical practice: Consider contraindications and side effects Celecoxib Na KS, Lee KJ, Lee JS, Cho YS, Jung HY (2014). Efficacy of adjunctive celecoxib treatment for patients with major depressive disorder: a meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry 48, 79-85.

Role for specific anti-inflammatory agents Useful as adjunct to first-line treatment Meta-analysis: celecoxib Unclear evidence In clinical practice: Consider contraindications and side effects Celecoxib Na KS, Lee KJ, Lee JS, Cho YS, Jung HY (2014). Efficacy of adjunctive celecoxib treatment for patients with major depressive disorder: a meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry 48, 79-85.

Role for specific anti-inflammatory agents Useful as adjunct to first-line treatment Meta-analysis: celecoxib Unclear evidence In clinical practice: Consider contraindications and side effects Celecoxib Na KS, Lee KJ, Lee JS, Cho YS, Jung HY (2014). Efficacy of adjunctive celecoxib treatment for patients with major depressive disorder: a meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry 48, 79-85.

Key Points Inflammatory processes: Celecoxib May play an important role in depression Celecoxib Might be helpful as adjunct to first-line treatment It hasn’t been systematically studied yet

Key Points Inflammatory processes: Celecoxib May play an important role in depression Celecoxib Might be helpful as adjunct to first-line treatment It hasn’t been systematically studied yet

Key Points Inflammatory processes: Celecoxib May play an important role in depression Celecoxib Might be helpful as adjunct to first-line treatment It hasn’t been systematically studied yet

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