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

3. Experimental treatments
Focus: repurposing treatments
Psychiatric research is slow

4. Experimental treatments
Focus: repurposing treatments
Psychiatric research is slow

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

6. 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,

7. 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,

8. 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,

9. 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,

10. 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,

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

12. Antidepressant response and CRP levels
Patients with MDD
Escitalopram
Nortriptyline

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

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

15. 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,

16. 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,

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

18. 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

19. 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,

20. 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,

21. 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,

22. 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,

23. 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,

24. 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,

25. 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,

26. 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

27. 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

28. 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

29. Next Presentation: Ketamine