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Role of Noradrenaline Reuptake Inhibitor (NaRI) in Depression

Role of Noradrenaline Reuptake Inhibitor (NaRI) in Depression. Unipolar depression: facts and figures. Epidemiological Statistics Depression is 1.5- 3 times as common in females as in males Twelve-month prevalence rate is 5% and lifetime risk is 15%

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Role of Noradrenaline Reuptake Inhibitor (NaRI) in Depression

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  1. Role of Noradrenaline Reuptake Inhibitor (NaRI) in Depression

  2. Unipolar depression: facts and figures • Epidemiological Statistics • Depression is 1.5- 3 times as common in females as in males • Twelve-month prevalence rate is 5% and lifetime risk is 15% • Lifetime prevalence of suicide is approximately 2% (hospitalized cohorts 10-15%) • Illness Characteristics • Mean age of onset is 27 years, but 40% have 1st episode = 20 years • Average duration of episodes is 3-4 months • forty percent experience recurrence within 12 months • Treatment Responsiveness • Antidepressant/ psychological interventions are effective in around 50% • Thirty-three percent fail to recovery

  3. Treatment Phases Remission Recovery Recurrence Relapse Asymptomatic X X Response Symptoms X Syndrome Depression:Treatment Phases Maintenance Acute Continuation 4-9 Months 12 Weeks 1 or More Years Kupfer DJ. J Clin Psychiatry. 1991;52(suppl):28-34; AHCPR. Rockville, Maryland: U.S. Dept of Health and Human Services; 1993. Publication 93-0551.

  4. Serotonin and Norepinephrine in Depression Limbic System Prefrontal Cortex Locus Coeruleus (NE source) Raphe Nuclei (5-HT source) Kaplan and Sadock, eds. Comprehensive Textbook of Psychiatry 6th ed.Baltimore: Williams & Wilkins; 1995; p 27-28.

  5. Monoamine and Differential effects

  6. The Mechanism of Action of Antidepressant

  7. DSM-IV and ICD-10 major depressive disorder diagnostic criteria: symptoms

  8. SSRI are generally better tolerated than other classes of antidepressant and suitable first-line. Sexual dysfunction and GI symptoms arecommon. Many SSRI (especially fluoxetine and paroxetine) cause significant CYP450 inhibition and care is needed when co-prescribed with other medication. • NaRI (reboxetine) is suitable first-line. Common side effect include insomnia and agitation • NaSSA (mirtazapine) is suitable first-line option, is associated with weight gain and drowsiness

  9. Edronax Profile

  10. Reboxetine (Edronax) Noradrenaline Reuptake Inhibitor (NaRI) Onset 10-14 days Metabolism CYP3A4 Half life 12-14 hrs.

  11. Pharmacokinetic parameters • Edronax: • Noradrenaline Reuptake Inhibitor (NRI) • Bioavailability 94% • CMAX 111 ng/ml • TMAX 2 hr • Vd 34 L/kg • Protein binding 96% • Metabolism pathway CYP3A4 • % unchanged in urine 9% • Time to steady state 3-5 days Scates AC, Doraiswamy PM. Ann Pharmacother 2000;34:1302-12

  12. Edronax # Recommended starting dose is 4 mg twice daily # Maximum daily dose of 10 mg given in divided odses # Elderly>65yr 2 mg bid, may be increased up to 6 mg/day after 3 wk # Patient w/ renal or moderate to severe hepatic insufficiency 2 mg bid

  13. Reboxetine (Edronax)

  14. Reboxetine (Edronax)

  15. CYP450 isozymes involved in themetabolism of second-generation antidepressantsand the isozymes they inhibit. Spina et al, 2008.

  16. Edronax in MDD

  17. Mean HAM-D, MADRS and Zung self-Rating Depression Scale During the 6-Weeks Marcio Versiani et al: Reboxetine a Unique Selective NRI. J Clin Psychiatry 60:6, June 1999

  18. Cumulative Probability of RelapseDuring the Long-Term Phase Marcio Versiani et al: Reboxetine a Unique Selective NRI. J Clin Psychiatry 60:6, June 1999

  19. Compare with Other Antidepressant

  20. A meta-analysis of clinical trials comparing reboxetine, a Norepinephrine Reuptake Inhibitor, with selective serotonin reuptake inhibitors for the Treatment of major depressive disorder

  21. A meta-analysis of clinical trials comparing reboxetine, a Norepinephrine Reuptake Inhibitor, with selective serotonin reuptake inhibitors for the Treatment of major depressive disorder(cont.)

  22. The Efficacy of Reboxetine as an Antidepressant, a Meta-analysis of Both Continuous (Mean HAM-D Score) and Dichotomous (Response Rate) Outcomes

  23. Edronax vs. Fluoxetine

  24. Noradrenaline selective versus Serotonin selective antidepressant therapy: differential effect on social functioning 168 adult outpatients with DSM-IV major depressive disorder (MDD) Reboxetine 8-10 mg/day or Fluoxetine 20-40 mg/day Efficacy Measures: HAM-D, CGI, SASS Journal of Clinical Psychopharmacology 1997, 7:S17-23

  25. Switching to Reboxetine: An Efficacy and Safety Study in Patients With Major Depressive Disorder Unresponsive to Fluoxetine 128 adult outpatients with DSM-IV major depressive disorder (MDD) who not respond to at least 6-12 weeks of fluoxetine treatment Switching to Reboxetine 4mg twice daily (max dose 10 mg/day) Efficacy Measures: HAM-D 17 item, CGI Journal of Clinical Psychopharmacology 2007, 23:4; 365-369.

  26. Mean HAM-D-25 and HAM-D-17 scores, After switching to Reboxetine 8-10 mg/day Journal of Clinical Psychopharmacology 2007, 23:4; 365-369.

  27. Percentage of Patient after switching to Reboxetine Journal of Clinical Psychopharmacology 2007, 23:4; 365-369.

  28. Treatment Resistance Depression (TRD)

  29. TRD, 79 depressive outpatients MDD who not responded mono- therapy with duloxetine • Plus Reboxetine 2-8 mg/day, prospective 12-weeks • Assessment with Hamilton Depression Rating Scale (HDRS) and Clinical Global Impression-Improvement (CGI-I) J Psychopharmacol OnlineFirst, published on March 12,2009 as doi:10.1177

  30. Score in HDRS and CGI-I and number (percentage) of patients improving (CGI-I <4) J Psychopharmacol OnlineFirst, published on March 12,2009 as doi:10.1177

  31. Frequency (percentage) of adverse events after addition of reboxetine J Psychopharmacol OnlineFirst, published on March 12,2009 as doi:10.1177

  32. Hypothetical model showing differential actions of antidepressant agents on symptoms of positive and negative affect Nutt DJ, 2008.

  33. Summary Edronax (Reboxetine) Noradrenaline Reuptake Inhibitor (NRI) Efficacy equivalent other antidepressant TRD case can combine with other drug CANMAT: First-line Recommendation

  34. Thank you & Questions

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