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Drug Treatment of Resistant Depression
- 1. DRUG TREATMENT OF RESISTANTDEPRESSION DR SUSHIL KUMAR S V, MB BS, MD (PSYCHIATRY), MHA, FIPS, ASSISTANT PROFESSOR, DEPT. OF PSYCHIATRY SS INSTITUTE OF MEDICAL SCIENCES, DAVANGERE, INDIA
- 2. INTRODUCTION • Degree ofsymptom reduction is related to functioning • Partial responders with residual symptoms have a poorer prognosis compared to complete remitters
- 3. CATEGORIES OF RESPONSE •Response without remission (< 50% but > 25% from baseline scores) • Non-response • Relapse (< 6 months of acute response) • Recurrences ( > 6 months) • Recovery (8 week period) • Breakthrough (Poop out)
- 4. CATEGORIES OF RESPONSE •Residual symptoms: irritability, social functioning, dysfunctional attitudes, depressive cognitions • Complete remission is the optimal goal (Trivedi &Kleiber, 2001) • HAMD Score of < 7
- 5. DEFINITION OF TRD •Failure to respond to 2 adequate trials of different chemical classes (Sourey et al, 1999) • Several Staging Methods -- CPMP Guidelines -- Thase & Rush (1997) -- Massachusetts General Hospital
- 6. DEFINITION OF TRD •Adequate dose & adequate duration • Treatment intolerance (Schatzberg et al, 1983) • 20% are treatment intolerant
- 7. FACTORS RELATED TOTRD • Patient and Treatment related factors • Diagnosis -- Bipolarity -- Psychotic depression -- Atypical depression -- Co-morbid conditions
- 8. STRATEGIES FOR TRD •Optimizing the dose • Augmentation • Combination • Switching • No conclusive data identifies the optimal strategy (Nelson, 2003)
- 9. OPTIMIZING DOSE • Mostdo not receive adequate trial (Keller et al, 1986; Dawson et al, 1999) • Pseudo Resistant (Sackeim, 2001) • Failure to use adequate dose for adequate duration have an iatrogenic effect in increasing resistance
- 10. OPTIMIZING DOSE • Dose-300 mg / day of imipramine • SSRI- Flat dose response curve • Duration- 4-6 weeks ; Extending to 10-12 weeks ( Nemeroff, 2001; Thase & Rush, 1995)
- 11. OPTIMIZING DOSE • StructuredAntidepressant Treatment History Form (Sackeim, 2001) • Initial Choice of medication may depend on depressive symptoms • Mirtazapine for insomnia; Venlafaxine for anxious depression (Meoni et al, 2004) • Venlafaxine > SSRI
- 12. AUGMENTATION • Adding anagent that is not a standard antidepressant • Lithium (Joffe et al, 1993; Nierenberg et al, 2003) • Triiodothyronine (T3 > T4) (Joffe et al, 1993)
- 13. AUGMENTATION • Mood Stabilizers( Lamotrigine, Valproic acid, Carbamazepine) • Pindolol (Nelson 2003; Fava 2001) • Buspirone (Dimitriou & Dimitriou, 1998; Landen et al, 1998)
- 14. AUGMENTATION • Atypical antipsychotics(Olanzapine, clozapine, Risperidone, Aripiprazole) • Psychostimulants (Methylphenidate) (Thase & Rush, 1995) • Lithium has been best studied
- 15. COMBINATION STRATEGIES • Combiningone antidepressant with another antidepressant • SSRI+ Mirtazapine (de la Gandara et al, 2005) • SSRI+ Reboxetine ( Fava, 2001) • SSRI+ Bupropion (STAR٭D) • SSRI+ TCA (Nelson et al, 1991)
- 16. COMBINATION STRATEGIES • Venlafaxine+ Bupropion (Keller, 2005) • Fluoxetine + Olanzapine (Nemeroff, 2005) • SSRI + Risperidone (Nemeroff, 2005) • AD + Antipsychotic at 400 mg/ day ofCPZ
- 17. SWITCHING STRATEGIES • TCA►TCA (Thase & Rush, 1995; Nierenberg et al, 1990; Shelton, 1999) • TCA ►Newer Heterocyclics (Thase & Rush,1995) • TCA►SSRI (Thase & Rush, 1995)
- 18. SWITCHING STRATEGIES • SSRI►TCA(Fava, 2001) • SSRI►SNRI (Fava,2001, Poirier&Boyer,1999) • SSRI►Bupropion (Fava et al, 2003) • SSRI►SSRI (Zarate et al, 1996) • SSRI►MAOI (Thase & Rush, 1995)
- 19. SWITCHING STRATEGIES • SSRI→SNRI-------30-60% (Poirier & Boyer, 1999) • SSRI→ SSRI------ 40-50% (Zarate et al, 1996) • TCA → SSRI------ 30-50% (Thase & Rush,1995) • TCA → TCA------- Poorer Response
- 20. ALGORITHM • STAR٭D (Rushet al, 2003) • Level 1- Citalopram • Level 2- Switch to Bupropion, Sertraline, Venlafaxine Augment -Bupropion,Buspirone
- 21. ALGORITHM • Level 3-Switch to Mirtazapine, TCA Augment- Lithium / T3 • Level 4- Switch to Tranylcypromine Augment- Mirtazapine + SNRI
- 22. ALGORITHM • Level 1-SSRI • Level 2- SSRI or SNRI • Level 3- Augment with Bupropion, Lithium • Treatment with MAOI or Lithium before ECT (Keller, 1995)
- 23. CONCLUSIONS • Correct Diagnosis •Therapeutic Goal– Full Remission • Optimizing initial treatment • Augmenting and Combination strategies in development • Factors resulting in TRD