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Treatment of resistant depression


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resistant depression: a prison

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Treatment of resistant depression

  2. 2. Depression: a prison ► By the year 2020, unipolar major depression is projected to be the second leading cause of disability- adjusted life years (DALYS) all over the world. ► Depressive disorders have great impact morbidity, health care utilization, and medical costs. ► Despite advances in psychopharmacology, less than half of patients beginning a course of antidepressant treatment will reach remission with that treatment Dialogues in Clinical Neuroscience - Vol 6 . No. 1 . 20
  3. 3. Treatment resistant depression ► A significant proportion of depressed patients either do not respond or continue to have residual symptoms despite treatment with antidepressants. ► Major depression that does not resolve with adequate antidepressant treatment is termed Treatment-resistant depression (TRD). Dialogues in Clinical Neuroscience - Vol 6 . No. 1 . 20
  4. 4. ANNALS OF CLINICAL PSYCHIATRY 2014;26(3):222-232
  5. 5. European staging method ANNALS OF CLINICAL PSYCHIATRY 2014;26(3):222-232
  6. 6. Impact of TRD TRD is associated with extensive use of depression-related and general medical services and poses a substantial economic burden. TRD was also associated with use of 1.4 to 3 times more psychotropic medications (including antidepressants). Patients in the hospitalized TRD group had over 6 times the mean total medical costs of non-TRD patients Treatment-resistant patients were at least twice as likely to be hospitalized (general medical and depression related) and had at least 12% more outpatient visits. Dialogues in Clinical Neuroscience - Vol 6 . No. 1 . 20
  7. 7. Prevalence of TRD  TRD is the most debilitating or distressing form of MDD.  Multiple studies found that approximately 20% of depressed patients continued to suffer from depression for up to 2 years after initial onset of a major depressive episode (MDE).  Despite the completion of multiple antidepressant medication, 15% of patients diagnosed with MDD will continue to suffer from depression.  Even among patients who experience a significant reduction in their depressive symptoms following an adequate antidepressant trial, 60% to 70% of these patients fail to obtain complete remission of depressive symptoms.
  8. 8. Factors contributing to TRD ► Unrecognized comorbid medical or psychiatric illness, ► The use of concomitant medications, intolerance ► Inadequate treatment of earlier episodes ► Greater number of somatic symptoms and reported history of childhood emotional abuse and sequelae of that abuse ► Psychotic and melancholic depression ► Noncompliance (up to 50% of patients do not take the medication as prescribed, and tend to stop treatment when symptoms remit) ► Individual differences in drug metabolism ► Nutritional status of the patient (deficiencies in folate, thiamine, vitamin B6, vitamin B12, copper, and zinc) ► Psychosocial stressors. Dialogues in Clinical Neuroscience - Vol 6 . No. 1 . 20
  9. 9. Absolute and relative treatment resistance ► Absolute treatment resistance: Failure to respond to one adequate antidepressant trial (i.e, 20-40 mg fluoxetine or its equivalent, or 4 weeks of 150 mg imipramine or its equivalent) ► Relative treatment resistance: nonresponse to an inadequate treatment. Dialogues in Clinical Neuroscience - Vol 6 . No. 1 . 20
  10. 10. Treatment-refractory depression ► Failure to respond to two drugs of different pharmacological classes, each used in an adequate dose for an adequate duration. ► The term Treatment-Refractory Depression also has been used to describe and/or refer to patients experiencing TRD. ► Although the term REFRACTORY suggests a greater degree of resistance, the terms RESISTANCE AND REFRACTORY appear to represent overlapping constructs and have been used interchangeably within the literature Annals of Clinical Psychiatry Vol. 26 No. 3 2014 Dialogues in Clinical Neuroscience - Vol 6 . No. 1 . 20
  11. 11. Brain imaging studies ► Patients with chronic TRD had reduced gray matter density in the left temporal cortex including the hippocampus, with a trend toward reduction in the right hippocampus. ► SPECT: significant increase in hippocampus amygdala activity ► PET scan: cingulate hypometabolism Dialogues in Clinical Neuroscience - Vol 6 . No. 1 . 20
  12. 12. Am Fam Physician. 2009;80(2):167-172
  13. 13. Approaches in the management of TRD ► Optimization: Increase dose of antidepressants ► Augmentation strategy: adding another agent to an ongoing antidepressant treatment that has failed. ► Combination strategies: TCAs and SSRIs, TCAs and MAOIs, bupropion and SSRIs, anticonvulsants and antidepressants, and benzodiazepines and antidepressants. ► However, SSRIs, venlafaxine, or clomipramine should not be combined with MAOIs and the MAOI and TCA combination should be used with caution. Dialogues in Clinical Neuroscience - Vol 6 . No. 1 . 20
  14. 14. Drugs used in augmentation approach for TRD  Lithium  Bupropion/mirtazepine combination therapy  Anticonvulsants  Thyroid hormones (T3)  Dopamine agonist (pramipraxole)  pindolol  Buspirone  Modafinil  Testosterone, oestrogen  Burpenorphine, SAMe, Inositol
  15. 15. Switching strategies ► Switching involves stopping the antidepressant to which the patient is not responding and switching to another antidepressant, usually from a different class ► The options for SSRI non-responders: bupropion, nefazodone, venlafaxine, tianeptine, and mirtazapine. ► MAOI can be used in TCA- or SSRI-resistant patients. However, Dietary restrictions are essential and an appropriate washout period is required after SSRI discontinuation before initiating treatment with MAOIs. Dialogues in Clinical Neuroscience - Vol 6 . No. 1 . 20
  16. 16. STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study, a seven-year randomized controlled trial (RCT) that evaluated medication switching and augmentation in 3,671 outpatients with unipolar depression. Am Fam Physician. 2009;80(2):167-172
  17. 17. Am Fam Physician. 2009;80(2):167-172
  18. 18. Other treatment modalities ► ECT: Potent, though underutilized, option for resistant depression. ► Newer biological approaches: repetitive transcranial magnetic stimulation (rTMS) and vagus nerve stimulation ► Novel psychopharmacological agent: S-adenosylmethionine (SAMe), second-messenger system modulators (inositol), and neuroendocrine system–modulating agents, eg, dexamethasone ► Cognitive behavioural therapy Dialogues in Clinical Neuroscience - Vol 6 . No. 1 . 20
  19. 19. Comparison of devices for Treatment Resistant Depression (TRD). ECT : Electroconvulsive Therapy; TMS Transcranial Magnetic Stimulation; VNS : Vagal Nerve Stimulation, DBS; Deep Brain Stimulation Cusin and Dougherty Biology of Mood & Anxiety Disorders 2012, 2:14
  20. 20. Future treatment options Patient Preference and Adherence 2012:6 369–388