1. How to Approach the Patient with Treatment Resistant Depression (TuRD) Terry L. Correll, D.O. Chief of Aerospace Psychiatric Consultation Aerospace Medicine Consultation Division United States Air Force School of Aerospace Medicine Clinical Professor of Psychiatry, Boonshoft School of Medicine

2. Please Select FALSE Statement 1. Dysthymic disorder is re-characterized as persistent depressive disorder in DSM-5 2. Dysthymic disorder used to be called depressive personality disorder in prior DSM’s 3. **Most major depressive episodes are self- limiting and typically resolve within 6-9 weeks 4. Alcohol is a powerful depressant and disruptor of sleep (light, broken sleep)

3. Please Select FALSE Statement 1.**Depressive disorders tend to improve and often resolve later on in life 2.Depression is comparable to obesity, smoking, inactivity, hyperlipidemia, hypertension, and hostility as a cardiovascular risk factor 3.Healthy lifestyle interventions are equally or more effective treatment for depression compared to antidepressants 4.Chronic use of benzodiazepines or opiates can cause depression.

4. Treatment Resistant Depression (TuRD) I mean no disrespect with this TuRD abbreviation – I try to teach in memorable ways TuRD = most challenging patients – High utilizers, somaticizers, “depressive equivalents” TuRD can be avoided Most TuRDs are not true TuRDs If true TuRD, please refer to mental health

5. Mood Disorders Idiopathic mood disorders – Major depressive disorder – Dysthymic disorder Persistent depressive disorder – Bipolar disorder Differential diagnosis: – Mood disorder due to a general medical condition – Mood disorder due to a substance – Other mood disorders Adjustment disorder with depressed mood Bereavement (removed in DSM-5) – Other: Dementia, ADHD, Normal vs. Abnormal Mood

6. Stahl S M, Essential Psychopharmacology DEPRESSION NORMAL MOOD MANIA HYPOMANIA MIXED EPISODE DYSTHYMIC DISORDER

7. Major Depressive Episode SIG E CAPS (one must be dysphoric mood or loss of interests or pleasure) Major Depressive Episode SIG E CAPS  2 weeks of 5 or more of the following (one must be dysphoric mood or loss of interests or pleasure) Sleep disturbance Loss of Interests or Pleasure Guilt, Rumination (hope/help/worth-lessness) Diminished Energy Trouble Concentrating or Impaired Memory Appetite Disturbance Psychomotor Agitation or Retardation Suicidal Ideation, Homicidal Ideation

8. Manic Episode SIG E CAPS (“Driven by extreme energy like on cocaine”) Manic Episode SIG E CAPS  1 week (“Driven by extreme energy like on cocaine”) Sleep disturbance INCREASED Interests or Pleasure NO Guilt, Rumination INCREASED Energy Trouble Concentrating or Impaired Memory Appetite Disturbance Psychomotor Agitation Suicidal Ideation, Homicidal Ideation

9. Dysthymic Disorder Persistent Depressive Disorder Depressed mood for more days than not for at least 2 yrs with 2 (or more) of the following: Appetite Disturbance Trouble Concentrating or Making Decisions Diminished Energy Sleep disturbance Low Self-esteem Feelings of Hopelessness (social, cognitive, and motivational problems)

10. Course of (Unipolar) Major Depressive Illness

11. Dysthymic Disorder

12. Double Depression

14. Morbidity and Mortality in Major Depression Suicide – 10-15% Cardiovascular risk – comparable to obesity, smoking, inactivity, hyperlipidemia, hypertension, hostility Cerebrovascular risk Poorer self-care, adherence to medical regimen for any medical illness

15. Stahl S M, Essential Psychopharmacology acute 6 - 12 weeks continuation 4-9 months maintenance 1 or more years TIME DEPRESSION NORMAL MOOD RELAPSE RECURRENCE

17. Some General Medical Conditions that May Cause or Mimic Depression Cardiovascular – infarct, congestive heart failure Endocrine – adrenal insufficiency, hypothyroidism Nutritional – Vitamin B12, D, folate, thiamine deficiency Metabolic – anemia, post-ictal, sleep apnea, end-stage renal disease, hypercalcemia, hepatitis, hypoglycemia Infectious – HIV, encephalitis, aseptic meningitis, post-viral states, systemic Neurodegenerative – Parkinson’s / Huntington’s Tumor – Primary cerebral, pancreatic CA, systemic neoplasms

21. Some Drugs that May Cause or Mimic Depression Corticosteroids Anabolic steroids Anticonvulsants First generation antipsychotics Centrally-acting antihypertensives Alcohol, sedatives, narcotics/opioids Stimulant withdrawal

22. Treatments for Mood Disorders Non-medication remedies Psychotherapy Light therapy Antidepressant medications Antidepressant augmentors (adjuncts) Electroconvulsive therapy (ECT)

23. Treatment Resistant Depression (TuRD) Moderate >>>

24. Treatment Resistant Depression (TuRD) May be considered TuRD – When not returning to 100% best baseline – After adequate dose, duration, and compliance Before labeling patient a TuRD – Reassess diagnosis – Assess medication compliance – Consider overwhelming life struggles/stressors – Consider etiology/exacerbation by medical or substance abuse conditions

26. Antidepressant Medications How to select

27. Antidepressant Medications How to select Successful/unsuccessful prior trial Proper dose, duration, compliance, lifestyle? Family member’s successful/unsuccessful prior trial Strong belief regarding certain treatment Positive/negative expectation? Direct to consumer commercials Affordabilty

28. Antidepressant Medications Monoamine Oxidase Inhibitors (MAOIs) –phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan), selegeline patch (Emsam) Tricyclic Antidepressants (TCAs) –amitriptyline (Elavil), nortriptyline (Pamelor), desipramine (Norpramin), imipramine (Tofranil), clomipramine (Anafranil) Selective Serotonin Reuptake Inhibitors (SSRIs) –fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro) Mixed/Other Mechanism Antidepressants –trazodone (Desyrel), buproprion (Wellbutrin), venlafaxine (Effexor), mirtazepine (Remeron), duloxetine (Cymbalta), desvenlafaxine (Pristiq)

29. Antidepressant Medications Monoamine Oxidase Inhibitors (MAOIs) –phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan), selegeline patch (Emsam) Tricyclic Antidepressants (TCAs) –amitriptyline (Elavil), nortriptyline (Pamelor), desipramine (Norpramin), imipramine (Tofranil), clomipramine (Anafranil) Selective Serotonin Reuptake Inhibitors (SSRIs) –fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro) Mixed/Other Mechanism Antidepressants –trazodone (Desyrel), buproprion (Wellbutrin), venlafaxine (Effexor), mirtazepine (Remeron), duloxetine (Cymbalta), desvenlafaxine (Pristiq)

31. Antidepressant Medications Switching antidepressant (ATD) After 4 weeks of taking medication regularly without any “toxic distractors” and there is zero improvement Toxic distractors are life stressors or substance abuse Surprising that switching to any reasonable antidepressant will give comparable rates of improvement Typical to get ~75% response rate with ATD Typical to get ~50% remission rate with ATD Follow up clinical pearl “What has improved/gone better since we last met?” “What have you done differently (better – to help yourself)?” Validates they are “large and in charge” of their life They are “driving the bus” We are glad to give helpful instructions along the way

32. Pharmacologic Augmentation Strategies Second antidepressant Trazodone Lithium Thyroid (T3) augmentation – Triiodothyronine Stimulants – methylphenidate (Ritalin), dextroamphetamine (Dexedrine) Atypical antipsychotics – risperidone (Risperdal), o lanzepine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify) Others – b uspirone (BuSpar), folate, Omega-3 fatty acids

33. Electroconvulsive Therapy (ECT) Most efficacious treatment Most rapid onset of action Effective for severe depression, mania May be treatment of choice for severe depression with psychosis, pregnancy, suicidality, catatonia, geriatrics, multiple medical comorbidities Requires general anesthesia Memory loss, cardiovascular risk Can be done as outpatient

34. Other Non-medication Treatments Healthy Lifestyle Interventions

35. Other Non-medication Treatments Healthy Lifestyle Interventions – Multivitamin/multimineral – Exercise – Deep Breathing – Rest/Relaxation/SLEEP – Prayer/meditation – Participate in healthy spiritual practices, social relations, meaningful pursuits in life – Fish Oil – Avoid toxins – alcohol, drugs, excessive caffeine, negative thoughts, people, situations

37. Light Therapy (Phototherapy) For Major Depression with Seasonal Pattern (or Seasonal Affective Disorder - SAD) Helpful with all types of depression Useful in women who are pregnant, nursing ~20 minutes daily – Walk outside hand in hand with loved one Search for Seasonal Affective Disorder (SAD) bulbs online

38. Other Non-medication Treatments Decide to create or cultivate positive situations that fulfill your personal needs, encourage growth, and promote self-esteem and self-development Become involved with people who have a positive attitude, who share in giving and receiving, and who show their love (find a mentor, growth seeking friends) Meaningful Activity/Work/Education/Volunteering: – Find a form of service that contributes to your sense of purpose and identity Schedule humorous and FUN times

39. Other Non-medication Treatments

40. Individual psychotherapy Group therapy Journaling Bibliotherapy (Bible, sacred texts, Feeling Good Book, online reading, Youtube, TED talks…ANY SOURCE they personally select) Authentichappiness.org Goals & Visions for the Future – Visualize desirable changes there in your life and make goals for working toward them – Write your goals down and refer to them often

41. Treatment Resistant Depression (TuRD) I mean no disrespect with this TuRD abbreviation – I try to teach in memorable ways TuRD = most challenging patients – High utilizers, somaticizers, “depressive equivalents” TuRD can be avoided Most TuRDs are not true TuRDs If true TuRD, please refer to mental health

42. Conclusion Depression very common & disabling Avoid TuRD like the plague Rule out general medical causes or substances causing the mood disorder Assess for mania/hypomania Maximize antidepressant – Dose and duration – And COMPLIANCE Recommend healthy lifestyle interventions Psychotherapy?

43. QUESTIONS? COMMENTS terry.correll@wright.edu terry.correll.1@us.af.mil

44. Please Select FALSE Statement 1. Dysthymic disorder is re-characterized as persistent depressive disorder in DSM-5 2. Dysthymic disorder used to be called depressive personality disorder in prior DSM’s 3. **Most major depressive episodes are self- limiting and typically resolve within 6-9 weeks 4. Alcohol is a powerful depressant and disruptor of sleep (light, broken sleep)

45. Please Select FALSE Statement 1.**Depressive disorders tend to improve and often resolve later on in life 2.Depression is comparable to obesity, smoking, inactivity, hyperlipidemia, hypertension, and hostility as a cardiovascular risk factor 3.Healthy lifestyle interventions are equally or more effective treatment for depression compared to antidepressants 4.Chronic use of benzodiazepines or opiates can cause depression.

46. Thank you for your time and attention terry.correll@wright.edu terry.correll.1@us.af.mil