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Understanding Major Depression: Causes, Symptoms, and Treatment

Explore the causes, symptoms, and treatment options for major depression, a common mental health disorder. Discover how medication, psychotherapy, and other therapies can help individuals achieve remission and improve their quality of life.

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Understanding Major Depression: Causes, Symptoms, and Treatment

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  1. Kerry Pierce, MDBoard CertifiedAdult and Geriatric PsychiatryMidMichigan Physicians Group

  2. Major Depression, Seasonal Depression, Winter Blahs

  3. Major Depressive Disorder

  4. Depression: Emotional and Physical Signs Emotional Physical • Hopelessness • Low self-esteem • Impaired memory • Difficulty concentrating • Anhedonia • Anxiety • Preoccupation with negative thoughts • Fatigue • Vague abdominal pain • Vague joint pain • Headache • Disturbed sleep • Sexual dysfunction/apathy • “Stressed out” • GI complaints (constipation, diarrhea…)

  5. Epidemiology of Depression • Lifetime prevalence of a major depressive episode (MDE): 17% • Male: 13% • Female: 21% • 16 million adults currently with MDD (2016) • Trends • Age at onset: younger • Incidence: increasing • Etiology: biologic vs psychological

  6. Medical ConditionsAssociated With Depressive Symptoms • Cardiovascular disease 60% of post MI • Endocrine disorders – thyroid, menopausal… • Rheumatoid arthritis • Irritable bowel syndrome • Fibromyalgia • Brain trauma, tumors • Vitamin B12 deficiency – after gastric bypass, alcoholism… • Parkinson’s disease – 50% • Viral infections (e.g., influenza, HIV) • Cancers

  7. Consequences of Untreated Depression • Prolonged and increased suffering • Poorer quality of life • Poorer physical, social, and role functioning – decreased productivity (absenteeism, presenteeism) • Increased use of healthcare resources • Increased morbidity, mortality in other medical illnesses • Psychiatric or medical hospital admissions • Suicide

  8. Depression May Worsen Outcome of General Medical Conditions • Depression may worsen morbidity and mortality after myocardial infarction1,2 and in patients with CHF3,4 • Depression increases risk of mortality in patients in nursing homes5 • Depression worsens morbidity post-stroke6 • Depression may worsen outcomes of cancer, diabetes, AIDS, and other disorders7 5.Rovner BW, et al. JAMA. 1991;265:993-996. 6. Pohjasvaara T, et al. Eur J Neurol. 2001;8:315-319. 7. Petitto JM, Evans DL. Depress Anxiety. 1998;8(suppl 1):80-84. 1. Frasure-Smith N, et al. JAMA. 1993;270:1819-1825. 2. Penninx BW, et al. Arch Gen Psychiatry. 2001;58:221-227. 3. Jiang W, et al. Arch Intern Med. 2001;161:1849-18 4. Vaccarino V, et al. J Am Coll Cardiol. 2001;38:199-20

  9. Response Remission Is the Goal of Treatment in Major Depression • Remission • Relapse • Recurrence • Euthymia • + • Relapse • Increasedseverity • Symptoms • Progression • to disorder • + • Syndrome • Treatment phases • Acute • (6 to 12 wk) • Continuation • (4 to 9 mo) • Maintenance • (1 y) • Time • Adapted from: Kupfer DJ. J Clin Psychiatry. 1991;52(suppl 5):28-34.

  10. Recurrence Becomes More Likely With Each Episode of Depression • First • episode • <50% • Second • episode ≈70% • Third + • episode • >90% • 0 20 40 60 80 100 • % of patients expected to experience recurrence Stahl SM. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2nd ed. Cambridge, UK: Cambridge University Press; 2000:150.

  11. Major Depression Common Treatment Options • ANTIDEPRESSANT MEDICATIONS • MAOIs – Nardil, Parnate, SelegilineTricyclics – Elavil, Pamelor, Tofranil, Norpramin, DoxepinSRIs – Prozac, Zoloft, Paxil, Luvox, Celexa, LexaproDual action – Effexor, Pristiq, Wellbutrin, Remeron, Serzone, Cymbalta, Viibryd, Fetzima, Trintellix • Misc. – mood stabilizers, stimulants, atypical antipsychotics, thyroid, ketamine? • Psychotherapy - Cognitive behavioral, Interpersonal • Medication + Psychotherapy = optimal outcome • Electroconvulsive Treatment (ECT) - 1938 • Bright Light Therapy – 1984, not just for SAD • Vagal Nerve Stimulation (VNS) - 2005 • Transcranial Magnetic Stimulation (TMS) - 2008

  12. The Evolution Of Antidepressants 1980s 1990s >2000 1970s 1950s 1960s Duloxetine Desvenlafaxine Vilazodone Levomilnacipran Vortioxetine Fluoxetine Sertraline ParoxetineFluvoxamine Citalopram Phenelzine Isocarboxazid Tranylcypromine Maprotiline Amoxapine Doxepin Imipramine Clomipramine Nortriptyline Amitriptyline Desipramine Nefazodone Mirtazapine Venlafaxine Escitalopram

  13. Likelihood of Discontinuing Treatment Increases With Each New Medication Attempt Systemic Drug Side Effects • Weight Gain • Constipation • Diarrhea • Nausea • Drowsiness • Insomnia • Decreased Libido • Nervous Anxiety • Increased Appetite • Decreased Appetite • Fatigue • Headache/Migraine • Abnormal Ejaculation • Impotence • Sweating • Tremor • Treatment Discontinuation Side Effects • Weakness • Dry Mouth • Dizziness Trivedi (2006) Am J Psychiatry; Rush (2006) Am J Psychiatry; Fava (2006) Am J Psychiatry; McGrath (2006) AmJ Psychiatry; Neuronetics, Inc. (data on file)

  14. Psychotherapy • Cognitive Behavioral (CBT) – examination of ones thoughts (cognitions) in relation to situation to eliminate ANTs(automatic negative thoughts) • CBT + medications or phototherapy shown to be beneficial in acute MD and SAD episodes and to prevent or diminish future episodes • Mindfulness Meditation – moment to moment awareness of what is going on within and around you, sadness is part of daily emotional spectrum • Transcendental Meditation – use of a mantra to attain clarity of mind (transcend time and space)

  15. MDD Treatment Algorithm Primary Care • Initial Diagnosis • Early Treatment Attempts Psychiatry • Improved Diagnosis • Improved Dosing • Psychotherapy • New Treatment Options 10M 8M 6M 4M 2M SSRI Number of MDD Patients SNRINDRI Combination & Augmentation • Atypical Antipsychotics • Mood Stabilizers MAOI & TCA TMS ECT VNS 0 1 2 3 4 5 6 7 8 Failed Treatment Attempts in Current Episode Treatment-Resistance Continuum Kessler RC et al. Arch Gen Psychiatry. 2005;62(6):617-627; Kessler RC et al. JAMA. 2003;289(23):3095-3105; Herrmann RC. Am J Psychiatry. 1995;152(6):869-875. 16

  16. Electroconvulsive Therapy • ECT is the electrical induction of a generalized seizure under general anesthesia for therapeutic purposes • In the USA, ECT is one of the most common procedures (>100,000/year) performed under anesthesia and the safest with a mortality rate ≤ 0.002% • Two treatment schedules are used: • An acute course (2 - 3 times per week for 3 -6 weeks) achieves current episode remission • Continuation/Maintenance ECT every 2 – 6 weeks to inhibit recurrence

  17. What is TMS?(Transcranial Magnetic Stimulation) 1831 – Michael Faraday, principles of magnetic induction 1985 – Anthony Barker, first electro-magnet for human use (spinal cord..) 1995 – NIH, first TMS trial for TRD Electric current through the coil induces MRI-strength magnetic field Magnetic field pulses pass 2-3 cm into the cortex inducing electrical current in the brain This stimulates the firing of nerve cells and the release of neurotransmitters 30 treatments, with no anesthesia, 5 days/week, for 26-40 minutes each 1 Richelson, E. Mechanisms of Action of Repetitive Transcranial Magnetic Stimulation (rTMS) and Vagus Nerve Stimulation (VNS). Psychiatric Annals, 2007; Vol 37-No. 3, 181-187.

  18. SEASONAL AFFECTIVE DISORDER (SAD)

  19. DSM-V Criteria For MD Seasonal Pattern Specifier • Regular temporal relationship between the onset of a major depressive episode and a particular time of the year (not including seasonal stressors – layoffs, holidays...) • Full remissions at a particular time of year • 2 depressive episodes in the last 2 years to demonstrate the temporal / seasonal relationship, no non-seasonal episodes • Seasonal episodes > non-seasonal • Symptoms cause significant distress or impairment in social, occupational or other areas of functioning

  20. SAD SymptomsSimilar to “Atypical” Depression • Energy Crisis • Hypersomnia, fatigue • Irritability • Decreased concentration • Loss of interest in routine activities • Increased appetite • Carbohydrate craving • Weight gain

  21. Prevalence Of SAD In North America 6% overall in the U.S. 10% in northern regions (U.S., Canada, Scandanavia…) 1 - 2% in southern areas 2 - 9 times more common in females 50% have 1st degree relative with mood disorder >20% in those with major depression 10% of all SAD symptomatic in summer Seasonal patterns identified in bulimia, anxiety disorders and other mood disorders

  22. Total Daylight Hours On Shortest Day Of The Year In Northern Latitudes • Fairbanks, AS 65 deg 3h 42m • Anchorage, AS 61 deg 5h 28m • Vancouver, BC 50 deg 8h 11m • Toronto, ON 43 deg 8h 56m • Detroit, MI 42 deg 9h 4m • S.F., CA 38 deg 9h 33m • Miami, FL 26 deg 10h 26m

  23. Lake Effect • Cold air masses moving south and east across the relatively warmer waters of the Great Lakes produces clouds • Late fall and early winter are when there is the greatest differences in temperature between the air masses and lakes • This difference leads to heavy cloud cover in the Upper Peninsula and western Lower Peninsula

  24. Average Cloudy Days / Year In Michigan Sault Ste. Marie 209 Grand Rapids 205 Muskegon 202 Houghton Lake 200 Flint 195 Alpena 194 Lansing 191 Detroit 185

  25. SAD Theories • Physiological vulnerability to experience atypical mood symptoms during winter • Circadian rhythm dysregulation, melatonin • Neurotransmitters - serotonin, norepinephrine, dopamine • Psychological vulnerability to develop mood symptoms in response to vegetative symptoms (decreased activity, increased sleep + appetite)

  26. Circadian Rhythm • Human brain has a 24 hourrepeating rhythm to regulate day and night activities • Melatonin secreted by the pineal gland in response to darkness and induces sleep • Melatonin levels peak~ midnight to 2 am then fall gradually until morning • Morning lightsensed by the retina informs the brain of a new day, suppressing melatonin • Winter with less morning light, melatonin levels peak later and remain elevated 2 or more hours longer – body thinks it needs more sleep

  27. Circadian Rhythm: Peak Time of Functions Gastric acid secretion WBC Peripheral blood flow Urination midnight Cholesterol/ Triglycerides 6pm6am Insulin noon Respiratory Rate Hemoglobin Blood viscosity Growth hormone Prolactin Melatonin Cortisol Blood Pressure/ heart rate Arterial elasticity/ venous resistance Platelet adhesiveness

  28. CHANGES IN LATITUDE + HOURS OF DAYLIGHT + LAKE EFFECT CLOUDS + CIRCADIAN RHYTHM CHANGES IN ATTITUDE Apologies to Jimmy Buffett

  29. “It is certainly very cold,” said Peggotty.“Everybody must feel it so.”“I feel it more than other people,” said Mrs. Gummidge. Charles Dickens, David Copperfield

  30. “Growing up in a place that has winter, you learn to avoid self-pity. Winter is not a personal experience; everyone is as cold as you are; so don’t complain about it too much. It could be worse”.

  31. SAD Theories - Melatonin • Sleep promoting hormone - 90% from pineal gland, 10% from retina • Dim and bright light suppresses secretion • Body temperature drops as melatonin levels rise at night, with darkness • SAD individuals show longer duration of melatonin release through the nights/winter • Beta-blockers (propranolol, atenolol…) suppress secretion but are effective only for 1-2 weeks

  32. SAD Studies • SAD / depressed patients use more medical resources, prescriptions, tests, referrals… • Retinal sensitivity decreased with age • Increased serotonin turnover on sunny days • Visual impairment not a factor, myopia? • Decreased attention and concentration (NE,DA?) • Bright light therapy offers some improvement in non-SAD mood disorders • High carbohydrate diet increases energy in those w/ SAD, non-SAD persons felt lethargic

  33. Prevalence of SAD, WB by Latitude

  34. Genetic predisposition? • No difference in Finns vs. Lapps of Norway • 3x prevalence in Asians living in Britain • Less prevalence in Iceland vs. Eastern US • 2x prevalence in Russians vs. Norwegians • Acclimatization? – fewer seasonal symptoms in those living in an area for a longer time • Japanese in Stockholm had more seasonal variation over time

  35. SAD Treatments • Bright light therapy • Sleep deprivation • Antidepressants - Prozac = BLT, Wellbutrin XL (FDA approved for episode prevention) • Tricyclic, MAOI antidepressants • Stimulants - Ritalin, Adderall, Dexedrine, Provigil, Nuvigil… • 30-60 minutes of morning exercise • Psychotherapy – CBT, Mindfulness, TM...

  36. Supplements Chromium Picolinate • Studied for mood effect in SAD, 600 mcg daily • No mood effect found • Decreased carbohydrate cravings, food intake • Minimal side effects – insomnia, headache, irritability, nausea Melatonin • 1-10 mg, 1-2 hours before bedtime • Minimal tolerance or daytime sedation • Rare drug interactions

  37. Bright Light Therapy - Studies • > 200 studies since 1979, poor funding, small studies • Recognized effective treatment since 1984 • Morning vs. midday vs. evening • Difficult to include placebo • Eyes vs. skin • Duration • Distance • Color, frequency

  38. Meta-analysis of Studies

  39. Measurement Of Illumination - LUX • 100w bulb at 3ft 100 • Fluorescent overhead at 3ft 400 • Ambient light home 500 • Sky at twilight 750 • Phototherapy Light Box 2,500-10,000 • Bright, overcast day 10 - 25,000 • Clear, noon - temperate 80,000 • Clear, noon - equator 100,000

  40. Blue Light Special? • Visible light spectrum 400-700nm, Sunburn from UV rays, <400nm Incandescent lamps have most output near infrared end of spectrum • Retinal sensors - Rods (B&W) and Cones (color) - may not be involved in light transmission for circadian/melatonin effect • Ganglion cells of retina coated with melanopsinwhich responds preferentially to 446 – 477 nm (blue)

  41. Blue Light Special? • Light triggers retinal sensors, especially melanopsin, sending signals to the suprachiasmic nuclei of the hypothalamus to turn off melatonin production • Blue wavelengths are close to UV in spectrum, poorly calibrated light could be dangerous • Increased risk of macular degeneration? • Cataracts may filter out blue light • Some clinicians recommend use of goggles to filter out Blue / UV rays when using BLT

  42. Blue Light Special?

  43. Phototherapy Lights • Insurance may cover as medical equipment • Full spectrum fluorescent vs Blue LED • Dawn simulation • Visor

  44. Bright Light Therapy • Morning light - advance melatonin rhythm • Evening light - delay melatonin rhythm, may be beneficial for elderly to delay early bedtime • Both can improve SAD symptoms- most studies show superiority of am light • Improved atypical sx better more than exercise • Severity of overeating/oversleeping are best predictors of improvement with light therapy • Possible benefit in PMDD, Bulimia, Adult ADHD • Safe in pregnancy

  45. Bright Light Therapy • 70% response rate in SAD, similar to medications for MD • 2 – 4 days for onset of effect • 2 – 4 weeks for peak treatment effect • 2,500 - 10,000 lux for 30 minutes – up to 2 hours/day (typical box has 10,000 lux @ 20 inches, 2,500 @ 40 inches) • Early morning most beneficial - Start with am light for 2-3 weeks, change to pm light if am is ineffective • Cool white fluorescent = full spectrum • Dawn simulation (<100 lux) – 1 - 2 hrs am brightening • Dim light visor for 30 - 60 minutes

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