Prevalence of Sad in North America

Prevalence of Sad in North America

Kerry Pierce, MD Board Certified Adult and Geriatric Psychiatry MidMichigan Physicians Group Major Depression, Seasonal Depression, Winter Blahs Major Depressive Disorder Depression: Emotional and Physical Signs Emotional Physical Hopelessness

Fatigue Low self-esteem Vague abdominal pain Impaired memory Vague joint pain Headache Difficulty concentrating Disturbed sleep Anhedonia Sexual dysfunction/apathy

Anxiety Stressed out Preoccupation with negative thoughts GI complaints (constipation, diarrhea) 4 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: Incidence: Etiology: younger increasing biologic vs psychological 5 Medical Conditions Associated With Depressive Symptoms Cardiovascular disease 60% of post MI

Endocrine disorders thyroid, menopausal Rheumatoid arthritis Brain trauma, tumors Vitamin B12 deficiency after gastric bypass, alcoholism Parkinsons disease 50% Viral infections (e.g., Irritable bowel syndrome influenza, HIV) Fibromyalgia Cancers 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 Depression May Worsen Outcome of General Medical Conditions Depression may worsen morbidity and mortality after myocardial infarction 1,2 and in patients with CHF 3,4 Depression increases risk of mortality in patients in nursing homes 5 Depression worsens morbidity post-stroke 6 Depression may worsen outcomes of cancer, diabetes, AIDS, and other disorders 7 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 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. Remission Relapse Euthymia Syndrome + Response on

ssi gr e er Pro or d di s Symptoms Relapse Recurrence to Increased severity Remission Is the Goal of Treatment in

Major Depression Treatment phases + Acute (6 to 12 wk) Continuation Maintenance (4 to 9 mo) (1 y) Time Adapted from: Kupfer DJ. J Clin Psychiatry. 1991;52(suppl 5):28-34. 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. Major Depression Common Treatment Options ANTIDEPRESSANT MEDICATIONS MAOIs Nardil, Parnate, Selegiline Tricyclics Elavil, Pamelor, Tofranil, Norpramin, Doxepin SRIs Prozac, Zoloft, Paxil, Luvox, Celexa, Lexapro Dual 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 The Evolution Of Antidepressants 1950s 1970s 1960s Phenelzine Maprotiline Isocarboxazid Amoxapine

Tranylcypromine Doxepin Imipramine Clomipramine Nortriptyline Amitriptyline Desipramine 1980s 1990s >2000 Fluoxetine Sertraline

Duloxetine Paroxetine Desvenlafaxine Fluvoxamine Vilazodone Citalopram Levomilnacipran Vortioxetine Nefazodone Mirtazapine Venlafaxine Escitalopram

Likelihood of Discontinuing Treatment Increases With Each New Medication Attempt Systemic Drug Side Effects Weight Gain Fatigue Constipation

Diarrhea Headache/ Migraine Abnormal Ejaculation Nausea Drowsiness

Impotence Insomnia Sweating Decreased Libido Tremor

Nervous Anxiety Increased Appetite Treatment Discontinuation Side Effects Weakness

Dry Mouth Dizziness Decreased Appetite 13 Trivedi (2006) Am J Psychiatry; Rush (2006) Am J Psychiatry; Fava (2006) Am J Psychiatry; McGrath (2006) Am J Psychiatry; Neuronetics, Inc. (data on file) 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) MDD Treatment Algorithm 10M Primary Care Psychiatry

Initial Diagnosis Early Treatment Attempts Number of MDD Patients 8M Improved Diagnosis Improved Dosing Psychotherapy New Treatment Options 6M 4M

2M Combination & Augmentation Atypical Antipsychotics Mood Stabilizers SSRI SNRI NDRI MAOI & TCA ECT TMS 0 1 2

3 4 5 6 7 VNS 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. 16

2003;289(23):3095-3105; Herrmann RC. Am J Psychiatry. 1995;152(6):869-875. 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 18 What is TMS?

(Transcranial Magnetic Stimulation) 1831 Michael Faraday, principles of magnetic induction 1985 Anthony Barker, first electromagnet 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.

19 SEASONAL AFFECTIVE DISORDER (SAD) 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 SAD Symptoms Similar to Atypical Depression Energy Crisis Hypersomnia, fatigue Irritability Decreased concentration Loss of interest in routine activities Increased appetite Carbohydrate craving Weight gain

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 Total Daylight Hours On Shortest Day Of The Year In Northern Latitudes

Fairbanks, AS Anchorage, AS Vancouver, BC Toronto, ON Detroit, MI S.F., CA Miami, FL 65 deg 61 deg 50 deg 43 deg 42 deg

38 deg 26 deg 3h 42m 5h 28m 8h 11m 8h 56m 9h 4m 9h 33m 10h 26m 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 Average Cloudy Days / Year In Michigan Sault Ste. Marie Grand Rapids Muskegon Houghton Lake Flint Alpena Lansing Detroit 209 205 202 200 195 194

191 185 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) Circadian Rhythm Human brain has a 24 hour repeating 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 light sensed 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 Circadian Rhythm: Peak Time of Functions Gastric acid secretion WBC Peripheral blood flow Urination Cholesterol/ Triglycerides 6pm Insulin noon Respiratory Rate Growth hormone

Prolactin midnight Melatonin Cortisol 6am Blood Pressure/ heart rate Arterial elasticity/ venous resistance Hemoglobin Platelet adhesiveness Blood viscosity CHANGES IN LATITUDE

+ HOURS OF DAYLIGHT + LAKE EFFECT CLOUDS + CIRCADIAN RHYTHM CHANGES IN ATTITUDE Apologies to Jimmy Buffett 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 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 dont complain about it too much. It could be worse. 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 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 Prevalence of SAD, WB by Latitude Location Latitude SAD WB Total

Sarasota, FL 27 1.4 2.6 4.0 Maryland 39 6.3 10.4 16.7

New York City 40 4.7 12.5 17.2 Nashua, NH 42 9.7 11.0

20.7 Fairbanks, AK 65 9.2 19.1 28.3 Stockholm, SE 59 3.9 13.9

17.8 Helsinki, FI 59 7.1 11.8 18.9 Oslo, NO 59 14.0

12.6 24.6 Reykjavik, IS 64 3.8 7.6 11.3 Tromso, NO 69 13.7

10.7 24.4 Nagoya, JP 35 0.9 0.8 1.7 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 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... 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 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 Meta-analysis of Studies Diagnosis/treatment Effect size Clinical effect Bright light 0.84 Large

Dawn simulation 0.73 Large Bright light 0.53 Medium Adjunctive bright light 0.01 None

Seasonal Affective Disorder Non-seasonal depression 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 Bright, overcast day Clear, noon - temperate Clear, noon - equator 2,500-10,000 10 - 25,000 80,000 100,000 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 melanopsin

which responds preferentially to 446 477 nm (blue) 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 Blue Light Special? White Light Blue Light Wavelengths

400 - 700 nm 440 - 480 nm Brightness for clinical effect 3000 - 10,000 lux 400 - 3000 lux Efficacy Well-established Few trials, conflicting results

Safety Well-established Controversial Advantages Long-track record Lower intensity for effect Phototherapy Lights

Insurance may cover as medical equipment Full spectrum fluorescent vs Blue LED Dawn simulation Visor Bright Light Therapy Morning light - advance melatonin rhythm Evening light - delay melatonin rhythm, be beneficial for elderly to delay early bedtime Both can improve SAD symptomsstudies show superiority of am light may most 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 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 Light Therapy Potential Side Effects

Eyestrain Headache Anxiety Restlessness Irritability Nausea Dizziness Insomnia Muscle tension

Relatively contraindicated in those with retinal and optic nerve disorders, glaucoma, cataracts, SLE, skin CA Photosensitizing drugs diuretics HCTZ, herbals SJW, antibiotics tetracycline, antipsychotics thorazine No evidence of long term adverse effects SAD Studies - Cognitive Behavioral Therapy SAD and nonseasonal depressed patients exhibit similar ANTs toward themselves and environment. SAD females > males show this negativity all year Negative cognitions relating to winter, light availability, weather/environmental cues identified and challenged. Schedule winter activities to counteract hibernation. CBT found to be as effective as light therapy for episode.

May be more effective for future relapse prevention. Aerobic exercise- (morning / afternoon, 60 min. / daily) shown to be effective in depression and SAD, especially under bright lights. (Normalization of daily calorie expenditure as an underlying cause?) SAD Survival Guide Get out of the house - bundle up, walk Get off of the couch exercise, hobbies, sports Bright lights, shades up, curtains open...

Sleep hygiene regular sleep/wake times Avoid napping keep them brief and regular Dont expect a vacation miracle cure Watch what you eat maintain a balanced diet (fresh fruits, salads) Beach / tropical music and boat drinks? Resources Lam, R. Seasonal Affective Disorder and Beyond Rosenthal, N.E. Seasonal Affective Disorders & Phototherapy Seasons Of The Mind Transcendence: Healing and Transformation through TM Winter Blues 4th ed. 2013 Terman, M. - Chronotherapy: Resetting Your Inner Clock to Boost Mood, Alertness and Quality of Sleep Resources - Websites (www.) (Philips)

Resources National Institute of Mental Health National Alliance for the Mentally Ill Depression & Bipolar Support Alliance Center for Environmental Therapeutics Beck Institute for CBT Society for Light Therapy and Biological Rhythms Seasonal Affective Disorder Growing up in a place that has winter, you learn to avoid self-pity. Winter is not a personal experience, everyone else is as cold as you, so you shouldnt complain about it too much. You learn

this as a kid, coming home crying from the cold, and Mother looks down and says, Its only a little frostbite. Youre okay. And thus you learn to be okay. Whats done is done. Get over it. Drink your coffee. Its not the best youll ever get but its good enough.

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