DEPRESSION - uofthenet.org

DEPRESSION - uofthenet.org

DEPRESSION PREVALENCE OF CLINICAL DEPRESSION (1994) LIFETIME

YEARLY Bipolar 17% (?) 10% 5% TREATMENT OF DEPRESSION IN PRIMARY CARE*

Depression: 2nd. Most Common Disorder in Primary Care 40% Diagnostic Hit Rate 87% Somatic Sx, 13% Mood Sx (Greist, 2002) A RECURRING ILLNESS 20% SINGLE EPISODE 80% RECURRENT or CHRONIC

Depression: Fluctuating Course N= 431 ( : 1 .episode, recurrent, : double D.) 12 year Follow-up Symptomatic: 58%, 42%: Sx-free Time Symptomatic:

> 15% MDD > 43% Sub-Syndromal st Depression: Fluctuating Course

N= 431 ( : 1 .episode, recurrent, : double D.) 12 year Follow-up Symptomatic: 58%, 42%: Sx-free Time Symptomatic: > 15% MDD > 43% Sub-Syndromal st WORLD HEALTH ORGANIZATION STUDY

Each day in Primary Care Medical Settings: > 25% of patients have Clinical Depression > 10% have Anxiety Disorders > 10% have Substance Abuse Disorders cont. MOST COMMON DISORDERS SEEN IN PRIMARY CARE Hypertension

Depression Anxiety Disorders Most Reactive Depressions If they reach the intensity level of Major Depression, will show vegetative symptoms. BIOLOGIC SYMPTOMS

ANHEDONIA SLEEP DISTRUBANCES APPETITE DISTURBANCES LOSS OF SEXUAL DRIVE FATIGUE

Dysthymia Ill-Humor 5% Of the Population (lifetime prevalence) Most eventually also develop Major Depression

Dysthymia Pharmacologic Outcome: 33% Excellent Response 33% Good Response 34% Poor Response (Akiskal, 1997) Has the Success of Antidepressants Been Over-Sold?

15 Patients Recruited in Antidepressant Drug Studies Zimmerman, et al. (2002) N= 346 (MDD, outpatient practice) 86% would be excluded from drug studies

ITT: Intent to Treat Response Rates: MDD Single Antidepressant trial Do not tolerate: 15% No response: 35% Responders:

50% ITT Rates Responder = 50% HAM-D, or HAM-D Score of 7 or less Responders: > Full Responders: HAM-D < 7 50% > Partial Responders: HAM-D: 9-14:

50% ITT: The Rest of the Story Full Responders: > 18% truly asymptomatic > 82% subtle residual symptoms Nierenberg, et al. (1999) Partial Responders:

Is Symptomatic Improvement Good Enough? Partial Responders Time to Next Episode: * 3 times longer to next episode remitters vs. partial responders Quality of life (espec. Social Functioning)

Evidence-Based Medicine and Treatment Algorithms Depression Implications for Treatment Success

1. Hopelessness and Drop-outs (long time to response) 2. Compliance: high risk patients 3. Extreme response to side effects 4. Premature discontinuation (skepticism about meds : 62% in DC) 5. Patient preferences 6. Inaccurate diagnosis

Rating Scales First weeks of Treatment Aim to get some immediate relief

Medication strategies Exercise Bright light (details later) Combat social withdrawal 26 On-Line Algorithms International Psychopharmacology Algorithm Project:

endorsed by WHO www.IPAP.org www.MHC.com (also P 450: drug interactions) Choosing a First-line Antidepressant

29 Targeting Neurotransmitters NE: norepinephrine 5-HT: serotonin DA: dopamine 33

NEWER GENERATION ANTIDEPRESSANTS SSRIs: Serotonin (5-HT) NRIs: Norepinephrine (NE) Dual Action: Wellbutrin: NE and Dopamine Effexor: 5-HT and NE (SNRI) Remeron: 5-HT and NE (SNRI) Cymbalta (duloxetine): 5-HT and NE

Pristiq 5-HT and NE Neurotransmitters and Behavior Serotonin: Anxiety, Rumination, Irritability, Aggression, Suicidality Shelton and Tomarken (2001); Metzner, (2000) Neurotransmitters and Behavior Catecholamines:

Dopamine and Norepinephrine: Anhedonia, Apathy, Impaired Attention Shelton and Tomarken (2001); Metzner, (2000) Antidepressants Agorithm Texas Medication Algorithm Project TMAP

ANTIDEPRESSANT ALGORITHM With Anxiety or Agitation: SSRIs Anergic: Atypical: PMDD: 38 Activation vs Switching Activation: within hours; anxiety

and/or initial insomnia Switching: 3+ weeks; manic symptoms 39 Benzodiazepine Augmentation Start up (Ward Smith, et al.)

Check for history of substance abuse Antidepressant and tranquilizers Early responsefewer drop outs 40 Benzodiazepine use: HMO Setting (Samari, 2007) N: 2440

Treated for 2 years with tranquilizers Percent of those requesting increased doses: 1.6 % 41 ANTIDEPRESSANT ALGORITHM With Anxiety or Agitation: Anergic: Wellbutrin Atypical

PMDD 42 Stimulant augmentation with anergic depressions 43 ANTIDEPRESSANT ALGORITHM

With Anxiety or Agitation: Anergic Atypical: watch for bipolar PMDD 44 ANTIDEPRESSANT ALGORITHM Pre-Menstrual Dysphoria:

SSRIs 45 ANTIDEPRESSANT ALGORITHM Very Severe and/or Recurrent: Dual Action: Effexor, Pristiq, Cymbalta, Remeron, Wellbutrin

46 Metzner, 2000 47

P r elim in ar y s t udy o f d epr es s edpa tient s s am pled pa STD: tient Sp tr and iv at ar eprdRx ac tice sin out etti ng TD: Ta rr get

aT ntidep es s ea d nt: ss eo lenlctive y Standard Targeted Improved 100% 90%

80% 70% 60% 50% 40% 30% 20% 10% 0%

65% 96% % of Patients Improved Standard vs. Targeted Treatment GUIDELINES for MEDICAL TREATMENT of DYSTHYMIA

IRRITABILITY: SSRIs LOW ENERGY, APATHY, LOW-GRADE ANHEDONIA: Wellbutrin not based on empirical studies Additional Considerations in Medication Choices

Side Effects Patient Preferences Pharmacokinetics PHASES OF TREATMENT ACUTE: Until Asymptomatic CONTINUATION: 6 months @ Same Dose MAINTENANCE: Third Episode:

Lifetime Treatment Continuation Phase of Treatment

Minimum of six monthssame dose Patient-initiated discontinuation High rates of acute relapse Serotonin and emotional blunting Dampens dopamine Antidepressant Discontinuation Syndromes

Symptoms: nausea, dizziness, malaise, electric shock-like sensations Most likely: Paxil, Effexor, Cymbalta, Pristiq Least likely: Prozac Maintenance Phase

ADEQUATE TRIAL DOSE COMPLIANCE TIME BLOOD LEVELS TIME TO RESPONSE EARLY RESPONDERS: 2-4 WEEKS

LATE RESPONDERS: SEVERE SYMPTOMS FIRST EPISODE BEFORE 18 LONG DURATION (more than three months) 4-6 WEEKS Response Remission Partial

Poor Overview: Options for Inadequate Response Optimization Augmenting > Combination Treatments Switching Drug Classes Optimization

dose; time Augmenting: Combination Switching Classes e.g serotonin norepinephrine reuptake inhibitor

Empirical Studies STAR-D: Sequenced Treatment Alternatives to Relieve Depression (NIMH) STAR-D (2007) N= 4100

Ages 18-75 Average patient: 3 medical illnesses 65%: psychiatric co-morbidity 62 STAR-D 80%: chronic or recurrent 25%: have been depressed for 2+ years

53%: anxious depressions 63 STAR-D Rating Scale page Side effect scale Page Overview: Options for

Inadequate Response Optimization Augmenting > Combination Treatments Switching Drug Classes 65 STAR-D (2006)

PHASE ONE: Celexa: average doses 40 mg Response rates: 60% Remission rates: 30% Average time to remission: 7 weeks KEY: aggressive dosing 66 STAR-D (2006)

PHASE TWO Non-remitters: randomized: > Switch > Augmentation 67 STAR-D: Switch (2006)

Effexor: Wellbutrin: Zoloft: 25% 21% 17% Average time to remission: six weeks

68 STAR-D: Augment (2006) Wellbutrin: BuSpar: 30% 30%

Augmenting: slightly higher yield than switching 69 New Study 70 STAR-D: After Phase 2

55% reach remission 71 STAR-D (2006) PHASE Three: > Switch:

nortriptyline (tricyclic) or Remeron > Augment: lithium T3 72 STAR-D (2006)

PHASE Three: > Switch: nortriptyline or Remeron 13% > Augment: lithium 20% T3 20% 73

T3 Augmentation 4 double bind studies: indicate efficacy STAR-D study: very high yield Few Side Effects Dose: Cytomel 25-75 micrograms qd

74 STAR*D Final Outcomes 67% Complete remission 75

STAR-D Cumulative Sustained Recovery Rate 43% 76 STAR-D Monotherapy STAR-D Monotherapy

STAR-D Augmentation Guidelines What Can Be Learned from STAR-D

Use of rating scales Aggressive dosing Some suggestions: next steps Testament to the difficulties in treating very severe depression Head-to-Head Comparisons: SSRIs N= 26,000.117 trials Efficacy and tolerability

Among SSRIs: Sertraline (Zoloft) comes out on top Lexapro #2 (not generic.no drug-drug interactions) Cochran Database Surveys (2009) 81 Head-to-Head Comparisons SSRIs: versus Effexor and Remeron

better efficacy (dual action drugs) SSRIs versus Wellbutrin: Wellbutrin: better tolerability Best for headaches: Elavil Cochran Database Surveys (2009) 82 PARTIAL RESPONSE STRATEGIES FIRST: Check Compliance &

Substance Abuse INCREASE DOSE AUGMENT Other augmentation Strategies Augmentation Strategies Lithium: 0.3-0.6 mEq/l > relapse x 3

> 7 fold suicides THYROID Adding T3 or T4: augmentation T4 for rapid cycling Hypothyroid in Lithium therapy

Thyroid Augmentation T4: levo-thyroxine: > Synthroid, Levothyroid, Levoxyl > 1 mcg per pound of weight qd T3: triiodothyronine: > Cytomel > 25-75 mcg. qd Hypothalamus

TRH Pituitary TSH Thyroid T3 Gland T4

TSH Thyroid Stimulating Hormone Depression and Hypo-Thyroid The most common medical cause of depression (10%) Grade I: T3 and T4: TSH Grade II: Normal T3/T4, but TSH

(Wolkowitz, 2003; Zweifel, 1997) Normal TSH Levels High Normal Range 3.0 | | Median 1.3 | |

Low Normal Range 0.3 miliIU/Liter Normal TSH Levels High Normal Range | | Median | |

Low Normal Range 3.0 2.5 1.3 0.3 miliIU/Liter Stimulant Augmentation

MAOIs New MAOI: Emsam selegiline transdermal: 6-12 mg per day Augmentation Strategies

Atypical Antipsychotics: Antipsychotics * Zyprexa *Abilify *Geodon *Risperdal * Seroquel ? Reducing Treatment-Resistant Unipolar Depression

MADRS Total: Acute Treatment Fluoxetine Mean Change from Baseline (LOCF) Improvement 0

(n=10) -5 Olanzapine (n=8) *p<0.05 vs Flx. +p<0.05 vs Olz.

-10 -15 *+ -20 0

*+ *+ * *+ *+

*+ *+ 1 2 3

4 5 6 7 Weeks of Double-Blind Therapy Mean modal dose during double-blind therapy: Flx = 52 mg/d, Olz = 12.5 mg/d, Olz + Flx = 13.5 mg/d + 52 mg/d.

Shelton RC et al. Am J Psychiatry 2001; 158:131-134. 8 Olanzapine/ Fluoxetine (n=10) Folic Acid Low serum levels in treatmentresistant depression and early

relapse Co-factor: Serotonin 500 mcg 2 X per day With Depakote: 1-2 mg per day High Intensity Light Therapy Seasonal and non-seasonal Caution with: Bipolar

POOR RESPONSE STRATEGIES CHECK COMPLIANCE and SUBSTANCE ABUSE INCREASE DOSE SWITCH CLASSES: e.g. SSRI NE NE SSRI

Within Class Switches Reasons for switch: > Tolerability > Efficacy (espec. with partial Response) Two SSRI failures: switch classes LATE EMERGING SEROTONIN SIDE EFFECTS SEXUAL DYSFUNCTION > Inorgasmia

APATHY and EMOTIONAL BLUNTING WEIGHT GAIN (10% after one year) Prevalence Sexual Problems / Complaints Reporting: 14% Elicited on questionnaire 60% N: 6300: only 29% had no

other risk factors except antidepressant exposure Prevalence Sexual S.E. without other probable causes

Celexa, Lexapro, Effexor 30% Zoloft, Paxil 28% Prozac, Remeron 24% Serzone 14% Wellbutrin

7% Clayton, et al. 2002 LATE EMERGING SEROTONIN SIDE EFFECTS SEXUAL DYSFUNCTION > Inorgasmia APATHY and EMOTIONAL BLUNTING WEIGHT GAIN (10% after one year)

GENDER DISTRIBUTION DEPRESSION Disorder Female : Male

CHILDREN TEENS ADULTS 1:1 2:1 2:1 BI-POLAR I BI-POLAR II

1:1 2:1 Premenstrual Dysphoric Disorder: PMDD Average female: 400 periods 70 %: PMS at some point in time 30 %: significant PSM

4 %: PMDD Premenstrual Dysphoric Disorder: PMDD Premenstrual exacerbation of Major Depression symptoms 90% of women who successfully commit suicide: premenstrual

Premenstrual Dysphoric Disorder: PMDD Treatments: > reduce caffeine, alcohol, salt, sugar, and stop smoking > exercise > Serotonin antidepressants > St. Johns Wort (case reports) Premenstrual Dysphoric

Disorder: PMDD Antidepressant treatments Must target Serotonin Intermittent versus continuous Quick onset of actions PMDD and SEROTONIN Fluctuating estrogen levels can have an impact on

Tryptophan hydroxylase (rate-limiting enzyme for production of 5-HT) Allopregnenolone Neuro-steroid: synthesized in the brain Potent GABA-A agonist Low levels in MDD CSF ( with successful treatment)

Allopregnenolone PMDD: marked reduction Rapid increase with SSRIs but not with nonserotonin antidepressants Premenstrual Dysphoric Disorder: PMDD Calcium supplementation 2 double blind, placebo controlled

studies 1200 mg per day (4 Tums) 55% vs 36% Myths about Pregnancy and Well Being Risks of major depression: prenatal and postpartum: 21% (highest risk for women) Risks of discontinuing medications: Bipolar: 83% acute relapse

Major depression: 68% relapse 116 Depression and Pregnancy Depression and pregnancy: > > > >

Hypercortisolemia Substance abuse Suicide attempts Post-partum exacerbation (bonding and attachment) Depression and Pregnancy Depression and pregnancy: > Hypercortisolemia

> Substance abuse > Suicide > Poor self care > Post-partum exacerbation (bonding and attachment) FDA RATINGS: USE DURING PREGNANCY A: B:

C: D: X: No Risk. Well controlled studies No Evidence of Risk Risk Cannot Be Ruled Out Positive Evidence of Risk Contraindicated in Pregnancy 120

Newer Antidepressants and Pregnancy FDA classifications: all C except: Paxil: D > Discontinuation syndrome > 2nd and 3rd trimester exposure: risk of cardiac defects (2% vs 1%) 121

Antidepressants: Meta-analysis (Einarson and Erinarson, 2005) N: 1774 exposed fetuses

First trimester exposure Major malformations: 2-3% This equals the base rate in un-exposed fetuses 122 Antidepressants: Risks (Hauser, et al., JAMA 2009) Small but statistically non-significant

increase in miscarriages Not compared to non-depressed subjects Premature birth: 20% greater: in both medicated and non-med mothers 123 Antidepressants: Risks No specific birth defects

??? Cardiac defects in SSRIs ??? 124 The Jury is Still Out 126 PSYCHOTIC DEPRESSIONS

Antidepressants (AD) Antipsychotics (AP) AD + AP ECT 35%

45% 75% 90% Note: Continuation Phase: One Year AD and AP Electroconvulsive therapy

ECT: Electro-convulsive Therapy Shock Treatments V DEPRESSION IN CHILDREN and ADOLESCENTS MAJOR DEPRESSION

Children 3% Teens: 10% 35% recurrent 50% bipolar Depression in Young Children

Luby, et al. (2002) N=49 Using DSM-IV criteria: 12 Dx as MDD Thus must use modified criteria MDD Children: Modified Diagnostic Criteria

Most of the day, more days than not Play: themes of death, suicide, selfdestruction (61%) Depressed or irritable mood or Diminished interest plus 4 Sx (vs 5 for adults) SYMPTOMS IN CHILDREN

ANHEDONIA / WITHDRAWAL (60%) IRRITABILITY (81%) LOW SELF-ESTEEM (78%) SCHOOL FAILURE LONLINESS

VEGETATIVE Sx: Sleep and Appetite Disturbance (80%) LOW ENERGY (58%) .. Child and Adolescent Depression:Additional Signs

Vague, non-specific physical complaints Running away from home Being bored Extreme sensitivity to rejection or failure Reckless behavior; Acting Out Difficulty with relationships

Substance Use / Abuse Problems with the studies Meta analysis: Effect Size: 0.25 TADS Treatment for Adolescents with Depression Study

Effectiveness Outcomes (2004) Random Assignment

NIMH Study N: 432 Placebo Prozac Cognitive Behavioral Therapy Combo: drug and CBT Responders

Perc ent Treatment Response: Week 12 100 90 80 70 60 50

40 30 20 10 0 71 61 43 35

COMB FLX CBT PBO TADS

Effect Size 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2

0.1 0 COMB FLX CBT TADS

Time to Onset of Effects Anxiety: 1-2 weeks Depression: 4-6 weeks but responders in 10-12 week range ! Paxil and Increased Suicidality UK studyN=1300 adolescents Increased suicidality: Placebo: 1.2%

Paxil: 3.4% No actual Suicides 33 suicidal incidents .. Paxil and Increased Suicidality Acute Treatment data Discontinuation State of Connecticut: Human Implications

TADS (2004) At baseline: 29% suicidal ideas Attempts: 1.6% Actual Suicides: 0 Suicidality Is Reduced

Overall 29.2 30 27 Perc ent 25

20 14.6 15 13 11.6 10

5 0 CDRS13 > 1 SIQ >= 31 2.7 Baseline

Week 6 Week 12 TADS FDA Data N= 4400 N= 300 http://www.fda.gov/ohrms/dockets/ac/04/slides/2004-4065s1.htm

All trials, all indications (Fixed effect model) Risk ratio (95% CI) % Weight Study

CELE(MDD,18) CELE(MDD,94404) EFFEX(MDD,382) EFFEX(MDD,394) PAXIL(MDD,329) PAXIL(MDD,377) PAXIL(MDD,701) PAXIL(SAD, 676) PROZ(MDD,HCCJ) PROZ(MDD,HCJE)

PROZ(MDD,X065) PROZ(OCD,HCJW) REMER(MDD,045) SERZ(MDD,141) SERZ(MDD,187) ZOLO(MDD,501001) ZOLO(MDD,501017) 0.42 (0.15,1.15) 0.41 (0.16,1.04)

1.82 (0.75,4.39) 0.84 (0.37,1.88) 2.00 (0.96,4.18) 0.70 (0.25,1.97) 3.92 (0.45,34.50) 4.73 (0.23,97.73) 0.90 (0.26,3.12) 0.78 (0.44,1.39) 0.71 (0.35,1.45) 0.90 (0.08,9.58)

0.81 (0.40,1.65) 0.80 (0.33,1.94) 1.28 (0.58,2.79) 1.04 (0.44,2.45) 0.93 (0.43,1.99) Overall (95% CI) 0.93 (0.75,1.15)

.01 .1 1 7.2 8.9 4.2 7.1

5.8 4.9 0.6 0.3 2.6 13.7 8.7 0.9 9.0 6.2

6.6 5.8 7.4 10 100 Risk ratio Emergence of Suicidality

147 Discontinuation All trials, all indications (Fixed effect model) Risk ratio (95% CI)

% Weight Study CELE(MDD,18) CELE(MDD,94404) EFFEX(MDD,382) EFFEX(MDD,394) PAXIL(MDD,329) PAXIL(MDD,377) PAXIL(MDD,701)

PAXIL(SAD, 676) PROZ(MDD,HCCJ) PROZ(MDD,HCJE) PROZ(MDD,X065) PROZ(OCD,HCJW) REMER(MDD,045) SERZ(MDD,141) SERZ(MDD,187) ZOLO(MDD,501001) ZOLO(MDD,501017)

0.82 (0.19,3.57) 0.60 (0.26,1.38) 2.50 (0.52,11.93) 0.81 (0.21,3.19) 1.55 (0.49,4.94) 0.80 (0.21,3.10) 1.69 (0.36,7.98) 8.79 (0.47,165.62) 0.67 (0.15,2.98)

1.34 (0.66,2.71) 0.88 (0.31,2.48) 1.09 (0.11,10.83) 1.31 (0.39,4.46) 0.51 (0.11,2.30) 1.29 (0.12,13.43) 1.75 (0.21,14.28) 1.50 (0.29,7.65) Overall (95% CI)

1.11 (0.81,1.50) .01 .1 1 10

100 Risk ratio Worsening/Emergence of Suicidality/discont 5.1 18.3 3.1 5.8 6.1

6.2 3.7 0.7 3.7 16.5 8.5 2.0 5.9 7.3 1.9

2.1 3.1 149 Impact of Antidepressants on Suicide Rates

1957-1985: USA: suicide rates 31% 1986-1999: USA: suicide rates 13.5% 1986-1999: 4-fold Rx for antidepressants Most people who die from suicide were not receiving treatments for depression Grunebaum, et al. (2004)

CDC Data: Ages 5-14 (Am. J. Psychiatry, 2006) 1996-1998Suicides: 933 Low rates of SSRI Rx: 1.7 / 100,000 / year High rates of SSRI Rx: 0.7 / 100,000 / year Impact on Prescribing

CDC: Lubell, et al. 2007 1990-2003: suicides 29% (ages: 10-24) 30-40% decrease in prescriptions for antidepressants for kids and teens 2003-2004: teenage suicides increased by 18%

When antidepressants can provoke suicide V:OTC Products Endorsed By: USP (US Pharmacopia) ST. JOHNS WORT

157 Cochrane Data Base: Systematic Studies Meta analysis St. Johns Wort; equal efficacy to prescription antidepressants Linde, et al. (2008)

158 ST. JOHNS WORT TREATMENT Reasons for use 900-1800 mg per day Three, divided doses Cost: $1.00 per day 159

ST. JOHNS WORT Side effects: mild GI, sedation. No: weight gain or sexual dysfunction Watch for Drug-Drug Interactions! Washout time before starting another antidepressant: 5 Days 160

S-Adenosylmethionine SAM-e Comprehensive review of literature (Papakostas, et al. , 2003) 76 studies world-wide Comparable efficacy to ADs

Much better tolerated 162 SAM-e Treatment: Major Depression 400-1600 mg per day $3-5 per day IV Dosing Methyl donor: serotonin

and norepinephrine 163 SAM-e So Far lack of significant drug-drug interactions Problems: homocysteine Take: B vit. including Folate Can provoke mania Treats osteoarthritis

164 Low Folic Acid: Associated with Depression: > meta analysis: 10 epidemiologic studies: > significant relationship between low folate and depression (Gilbody, et al. 2007)

165 Low Folic Acid: Associated with Decreased CSF metabolites: Serotonin (5-HIAA) Dopamine (HVA) Norepinephrine (MHPG) Depression may lead to

low folate 166 Folic Acid Low serum levels in treatmentresistant depression and early relapse Low folate: increased risk for dementia 167

Folic Acid Dosing: 500 mcg per day Significant augmenter vs placebo Prozactook ten weeks (Coppen, 2000) Deplin (L-methylfolate) > no advantage over folic acid With Depakote: 1-2 mg per day 168 Omega-3

Fatty Acids: essential fatty acids Families of Fatty Acids Omega-3 > LNA: seed and nut oils > EPA: fish oil > DHA: fish oil

Omega-6 > LNA: seed and nut oils > Soy bean oil and corn oil > Arachidonic acid: Animal Tissue 170 Omega 3:6 ratios Typical USA diet: 1:20 Ideal: 1:3

Omega 3 Fatty Acids: Bipolar Disorder Mixed findings (Stoll, et al. 1999; Peet and Horrobin, 2002; Nemets, et al., 2002) 172 Omega-3 and Depression Fish oil: Much better bio-availability

1-2 grams a day (EPA + DHA) 6 published studies: major depression > all: add-on studies > all significant better than placebo omega 3, serotonin and dopamine transmission 173 Omega-3, Pregnancy and Major Depression

(Su, Chin, et al. 2008) N: 36

8 weeks, double blind, placebo EPA: 2.2 grams, DHA: 1.2 grams Response: Omega-3: 62%...placebo: 27% Remission: Omega-3: 38%...placebo: 18% No side effects Omega-3 Fatty Acids Side effects: GI (diarrhea, nausea) Take with foodginger root

or ginger ale The mercury issue 175 176 5-HTP Tryptophan 5-HTP 5-HT (serotonin)

5-HTP 2 well controlled double-blind studies (total 108) 300 mg per day (600 TRD) Main Side effect: Sedation (pm) Compounding pharmacy Watch for serotonin syndrome Other OTC Options

Melatonin Kava Kava Valerian CAUTION! High-Intensity Light Therapy High Intensity Light Therapy SAD and winter blues: 1:4

Psychoanalytic views of seasonal mood changes (1945) High Intensity Light Therapy Dosing: 2500 lux Average time: 20 minutes Morning light is 2 x more effective Effects seen: 2-3 days Lost with placebo or

discontinuation High Intensity Light Therapy Use in non-seasonal depression Side effects: nausea, jitteriness, eye strain, dizziness Blue lights: forget it High Intensity Light Therapy

Contraindications: macular degeneration, retina diseases, post cataract surgery UV effect on the skin Bipolar disorder Dawn Simulation Sunlight Exposure (melanocytesendorphins)

Exercise Dosing 10,000 steps per day Aerobic in keeping with fitness Two 10 minute sessions a day

20 minutes: 3 times a week St. Moms Wort Given to pre-schoolers: renders them unconscious for 6 hours Practice Case: 1 54 year old man. Profession: undertaker. No

history of depression. 6 months ago funeral home was sold and he was not hired by the new owner. He had worked for the former funeral home for 25 years 3 months of unsuccessful job searching. Felt frustrated. Possibly low grade depression Practice case: 1 3 months ago at family gathering, a relative

made a comment about his chronic unemployment From that point there has been a downward spiralincreasing low self-esteem.. increasing depression Clinical Symptoms

Marked apathy and anhedonia Early morning awakening 11 pound weight gain Suicidal ideas Fatigue

Social withdrawal (impact on job search) No sex drive (impact on marriage) Other factors to consider

Caffeine use: 4 12 oz. cups of coffee per day Occasional alcohol use Chronic headaches (takes OTC meds) No significant medical illnesses No use of prescription drugs No drug abuse Initial Questions What is the diagnosis?

Given the clinical picture, what class of antidepressants should be considered as a first-line choice?....and why? He is started with an antidepressant (one that does not require initial titration)the dose is considered to be in the therapeutic range Three weeks He reports: no noticeable changes since starting medication

treatment What do you do first? And why? (highest yield next step strategies) You implement revised treatment plan Week 6 (since first dose): no improvement What do you do?...and why New Strategy Works

4 weeks into new treatment: 20% improvement on current medications What do you do? New scenario: 4 weeks: 50% improvement 4 additional weeks: still at 50% improvement What do you do? New Scenario Week 3 into the initial treatment and you discover that the patient has cold intolerance.

What might this suggest and how might it affect your treatment? New Scenario: Different Presenting Clinical Symptoms

Significant anxiety; lots of rumination Early morning awakening 11 pound weight loss Suicidal ideas Anger outbursts and marked irritability Social withdrawal (impact on job search) No sex drive (impact on marriage)

Questions Given the clinical picture, what class of antidepressants should be considered as a first-line choice?....and why? He reports that after the first day of treatment there is an increase in anxiety and agitation what is going on and what might you do to address this situation?

Side Effect Problems: how might you address each? Significant nausea Onset of initial insomnia After he begins to respond positively, there is some return of libidohe is relieved 4 weeks later he reports an inability to reach an orgasm..what is likely to be happening? What can you do?

Side Effect Problems: how might you address each? Different scenario: after 4 weeks, he starts to experience impotencywhat is happening/ What might you do? New Scenario Treatment is successful he has reached remission. What do you do now?

New Scenario Treatment is successful he has reached remission. 2 months into continuation he reports break-thru depressive Sx.what might be happening?....what can you do?

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    Zaměření EK na rok 2011 Monitorování správné implementace evropských zákonů o rovném zacházení (především ve vztahu k direktivám 2004/113/ES and 2006/54/ES). ... založeného na pohlaví a obchodování s lidmi Překonávání genderových stereotypů Priority a postupy MV při ...