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DEPRESSION

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Title: DEPRESSION


1
DEPRESSION
2
PREVALENCE OFCLINICAL DEPRESSION(1994)
  • LIFETIME 17 (?)
  • YEARLY 10
  • Bipolar 5

3
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)

4
A RECURRING ILLNESS
  • 20 SINGLE EPISODE
  • 80 RECURRENT or CHRONIC

5
Depression Fluctuating Course
  • N 431 ( ¼ 1st.episode, ½ recurrent, ¼ double
    D.)
  • 12 year Follow-up
  • Symptomatic 58, 42 Sx-free
  • Time Symptomatic
  • gt 15 MDD
  • gt 43 Sub-Syndromal

6
Depression Fluctuating Course
  • N 431 ( ¼ 1st.episode, ½ recurrent, ¼ double
    D.)
  • 12 year Follow-up
  • Symptomatic 58, 42 Sx-free
  • Time Symptomatic
  • gt 15 MDD
  • gt 43 Sub-Syndromal

7
WORLD HEALTH ORGANIZATION STUDY
  • Each day in Primary Care Medical Settings
  • gt 25 of patients have Clinical Depression
  • gt 10 have Anxiety Disorders
  • gt 10 have Substance Abuse Disorders


  • cont.

8
MOST COMMON DISORDERS SEEN IN PRIMARY CARE
  • Hypertension
  • Depression
  • Anxiety Disorders

9
Most Reactive Depressions
  • If they reach the intensity level of Major
    Depression, will show vegetative symptoms.

10
BIOLOGIC SYMPTOMS
  • ANHEDONIA
  • SLEEP DISTRUBANCES
  • APPETITE DISTURBANCES
  • LOSS OF SEXUAL DRIVE
  • FATIGUE

11
DysthymiaIll-Humor
  • 5 Of the Population (lifetime prevalence)
  • Most eventually also develop
  • Major Depression ?

12
Dysthymia
  • Pharmacologic Outcome
  • 33 Excellent Response
  • 33 Good Response
  • 34 Poor Response (Akiskal, 1997)

13
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14
Has the Success ofAntidepressantsBeen
Over-Sold?
15
Patient selection criteria
16
Patients Recruited inAntidepressant Drug
StudiesZimmerman, et al. (2002)
  • N 346 (MDD, outpatient practice)
  • 86 would be excluded
  • from drug studies

17
ITT Intent to TreatResponse Rates MDD
  • Single Antidepressant trial
  • Do not tolerate 15
  • No response 35
  • Responders 50

18
ITT Rates
  • Responder 50 ? HAM-D, or
  • HAM-D Score of 7 or less
  • Responders
  • gt Full Responders HAM-D lt 7
  • 50
  • gt Partial Responders
  • HAM-D 9-14 50

19
ITT The Rest of the Story
  • Full Responders
  • gt 18 truly asymptomatic
  • gt 82 subtle residual
  • symptoms

  • Nierenberg, et al. (1999)

20
Partial RespondersIs Symptomatic
ImprovementGood Enough?
21
Partial Responders
  • Time to Next Episode
  • 3 times longer to next episode
  • remitters vs. partial
  • responders
  • Quality of life
  • (espec. Social Functioning)

22
Evidence-BasedMedicine andTreatmentAlgorithms
23
Depression
24
Implications forTreatment Success1.
Hopelessness and Drop-outs(long time to
response)2. Compliance high risk patients3.
Extreme response to side effects4. Premature
discontinuation(skepticism about meds 62 ? in
DC)5. Patient preferences6. Inaccurate
diagnosis
25
Rating Scales
26
First weeks of Treatment
  • Aim to get some immediate relief
  • Medication strategies
  • Exercise
  • Bright light (details later)
  • Combat social withdrawal

27
On-Line Algorithms
  • International Psychopharmacology
  • Algorithm Project
  • endorsed by WHO
  • www.IPAP.org
  • www.MHC.com
  • (also P 450 drug interactions)

28
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29
Choosing a First-lineAntidepressant
30
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31
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32
Targeting Neurotransmitters
  • NE norepinephrine
  • 5-HT serotonin
  • DA dopamine

33
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34
NEWER GENERATIONANTIDEPRESSANTS
  • 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

35
Neurotransmitters and Behavior
  • Serotonin
  • Anxiety, Rumination, Irritability,
  • Aggression, Suicidality
  • Shelton and Tomarken (2001) Metzner, (2000)

36
Neurotransmitters and Behavior
  • Catecholamines
  • Dopamine and Norepinephrine
  • Anhedonia, Apathy, Impaired
  • Attention
  • Shelton and Tomarken (2001) Metzner, (2000)

37
Antidepressants AgorithmTexas
MedicationAlgorithm ProjectTMAP
38
ANTIDEPRESSANT ALGORITHM
  • With Anxiety or Agitation
  • SSRIs
  • Anergic
  • Atypical
  • PMDD

39
Activation vs Switching
  • Activation within hours anxiety
  • and/or initial insomnia
  • Switching 3 weeks manic symptoms

40
Benzodiazepine AugmentationStart up(Ward Smith,
et al.)
  • Check for history of substance abuse
  • Antidepressant and tranquilizers
  • Early responsefewer drop outs

41
Benzodiazepine use HMO Setting(Samari, 2007)
  • N 2440
  • Treated for 2 years with
  • tranquilizers
  • Percent of those requesting
  • increased doses 1.6

42
ANTIDEPRESSANT ALGORITHM
  • With Anxiety or Agitation
  • Anergic Wellbutrin
  • Atypical
  • PMDD

43
Stimulant augmentationwith anergic depressions
44
ANTIDEPRESSANT ALGORITHM
  • With Anxiety or Agitation
  • Anergic
  • Atypical watch for bipolar
  • PMDD

45
ANTIDEPRESSANT ALGORITHM
  • Pre-Menstrual Dysphoria
  • SSRIs

46
ANTIDEPRESSANT ALGORITHM
  • Very Severe and/or Recurrent
  • Dual Action
  • Effexor, Pristiq, Cymbalta,
  • Remeron, Wellbutrin

47
Standard vs. Targeted Treatment of Patients
Improved
Metzner, 2000
  • Preliminary study of depressed patients sampled
    in outpatient private practice settingSTD
    Standard Rx
  • TTD Targeted selective antidepressants only

48
GUIDELINES forMEDICAL TREATMENT ofDYSTHYMIA
  • IRRITABILITY SSRIs
  • LOW ENERGY, APATHY, LOW-GRADE ANHEDONIA
    Wellbutrin
  • not based on
    empirical studies

49
Additional Considerationsin Medication Choices
  • Side Effects
  • Patient Preferences
  • Pharmacokinetics

50
PHASES OF TREATMENT
  • ACUTE Until Asymptomatic
  • CONTINUATION 6 months _at_
  • Same Dose
    ?
  • MAINTENANCE Third Episode
  • Lifetime Treatment

51
Continuation Phaseof Treatment
  • Minimum of six monthssame dose
  • Patient-initiated discontinuation
  • High rates of acute relapse
  • Serotonin and emotional blunting
  • Dampens dopamine

52
Antidepressant Discontinuation Syndromes
  • Symptoms nausea, dizziness,
  • malaise, electric shock-like
  • sensations
  • Most likely
  • Paxil, Effexor, Cymbalta, Pristiq
  • Least likely Prozac

53
MaintenancePhase
54
ADEQUATE TRIAL
  • DOSE
  • COMPLIANCE
  • TIME
  • BLOOD LEVELS

55
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

56
Response
  • Remission
  • Partial
  • Poor

57
Overview Options for Inadequate Response
  • Optimization
  • Augmenting
  • gt Combination Treatments
  • Switching Drug Classes

58
Optimization ? dose ? time
59
AugmentingCombination
60
Switching Classese.g serotonin ?
norepinephrinereuptake inhibitor
61
Empirical Studies
  • STAR-D Sequenced
  • Treatment
  • Alternatives to Relieve
  • Depression (NIMH)

62
STAR-D(2007)
  • N 4100
  • Ages 18-75
  • Average patient
  • 3 medical illnesses
  • 65 psychiatric co-morbidity

63
STAR-D
  • 80 chronic or recurrent
  • 25 have been depressed
  • for 2 years
  • 53 anxious depressions

64
STAR-D Rating Scalepage
  • Side effect scale
  • Page

65
Overview Options for Inadequate Response
  • Optimization
  • Augmenting
  • gt Combination Treatments
  • Switching Drug Classes

66
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

67
STAR-D(2006)
  • PHASE TWO
  • Non-remitters randomized
  • gt Switch
  • gt Augmentation

68
STAR-D Switch(2006)
  • Effexor 25
  • Wellbutrin 21
  • Zoloft 17
  • Average time to remission
  • six weeks

69
STAR-D Augment(2006)
  • Wellbutrin 30
  • BuSpar 30
  • Augmenting slightly higher yield
  • than switching

70
New Study
71
STAR-D After Phase 2
  • 55 reach remission

72
STAR-D(2006)
  • PHASE Three
  • gt Switch
  • nortriptyline (tricyclic)
  • or Remeron
  • gt Augment
  • lithium
  • T3

73
STAR-D(2006)
  • PHASE Three
  • gt Switch
  • nortriptyline or Remeron 13
  • gt Augment
  • lithium
    20
  • T3
    20

74
T3 Augmentation
  • 4 double bind studies indicate efficacy
  • STAR-D study very high yield
  • Few Side Effects
  • Dose Cytomel 25-75 micrograms qd

75
STARD Final Outcomes
  • 67
  • Complete remission

76
STAR-DCumulative Sustained Recovery Rate
  • 43

77
STAR-D Monotherapy
78
STAR-D Monotherapy
79
STAR-D AugmentationGuidelines
80
What Can Be Learned fromSTAR-D
  • Use of rating scales
  • Aggressive dosing
  • Some suggestions next steps
  • Testament to the difficulties in
  • treating very severe depression

81
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)

82
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)

83
PARTIAL RESPONSESTRATEGIES
  • FIRST Check Compliance
  • Substance Abuse
  • INCREASE DOSE
  • AUGMENT

84
Other augmentationStrategies
85
Augmentation Strategies
  • Lithium 0.3-0.6 mEq/l
  • gt ? relapse x 3
  • gt 7 fold ? suicides



86
THYROID
  • Adding T3 or T4 augmentation
  • T4 for rapid cycling
  • Hypothyroid in Lithium therapy

87
Thyroid Augmentation
  • T4 levo-thyroxine
  • gt Synthroid, Levothyroid, Levoxyl
  • gt 1 mcg per pound of weight qd
  • T3 triiodothyronine
  • gt Cytomel
  • gt 25-75 mcg. qd

88
Hypothalamus?TRH?Pituitary?TSH?ThyroidT3
? Gland ?T4
89
TSHThyroid StimulatingHormone
90
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)

91
Normal TSH Levels
  • High Normal Range 3.0
  • Median 1.3
  • Low Normal Range 0.3




  • miliIU/Liter

92
Normal TSH Levels
  • High Normal Range 3.0
  • 2.5
  • Median 1.3
  • Low Normal Range 0.3




  • miliIU/Liter

93
Stimulant Augmentation
94
MAOIs
95
New MAOIEmsamselegiline transdermal6-12 mg
per day
96
Augmentation Strategies
  • Atypical Antipsychotics
  • Zyprexa Abilify
  • Geodon Risperdal
  • Seroquel ?

97
Reducing Treatment-Resistant Unipolar Depression
  • MADRS Total Acute Treatment

Fluoxetine(n10)
0
-5
Olanzapine(n8)
Mean Change from Baseline (LOCF)
Improvement
plt0.05 vs Flx. plt0.05 vs Olz.
-10
Olanzapine/ Fluoxetine(n10)
-15















-20
0
1
2
3
4
5
6
7
8
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 158131-134.
98
Folic Acid
  • Low serum levels in treatment-
  • resistant depression and early
  • relapse
  • Co-factor Serotonin
  • 500 mcg 2 X per day
  • With Depakote 1-2 mg per day

99
High Intensity Light Therapy
  • Seasonal and
  • non-seasonal
  • Caution with
  • Bipolar

100
POOR RESPONSESTRATEGIES
  • CHECK COMPLIANCE and
  • SUBSTANCE ABUSE
  • INCREASE DOSE
  • SWITCH CLASSES
  • e.g. SSRI ? NE
  • NE ? SSRI

101
Within Class Switches
  • Reasons for switch
  • gt Tolerability
  • gt Efficacy (espec. with partial Response)
  • Two SSRI failures switch classes

102
LATE EMERGING SEROTONINSIDE EFFECTS
  • SEXUAL DYSFUNCTION
  • gt Inorgasmia
    ?
  • APATHY and EMOTIONAL BLUNTING
  • WEIGHT GAIN (10 after one year)

103
Prevalence SexualProblems / Complaints
  • Reporting 14
  • Elicited on questionnaire 60
  • N 6300 only 29 had no
  • other risk factors except
  • antidepressant exposure

104
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

105
LATE EMERGING SEROTONIN SIDE EFFECTS
  • SEXUAL DYSFUNCTION
  • gt Inorgasmia
  • APATHY and EMOTIONAL BLUNTING
  • WEIGHT GAIN (10 after one year)

106
GENDER DISTRIBUTIONDEPRESSIONDisorder
Female Male
  • CHILDREN
  • TEENS
  • ADULTS
  • BI-POLAR I
  • BI-POLAR II
  • 1 1
  • 2 1
  • 2 1
  • 1 1
  • 2 1

107
Premenstrual DysphoricDisorder PMDD
  • Average female 400 periods
  • 70 PMS at some point in time
  • 30 significant PSM
  • 4 PMDD

108
Premenstrual DysphoricDisorder PMDD
  • Premenstrual exacerbation
  • of Major Depression symptoms
  • 90 of women who successfully
  • commit suicide premenstrual

109
Premenstrual DysphoricDisorder PMDD
  • Treatments
  • gt reduce caffeine, alcohol, salt,
  • sugar, and stop smoking
  • gt exercise
  • gt Serotonin antidepressants
  • gt St. Johns Wort (case reports)

110
Premenstrual DysphoricDisorder PMDD
  • Antidepressant treatments
  • Must target Serotonin
  • Intermittent versus
  • continuous
  • Quick onset of actions

111
PMDD and SEROTONIN
  • Fluctuating estrogen levels can have
  • an impact on
  • Tryptophan hydroxylase
  • (rate-limiting enzyme for production of 5-HT)

112
Allopregnenolone
  • Neuro-steroid synthesized in
  • the brain
  • Potent GABA-A agonist
  • Low levels in MDD CSF
  • (? with successful treatment)

113
Allopregnenolone
  • PMDD marked reduction
  • Rapid increase with SSRIs
  • but not with non-
  • serotonin antidepressants

114
Premenstrual DysphoricDisorder PMDD
  • Calcium supplementation
  • 2 double blind, placebo controlled
  • studies
  • 1200 mg per day (4 Tums)
  • 55 vs 36

115
Depression and Pregnancy
116
Myths about Pregnancyand 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

117
Depression and Pregnancy
  • Depression and pregnancy
  • gt Hypercortisolemia
  • gt Substance abuse
  • gt Suicide attempts
  • gt Post-partum exacerbation
  • (bonding and attachment)

118
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119
Depression and Pregnancy
  • Depression and pregnancy
  • gt Hypercortisolemia
  • gt Substance abuse
  • gt Suicide
  • gt Poor self care
  • gt Post-partum exacerbation
  • (bonding and attachment)

120
FDA RATINGS USE DURING PREGNANCY
  • A No Risk. Well controlled studies
  • B No Evidence of Risk
  • C Risk Cannot Be Ruled Out
  • D Positive Evidence of Risk
  • X Contraindicated in Pregnancy

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

122
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

123
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

124
Antidepressants Risks
  • No specific birth defects
  • ??? Cardiac defects in SSRIs ???

125
The Jury is Still Out
126
Zoloft Lowest Level 2
Average antidepressant levels 7 of the mothers
blood level
127
PSYCHOTIC DEPRESSIONS
  • Antidepressants (AD) 35
  • Antipsychotics (AP) 45
  • AD AP 75
  • ECT 90
  • Note Continuation Phase One Year
  • AD and AP

128
Electroconvulsivetherapy
129
ECT Electro-convulsiveTherapy
  • Shock Treatments
  • V

130
DEPRESSION IN CHILDREN and ADOLESCENTS
  • MAJOR
  • DEPRESSION
  • Children 3
  • Teens 10
  • 35 recurrent
  • 50 bipolar

131
Depression in Young Children
  • Luby, et al. (2002)
  • N49
  • Using DSM-IV criteria 12 Dx as MDD
  • Thus must use modified criteria

132
MDD Children Modified Diagnostic Criteria
  • Most of the day, more days than not
  • Play themes of death, suicide, self-
  • destruction (61)
  • Depressed or irritable mood or
  • Diminished interest plus 4 Sx
  • (vs 5 for adults)

133
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) ..

134
Child and Adolescent DepressionAdditional 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

135
Problems withthe studiesMeta analysisEffect
Size 0.25
136
T A D S Treatment for Adolescents with
Depression Study
Effectiveness Outcomes (2004)
137
Random Assignment
  • NIMH Study
  • N 432
  • Placebo
  • Prozac
  • Cognitive Behavioral Therapy
  • Combo drug and CBT

138
Treatment Response Week 12
T A D S
139
Effect Size
T A D S
140
Time to Onset of Effects
  • Anxiety 1-2 weeks
  • Depression 4-6 weeks
  • but responders in 10-12
  • week range !

141
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142
Paxil and Increased Suicidality
  • UK studyN1300 adolescents
  • Increased suicidality
  • Placebo 1.2
  • Paxil 3.4
  • No actual Suicides
  • 33 suicidal incidents ..

143
Paxil and Increased Suicidality
  • Acute Treatment data
  • Discontinuation
  • State of Connecticut
  • Human Implications

144
TADS(2004)
  • At baseline 29 suicidal ideas
  • Attempts 1.6
  • Actual Suicides 0

145
Suicidality Is Reduced Overall
T A D S
146
FDA DataN 4400N 300http//www.fda.gov/ohrm
s/dockets/ac/04/slides/2004-4065s1.htm
147
147
148
Discontinuation
149
149
150
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)

151
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

152
Impact on PrescribingCDC 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

153
When antidepressantscan provoke suicide
154
VOTC
155
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156
Products Endorsed By
  • USP (US Pharmacopia)

157
ST. JOHNS WORT
158
Cochrane Data BaseSystematic Studies
  • Meta analysis
  • St. Johns Wort equal efficacy to
  • prescription antidepressants
  • Linde, et al. (2008)

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

160
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

161
S-Adenosylmethionine
162
SAM-e
  • Comprehensive review of literature
  • (Papakostas, et al. , 2003)
  • 76 studies world-wide
  • Comparable efficacy to ADs
  • Much better tolerated

163
SAM-e
  • Treatment Major Depression
  • 400-1600 mg per day
  • 3-5 per day
  • IV Dosing
  • Methyl donor ? serotonin
  • and norepinephrine

164
SAM-e
  • So Far lack of significant drug-drug interactions
  • Problems ? homocysteine
  • Take B vit. including Folate
  • Can provoke mania
  • Treats osteoarthritis

165
Low Folic Acid Associated with
  • Depression
  • gt meta analysis 10 epidemiologic
  • studies
  • gt significant relationship
  • between low folate and
  • depression (Gilbody, et al.
    2007)

166
Low Folic Acid Associated with
  • Decreased CSF metabolites
  • Serotonin (5-HIAA)
  • Dopamine (HVA)
  • Norepinephrine (MHPG)
  • Depression may lead to
  • low folate

167
Folic Acid
  • Low serum levels in treatment-
  • resistant depression and
  • early relapse
  • Low folate increased risk for
  • dementia

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

169
Omega-3Fatty Acidsessential fatty acids
170
Families of Fatty Acids
  • Omega-3
  • gt LNA seed and nut oils
  • gt EPA fish oil
  • gt DHA fish oil
  • Omega-6
  • gt LNA seed and nut oils
  • gt Soy bean oil and corn oil
  • gt Arachidonic acid Animal Tissue

171
Omega 36 ratios
  • Typical USA diet 120
  • Ideal 13

172
Omega 3 Fatty Acids Bipolar Disorder
  • Mixed findings
  • (Stoll, et al. 1999 Peet and Horrobin, 2002
    Nemets, et al., 2002)

173
Omega-3 and Depression
  • Fish oil Much better bio-availability
  • 1-2 grams a day (EPA DHA)
  • 6 published studies major depression
  • gt all add-on studies
  • gt all significant better than
    placebo
  • ? omega 3, ? serotonin and
  • dopamine transmission

174
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

175
Omega-3 Fatty Acids
  • Side effects GI
  • (diarrhea, nausea)
  • Take with foodginger root
  • or ginger ale
  • The mercury issue

176
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177
5-HTP
  • Tryptophan ?
  • 5-HTP?
  • 5-HT (serotonin)

178
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

179
Other OTC OptionsCAUTION!
  • Melatonin
  • Kava Kava
  • Valerian

180
High-IntensityLight Therapy
181
High Intensity Light Therapy
  • SAD and winter blues 14
  • Psychoanalytic views of
  • seasonal mood changes (1945)

182
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

183
High Intensity Light Therapy
  • Use in non-seasonal depression
  • Side effects
  • nausea, jitteriness, eye strain,
  • dizziness
  • Blue lights forget it

184
High Intensity Light Therapy
  • Contraindications
  • macular degeneration,
  • retina diseases,
  • post cataract surgery
  • UV effect on the skin
  • Bipolar disorder

185
Dawn SimulationSunlight Exposure(melanocytes
endorphins)
186
Exercise Dosing
  • 10,000 steps per day
  • Aerobic in keeping with fitness
  • Two 10 minute sessions a day
  • 20 minutes 3 times a week

187
St. Moms Wort
  • Given to pre-schoolers
  • renders them
  • unconscious
  • for 6 hours

188
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

189
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

190
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)

191
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

192
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

193
Three weeks
  • He reports no noticeable changes since starting
    medication treatment
  • What do you do first? And why?
  • (highest yield next step strategies)

194
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195
You implement revised treatment plan
  • Week 6 (since first dose) no improvement
  • What do you do?...and why

196
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?

197
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?

198
New ScenarioDifferent 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)

199
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
    agitationwhat is going on and what might you do
    to address this situation?

200
Side Effect Problemshow 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?

201
Side Effect Problemshow might you address each?
  • Different scenario after 4 weeks, he starts to
    experience impotencywhat is happening/
  • What might you do?

202
New Scenario
  • Treatment is successful
  • he has reached remission.
  • What do you do now?

203
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?

204
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