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DEPRESSION

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					                               Peter M. Hartmann, M.D.
Clinical Professor of Family and Community Medicine at
                          Penn State College of Medicine
                                          June 23-25, 2011
                Objectives
1. List criteria for major depressive disorder.
2. Distinguish major depression from
   dysthymia and adjustment disorder.
3. Provide optimal treatment for patients
   with depression.
     Essential Feature of MDD
Patient must have either:

       Depressed mood (irritable in children)
                         Or
            Loss of interest or pleasure

                  For at least 2 weeks

      (Als0, must have at least 4 other symptoms.)
SIG E-CAPS
 Sleep
 Interest
 Guilt (worthless)
 Energy
 Concentration
 Appetite
 Psychomotor agitation or retardation
 Suicidal ideation
48 yo MWF high school teacher with MDD
 Given paroxetine (Paxil) 20 mg X 6 weeks
 without benefit.

 Changed to venlafaxine er (Effexor XR) 150
 mg X 6 weeks also without benefit.

  What additional information do you want?
Has resistant depression.
 Endorses the symptoms of MDD.
 Was sexually abused as a child.
 Is compliant with treatment.
 TSH is normal.
 Does not drink alcohol.
Causes of Resistant Depression
 Wrong diagnosis (e.g., personality disorder)
 Inadequate dose or length of treatment
 Non-compliant
 Substance abuse
 Requires different treatment
 Childhood abuse
 Co-morbid dysthymia
 Bipolar depression
Childhood Abuse
 Rarely will antidepressants work alone.


 Need to combine medication with therapy.
Bipolar Depression
 History of mania or hypomania?
 Family history of bipolar disorder, suicide,
  prolonged psychiatric hospitalization or non-
  schizophrenic psychosis.
Treatment of Bipolar Depression
 Stop antidepressant if Bipolar I Disorder

 Start mood stabilizer:
1. Lithium (level 0.6 to 1.2)
2. AED (lamotrigine good choice)
3. Atypical antipsychotic (quetiapine or aripiprazole)*
4. ECT

* Only FDA approved are quetiapine XL and
   olanzapine/fluoxetine combined.
Major Depressive Disorder


    Resistant Depression
Picasso Painting of Depression
                    STAR*D
Sequenced Treatment Alternatives to Relieve
  Depression (NIMH, 2876 patients, 6 years)
1. Majority fail to achieve & sustain remission (only
   30%).
2. Cognitive behavioral therapy (CBT) = medication
   (CBT takes twice as long)
3. Start with citalopram; if no remission, proceed to
   sequenced treatments (Phase II – IV)
Phase I: Citalopram
 Better response:
Higher education
Employed
Married
Caucasian
Female
Few complicating problems
 Worse response:
Co-occurring anxiety
Substance abuse
Physical illness
Lower quality of life
Inadequate Response
 Increase dose
 Reinforce need to comply
 Refer for therapy (cognitive behavioral or
  interpersonal)
 Assess other factors such as diagnosis
Phase II
 Three options if not in remission in 14 weeks:


Option 1: Switch from citalopram to :
1. Sertraline
2. Bupropion SR
3. Venlafaxine XR


   25% remission
   No difference among choices
 Option 2: Augment
1. Bupropion SR
2. Buspirone


    33 1/3 % remission within 14 weeks
    No difference in remission rate
 Option 3: Cognitive therapy (CBT)*
1. Switch to CBT
2. Add on CBT


    23-25% remission
    No difference between switch and add on
    CBT = medication but takes twice as long

*16 sessions over 12 weeks
Phase III
 For the 50% not in remission after Phase II
 Two options:


Option 1: Switch up to 14 weeks
1. Mirtazapine
2. Nortriptyline


   10-20% remission
   No advantage of one over the other
 Option 2: Add different agent:
1. Lithium
2. T3


    20% remission
    Fewer SE with T3 (many dropouts with Lithium)
Phase IV
 Take off all medications and change to one of 2
 options:
Option 1:
  Venlafaxine XR + Mirtazapine (10% remission)

Option 2:
  Tranylcypromine (10% remission; more SE and
  harder to take)
STAR*D Remission & Relapse Rates
 Level   Remission   Relapse



 I       36.8%       40.1%

 II      30.6%       55.3%

 III     13.7%       64.6%

 IV      13.0%       71.1%
Conclusions:
 Switch from one SSRI to another.
 Adding another agent helpful:
     Lithium        Buspirone
     T3             Mirtazapine
      Bupropion Nortriptyline
 Switch to Venlafaxine XR plus Mirtazapine
 Switch to MAOi
 Switch to or add CBT
Other Options from Different
Studies:
 Supplement with low dose atypical
  antipsychotic (e.g., aripiprizole 5 mg hs)
 Methylphenidate or mixed amphetamine salt
 Modafinil or Armodafinil
 Folate may help depressed dementia patients
 ECT, TMS, vagal nerve stimulation
  (Brain is electrochemical organ)
                  Bright Light
 Dutch study of 89 outpatients, age 65 and older
 7500 lux of pale blue light for 1 hour in early AM
                       vs.
 50 lux of dim red light for 1 hour in early AM (placebo)


 Active > Placebo
 Salivary cortisol down 34% with active
        vs. increase 7% with placebo.
SSRI PLUS ATOMOXATINE
   Michaelson et al J Clin Psych 2007; 68(4): 582
32 yo SWF secretary has been depressed “all my life;”
low self-esteem; overeats and oversleeps; has therapist

What additional information do you want?
More History
 Sad mood most days for “my whole life”
 Not anhedonic
 Never had sex but libido seems normal to
  her
 Never had suicidal thoughts
 Mother and maternal aunt had major
  depression responsive to fluoxetine
Lab
 TSH normal
 Had polysomnography because of excessive
  sleeping. Results:
1. Decreased REM latency
2. Decreased slow wave sleep
3. Impaired sleep continuity
4. No PLMD or sleep apnea
Dysthymia
 Chronically depressed mood most days for 2 years
  or more (one year in children)
 At least two of the following:
1. Decreased appetite or overeating
2. Decreased sleep or oversleeping
3. Low energy
4. Poor concentration or trouble making decisions
5. Low self-esteem
6. Hopelessness
Considerations
 Prevalence 6% (M:F is 2:1 in adults; kids 1:1)
 Usually family Hx of MDD
 Less vegetative symptoms than in MDD
 “B,M,C”
 “Double dippers”
 25-50% have same polysomnography as
  MDD
 Cause of resistant depression
17 yo SF high school student broke
up with boyfriend 2 weeks ago.
 Cries “constantly”
 Skipping classes
 Won’t do her homework
 Avoiding her friends
 Mother reports she wishes she was dead


What do you want to know?
More History
 Does not meet criteria for MDD
 Does not meet criteria for Acute Stress
  Disorder or PTSD
 Has been a superior student who always did
  her homework and never missed class
  unless sick.
 No substance abuse
Adjustment Disorder
 Significant emotional or behavioral symptoms due
  to psychosocial stressor(s) within 3 months of
  onset of stressor(s)
 Excessive distress or impaired social or
  occupational (school) functioning
 Does not meet criteria for MDD
 Does not apply if due to Bereavement
 Symptoms last less than 6 months unless
  stressor(s) are continuing
                Treatment
 Therapy


 Suicide is increased risk


 Symptom relief based on clinical judgment (e.g.,
  insomnia or anxiety)

 No role for antidepressants unless also MDD
24 yo SBM with schizophrenia, bright,
unemployed, c/o “depressed”
History
 Distressed about cognitive difficulties and
  unemployment despite high IQ.
 Lives with parents who are highly critical (negative
  expressed emotion).
 Endorses sad mood, anhedonia, sleep and appetite
  decreased, never had much sex drive, poor
  concentration and self attitude, admits suicidal
  ideation.
Lab studies and Physical Exam
 TSH normal
 CBC, metabolic profile normal, elevated
  LDL
 Urinalysis normal
 Urine drug screen shows cannabis
 Nicotine stains on fingers
 Below ideal body weight
Treatment Considerations
 Increased risk for relapse of schizophrenia
  due to parental negative expressed emotion.
 High suicide risk (schizophrenia).
 Pot smoking aggravating condition.
 Cigarette abuse and limited self care.
 Consider bupropion for depression and
  nicotine dependence.
 Consider Omega 3 (4 capsules per day)
Stigma
 Stress biological nature of MDD (just like
 diabetes)

 Not your fault (allow yourself sick role)


 Terry Bradshaw story
Terry Bradshaw
Bradshaw’s Story:
 Born Sep 2, 1948 in Shreveport, Louisiana
 Hyperactive and poor student as child
 All American in college at Louisiana Tech
 6’3” 215 lb quarterback
 Hall of Fame 1989 (broke all records)
 Three time pro bowler with Steelers
 8 AFC Central Champs, 4 Super Bowl winners
    (MVP in 2)over 6 year timespan
 Threw an 87 yard pass (AFC longest)
 TV host, author, actor, singer, motivational
  speaker
 Well known on “NFL Today” and “Fox NFL
  Sunday”
 Married and divorced 3 times (2 kids to third wife)


 “Bottomed out” at age 26 (marriage failed,
 shoulder injured, sullen and depressed)
Bradshaw and Depression
 Frequent anxiety attacks after games

 After 3rd divorce lost weight, crying spells, insomnia –
  diagnosed with depression and treated with Paxil

 Is now a frequent speaker about men and depression.

 Tries to destigmatize depression as an illness.

 Is still in therapy and takes medication for ADHD.
25 yo MWF school teacher is 2 months pregnant.
Presents with MDD. Prior Hx post partum depression.
More history
 Meets criteria for MDD.
 Not suicidal.
 One male child age 6 with ADHD.
 Supportive husband is worried about
  medications during pregnancy.
 Had non-psychotic post partum depression
  successfully treated with sertraline.
Depression in Pregnancy
 Depressive symptoms in 14-23 %.
 Depression per se harms the fetus.
 Depression assoc. with 2.5 fold increase in
  preeclampsia.
 Goal is to optimize pregnancy outcome.
 Encourage good health behaviors (prenatal
  vitamins, good eating habits, regular sleep,
  avoid alcohol and smoking).
                 Treatment
 Cognitive-behavioral or interpersonal therapy for
  mild to moderate
 Antidepressants for severe
 Antipsychotics if psychotic depression
 May need to increase dose in later pregnancy
 Post Partum depression may be due to MDD or
  Bipolar Disorder (most psychotic forms are
  bipolar)
 Consultation is helpful
St. John’s Wort
St. John’s Wort (Hypericum
perforatum):
 Good for mild depression.


 Inhibits uptake of NE, DA and serotonin.


 Safe for up to 1 year.


 Dose: 300 mg tid      (2-4 gm/day may cause
                               phototoxicity).
 Does not affect cognitive functioning.
St. John’s continued:
 Active ingredient is hyperforin (3-5%) but often
  standardized to hypericin 0.3%.
 Side-effects:
1. Drowsiness
2. Orthostatic hypotension
3. Insomnia, vivid dreams
4. Serotonin syndrome
5. Restless, agitated, anxious
6. GI upset, diarrhea
St. John’s and other drugs:
 Reduces effectiveness of bc pills.
 Clopidogrel (Plavix) - more bleeding
 Alprazolam (Xanax) – less effective
 Warfarin – lowers INR
 SSRIs – serotonin syndrome
 Statins – lowers blood level
St. John’s Withdrawal:
 Usually starts within 2 days but can be > 1
 week.

 Symptoms: headache, nausea, anorexia,
 dry mouth, thirst, cold chills, weight loss,
 dizziness, insomnia, paresthesias, confusion
 and/or fatigue.
QUESTIONS?

				
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posted:11/12/2011
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