Peter M. Hartmann, M.D.
Clinical Professor of Family and Community Medicine at
Penn State College of Medicine
June 23-25, 2011
1. List criteria for major depressive disorder.
2. Distinguish major depression from
dysthymia and adjustment disorder.
3. Provide optimal treatment for patients
Essential Feature of MDD
Patient must have either:
Depressed mood (irritable in children)
Loss of interest or pleasure
For at least 2 weeks
(Als0, must have at least 4 other symptoms.)
Psychomotor agitation or retardation
48 yo MWF high school teacher with MDD
Given paroxetine (Paxil) 20 mg X 6 weeks
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
Requires different treatment
Rarely will antidepressants work alone.
Need to combine medication with therapy.
History of mania or hypomania?
Family history of bipolar disorder, suicide,
prolonged psychiatric hospitalization or non-
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)*
* Only FDA approved are quetiapine XL and
Major Depressive Disorder
Picasso Painting of Depression
Sequenced Treatment Alternatives to Relieve
Depression (NIMH, 2876 patients, 6 years)
1. Majority fail to achieve & sustain remission (only
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
Few complicating problems
Lower quality of life
Reinforce need to comply
Refer for therapy (cognitive behavioral or
Assess other factors such as diagnosis
Three options if not in remission in 14 weeks:
Option 1: Switch from citalopram to :
2. Bupropion SR
3. Venlafaxine XR
No difference among choices
Option 2: Augment
1. Bupropion SR
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
No difference between switch and add on
CBT = medication but takes twice as long
*16 sessions over 12 weeks
For the 50% not in remission after Phase II
Option 1: Switch up to 14 weeks
No advantage of one over the other
Option 2: Add different agent:
Fewer SE with T3 (many dropouts with Lithium)
Take off all medications and change to one of 2
Venlafaxine XR + Mirtazapine (10% remission)
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%
Switch from one SSRI to another.
Adding another agent helpful:
Switch to Venlafaxine XR plus Mirtazapine
Switch to MAOi
Switch to or add CBT
Other Options from Different
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)
Dutch study of 89 outpatients, age 65 and older
7500 lux of pale blue light for 1 hour in early AM
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?
Sad mood most days for “my whole life”
Never had sex but libido seems normal to
Never had suicidal thoughts
Mother and maternal aunt had major
depression responsive to fluoxetine
Had polysomnography because of excessive
1. Decreased REM latency
2. Decreased slow wave sleep
3. Impaired sleep continuity
4. No PLMD or sleep apnea
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
Prevalence 6% (M:F is 2:1 in adults; kids 1:1)
Usually family Hx of MDD
Less vegetative symptoms than in MDD
25-50% have same polysomnography as
Cause of resistant depression
17 yo SF high school student broke
up with boyfriend 2 weeks ago.
Won’t do her homework
Avoiding her friends
Mother reports she wishes she was dead
What do you want to know?
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
No substance abuse
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
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”
Distressed about cognitive difficulties and
unemployment despite high IQ.
Lives with parents who are highly critical (negative
Endorses sad mood, anhedonia, sleep and appetite
decreased, never had much sex drive, poor
concentration and self attitude, admits suicidal
Lab studies and Physical Exam
CBC, metabolic profile normal, elevated
Urine drug screen shows cannabis
Nicotine stains on fingers
Below ideal body weight
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
Consider Omega 3 (4 capsules per day)
Stress biological nature of MDD (just like
Not your fault (allow yourself sick role)
Terry Bradshaw 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
Well known on “NFL Today” and “Fox NFL
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.
Meets criteria for MDD.
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
Goal is to optimize pregnancy outcome.
Encourage good health behaviors (prenatal
vitamins, good eating habits, regular sleep,
avoid alcohol and smoking).
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
Consultation is helpful
St. John’s Wort
St. John’s Wort (Hypericum
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
Does not affect cognitive functioning.
St. John’s continued:
Active ingredient is hyperforin (3-5%) but often
standardized to hypericin 0.3%.
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
Symptoms: headache, nausea, anorexia,
dry mouth, thirst, cold chills, weight loss,
dizziness, insomnia, paresthesias, confusion