Transcript Mood Disorders - Association for Academic Psychiatry

Antidepressants and Treatment of
Mood Disorders
Anita S. Kablinger M.D.
Associate Professor
Departments of Psychiatry and
Pharmacology
Outline of Lecture
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Definitions
DSM-IV diagnoses and criteria
Epidemiology
Neurobiology
Psychosocial theories
Treatments
Definitions
• Depression can refer to many things and
mean different things to different people
• Symptom versus syndrome
• However, for a clinical depression
consistent with DSM-IV, this must lead to
functional impairment
DSM-IV Diagnostic Categories
• Major Depression
• Dysthymia
• Depressive Disorder
NOS
• Bipolar Disorder, Type
I or II
• Cyclothymia
• Bipolar Disorder NOS
• Mood Disorder
secondary to GMC
• Substance-Induced
Mood Disorder
• Adjustment Disorder
(separate
classification)
Epidemiology
• Depression is the most common cause of
disability in the world
• U.S. costs approximate 43$ billion per year
for mood disorders
• Lifetime prevalence rates: (according to
NCS), 21-24% for women and 12-15% for
men
Major Depressive Disorder
(MDD)
• >2 week period of
change in behavior
with 5 of the
following:
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*depressed mood
*anhedonia
appetite disturbance
sleep disturbance
psychomotor
disturbance
– fatigue or loss of
energy
– worthlessness or guilt
– impaired concentration
– suicidal thoughts
• * 1/5 symptoms must
be these
• Rule out physical
cause
Time Course of MDD
• Often lasts for a year without treatment
• Chances increase by 50% for another
episode after current episode (i.e. high
relapse and recurrence rates)
• Many go on to experience chronic
depression (but may be a result of
inadequate treatment)
Heritability of Mood Disorders
• Genetic factors very important
• RR of MDD is 2-5x greater in relatives of
depressed patients than controls
• First degree relatives of Bipolar patients are
24x more likely to develop BAD than
general population
• Twin and adoption studies help to
understand and define this illness
Psychosocial Theories of
Depression
• Risk factors include:
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recent stressors
poor social support system
history of early parental loss
gender
family history of depression
negative cognitive style
Theories of Depression
• NE and DA broken down to variety of products
through MAO and COMT
• 5HT is broken down by MAO to 5-HIAA
• Major mechanism for terminating signal is
neuronal reuptake
• Monoaminergic Theories
– Reserpine (early antihypertensive)
– Iproniazid (used to treat TB)
– Imipramine (originally studied as an
antipsychotic)
– Drugs enhancing noradrenergic functioning
were antidepressants (eg. stimulants)
Indoleamine Hypothesis of
Depression
• Serotonin is functionally deficient in
depression
– Decreased brain 5-HT and CSF 5-HIAA in
many depressed patients
– Antidepressants tend to increase central
serotonin transmission
– Depressed patients show reduction in 5-HT
reuptake sites
– Blunted neuroendocrine challenges
Neurotransmitter Hypothesis of
Mood Disorders
• Led to catecholamine hypothesis
– NE ↓ in depression and in mania
– 5-HT ↓ production or reuptake in depression
• Flaws: depression or mania not reliably
produced and clinical response exceeds
mechanism of action of drug
Neurobiology of Mood Disorders
• Neuroendocrine abnormalities: reflect
central neurotransmitter dysfunction
– hyperactivity of HPA: increased cortisol,
nonsuppression of cortisol in DST
– blunting of TSH release following TRH
infusion
– blunting of GH release with alpha-2 adrenergic
agonism and serotonin-mediated increases in
prolactin
Other Alterations in Depression
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CRH

acetylcholine activity

GABA levels
Excessive glucocorticoid activity in psychotic
depression
– Hippocampal volume loss
Neurobiology of Mood Disorders
• Sleep abnormalities: usually found in
endogenous depression
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prolonged sleep latency
shortened REM latency and change in timing
increased wakefulness
decreased arousal threshold
early morning awakening
reduced stage 3 and 4 sleep
Kindling-Sensitization
Hypothesis of Mood Disorders
• Suggests that repeated exposure to stress
and/or neurochemical changes during
depressed episode sensitize brain regions
responsible for affect
• Repeated episodes may permanently alter
systems within the CNS
• Leads to shorter well periods, increased
frequency and severity of illness
Treatments
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Pharmacotherapy
Psychotherapy
Social interventions
ECT
TMS
VNS
Which Medication?
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Safety
Tolerability
Efficacy
Payment
Simplicity
Available Types of
Pharmacotherapy
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Tricyclic antidepressants (TCA)
MAOI’s
SSRI’s
SNRI’s
Atypical antidepressants
Mood stabilizers
Antipsychotics
General Treatment Rules
• Often takes 4-6 weeks for response
• Monitor for response versus remission
• Vegetative symptoms tend to improve first,
cognitive symptoms take longer
• SSRI’s are the first line of treatment for
most MDD’s
• Address biopsychosocial needs and
maintain meds for 6-12 months
Tricyclic Antidepressants
• Available for more than 30 years
• Cheap but not clean
• Act by NE and/or 5 HT presynaptic
reuptake inhibition
• Side effects include anticholinergic effects,
orthostasis, slowing of cardiac conduction
• Secondary better than tertiary compounds
Selective Serotonin
Reuptake Inhibitors
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Produce response rates close to 70%
Safer and better tolerated than TCA’s
Given once daily
Starting and therapeutic doses often similar
Most common side effects include GI
symptoms, HA, insomnia, anxiety, and
sexual dysfunction
• Five available in the U.S.
Novel or Atypical
Antidepressants
• Bupropion (NE and DA reuptake inhibition)
• Trazodone (5 HT2 alpha-ANT)
• Venlafaxine and Duloxetine (NE and 5 HT
reuptake blockers – SNRI’s)
• Mirtazapine (presynaptic alpha 2 ANT and
5 HT2 and 5 HT3 ANT)
Psychotherapy in Depression
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Supportive
Insight-oriented
Interpersonal
Cognitive-behavioral
Psychodynamic
Individual, group or family