Affective Disorders
Brian E. Wood, D.O.
Department Chair, Psychiatry
Edward Via Virginia College of Osteopathic Medicine
Assistant Professor of Clinical Psychiatric Medicine
University of Virginia, School of Medicine
Mood Disorders
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Major Depressive disorder
Bipolar disorder
Dysthymic disorder
Cyclothymic disorder
Mood Disorder due to secondary sources
– General medical conditions
– Substance use/abuse
Major Depressive Episode
Time
Mood
Manic Episode
Mood
Time
Epidemiology
• Major Depressive Disorder
– Prevalence 2-3/100 men, 5-10/100 women
– Lifetime expectancy 10% in men, 20% in women.
– Risk increases throughout life for men, peaks in 40’s
then decreases in women
• Bipolar Disorder
– Prevalence 1/100 in men and women
– Lifetime expectancy 1% in men and women
– Usually occurs in the mid 20’s and 30’s perhaps slightly
later in women
Epidemiology
• Dysthymic Disorder
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Much less studied
More common in females
Onset frequently in 20’s to 30’s
More common among first degree relatives with MDD.
• Cyclothymic Disorder
– Essentially occurs more frequently in the same groups
and age ranges as Bipolar Disorder
– More common among first degree relatives with MDD
or Bipolar Disorder.
Etiology
• Major Depressive Disorder
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Heritability 10-13% in first degree relatives
Mz concordance rate higher than Dz rate
Increased risk in lower socioeconomic classes
Increased risk with family history of ETOH,
depression or early parental loss.
Etiology
• Bipolar Disorder
– Heritability 20-25% in first degree relatives
• Child with 1 Bipolar parent 25% risk
• Child with both parents bipolar 50-75% risk
– Slightly increased risk in higher socioeconomic
groups
– Mz concordance rate 40-70%, Dz concordance
rate 20%.
Etiology
• Dysthymic Disorder
– Occurs more frequently in first degree relatives
with MDD but rate essentially unknown
• Cyclothymic Disorder
– Thought to be a less severe form of Bipolar
Disoder
DSM IV – TR
MDD
• One or more major depressive episodes for at least
2 wks. Duration
• Five or more symptoms of depression (wt. Loss,
insomnia or hypersomnia, psychomotor agitation
or retardation, fatigue, feelings of worthlessness or
innappropriate guilt, diminished concentration,
recurrent thoughts of death or suicide) including
either depressed mood or loss of interest or
pleasure.
• Rule outs for bereavement, substance induced, etc.
DSM IV –TR
Bipolar Disorder
• One or more manic or mixed episodes usually
accompanied by MDE
• Manic episode characterized by at least 1 wk of
elevated, expansive, or irritable mood with at least
three symptoms including grandiosity, insomnia,
talkativeness, flight of ideas or racing thoughts,
distractibility, increased activity, excessive
involvement in pleasurable activity.
• Rule outs for substances, medical conditions, etc.
• Occupational or social dysfunction
Differential Diagnosis
• MDD
– Mood disorder due to general medical condition
or substance induced
– Manic or mixed episodes with irritable mood
– Adjustment Disorder
– Simple or complicated Bereavement
– Dementia with prominent apathy
Differential Diagnosis
• Bipolar Disorder
– Mood disorder due to general medical condition
or substance induced
– Hypomanic episode
– MDE with prominent irritability
– Attention Deficit/Hyperactivity Disorder
Pharmacologic Treatment
MDD
• Pharmacologic Treatment (monotherapy)
– Antidepressants
• TCA’s
• MAOI’s
• SSRI (generally first line treatment)- steady state
from 6 - 15 days.
• Other antidepressants (Venlafaxine, Mirtazapine)
– Psychostimulants
Tricyclic Antidepressants
• Primary action on NE, SE.
• Also have alpha 1 blocking, histamine blocking
and anticholinergic effects
• AV nodal block
• Lethal in overdose
• Infrequently used today for treatment of
depression but some resurgence in use due to tx.
Resistance and off label uses (ex. Pain control)
Monoamine Oxidase Inhibitors
• Primary action on MAO that breaks down
NE
• Significant alpha 1 and histaminergic effects
but little antcholinergic or AV node effects.
• Risk of hypertensive crisis with Tyramine
containing foods or with noradrenergic
agents (ex. Pseudoephedrine)
SSRI’s
• Primary action at 5HT2 receptor.
• Most widely prescribed psychotropic medication
in use today and generally first line treatment for
depression.
• Generally very well tolerated with minimal
incidence of side effects.
• Not lethal in overdose.
• Do have significant drug-drug interactions due to
CP450 metabolism.
Effects of SSRI’s on Cytochrome P450 Enzymes
Cytochrome
Polymorphism
Inhibitors
Potentially significant Interactions
1A2
Possible
Fluvoxamine
Haloperidol
Phenytoin
Theophylline
Caffeine
2C9
Yes; 2-3%of whites; 15-20%of Asians
Fluoxetine
Fluvoxamine
Sertraline
Phenytoin
Diazepam
Tolbuamide
2D6
Yes; 5-8% of whites; lower in Asians and
African Americans
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
Citalpram
TCA’s
Haloperidol
Perphenazine
Thioridazine
Clozapine
Risperidone
B-Blockers
Type 1C antiarrhythmics
3A
Possible
Fluoxetine
Fluvoxamine
Sertraline
Citalpram
TCA’s
Carbamazepine
Alprazolam
Triazolam
Terfenadine
Astemizole
Adapted from DeVane (1994)
ECT
• Application of brief electrical pulse to induce
controlled generalized seizure.
• Mechanism of action unknown but correlates with
“surge” of neurotransmitters in the CNS and
changes in permeability in the blood-brain barrier.
• Modern ECT applied with general anaesthesia and
neuromuscular blockade.
• Probably the highest efficacy of any single agent
used to treat affective disorders.
Other Treatments
• Interpersonal psychotherapy
• Cognitive-behavioral therapy
• Psychodynamic psychotherapy
Pharmacologic Treatment
of Bipolar Disorder
• Li compounds – primary effect at voltage
gated Na channel of the neuron
• Anticonvulsants – effect at the voltage gated
Na channel and membrane stabilization
effects.
– Valproic acid
– Carbamazepine
– Other anticonvulsants
Summary
• Affective disorders are disorders of mood regulation and
include both hyper-excitable and hypo-excitable states
defined by episodes.
• They are generally recurrent diseases but occasionally
occur in single episodes.
• They are familial with probable genetic inheritance but
with significant environmental factors affecting
expression.
• Affective disorders are treatable diseases requiring careful
evaluation, initiation of appropriate treatment, and follow
up in order to improve condition, quality of life and
minimize risks.