Disorders of mood

1
What are affective disorders?

• Disorders of mood
• found throughout history
• unipolar or major depression
• bipolar or manic depression

2
Depression

• Depression
• over 10 with 5 (11,000,000) suffering from a
  depressive episode in any given year
• untreated - 25 - 30 will attempt or commit
  suicide
• 2X greater prevalence in women than men
• estimated only 50 receive specific treatment

3
Characteristics of Depression
4
Biological Factors Influencing liklihood of
depression

• Genetics
• concordance rates
• fraternal twins - 20 concordance
• monozygotic or identical twins - 50 concordance

5

• Neurochemical Theory
• monoamine theory
• supportive data
• 1. Reserpine
• 2. Drugs used to treat depression increase
  activity of NE and/or 5HT neurons

6
How do we treat depression?

• Pharmacologically
• drugs have been available for 40 years
• two categories of drugs emerged about the same
  time tricyclic antidepressants and MAO
  inhibitors
• more recently SSRIs have taken over the market
• Even more recently SNRI (ex. Effexor or
  venlafaxine)

7
So how do these antidepressants work?
8
Tricyclic antidepressants

• Blocks reuptake of NE and 5HT
• very widely used
• fairly significant side effects
• effects on other NT
• sedation, weight gain

9
MAO inhibitors

• mechanism of action block the enzyme that
  breaks down excess NE and 5HT
• proved as effective (if not more so) than
  traditional tricyclics or SSRIs
• not used as first level txt due to risk of
  adverse side effects- related to diet

10
Limitations of MAO inhibitors

• Alters the metabolism of amino acid tyramine
• foods high in tyramine include aged cheeses,
  wine, smoked fish, yeast products
• consumption of these can result in a hypertensive
  crisis
• severe headaches, heart palpitations. Flushing,
  nausea, vomiting, stroke
• very long 1/2 life (2 weeks)

11
SSRIs

• Fluoxetine (Prozac) - first introduced in US in
  1988
• SSRIs have a more favorable side effect profile
  than earlier antidepressants
• relatively safe (esp in OD situations)
• some controversy... increased risk of suicide
  especially in kids

12
dual action antidepressants

• SNRI serotonin and norepinephrine reuptake
  inhibitors

13
Current problems that still exist with
pharmacotherapy of depression

• Some patients do not respond well to first
  treatment
• most take 3 - 4 weeks to exert significant
  therapeutic effects
• what does this suggest?

14
Three alternatives to drug treatment

• 1. ECT - electroconvulsive therapy
• may cause the most rapid change in receptor
  density
• 2. Sleep deprivation
• many sleep abnormalities associated with
  endogenous depression
• reduced SWS, increased stage 1, increased REM

15

• 3. Phototherapy - Seasonal Affective Disorder

16
bipolar

• Shifts between manic and depressive states
• Treatment
• Lithium extremely toxic!

17
anticonvulsants

• introduced in 1990s to treat bipolar
• possible mechanism?