Affective and Anxiety Disorders

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Affective and Anxiety Disorders
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What are affective disorders?

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

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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

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Characteristics of Depression
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Biological Factors Influencing liklihood of
depression

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

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

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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

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So how do these antidepressants work?
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Tricyclic antidepressants

• Blocks reuptake of NE and 5HT
• very widely used
• fairly significant side effects
• mainly because they block ACh receptors
• blurred vision, dry mouth, urinary retention,
  irregular heart rate, constipation, sexual
  dysfunction,
• effects on other NT
• sedation, weight gain

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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

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(Celexa)
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How do SSRIs work?

• Block reuptake of 5HT
• selective serotonin reuptake inhibitor

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MAO inhibitors

• definitely not first line for treatment
• MAO- enzyme that breaks down excess DA, NE, 5HT
  so MAO inhibitors result in increased DA, NE and
  5HT

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Limitations of MAO inhibitors

• can cause significant interaction when people
  consume certain foods
• consequence potentially hypertensive crisis
  could be stroke
• Alters the metabolism of an amino acid that fools
  sympathetic nervous system into getting
  overstimulated

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Limitations of MAO inhibitors

• Alters the metabolism of amino acid tyramine
• foods high in tyramine include aged cheeses,
  wine, smoked fish, yeast products

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Limitations of MAO inhibitors

• consumption of these can result in a hypertensive
  crisis
• severe headaches, heart palpitations. Flushing,
  nausea, vomiting, stroke
• very long ½ life (drugs stay in body for at least
  a couple of weeks)
• There are now some MAO inhibitors that clear the
  body more quickly but still these are never the
  first drugs considered

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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

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How is this explained in terms of NT activity?

• NT activity is changed very quickly with
  psychotropics
• Most believe it is more related to change in
  number or sensitivity of postsynaptic receptors
  (down or up regulation)

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Current problems that still exist with
pharmacotherapy of depression

• Amount of time needed to see therapeutic effect
  (already discussed)
• Some patients do not respond well to first
  treatment

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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

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• 3. Phototherapy - Seasonal Affective Disorder
• 92 survey responders noticed seasonal change
  in mood
• 27 claim it causes them problems
• 4 diagnosed with SAD

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Bipolar

• 1 incidence (lower than depression)
• symptoms usually emerge during adolescence or
  early adulthood
• no sex differences in incidence
• without effective treatment - 20 result in
  suicide

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Bipolar disorder

• Treatments
• oldest - lithium
• odd history-
• lithium metal isolated in early 1800s
• 1940s - replaced sodium chloride with lithium
  chloride for hypertensive patients
• reintroduced to treat bipolar in 1970

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Bipolar disorder

• Treatments
• oldest - lithium
• odd history-
• lithium metal isolated in early 1800s
• 1940s - replaced sodium chloride with lithium
  chloride for hypertensive patients
• reintroduced to treat bipolar in 1970
• limitations of lithium
• effective dose and toxic dose are TOO close
• regular blood monitoring

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Newer treatments

• newer anticonvulsants
• Anticonvulsants MUCH SAFER THAN LITHIUM!!!
• carbamazepine (Tegretol) or valproic acid
  (Divalproex)
• Potential issue recent study showed that the
  anticonvulsants may improve symptoms but are not
  as effective as lithium at reducing suicides and
  suicide attempts