Transcript Affective and Anxiety Disorders

Affective and Anxiety
Disorders
What are affective disorders?
• Disorders of mood
• found throughout history
• unipolar or major depression
• bipolar or manic depression
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
Characteristics of Depression
Biological Factors Influencing
liklihood of depression
• Genetics
– concordance rates:
• fraternal twins - 20% concordance
• monozygotic or identical twins - 50% concordance
• 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
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
So how do these
antidepressants work?
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
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
(Celexa)
How do SSRIs work?
• Block reuptake of 5HT
– selective serotonin reuptake inhibitor
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
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
Limitations of MAO inhibitors
• Alters the metabolism of amino acid
tyramine
– foods high in tyramine include: aged
cheeses, wine, smoked fish, yeast
products
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
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
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)
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
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
3. Phototherapy - Seasonal Affective
Disorder
– 92% survey responders noticed
seasonal change in mood
– 27% claim it causes them problems
– 4% diagnosed with SAD
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
Bipolar disorder
• Treatments
– oldest - lithium
• odd history– lithium metal isolated in early 1800’s
– 1940’s - replaced sodium chloride with lithium chloride
for hypertensive patients
– reintroduced to treat bipolar in 1970
Bipolar disorder
• Treatments
– oldest - lithium
• odd history– lithium metal isolated in early 1800’s
– 1940’s - 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
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