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