Affective and Anxiety Disorders

What are affective disorders? Disorders of mood found throughout history unipolar or major depression bipolar or manic depression

Depression –over 10% with ~ 5% (11,000,000) suffering from a depressive episode in any given year –untreated % 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 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