Week 7 - Depressive Disorders

What is the central feature of affective disorders?

Mood disturbances

What is dysthymia?

Less severe but long lasting depression (>2 years)

What % of the US population suffers from depression?

9-10% (20 million adults)

What is the mean age of onset of depression?

25-35 years

What are symptoms of major depression?

Persistent sadness, loss of interest, sleep and appetite disturbances, feelings of worthlessness

What is the criteria for diagnosing major depression?

4-5 symptoms during 2 week period (1 symptom either depressed mood or loss of pressure)

What is the criteria for dysthymic disorder?

Depressed mood more days than not over 2 year period + 2 more depressive symptoms

What % of individuals with major depression will eventually develop bipolar disorder?

5-10%

How does depression affect one’s sense of pleasure?

Depression interferes with pleasure circuits, which reinforces actions and behaviors that provide pleasure through dopamine rewards

What is the monoamine theory of depression?

Dereased levels of norepinephrine, serotonin, or dopamine results in depression

Why do patients with depression have increased 5-HT2 binding?

5-HT2 receptors are G-coupled stimulatory receptors => upregulated in depression to compensate for low levels of serotonin

Why do patients with depression have increased prolactin?

Dopamine normally inhibits prolactin => decreased DA leads to disinhibition

Why do patients with depression have decreased corticotropin-releasing factor (CRF) binding?

CRF receptors down regulate in response to high levels of CRF

How are antidepressants classified?

1. Function

2. Target

3. Structure

Why are tricyclic antidepressants (TCAs) called dirty drugs?

They affect many different receptors

How does adding carbons to TCAs affect selectivity?

Adding more carbons makes TCAs more nonselective

What are side effects of TCA?

Tachycardia, dry mouth, constipation, urinary retention (atropine effect), sedation

Why do TCAs increase risk for suicide?

They take 2-3 weeks to take effect and can lead to overdose

Why are SSRIs the first line of treatment for depression?

• They are equally effective but have less side effects than TCAs

• They are safer than TCAs and cannot be used to commit suicide

What are side effects of SSRIs?

Anxiety, insomnia, GI symptoms (increased peripheral serotonin)

What are symptoms of serotonin syndrome?

• Autonomic hyperactivity (fever, diarrhea)

• Cognitive symptoms (agitation, hypomania)

• Motor dysfunction (muscle jerking, tremors, ataxia)

Why are SSRIs contraindicated with MAOIs?

Taking SSRIs and MAOIs at the same time can lead to serotonin syndrome

What other disorders are SSRIs effective for?

Anxiety and eating disorders

Why are SSRIs effective for eating disorders?

They decrease binge eating by regulating mood

What are examples of SSRIs?

Fluoxetine (Prozac) and Sertaline (Zoloft)

What are examples of TCAs?

Imipramine and desipramine

What are secondary TCAs selective towards?

NE transporters

What function do second and third generation antidepressants have?

They block SE and NE and have other actions

What is the mechanism of mirtazapine?

Alpha 2, 5-HT2, and 5-HT3 antagonist

How do MAOIs improve depression?

They inhibit metabolism of monoamines to increase synaptic levels

Why are MAOIs considered 2nd line treatments for depression?

Their effects last at least 2 weeks after discontinuation

What are MAOIs typically indicated for?

Atypical depression (increased eating and sleeping) and severe depression

What are side effects of MAOIs?

Postural hypotension, dry mouth, headaches, weight gain

What percent of patients with depression fail to respond to treatment?

30%

What is the mechanism of ketamine?

Blocks NMDA receptors on GABA => decreased inhibition leads to increased glutamate