Depression

What is the lifetime prevalence of major depressive disorder in the U.S.?

21%

Are females or males more likely to develop depression?

females

What causes depression?

interaction between chronic stress, genetic predisposition, and environment

Biogenic amine hypothesis

deficit of NE, DA, 5-HT at the synapse

Note about symptoms of depression

at least five of the symptoms must be present during the same 2-week time frame and represent a change from previous functioning

Symptoms of depression

- depressed mood

- markedly diminished interest or pleasure in usual activities

- increase or decrease in appetite or weight

- increase or decrease in amount of sleep

- increase in psychomotor activity

- fatigue or loss of energy

- feelings of worthlessness or guilt

- diminished ability to think, concentrate, or make decisions

- recurrent thoughts of death, suicidal ideation, or suicide attempt

What conditions are often comorbid with MDD?

- anxiety disorders

- eating disorders

- personality disorders

- substance use disorders

Which medical conditions are associated with depression?

- HTN

- CV disease

- asthma

- congestive HF

- parkinsons disease

- DM

- coronavirus

- stroke

- cancer

- chronic pain

- hypothyroidism

- hepatitis/HIV

- MS

- irritable bowel

- obesity

- CKD

- TB

- substance use

- hyperlipidemia

Which medications are associated with depression?

- CNS depressants

- corticosteroids

- contraceptives

- phenobarbital

- brivaracetam and levetiracetam

- perampanel

- tiagabine

- topiramate

- interferon and interleukin

- varenicline

- isotretinoin

- clonidine

- methyldopa

- reserpine

Goals of therapy for MDD

- resolution of depressive symptoms (remission)

- return to euthymia

- prevention of future episodes (relapse or recurrence)

- improvement in quality of life

What non-pharm therapies are available for individuals with depression?

- psychotherapy

- exercise

- light therapy

- electroconvulsive therapy

- transcranial magnetic stimulation

MOA: SSRIs

inhibit reuptake of serotonin

Which SSRI has mild anticholinergic effects?

paroxetine

Which SSRI can cause QT interval prolongation and must be dose limited?

citalopram

Side effects of SSRIs

- normally dissipate after first week of use

- HA

- anxiety

- GI upset

Adverse effects of SSRIs

- hyponatremia

- bleeding

- discontinuation syndrome

- sexual dysfunction

MOA: SNRIs

inhibits reuptake of serotonin and NE

Side effects of SNRIs

- HA

- anxiety

- GI upset

Adverse effects of SNRIs

- small increases in BP

- sexual dysfunction

- diaphoresis

- hyponatremia

- bleeding

- discontinuation syndrome

Which SNRI should be avoided in individuals with liver disease?

duloxetine

MOA: TCAs

inhibit reuptake of 5-HT and NE AND blocks alpha 1 adrenergic, H-1 and muscarinic-cholinergic receptors

What is a lethal dose of a TCA?

10 mg/kg

Side effects of TCAs

- sedation

- dry mouth

- blurry vision

- constipation

- urinary retention

Adverse effects of TCAs

- orthostatic hypotension

- QT prolongation

- tachycardia

- heart block

- weight gain

- sexual dysfunction

- seizure activity

MOA: bupropion

NE and DA reuptake inhibitor

Why should bupropion be given in the morning?

NDRIs are activating and can be used to improve energy

Side effects of bupropion

- GI effects

- insomnia

- dry mouth

Adverse effects of bupropion

- mild blood pressure increases

- anxiety

- seizures at high doses

MOA: trazodone

Serotonin antagonist and reuptake inhibitor (SARI); also blocks histaminic and alpha-adrenergic receptors

Which properties is trazodone often used for?

its sedating properties

Noradrenergic and specific serotonergic antidepressant (NaSSA) example

mirtazapine

Besides increasing NE and 5-HT in the synaptic cleft by blocking presynaptic alpha-2 auto receptors and heteroreceptors, which other receptors does Mirtazapine block?

post-synaptic serotonergic receptors and H-1 receptors (at lower doses)

Which antidepressants have short elimination half-lives compared to other antidepressants?

nefazodone and venlafaxine

Which antidepressant has a long half life?

fluoxetine

What are symptoms of serotonin syndrome?

- spontaneous clonus

- inducible clonus w/ agitation or diaphoresis OR

- ocular clonus with agitation or diaphoresis OR

- tremor and hyperreflexia OR

- hypertonia, temperature >100.4 degrees, ocular or inducible clonus

What is the approximate response rate of each antidepressant?

50% - 75%

Which antidepressants are recommended 1st line for patients with moderate to severe MDD?

SSRI, SNRI, bupropion, mirtazapine

How do we select antidepressant for a particular patient?

- pts hx of previous response to antidepressants

- adverse effect profile (can affect adherence)

How long does it take an antidepressant to start working?

2-4 weeks for initial improvement of sadness and anhedonia

6-8 weeks may be needed for optimal antidepressant effects

How long should an antidepressant be continued when treating the 1st depressive episode?

additional 4-9 months in the continuation phase to prevent relapse

How is a partial response managed?

- extend med trial and/or use a higher dose within recommended dosage range

- augmentation --> add a non-antidepressant (lithium, buspirone, tioodothyronine)

Symptoms of antidepressant withdrawal

- flu-like symptoms (nausea, HA, light-headedness, chills, body aches)

- insomnia

- paresthesia

Which antidepressants are considered initially in the pediatric population?

SSRIs

Which antidepressants are chosen frequently for geriatric depression?

SSRIs

Which antidepressants have significant toxicity risk on overdose?

TCAs and MAOIs