Depression

DSM-IV

DSM-IV

Must meet FIVE of following criteria, at least one being depressed mood or anhedonia:

• depressed mood

• anhedonia

• weight loss/gain

• insomnia/hypersomnia

• psychomotor agitation

• fatigue

• feelings of worthlessness

• decreased concentration

• recurrent thoughts of death

MDD diagnosis

• 5 of DSM-IV criteria

• symptoms cause significant distress/impairment of function

• not better accounted for by bereavement after loss of loved one

• symptoms persist for at least 2 weeks

medical conditions

cause of depression

• hypothyroidism

• stroke, heart attack

• hepatitis C

drugs

cause of depression

• alpha-interferon

• reserpine

• substance abuse → MDMA, cocaine

etiology of depression

• not fully understood

• most likely related to combo of 3 factors:

  • genetic predisposition

  • environmental influences

  • biological factors

biogenic amine theory

• 3 neurotransmitters believed to be involved in depression (the monoamines)

  • serotonin (5HT)

  • norepinephrine (NE)

  • dopamine (DA)

• monoamine reuptake transporters believed to be responsible for removing NTs from synapse

  • inhibiting these transporters would increase levels of NT in the synapse

• monoamine oxidase

  • metabolizes monoamines → decreases NT levels

  • inhibition of enzyme → increases NT levels

neurotransmitter

a chemical substance released from a neuron that transmits a nerve impulse across a synapse

depression treatment

• pharmacotherapy

• psychotherapy

  • cognitive behavioral therapy

  • interpersonal therapy

• electroconvulsive therapy

SSRIs

• MOA: inhibit serotonin transporters

• most frequently used antidepressants

• generally dosed once per day

• typically given in the morning, but can be taken any time of day

• none more effective than another

SSRI ADRs

• side effects r/t increased serotonergic stimulation + nonselective receptor profiles of some agents

• activation/sedation

• nausea

• sleep disturbances

• sexual side effects

• weight gain

SNRIs

• MOA: inhibit neuronal reuptake of 5HT and NE

• venlafaxine (Effexor)

• desvenlafaxine (Pristiq)

• duloxetine (Cymbalta)

effexor

• serotonin reuptake inhibition across dosage range

• NE reuptake inhibition at doses >200 mg/day

  • dose related increases in BP

• XR (extended release) - dosed once daily

• IR (immediate release) - dosed 2 or 3 times daily

effexor ADRs

• nausea

• GI complaints

• insomnia

• sexual side effects

• increased BP

• sweating

• agitation

pristiq

• active metabolite of venlafaxine

• ADRs: similar to effexor

  • GI, nausea, BP, sexual dysfunction, etc.

duloxetine (cymbalta)

• MOA: balanced NE and serotonin reuptake inhibition across dosage range

• FDA approved for neuropathic pain associated w/ DM

• ADRs: similar to effexor, significant nausea

atypical antidepressants

• bupropion (Wellbutrin)

• mirtazapine (Remeron)

• trazodone (Desyrel)

bupropion

• MOA: inhibition of dopamine and NE reuptake

• FDA approved for smoking cessation (called Zyban)

bupropion ADRs

• lowers seizure threshold

• lower incidence of sexual side effects

remeron

• MOA: enhances NE and serotonin activity

• ADRs:

  • sedating antihistamine effect

    • take at bedtime, good for insomnia, more common at lower doses

  • significant weight gain

  • low rate of sexual dysfunction

trazodone

• MOA: enhances serotonin activity

• very sedating - used for INSOMNIA

• doses <300 mg for insomnia

• antidepressant activity at higher doses

trazodone ADRs

• sedation

• nausea

• GI upset

• priapism (prolonged erection)

TCAs

• amitriptyline (Elavil)

• desipramine (Norpramin)

• Imipramine (Tofranil)

• Nortriptyline (Pamelor)

tricyclic antidepressants

• MOA: inhibits NE and serotonin reuptake

• lethal in overdose

• affect many other receptor systems → unfavorable side effect profile

TCA ADRs

• anticholinergic - dry mouth, eyes, constipation, blurred vision

• alpha-adrenergic - orthostasis

• very sedating

• weight gain

• glucose dysregulation

• effects on cardiac conduction

MAOIs

• reserved for treatment of resistant depression

• food interactions: high in tyramine (aged cheese, cured meats, saurkraut, beer)

• Many ADRs

• Agents

  • phenelzine (Nardil)

  • selegiline (Eldepryl)

  • tranylcypromine (Parnate)

brexanolone

• specialty antidepressant

• indicated for postpartum depression

• aqueous formulation of allopregnanolone

• IV infusion administered over 60 hours w/ continuous monitoring

• $$$

esketamine

• speciality antidepressant

• indicated for treatment resistant depression

• nasal spray

• only available at treatment centers

• monitored for 2 hours

• associated w/ sedation, dissociation, abuse/misuse

response

significant reduction in, but not complete resolution of depressive symptoms

remission

complete resolution of depressive symptoms

recovery

sustained remission of at least 6 months

relapse

return of depressive symptoms within 6 months of achieving remission

recurrence

successive episodes of MDD after recovery from initial episode of MDD

acute phase

• phase of treatment

• initial 6-12 weeks of treatment

continuation phase

• phase of treatment

• treatment bridging remission to recovery

• typically 6-9 months

• continuation of antidepressant at full therapeutic dose

• antidepressant may be d/c at conclusion of phase

maintenance phase

• phase of treatment

• prevention of future episodes

• continuation of antidepressant at full therapeutic dose for extended periods of time, perhaps indefinitely

• not necessary for all pts

• may be beneficial in pts at high risk of relapse/recurrence

unpredictable

individually, response to specific agents is generally __________.

• past hx of response to a particular agent may predict future response

• hx of family member w/ response to a particular agent may predict response

choosing antidepressants

• based on

  • past hx of response

  • side effect profile

  • comorbid psychiatric or medical conditions

  • potential for drug interactions

  • cost

remission

_______ is the goal of treatment for MDD

• results in improved overall functioning

• decreases risk of experiencing another depressive episode

• increases amount of time until another episode in those who experience recurrence

insomnia

• ADR management

  • caffeine?

  • morning dosing

  • reduce dose

  • change antidepressant

  • adjunct w/ sleep medication

anxiety

• ADR management

  • may be transiently increased w/ initiation of antidepressant treatment

  • minimize/avoid caffeine intake

  • reduce dose/titrate gradually

  • beta-blocker or benzodiazepine

nausea

• ADR management

  • start low, titrate dosage up

  • take w/ food

  • decrease dose

  • change antidepressant

sexual dysfunction

• ADR management

  • decrease antidepressant dose

  • switch to another antidepressant

    • bupropion

  • add on a medication

    • sildenafil

  • wait to see if pt builds tolerance to the side effect

SSRIs

1. fluoxetine

2. sertraline

3. paxil

4. paxil CR

5. citalopram

6. escitalopram

7. fluvoxamine