Depression

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

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