Depression Flashcards
Other criteria for MDD besides sigecaps
Depressed mood or lack of interest pleasure
- dont meet criteria for mixed episode
- same two weeks, 5 sx nearly every day incl depression/interest pleasure loss
- sx cause significant effect on distress or impact social, employment, adl
- Not due to a substance or other dz eg hypothyroid
- not accounted for by bereavement - sx persist for >2 months or are characterized by morbid preoccupation with worthlessness, suiicide, psychosis sx, psychomotor
Criteria for major depressive disorder
Five 5 of following: nearly every day During same 2 week period One of sx must be loss of interest/pleasure OR depressed mood Sig e caps Sleep Interest decreases (anhedonia) Guilt or worthlessness (not major criteria) Energy decrease Concentratin decrease Appetite decrease (or increase) Psychomotor retardation (or agitation) Suicidal thoughts
Risk factors for mdd
Female Native American Middle age Widow separated divorced Other psych dx- substance abuse, panic do, GAD Personality do: avoidant, Dependent, paranoid, schizoid Stressful life events Medical condition eg dm ca stroke First degree relative with mdd
Sx in first 1-3 days of depression that improve
Decreases agitation and anxiety, improved sleep and appetite
Sx that improve in 1-3 weeks
Increased activity and sex drive
Improvement in self care, concn, memory, thinking, psychomotor normalizes
Sx that improve in 2-4 weeks
Some relief of depressed mood
Return of pleasure experience
Fewer hopeless feelings
Subsiding of suicidal thoughts
Duration of AD therapy
First major dep episode:
At least 6-12 months
Two or more lifetime episodes:
Continue tx for 15 months to 5 years
How to discontinue antidepressant
Fluoxetine - no taper needed due to half life of 7-9 days and norfluoxetine 7-15 days
Other SSRI taper over 2-4 weeks
*withdrawl sx include nightmares, GI upset, dizzy, chills, anxiety irritable insomnia
Does serotonin syndrome contraindicated future antidepressant tx?
No, just avoid offending agent, use lowest dose and titrate slowly.
Tx of serotonin syndrome
- dc seronergic drug(s)
- fluids IV
- benzos for agitation, hyper reflexes hyperthermia myoclonus
- cyproheptadine for moderate severe - 2mg q2h till sx improve
Citalopram notes
Prolong QT so ECG pre-rx in CHF, bradyarrhythmias, coadministered meds that prolong QT
20 mg prolongs 8.5ms, 40mg prolongs 12.6ms, 60mg prolongs 18.5ms.
No more than 40mg qday due to no more efficacy in higher doses
Max dose 20mg in pt with: hepatic impairment, age over 60, cyp19 poor netabolizers, taking cimetidine
Medications that can INCREASE tCA levels by cyp 2D6 inhibition
Cimetidine Fluoxetine Paroxetine Haloperidol Phenothiazines (chlorpromazine, fluphenazine, promethazine)
Medications that can DECREASE TCA levels by 2D6 enzyme induction
Barbiturates
Phenytoin
Carbamazepine
Pharmacology of des and venlafaxine, and of duloxetine
- sort of like TCA with less se’s
Des and venlafaxine inhibit serotonin and norepinephrine reputable as well as weak inhibitors of dopamine reuptake
Duloxetine is selective for serotonin and norepinephrine
Moa of TCA
Increase synaptic concentration of norepinephrine and serotonin by reuptake inhibition
- all have slightly different moa and anticholinergic and other se’s leading different se’s
Metabolism of SNRI
Desvenlafaxine is active metab of venlafaxine
Venla 2d6 half life 5 hr
Desvenla 3a4 t1/2 10-11 hrs
Duloxetine 1a2, 2d6, 12 hr t1/2
MOA of MAO-I drugs
Inhibit MAO which is enzyme responsible for degradation of NE, serotonin, DA
MAO-A - primarily responsible for NE, serotonin, tyramine metabolism
MAO-B dopamine metabolism (eg selegiline, but over 9mg a and b are inhibited
All us Mao -I are irreverisiblr so takes 2 weeks for enzymes to return after medication dc
Drug interactions of MAO-I’s
- due to dangers, wait 4-5 half lives of drug or active metabolite before start MAO-I
- at least 2 weeks after stopping MAO-I to start interacting drug
Include: SSRI, TCA, SNRI other serotonin drugs Amphetamines Carbamazepine Decongestants Dextromethorphan- serot syn risk Ephedrine Epinephrine Meperidine (cardiac instability and coma)
Dietary restrictions MAOI’s
Aged products
Smoked
Picked
Yeast extracts
Aged: cheddar, meat, beer, wine
Smoked: meat fish sausage salami
Indication for nefazodone
Mdd (FDA ok)
Non fda| for PTSD
MOA of nefazodone, trazodone
Weak inhibition of serotonin and norepinephrine reuptake
Weak alpha 1 blocker
Serotonin 5ht-2 antagonist
Histamine blocker (trazodone >nef)
Drug interactions of nefazodone, trazodone
Nefazodone inhibits 3a4 (statins cbz digoxin alprazolam triazolam)
Trazodone - is metab by 3a4 but no clinically significant drug intxns
Vilazodone
Inhibits pre synaptic serotonin like SSRI
Also partial agonist at 5ht1a receptor
- take with food improves bioavailability
- 10mg x 7d then 20mg qdayx 7d
Target 40mg qday - ADR include diarrhea nv insomnia
- with 3a4 inhibits use 20mg qday
Mirtazapine
Lower doses - appetite stimulation
More Sedating at lower doses
Food minimally affects F
Some metab by 2d6 3a4 1a2 but no significant drug interactions
Bupropion
Apparently can decrease levels of cbz and increase levels of cimetidine - refer to p 226 for more info
St. John’s wort
Standardize extract 0.3% hypericin - 300mg tid for mild mod dep
Adv effects GI sexual headache anxiety kind of like SSRI
- weak MAO inhibitor and inhibits serotonin Doapmjne and norepinephrine with approximate equal affinity
Weak inducer of 3a4 2d6 1a2 -MaNY DRUg INTERACTIONS Decrease efficacy of cyclosporine - organ rejection has occurred -protease inhibitor Non nucleoside reverse transcriptase inhibitors Oral contraceptives Digoxin Warfarin Theophylline SSRI
1st line tx of depression
Consider CBT psychotherapy, maybe non pharm like light for SAD
First pharmacological selection
SSRI bupropion mirtazapine SNRI
2nd pharmacological selection
Different SSRI or other 1st line as mono therapy
OR
Augment with antidepressant with different mechanism than medication chosen above
3rd pharmacological choice-
- augment with AD with different mechanism or TCA
Augment with lithium or thyroid
4th pharmacological selection
And
5th line
- change to different augmenting agent
- or consider ECT or Vgus nerve stim
5th: continue to select alternate combo of various mechanism AD till adequate symptom improvement achieved
Definition of treatment resistant depression
Not responded to 2 separate trials of different antidepressants of adequate dose and duration in current episode
- after 2 trials the likelihood of responding to future trials significantly declines
- up to 46% don’t get adequate response
Approach to treatment resistant depression
1 optimize current therapy for dose, adherence, duration, se’s .
Continue tx for longer period 9-12 weeks
Combo antidepressant
Safe and effective combo include
- SSRI or SNRI plus
* Plus mirtazapine or bupropion
Or
- SSRI plus TCA
** use two different MOA, not same therapeutic classSwitching AD medications
Various strategies
- cross titration
Slowly taper off taper on
- benefits include prevent relapse and withdrawal
- risks include serotonin syndrome and complicated instructions
Or
Discontinuation strategy - stop when current med done then start new med
- risks include withdrawal sx benefits include ease of switching
Antidepressant augmentation with lithium
Level target 0.6-1.2 Recommended dose 900mg/day - response can occur within 48-72 hrs, full effect 2-3 weeks Effective with ANY antidepressant -13-fold decrease in suicide rate
Stimulant as ad augmentation
Improves sx of fatigue concentration and interest, not depression
Augment - pindolol
- potentiate an depressant effects of SSRI but no diff at end of study
- well tolerated
- more study needed to determine role
Dopamine agonist
Folic acid
For augmentation of depression
Bromocriptine - effective as imipramine for tx of depression
Pramipexole - has been studied as adjunct AD
GI sx limit potential for use
No FDA approval and no dose established
Folio acid - may be result rather than cause of depression
Limited data supports efficacy of folic acid (400 mcg) and l-methylfolate (7.5 mg) as augment tx
Thyroid for depression augmentation
May be effective for pts with subclinical hypothyroid
May produce more rapid response
T3 is most studied, recommended dose 25-50 mcg/day
atypical antipsychotic augmentation for depression
Aripiprazole and quetiapine XR are approved for adjunctive tx
Aripiprazole 2-5 mg once dusky
Quetiapine XR start 50mg qhs up to 150 in 3 days (max 300mg)
Pregnant and lactation with depression
Interested maternal depression associate with bad outcomes for baby - Low birth rate postnatal complication etc
- shared decision making
- no confirmed birth defects with use of medications - SSRI SNRI TCA
- MAO–I animal studies indicate teratogenic - should switch to other agents
St. John’s wort contraindicated during PG
Lithium for augmentation
900 mg per day
Level 0.6-1.2
May get quick onset 48-73 hrs then full effect 2-3 weeks
Antipsychotics approved for augmentation of depression
Quetiapine XR start 50mg qday
Aripiprazole start 2-5mg qday
Pregnancy most dangerous SSRI
Paroxetine D others are C
Safest TCA in pregnancy
Maprotiline B
Most dangerous antidepressant in pregnancy
MAO inhibitor
