Term
| Changes of relapsing in depression |
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Definition
1 episode: 50-60% will have 2nd episode
2 episodes: 70% will have a 3rd episode
3 episodes: 90% will have a 4th episode
episodes often follow sere psychosocial stressor - death of loved on, divorce, loss of job |
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Term
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Definition
1/3 genetic; 2/3 environmental
monoamine hypothesis:
decreased synaptic concentrations of NE, 5HT, and DA
dysregulation hypothesis:
dysregulation of NT resulting in changes in pre and post synaptic receptors
this helps explain the delay in AD effect
5HT system targeted in this theory
changes in presynatpic and postsynaptic receptor densities (sensitivity) is described as being "down regulated"
neuroendocrine hypothesis:
thyroid and hypothalamic pituitary axis dysregulation
hypothyroidis can look like depression, hyperthyroidism can look like mania |
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Term
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Definition
D + SIGECAPS
depressed mood and/or anhedonia
sleep changes
interest (loss of)
guilty or worthless
energy changes (low)
concentration (low)
appetite (increase or decrease)
psychomotor slowed or agitated
suiciality |
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Term
| diagnosis of a major depressive episode |
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Definition
A.
period of at least 2 weeks in which patient exhibits a depressed mood and/or anhedonia
B.
greater than or equal to 5 out of 9 symptoms
changes in weight (~5% over 1 month)
sleep
psychomotor agitation or retardation
loss of energy (small tasks - getting out of bed)
feelings of worthlessness/guilt
difficulty concentrating and making decisions
suicidal ideation
C.
symptoms do not meet the criteria of mixed episode
D.
must impair social or occupational areas of functioning
E.
not due to substance abuse or general medical conditions
F.
not due to bereavement
major depressive disorder = greater than or equal to 1 major depressive episode
the episode has ended with the full criteria for the major depressive episode have not been met for at least 2 consecutive months
rule out mania or hypomania |
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Term
| DEPRESSIVE DISORDER SPECIFIERS |
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Definition
mild, moderate, severe
psychotic features (AH/VH, delusions)
catatonic features: expressionless
melancholic features (elderly patients)
early morning awakening, anhedonia, marked psychomotor agitation/retardation, significant weight loss
atypical features (younger patients)
overeating (weight gain), hypersomnia, leaden paralysis (arms and legs feel really heavy)
postpartum features
onset < 30 days after postpartum, severe labile mood symptoms |
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Term
| diagnosis of dysthymic disorder |
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Definition
less severe symptoms -> more chronic and persistent
depressed mood is present for > 2 years
during periods of depressed mood, must exhibit greater than or equal to 2 of the following: change in appetite, change in sleep, low energy, low self-esteem, poor concentration, hopelessness
cannot be with out symptoms for > 2 month period
the disturbance is not better accounted for by chronic MDD or MDD in partial remission and there has never been manic episode |
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Term
| medications that can cause depression |
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Definition
CARDIOVASCULAR AGENTS:
methyldopa (more sedating)
clonidine (more sedating)
reserpine
beta-blockers (propranolol - more lipophilic, crosses the BBB more quickly)
SEDATIVE HYPNOTICS:
alcohol
benzodiazepines
barbiturates
chloral hydrate
ANALGESICS:
opioids
HORMONES:
corticosteroids (prednisone long term, short courses are more likely to cause a manic episode)
progesterone
estrogen withdrawal
anabolic steroids
OTHER:
INTERFERON (50% of people will develop depression)
ACCUTANE (suicidality, depressed mood)
CHANTIX (suicidality, depressed mood)
withdrawal from stimulants (cocaine, crystal meth) |
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Term
| medical causes of depression |
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Definition
medical illness may be a biological cause:
stroke
hypothyroidism
anemia
parkinson's disease
premenstrual dysphoria
syphilis
lupus
medical illness may trigger a psychological reaction:
chronic pain
HIV/AIDS
cancer
diabetes
CHF |
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Term
| use of electroconvulsive tehrapy (ECT) in depression |
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Definition
indications: major depression (90% efficacy), treatment resistant depression, depression with psychosis, depression in pregnancy
6-12 treatments are usually required, administered 2-3 times per week
seizure lasts 30-90 seconds
response in 1st 1-2 weeks, follow up with pharmacotherapy
ADRs: HA, cognitive impairment, confusion, memory impairment (anterrograde,retrograde amnesia), muscle soreness
informed consent required |
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Term
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Definition
glycopyrrolate: to minimize oral and airway secretions
short acting barbiturate: anesthesia (not BZD b/c they decrease the seizure threshold)
succinylcholine: muscle relaxant
nifedipine or esmolol: antihypertensive, control increased pulse and BP |
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Term
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Definition
affinity for GABA-A, GABA-B, 5HT1, 5HT3 (antagonism), 5HT4 (antagonism), 5HT reuptake inhibition
efficacy:
placebo < St. John's Wort = TCA |
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Term
| St. John's Wort drug interactions |
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Definition
CYP2C9/3A4 inducer
CYP1A2 inducer (mild)
reports of decreased serum concentration of OC, theophylline, warfarin, protease inhibitors
serotonin syndrome
only for people with mild depression that are not taking any other medication |
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Term
| selection of an antidepressant |
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Definition
PATIENT SPECIFIC
1. history of prior response
2. family history of response to medication
3. safety in overdose
4. chronicity of the disorder
5. ADR profile
6. patient age
7. concurrent medical illness (HTN, seizure d/o)
8. concurrent medications (drug interactions)
9. adherence (QD dosing)
10. cost
11. PATIENT PREFERENCE |
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Term
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Definition
inhibit the enzyme responsible for metabolism of 5HT, NE, and DA
IRREVERSIBLE INHIBITION: takes ~2 weeks to reproduce MAO after stopping therapy |
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Term
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Definition
useful for refractory depression
atypical depression |
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Term
| examples of MAOIs used for depression |
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Definition
phenelzine
tranylcypromine |
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Term
| ADRs of MAOIs (phenelzine and tranylcypromine) |
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Definition
ORTHOSTATIC HYPOTENSION
bradycardia
INSOMNIA
weight gain
sexual dysfunction
dry mouth
constipation |
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Term
location and NT metabolized by MAOA and MAOB
effects of selegiline and tranylcypromine and phenelzine on MAOA and MAOB |
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Definition
MAO-A
receptor locations: brain, liver, placenta, GI tract
NTs metabolized: SEROTONIN, NOREPINEPHRINE, DOPAMIN
MAO-B:
receptor location: brain, platelets
NTs metabolized: dopamine
selegiline irreversibly inhibits type A at HIGHER doses, irreversibly inhibits type B at all doses
tranylcypromine and phenelzine irreversibly inhibit BOTH type A and B at ALL doses |
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Term
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Definition
MEPERIDINE (DEMEROL): CIRCULATORY COLLAPSE
SEROTONERGIC AGENTS: SEROTONIN SYNDROME (takes 2 weeks to regenerate MAO)
dextromethorphan
buspirone
SSRIs/SNRIs
TCAs
sympathomimetics: HTN crisis
amphetamines
pseudoephedrine
ADHD treatments (methylphenidate) |
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Term
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Definition
avoid tyramine containing foods:
aged cheese
aged meats
pickled meats/fish
liver
pepperoni
sauerkraut
fava beans
avocados
alcohol (chianti wine, champagne, beer)
may lead to hypertensive crisis
life threatening increase in BP |
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Term
| mechanism of hypertensive crisis caused by tyramine ingestion + MAOI |
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Definition
normally MAO in the GI inactivates tyramine
inhibition of MAO in the GI tract and liver by MAOIs results in systemic absorption of large amounts of tyramine -> severe hypertension b/c of the massive release of NE
signs/symptoms: occipital HA, flushing, palpitation, HTN, neck stiffness or soreness, N/V, diaphoresis, fever, chills, photophobia |
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Term
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Definition
pheochromocytoma: tumor that produces excessive NE
hepatic or renal dysfunction
cardiovascular disease or defect
excessive caffeine use
elective surgery
sympathomimetic therapy
SSRIs (2 week wash-out; 5 weeks for fluoxetine) |
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Term
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Definition
major depression
neuropathic pain
anxiety disorders: OCD, panic disorder
enuresis (bed wetting) |
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Term
| MOA of TCAs - secondary amines |
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Definition
NE and 5HT reuptake inhibitors
H1, ACh, and alpha 1 blockade
PRIMARY EFFECTS ON NE
better tolerated than tertiary amines
more effective for pain conditions b/c more effective on NE |
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Term
| examples of TCAs - secondary amines |
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Definition
desipramine (metabolite of imipramine)
nortriptyline (metabolite of amitriptyline)
DRUG OF CHOICE FOR PAIN CONTROL
protriptyline |
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Term
| MOA of TCAs - tertiary amines |
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Definition
NE and 5HT reuptake inhibitors
H1, ACh, and alpha1 blockade
PRIMARY EFFECTS ON 5HT
> ADRS THAN THE SECONDARY AMINES
anticholinergic effects - limits use int he geriatric population (lass, cognitive effects)
orthostasis
sedation |
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Term
| examples of TCAs - tertiary amines |
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Definition
amitriptyline
used for sleep at low doses, anxiety)
imipramine
used for bed wetting
clomipramine
used for OCD
doxepine
trimipramine |
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Term
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Definition
anticholinergic side effects
dry mouth, urinary retention, blurred vision, constipation
sedation
weight gain
SEXUAL DYSFUNCTION
DECREASE IN SEIZURE THRESHOLD
CARDIOVASCULAR COMPLICATIONS:
orhtostatic hypotension
tachycardia
cardiac conduction abnormalities: ST depression, T wave flattening, QRS prolongation, QTc prolongation, ventricular fibrillation
LETHAL IN OVERDOSE DUE TO CV COMPLICATIONS
ECG at baseline (contraindicated in heart block) |
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Term
| in what patients should TCAs be avoided (due to anticholinergic ADRs)? |
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Definition
elderly
prostatic hypertrophy
narrow angle glaucoma
erectile dysfunction
memory impairment
taper patients off when d/c to avoid cholinergic rebound (SLUD) |
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Term
examples of SSRIs
FIRST LINE THERAPY |
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Definition
fluoxetine
sertraline
paroxetine
fluvoxamine
citalopram
escitalopram |
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Term
| clinical pearls and of fluoxetine |
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Definition
long t1/2 and active metabolite
(norfluoxetine) - 7 days
good alternative for nonadherence
only SSRI that may cause weight loss or no change
more stimulating SSRI |
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Term
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Definition
NAUSEA: 5HT receptors that line the GI tract; will go away
HEADACHE: will go away
SEXUAL DYSFUNCTION: WILL NOT GO AWAY
insomnia |
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Term
| clinical pearls for sertraline |
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Definition
must be given with food (increased BA)
more GI upset than other SSRIs |
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Term
| clinical pearls of paroxetine |
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Definition
| shortest 1/2 (<24 hours) and no active metabolite |
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Term
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Definition
only SSRI with mild anticholinergic ADRs (but not as bad as a TCA):
constipation, dry mouth
sedation
nausea
headache
weight gain
sexual dysfunction
sedation may be beneficial in certain patients |
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Term
| clinical pearls of fluvoxamine |
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Definition
drug interactions more common
only FDA indicated for OCD (approved for OCD in children > 6 yo |
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Term
| clinical pearls for citalopram and escitalopram |
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Definition
citablopram comes in ODT, solution
FDA NOTIFICATION IN 2011: SHOULD NO LONGER BE USED AT DOSES > 40 MG/DAY DUE TO QT PROLONGATION
10mg of escitalopram = 20 mg citalopram
escitalopram has the fewest drug interactions of the SSRIs
no differences in terms of efficacy between them
exactly the same in terms of tolerability |
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Term
| which SSRIs have potent interactions with CYP enzymes |
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Definition
FLUOXETINE: CYP2D6
PAROXETINE: CYP2D6
FLUVOXAMINE: CYP1A2, 2C19 |
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Term
| symptoms of discontinuation syndrome from SSRIs |
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Definition
anxiety, agitation, irritability, sleep disturbances, dizziness, nausea, electric-shock like sensation in extremities or head (paresthesias)
usually occurs 1-3 days after d/c SSRI; lasts up to 2 weeks
Worst with paroxetine, fluvoxamine, and venlafaxine (shortest t1/2)
taper all SSRIs slowly @5-7 day intervals (except fluoxetine) |
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Term
| causes of serotonin syndrome |
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Definition
causes/examples with an SSRI:
SSRIs, MAOIs, clomipramine, dextromethorphan, meperidine, TCAs, lithium, SAM-e, St. John's Wort, trazodone, buspirone, triptans, linazolid, tramadol
dispense:
trazodone
dextromethorphan (CANNOT TAKE DEXTROMETHORPHAN WITH AN MAOI THOUGH!!)
triptans
DO NOT DISPENSE:
tramadol
St. John's Wort
linezolid (will need monitoring) |
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Term
| symptoms of serotonin syndrome/treatment |
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Definition
symptoms:
confusion/delirium (mental status change)
agitation
GI (abdominal pain, diarrhea, N/V)
tremor
restlessness
hyperreflexia
HTN
tachycardia (autonomic instability)
fever
diaphoresis
myoclonus
rigidity
treatment:
avoid cominations if possible
allow appropriate wash-out periods (2 weeks)
d/c offending agents if observed |
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Term
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Definition
sedation:
fluvoxamine > paroxetine > sertraline > citabloporam/escitalopram > fluxoetine
nausea, diarrhea (5HT-3) - especially sertraline
headache, anxiety, insomnia
hyponatremia
prolonged bleeding (decreased platelet aggregation)
sexual dysfunction (5HT-2)
anorgasmia, delayed ejaculation, decreased libido, impaired erection |
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Term
| SSRI sexual dysfunction treatment |
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Definition
sexual dysfunction may be from stimulation of postsynaptic 5HT2/3 receptors
dose reduction of antidepressant or drug holiday (not recommended)
choose another antidepressant
add on or switch to bupropion or mirtazapine
bupropion is a dopamine reuptake inhibitor (doesn't work on 5HT so there is no sexual dysfunction
mirtazepine is a 5HT 2 blocker (not stimulator)
for delayed ejaculation or erectile dysfunction PDE5 inhibitors:
sildenafil
vardenafil
tadalafil |
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Term
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Definition
| blocks 5HT reuptake, postsynaptic 5HT-2A and H1 |
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Term
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Definition
for depression:
200-600 mg/day
for insomnia:
25-50 mg qHS |
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Term
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Definition
SEDATION
ORTHOSTASIS
RISK OF PRIAPISM
no anticholinergic ADRs
safer in OD |
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Term
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Definition
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Term
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Definition
| inhibits DA and NE (minimal) reuptake |
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Term
| Max doses of bupropion formulations |
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Definition
bupropion IR = MAX 450 MG/D
bupropion SR = MAX 400 MG/D
bupropion XL = 450 MG/D |
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Term
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Definition
HA
INSOMNIA: dose no later than 4pm
nausea
AGITATION
seizure
WEIGHT LOSS
NO SEXUAL DYSFUNCTION
contraindications: active eating disorders, epilepsy, chronic drinkers (all lower seizure threshold) |
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Term
| MOA of venlafaxine and desvenlafaxine |
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Definition
| SNRI: 5HT and NE reuptake inhibitors |
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Term
| dose of venlafaxine and desvenlafaxine |
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Definition
venlafaxine: 150 mg/d
desvenlafaxine: 50 mg/d |
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Term
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Definition
| SNRI: 5HT and NE reuptake inhibitor |
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Term
| clinical pearls for duloxetine |
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Definition
also used for diabetic neuropathy and fibromyalgia
BBW: HEPATOTOXICITY |
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Term
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Definition
5HT and NE release
blocks postsynaptic 5HT2/3
inhbits presynaptic alpha2 and H1 receptors
comes in ODT |
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Term
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Definition
sedation - should be dosed at bedtime
increased appetite
weight gain
dizziness
LESS sexual dysfunction
may increase cholesterol (TGs) |
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Term
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Definition
| SSRI + 5HT-1A partial agonist = minimal to NO sexual dysfunction |
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Term
| serotonin receptor activity: 5HT reuptake inhibition, 5HT2 antagonism, and 5HT3 antagonism |
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Definition
5HT reuptake inhibition: decreased anxiety, enhanced mood, nausea, vomiting, sexual dysfunction
5HT 2 antagonism: weight gain, no sexual dysfunction
5HT3 antagonism: anti-nausea |
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Term
| alpha receptor activity: alpha1 antagonism and alpha2 antagonism |
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Definition
alpha1 antagonism: orthostasis, priapism
alpha2 antagonism: increased NE |
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Term
| NE receptor activity: NE reuptake inhibition |
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Definition
| NE reuptake inhibition: tachycardia, increased BP, sweating, tremors, enhanced arousal and attention |
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Term
| antidepressants for refractory depression (2+ failures) |
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Definition
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Term
| what antidepressant should be avoided in patients with psychosis |
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Definition
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Term
| what antidepressant should be used in patients with significant nausea/cancer/HIV? |
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Definition
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Term
| what antidepressants should be used in patients with high risk of suicide by OD? |
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Definition
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Term
| what antidepressant should be used in patients with intolerable sexual dysfunction? |
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Definition
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Term
| treatment for resistant depression |
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Definition
continue at therapeutic dose x4-6 weeks
try a dual mechanism antidepressant (mirtazapine, SNRI, MAOIs)
augmentation stragegies:
thyroid hormone 20-25 mcg/day
lithium 900-1200 mg/day
aripiprazole 2-15 mg/day AS ADJUNCT
quetiapine 50-150 mg/day AS ADJUNCT
ECT: especially for pregnant patients, suicidal patients |
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Term
| antidepressants and pregnancy |
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Definition
SSRIs are category C
PAROXETINE RECENTLY MOVED TO CATEGORY D
may increase the risk of fetal heart defects
untreated depression during pregnancy: suicide risk, poor prenatal care, postpartum depression |
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Term
| time couse of response to antidepressants |
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Definition
1-2 weeks: increased energy, improved sleep, improved appetite, much more likely to act on a suicidal thought during the first 1-2 weeks after starting therapy
3-4 weeks: improved mood and less anhedonia, decreased hopelessness/helplessness, decreased suicidal ideathion, increased self care, concentration, and memory
4-6 weeks: relief of depressed mood, adequate trial at adequate dosage |
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Term
| medication discontinuation |
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Definition
1st episode: continue treatment for 4-9 months
2nd episode: continue treatment for > 1 year
recurrent depression: lifelong treatment |
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