69 - depression (ott) Flashcards
Risk of Recurrence
1 episode: ___ - ___ %
2 episodes: ___ %
3 episodes: ___ %
50-60%
70%
90%
risk factors for depression
- female sex
- middle age
- single
- white
- low economic status
- unemployment
- physical disability
- lack of social support
- stressful life events/adverse childhood experiences
- prior episodes or suicide attempts
- co-morbid medical disorders
- co-morbid substance use disorder
disease course
occurs at any age, but commonly seen in early adulthood ___ - ___ s
symptoms develop over ___ to ___
usually see a response to treatment, but not aggressive enough to achieve ___
remission = a period of __ or more months with no symptoms or only __ - __ symptoms
- remission is possible and is the treatment goal
- 20-30
- days, weeks
- remission
- 2, 1-2
Recurrence
- risk becomes lower overtime as duration of ___ increases
- persistent mild symtpms during remission is a predictor of ___
- function ___ during the episode and goes back to baseline upon remission
- remission
- recurrence
- deteriorates
DSM-5 Diagnostic Criteria
at least one of the symptoms must be ___ mood or loss of ___ or pleasure in doing things
- symptoms must cause clinically significant impairment in functioning
- no history of ___
- not attributed to the psychological effects of a ___ or another condition
- depressed
- interest
- mania
- substance
DSM-5 Diagnostic Criteria Mnemonic
SIGE CAPS
- sleep (insomnia/hypersomnia)
- interest decreased
- guilt/worthlessness
- energy loss/fatigue
- concentration difficulties
- appetite change
- psychomotor agitation/retardation
- suicidal ideation
depression specifiers
with anxious distress
- higher ___ risk
- longer duration of illness
- ___ treatment response
with melancholic features
- anhedonia
- psychomotor ___ /agitation worse in the ___ , more likely in ___
with atypical features
- ___ mood
- weight ___
- hypersomnia, more likely in ___ patients
- suicide
- poor
- retardation, elderly
- reactive
- gain
- younger
depression specifiers
with psychosis
- hallucinations/delusions
- may or may not be congruent with ___
with catatonia
- stupor, blunt affect, extreme ___ , negativism, psychomotor ___ , posturing, echolalia
with peripartum onset
- occurs during pregnancy or ___ weeks following birth
with seasonal pattern
- symptoms have a relationship to the time of the year (fall/winter) and remit in the spring
- mood
- withdrawals, retardation
- 4
self administered rating scales
- depression: ___
- depression (clinical trials): ___
- bipolar: ___
- (PHQ9) - patient health questionnaire
- (QIDS-R-16) - quick inventory of depressive symptomatology self report
- (MDQ) - mood disorder questionnaire
goals of treatment
1) reduced or eliminate s/s of depression
2) restore ___ and psychosocial functioning to baseline
3) reduce the risk of ___ and recurrence
4) reduce the risk of harmful consequences ( ___ ideation)
- occupational
- relapse
- suicidal
phases of treatment
acute:
- __ - __ weeks or remission of symptoms
- Goal: induce ___
continuation:
- __ - __ additional months, recommended for all patients
- Goal: prevent ___
maintenance:
- patient-specific ___
- often indefinite treatment if ___ or greater major depressive episodes
- Goal: prevent ___
- 6-12
- remission
- 4-9
- relapse
- duration
- 3
- recurrence
SSRIs
___ (Lexapro)
dose range: 5-10 mg/day
clinical pearls
- pure S enantiomer of citalopram
- substrate of ___
escitalopram
- 2C19
Risk of Suicidality
boxed warning for suicidaily in ___ antidepressant medications (for patients less than or equal to ___ years of age)
- decreased risk in those __ and onlder
closely monitor for increased ___ and changes in behavior during the first 1-2 months of therapy and after any dose changes
- ALL, 24
- 65
- suicidality
SSRIs
___ (Celexa)
dose range: 10-40 mg/day
- > 60 years: do not exceed 20 mg
clinical pearls
- dose dependent ___ prolongation
- substrate of ___ and ___
citalopram
- QTc
- 2C19 and 3A4
SSRIs
___ (Prozac)
dosage range: 10-80 mg/day
clinical pearls:
- weekly DR oral formulation (90 mg/week)
- ___ t 1/2 (96-144 hrs)
- activating potential
- ___ and ___ inhibitor (norfluoxetine) - active
flucoxetine
long
CYP 2D6, 3A4
SSRIs
___ (Luvox)
dosage range: 50-300 mg/day
clinical pearls
- indicated for ___ treatment
- inhibitor of ___ and ___
fluvoxamine
- OCD
- 1A2, 2C19
not super common
SSRIs
___ (Paxil)
dosage range:
- 10-60 mg/day
- 12.5-75 mg/day
clinical pearls
- must ___ due to ___ effects
- weight ___, sedation
- ___ wall defect risk to fetus
- inhibits ___ and ____
paroxetine
- taper, anticholinergic
- gain
- septal
- 2D6, 2B6
Ott doesnt like this drug (hard to stop)
SSRIs
___ (Zoloft)
dosage range: 25-200 mg/day
clinical pearls
- more ___ upset than other antidepressants
- inhibitor of ___ , ___ , and ___
sertraline
- GI
- 2C19, 2D6, 3A4
SSRIs - Adverse Effects/Key Points
- onset of action in __ - ___ weeks
- full dose response in ___ - ___ weeks
AE
- variable sedation
- weight gain ( ___ )
- weight loss ( ___ )
- increased ___ risk ( ___ inhibition)
- hypo ___ (especially in elderly)
- ___ dysfunction
- anxiety/agitation (upon initiation)
- emotional blunting
- decreased ___ mineral density
- 1-2
- 4-6
- paroxetine
- fluoxetine
- bleeding, platelet
- hyponatremia
- sexual
SNRIS
___ (Pristiq)
dose range: 50-400 mg/day
clinical pearls
- active metabolite of ___
- dose limiting SE: ___
- flate dose response curve for doses 50-400 mg/day
- no major ___ interactions
desvenlafaxine
- venlafaxine
- nausea
- CYP
Ott has never had a patient go above 100 mg/day
SNRIs
___ (Cymbalta)
dose range: 30-120 mg/day
- doses > 60 mg do not increase the response
clinical pearls
- slow titration or divided dosing help with ___
- FDA warning for ___
- new dosage form: Drizalma Sprinkle
- inhibitor of ___
Otts favorite, can also help with pain
duloxetine
- nausea
- hepatotoxicity
- 2D6
SNRIs
___ (Fetzima)
dosage range: 40-120 mg/day
clinical pearls
- must adjust in ___ impairment or strong ___ inhibitors
- rare - seizures/glaucoma
- substrate ___
levomilnacipran
- renal, 3A4
- 3A4
SNRIs
___ (Savella)
dosage range: 12.5-200 mg/day
clinical pearls
- indicated for ___
- renal dosing adjustments
milnacipran
- fibromyalgia
SNRIs
___ (Effexor)
dosage range: 75-327 mg/day
clinical pearls
- must be > ___ mg/day to have NE effects
- ___ inhibitor at higher doses
- substrate ___ and ___
venlafaxine
- 150
- 2D6
- 2D6, 3A4
SNRIs - AE/Key Points
- onset of action in __ - ___ weeks
- full dose response in ___ - ___ weeks
useful in ___ syndrome, musculoskeletal pain, fibromyalgia, and ___ pain
duloxetine: obtain ___ at baseline and when symptomatic or every ___ months
- 1-2
- 4-6
- pain, neuropathic
- LFTs, 6
SNRIs - AE/Key Points
- ___ elevation
- sweating
- variable sedation
- increased bleeding risk (platelet inhibition)
- hyponatremia (especially in elderly)
- sexual dysfunction
- anxiety and agitation
- ___
- decreased bone mineral density
- BP
- nausea
TCAs
blockade of reuptake transporter ( ___ , ___ , and ___ ) inhibits the reuptake of 5HT, NE, and DA
___ (Elavil) - ___ amine
dose range: 50-300 mg/day
Clinical pearls
- used to lower doses for neuropathic pain
- SERT, NET, DAT
amitriptyline, tertiary
TCAs - AE/key points
more often used for ___ ___ syndromes than depression
- amitriptyline or nortriptyline
side effects often limit higher doses
- ___ : sedation, reduced seizure threshold, confusion
- ___ : blurred vision, urinary retention, consipation
- cardiovascular: orthostatic hypotension, ___ cardia
- other: weight ___ , sexual dysfunction
Narrow therapeutic index
- fatal in overdose as low as 1000 mg (4-10 tablets) due to cardiac ___ or ___
neuropathic pain
- CNS
- anticholinergics
- tachycardia
- gain
- arrhythmias, seizures
MAO Inhibitors
___ (Marplan)
- 20-60 mg/day
___ (Nardil)
- 45-90 mg/mL
___ (Ensam)
- patch: 6-12 mg/day
___ (Parnate)
- 20-60 mg/day
- iscarboxazid
- phenelzine
- selegiline
- tranylcypromaine
MAO Inhibitors
Clinical pearls
- must have ___ week washout period before switching antidepressants ( 5 week washout period if switching from ___ )
- all require ___ diet, except ___
- caution due to HTN ___ and ___ syndrome
- 3rd-4th line option
- 2, fluoxetine
- tyramine, selegiline patch
- ## crisis, serotonin
Selegiline Patch (Ensam)
selective ___ inhibition at lower dose at lower doses
- must be used as monotherapy
administration
- rotate patch ___ to prevent irritation, do not cut or expose to direct heat
tyramine diet NOT required with the ___ mg patch
- required for 9 mg and 12 mg
adverse effects
- ___ tension, dry mouth ___ , headache, GI upset
- MAO-B
- daily
- 6 mg
- hypotension, insomnia
MAOis CI
- ____ - adrena tumor causing increased BP
- ___ or ___ dysfunction
- ___ diseases
- excessive ___ use
- elective surgery
- concomitant ____
- cardiovascular disease
- use of other ___ medications
- pheochromocytoma
- hepatic, renal
- cerebrovascular
- caffeine
- sympathomimetics
- serotonergic
MAOis - hypertensive crisis
___ diet is required with MAOis - when this builds up, caused increased BP
tyramine
bupropion (Wellbutrin)
MOA: ___ and ___ reuptake inhibitor
- stimulating - ___ and ___ suppression
- some misuse potential, similar structure to cathinones/ ___
Dosing
- SR/ __ dosing: 150-450 mg/day
- if using SR, give second dose no later than __ pm
clinical pearls
- ___ inhibitor
- CI in active ___ and ___ disorders
- can be used in combination with ___ and ___
- DA, NE
- insomnia, appetite
- bath salts
- XL
- 4 pm
- 2D6
- seizure, eating
- SSRIs, SNRIs
Ott prefers XL (SR seizures) even for smoking cessation
mirtazapine (Remeron)
Mechanism
- presynaptic ____ blockage as well as 5HT __ , 5HT __ , and ___ blockade
dosing - 7.5-45 mg/day
- sedation and increased appetite occur with doses less than or equal to ___ mg/day
clinical pearls
- substrate ___ , ___ , ___
- warnings: ___ increased ___
- can be used in combination with ___ and ___
- a2, 5HT2, 5HT3, H2
- 15
- 1A2, 2D6, 3A4
- agranulocytosis, cholesterol
- SSRIs, SNRIs
trazodone (Desyrel)
Mechanism
- selectively inhibits ___ reuptake and acts as antagonist at 5HT __ , 5HT2, H1, and a1
dosing: 150-600 mg/day
- ___ doses needed for depression
- off label for ___ : 50-150 mg at bedtime
drug interactions
- trazodone → (CYP ___ ) → m-CPP → (CYP ___ ) → inactive metabolites
SE
- orthostatic hypotension
- risk of ___ - medical emergency
- 5HT, 5HT1
- high
- insomnia
- 3A4, 2D6
- priapism
vilazodone (Viibryd)
mechanism
- primarily SSRI, may have some 5HT1a ___ which may provide anxiolytic effects
- do not use in combination with ___ and ___
dosing
- 10 mg once daily x7 days, 20 mg once daily x7 days for a target dose of 40 mg once daily
clinical pearls
- take with ___
- significant ___
- ___ increases bioavailability
- substrate ___
- reduce target dose to 20 mg with strong 3A4 inhibitors
- AE: insomnia, nausea, diarrhea, sexual dysfunction
- agonism
- SSRIs, SNRIs
- food
- nausea
- food
- 3A4
vortioxetine (Trintellix)
mechanism
- SSRI + 5HT1A ___ + 5HT3 ___
- do not use in combination with ___ and ___
dosing
- 10 mg once daily with meals
- target dose of 20 mg once daily
clinical pearls
- possibly less ___ dysfunction
- substrate ___
- reduce target dose to 10 mg daily with strong inhibitors
- AE: ___ , vomiting, constipation
- agonist, antagonist
- SSRIs, SNRIs
- sexual
- 2D6
- nausea
serotonin sydrome
medical ___ due to excessive amounts of serotonin in the CNS
may be caused by:
- overdose
- combined use of serotonergic drugs
- drug inteactions
serotonergic agents
- Li
- serotonergic antidepressants
- buspirone
- linezolid
- amphetamines
- dextromethorphan
- triptans
- st john’s wort
- tramadol
- fentanyl
- cocaine
- LSD
emergency
serotonin syndrome - treatment
___ the offending agent + supportive care
potentially could use serotonin blockers
- ___ (variable efficacy)
70% of patients recover within 24 hours
stop
cyproheptadine
antidepressant withdrawal syndrome
- occurs due to abrupt cessation of antidepressant
- common with ALL antidepressants EXCEPT ___
- risk can be minimized by slow dose taper over 1-2 weeks
- antidepressants with ___ activity should be tapered no matter what
- symptoms can mimic those of depresion (agitation, irritability, GI disturbance, “brain ___ “)
- NOT ___ but extremely uncomfortable
- fluoxetine
- anticholinergic
- zaps
- life-threatening
augmentation agents (8)
- antipsychotics
- Li
- anticonvulsants
- pindolol
- triiodothyronine (T3)
- BZDs
- buspirone
- atomoxetine
augmentation - atypical antipsychotics
5HT2a ___ and partial 5HT1a ___
- indirect effects on NE transmission
- dosing is ___ for depression than with other disease states
FDA approved augmentation agents (4)
- ___ (Abilify) 2-15 mg/day
- ___ (Rexulti) 0.5-3 mg/day
- ___ (Vraylar) 1.5-3 mg/day
- ___ (Seroquel) 50-300 mg/day
additional agents
- ___ / fluoxetine (Symbyax) 6/25-25/50 mg/day
- ___ (Risperdl) 1-3 g/day
- antagonism, agonism
- lower
- aripiprazole
- brexpiprazole
- cariprazine
- quetiapine
- olanzapine
- risperidone
aripiprazole is Ott’s favorite
antidepressants for specific purposes
post-partum depression - allosteric modulator of allopregnanolone
- ___ - IV only, __ hours infusion, excessive ___ boxed warning, REMS program
- ___ - oral dose, 14 day dosing, boxed warning for ___ driving (CNS depression)
treatment-resistant depression
- ___ nasal spray - NMDA receptor antagonist
- also use for MDD with suicidal ideation
- induction and maintenance phases, REMS program to give in clinic, stay in clinic for 2 hours post dose
- brexanolone, 60, sedation
- zuranolone, impaired
- esketamine
overall key counseling points
- may take ___ - ___ weeks to see beneficial effects of antidepressant
- must be taken as prescribed
- need to continue medication for ___ - ___ months yo decrease risk of recurrence
- abrupt d/c can lead to antidepressant ___ syndrome
- possible increase in suicidal thinking during the first few ___ of therapay
- 2-4
- 6-9
- withdrawal
- weeks
non-pharmacologic treatment
___ is most common
mild depression or episodes without psychosis may use psychotherapy without drug therapy if
- history of response
- patient preference
- medication CI
- pregnancy
psychotherapy
only paroxetine is teratogenic
electroconvulsive therapy (ECT)
unilateral or bilateral placement of ___
- 10-15 min procedure
administration
- 2-3 times weekly as induction
- usual course if 6-12 treatments
- continue until maximal response
- can use as maintenance
advantages
- efficacy in treatment ___
- can continue drug therapy
- age not a factor
- safe in pregnancy
disadvantages
- temporary memory loss
- stigma
- CI in recent ___ or hemorrhagic stroke or if loose teeth
- electrodes
- resistance
- MI
other non-pharmacologic optioins
- ___ nerve stimulation
- transcranial ___ stimulation
- vagus
- magnetic
steps to manage depression
