CANMAT Guidelines: Depression Part 3 (neurostimulation etc) Flashcards
name the first line neurostimulation treatment recommended by the guidelines for MDD?
under what conditions is this recommended?
tTMS
(if FAILED at least one antidepressant)
what level evidence is there for rTMS for MDD in the acute and maintenance phases
level 1 for acute and level 3 for maintenance
(has level 1 evidence for safety and tolerability)
what is the second line neurostimulation treatment recommended by the guidelines for MDD
ECT (it is first line in some situations)
what level evidence is there for ECT for MDD
level 1 for acute and maintenance, and for safety and tolerability
WE HAVE GOOD EVIDENCE ECT WORKS AND IS SAFE AND TOLERABLE
list two third line neurostimulation treatments for MDD
tDCS
VNS
list two investigational neurostimulation treatments for MDD
DBS
MST
what is tDCS
transcranial direct current stimulation
a form of brain stimulation that delivers a CONTINUOUS, LOW AMPLITUDE electrical current to a specified cortical region using SCALP electrodes
list some advantages of tDCS
ease of use
low cost
portability
potential for home based use
ability for combination with other treatments
low potential for adverse effects
what is the effect of ANODAL stimulation in tDCS
anodal stimulation over the cortex INCREASES cortical excitability through DEpolarization of neuronal membrane potential
what is the effect of CATHODAL stimulation in tDCS
cathodal stimulation DECREASES cortical excitability through HYPERpolarization of the neuronal membrane potential
what is the hypothesized mediator of the effects of tDCS
NMDA receptor-dependent mechanisms
are there clear parameters for the optimal delivery of tDCS
no cohesive summary
exact frequency and duration of stimulation have not been established
how is tDCS generally delivered (i.e placement of electrodes etc)
anodal stimulation over the left DLPFC
+
cathode used as a ground over a noncortical region
OR
anodal stimulation over the left DLPFC and cathodal stimulation over the right DLPFC
what is an often used parameter for frequency and intensity for tDCS treatment (to observe and antidepressant effect)
seems that minimum stimulation with 2 milliamperes (mA) for at least 30 min per day for 2 weeks is necessary to observe an antidepressant effect
is tDCS monotherapy or combo therapy with SSRI better
combo
is tDCS well tolerated
yes generally
what are the most common side effects of tDCS
regional effects at skin–> redness, itching, burning, heat, tingling
low rates observed of headaches, blurred vision, ear ringing, fatigue, nausea, mild euphoria, reduced concentration, disorientation, insomnia, anxiety
is there a risk of hypomania or mania with tDCS
yes–> found in study where tDCS was combined with sertraline though
what is rTMS
uses powerful (1-2.5 Tesla), focused MAGNETIC FIELD PULSES to induce electrical currents in neural tissue noninvasively via an inductor COIL placed against the SCALP
is anesthesia required for rTMS
no
do we have a clear understanding of the mechanism by which rTMS has antidepressant effects
no–> mechanisms proposed at both cell-molecular and network levels
what is a standard protocol for rTMS
once daily, 5 days per week
(there are some slower and faster schedules being investigated)
maximal effects found at about 26-28 sessions
stimulation delivered in 2-10 second trains at 10-60 sec intervals in 15-45 min sessions
how is stimulus intensity determined for rTMS? what is the most common stimulus intensity prarameter for rTMS?
stimulus intensity based on individually determined resting motor threshold (RMT–> minimum intensity to elicit muscle twitches at relaxed upper and lower extremities)
most common intensity is 110%-120% RMT
what are the two first line rTMS stimulation protocols
high frequency rTMS to left DLPFC
low frequency rTMS to right DLPFC
*there are other protocols as well but i will never remember them
is high frequency rTMS considered excitatory or inhibitory
high frequency rTMS is generally considered EXCITATORY
(low frequency rTMS generally considered inhibitory)
does rTMS have evidence in treating treatment resistant depression
rTMS targeting the left DLPFC showed superior response and remission rates vs sham in this population
following successful rTMS is there evidence for maintenance rTMS ongoing
yes–> evidence for more sustained remission with maintenance rTMS
is rTMS as effective as ECT
no–> rTMS is consistently LESS EFFECTIVE than ECT (especially for psychosis)
are rTMS and ECT complementary or competing treatments
best understood as complementary
is rTMS effective when ECT has failed
no–> response rates are poor to rTMS when ECT has failed
*consider rTMS prior to pursuing ECT
what are common side effects of rTMS
scalp pain during treatment (40%)
transient headache after treatment (30%)
SEs diminish steadily over treatment
are there any cognitive side effects of rTMS
no worsening (no difference vs sham)
what is the most serious rTMS adverse event
seizure induction
*less than 25 cases worldwide
what is a contraindication for high frequency rTMS
seizure history
is low frequency rTMS safe in epilepsy
yes
*but for most practictioners a history of seizures is a contraindication for rTMS
what is the incidence of seizure with rTMS?
how does this compared to baseline spontaneous risk of seizures?
rTMS: 0.01-0.1% risk
spontaneous: 0.07-0.09% risk
name two absolute contraindications to rTMS
metallic hardware in head (except mouth)
(many consider seizure hx absolute contraindication)
list 4 relative contraindications to rTMS
cardiac pacemaker
implantable defibrillator
hx epilepsy
brain lesion (vascular, traumatic, neoplastic, infectious, metabolic)
what is ECT
a therapeutic procedure that entails induction of a seizure by applying electrical stimulus to the brain
it is an EFFECTIVE and WELL ESTABLISHED treatment method for depression and other mental disorders
how is ECT delivered
in a controlled setting under induction of general anesthesia and the application of a muscle relaxant
are there any ABSOLUTE contraindications to ECT
no
(according to CANMAT guidelines)
list 7 conditions that may be associated with increased safety risk in ECT
- space occupying cerebral lesion
- increased ICP
- recent MI
- recent cerebral hemorrhage
- unstable vascular aneurysm or malformation
- pheochromocytoma
- class 4 or 5 anesthesia risk
what is the proposed mechanism of action of ECT
still being investigated
main hypotheses = seizure induced changes in neurotransmitters, neuroplasticity, and functional connectivity
i.e ECT can increase levels of brain derived neurotrophic factors (BDNF) which may contribute to the antidepressant effect
what effect does ECT have on brain derived neurotrophic factors
increases levels of BDNF which may contribute to the antidepressant effect
why is ECT considered second line in treatment of MDD
because of adverse events
but can be considered first line in some situations
list 3 treatment parameters of ECT to consider
electrode position
electrical intensity
pulse width
that are the three most common electrode placements in ECT
right unilateral
bitemporal
bifrontal
what is the basis of the electrical intensity used in ECT treatment
based on the minimum intensity to produce a generalized seizure–> SEIZURE THRESHOLD
what electrical intensity is generally used in bitemporal and bifrontal ECT
1.5-2x seizure threshold
what electrical intensity is generally used in RUL ECT
5-6x (or even up to 8x) seizure threshold
which electrode placement is most efficacious in ECT
BT, BF and RUL have EQUAL efficacy but have different cognitive side effect profiles
which two electrode placements in ECT are recommended first line
BF and RUL
BT is recommended second line due to higher rates of short term cognitive adverse effects
what pulse width is generally used with ECT
brief pulse (BP)
*clinical and research interest in ultra brief pulse width treatments
why might ultra brief pulse width ECT be beneficial
may be associated with less short term cognitive impairment and specifically the loss of autobiographical memory
*BUT ultra brief pulse width may have slower speed of improvement and require more treatments that brief pulse
what is the typical index course of ECT
6-15 treatments
*usually delivered 2-3x per week in the index course
are more than 3 ECT treatments per week recommended
no–> associated with more cognitive side effects
list 9 clinical indications for ECT as a FIRST LINE treatment for MDD
- acute suicidal ideation
–level 1 - psychotic features
–level 1 - treatment resistant depression
–level 1 - repeated medication intolerance
- catatonic features
- prior favorable response to ECT
- rapidly deteriorating physical status
- during pregnancy, for any of the above indications
- patient preference
is ECT effective in treating MDD? what is the response rate?
it is one of the MOST effective treatments for MDD
response rates can reach 70-80% with remission rates 40-50% or higher depending on patient population and type of stimulus
what is the strongest predictor of non response to ECT
the degree of resistance to previous treatments
what is the response rate to ECT in patients with a previous treatment failure to psychological or pharmacolgical treatment
50%
(compared to 65% response for those who had not failed another treatment)
list clinical factors associated with higher response rates to ECT
older patients
psychotic features
shorter episode duration
?lesser depressive severity
what are the relapse/recurrence rates associated with ECT
also high
highest in first 6 months post ECT
relapse rates of about 50% have been observed within 1-2 years
how does maintenance ECT compared to pharmacotherapy post ECT
maintenance ECT is as effective as pharmacotherapy (in preventing relapse and recurrence)
what pharmacotherapy should be used post ECT for maintenance
an untried antidepressant
OR
nortriptyline + lithium
OR
venlafaxine + lithium
how does pharmacotherapy post ECT compare to continuation/maintenance ECT with regard to preventing relapse/recurrence
about equally effective
what is a typical schedule for continuation/maintenance ECT
weekly x 4 weeks
then
biweekly x 8 weeks
then monthly
if deteriorates, increase frequency
what is the impact of antidepressants post ECT on relapse rates
decreases relapse rates by half
have any studies demonstrated damage to brain structures related to administration of ECT
no
what is the mortality rate associated with ECT
less than 1 in 73440 treatments (0.0014%)
list the 3 most common side effects of ECT
headache (about half)
muscle soreness (20%)
nausea (up to 25%)
*most are associated with treatment, are transient and can be treated symptomatically
what is the rate of manic switch with ECT
7%
list possible cognitive side effects of ECT
- transient disorientation when recovering from ECT (post ictal + effects of general anesthesia)
- retrograde amnesia
- anterograde amnesia
- there is mild, short term impairment in memory and other cognitive domains during and immediately following a course of ECT
–> impairments are usually TRANSIENT with recovery of cognitive functioning occurring within weeks to months after an acute course of ECT–> no eventual cognitive differences between ECT parameters including electrode placement or pulse width
list 3 factors associated with greater risk of cognitive impairment related to ECT
pre-existing cognitive impairment
older age
use of bitemporal placement
is the retrograde amnesia sometimes seen in ECT also transient?
some studies suggest PERSISTING DEFICITS
others suggest objective tests of autobiographical memory did not persist beyond 6 months post ECT
patient self reports indicate some persistent cognitive dysfunction, especially retrograde amnesia, but self reports of cognitive dysfunction are usually highly correlated with PERSISTENT DEPRESSIVE SYMPTOMS and are NOT correlated with objective testing
is there a benefit to treating with ADs during the ECT course (rather than sequentially after)
yes–> lower relapse rates
why might you reconsider lithium treatment in a patient undergoing ECT
may increase risk of side effects
higher risk of cognitive symptoms
risk of encephalopathy
risk of spontaneous seizures
why might you reconsider benzodiazapine or anticonvulsant treatment during a course of ECT
likely to raise the seizure threshold and decrease seizure efficacy
*lamotrigine may be less problematic
what is magnetic seizure therapy (MST)
noninvasive convulsive neurostimulation therapy that relies on the principle of ELECTROMAGNETIC INDUCTION to induce an electric field in the brain strong enough to elicit a generalized tonic clonic seizure
being investigated as alternative to ECT
seizure is elicited under GA with assisted ventilation and EEG monitoring
why might you opt for MST over ECT
MST has potential for fewer side effects such as cognitive dysfunction
how is MST performed
uses a neurostimulator and coil that is placed in direct contact with the skull
when electrical current passes through the coil, a strong FOCAL MAGNETIC FIELD is generated (around 2 Tesla)
magnetic field crosses the skull and soft tissue unimpeded to reach brain tissue–> induces electrical current that causes neuronal depolarization and eventually triggering seizure
what are the delivery parameters of MST
The optimal delivery parameters for MST are still being investigated.
Most studies have used a coil placement at the vertex
(i.e., Cz in 10-20 electroencephalogram [EEG] system) with a
frequency of stimulation of 100 Hz, pulse width of 0.2to 0.4 ms,
and stimulation duration of 10 seconds.
how often is MST given? how long is an index course?
usually similar to ECT
index around 12 treatments, 2-3 x per week
are there any studies comparing MST to sham?
no
how does efficacy compare between MST and ECT
MST vs RUL ECT showed no significant differences in response/remission rates
but there are no studies of MST in relapse or relapse prevention
*recommended as investigational treatment alternative to ECT
how do side effects comapre between MST and ECT
MST showed (compared to ECT):
lower rates of headache and muscle ache
no significant impact on retrograde and anterograde amnesia
shorter reorientation time
in MST vs RUL ECT there was no difference in neuropsych testing after 12 treatments
what is vagus nerve stimulation (VNS)
an IMPLANTABLE neurostimulation technology originally approved i 1997 for treatment of drug resistant epilepsy
comprises an implantable pulse generator (IPG) which is SURGICALLY inserted underneath the skin of the chest, connected to an electrode placed in one of the VAGUS NERVES in the neck
electrical stimulation of the vagus nerve provides stimulation to the NUCLEUS TRACTUS SOLITARIUS–> in turn able to modulate multiple regions of brain via its neuronal connections to anatomically distributed subcortical and cortical regions of the brain
what specific brain area is stimulated via the vagus nerve during VNS
the nucleus tractus solitarius
(which in turn is able to modulate
multiple regions of the brain via its neuronal connections to
anatomically distributed subcortical and cortical regions of
the brain)
what are the optimal treatment parameters for VNS
under investigation
is VNS approved by the US FDA
yes–> as adjunctive treatment for chronic/recurrent depression in those who have failed to response to 4 or more adequate antidepressant trials
are there studies comparing VNS to sham?
yes–> showed NO significant differences at 12 weeks
BUT open label studies have shown response rate of about 30%
*therefore is 3rd line
does VNS seem to be more effective in short term or longer term treatment
longer term–> ?antidepressant effects ACCRUE over time
median time to response seems to be between 3-9 months
effects may be sustained at 12-24 months
what are the most common side effects of VNS
VOICE ALTERATION (69%)
dyspnea (30%)
pain (28%)
increased cough (26%)
*voice + cough SEs are direct effects and improve by turning VNS off
name two possible serious adverse psychiatric events that have been associated with VNS
suicide + attempted suicide –> 4.6%
treatment emergent hypomania/mania –> 2.7%
how does all cause mortality differ between treatment for MDD with VNS vs treatment as usual
LOWER all cause mortality (including suicide) with VNS than treatment as usual
what is deep brain stimulation (DBS)
INVASIVE neurosurgical procedure involving implantation of electrodes under MRI guidance into discrete brain targets
electrodes internalized and connected to an IPG (implantable pulse generator) that is typically implanted in the chest below right clavicle
what is currently the most common indication for DBS
movement disorders (more specifically Parkinsons)
–> DBS for difficult to treat psychiatric disorders including treatment resistant depression is growing research field
what are the treatment parameters to consider in DBS
pulse width
frequency
amplitude
list the four anatomical targets for DBS in the treatment of treatment resistant depression
- subcallosal cingulate white patter (SCC) (majority of reports focus on this)
- ventral capsule, ventral striatum (VC/VS)
- nucleus accumbens (NA)
- medial forebrain bundle (MFB)
what are the response and remission rates currently seen in DBS
response between 30-60%
remission between 20-40%
at 3 or 6 months
*note that these studies done in highly treatment refractory patients
one small study (n=7) showed response rate of 85.7% and remission rate above 50%
HOWEVER–> two sham controlled RCTs of DBS were stopped early due to LACK of an efficacy signal for acute treatment resistant depression
how effective is DBS over extended treatment
antidepressant effects seem to accrue over months and years of chronic stimulation with improved rates of functional and clinical outcomes observed beyond 1 year post surgery
but data does not yet demonstrate efficacy for acute treatment of TRD
likely ongoing DBS required to maintain remission
is there evidence of negative impact of performance on neuropsych testing due to DBS
no–> may actually improve it
list psychiatric adverse events associated with DBS
psychosis, hypomania–> transient, reversible
reports of suicidality, completed suicide–> unclear association
list some possible non-psych adverse events associated with DBS
oculomotor adverse event–> blurred vision, strabismus
risks of surgical procedure itself, perioperative risks
list 5 CAM treatments for MDD in the “physical and meditative treatments” section
exercise
light therapy
yoga
acupuncture
sleep deprivation
is exercise a first or second line treatment for MDD
both!
first line as monotherapy for mind-moderate MDD
second line as adjunctive treatment for mod-severe MDD
is light therapy first or second line for MDD
both!
first line monotherapy for seasonal (winter) MDD
second line as either mono or adjunctive treatment for mold to moderate non-seasonal MDD
list two first line physical/meditative treatments for MDD
exercise and light therapy
list 3 second line physical/meditative treatments for MDD
exercise
light therapy
yoga
list 2 third line physical/meditative treatments for MDD
acupuncture (for mild to mod MDD)
sleep deprivation (for mod-severe MDD)
what is the standard protocol for light therapy for MDD
10 000 lux during the early morning
30 min per day for 6 weeks
see response within 1-3 weeks
what are the proposed mechanisms of light therapy for MDD
alteration of circadian rhythm
modulation of serotonin and catecholamine systems
name common side effects of light therapy for MDD
eye strain
headache
agitation
nausea
sedation
*generally well tolerated
what is/are the protocols for sleep deprivation in treating MDD
keep patients awake for an extended period of time
2-4 times over 1 week
total SD–> up to 40 hours
partial SD–> 3-4 hours of sleep per night
total SD often interspersed with partial SD or normal/recovery sleep
is sleep deprivation effective at treating symptoms of depression
“continues to demonstrate rapid antidepressant effects in recent publications”
*relapse after discontinuation is often rapid
what are the proposed mechanisms for the antidepressant effects of sleep deprivation in MDD treatment
increased activity of all neurotransmitter systems
increased synaptic potentiation + glial signalling
what are the practical limitations of sleep deprivation as treatment for MDD
difficult to maintain use for more than a few weeks
often rapid relapse after discontinuation
sleep deprivation in combination with what other therapy may be more practically useful than sleep deprivation alone
combined SD + chronotherapy (sleep phase advance)
rapid onset of efficacy, greater clinical utility + sustained response
what is the most common side effect of sleep deprivation for MDD treatment
may have recurrence of panic attacks
low rates of SD-induced mania
what is a contraindication to sleep deprivation therapy
epilepsy
*high risk of seizure induction
which is more effective for exercise therapy for MDD, aerobic or anaerobic exercise
same–neither is superior
how often should you work out in exercise therapy for MDD
30 min 3x/week for 9 weeks
what are proposed potential mechanisms that explain the efficacy of exercise therapy for MDD
biological–> increased turnover of neurotransmitters, endorphins, BDNF; decreased cortisol levels
psychological–> increased self efficacy
long term benefits in MDD less clear
what are the proposed mechanisms behind yoga therapy for MDD
increased turnover of dopamine and GABA
regulation of HPA axis
normalization of HR variability
are there any side effects to yoga for MDD
rarely
case reports of meditation induced mania/psychosis
excessive/incorrect practice can lead to artery occlusion, neuropathy
how often is it recommended to practice yoga for treatment of MDD
2-4 sessions per week for 2-3 months
are there any first line natural health products for the treatment of MDD
yes–> St. John’s Wort
monotherapy for mild to moderate MDD
list the second line natural health product treatments for MDD
St. Johns Wort
Omega 3
SAME-e
list the third line natural health products for treatment of MDD
acetyl-L-carnitine
saffron
DHEA
folate
lavender
are there any natural health products NOT recommended for treatment of MDD
inositol
tryptophan
roseroot
what are the proposed mechanisms for how st johns wort works
direct effect of serotonin receptors
MAOi
neuroendorine and ion channel modulation
what are the side effects of st johns wort
GI upset
headaches
skin irritation
photosensitivity
dry mouth
*risks of P450 drug interactions
*better tolerated than many SSRIs
what are risks of st johns wort
reports of serotonin syndrome, hypomania if using concurrent ADs
how is st johns wort recommended to be used for MDD treatment
first line monotherapy for mild-moderate MDD
second line adjunct for mod-severe MDD
how do the guidelines recommend omega-3s be used
second line monotherapy for mild-mod MDD
second line adjunct for mod-severe MDD
what is SAM-e
a natural substrate found in the body, including in the brain, that is thought to function as a methyl donor in various physiological processes
prescribed in europe for MDD (is OTC in canada)–> 800-1600mg po/day for 4-12 weeks
– what is the proposed mechanism for SAM-e in the treatment of MDD
modulation of monoaminergic neurotransmission
what are possible side effects of SAM-e
GI upset
tachycardia
sweating
headache
irritability
restlessness
anxiety
insomnia
fatigue
what is the guidelines recommendation for use of SAM-e
second line adjunct for mild-mod MDD
how do MDD symptoms tend to differ in adolescents
more HYPERsomnia
fewer appetite/weight changes
fewer psychotic symptoms
what is a semi-structure interview approach for kids and teens who screen positive for MDD
K-SADS (kiddie schedule for affective disorders)
what psychotherapeutic interventions are recommended in the C&A population for MDD
CBT + IPT
are there clear advantages of pharmacotherapy vs psychotherapy in treating MDD in C&A populations?
no clear advantage for either
*combining them showed no significant differences in achieving remission or preventing relapse but combo DID reduce FUNCTIONAL IMPAIRMENT in the short term
what approach to treatment showed greatest improvements in depressed youth who had recently attempted suicide
CBT for suicide prevention + pharmacotherapy
is psychotherapy first line for MDD in depressed youth
yes–for mild - mod depression
does paroxetine have evidence for efficacy in C&A population
no efficacy shown
does citalopram have evidence in C&A populations
little evidence–> does have higher remission rates compared to placebo
what is the first choice SSRI for depressed youth
FLUOXETINE
–> superior to placebo (we have the best evidence for fluoxetine)
list 3 SSRIs that do have evidence for efficacy in treating depressed youth
fluoxetine
escitalopram
–> superiority on function and depression scores compared to placebo
sertraline
–> some evidence superior to placebo but small effects
what SSRI should be avoided in patients with congenital longQT syndrome
citalopram
are TCAs useful in children?
NO
only marginal evidence in teens, but not useful in children
are MAOIs recommended in the C&A population
NO
(limited data + safety concerns)
what is first line for mild depression in youth
Psychotherapy (CBT, IPT first)
what should be the treatment approach for moderate MDD in youth
consider medication if psychotherapy not accessible
what should be the treatment approach for severe MDD in youth
pharmacotherapy is first line
fluoxetine = first choice
escitalopram, sertraline, citalopram = second choice
how often should you monitor youth when starting an antidepressant
WEEKLY for the first MONTH (both USFDA and CPA recommend this)
q2weeks for 2nd month
then after 12 weeks
(second two are only recommended by the USFDA)
*especially for more depressed patients, high SI and family conflict
how should you titrate SSRIs in youth with MDD
initial LOW dose for FOUR WEEKS at least before considering increase
if only partial response after 12 weeks, CHANGE TREATMENT
how long should you treat a youth with antidepressants after presenting with MDD
very little data and this is based on adult research
if no MDD hx–> 6-12 months
if hx 2 or more MDEs or 1 severe/chronic MDE–> tx for 1 year or longer
*if want to d/c, d/c with slow taper during stress free time
according to the TORDIA trial, what should you do if less than 20% response after initial SSRI trial in depressed youth
switch to another SSRI
why is venlafaxine less preferable in treatment of MDD in depressed youth
venlafaxine is LESS preferable as has equal response but leads to more self harm events
is ECT recommended in kids younger than 12
no
use with extreme caution in tens (i.e severe MDD, TRD)
fluoxetine can work for what other often comorbid conditions in youth with depression
for mild-mod AUD
oppositional symptoms
are there ANY health canada approved antidepressants for C&A population
NO
are there ANY FDA approved antidepressants for C&A populations
fluoxetine for ages 8+
escitalopram for ages 12+
what is the black box warning associated with antidepressants
SSRI use in people under 24–> risk of increased suicidal ideation and behaviour
4% risk vs baseline 2.5% risk (1.5-2x risk)
what is first, second and third line for mild-moderate perinatal depression
first line–> CBT, ITP
second line–> citalopram, escitalopram, sertraline
third line–> combo SSRI + CBT/IPT
what three SSRIs are considered “best” in pregnancy/lactation
citalopram
escitalopram
sertraline
name two antidepressants that have risks of fetal cardiac defects
paroxetine
clomipramine
why aren’t MAOIs recommended for treating perinatal depression
interactions with anesthetics, analgesics
what is recommended first, second and third line for severe perinatal depression
first line–> citalopram, sertraline, escitalopram
or combo of one of those SSRIs with CBT/IPT
second line–> other SSRIs (except paroxetine), newer ADs, TCAs
third line–> consider ECT
list antidepressants with risk of major congenital malformations if used during pregnancy
paroxetine–> cardiac defects
fluoxetine (early in pregnancy)–> small increase in congenital malformations
clomipramine–> cardiac defects
should you use fluoxetine in pregnancy
no–> small increase in congenital malformations
are there risks in pregnancy of other (non-fluoxetine, paroxetine) SSRIs, buproprion, mirtazapine, SNRIs, TCAs?
no significant risk
what are the risks of SSRI use generally in pregnancy
very modest link with SPONTANEOUS ABORTION
SHORTENED gestational duration (by 4 days)
DECREASED birth weight (by 74 grams)
what are the symptoms of neonatal adaptation syndrome
jitteriness
irritability
tremor
respiratory distress
excessive crying
**NO association with increased mortality or long term neurodevelopmental problems)*
what is the etiology of neonatal adaptation syndrome
SSRI exposure during THIRD trimester
15-30% of exposed infants will develop
what antidepressants (3) have the highest risk of causing neonatal adaptation syndrome if taken by women in pregnancy
paroxetine
fluoxetine
venlafaxine
how long does neonatal adaptation syndrome usually last
time limited–> 2-14 days
other than neonatal adaptation syndrome, what is another risk of taking SSRIs late in pregnancy
persistent pulmonary hypertension of the newborn –> limited data
is breastfeeding contraindicated in post partum depression
no
what antidepressant must you absolutely avoid in breastfeeding mothers
doxepin
significant adverse effects in breastfeeding infants
what is first line in mild to moderate post partum depression
similar to perinatal depression (CBT/IPT first, then citalopram/escitalopram/ sertraline)
what is first line treatment for severe post partum depression
pharmacotherapy–> citalopram, escitalopram, sertraline
ECT can be first line, especially if psychosis is present
can you continue breastfeeding during ECT
yes
how does breastfeeding exposure compared to in utero exposure to antidepressants
5-10x lower exposure during breastfeeding compared to in utero
what 3 antidepressants have the lowest relative infant dose during breastfeeding
sertraline
paroxetine
fluvoxamine
(minor reactions with sertraline, paroxetine)
what 2 antidepressants have the highest rate of infant reactions when taking by breastfeeding mothers
citalopram
fluoxetine
what symptoms may be seen in infants whose mothers are breastfeeding while taking an antidepressant
irritability
restlessness
sedation
insomnia
how does menopause affect the risk of depression
increased risk of depression
increased depressive symptoms
increased risk of recurrence + new MDE
what is the only antidepressant specifically studied via RCT for perimenopausal depression
desvenlafaxine
was superior to placebo
what are the recommendations for treatment for perimenopausal depression
same as general adult population due to lack of data
is HRT considered effective augmentation treatment for perimenopausal depression
perimenopause–> estrogen superior to placebo
post menopause–> transdermal estradiol NOT superior to placebo
post menopause–> methyltestosterone superior to placebo
are hormonal agents first line for treating depression around menopause
no–> second line
for women who understand the risks and have no contraindications
what is different about late life depression (above age 60)
worse prognosis
more chronic course
higher relapse rates
more medical comorbidity, cognitive impairment, mortality
may be DEMENTIA PRODROME
what is the vascular depression hypothesis
considers cerebrovascular disease as predisposing/precipitating/perpetuating factor for depression
affects FRONTOSTRIATAL circuitry–> depression and cognitive impairment
which psychotherapy has the strongest evidence in late life depression
(vs supportive therapy)
Problem Solving Therapy
showed significant decrease in depression scores and decreased disability
what age is considered “young-old”? what about “old-old”
young-old = under 75
old old is 75 and above
how do you titrate antidepressants in older people
start low and go slow (and keep going)
suggest longer AD trials up to 10-12 weeks
list 3 changes in pharmacokinetics that occur with aging
- decrease absorption rate and bioavailability
- increased half life for lipid soluble drugs
- increased concentration for water-soluble drugs/metabolites
what antidepressant side effects are more common in the elderly
bone loss
serotonin syndrome
NMS
EPS
falls, hyponatremia, GI bleeding (with SSRIs)
QTc prolongation (citalopram)
what medication has evidence for treating severe MDD in old-old people
citalopram
(also better tolerability and fewer drug interactions)
what SSRIs are often avoided in the elderly
paroxetine–> anticholinergic
fluoxetine–> drug interactions
(in RCTs there is positive evidence for efficacy though in late life depression)
what SSRI is often clinically considered first line for late life depression
citalopram/escitalopram
due to better tolerability and fewer drug interactions but a RCT showed no superiority over placebo in the elderly
is there evidence for vortioxetine, duloxetine and agomelatine in treating late life depression
yes–> improved depression scores
vortioxetine and duloxetine also improved verbal learning and vortioxetine improved processing speed
what two atypical antipsychotics have evidence as treatment for late life depression
aripiprazole adjunctive + AD = EFFECTIVE (more common side effects)
quetiapine XR monotherapy = EFFECTIVE (higher dropout rates, less effective over age 75)
is there evidence that using a sedating AD for sleep improves overall outcomes in the treatment of late life depression
no
how do you approach treatment of treatment resistant depression in populations above age 55
50% respond to switch or augmentation
lithium augmentation has the most consistent data
sequential treatment strategy has the highest response rates
