Managing S/E of AD's Flashcards
When do pts commonly experience Nauseau and stomach upset?
Very common (17-26%)
Majority of patients will experience this by 2nd week of treatment (up to 83%) and up to 3 months into therapy
Rate AD’s Nauseau
Venlafaxine > SSRI > Bupropion > Moclobemide > Mirtazapine (less, histamine blockade)
How can nauseau be managed?
Divide doses / reduce SSRI dose if patient stable
Take the medication with small amount of food (e.g. crackers)
? Ginger-containing food or beverages
When does diarhhea occur? Does it resolve?
May be transient and resolve within weeks
Most experience this by 2 weeks and some will have it persist up to 3 months
Managemeng of Diarhhea?
Should resolve on its own
May use antidiarrheal agent (e.g., loperamide)
May wish to try probiotics and/or psyllium, etc.
When should loperamid enot be taken?
If blood in the stool +/- fever, don’t take loperamide, risk of toxic mega colon
What AD”s cause the most constipation?
Paroxetine associated with highest rates of constipation out of all SSRIs
Common with TCAs
Management of Constipation?
Should resolve on its own (up to 3 months)
Adequate activity, fiber
OTC / self-care as normal
Which SSRI is associated with constipation (most)?
Paroxetine
What blackbox warning do AD’s have?
Current FDA (USA) black box warning of increased risk of suicidality in children, adolescents, and young adults (18-24) during initial therapy (first 1-2 months) with any antidepressant
What AD’s are most associated with suicidality?
Paroxetine and Venlafaxine
In regards to sucidality, is there an association with age?
<18 –> possible association
> 18 –> Ambigous
–> Systematic review of observational studies that reported completed and attempted suicides showed there is a protective effect of SSRIs on suicidality in this age group
25-64 - Neutral-protective
> 65 –> Possible protective effect
What antidepressants are commonly associated with sexual dysfunction?
Antidepressants associated with an increased frequency of sexual dysfunction are:
SSRIs
TCAs
SNRIs
Which has the lowest risk of sexual dysfx?
Lowest risk: bupropion
Mirtazapine, trazodone, moclobemide typically lower risk
Vilazodone and vortioxetine appear to be lower risk as well
Sexual Dysfx Management
- No intervention
Some case reports of spontaneous remission or improvement, although infrequently
This strategy may increase the risk of non-compliance among patients for whom sexual side effects are concerning
- Reduce
Reducing doses of antidepressants to improve antidepressant-related sexual dysfunction while still maintaining efficacy as antidepressant
Potential disadvantage = relapse - Drug holidays or eliminating doses for a few days prior to sexual intercourse (not preferred)
Some evidence of efficacy with sertraline, citalopram, and paroxetine
Potential disadvantages = withdrawal side effects (especially venlafaxine) after missing more than 2 doses, relapse of depressive symptoms, and increasing patient non-adherence - Using medications to augment sexual side effects
Adjunct anti-depressant (bupropion or mirtazapine)
Evidence is inconsistent - some studies show benefit and others do not
Sildenafil or tadalafil
Greatest evidence for men with anti-depressant induced erectile dysfunction (ED)
Efficacy in one trial was similar to those found in ED secondary to other causes
- Switching antidepressant
Switch to an agent with lower rates of sexual side effects
Bupropion = greatest amount of evidence for successful treatment of AD-induced sexual dysfunction
Mirtazapine = some small RCTs show resolution of sexual dysfunction when switching to mirtazapine
SNRI instead of SSRI
QT prolongation Risk, High and Low risk drugs
Generally safe at therapeutic doses
TCAs high risk especially at higher doses
Cital, escital, venla, desvenla, mirtaz – conditional/possible risk, esp with higher doses
Other SSRIs, bupropion, moclobemide may have lowest risk
Risk factors for QT prolongation
Cardiomyopathy
M.I.
Long QT syndrome
Hypokalmeia
Hypomagnesemia
Age
Female Sex
Drugs
What causes serotonin syndrome?
Concomitant use of multiple serotonergic agents
What is serotonin syndrome described as?
Classically described as a “triad” of
mental status changes
autonomic hyperactivity
neuromuscular abnormalities
TX of Serotonin Syndrome
Treatment: supportive, discontinue serotonergic agents, cyproheptadine serotonin antagonist
CAuse sof serotonin syndrome
Antidepressants: MAOIs, TCAs, venlafaxine, St. John’s Wort,
Others: linezolid, dextromethorphan, meperidine, tramadol, opioids
Which drugs are the worst for discontinuation syndrome?
venlafaxine, paroxetine
What is the mechanism of disocntinuation syndrome?
Exact mechanism unknown, but multiple theories exist
Who is more likely to have discontinuation syndrome?
More likely in those who have been on tx >6-8 weeks
Risk appears to also relate to affinity for serotonin transporter
Rate SSRI discontinuation syndrome
Paroxetine > fluvoxamine, sertraline, citalopram > fluoxetine
What does discontinuation syndrome present as?
F = flu-like symptoms fatigue, lethargy, malaise, muscle aches
I = Insomnia
N = Nausea
I = Imbalance
S = Sensory disturbances paresthesias (numbness), electric-shock sensations
H = Hyperarousal anxiety, agitation
Describe symtpoms onset, duration of discontinuation syndrome?
Symptoms start 24-72 hours after AD stop
Generally mild and transient
But can be intolerable
Symptoms spontaneously resolve in 1-2 weeks
May persist for weeks to months for some patients
Be sure to counsel patients about this!
Especially once they have been taking it for a longer period of time (>6-8 weeks)
How can discontinuation syndrome be prevented?
Reduce the dose over ~2-4 wks at the end of the tx
May be able to stop fluoxetine without taper due to long t1/2
What to do if discontinuation syndrome occurs?
Consider restarting medication with a slow taper
If symptoms occur during tapering
–> Consider restarting at original dose and taper slower
If slow tapering is poorly tolerated
–> Consider substituting fluoxetine
What should be monitored and followe dup on?
Adherence
Tolerability
Response
Sucidality
What to do if symptoms of MDD persists?
If symptoms persist after an adequate trial of initial medication (6-8 weeks) at an adequate dose
switch to alternate first line agent
or
augment with an alternate mechanism antidepressant, Secondgeneration antipsych, or psychotherapy
How many fail to achieve remission with intial pharmacotx?
2/3 will fail to achieve remission with initial pharmtx
> 30% will have a less than satisfactory response to 4 courses of antidepressants
What are some factors to condier when switching or augmenting?
Augment–> PArtial repsonse, faster or synergistic response
Switch –> No response, less pill/cost burden, fewer A/e
What is tx-resistant depresison?
Lack of improvement (<20% reduction in depression scores) following adequate trials of two or more antidepressants
Is tx-resistance a type of depression?
NO
Consensus is that TRD is not a subtype of depression, but rather occurs along a spectrum from partial response to complete treatment resistance
Options for tx-resistant depression
May switch antidepressant – again
May choose to use augmentation therapy
Lithium
Atypical antipsychotic
Thyroid (T3)
Other (buspirone, methylphenidate, modafinil) weak evidence
Or, combining antidepressants
SSRI/SNRI + mirtazapine
SSRI/SNRI + bupropion
SSRI + TCA
When switching antidepressants, what are the ways to do it?
SSRI/SNRI within class: direct switch
May directly switch between SSRI<->SSRIs and between venlafaxine<->duloxetine due to similar mechanisms of action but often will cross taper
Other drugs: cross-tapering
Cross-tapering is recommended between drugs of different mechanisms of action
MAOIs: washout
Allow washout of 2 weeks when switching between MAOI and other antidepressants
5 weeks between stopping fluoxetine & starting MAOI
What is lithiums role in MDD?
Has antidepressant effect (TRD) and is one of the most investigated augmentation strategy
Although, most evidence is in older studies that used TCAs and MAOIs; short duration of therapy
Should see response by 3-4 weeks
If patient responds, continue the combination for at least 6-9 months
Role of Triiodothyronine (T3)
Improves and accelerates antidepressant effect in studies (TRD use)
Recommended trial is 2 weeks at 50mcg/day
Rarely stopped related to side effects
may cause tachycardia, insomnia, sweating
Caution in patients with cardiac insufficiency or elderly
May preferred over lithium due to better tolerance
What atypical anti-psychotics may be used for TRD?
Ariprazole, Risperidone, Quietiapine, Olanzapine
Usually used at lower doses than used for schizophrenia or bipolar disorder
When is maintenance phase tx recommended?
Maintenance Phase treatment is recommended for patients with chronic symptoms or with a history of 3 or more depressive episodes
What is response?
If response to tx (50% ↓ in sxs) after 4 weeks of treatment, continue at an optimal dose (e.g. increase dose if indicated) and re-evaluate at 6, 8 and 12 weeks
What is continuation phase?
Antidepressant should continue at the same dosage as required in Acute Phase for additional 4-9 months
What is maintenance phase?
Duration is indefinite and may be lifelong
Factors to consider longer term maintenance treatment (> 2 yr)
Depression Sx in Elderly
Anhedonia, cognitive impairment, decreased appetite, increased irritability
Elderly TX onset and length
Less likely to achieve remission with greater chance of relapse: consider maintenance therapy
Symptoms may take longer to respond to tx (12 wk+)
Starting Tx in elderly
Start low and go slow” – increased risk of a/e, comorbidities, D.I.
Monotherapy preferred over polypharmacy
Difficulties of treating depression in elderly
↑ risk AEs, ↓ elimination, ↑ comorbidities, ↑ DIs
What AD’s are on the BEER’s list?
SSRI, SNRI, TCA, mirtazapine on BEERS
Increased risk of falls, fractures, hyponatremia, hypotension
Extra caution with anticholinergic drugs
What are better choices for elderly patients?
duloxetine, bupropion, sertraline
How to manage depression in children/adolescants?
Emphasize: active monitoring rather than treatment right away (unless severe), supportive care
Psychological treatment strongly recommended as first-line (e.g. psychotherapy, counselling)
AD”s in Children????
No AD approved by HC for use in < 18 yrs
FDA: fluoxetine, escitalopram
Off-label: sertraline, citalopram
Avoid SNRI, TCA (more susceptible to increased NE s/e)
AEs more common. Titrate slowly with close monitoring (esp suicidality)
Depresison and Preganncy
What is critical to understand about depression in preganncy?
Untreated, or undertreated, maternal depression poses significant risks to both the mother and child
- Worsening sx, comprimise maternal and fetal health, maternal-infant bonding, and infant care post-partum
The risks of stopping often outweigh the risks associated with pharmacotherapy
Inconsistent findings related to risk of neonatal pulmonary HTN, congenital malformations, or spontaneous abortion
AD’s in preganncy
SSRIs are 1st line in pregnancy; most safety data for sertraline, citalopram, escitalopram
Paroxetine may have higher risk of cardiac malformations in fetus
Less data: SNRI, mirtazapine, bupropion
Breastfeeding AD’s
Citalopram, nortriptyline, sertraline, and paroxetine are 1st line in breastfeeding mothers, because they have low-to-undetectable serum concentrations (at therapeutic doses) in breast-fed infants/children
Breastfeeding generally not a contraindication to any ADs
