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Which antidepressants inhibit CYP 1A2?
Which antidepressants inhibit CYP 2C?
fluoxetine, fluvoxamine, sertraline
Which antidepressants inhibit CYP 2D6?
(very high)
fluoxetine, paroxetine


(very low)
bupropion, citalopram, escitalopram, sertraline
Which antidepressants inhibit CYP 3A4?
(very high)



(very low)
Which antidepressants have the fewest CYP interactions?
How do tricyclic antidepressants work?
block the reuptake of 5-HT and NE

(tertiary amines have greater effect on 5-HT but are metabolized to secondary amines, which have a greater effect on NE)

adverse effects: alpha-adrenergic blocking effects, antihistaminic effects, anticholinergic effects, effects on cardiac conduction
Is it okay to discontinue TCAs abruptly?
no, gradually decrease dose by 25-50 mg/day/week to help reduce symptoms of withdrawal

(GI complaints, dizziness, insomnia, restlessness)
What is the MOA of MAOIs?
inhibit the enzyme responsible for the breakdown of certain neurotransmitters, including NE

enzyme has 2 forms; drug can block both or type B form
Name 3 nonselective MAOIs available in the US.
phenelzine (Nardil),
isocarboxazid (Marplan),
tranylcypromine (Parnate)
What are the dietary issues associated with MAOIs?
avoid foods high in tyramine (aged cheese, preserved meat) due to potential to precipitate a hypertensive crisis
What significant drug interactions are associated with MAOIs?
OTC decongestants (avoid)

do not combine with other antidepressants (wash out perioud when switching)
Which MAOI is available as a patch?
selegiline (Emsam)

dietary restrictions necessary when dose reaches 9 mg/24 hrs
Which SSRI has the longest half-life?
(1-4 days)
Which SSRI has an active metabolite?
Which SSRI is indicated for the treatment of OCD?
What is the MOA of SSRIs?
selectively inhibit the reuptake of 5-HT into the presynaptic neuron
What are the symptoms of serotonin syndrome?
confusion, hypomania, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, tremor, diarrhea, incoordination
How is serotonin syndrome treated?
discontinue offending agent

supportive: cooling blankets, respiratory support

myoclonus: clonazepam

seizures: anticonvulsants

hypertension: nifedipine
If a patient does not respond to one SSRI, is it worth trying another?
yes, patients who do not respond to one SSRI may respond to another
(STAR*D trial)
What are the most common adverse effects of SSRIs?
GI complaints, insomnia, restlessness, headache, sexual dysfunction
What antidepressant might have a beneficial effect on sexual function?
Which class of antidepressants has been associated with EPS (extrapyramidal symptoms)?
SSRIs - but not common

(akathesia, dystonia, bradykinesia)
Is it okay to abruptly stop SSRIs?
depends - a withdrawal syndrome can be seen in patients stopping a SSRI with a shorter half-life; gradual dose reduction over 2-4 wks may be indicated

most common: paroxetine

least common: fluoxetine

(GI complaints, headache, dizziness, impaired concentration, flulike symptoms, anxiety, insomnia)
What is the MOA of venlafaxine?
balanced NE and 5-HT reuptake inhibitor

negligible effects at other receptors

mostly 5-HT at lower doses; NE effect increases with dose (think BP)
What are the adverse effects of venlafaxine?
GI complaints common

dose-related increase in BP; of concern in patients with uncontrolled hypertension
Is it okay to abruptly stop venlafaxine?
abrupt discontinuation can lead to withdrawal syndrome similar to SSRIs
What is Pristiq?
desvenlafaxine, active metabolite of venlafaxine
What is the MOA of trazodone?
serotonin reuptake inhibitor that also blocks 5-HT2A receptors

does not have anticholinergic or cardiotoxic effects of TCAs
What are some adverse effects of trazodone?
does cause orthostatic hypotension and is quite sedating

rare: priapism (0.1% or less)
What is the MOA of nefazodone?
blocks reuptake of 5-HT and NE, also 5-HT2A antagonist (like trazodone)

5-HT2A antagonism may make this med more effective for anxiety associated with depression

minimal effects on sexual function; less likely to cause orthostatic hypotension
How often is nefazodone dosed?
What are some advese effects of nefazodone?
sedation, GI complaints, dry mouth, constipation, confusion, light-headedness

Black Box: liver toxicity
What must be monitored for patients on nefazodone?
What are some drug interactions with nefazodone?
drug metabolized by 3A4

(nefazodone is a potent inhibitor of 3A4)
What is the MOA of bupropion?
primarily inhibitor of dopamine and NE reuptake, minimal effects on 5-HT

(exact mechanism not known)
What is the most improtant adverse effect of bupropion?
increased risk of seizures

minimize by avoiding in pts at risk; titrating dose every few days; max 450 mg/day (immediate release) or 400 mg/day (sustained release)
What are the most common adverse effects of bupropion?
nervousness, headache, insomnia; may cause psychosis

no adverse effect on sexual function, may actually improve
What is the MOA of mirtazapine?
primarily antagonism of alpha-2 (presynaptic autoreceptor) and heteroreceptor that prevent release of NE and 5-HT; net result is increased NE and 5-HT in synapse

also blocks 5-HT2A and 5-HT3 receptors; may lead to less activating adverse effects, fewer GI effects, and more pronounced effect on comorbid anxiety
What are the adverse effects of mirtazapine?
increased appetite, weight gain, constipation, asthenia; abnormal LFTs; very small risk of neutropenia or agranulocytosis

lower doses: sedating
higher doses: insomnia
What is the MOA of duloxetine?
mixed NE/5-HT reuptake inhibitor
What drug interactions are of concern with duloxetine?
caution when using duloxetine with inhibitors of 2D6
What adverse effects should be kept in mind with duloxetine?
BP increased have been observed

can cause liver toxicity
What are some medications used to augment antidepressants in the treatment of depression?
second-generation antipsychotics
What is the usual dose of thyroid when used to augment antidepressant therapy?
25 mcg/day

(not dependent on thyroid dysfunction)
What is considered an adequate trial of an antidepressant medication?
full therapeutic doses for 6-8 weeks (or up to 12 weeks)
What is the difference between Bipolar I and Bipolar II?
Bipolar I: presence of manic episodes; includes major depressive episodes in a majority of patients

Bipolar II: presence of major depressive episodes and hypomanic episodes
How long does it take to see the full effects of lithium?
1-2 weeks
What is the desired serum concentration for lithium?
acute mania: 0.8-1.2 mEq/L

maintenance: 0.8-1.0 mEq/L
When should lithium levels be drawn?
12 hours after after dose
How long does it take for lithium levels to reach steady state?
5-6 days
(half-life 20-24 hrs)

may be prudent to check level 3 days after dose change
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