Antidepressants Flashcards
Which emerging drug has been found to result in rapid relief of SI?
Ketamine
What do we think major depressive disorders result from?
Deficiency of NE or 5-HT
Changes in trophic factors & hormones play a role
When NTs bind to a specific receptor, what occurs?
Coupling –> cascade of events
NTs are ______ back into nerve cells by reuptake pumps (transporter molecules)
reabsorbed
What is the primary MOA of antidepressants?
Inhibit transporter molecules & allow more NT to remain in the synapse
Depression is a/w changes in ______ or _______
serotonin
norepinephrine
Most antidepressants cause changes in ______
amine signaling
What is a/w more severe forms of major depression?
Abnormal HPA axis
Elevated cortisol
What are other neuroendocrine factors seen in depression?
Thyroid dysregulation
Estrogen deficiency
Testosterone deficiency
Describe the acute phase in the tx of MDD
What is the goal?
Lasts 6-12 wks
Goal = remission
Describe the continuation phase in the tx of MDD
What is the goal?
Lasts 4-9 months after remission is achieved
Goal = eliminate residual sx or prevent relapse
Describe the maintenance phase in the tx of MDD
What is the goal?
12-36 months
Goal = prevent recurrence
Which types of medications are a/w drug-induced depressive sx?
Acne tx Anticonvulsants Antimigraines CV meds Hormone therapy Immunologic agents Smoking cessation
What are the different classes of antidepressants?
TCAs MAO inhibitors SSRIs, SNRIs 5-HT2 Heterocyclic
What are 4 characteristics of antidepressants?
Rapid oral absorption
Tightly bound to plasma proteins
Undergoes hepatic metabolism
Renally cleared
Which group of antidepressants can also be used for chronic pain & enuresis?
TCAs
What are examples of TCAs?
Amitriptylline (prototype) Imipramine Desipramine Doxepine Nortriptyline
Which drug class is also used to treat Selegiline-Parkinson’s disease?
MAOIs
What are examples of MAOIs? (3)
Phenelzine
Tranylcypromine
Selegiline
What are ADEs/drug interactions of MAOIs?
Combined w/ tyramine & sympathomimetics –> HTN
Combined w/ SSRIs –> serotonin syndrome
Toxicity: hypotension, insomnia
What are sx of serotonin syndrome?
Range from mild to lethal & include cognitive, autonomic & somatic effects
What foods should be avoided w/ MAOIs?
Cheese Beer Soy Sausage *All contain high tyramine
What drug class does warfarin interact w/?
SSRIs
What is an ADE of SSRIs?
Sexual dysfunction
Which SSRI is not used in pregnancy? Why?
Paroxetine
Has NE & anticholinergic activity
Which SSRI can cause QT prolongation?
Citalopram
Therefore doses > 40mg/day are not recommended
When can you increase escitalopram (SSRI) to max daily dose?
After 1 week if needed
What is important to know in regards to fluoxetine (SSRI) dosing?
Doses > 20mg/day may be given in a single daily dose or divided BID
How much do you titrate paroxetine (SSRI) weekly?
10 mg/day OR
- 5 mg/day
* Depends on max daily dose
How much do you titrate sertraline (SSRI) weekly?
25 mg/day
What is an ADE common to all antidepressants?
Suicidality
*Monitor behavior changes & mental status
What is an ADE of venlafaxine (SNRI)?
HTN
*Dose reductions may be required if sustained HTN occurs
Is there a benefit of exceeding 50 mg/day of desvenlafaxine (SNRI)?
No - ADE’s are increased & no additional benefit has been shown
Are doses exceeding 60 mg/day of duloxetine (SNRI) more efficacious?
No - not shown to provide increased efficacy
Besides major depression, what else are 5-HT2 antagonists & 5-HT reuptake inhibitors used for?
Depressed pts w/ anxiety
Depression w/ cognitive difficulties
How should daily doses of nefazodone (Mixed 5-HT) be taken?
Divided BID
How should daily doses of trazodone (Mixed 5-HT) be taken?
Divided TID
What is the highest dose of vilazodone (Mixed 5-HT) that has been assessed?
40 mg/day
What are 2 examples of other heterocyclics?
Bupropion (NE & dopamine reuptake inhibitor - NDRI)
Mirtazepine (serotonin & alpha2-receptor antagonist)
What is the MOA of other heterocyclics?
Mirtazepine blocks presynaptic alpha2
Buproprion - NET> SERT
Besides major depression, what else are other hertocyclics used for?
Smoking cessation (bupropion)
Sedation (mirtazepine)
What are ADEs of bupropion?
Lowers seizure threshold
*Seizures are dose-related, & may be increased by predisposing factors (hx of seizures, alcohol withdrawal, head trauma, CNS tumor)
What are ADEs of mirtazepine?
Sedation & wt gain
How often can you increase the dose of mirtazapine?
No more than every 1-2 wks
What is the MOA of folate?
Synthesis of NTs, s/a 5-HT
In regards to folate, the task force states that…
augmentation w/ folate is reasonable, but more work is needed to clarify which subgroup of pts may achieve the greatest response
What is the MOA of TCAs?
Block reuptake transporters of NE & serotonin
What ADEs are common to all SNRIs?
CV changes Insomnia Nausea Serotonin syndrome Sexual dysfunction
What ADE is unique to desvenlafaxine (SNRI)?
Dose-related HLD
What ADE is unique to duloxetine (SNRI)?
Orthostatic hypotension
