PHRX 4040 Psychiatry Module - Exam 1 Drug Chart Info

what 7 antidepressants are considered to be first-line for treatment of MDD

- SSRIs

- SNRIs

- bupropion

- mirtazapine

- vortioxetine

- vilazodone

- trazodone

what 4 treatments are considered second-line for treatment of MDD?

- switch to alt 1st line therapy

- add second antidepressant or augmentation

- TCAs

- dextromethorphan-bupropion

what 2 treatments are considered third-line for treatment of MDD?

- MAOIs

- ketamine/esketamine

how long does the acute phase of MDD treatment last?

4-8 weeks

define treatment resistance in MDD

inadequate response to 1 or more trial of antidepressants, requires a fill trial of 4-6 wks with a therapeutic dose to determine

what are 5 treatment resistance risk factors?

- SUD

- inadequate dose or duration

- incorrect diagnosis

- med non-adherence

- adverse effects

describe the continuation phase of MDD treatment

continue medication used successfully during the acute phase for 6-12 months

when is the maintenance phase for MDD treatment recommended?

recommended for chronic depressive symptoms OR a history of 3 or more depressive episodes, duration is indefinite and can be lifelong

during the acute phase of MDD treatment, what should occur in weeks 1-4 if a partial or no response is observed?

- check adherence

- increase dose

- ECT if severe

during the acute phase of MDD treatment, what should occur in weeks 1-4 if a full response is observed?

maintain

during the acute phase of MDD treatment, what should occur in weeks 4-8 if a partial or no response is observed?

- increase dose

- switch antidepressant

- augment (pharm or non-pharm)

- ECT

during the acute phase of MDD treatment, what should occur in weeks 4-8 if a full response is observed?

move to continuation phase

define partial response to treatment

less than 50% reduction in symptoms

what 3 treatments may be used for antidepressant augmentation after partial/no response?

- second gen antipsychotic

- lithium

- ketamine/esketamine

describe the augmentation strategy of adding an additional antidepressant

- add an alternate mechanism antidepressant

- would NOT combine SSRI + SNRI

- common ones are SSRI or SNRI + bupropion or mirtazapine

what should be done if symptoms reemerge in the continuation treatment phase of MDD

evaluate for non-adherence, substance use and psychosocial stressors

what is the brand name and pharmacological class of citalopram?

celexa, SSRI

what is the brand name and pharmacological class of escitalopram?

lexapro, SSRI

what is the brand name and pharmacological class of fluoxetine?

prozac, SSRI

what is the brand name and pharmacological class of paroxetine?

Paxil, SSRI

what is the brand name and pharmacological class of sertraline?

zoloft, SSRI

what is the brand name and pharmacological class of fluvoxamine?

Luvox, SSRI

what is the brand name and pharmacological class of duloxetine?

Cymbalta, SNRI

what is the brand name and pharmacological class of venlafaxine?

Effexor, SNRI

what is the brand name and pharmacological class of desvenlafaxine?

Pristiq, SNRI

describe the MOA of SSRIs

inhibit presynaptic serotonin reuptake by inhibition of the 5HT transporter; leads to increase 5HT in the synaptic cleft

describe the MOA of SNRIs

inhibition of the 5HT and NE transporters leads to increased neurotransmitters in the synaptic cleft

what is the starting dose for citalopram?

20 mg/day

what is the starting dose for escitalopram?

10 mg/day

what is the starting dose for fluoxetine?

20 mg/day

what is the starting dose for paroxetine?

IR = 20 mg/day

CR = 25 mg/day

what is the starting dose for duloxetine?

20-30 mg BID (40-60 mg daily)

what is the starting dose for venlafaxine?

37.5-75 mg/day

what is the starting dose for desvenlafaxine?

50 mg/day

what dose adjustments are required for citalopram?

geriatric and hepatic

what dose adjustments are required for escitalopram?

geriatric and hepatic

what dose adjustments are required for fluoxetine?

geriatric and hepatic

what dose adjustments are required for paroxetine?

geriatric, renal and hepatic

what dose adjustments are required for sertraline?

renal and hepatic

what dose adjustments are required for duloxetine?

geriatric, renal and hepatic

what dose adjustments are required for venlafaxine?

renal and hepatic

what dose adjustments are required for desvenlafaxine?

renal and hepatic

what are 2 unique considerations to take with citalopram?

- dose related risk of QT prolongation

- on beers list

what other dose adjustment needs to be taken for citalopram use?

poor CYP2C19 metabolizer or with concomitant CYP2C19 inhibitor

what are 2 unique considerations to take with escitalopram?

- dose related risk of QT prolongation, but not as common as citalopram

- S enantiomer of citalopram

what is a unique consideration to take with fluoxetine?

activating, so it may make pts jittery and increase anxiety

what CYP consideration must be taken with fluoxetine?

potent CD6 inhibitor, will require dose adjustment

what consideration regarding fluoxetines active metabolite should be taken?

active metabolite is norfluoxetine and has a long half life, so a taper is not required

what are 3 unique considerations to take with paroxetine?

- anticholinergic side effects

- risk of discontinuation syndrome due to short half life

- on beers list

what CYP consideration must be taken with paroxetine?

potent CD6 inhibitor, will require dose adjustment

what unique consideration should be taken with sertraline?

GI side effects are common, so start with lower dose and slowly titrate to avoid

what is the active metabolite of sertraline?

N-desmethylsertraline

what CYP considerations must be taken with sertraline?

requires adjustment with CYP 2B6 and 2C19 phenotypes

what is a unique consideration to take with fluvoxamine?

generally only used for OCD

what unique consideration should be taken with duloxetine?

monitor liver function due to risk of liver failure, do not use if pt has liver problems

what additional dose adjustment needs to be taken with duloxetine?

adjust with concomitant potent CYP 1A2 inhibitor

describe the affinity that duloxetine has for 5HT and NE reuptake

has equal affinity for 5HT and NE reuptake

what unique consideration should be taken with venlafaxine?

dose related increase in BP, should avoid if BP issues exist

describe 5HT and NE inhibiton seen with venlafaxine

- doses greater than 150 mg are requires to achieve both NE and 5HT inhibiton

- works more like an SSRI at lower doses

what are 2 unique considerations to take with desvenlafaxine?

- active metabolite of venlafaxine

- requires 2D6 for metabolism

what is the brand name and pharmacological class of mirtazepine?

- remeron

- antidepressant alpha 2 antagonist

describe the MOA of mirtazapine (alpha-2 antagonist)

- increase synaptic concentration of 5HT and NE

- antagonist of 5HT, peripheral alpha-1 and muscarinic receptors, which generates different side effects

what 5 ADEs are seen with mirtazapine?

- increased appetite

- weight gain

- constipation

- xerostomia

- sedation

what is the starting dose for mirtazapine?

15 mg qhs

what dose adjustments are required for mirtazapine?

geriatric and hepatic

what unique features are seen with mirtazapine?

- often scheduled at night for sedating and appetite stimulating effects

- sedation, increased appetite and weight GAIN

what is the brand name and pharmacologic class of bupropion?

- Wellbutrin

- dopamine norepinephrine reuptake inhibitor

describe the MOA of bupropion ( dopamine norepinephrine reuptake inhibitor)

NE and DA reuptake blockade with no 5HT effects

what are 4 important ADEs associated with bupropion?

- insomnia

- weight loss

- anxiety

- seizures

what are the starting doses for bupropion? (IR, SR and XL)

IR = 100 mg BID

SR = 150 mg daily

XL = 150 mg daily

what dose adjustments are required for bupropion?

renal and hepatic

what are 3 unique considerations to take with bupropion?

- has activating, stimulant like effects; may be useful for fatigue and poor concentration but it may also worsen anxiety or insomnia

- no sexual dysfunction (since it doesn't involve 5HT)

- also indicated for smoking cessation

what 2 CYP considerations must be taken with bupropion?

CYP 2B6 major pathway, strong CYP 2D6 inhibitor

what is the brand name and pharmacological class of Vilazodone

- Vilbryd

- SSRI/5HT1a receptor partial agonist

describe the MOA of vilazodone (SSRI/5HT1a receptor partial agonist)

inhibition of presynaptic 5HT transporter and 5HT1a partial agonist

- INCREASED 5HT activity (know this)

what are 3 ADEs seen with vilazodone? what consideration should be taken?

- more GI side effects = diarrhea, nausea and vomiting

- should be taken with food

what are 2 unique considerations to be taken with vilazodone?

- pregnancy category C

- more GI side effects than other SSRIs

what is the brand name and pharmacologic class for vortioxetine?

- Trintellix

- SSRI, 5HT1a receptor agonist, 5HT1b partial agonist and several other 5HT receptor antagonists (lots of serotonergic activity)

what are 3 ADEs seen with vortioxetine? what is an important consideration with these?

- nausea

- constipation

- vomiting

highest % of reported nausea of all meds

what is the starting dose for vortioxetine?

10 mg daily

what dose adjustment should be taken with vortioxetine?

avoid with CYP 2D6 ultra rapid or poor metabolizers

what are 3 unique considerations for vortioxetine?

- pregnancy category C

- long half life

- more GI side effects than SSRIs

what CYP consideration should be taken with vortioxetine?

metabolized by CYP 2D6

what is the pharmacologic class of trazodone?

SSRI, alpha-1, H-1 antagonist

describe the MOA of trazodone

- weak 5HT reuptake inhibitor

- significantly blocks H1 and alpha-1 receptors

what are 7 ADEs seen with trazodone?

- sedation

- headache

- dizziness

- fatigue

- dry mouth

- nausea

- constipation

what is a unique consideration to take with trazodone?

used commonly as a sleep aid and rarely as an antidepressant but has anticholinergic effects

can antidepressants be used with MAOIs?

NO, all antidepressants interact with MAOIs and use together is contraindicated

when is there an increased risk of serotonin syndrome?

when combining multiple serotonergic agents

which CYP isoform does fluvoxamine show potent inhibition with?

1A2

What 3 drugs should be avoided or used with caution when taking fluvoxamine due to CYP1A2 inhibition?

- clozapine

- warfarin

- methylxanthines

what 2 SSRIs show potent inhibition of CYP 2D6?

- fluoxetine

- paroxetine

what meds should be avoided when taking fluoxetine or paroxetine due to 2D6 inhibition? why?

- avoid meds solely metabolized by 2D6 (metoprolol, desipramine)

- may increase concentrations of these meds and TCAs

which CYP enzyme does bupropion potently inhibit?

2D6

describe the clinical relevance of bupropion 2D6 inhibition

- may increase concentrations of 2D6 substrates

- may also increase risk of seizure with other agents that lower seizure threshold

what 9 drugs increase TCA concentration?

- amiodarone

- bupropion

- cimetidine

- duloxetine

- fluoxetine

- haloperidol

- paroxetine

- quinidine

- valproic acid

what 3 drugs decrease TCA concentration?

- barbiturates

- carbamazepine

- phenytoin

what are 9 other substances that have TCA interactions?

- alcohol

- amphetamines

- anticholinergics

- clonidine

- dopamine antagonists

- lithium

- MAOIs

- phenytoin

- sedatives

describe the effect of the interaction between alcohol and TCAs

increased CNS depression

describe the effect of the interaction between amphetamines and TCAs

increased stimulant effect