Depression

risk factors for depression:

inherited (first degree relatives), female, middle age, alone (widowed, separated, divorced), low income/unemployed, comorbidities, stressful life events

medical causes of depression symptoms:

hypothyroidism, anemia, HIV/AIDs/STDs, autoimmune disease, CVD, neurologic disorders (epilepsy, Huntington’s disease, Parkinson’s disease, Alzheimer’s disease, Post-stroke

medication-induced causes of depression symptoms:

beta-blockers, CCBs, oral contraceptives, steroids, topiramate, levetiracetam, opioids, stimulants, etc.

What are the three phases of depression (MDD)?

acute, continuation, and maintenance.

the initial choice of antidepressant for acute phase is based on several factors such as:

Patient preference, Prior response, Safety Tolerability and adverse effects, Comorbid disorders, Potential drug-drug interactions, Pharmacokinetic parameters and Cost

describe the treatments for continuation phase of MDD

Antidepressant treatment should continue at the same dosage as required in the Acute Phase for an additional 4-9 months. Should depressive symptoms recur, potential causes of relapse should be addressed (non-adherence,
substance use, and psychosocial stressors)

describe the maintenance phase of MDD

Maintenance antidepressant treatment is recommended for patients with chronic depressive symptoms or with a history of 3 or more depressive episodes — duration of therapy is indefinite and may be lifelong

what are some of the factors to consider for MDD maintenance treatment?

Presence of residual depressive symptoms, Stressors, Family history, Severity of depressive episodes

what are the first line therapy options for uncomplicated MDD?

psychotherapy or pharmacotherapy such as SSRIs, SNRIs, bupropion, mirtazapine, trazodone, vilazodone, vortioxetine

what is second line for uncomplicated MDD?

Therapy is based on whether they are non-response or partial response

Which complicated MDD patients can use ECT with or without psychotherapy first line?

Patients that also have:

• catatonia

• psychotic depression

• severe suicidality

• hx of previous ECT success

• need for rapid response

• risks for other treatments

• hx of poor response to antidepressants

what are the second line therapy options for complicated MDD?

therapy is based on whether or not the patient is non-response or partial response

what are the first-line pharmacotherapy options for complicated MDD?

SSRI, SNRI, bupropion, mirtazapine, trazodone, vilazodone, vortioxetine

if after 4 weeks of adequate treatment, response is a 50% reduction in symptoms, what should be done?

continue optimal dose and reevaluate at 6,8, and 12 weeks

If after an adequate trial of initial therapy (4-8 weeks) at adequate dose, full symptoms persist, what do the guidelines say to do?

switch to an alternative antidepressant — alternatively, augmentation with an antipsychotic (SGA) or other off-label strategies

If partial symptoms remain after initial treatment, what can be done?

unclear if dose increase, switch to another agent or augmentation is best — if there is less than 50% improvement in symptoms response after 8 weeks of treatment, switching treatment is recommended

what is the BBW for all antidepressants?

increased risk of suicidal thoughts and behavior ages 24 and younger

What are the contraindications of all antidepressants?

allergy/concomitant MAO-I or MAO-I use within 14 days or less of stopping med (may require longer “agent specific” wash out), review drug interactions for more contraindications

What are the pearls for treating older adults with antidepressants?

may require lower doses, but “adult” dose is appropriate

what are the pearls for treating pediatric patients with antidepressants?

FDA will indicate if approved for use in peds — off label prescribing otherwise driven by case reports, guidelines, etc.

what are the pearls for treating pregnant patients with antidepressants?

Refer to package insert, some ADs are not recommended during
pregnancy, however untreated depression during pregnancy is high risk (consider risk/benefit; avoid contraindicated agents.

Use of antidepressant monotherapy in patients with underlying bipolar disorder can precipitate a switch to __________

mania

Which CYP enzyme plays a major role in the DDIs with antidepressants?

CYP2D6

When do antidepressants start working?

Week 1: improved sleep and appetite, lessening of anxiety

Week 1-3: improved self-care, sex drive, memory, thinking and movements

Week 2-4: relief of depressed mood, subsiding of hopelessness and suicidal thoughts, return of pleasure experiences

How do you help patients who experience anxiety from antidepressants?

lower doses and titrate slowly

How do you help patients who experience insomnia or sedation from antidepressants?

switch administration time

How do you help patients who experience headaches from antidepressants?

can treat with OTC PRN for few days trial to resolve

How do you help patients who experience GI effects from antidepressants?

give with food

How do you help patients who experience weight gain from antidepressants?

explore diet/exercise or switch agents if needed

How do you help patients who experience sexual side effects from antidepressants?

usually a switch is needed — alternatives are bupropion or vortioxetine

which medications are SSRIs?

citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertralinee

what is citalopram FDA indicated for?

MDD

what is escitalopram FDA indicated for?

MDD and GAD

what is fluoxetine FDA indicated for?

MDD, OCD, Panic, PMDD, Bulimia nervosa

what is fluvoxamine FDA indicated for?

OCD

what is paroxetine FDA indicated for?

MDD, GAD, OCD, Panic, PTSD, PMDD, SAD

what is sertraline FDA indicated for?

MDD, OCD, Panic, PTSD, PMDD, SAD

what are the universal ADRs of SSRIs?

Increased bleeding, hyponatremia, serotonin syndrome, sexual side effects,
seizures, activation of mania, angle closure glaucoma, discontinuation syndrome.

CI to SSRIs

Allergy/Concomitant MAO-I or MAO-I use within 14 days or less of stopping med. Review drug interactions for additional contraindications (longer with fluoxetine=5 weeks)

What are the first dose monitoring considerations for SSRIs?

Cognitive/motor impairment/sedation-use caution with first dose, monitor for any potential allergic reaction with first dose, first few days/weeks: increased anxiety, GI symptoms, headache. Anticholinergic alert: glaucoma, etc

What ADR is specific to citalopram?

QTc prolongation

What is the MDD of citalopram for elderly pts over 60 years?

20 mg/day

which SSRI have a risk of use in patients with concomitant illness?

escitalopram

MDD for escitalopram in elderly patients over 60 years old

10 mg/day

what are the ADRs specific to fluoxetine?

reduced appetite and weight, anxiety and insomnia

which SSRI has a long half-life which means it can be a once weekly dose option?

fluoxetine

T/F: fluvoxamine has many significant DDIs

true

which SSRI is not approved for depression?

fluvoxamine

what are the risks/warnings for using paroxetine?

risk for use in pregnancy, risk of bone fractures, akathisia

which SSRI has a short half-life and anticholinergic side effects?

paroxetine

which SSRI can have false positive urine screens for benzos?

sertraline

what is desvenlafaxine FDA indicated for?

MDD

what is duloxetine FDA indicated for?

MDD, GAD, fibromyalgia, musculoskeletal pain, neuropathic pain.

what is venlafaxine FDA indicated for?

MDD, GAD, panic disorder, social phobia (SAD)

what is levomilnacipran FDA indicated for?

MDD

what are the universal ADRs for SNRIs?

Increased bleeding, hyponatremia, serotonin syndrome, sexual side effects,
seizures, activation of mania, angle closure glaucoma, discontinuation syndrome, and constipation

CI for SNRIs:

Allergy/Concomitant MAO-I or MAO-I use within 14 days or less of stopping med. Review drug interactions for additional contraindications

What first dose monitoring consideration is specific for SNRIs?

all agents may pose an increased risk of BP elevation (noradrenergic action)

what is amitriptyline FDA approved for?

depression

what is amoxapine FDA approved for?

depression

what is clomipramine FDA approved for?

OCD

what is desipramine FDA approved for?

depression

what is doxepin FDA approved for?

depression

what is imipramine FDA approved for?

depression

what is nortriptyline FDA approved for?

depression

what is maprotiline (tetracycline) FDA approved for?

depression

considerations for amitriptyline

it is a tertiary amine and may cause urine discoloration

considerations for amoxapine

EPS (TD) and NMS reported with use

considerations for clomipramine

side effects and availability of other agents with less risk limits use, can cause blood dyscrasias

considerations for desipramine

metabolite of imipramine and is a secondary amine

considerations for doxepin

Silenor (low dose doxepin) brand name only for insomnia, not depression

considerations for imipramine

it is a tertiary amine

considerations for nortiptyline

metabolite of amitriptyline and is a secondary amine

considerations for maprotiline

not readily available

what is the MOA of isocarboxazid?

non-selective irreversible MAO-I — increases 5-HT, NE, and DA in synapse

is isocarboxazid FDA approved for MDD?

yes

what is the MOA of selegiline (patch)?

irreversible selective MAO-B inhibitor (selectivity dose dependent) - MAO-B at clinical doses and MAO-A at higher doses

is selegiline patch FDA approved for MDD?

yes

what the CI for isocarboxazid?

CVD, HTN or treatment with BP meds, hepatic impairment, severe renal impairment, history of headache, excessive caffeine intake

What are the pearls for selegiline patches?

patch avoids first pass metabolism, must rotate patch, cannot be used in children under 12, and heat should be avoided as it may increase absorption 

Inhibition of MAO-A is responsible for: ____________________

antidepressant effects - metabolizes 5-HT, NE, and DA

MAO-B metabolizes _____________

DA and phenethylamine

T/F: all MAO-I available in the US are irreversible

true

how long does it take to synthesize new MAO enzymes?

2-3 weeks

describe MAO-A inhibition

inhibition reduces the breakdown of primarily serotonin, norepinephrine, and
dopamine; selective inhibition of MAO-A allows for tyramine metabolism via MAO-B

describe MAO-B inhibition

reduces the breakdown mainly of dopamine and phenethylamine so there
are no associated dietary restrictions

which MAO-I are nonselective?

phenelzine and tranycypromine

is phenelzine FDA approved for MDD?

yes

is tranylcypromine FDA approved for MDD?

yes

CI for phenelzine

Heart failure, hypertension or treatment with BP meds, hepatic
impairment, severe renal impairment, avoid in pregnancy

which MAO-I has had reports of peripheral neuropathy?

phenelzine

how can you help with phenelzine induced peripheral neuropathy?

give supplemental B6

which MAO-I has additional effects like amphetamines (increase DA release into synapse and inhibits NE at higher doses)?

tranylcypromine

What are the CI for tranylcypromine?

CVD, HTN or treatment with BP meds, hepatic impairment, history of headache

T/F: tranylcypromine has risk of hypoglycemia in diabetics

true

what are the universal CI for MAO-I?

Allergy/Concomitant MAO-I or MAO-I use within 14 days or less of stopping SNRI, Pheochromocytoma, Concomitant use of sympathomimetics or serotonergic agents, Tyramine containing foods, Discontinue for no less than 10 days prior to elective surgery (risk with anesthesia), Review drug interactions for additional contraindications

which medications have serotenergic effects?

antidepressants, antihistamines (chlorpheniramine), opioids, buspirone, DM, triptans, migraine meds, St. John’s Wort, linezolid

which medications are sympathomimetics?

decongestants, stimulants, SNRI, TCAs, bupropion, and many others!

What are the CI specific to bupropion?

Seizure disorder or any other condition predisposing risk (such as abrupt
discontinuation of alcohol, BZD, AED -will lower threshold). Current or prior diagnosis of bulimia or anorexia nervosa

ADRs specific to bupropion:

may increase bp, can cause wakefulness/activation and insomnia, transaminase elevations, and should consider neuropsychiatric adverse events suicide risk (smoking cessation)