EXAM 4 Pharmacotherapy of Depression Dr. Thomason Flashcards
How is depression with hallucination or delusion treated?
antidepressants + antipsychotics
hallucination: things that aren’t there (see, hear, feel)
delusion: false beliefs (ex: wife has an affair)
What are other diseases that come with depression?
CNS
-Alzheimer
-Parkinson’s disease
-CVA (cerebrovascular accident, stroke)
-HIV dementia
-Multiple sclerosis
What are other diseases that come with depression?
Cardiovascular
-Cerebral ateriosclerosis
-CHF
-MI
What are other diseases that come with depression?
Endocrine
Addison’s disease
Diabetes
Hypothyroidism (treated with Levothyroxine)
What are other diseases that come with depression?
Womens Health
-Perimenopause
-Postpartum
-PMDD (around the time of the menstrual cycle)
What are other diseases that come with depression?
Other
-Chronic fatigue syndrome, chronic pain syndrome
-fibromyalgia
-IBS
-Malignancies
-Rheumatic arthritis
-headaches
-lupus
Cardiovascular meds causing depression
-ß-blockers !!! (most common, especially propranolol since causes BBB)
-Reserpine !!! (NAPLEX question)
-Clonidine
-Methyldopa
-Procainamide
CNS agents causing depression
-Barbiturates
-Benzos
-Chloral hydrate
-Ethanol
-Phenytoin
Hormonal agents causing depression
-Anabolic steroids
-Corticosteroids
-Estrogen? (data says probably not)
-Progestin
-Tamoxifen
Other meds causing depression
-Indomethacin
-Interferon
-Isotretinoin (retinoid, for severe acne)
-Mefloquine
What is an entry tool to screen for depression?
-questionnaire PHQ-2 (2 questions)
if they affirm either of the questions -> give them the PHQ-9
When is a patient considered to have depression?
5 or more symptoms for 2 weeks -> must have depressed mood or anhedonia (inability to feel pleasure)
What are the symptoms of depression
-depressed mood
-loss of interest or pleasure (anhedonia)
-weight change
-sleep disturbance
-psychomotor agitation or retardation
-fatigue
-feelings of worthlessness or guilt
-decreased concentration
-recurrent thoughts of death, suicidal ideation or attempt
older patients have more somatic symptoms (ex: back pain)
What happens if a patient is treated with antidepressants but actually has bipolar disorder?
it can cause them to have a manic episode (feel very happy or irritable and angry)
-they need a mood stabilizer
-always rule out bipolar disorder before starting an antidepressant (ex: with the rapid mood screen tool)
What is a grief reaction?
depression after someone passed away: symptoms must persist for 2 months to be considered depression
What is the Gold standard for assessing depression?
Hamilton Rating Scale for Depression (Ham-D): often used in clinical trials, but they are very long and not the best for practice
What are the risk factors of suicide?
-detailed plan
-living alone
-unemployed
-physical illness
-15-24y or older than 65
-hx of substance abuse
-family hx or suicide !!!
What are the symptoms of suicide?
D Sig E Caps
-Depression
-Sleep
-Interest (loss of interest, including libido)
-Guilt
-Energy
-Concentration
-Appetite
-Psychomotor (agitationon or retardation)
-Suicide
Which drug should be avoided in patients who are at risk for suicide?
antidepressants with a narrow therapeutic index
-TCA
-MAO inhibitor
Which drug should be avoided in patients having depression and anxiety?
Bupropion (NET/DAT reuptake inhibitor)
-> activating effect -> more anxiety
-also other antidepressant can cause it
-reduce the dose of antidepressants
What is the most common side effect of SSRIs?
-GI: nausea, diarrhea (fluoxetine, sertraline, and citalopram are worst - Paroxetine cause constipation (anticholinergic) avoid in patients over 65
-headache
->transient, they go away
take it with food in the first week
What is a long-term side effect of SSRIs?
-sexual dysfunction
-weight gain
-increased bleeding (antiplatelet effects)
-sometimes Hyponatremia (check the Na levels)
Which antidepressants don’t cause sexual dysfunction?
-buproprion
-Mirtazepine
-Duloxetine (low)
-Vilazodone
Which SSRI can cause weight loss?
Fluoxetine
One difference between Fluoxetine and Paroxetine?
Fluoxetine has a long halflife: patients who forget to take it will still have sufficient levels and no discontinuation symptoms
Paroxetine has a short half-life - have to taper
Venlafaxine also has discontinuation symptoms
Common side effects of Paroxetine
anticholinergic:
-sedating
-constipation
-sedation (take it at night)
-sexual dysfunction (it slows things down so much)
-extrapyramidal side effects (Parkinson-like: stiffness, tremor)
-akathisia (cant stay still)
-weight gain (most of all SSRIs)
When would Duloxetine be the preferred choice?
fibromyalgia (with chronic pain) and depression
Is Duloxetine activating or does it make patients tired?
activating -> SNRI (mixed serotonin and NE)
NE is activating
->take it in the morning, once a day
(also Fluoxetine)
-some patients get tired on it (take it in the evening)
Which antidepressants are activating and should be given in the morning?
sertraline
fluoxetine
duloxetine
What is special about Mirtazepine dosing?
the lower the dose, the greater the antihistamine effect
-7.5 mg and 15 mg causes sleepiness
-from 30 mg we see more of the anxiolytic and antidepressant effect
When might Mirtazepine be a good choice?
Patients with depression, insomnia, and weight loss
side effects:
-somnolence (may cause a hangover the next day though)
-weight gain
Common side effects of SNRIs?
sweating (especially in women)
-Duloxetine
-Venlafaxine
Which antidepressant is preferred in pregnant women?
sertraline
citalopram
escitalopram
Which antidepressant should not be used in pregnant women?
paroxetine
can cause malformation
Which antidepressants are big CYP2D6 inhibitors?
!!!
fluoxetine, paroxetine
others are:
-sertraline
-bupropion
Which antidepressants are CYP3A4 inhibitors?
-citalopram
-fluoxetine
What is the BBW for citalopram?
Qtc prolongation
max dose of 40 mg
in practice they don’t go over 20 mg
What is the role of TCAs in therapy?
not really used in depression due to the side effects
-used for migraine prophylaxis, neuropathic and chronic pain
-may be used in melancholic depression (with atypical features)
What are the contraindications of TCAs?
NAPLEX
it is anticholinergic, so avoid it in
-BPH
-arrhythmias (prevent the slowing of the heart -> tachycardia -> can be fatal)
-narrow-angle glaucoma
-dementia
-it lowers seizure threshold
What are the MAO inhibitors and what is their role?
1st gen
-Tranylcypromine
-Phenelzine
2nd gen:
-selegiline
-last line antidepressant
Why are selegiline and Phenelzine dosed in the morning and at noon?
because it produces amphetamine metabolites and would keep patients awake when taken at bedtime
What are the drug interactions of MAO inhibitors?
-hypertensive crisis (accumulation of tyramine and NE reverse transport -> hypertensive crisis)
-interaction with amphetamine precursor:
Phenylpropanolamine, pseudoephedrine
-DDI with Meperdine (a synthetic opioid)
-serotonin syndrome when used with serotonergic
A patient switches from an SSRI to an MAO-i. What should be taken care of?
NAPLEX, EXAM QUESTION
washout period of 14 days to prevent serotonin syndrome
-5 weeks for Fluoxetine due to its long half-life
What are symptoms of hypertensice crisis?
-worst headache of their life
-BP up to 220/130
-flushing
-palpitations
-diaphoresis
-N/V
Which foods contain tyramine?
-aged cheese
-smoked, aged, or pickled meat or fish
-Sauerkraut
-yeast extracts
-fava beans
moderate:
-beer
-red wine
-avocados
-meat extracts
What is a common formulation for selegiline?
transdermal patch
-at higher doses, it inhibits both MOA-A and MOA-B irreversibly
-both need to be inhibited to see the antidepressant effect
-can’t use it with other antidepressants, some opioids, st. John wort, amphetamines
-cautious with dietary restrictions (aged meats, tyramine)
What are the serotonin syndrome symptoms?
seen when used 3 or more serotonergic drugs
TRIAD of symptoms: mental autonomic, neurological
-confusion
-agitation
-insomnia
-fever
-diaphoresis (excessive sweating)
-myoclonus
-tremor
-hyperreflexia
severe but rare: cardiovascular collapse, coma, death
How is Serotonin syndrome treated?
-remove causing agents
-giving fluid
-managing the blood pressure
-control hyperthermia
-if needed: control agitations with benzo
with 5-HT2A antagonists
-Cyproheptadine (antihistamine)
-sublingual olanzapine
What is the starting dose of Duloxetine?
SNRI
30 mg
maintenance: 30-90 mg
What is the starting dose of Desvenlafaxine?
SNRI
(metabolite of Venlafaxine)
50 mg
then 50-100 mg (there is no evidence that 100 mg has benefits)
What is the starting dose of Venlafaxine?
SNRI
37.5 - 75 mg
75-225 mg (the higher the dose, the more difficult to taper off, discontinue syndrome)
Which SNRI causes elevation of blood pressure?
Venlafaxine
avoid if BP is uncontrolled -> go with Duloxetine
Side effects of Trazodone
-sedation
-Orthostasis
-priapism (prolonged erection, rare)
Side effects of Bupropion
-nausea
-tremor
-seizure (dose-related, max dose 450 mg in divided doses)
Side effects of Mirtazapine
-somnolence
-weight gain
-dry mouth
-constipation
-rare: agranulocytosis, LFT elevation
How is bupropion/DXM (Auvelity)
-bupropion 45mg/DXM 105mg
start: one tablet in the morning for 3 days
then: one in the morning -> space 8h -> 2nd dose
max dose: not more than 2 tablets a day
-swallow as a whole (not crushed or chewed)
When not using Gepirone
-Qtc > 450 msec !!!
-congenital long Qtc syndrome !!!
-strong CYP3A4 inhibitors
-liver impaired (cause accumulation)
-MAOI in 14 days
Which meds are used for post-partum depression
-Zuranalone: take it with food in the eveneing (makes sleepy, food improves absorption)
-Brexanalone: continuous infusion (inpatient)
BBW: excessive sedation, may pass out
->not often seen bc very expensive and people need to stay inpatient
How to manage sexual dysfunction in anti-depression therapy
-healthy lifestyle: exercise, lose weight, smoking cessation, substance use disorder (marijuana, meph causes sexual dysfunction)
-change to bupropion, mirtazapine, nefazodone (not often used due to hepatotoxicity)
-add bupropion 150 mg in the morning (make sure she doesn’t have a seizure disorder or eating disorder), mirtazapine or sildenafil
-it might go away, or they get tolerant
-may drop the dose, but depression may come back
What to watch out for when adding bupropion for sexual dysfunction?
-(make sure she doesn’t have a seizure disorder or eating disorder
throwing up would cause electrolyte drop and lower the seizure threshold
-watch out that it doesn’t make anxiety worse
What happens if TCAs are discontinued abruptly?
Cholinergic rebound (opposite of anticholinergic side effects)
-diarrhea, dizziness, insomnia, restless
taper by 25-50 mg per week
What happens if SSRIs and venlafaxine are discontinued abruptly?
-flu-like symptoms
-brain zaps
-headache
-dizziness
-can’t concentrate
-anxiety, insomnia
takes longer with velnafaxine
What is the drug of choice when starting depression therapy?
SSRI
switch to another SSRI or non-SSRI if there is no response or adverse effects that are not tolerable
How long should patients stay on the maintenance dose?
at least 6-12 months
12-36 months
Which drug is commonly used for augmentation?
Lithium: 600-900 mg, quick response
Triiodothyronine T3: 25-50 mcg
->may lead to hyperthyroidism
long-term risk for osteoporosis, arrhythmias
check TFT at baseline and 3 months; check DMX for post-menopausal patients
What are common antipsychotics that are used as adjunctive drugs?
-Ariprazole
-brexpriprazole
-Olanzapine
-Quietapine
Which drug is a Folate supplement?
Rx: Deplin
low folate levels correlate with depression
L-methylfolate is a cofactor for 5-HT, DA and NE
Which drugs are approved for depression treatment in children?
Fluoxetine
Escitalopram (12-17y)
Which drugs are approved for enuresis (bed-wetting) treatment in children?
Imipramine
Which drugs are approved for OCD (obsessive-compulsive disorder) in children?
-Clomipramine (older than 12)
-Fluvoxamine, Fluoxetine, sertraline (children)
What are the symptoms/signs of sudden suicide attempts in children on antidepressants?
agitation and restlessness
regular follow-up is essential (active outreach)
Which antidepressants are most studied in pregnant women?
-Fluoxetine (but when the mom breastfeeds it can agitate (and colic) the child - so not the best choice)
-citalopram
-escitalopram
avoid paroxetine!
if they are not on an antidepressant cognitive behavioral therapy is appropriate
Drug of choice for patients who breast-feed?
sertraline
When is electric convulsive therapy (ECT) used in pregnant patients?
when they are psychotic or suicidal
What is the drug of choice in elderly patients?
SSRIs
-avoid paroxetine
