Depression -Test 2 Flashcards
What is the most common diagnosis associated with psych admins?
Depression
How can depressive symptoms present?
—patients look sad, guilt-ridden, and hopeless
—Other patients look nervous, and irritable
—Others complain of somatic problems
—Psychosis can accompany depression
—Depression can lead to a dementia-like state
What are the DSM-V classifications for depression?
—Unipolar major depression (major depressive disorder)
—Persistent depressive disorder (dysthymia)
—Disruptive mood dysregulation disorder
—Premenstrual dysphoric disorder
—Substance/medication induced depressive disorder
—Depressive disorder due to another medical condition
—Other specified depressive disorder (eg, minor depression)
—Unspecified depressive disorder
What is the criteria for unipolar major depression?
—Characterized by a history of one or more major depressive episodes and no history of mania or hypomania .
—A major depressive episode manifests with five or more of the following symptoms for at least two consecutive weeks; at least one symptom must be either depressed mood or loss of interest or pleasure
What is the criteria for major depression?
—Depressed mood most the day, nearly every day
—Loss of interest or pleasure in most or all activities, nearly every day
—Insomnia or hypersomnia nearly every day
—Fatigue or low energy, nearly every day
—Significant weight loss or weight gain (eg, 5 percent within a month) or decrease or increase in appetite nearly every day.
—Psychomotor retardation or agitation nearly every day that is observable by others
—Decreased ability to concentrate, think, or make decisions, nearly every day
—Thoughts of worthlessness or excessive or inappropriate guilt, nearly every day
—Recurrent thoughts of death or suicidal ideation, or a suicide attempt
—In addition, the symptoms cause significant distress or psychosocial impairment, and are not the direct result of a substance or general medical condition. Bereavement does not exclude the diagnosis of a major depressive episode.
What is SIG E CAPS for? What does it stand for?
A pneumonic to help with the symptoms of major depression —S leep disturbance —I nterest loss —G uilt —E nergy loss —C oncentration difficulties —A ppetite disturbance —P sychomotor retardation/ agitation —S uicidality
What are the big culprits of drug induced depression?
CV agents/AntiHTN: clonidine, methyldopa, propranolol, prazosin
Misc: disulfiram
CNS: alcohol, alpha interferon
Hormones: corticosteroids
What are major causes of depression?
CNS: stroke, AD, MS, HD
Endocrine: hypothyroid, cushing/Addison, DM
Autoimmune: RA, SLE
In the monoamine hypothesis for major depression, depression results from a dysregulation of what?
—Norepinephrine (NE)
—Serotonin (5-HT)
—Dopamine (DA)
decrease in NT
What happens to post-synaptic 5-HT, DA, and NE receptors when the amount of these neurotransmitters is decreased?
—Up-regulation of post-synaptic receptors
—Decreased receptor sensitivity
—Altered genetic expression
What is the drug model for depression in the monoamine hypothesis?
—Reserpine
—Induces depression depletion of monoamines
—Depression is reversed by the 5-HT precursor and (less well) by the NE precursor
In the monoamine hypothesis, what leads to depression? What can reverse depression?
—Low 5-HT and/or NE in limbic system leads to depression
—Increased limbic 5-HT and/or NE can reverse depression
What happens when there is hyperregulation of the HPA axis?
Increased CRF and blunted cortisol suppression
What can dysregulation of the HPA axis lead to?
Hippocampal toxicity and if severely stressed increased glucocorticoids
What triggers the negative feedback loop btwn the hippocampus and the HPA loop?
Glucocorticoids
When are prolonged levels of glucocorticoids seen? What can this cause?
Prolonged and severe stress
This damages hippocampal neurons reducing the negative feedback loop causing the “snowball” effect
What does the brain derived neurotropic factor play a role in?
It is a potent regulator of plasticity of adult neurons and glia linked to the HPA activation theory important for the survival of neurons, acute and chronic stress cause a decrease in the expression of BDNF
What regions other than the hippocampus are involved in depression?
Nucleus accumbens and amygdala- these work in the dopaminergic pathway and lead to amotivation and anhedonia
What are the goals for tx for MDD?
—Reduce the acute symptoms of the depressive episode
—Facilitate the patient’s return to premorbid function (prior to illness)
—Recovery should be the rule, not the exception!
—Prevent further episodes of depression
What are tx options for major depression?
—Selective Serotonin Reuptake Inhibitors (SSRIs) —Tricyclic Antidepressants (TCAs) —Tetracyclic Antidepressant —Alpha 2 antagonists —Dopamine Reuptake Inhibitors —SSRI and 5HT-1a agonist —SSRI and 5HT3 antagonist —Serotonin/Norepinephrine Reuptake Inhibitor —Monoamine Oxidase Inhibitors (MAOIs)
What are the SSRIs?
—Fluoxetine —Sertraline —Paroxetine —Fluvoxamine —Citalpram —Escitalopram —Symbyax
What are the most commonly prescribed antidepressants?
SSRIs
What is the MOA for SSRIs?
Block the reuptake of serotonin
When is the typical ssri’s dosing schedule?
Once daily dosing usually in the morning
What are the SSRI ADRs?
—Nausea —Headache —Sleep disturbances —Changes in weight —Agitation/increased anxiety (initial) —Sexual Dysfunction —Tremor —Sweating —Rare hyponatremia
What are the specific side effects of paroxetine?
more likely to cause sedation, constipation, and dry mouth
What are the specific side effects of sertraline?
may be more likely to have GI distress, insomnia or activation
What is the order of SSRIs from worst to least amount of change with discontinution?
Paroxetine > sertraline = citalopram = escitalopram > fluoxetine
What is antidepressant discontinuation syndrome?
—Flu-like symptoms, malaise
—Dizziness
—GI (nausea, diarrhea)
—Transient changes in mood, affect, appetite, and sleep
—Electric “shock-like” sensation in upper extremities
—Vivid dreams/nightmares
—Poor concentration
What is vilazodone?
SSRI and 5-HT1A Receptor Partial Agonist
How often is vilazodone given and what should it be taken with?
Once daily with food
What are the ADRs of vilazodone?
Diarrhea, nausea, withdrawl syndrome with abrupt stop of drug
What is vortioxetine?
SSRI and selective 5-HT1a receptor agonist and 5-HT3 receptor antagonist
What is the MOA of vortioxetine?
Enhanced 5-HT1 neurotransmission through 5-HT2 blockade
What is the dosing schedule for vortioxetine?
Once daily without regard to meals
What is the most common ADR of vortioxetine?
Sexual dysfxn
What is nefazodone?
SSRI plus potent 5-HT2 receptor antagonist
What is the MOA for nefazodone?
Enhanced 5-HT1 neurotransmission through 5-HT2 blockade
Why is nefazodone considered 2nd or 3rd line tx even though it has comparable efficacy for tx of depression as standard antidepressants?
Risk of hepatotoxicity
What symptoms can nefazodone improve?
symptoms of poor sleep quality, sleep disturbance, anxiety and agitation in depressed patients
What is the recommended dosing of nefazodone?
—Twice daily dosing recommended, but frequently it is administered at bedtime because of its sedative properties
—Initial starting dose is 200 mg/day
—Generally need doses of 300-600 mg/day for antidepressant activity
What are the ADRs of nefazodone?
—Sedation —Orthostasis —Dry mouth —Nausea —Increased appetite —Blurred vision —Hepatotoxicity
What is the MOA of trazodone?
—Blocks 5-HT2A receptors (potently); Blocks 5-HT reuptake less potently
—Also has antihistaminic properties → Sedation
What is the dosing of trazodone for antidepressive tx? For insomnia?
Initial: 150 QD, max: 400 QD
50-200 QHS…losing sedative properties at >200
What are the serotonin/NE reuptake inhibs?
Venlafaxine Desvenlafaxine Duloxetine Milnacipran —Levomilnacipran
What are the options for Venalfaxine?
IR (immediate release) and XR
What is the MOA of venlafaxine?
—Inhibits reuptake of NE and 5-HT
—Also inhibits DA reuptake (to lesser extent)
What are the doses needed for NE/DA reuptake? What is the starting and max dose?
—Starting dose 37.5-75 mg/day, max dose 225 mg/day
—Doses ≥ 200 mg needed for NE and DA reuptake
What are the ADRs of venlafaxine?
Nausea Headache Somnolence Sexual dysfunction Insomnia Agitation Increase in DBP: (dose related)
What is desvenlafaxine?
Active metabolite of venlafaxine
DO NOT EVER PICK THIS ANSWER FOR ANY EXAM QUESTION
What is duloxetine?
Potent 5-HT NE reuptake inhibitor
What are the starting and max doses for duloxetine?
Starting dose 40 mg/day, max dose 60 mg/day → Has been studied up to 120 mg/day
What else does duloxetine work for?
Urinary incontinence and diabetic neuropathic pain
What are the ADRs of duloxetine?
—Insomnia/sedation —Nausea, diarrhea, decreased appetite —Sexual dysfunction —Sweating —Urinary hesitancy —Hepatotoxicity —Increase in BP
What is milnipracin approved for?
management of fibromyalgia
What is the BBW for milnipracin?
Same as all antidepressants- risk of suicide
What is levomilnacipran?
More active enantiomer of milnacipran, potent inhibitor of NE and 5-HT reuptake
What are the indications for levomilnacipran?
Once daily for depression
What are the ADRs of levomilnacipran?
—Orthostatic hypotension
—Nausea
What are the 2 categories of TCAs?
Secondary amines and tertiary amines
What are the secondary amines?
Nortriptyline, despramine, protriptyline, amoxapine
What are the tertiary amines?
Amitriptyline, imipramine, clomipramine, doxepin, trimipramine
What is the MOA of TCAs?
Block the reuptake of NE and 5-HT (NE > 5-HT) Also block: —Muscarinic receptors —Histamine receptors —Alpha-1 receptors
What is the half life of all TCAs?
About 24 hrs
What do you need to draw for TCA?
Blood sample 12 hrs past last dose to check for therapeutic concentrations
What are the side effects of TCAs?
—Tachycardia —Orthostasis —Weight gain —Sedation —Sexual dysfunction Anticholinergic effects —Dry mouth —Constipation —Dry eyes —Urinary retention Cardiac conduction changes —Prolongation of QRS, ST depression, flattened or inverted T-waves —Baseline ECG Tertiary amines>secondary amine —Anticholingeric effects —Antihistiminic effects —Hypotensive effects
What is the maprotiline? What is the MOA?
—Tetracyclic antidepressant
—NE reuptake inhibitor, desensitization of adenyl cyclase, down regulation of beta adrenergic receptors and serotonin receptors
What are the ADRs of maprotiline?
—Drowsiness
—Xerostomia
What is the MOA of mirtazapine?
Dual neurotransmitter action:
—A potent and direct alpha-2 receptor antagonist
-Enhances 5-HT and NE transmission
—Blocks 5-HT2 and 3 receptors
-Results in enhances 5-HT1 reception
What are the ADRs of mirtazapine?
Less nausea and sexual dysfunction than SSRIs Somnolence* Dry mouth Constipation Orthostasis Increased appetite => weight gain
How is mirtazapine dosed?
once daily at bedtime due to sedation
What is the MOA of Bupropion?
Believed to block reuptake of dopamine and norepinephrine
How is bupropion administered?
IR, SR, and XL formulations
SR or XL formulations result in:
Slower absorption rate; More gradual rise and decline of plasma levels; lower peak plasma levels
Is bupropion 1st or 2nd line for depression?
Considered first line
What is a risk dose related to bupropion?
Seizures
What are the ADRs of buproprion?
Anxiety, agitation Headache Seizures Increased risk with higher doses sweating Tremor Insomnia GI disturbances (anorexia, nausea, constipation) Weight loss
What is the MOA of MAOIs?
Block the break down of NE, 5-HT, DA, and epinephrine
What are the 2 types of MAOIs?
MAO-A (EPI, NE, 5-HT, DA, tyramine)
MAO-B (DA, tyramine, benzylamine and phenylethylamine)
What are the irreversible and reversible mixed inhibs?
Irreversible: phenelzine, isocarboxazid, selegiline
Reversible: tranylcypromine
What are the ADRs of MAOIs?
Not used as often due to drug-drug and dug-food interactions
Aged, hard cheeses and strongly flavored cheeses contraindicated
SE: orthostasis, dizziness, mydriasis, piloerection, edema, sexual dysfunction, insomnia, weight gain
High risk of serotonin syndrome
High risk of hypertensive crisis
What are the MAOIs drug interactions?
Other antidepressant medications, including herbals
Buspirone
Meperidine
Dextromethorphan
Direct sympathomimetics (e.g., L-dopa, epinephrine, isoproterenol, norepinephrine)
Indirect sympathomimetics (e.g., amphetamines, methylphenidate, phenylpropanolamine, ephedra, pseudoephedrine and tyramine)
Cocaine
What is serotonin syndrome?
An adverse effect due to excessive serotonin in the periphery
What are the symptoms of serotonin syndrome?
Sternbach Criteria: Neuromuscular hyperactivity Tremor, myoclonus, hyperreflexia, restlessness Autonomic hyperactivity Hyperpyrexia, hypertension, tachycardia Cognitive/behavioral changes confusion
What is the starting drug recommended for major depression?
SSRI
What is the time frame for response to antidepressants?
Most responders will have an onset of response within 4 weeks
No response at 4 weeks, consider ↑ in dose and waiting another 2-3 weeks
Patients showing minimal to no response should not exceed a trial of 8 weeks
Patients showing a partial response can be treated for up to 12-16 weeks
What needs to be tapered when switching drug choice?
All SSRIs, except FLX, should be tapered before discontinuation or within class switch
What are the drug options for pregnancy and lactation?
SSRI or TCA: FLX most studied
Should you give TCAs in geriatrics?
Generally problematic due to SE profile
DESI and NORT recommended if required
