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Major Depressive Disorder (MDD) (etiology and pathophysiology (hypotheses…
Major Depressive Disorder (MDD)
treatment goals
reduce severity of current symptoms
prevent relapse/recurrence
improve pt's QoL
etiology and pathophysiology
hypotheses for depression
monoamine hypothesis
patients with depression have a deficiency in monoamines (5-HT, NE and dopamine)
doesn't account for lag in mood changes with drug therapy
postsynaptic receptor sensitivity hypothesis
adults 18 to 29 years of age experience the highest rates of major depression
risk factors: gender (more common in women), family history, comorbid substance abuse
signs and symptoms
physiological
loss of appetite
unintended weight gain/loss
insomnia/hypersomnia
slowed movements
fatigue
poor concentration
emotional/ behavioral
suicidal ideations
anhedonia (the inability to experience pleasure in normally pleasurable acts)
feelings of worthlessness or inappropriate guilt
treatment of MDD
pharmacologic
first-line agents
SSRIs
citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac) paroxetine (Paxil), sertraline (Zoloft)
AEs: QTc prolongation, sedation, weight gain, anticholinergic effects
fluoxetine
has the longest half-life,
paroxetine
has the shortest!
MOA: inhibits neuronal reuptake of 5-HT to prolong its concentration and time in the synaptic cleft
second-line agents
trazodone (Desyrel, Oleptro)
AEs: sedation, orthostatic hypotension, N/V, HA, nervousness
MOA: inhibits 5-HT reuptake and significantly blocks H1 and alpha1-adrenergic receptors
second-generation antipsychotics (SGAs)
quetiapine (Seroquel), risperidone (Risperdal), aripiprazole (Abilify)
AEs: sedation, weight gain, increased BP, restlessness
tetracyclic antidepressants (TCAs)
AEs: sedation, weight gain, restlessness, increased TGs, hypercholesteremia
MOA: blocks autoreceptors to increase 5-HT and NE release to the synapse
mirtazapine (Remeron)
SNRIs
desvenlafaxine (Pristiq), duloxetine (Cymbalta), venlafaxine (Effexor XR)
AEs: increased BP
MOA:
bupropion (Wellbutrin)
MOA: inhibits NE and dopamine reuptake to prolong its concentration and time in the synaptic cleft
AEs: insomnia, agitation
third-line agents
monoamine oxidase inhibitors (MAOIs)
MOA: irreversibly increases 5-HT, NE, and dopamine concentrations in synapse by MAO enzyme inhibition
increases tyramine in the gut and liver (increases NE release and BP)
AEs: orthostatic hypotension, insomnia, weight gain
hypertensive crisis
, a life-threatening but rare adverse reaction, may occur when MAOIs are taken with certain foods high in tyramine
tricyclic antidepressants (TCAs)
MOA: inhibits neuronal reuptake of 5-HT and NE in synaptic cleft
very low tolerability for TCAs at anti-depressive dosages due to adverse effects
AEs: anticholinergic effects, sedation, tachycardia, arrhythmias, increased seizure risk, delirium in elderly, weight gain
esketamine (Spravato)
FDA approved as an adjunct agent in conjunction w/ an oral antidepressant
CIs: aneurysm, intracerebral hemorrhage
AEs: dissociation, sedation, dizziness, abusepotential
reserved for pts who have failed at least 2 adequate trials of antidepressants
self-administered under supervision
non-pharmacologic
cognitive behavioral therapy (CBT)
physical activity
electroconvulsive therapy (ECT)
only used for urgent/emergent circumstances
no contraindications!
goal is high-quality seizure x 1 minute
barriers: stigma, anesthesia, access, consent, index series as inpatient
requires extra planning if pt is on BZDs or AEDs
behavioral activation (BA)
increase patient's contact with sources of reward and pleasurable activities
transcranial magnetic stimulation (TMS)
monitoring and follow-up
symptom timeline
in 1-2 weeks...
feelings of anxiety, sleep patterns, and appetite improve
in 2-3 weeks...
concentration, libido, and energy levels improve
suicidal risk is reduced during this phase
in 4-8 weeks...
relief from anhedonia, depressed mood, and feelings of hopelessness
tolerability
serotonin syndrome
usually occurs when taking other medications (e.g. lithium, sumatriptan, fentanyl, tramadol) that may affect serotonin levels with an antidepressant
mental status changes (agitation, confusion, hyperactivity)
neuromuscular effects (restlessness, tremor)
autonomic effects (diarrhea, fever, HTN, sweating, mydriasis)
discontinuation syndrome
FInISH
(flu-like symptoms, insomnia, imbalance, sensory disturbances, hyperarousal)
safety
presence of side effects does not necessarily indicate adequate dosage!
pts > 40 YO should receive a pretreatment ECG before starting TCA therapy
check pts for the emergence of suicidal ideation after initiation of ANY antidepressant
if significant hyperactivity or insomnia occurs after antidepressant initiation, a short-term anxiolytic/hypnotic may be appropriate
weight gain and sexual dysfunction are associated with non-adherence and should be discussed with the pt
efficacy
partial response
= 26-49% decrease in baseline symptoms
partial remission or response
= > 50% decrease in baseline symptoms
nonresponse
= < 25% decrease in baseline symptoms
diagnostic criteria and testing
PHQ-9
rates severity of depression
used more often in clinical settings
DSM-5 criteria
