Major depression sx
D SIG E CAPS
- Depressive mood
- Sleep (decreased > increased)
- Interest decreased (anhedonia)
- Guilt/worthlessness increased
- Energy (decreased > increased)
- Concentration decreased
- Appetite/weight (decreased > increased)
- Psychomotor (decreased > increased)
- Suicide/thoughts of death increased
Major depression – DSM IVR criteria for diagnosis
- Presence of sx for > 2 weeks
- At least 5 sx present; at least 1 depressed mood or loss of interest/ pleasure
- Sx occur nearly every day
- Sx cause significant distress or impairment of functioning
- Sx not due to bereavement or last > 2 months
Additional sx of depression
- Emotional – anxiety, irritability
- Cognitive – decreased concentration, indecisiveness, poor memory
- Psychotic – bizarre behaviour, hallucination, delusions
- Physical – fatigue, decreased libido, decreased hygiene, crying spells
Secondary depression causes
- Medical disorders – thyroid disorder, malignancy, stroke, CHF/ MI, Parkinson’s
- Psychiatric disorders – alcoholism, schizophrenia, anxiety
Non-pharms for depression
- Cognitive behavioural therapy
- Change distorted thinking
- Alteration of target thoughts
- Change erroneous assumptions
- Promote self-control over thinking
- Interpersonal
- Bright light therapy – for seasonal affective disorder
- Exercise & good nutrition
Major depression – time course
- Most last 6-24 months
- > 2 years in 5-10%
- Often recurrent episodes
Tx goals for depression
- Shorten episode
- Decrease sx (response)
- Restore function
- Eliminate sx (remission)
- Prevent relapse
- Minimize adverse effects of tx
- Minimize drug interactions
- Promote adherence to therapy
What determines the urgency of tx for depression
- Severity of depressive sx
- Severity in impairment of functioning
- Psychotic sx
- Suicidal thoughts
Typical response for anxiety and insomnia to antidepressants
Few days
Typical response for energy and somatic sx to antidepressants
2nd or 3rd week
Typical response for sleep patterns to antidepressants
Several weeks
Typical response for depressed mood and sexual dysfunction to antidepressants
4th week
MOA of SSRIs
Increase 5-HT
MOA of SNRIs
Increase 5-HT and NE
MOA of NDRIs (norepinephrine dopamine reuptake inhibitors)
Increase NE and dopamine
MOA of NaSSA (noradrenergic and specific serotonergic antidepressant)
Increase 5-HT and NE
MOA of TCAs
Increase 5-HT and NE
MOA of MAOIs
Increase 5-HT, NE, and DA
MOA of RIMA (reversible inhibitor of monoamine oxidase)
Increase 5-HT, NE, and dopamine
Describe the general guidelines for depression tx
- Uncomplicated (physically healthy, outpatient, no CI) –> SSRI (all about equally effective; choice of one over another depends on pt profile & drug profile)
- Failed trial due to non-response or limiting adverse effect –> ensure adherence, maximize dose (try to wait 8 weeks until increasing); then consider switching to alternative agent (different SSRI, non-SSRI)
- Partial response –> consider augmentation w/ 2nd antidepressant, lithium, or T3 or T4 or switch to alternative agent
- Failed trail –> switch to alternative agent
- Consider ECT?
- Response/ remission = maintain for at least 4-9 months for continuation & if necessary 12-36 months for maintenance
- Similar response rates for all antidepressants
Which antidepressants can be used in combination?
- Venlafaxine + bupropion
- SSRI + bupropion
- SSRI + TCA
- TCA + MAOI **very cautiously
- *Never use SSRI + MAOI (will get serotonin syndrome)
Duration of tx for depression
- 4-9 months after remission
- Lifelong is < 40 y/o and 2+ episodes or any age and 3+ episodes
- Poop-out syndrome (initially have response but short lived)
Describe ECT (electroconvulsive treatment)
- Candidates = rapid response (suicidal, psychotic), hx of poor response to meds, pregnancy
- Course = 6-12 tx, unilateral or bilateral, 2-3 times/week
- Adverse effects = confusion, memory loss months pre & post ECT, CV dysfunction, headache, nausea
SSRIs - options, advantage, SE, toxic effects
- Fluoxetine, sertraline, fluvoxamine, paroxetine, citalopram, escitalopram
- *Remain on a dose for 8 weeks before increasing
- Advantage –> less SE vs. TCAs b/c lack alpha 1, M1, and H1 effects
- SE –> agitation, nervousness, restlessness, insomnia/ drowsiness (paroxetine, fluvoxamine), GI effects initially
- Toxic effects –> tremor, sinus tachycardia, N/V, diarrhea, seizures, serotonin syndrome
What determines the choice of an antidepressant over another?
- Personal and family hx
- Subtype of depression
- Medication hx/ concurrent meds
- Potential for drug interactions
- Adverse effect profile
- Cost
- Antidepressant MOA
Describe serotonin syndrome
- Diagnosis of exclusion
- Cognitive/behavioural = agitation, mental status changes (confusion, hypomania)
- Autonomic dysfunction = diaphoresis, diarrhea, fever, shivering
- Neuromuscular abnormalities = incoordination tremor, myoclonus, hyperreflexia
Causes of serotonin syndrome
- Drugs that inhibit breakdown of 5-HT (MAO inhibitors)
- Drugs that block reuptake of 5-HT (SSRIs, venlafaxine, clomipramine, dextromethorphan, trazodone)
- Drugs that are 5-HT precursors or agonists (lithium, buspirone)
- Drugs that enhance 5-HT release (MDMA)
Tx for serotonin syndrome
- Supportive care
- BZD for neuromuscular sx
- Tylenol for fever
- Cyproheptadine 4 mg q4h for severe sx
SSRI withdrawal sx
- Somatic:
- Disequilibrium – dizziness, vertigo, ataxia
- GI – N/V
- Influenza-like – fatigue, lethargy, myalgia
- Psychological – anxiety, agitation, irritability, crying spells
- *FINISH – flu-like sx, insomnia, nausea, imbalance, sensory disturbance, hyperarousal
- Occur w/in 1-3 days (up to 1 week)
- Last up to 7-14 days (may be several weeks)
- Tx:
- Prevent w/ gradual tapering
- If begins to appear, increase dose & taper more slowly
- If severe, switch to fluoxetine
Briefly describe the grapefruit interaction
- Single glass can decrease intestinal 3A4 content more than 50%
- Duration of action several hours or longer, so separating juice from dose may not prevent interaction
- Toxicity can occur when pt given higher than usual doses of susceptible med & drinks grapefruit juice for the first time
Venlafaxine (SNRI) – MOA and SE
- Increases NE & 5-HT
- Regarding overdose, not as safe as SSRI but safer than TCAs; once you get up to high doses then similar to TCAs
- SE = BP increases (dose dependent response, usually reversible on d/c, risk greater w/ increased age), dose related GI effects, dizziness, sexual dysfunction, dry mouth, constipation
Bupropion (NDRI) - MOA, SE, advantages
- Good option for px previously on venlafaxine but can’t tolerate GI side effects or BP was increasing too much
- Increased NE & DA
- SE = tremor, insomnia, agitation, restlessness, anxiety; seizures at high doses; dry mouth, headache, N/V, rash
- Advantages = little sexual dysfunction & little weight gain (b/c doesn’t affect serotonin)
- Other agents can cause disruptions to REM sleep, but bupropion doesn’t (quality of sleep can be better)
Mirtazapine (NaSSA) - MOA, advantages
- Affects serotonin as antagonist & affects alpha receptors (would cause orthostatic hypotension, so not great for elderly px) & has some histamine properties (not as bad as TCAs but can be fairly sedating)
- Advantages –> little sexual dysfunction, less serotonergic effects
TCAs - MOA, SE
- Gold standard of therapy; if others don’t work then go to this one (don’t pick this first b/c very non-selective)
- Increases NE & serotonin; affects histamine, alpha & muscarinic receptors (gives anti-cholinergic side effects)
- Antihistaminic effects = sedation, weight gain
- In usual doses, cardiac effects include – hypertension, tachycardia, slowed cardiac conduction, antiarrhythmic properties, orthostatic hypotension
“High risk” px for TCA use
- Elderly
- CV disease
- Drug interactions
- Overdose cases
Toxic effects of TCAs in overdose
- CV (sinus tachycardia, ventricular arrhythmias, hypotension)
- CNS (coma, delirium, seizures), other (hyperthermia, urinary retention)
TCA withdrawal sx and tx
- Cholinergic and adrenergic rebound
- Sx = dizziness, nausea, diarrhea, insomnia, hot or cold flashes
- Taper over 2-4 weeks, tx = restart at low dose or anticholinergic agent
MAOIs - MOA, indication, SE
- Irreversible inhibitors of MAO A & B
- Indicated for atypical or resistant depression
- Don’t combine w/ other antidepressants (can add to TCA w/ caution)
- SE = orthostatic hypotension, dry mouth, constipation, sexual side effects (impotence, decreased libido), insomnia
- Dosed in AM & mid-day to avoid overstimulation
General recommendations for washout w/ MAOIs
- Antidepressant –> MAOI = washout 5 t1/2 of antidepressant
- MAOI –> antidepressant = washout 10-14 days
RIMA – MOA, example, SE
- Reversible inhibitor of MAO-A
- Moclobemide
- SE = HTN, tachycardia, orthostatic hypotension, insomnia
General taper/ washout recommendations for all antidepressants
- Can taper when switching from SSRI, novel, or TCA to SSRI, novel or TCA
- Must washout when switching any antidepressant to a RIMA or MAOI or switching from RIMA or MAOI to another antidepressant
Antidepressant recommendations for seizure disorders
- Avoid bupropion and TCAs
- SSRIs, venlafaxine, mirtazapine (?) have less effect on seizure threshold
Antidepressant recommendations for sexual dysfunction
- Avoid SSRIs, venlafaxine, TCAs, MAOIs
- Bupropion, mirtazapine, trazodone have little to no effect
Antidepressant recommendations for weight gain
- Avoid TCAs, MAOIs, and mirtazapine
- Bupropion, venlafaxine have little to no effect
Antidepressant recommendations for elderly
- Use lower initial dosages
- Evaluate for orthostatic hypotension & cognition
- Can get excessive sedation from histamine blockade, TCAs, trazodone, & mirtazapine
- Can get urinary retention (anticholinergic) from TCAs & mirtazapine
Antidepressant recommendations for cardiac px
- Venlafaxine increases BP w/ increasing dose
- Orthostatic hypotension – caution in angina & CHF
- Increased HR w/ anticholinergic effect – watch in unstable angina
- Use TCAs w/ caution in hx of arrhythmia + IHD
Antidepressant recommendations for pregnancy
- Weigh risks vs. benefits to mother & fetus
- Most evidence for safety of fluoxetine, then TCAs
- Can do ECT
- After delivery – watch for direct drug effects & transient withdrawal sx in infants
Antidepressant recommendations for breastfeeding
- Safety evidence for paroxetine, sertraline, fluoxetine, clomipramine, and nortriptyline
- Monitor infant daily for changes in sleep, feeding patterns, and behaviour; monitor for drowsiness and difficulty feeding
Antidepressant recommendations for children and adolescents
- Moderate to severe MD (major depression)
- First line = fluoxetine and citalopram
- Second line = other SSRIs (paroxetine > adverse effects)
- Third line = venlafaxine
- Best outcomes w/ combine CBT w/ antidepressant
- TCAs not recommended b/c risks»_space; benefit (lethal in overdose, rare cases of sudden death)
- Increased risk for suicidal behaviour; *monitor suicidal thoughts
- Continue tx if effective for 6 months; gradually d/c over 6 weeks
Response vs. remission vs. recovery
- Response = 50% reduction in sx
- Remission = sx go away
- Recovery = remission lasting 6-12 months
