Drugs for Affective Disorders

jmanderson's version from 2016-02-21 20:10

Powerpoint Objectives


Question Answer
Apply the advantage of SSRIs over other AD classes to a clinically-relevant case scenario.Other anti-depressants had anti-muscarinic, antihistaminic and alpha adrenoceptor blocking actions, which may contribute to their toxicity. SSRIs are 5-HT selective and decrease ANS toxicity effects.
role of the metabolite of fluoxetine and its half-lifeFluoxetine’s demethylated metabolite, norfluoxetine has a half-life of 7-9 days at steady state; Fluoxetine’s is slightly shorter; So, give a high LOADING DOSE
Serotonin Syndrome Sxhyperthermia, muscle rigidity, myoclonus and rapid changes in mental status and vital signs.
Avoid mixing what with SSRIs due to Serotonin Syndrome?MAO-Is
Give the SSRI that inhibits microsomal enzymes least.Citalopram
the SSRI that is dosed differently than other ADs and howFluoxetine usually start with 20 mg/day and maintain for several weeks until the patient’s response can be determined
Apply one advantage for bupropion over SSRIs to a clinically-relevant case scenario.Improves attention and concentration more than SSRIs; Well tolerated by pts with orthostatic hypotension (alpha-receptor effect)
one tolerability advantage of bupropion over SSRIsNo sexual dysfunction
typical dosing regimen for tricyclic ADs (e.g., imipramine)Start low and increase by 25 mg every 2-3 weeks.; Inpatient → start ~100 mg/d; Outpatient → start 10-75 mg/d
three “adjunctive” therapies to antidepressantsLithium, thyroid hormones, atypical anti-psychotics (e.g., aripiprazole)
neurotransmitter systems affected by tricyclicsanticholinergic, anti-alpha adrenergic, anti-histaminergic
Anticholinergic AEs of TCAsABCD → Anorexia, Blurry vision, Constipation/Confusion, Dry mouth, Sedation/Stasis of urine; Can’t see, can’t pee, can’t spit, can’t shit
Anti-alpha adrenergic AEs of TCAsorthostatic hypotension
Anti-histaminergic AEs of TCAsdrowsy, lethargy
two ways to avoid tricyclic overdose1) Prescription < 1.25 g or 50 dose units of 25 mg, no refill; 2) entrust drug to relative.
Give the reason patients should take amitryptiline at bed time.Administration of the entire daily dose at bedtime may reduce daytime sedation.

Handout Objectives


Question Answer
amitriptyline selectivityanti-muscranic, anti-5HT, mild anti-NE
buproprion selectivityanti-5HT, maybe anti-NE
desipramine selectivityanti-NE, mild anti-muscarinic
fluoxetine selectivityanti-5HT, mild anti-muscarinic
imipramine "classic TCA" selectivityanti-5HT, some anti-muscarinic and anti-NE
protriptyline selectivityanti-NE, some anti-muscarinic
sertraline selectivityanti-5HT (thus serotonin-selective re-uptake inhibitor)
black box Warning SSRIs in kidsantidepressants may increase the risk of suicidal thinking and behavior in some children and adolescents with Major Depressive Disorder (MDD).
Monitoring with SSRIs in kidschildren and adolescents taking SSRI medications should be closely monitored for any worsening in depression, emergence of suicidal thinking or behavior, or unusual changes in behavior, such as sleeplessness, agitation, or withdrawal from normal social situations. Close monitoring is especially important during the first four weeks of treatment.
The FDA recently determined that the only SSRI approved for use in Pediatric populations was …..Fluoxetine (Prozac)
NMDA receptor hypothesis Prosglutamate is very important in brain (potential is great), many antidepressant treatments affect NMDA receptors long-term, preclinical data is positive
NMDA receptor hypothesis Consalmost no clinical evidence that NMDA antagonists are effective antidepressants
CRF hypothesis ProsCMST long has been a test of depression, CRF associated with control of GI system, CRF antagonists associated with reduced sleep, small clinical trial
CRF hypothesis Consno extensive clinical trials
Give the condition that anti-depressants are often used for but for which bupropion should not be used.Bupropion should not be used for panic or OCD as it may worsen panic and OCD (remember it seems to act on dopamine systems).
Dysthymia (or Depressive Neurosis)a chronic disturbance of mood involving depressed mood for most of the day more days than not, for at least two years.
Associated symptoms of dysthymiapoor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low self-esteem, poor concentration or difficulty making decisions, and feelings of hopelessness.
Summarize the three major points made by detractors of the usefulness of anti-depressants.There are many papers showing no effect of anti-depressants on depression that are never published that no conclusion can be made as to their effectiveness.

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