Pharm blk4- SSRI
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| what is the prototype SSRI | sertraline (zoloft)
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| what is the first group of depressive symptoms to subside, and how long does this take | neurovegetative symptoms - about two weeks
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| what symptoms were mentioned to be in this group (4) | 1) sleep disturbances; 2) altered appetite; 3) decreased energy; 4) increased anxiety
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| what group of symptoms subsides next, and how long after treatment begins | cognitive symptoms - 4-6 weeks
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| what symptoms were mentioned to be in this group (3) | 1) sadness; 2) hopelessness; 3) poor concentration
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| how do SSRI side effects compare to TCAs and MAOIs | milder
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| what are the main categories of adverse effects that occur with SSRIs (4) | 1) GI; 2) CNS; 3) sexual; 4) weight change
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| what are the most common GI side effects with SSRI | 1) nausea; 2) diarrhea
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| why does nausea occur | 5-HT-3 receptor is in the CTZ
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| what SSRI may have fewer GI side effects | paroxetine
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| what group of side effects does paroxetine have more of than other SSRIs | mild anticholinergic effects
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| what three were mentioned | 1) constipation; 2) urinary retention; 3) dry mouth
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| who should paroxetine be avoided in | patients taking other anticholinergic medication
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| what SSRI is the most activating in the CNS | fluoxetine
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| what are four common CNS side effects of SSRIs | 1) anxiety; 2) tremors; 3) insomnia; 4) extrapyramidal
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| what AE are activating SSRIs especially likely to cause | insomnia
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| what coincides with lessening of sleep disturbances/insomnia | sleep improves when depression subsides
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| in what patients are activating SSRIs desirable (1) and undesirable (2) | desirable in patients without energy, undesirable in patients complaining of: 1) too much anxiety; 2) lack of sleep
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| what SSRI has the highest propensity for extrapyramidal side effects | paroxetine
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| what is the incidence of sexual dysfunction with SSRIs, and in what sex is this most common | 30-50%, most common in men
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| what sexual side effects happen in males (2) | 1) delayed ejaculation; 2) lack of orgasm
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| what sexual side effects happen in females (3) | 1) decreased libido; 2) orgasm trouble; 3) lack of lubricaiton
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| what SSRI causes the most sexual dysfunction | paroxetine
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| what other sexual adverse effect can happen in both sexes | emotional blunting of feelings of romance
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| what may be the mechanism for this | excess 5-HT nonselectively taken up into DA terminals - 5-HT hijacking DA signaling in the brain
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| what other feelings are affected by emotional blunting (3) | 1) less ability to become angry; 2) less ability to care about others feelings; 3) less ability to feel pleasure
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| what generally happens to weight with SSRIs, and how does this compare to TCAs and MAOIs | weight is gained, but less than with TCA or MAOI
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| what SSRI causes the most weight gain | paroxetine
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| so, what side effects does paroxetine cause more than other SSRIs (4) | 1) GI; 2) extrapyramidal; 3) sexual dysfunction; 4) weight gain
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| what is the leading cause of noncompliance with SSRIs | sexual dysfunction
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| what are the underlying mechanisms that cause sexual dysfunction (2) | 1) postsynaptic stimulation of 5-HT2 receptors; 2) decreased sympathetic stimulation
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| is sexual dysfunction generally transient or does it persist | typically transient, but can persist
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| what SSRI has the least sexual side effects | escitalopram (lexapro)
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| what other drugs have low sexual side effects, and what MOA is each | 1) bupropion (SDRI); 2) mirtazapine (blocks presynaptic alpha-2 receptors); 3) nefazadone (blocks postsynaptic 5-HT2A receptors
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| what are the three stages in antidepressant therapy | 1) acute; 2) continuation; 3) maintenance
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| how long is the acute phase, and what is the goal | about 12 weeks, goal to induce remission
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| what is the goal of step two (continuation), and how long does it last (range) | keep in remission - lasts 4-9 months
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| what is the minimum duration for stages 1 + 2 | 7 months
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| how long must stage 3 last | stage 3 is not for all patients
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| what happens to the risk for depression in pregnancy, and what % of women have depression during pregnancy | risk increases, 10% of women have depression during pregnancy
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| what % of women who stop therapy early in pregnancy suffer relapse by the third trimester | 50%; 68% total relapse rate given in next slide for women who discontinue treatment
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| what is the relapse rate during pregnancy for women who maintain meds | 26%
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| does SSRI cross into the fetus, or into breast milk | yes
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| what is SSRI concentration in fetal brain compared to mother | 85%
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| what is SSRI use in pregnancy associated with | 1) lower birth weight (0.5 lb); 2) persistent pulmonary hypertension of the newborn (associated with late/3rd trimester use)
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| what are the long term developmental consequences | unknown
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| so, which groups of ADs were mentioned to be safe and effective in pregnancy (2), but with what caveat | 1) TCAs; 2) SSRIs - although increased short-term neonatal adverse effects after exposure to ADs in 3rd trimester can occur
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| which class (SSRIs or TCAs) has a more favorable side-effect profile | SSRIs
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| what should be done during discontinuation of antidepressants (what reduction per time, and how long between reductions) | slow taper - reduce dose by 25% per week
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| what exception is there, and why | unnecessary for fluoxetine - long half life
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| when is there tolerance or drug-seeking behavior | there is not
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| what symptoms were listed under "discontinuation syndrome" (list) | dizziness, vertigo, ataxia, parasthesia, numbness, electric-shock-like sensations, lethargy, headache, tremor, sweating, anorexia, insomnia, nightmares, excessive dreaming, nausea, vomiting, diarrhea, irritability, anxiety/axitation, low mood
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| what type of drug interactions do SSRIs have | P-450
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| what P450 enzymes were mentioned (3) | 1) 3A4; 2) 2D6; 3) 2C9
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| what SSRI was mentioned to have the greatest effect on P450s | fluoxetine
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| what SSRI has the least effect on P450s | sertraline (zoloft)
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| what drugs were SSRIs specifically said to be able to result in elevated levels of (2 classes, 1 example from each) | 1) benzodiazepenes (diazepam/valium); 2) anti-seizure (phenytoin)
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| what should SSRIs never be used with, and why | MAOIs - can precipitate 5-HT syndrome
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| what four symptoms were mentioned in this lecture for 5-HT (serotonin) syndrome | 1) agitation; 2) hypertension; 3) confusion; 4) fever
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| what are the two options for switching medications (and trying to avoid serotonin syndrome) | 1) immediate substitution; 2) cross-taper (introduction of new drug while tapering dosage of the first)
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| when switching medications, for what kinds of medications is it typically ok to use immediate substitution | one SSRI for another
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| what exception is there, and why | should stop fluoxetine for a few days to a week before introducing another SSRI, because of its long half life
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