Serotonin Sitcom SSRIs, SNRIs, Cyproheptadine

3.1 – “Ser “Serotonin otonin sitcom”: SSSRIs, SRIs, SNRIs, cyprohe cyproheptadine ptadine • Major depressive disorder (MDD) has 17% lifetime prevalence in US & is one of the major causes of disability in the developed world. While mechanisms are not clear, is thought to be related to a deficiency of CNS serotonin, NE, dopamine. There is a clear role for increasing available serotonin to address disease (serotonin smiley faces; 5H-TV). SSRIs, SNRIs are some of the most prescribed meds in the US. • Clinical indications: o MDD (comedy/tragedy masks): Acute episodes may last 6-14 months if untreated. About ⅓ of patients will achieve remission on treatment with a new med. Treatment is continued for at least 6 mos., and may be used for maintenance therapy. SIGECAPS for diagnosis criteria. o long-term treatment of anxiety disorders are the second most common indication, Benzos provide much more rapid anxiolytic effects, but SSRI/SNRIs at least as effective for maintenance therapy, without many of the Adverse effects. Include many of the major anxiety disorders, including ▪ GAD (anxious coworker). ▪ Panic disorder (same deal with the benzos) (Scream-saver) ▪ PTSD (dog tags). Usually require therapy as well ▪ OCD (obsessively organized desk) o Note that neither are for the management of acute symptoms of anything (depression, anxiety, pain). On average, 2 mos. before onset of efficacy (2-month calendar). SSRIs (selective serotonin reuptake inhibitors) (Express Trips) • Include fluoxetine (Fly out poster), paroxetine (parrot air poster), sertraline (desert airline poster), citalopram (Celexa®) (The City poster) • Inhibit presynaptic serotonin reuptake transporter (SERT) →↑ concentration at the synapse (Smiley face pad not kept in drawer) • Increased availability of monoamines at the synapse responsible for many of the beneficial and detrimental effects. • Clinical indications where SSRIs are preferred: o Bulimia (binge snack drawer with lady bending over). Not useful for anorexia. o Social anxiety disorder (shy guy) • adverse effects o Rare: SIADH → hyponatremia (guy sweating and spilling water while replacing bottle) o Diminished sexual function & interest in up to 50% of patients (girl rejecting guy’s advances) o Weight gain (rotund dude) o Drowsiness (sleeping on the job) o Rapid cessation can cause discontinuation syndrome, particularly with drugs with a short half-life (e.g. paroxetine or sertraline) ▪ Presents with flu-like symptoms (dizziness, fatigue, headache, nausea) 1-2 days after stopping meds (“Out with the Flu” note) ▪ Avoid by tapering o Serotonin syndrome (excessive smiley-face post-it notes in corner office). Potentially fatal. ▪ Presentation: Hyperthermia, hypertension, hyperreflexia & clonus (flushed angry boss tapping foot) ▪ Can look like the neuroleptic malignant syndrome precipitated by dopamine blocking agents (e.g. antipsychotics). Differentiation: Hyperreflexia & & clonus (NMS characterized by hyporeflexia & rigidity) ▪ Can occur with OD of a single drug or combos with other serotonergic drugs (e.g. TCAs, MAO-Is) (mousetraps & trike in corner office) ▪ Management: discontinuation of all serotonergic agents, stabilization of vital signs, ± serotonin antagonist (e.g. cyproheptadine, a 5HT-2 blocker) (“Silly Pranks Prohibited” for cyproheptadine) SNRIs (serotonin-norepinephrine reuptake inhibitors) (Compass rose on wall map) • Include Venlafaxine (fax), duloxetine (dual copier, scanner), sibutramine, milnacipran, levomilnacipran, and other derivatives • Inhibit presynaptic reuptake of norepinephrine & 5-HT, increasing availability of monoamines at the synapse. • Clinical indications where SNRIs are preferred: o Drugs that have 5-HT & norepinephrine reuptake blocking are helpful in pain management, particularly of neuropathic pain (frayed wire). Examples include diabetic neuropathy (venlafaxine, duloxetine) (hand stuck in Diasweeties vending machine). o Duloxetine has been found effective in many other pain conditions including lower back pain (guy bent in really uncomfortable position), osteoarthritis, & fibromyalgia (fiber bars) • Adverse effects o ↑noradrenergic transmission →HTN, ↑HR, CNS activation (insomnia, agitation) (angry coworker) o Discontinuation syndrome o Serotonin syndrome