SAD is not a distinct disorder but is listed as a specifier of MDD or bipolar. DSM IV Criteria: A Regular temporal relationship between the onset of majordepressive episodes and a particular time of the year (unrelated to obvious season-related psychological stressors)B Full remission (or change from depression to mania or hypomania) also occurs at a characteristic time of the year.
#’s in ( ) are the reference #.
Cardiac effects: hypertension (early and transient), tachycardia, orthostasis and hypotension, and arrhythmias.ECG changes:prolonged QRS, QT, and PR intervals.
Mirtazapine was more likely to cause weight gain or increased appetite and somnolence than SSRIs but less likely to cause nausea or vomiting and sexual dysfunction. This agent has no appreciable effects on SERT & NET. Better response compared to SRI SNRI were noted at 2 weeks.This drug is also known as Noradrenergic & Serotonin Specific Antidepressant (NaSSA). Mechanism includes blocking all of the receptors shown.
Adverse reactions: Asthenia, sweating, N/V, headache, diarrhea, constipation, anorexia, insomnia, somnolence, dry mouth, dizziness, nervousness, anxiety, abnormal ejaculation/orgasm, impotence in men. Listing of side effects from Wyeth is available here: http://en.wikipedia.org/wiki/VenlafaxineHalf-life of some bioactive metabolites is 10 hours.
Symptoms described as "brain zaps", "brain shocks", "brain shivers", "brain pulse-waves", "head shocks", or "cranial zings“. Very gradual discontinuation of dosing may be beneficial.
Newer agents include moclobemide (not yet approved in US).
Isoniazid (I so niazid): http://www.howjsay.com/index.php?word=isoniazid&submit=Submit
400 mg of tyramine may be needed to increase blood pressure in normal individuals but may be as low as 10 mg in individuals taking an irreversible/nonselective MAO-I (phenelzine).
Some international foods may be problematic (Marmite yeast extract, shrimp)
5-HT2A antagonists can prevent the effects of serotonin toxicity.
The intern was responsible for 40 patients at the same time! Meperidine has weak SRI effects.
Bupropion is a weak inhibitor of NET & DAT but metabolites are biologically active (weakly too). This may be good as too much DAT binding could lead to abuse. Dry mouth noted in 15% versus 7% receiving placebo. Half-life is 10 hours but longer for active metabolites.
Many depressed patients have other psychiatric and medical conditions.
Light-Therapy Meta-Analysis • Effect Size = (mean Experimental – meanControl)/ Standard Deviation) – 0.20: small – 0.50: medium – 0.80: large <- 0.84Golden et al. (1995). American Journal of Psychiatry, 162(4), 656-662.
Tricyclic Antidepressants (TCA)• Developed from antipsychotic drugs (1960s)• MOA: NET/SERT inhibition; anticholinergic• Gold standard for efficacy• Side effects: sedation• Concern with overdose
MAO-I & “cheese” effect • Old view: avoid cheeses, alcohol, etc. • New View: avoid aged cheese, spoiled meats, – Typical American diet does not contain clinically meaningful levels of tyramine (10 mg)Stahl, S. (2008). Essential Psychopharmacology, p. 587-589.
MAO-I & “cheese” effect • New View: avoid aged cheese (Cheshire, Danish bleu)McCabe-Sellers et al. (2006). J of Food Composition & Analysis, 19, S58-S65.
Serotonin Syndrome • Cluster of autonomic, motor & mental status changes resulting from excess 5-HT (5-HT2A) Agents MAO-Is TCA SSRIs opiate analgesics cough medicines (OTC) antibiotics triptans anti-nausea herbal products abused drugsBoyer & Shannon (2005). New England Journal of Medicine, 352, 1112-1120.
Case of Libby Zion• ER visit for fever, agitation, shaking movements 1965 - 1984• Interns administered meperidine, later restraints• Hyperthermia & cardiac arrest• Intern hours/week = 70
Bupropion • MOA: ?, NET & DAT inhibitor • Adverse Effects: dry mouth, high dose seizures • Efficacy: – monotherapy ≈ SRI – augmentation: better than monotherapy • Other: APA recommends as a first-line therapy for moderate depressionMoreira, R. (2011). Clinical Drug Investigation, 31(S1), 5-17.
Questions• If you had a family member with MDD, based on the STAR*D results, consider: – How good (efficacious) is the gold standard? – Is there an advantage of augmentation versus switching? – Were any other findings unexpected?
MDD: Endocrine Component?Stahl (2008). Essential Psychopharmacology, p. 616-616.
SRIs & Pregnancy• Pregnancy is a high-risk period for depression• SRIs may carry slight risks for the fetus – persistent pulmonary hypertension – low birth weight• Untreated MDD does cause fetal risk
Summary • Best ----------------------------------WorstTolerability SRI > SNRI > TCA > MAO-IEfficacy TCA > MAO-I > SNRI > SRI
-----------Stahl (2008). Essential Psychopharmaology, p. 519. -----------------
Saint John’s wort (Hypericum perforatum)• MOA: ?, SERT• Adverse Effects: photosensitivity• Concern: quality control• Efficacy: mild to moderate depression
MDD Trial ----------------------------------------------------------------------------- Quit 27%-29%Davidson et al. (2002). Journal of the American Medical Association, 287, 1807-1814.
Saint John’s wort • MOA: ?, SERT • Adverse Effects: photosensitivity • Other: ↑CYP3A4 • Efficacy: “The available evidence suggests that the hypericum extracts tested in the included trials: a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants.”Linde et al. (2009). Cochrane Reviews, DOI: 10.1002/14651858.CD000448.pub3
Self-Test• The only antidepressant whose mechanism of action includes inhibiting NET & DAT is: – A) hypericum perforatum – B) fluvoxamine – C) mirtazapine – D) bupropion – E) clomipramine
Sep. 5, 2019
Nov. 14, 2016
Sep. 20, 2014
This PPT is part of 2 of 2 lectures given to second year pharmacy students in a pharmacology & toxicology class.