More Related Content
Similar to TRANYLCYPROMINE.pptx
Similar to TRANYLCYPROMINE.pptx (20)
Recently uploaded
Recently uploaded (20)
TRANYLCYPROMINE.pptx
- 1. Role of Tranylcypromine in the treatment of resistant depression
- 2. HIT once upon a time
- 5. What is common thing in the list • Clozapine • Blonanserin • Penfluridol • Nortriptyline • Pimozide • Tianeptine • Opipramol
- 6. Which was the first antidepressant discovered ?
- 9. Classification of MAO-I MAO-I MAO-A Non - selective Selective MAO-B
- 10. • Nonselective MAO-A/ MAO-B – Hydrazine (antidepressant) • Isocarboxazid • Phenelzine • Hydracarbazine – Non-hydrazines • Tranylcypromine • Selective MAO-A inhibitors – Moclobemide • Selective MAO-B inhibitors – Selegiline Classification of MAO-I
- 11. MAO-A, MAO-B MAO-A MAO-B Acts on NE, 5HT DA, tyramine Phenylethylamine and trace amines DA, tyramine Mnemonic A for All Beer for DTs Location Brain Brain Gut, liver Platelets Placenta, skin Lymphocytes
- 13. TRANYLCYPROMINE (TCP) – First clinical trial in 1959 – Introduced as an antidepressant in 1962 – Temporarily withdrawn in 1964 because of the cheese reaction; later reintroduced – Available in USA and Europe (Parnate)
- 14. • Meta-analysis shows that – TCP>placebo (5 studies) – TCP=other ADs (18 studies) – TCP=other ADs in resistant depression (4 studies) • Also – TCP effective in atypical depression (many studies) – TCP effective in bipolar depression with ? low risk of switch – May improve negative s/s in schizophenia TRANYLCYPROMINE (TCP)
- 15. Comparison with Nortriptyline Eur Neuropsychopharmacol. 2017 Aug;27(8):714-731.
- 16. Comparison with other antidepressants Eur Neuropsychopharmacol. 2017 Aug;27(8):714-731.
- 17. ADVERSE EFFECTS • Commonest AEs are adrenergic AEs – Dry mouth – Insomnia • Also common: dizziness/postural hypotension, transient palpitations after dosing, sedation • No increase in appetite, weight • Few/no sexual AEs • No dependence potential • Need to taper and stop
- 19. MAOIs and Indian food • Case reports of tyramine reaction with Indian food--- ZERO
- 20. What about cheddar cheese? • 100 gm---about 22 mg tyramine
- 22. Fermented foods: Eat with care
- 23. Cheeses to avoid
- 24. Pizza
- 25. • Pizza with plain mozzarella cheese---OK • Veggie pizza----OK • Pepperoni (fresh) pizza---OK • Cottage cheese - OK Schulman and Walker (1999)
- 26. Beverages: Good news • Bottled beer: one or two 330 mL bottles per day • White wine (preferred): one or two glasses (100 to 120 mL) per day • Red wine: Better to avoid May cause benign headache
- 27. Food • Fresh chicken, meat, fish, beef---no problem! Aged, dried, fermented, smoked, pickled No banana, Avocados, ripe fruits, yogurt
- 28. Far-Eastern Tyramine-containing soya-related items: • Fermented soya bean • Fermented tofu • Tofu kept in the fridge for a few days • Chilli soyabean paste • Soyabean paste • Miso Wing and Chen (1997). PMID: 9169972
- 29. Use with caution or avoid in • Patients with unstable medical comorbidity • Severe CVS disorders • High BP • Liver disease • Severe renal disease • Patients who may not adhere to diet/drug guidelines • Pregnancy and lactation
- 30. TCP: PHARMACOKINETICS • Half-life, 2 h – So trough levels during treatment are nearly 0. – So washout in <1 day. – So monoamine release, monoamine reuptake mechanisms may be unimportant. • Steady-state is unnecessary because MAO inhibition is irreversible. • Distributed in all organ systems.
- 31. • Metabolism by ? TCP: PHARMACOKINETICS
- 32. Implications of irreversibility • For duration of action – For dietary restrictions – For drug interactions – For change of treatment • New enzyme must be synthesized – First the MAOI must be washed out – Then, it takes 1-2 weeks for new MAO to be synthesized and to reach adequate levels
- 33. TCP: DRUG INTERACTIONS • Sumatriptan, rizatriptan, almotriptan are metabolized by MAO-A – Almotriptan is also metabolized by CYP enzymes • Use lower doses in patients receiving TCP. • Avoid concomitant other antidepressants • Nicotine use • Benzodiazepines, Valproate
- 34. DOSING • Start at 30 mg/day in divided doses. • If no response, increase by 10 mg/day every 1- 3 weeks. • Usual dose, 40-60 mg/day • Maximum dose, 60 mg/day in divided doses. – Divided dosing reduces AEs such as dizziness, postural hypotension, etc.
Editor's Notes
- Adverse effects of tranylcypromine (n = 63 patients) in a placebo (n = 59) and nortriptyline (n = 61) controlled, randomized, double-blind, short-term trial with intensive study of adverse effects and including mild-to-moderate severity (significant differences of tranylcypromine vs. nortriptyline for dizziness (p < 0.05), insomnia (p < 0.01) and overexcitement (p < 0.05) and tranylcypromine vs. placebo for dizziness, insomnia and dry mouth (p < 0.01); 4.5 adverse effects per patient for tranylcypromine, 4.8 nortriptyline and 2.3 placebo (nonsignificant))
- Adverse effects of TCAs (n = 128 patients), SSRIs (n = 30), MAO inhibitors (n = 36, 61% tranylcypromine) and atypical antidepressants (n = 14, 71% bupropion) in an open, non-interventional, long-term trial with intensive study of adverse effects and including mild to moderate severity (mean number of adverse effects per visit = 2.6), comparison tranylcypromine vs. SSRIs: sedation and headache (p < 0.01 each), dry mouth, anxiety, nausea and sweating (p < 0.001 each), 61.5%, 16.4%, 37.4% and 17.5% of patients with treatment of TCAs, SSRIs, tranylcypromine and bupropion, respectively, received lithium augmentation