MAJOR DEPRESSIVE DISORDER Tricyclic Antidepressants (TCA)
TERTIARY Amines (↑Antichol & sedative s/e) Amitriptyline (Elavil) 30-300 mg/day Imipramide (Tofranil) 25-300 mg/day Doxepine (Sinequan) 50-300 mg/day Trimipramine (Surmontil) 25-250 mg/day Clomipramine (Anafranil) Dosage Range 50-300 mg/day NOTES Adverse Effects – Anticholinergic (muscarinic blockade): dry mouth, constipation, urinary retention, blurred vision, tachycardia, cognitive impairment. Alpha-1 receptor block: orthostatic hypoTN, sedation, sexual dysfn Histamine receptor block: sedation, wt gain Fast Na channel blockade in myocardium: conduction problems, arrhythmias (DON’T use in pts w/ heart problems @ high concentrations!) Drug Interactions Decreased TCA efx: (Hepatic enzyme INDUCERS) -Barbiturates, Phenytoin, carbamazepine, smoking, chronic alcohol, cimetidine Increased TCA efx: (Hepatic enzyme INHIBITORS) -SSRI, MAOI, L-dopa, oral contraceptives, acute alcohol Decreased antihypertensive effects of: clonidine, methyldopa, guanethidine SECONDARYAmines (more potent on mg-mg basis) 30-100 mg/day Nortriptyline (Pamelor) 25-300 mg/day Desipramine (Norpramin) 50-600 mg/day Protriptyline (Vivactil) 15-60 mg/day Amoxapine (Asendin) Least amt of sedation (Alpha 1, H1 blockade) Least amt of orthostasis (Alpha 1 blockade) Potentates anticoagulative effects of WARFARIN Increased vasopressin effects of direct sympathomimetics Serotonin syndrome potential: MAOI + TCA or SSRI + TCA Preferred for: Pregnancy, insomniacs, severe depression, migraine, Parkinson’s patient (Anticholinergic efx) , pain/fibromyalgia. Caution with: Elderly (worsens Alzheimer’s), daytime sedation, dementia, cardiac abnormalities, suicidal patients, bipolar pts, overweight pts (↑ carbohydrate cravings) NOTE: TCA Dose range is from 25-300mg & due to long t½, dosing is Q.D.
Used for psychosis and depression
STUDY GUIDES are FYI only & cannot be solely relied on for exam purposes... study at your own risk.
It was noted in class that you should focus on SSRI & TCA D/I & ADE
Page 1 of 4
MAJOR DEPRESSIVE DISORDER
SSRI Fluoxetine (Prozac) Dosage Range 20-80 mg/day t ½ 1-6days (4-16d for norfluoxetine) 50-200 mg/day t ½ - 24-100 hrs 20-60 mg/day t ½ - 30hrs 10-30 mg/day t ½ - 30 hrs 10-50 mg/day t ½ 10-24 hrs 50-300 mg/day t ½ - 16 hrs Notes Inhibits: 2D6 (MAJOR) 2C9, 3A4 (LESS) Adverse effects GI: N,V,D Neurological: akathisia, h/a, EPS Other: Anxiety, sexual dysfunction, insomnia, risk of bleeding, and of course… SEROTONIN SYNDROME Preferred for: elderly, bipolar pts, cardiac pts, overweight pts, severe depression Caution with: pts with sexual dysfunction, pts with HEPATIC OR RENAL DYSFUNCTION Note: All are equally efficacious – failure to one SSRI, doesn’t imply failure to another SSRI
Sertraline (Zoloft) Citalopram (Celexa) Escitalopram (Lexapro) Paroxetine (Paxil) Fluvoxamine (Luvox)
Slight 2C9, 2C19, & 2D6 inhibition
Slight 3A4 inhibition
NO enzyme inhibition! Inhibits: 2D6 (MAJOR) and (3A4-minor)
Major inhibition of 1A2 & 2C19
MAOI
Dosage Range
Pheneizine (Nardil) Tranylcypromine (Parnate)
45-90 mg/day t ½ – 1.5-4 hr 30-60 mg/day t ½ - 1.5-3 hr
NOTES MAOI’s are Irreversible & NON-selective!! Restrict to pts who don’t respond to other TX d/t potential S/E & necessity of dietary restrictions!! Adverse effects: Anticholinergic, wt gain, sexual dysfxn, insomnia, hypoTN, orthostasis. Interactions: Hypertensive crisis (noradrenergic syndrome) - observed with tyramine rich foods (wine, beer, aged cheeses, chocolate, etc - see slide for more foods) - observed with medications (narcotics, dopamine, decongestants, DM, selegeline, appetite suppress, zyvox, etc) - SX = N/V, diaphoresis (excessive sweating), occipital HA, HTN Serotonin Syndrome (Hyperpyrexic crisis) - may occur with two serotonergic agents used concomitantly - SX = (FLUSH) Flu like, Lightheadedness, Uneasiness/restlessness, Sleep & sensory disturbances, Headache Foods with high tyramine avoid and for 2 wks after dc MAOI Don’t use SSRI, TCA with an MAOI or w/n 14days of MAOI Allow > 14 days after d/c SSRI before starting MAOI Allow > 5 weeks after d/c of Fluoxetine (Paxil) before starting an MAOI Preferred for: atypical depression(mood reactivity, irritability, psychomotor retardation, leaden paralysis, hypersomnia, hyperphagia), F>M (2-3:1), refractory depression, panic attacks, bulimia, compliant pts, Caution in: not highly motivated/non compliant pts, insomniac/agitated pts.
Isocarboxazid (Marplan)
10-80 mg/day t ½ - 1.5-3 hr
STUDY GUIDES are FYI only & cannot be solely relied on for exam purposes... study at your own risk.
It was noted in class that you should focus on SSRI & TCA D/I & ADE
Page 2 of 4
MAJOR DEPRESSIVE DISORDER
OTHERS Dosing IR – MDD 450mg – 150mg TID SR – MDD 400mg; max 200mg BID Bupoprion (Wellbutrin) XL - MDD 450mg QD NE/DA reuptake inh NO 5HT activity SEIZURES (risk factors: head trauma, CNS tumor, seizure hx, bulimia, meds that lower seizure threshold) Adverse effects NE/DA reuptake inh. NO 5-HT activity – no serotonin syndrome Insomnia, nausea, anxiety, anorexia, agitation, Interactions Decreased effects: carbamazepine, phenytoin, Phenobarbital Increased effects: amantadine, levodopa, MAOI, ritonavir Bupoprion met. By CYP2B6 (orphenadrine, cyclophosphamide) Bupoprion inhibits CYP2D6 (recall AAP & SSRI’s are 2D6 as well!!) Caution HTN when used w nicotine patches.
Preferred for: pts who do not respond or tolerate SSRI addition, reverse SSRI induced sexual dysfxn. Smoking cessation, added to augment inadequate antidepressant effect. Caution in: pts with seizure disorder or seizure prone pts, agitation/insomniac, HEPATIC dysfunction, pts undergoing abrupt dc of alcohol or sedatives, pts on nicotine patches.
50-300 mg/day t ½ 6-11hr Trazodone (Desyrel) Selective 5HT reuptake inh 5HT Antagonist 150-300 mg/day t ½ 2-4hrs Nefazodone (Serzone) 5HT2 receptor antag with limited inh of 5HT and NE reuptake Selective activation of 5HT1 receptors – improvement in anxiety 15-45 mg/day t ½ 20-40hrs Antagonist of central alpha2 adrenergic autoreceptor.s Antagonist of both 5HT2 and 5HT3 receptors (Emesis control) Antagonist of H1 receptors
Priapism (Trazodone) Sedation Headache GI (N/V/C) Hepatotoxicity (Nefazodone) Asthenia Orthostasis Trazodone used as adjunct to other meds b/c it’s VERY sedative & can also cause orthostasis MAJOR 3A4 inhibition!! Intx with drugs that inh CYP2D6 > hepatic tox Preferred for: pts with depression related anxiety and agitation, insomniacs, pts with sexual dysfxn Caution in: noncompliant pts, pts with inhibition of CYP2D6(via SSRI) or lack of CYP2D6 (Nefazodone) **DON’T use in pts with hepatic dysfxn**
Mirtazapine (Remeron)
(just skim over) Sedation (H1) Dry mouth (H1) Dizziness Wt gain(H1) Constipation(H1) Elevations in TG, Cholesterol Transaminase elevations Agranulocytosis
Additive CNS effx with CNS depressants Potential intx with enzyme inducers and inhibitors
Preferred for: Mixed panic disorder/depression, MIXED anxiety/depression
Cautions in: pts with hepatic dysfn, overwt, cognitive slowing, motor retardation
STUDY GUIDES are FYI only & cannot be solely relied on for exam purposes... study at your own risk.
It was noted in class that you should focus on SSRI & TCA D/I & ADE
Page 3 of 4
MAJOR DEPRESSIVE DISORDER
IR75-375 mg/day in div. doses MDD 375 mg/day Venlafaxine (Effexor) XR – 75-225mg/day in div doses MDD 225 mg/day Inh of 5HT, NE and DA 5HT at lower doses NE at medium to high DA at high 40-60 mg/day t ½ 12hrs Duloxetine (Cymbalta) Balanced 5HT and NE reuptake inh (just skim over) Low doses: Nausea, agitation, sexual dysfxn, insomnia High doses: HTN, severe insomnia, sever agitation, h/a, mydriasis (excessive pupil dilation) Avoid w/ MAOI Venlafaxine is a weak inh of CYP2D6 – few intx *More rapid and superior response in severe depression* Preferred for: (med-high doses) melancholy, severely depressed w/ refractory depression; Elderly, hyposomniacs, psychomotor retardation, overwt; FDA appvd for SAD Cautions in: pts with agitation/anxiety, insomnia, HTN, sexual dysfxn.
(just skim over) NVCD, Dry mouth, Insomnia, Dizziness, Appetite decrease, fatigue, somnolence, sexual dysfn, diaphoresis, ↑LFT’s (may aggravate pre-existing liver dz) ↑BP
(skim over) Mod inh of CYP2D6
Preferred for: hypersomniacs, psychomotor retardation, overwt pts, FDA apprvd for diabetic peripheral neuropathic pain (DPNP) Caution in: pts with agitation/anxiety, insomniacs, HTN(but less risk than Venlafaxine), sexual dysfn, Don’t use w alcoholics or pt with evidence of liver dz.
MAOI PATCH 6mg without dietary restrictions Selegiline (Emsam) 9mg and 12mg with dietary restrictions(tyramine restrictions) t ½ 18-25 hrs (Selegiline and 3 metabolites: desmethylselegiline, amphetamine, and methamphetamine.) Selegiline ORAL - Low conc: inh MAOB – Parkinson’s Disease; High conc: also inh MAOA(depression and inc tyramine intx…diet) Transdermal – inhibits MAO A&B in CNS (Depression) & MAO B in periphery (↓tyramine intx) Transdermal PATCH (given Q.D.) – 1st one to treat MDD MAOB>MAOA inhibition MAOB – CNS MAOA – CNS+GI Adverse effects: skin irritation, orthostasis. Inh: 2D6, 3A4/5 Inh: 2D6, 3A4/5
Tx for Psychotic MDD SSRI + Antipsychotic TCA + Antipsychotic Venlafaxine + Antipsychotic Amoxapine (TCA) ECT; Others…?
**Antidepressants take several weeks of continuous use before sx improve; taking meds PRN won’t work! Meds usually taken for 6-12 months, won’t cause physical dependence**
STUDY GUIDES are FYI only & cannot be solely relied on for exam purposes... study at your own risk.
It was noted in class that you should focus on SSRI & TCA D/I & ADE
Page 4 of 4