TCA; Tertiary amine

Mechanism: Inhibit uptake of NE and 5-HT; also block muscarinic, adrenergic and histamine receptors

Pharmacokinetics: amitriptyline (elavil) and imipramine (tofranil) are broken down to active metabolites (secondary amines)

Uses: Depression, panic disorder, fibromyalgia, enuresis, ADHD

Effects: CNS = drowsiness and sedation, impairment of memory and cognition, analgesia; PNS = cardiac depression and increased irritability (torsade de pointes and other arrhythmias) and A1 blockade (postural hypotension, dizziness)

Side effects: decrease seizure threshold, SIADH, sexual dysfunction, tolerance, muscle aches/malaise if stopped rapidly; 

Safe in pregnancy

OD: dangerous, depressed may be suicidal, cardiac (torsade de pointes), hypotension, seizures.

Drug interactions: w/MAOI = serotonin syndrome; Fluoxetine and other SSRIs compete for metabolism, TCAs can reach toxic levels 

Other drugs: 

Imipramine (Tofranil^®) - Standard of efficacy in depression; enuresis

 Trimipramine (Surmontil^®): Doxepine (Sinequan^®)

Clomipramine (Anafranil^®)- only for OCD, works like SSRI

TCA; Secondary amine

Mechanism: Inhibit uptake of NE and 5-HT; also block muscarinic, adrenergic and histamine receptors

Uses: Depression, panic disorder, fibromyalgia, enuresis, ADHD

Pharmacokinetics: active metabolites

Effects: CNS = drowsiness and sedation, impairment of memory and cognition, analgesia; PNS = cardiac depression and increased irritability (torsade de pointes and other arrhythmias) and A1 blockade (postural hypotension, dizziness); Nortiptyline = least cardiac effects

Side effects: decrease seizure threshold, SIADH, sexual dysfunction, tolerance, muscle aches/malaise if stopped rapidly; 

Safe in pregnancy

OD: dangerous, depressed may be suicidal, cardiac (torsade de pointes), hypotension, seizures.

Drug interactions: w/MAOI = serotonin syndrome; Fluoxetine and other SSRIs compete for metabolism, TCAs can reach toxic levels

Other drugs: Desipramine (Norpramin^®) - worst for cardiac depression; Protriptyline (Vivactil^®)

MAOI: Antidepressant

Mechanism: MAOIs irreversibly inhibit MAO which breaks down circulating catecholamines; MAO-A breaks down NE and 5-HT, MAO-B breaks down DA;

Pharmacokinetics: effect lasts 1-3 weeks since MAO inhibition is irreversible

Drug of last choice; question will say "pt has been treated for depression for a long time and is given this now"

Foods to avoid: red wine, beer, aged cheese and prepared meats; alcohol, bean curd, aged cheese, smoked, fermented picled herring, spoiled meat and fish, ginseng, protein extract, sausage, bologna, pepperoni and salami sauerkraut, soups, yeat, brewere's or extracts; 

Other drugs: Tranylcypromine (Parnate^®)

Side effects: HTN crisis

SSRI

Fluoxetine may cause insomnia so take in AM

Use: DOC depression, Panic disorder, OCD, bulimia, alcoholism, children and teenagers

Pharmacokinetics: bound to plasma proteins, long lasting = fluoxetine T1/2 = 2-3 days, norfluoxetine (active metabolite)= 7-9 days

Side effects: GI, weight loss, CNS stim (fluoxetine), Sexual dysfunction, SIADH -> hyponatremia, photosensitivity

Drug interactions: Big for drug interactions; Metabolized by CYP-450, inhibits CYP3A4 and CYP2D6; MAOIS, St. Johns Wort or amphetamines = serotonin syndrome; TCAs increased; Warfarin increased; phenytoin or carbamazepin increased; B-blockers increased; opioid active metabolite conversion DECREASED; Tramadol = increased seizures; tamoxifen = decreased metabolism of pro drug to active compound (CA drug)

Other Drugs: Fluvoxamine (Luvox^®) 

Paroxetine (Paxil^®) - OCD and social anxiety too, may cause sedation (take at night); contraindicated in pregnancy due to cardiac effects

Sertraline (Zoloft^®) - may cause insomnia; like fluoxetine but less effect, and less sexual and hepatic side effects

Citalopram (Celexa^®)Escitalopram (Lexapro^®): Faster than SSRIs, little effect on CYPs

SNRI

Uses: Depression

Mechanism: inhibits 5-HT and NE reuptake

Adverse effects: increased BP, SIADH, GI, dizziness, nervousnes, abnormal ejaculation/orgasm, asthenia

Other drugs: Desvenlafaxine (Pritiq^®) 

Duloxetine (Cymbalta^®)- better in depression than SSRIs; may be hepatotoxic, contraindicated for liver disease pts; contraindicated in third trimester of pregnancy

Milnacipran (Savella) - fibromyalgia

Levomilnacipran (Fetzima)- Major depressive disorder

Antidepressant

Uses: antidepressant, childhood ADHD, recovery from drug of EtOH abuse or weight loss (decreases cravings)

Mechanism: inhibits reuptake of DA and NE

Side effects: CNS stim, psychois, headache, nausea, weight loss, NOT sexual dysfunction, seizures at high doses

Contraindications: pts with seizures or on drugs that lower seizure threshold (TCAs or antipsychotics)

Other Drugs: Mirtazapine (Remeron^®)

Atomoxetine (Strattera)- Inhibit NE reuptake only; ADHD (non-stimulant)

Maprotiline (Ludiomil^®)

Amoxapine (Asendin^®)- depression, schizophrenia, DA antagnist, may cause parkinson syndrom

Mechanism: Blocks presynaptic A2 which normally ihibits release of NE and 5-HT; increases release of NE and 5-HT; 

block 5-HT2A and 5-HT3 receptors, eliminating normal side effects of SSRIs (anxiety, insomnia, nausea, sex dysfunction)

Blocks histamine receptors causing drowsiness, advantage in insomnia

Antidepressant

Uses: Depression, sleep aid, pain management

Side effects: sedation, dizziness, hypotension, nausea, priapism (rare, but you see priapism, ALWAYS TRAZADONE)

Mechanism: partial 5-HT1A agonist and may block 5-HT2A receptor

Antidepressant

Drug interactions: MAOI, SSRI, TCA, L-dopa or selegiline (serotonin syndrome); may prolong general anesthetics

decreases effectiveness of digoxin, warfarin, theophylline, cyclosporine, antiretroviral protease inhibitors and oral contraceptives

Mechanism: UNKNOWN but may block reuptake of NE, 5HT and maybe DA