Antidepressants

Question 1

Biogenic amine hypothesis of mood disorders

Answer 1

1. Patients treated with reserpine developed DEPRESSION
2. Thought that biogenic amines were depleted due to reserpine
   Ultimately: depression = too little CNS NE and/or 5-HT

Question 2

Antidepressant drugs tend to block

Answer 2

reupatke of both NE and 5HT, but to VARYING degrees

Question 3

Pharm effect of antidepressants happens in; clinical improvement happens in

Answer 3

minutes to hours; weeks or months (6-8 wks);

Question 4

For very severe depression, how are meds viewed relative to placebo?

Answer 4

Thought to be BENEFICIAL for patients with severe depression

Question 5

Tranylcypromine (Parnate)

Answer 5

Class: MAOI
Mech: Irreversibly inhibit both MAOa (oxidizes mainly NE, 5HT, tyramine) and MAOb (oxidizes DA, phenylethylamine)
Thera: Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
Important SE’s: Hypertensive crisis (with tyramine-rich foods) since liver MAO is inhibited and lose first-pass metabolism; serotonin syndrome (MAOI + SSRI) with hyperthermia, muscle rigidity, myoclonus, rapid changes in mental status and vital signs; agitation (rare), delerium –> seizures
Other SE’s: Anticholinergic, orthostatic hypotension, sexual dysfunction, weight gain, sedation

Question 6

Phenelzine (Nardil)

Answer 6

Class: MAOI
Mech: Irreversibly inhibit both MAOa and MAOb
Thera: Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
Important SE’s: Hypertensive crisis (with tyramine-rich foods); serotonin syndrome (MAOI + SSRI); agitation (rare), delerium –> seizures
Other SE’s: Anticholinergic, orthostatic hypotension, sexual dysfunction, weight gain, sedation

Question 7

Desipramine (Norpramin)

Answer 7

Class: Tricyclic
Mech: Block reuptake of NE or 5-HT at varying potencies and selectivity; use N-demethylation followed by P450 oxidation and then glucuronide conjugation; also variably block muscarinic, a-adrenergic, dopamine, and histamine receptors
Thera: Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
Important SE’s: Sympathomimetic with tremor and insomnia (cardiac arrhythmias and conduction defects, especially at OD)
Other SE’s: Antimuscarinic like blurred vision and constipation, orthostatic hypotension, sedation (additive with alcohol), seizures
Misc: Not very safe; rarely used anymore; high protein binding and relatively high lipid solubility and thus a LARGE Vd; active metabolite of imipramine; half life 22 hr

Question 8

Imipramine (Tofranil)

Answer 8

Same as desipramine, but makes active metabolite that is desipramine; half life of 12 hr

Question 9

Amitriptyline (Elavil)

Answer 9

Same as desipramine, but makes active metabolite nortriptyline; half life of 21 hr

Question 10

Nortriptyline (Pamelor)

Answer 10

Half life 31 hr; same as amitriptyline but active metabolite of amitriptyline

Question 11

Fluoxetine (Prozac)

Answer 11

Class: SSRI
Mech: Inhibit reuptake of 5-HT (and NE to lesser extent)
Thera: Depression, anxiety (GAD, panic, OCD), PTSD, chronic pain, enuresis, bulimia, alcoholism; pre-menstrual dystrophic disorder
Important SE’s: Serotonin syndrom (with MAOIs)
Other SE’s: Fewer than tricyclics with no seizures or cardiac arrhythmia; mostly nausea, decreased sexual function
Misc: Potent P450 inhibitor; forms active metabolite (norfluoxetine)

Question 12

Paroxetine (Paxil)

Answer 12

Just that there is no thera for pre-menstrual dystrophic disorder; potent P450 inhibitor

Question 13

Sertraline (Zoloft)

Answer 13

no thera for pre-menstrual dystrophic disorder

Question 14

Escitalopram (Lexapro)

Answer 14

no thera for pre-menstrual dystrophic disorder

Question 15

Citalopram (Celexa)

Answer 15

no thera for pre-menstrual dystrophic disorder

Question 16

Duloxetine (Cymbalta)

Answer 16

Class: SNRI

Question 17

Venlafaxine (Effexor)

Answer 17

Class: SNRI

Question 18

Bupropion (Wellbutrin)

Answer 18

Class: Atypical
Mech: Blocks DA (notable selectivity for DAT) and NE reuptake
Thera: Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism; maintain nicotine abstinence in quitting smokers
Important SE’s: Lowers seizure threshold

Question 19

Mirtazapine (Remeron)

Answer 19

Class: Atypical
Mech: 5HT2a antagonists; also inhibit 5HT reuptake
Thera: Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism

Question 20

Lithium

Answer 20

Mech: Unknown; lithium depletes secondary messengers IP3 and DAG, important in a-adrenergic and muscarinic-cholinergic transmission
Thera: Anti-manic/mood-stabilizing (bipolar); long-term cluster headache prevention
Important SE’s: If elevated levels: neurotoxicity, cardiac toxicity, renal dysfunction
Other SE’s: Drowsiness, weight gain, tremor, polydipsia, polyuria
Misc: Nausea and vomiting early sign of lithium OD; indomethacin and Na-depleting diuretics should be avoided (increase [Li])

Question 21

Depressive phase of mania often requires what?

Answer 21

concurrent use of antidepressant, usually maoi, with lithium/carbamazepine/valproate (TCA’s might precipitate mania);

Question 22

LI onset can be slow, so use

Answer 22

benzos; if severe, add benzos or ANTIPSYCHOTIC drugs (pine, done, aripiprazole)