Depression

Question 1

TCA side effects

Answer 1

antihistaminic, anticholinergic, antiadrenergic, hypotension, dry mouth, constipation, lethal in OD, long QT even at therapeutic levels

Question 2

Secondary TCAs

Answer 2

often metabolites of tertiary amines. primarily block NOREPINEPHRINE. Side effects less severe than tertiary
Ex: desipramine, nortriptyline

Question 3

Tertiary TCAs

Answer 3

tertiary amine side chains, prone to cross react with other receptors -> more side effects. But act predominantly on SEROTONIN receptors.
Ex: clomipramine, amitriptyline, doxepin, imipramine (CADI)

Question 4

MAOI mechanism of action

Answer 4

IRREVERSIBLY bind MAO, preventing inactivation of biogenic amines (NE, Dopa, 5HT). Must wait 2 weeks for wash-out period before switching between SSRI and MAOI (5 weeks with fluoxetine).

Question 5

MAOI side effects

Answer 5

Orthostatic hypotension (most common), weight gain, dry mouth, sedation, sexual dysfunction, sleep disturbance. HYPERTENSIVE CRISIS with tyramine-rich foods or sympathomimetics - avoid pseudophed, etc. SEROTONIN SYNDROME with sympathomimetics.

Question 6

Woman with depression comes to the ED for abdominal pain, diarrhea, sweating, irritability, and delirium. She in tachycardic, hypertensive, and has myoclonus (muscle twitch).

Answer 6

Serotonin syndrome. Can lead to hyperpyrexia, CV shock, death.

Question 7

SSRI side effects

Answer 7

30% exhibit sexual dysfunction. Anxiety, restlessness, nervousness, insomnia. Or, fatigue, sedation, dzziness. Very little risk of cardiotoxicity in OD. Discontinuation syndrome with withdrawal (agitation, nausea, diequilibrium, dysphoria).

Question 8

Woman with depression presents with agitation, nausea, disequilibrium, dysphoria. She stopped her paroxetine a week ago.

Answer 8

Discontinuations syndrome - give SSRI.

Question 9

Paroxetine (paxil)

Answer 9

• No build-up (short half-life, no active metabolites)
• Give at night because sedating
• 2D6 inhibition!! Can increase TCA level!!!
• Sedating, wt gain, anticholinergic SE
• Discontinuation syndrome

Question 10

Sertraline (zoloft)

Answer 10

• Low build-up (short half-life, few metab)
• Less sedating than paroxetine
• Slight 2D6 inhibition
• Requires a full stomach
• GI side effects!!

Question 11

Fluoxetine (prozac)

Answer 11

• Longest half-life
• Initially activating
• Build up
• P450 interactions
• GOOD for noncompliance, low E, to prevent DC syndrome
• NOT good for mania, anxiety, insomnia, hepatic disease, multiple meds

Question 12

Citalopram (celexa)

Answer 12

• Intermediate half-life
• Low P450 interaction
• Dose-dep QT PROLONGATION (no more than 40mg daily)
• Sedating (antagonizes H1 receptor)
• GI side effects (less than sertraline)

Question 13

Escitalopram (lexapro)

Answer 13

• More effective than citalopram in acute response and remission
• Still intermediate half-life, low P450 interaction, dose-dep QT prolongation
• Nausea, headache

Question 14

Fluvoxamine (luvox)

Answer 14

• Shortest half-life
• Analgesic properties
• Inhibits 1A2 and 2C19!!!
• GI, HA, sedation, weakness

Question 15

SNRIs

Answer 15

• Inhibits both 5HT and NE reuptake (like TCAs) but no antiH, antiA, or antiC side effects

Question 16

Venlafaxine (effexor)

Answer 16

• Good for geriatrics short half-life, fast renal clearance, no build up, almost no P450)
• Dose-dep diastolic HTN, DC syndrome, QT prolong, nausea with IR tabs, sexual dysfunction

Question 17

Desvenlafaxine (pristig)

Answer 17

• Like venlafaxine, good for geriatrics (short half-life, fast renal clearance, no build up, almost no P450)
• Good for neuropathic pain, depression, anxiety
• Dose-dep cholesterol, dose-dep HTN, GI distress

Question 18

Duloxetine (cymbalta)

Answer 18

• Good for physical symptoms, less BP effect than venlafaxine
• 2D6 and 1A2 inhibitor
• Cannot break capsule
• Higher drop out rate

Question 19

Mirtazapine (Remeron)

Answer 19

• 5HT2 and 5HT3 receptor antagonist
• Augments SSRIs
• Increases appetite and sleep in AIDS (antiH effects)
• SE: cholesterol, weight gain, sedating -> 30mg activating

Question 20

Buproprion (Wellbutrin)

Answer 20

• MoA inhibits Dopa and NE reuptake
• No wt gain, sexual dysfx, sedation, cardiac, low mania, second-line ADHD agent
• SE: avoid in TBI/bulimia/anorexia due to SEIZURES; anxiogenic, abuse potential (psychotic sx at high doses)

Question 21

Woman with depression, no h/o mania. Hyperphagia, psychomotor retardation, hypersomnolence. What drug?

Answer 21

• Less sedating SSRI: Fluoxetine, Sertraline, or Citalopram
• Bupropion
• Bad: paroxetine (sedating), mirtazapine (sedation, weight gain)
• SNRI big gun unnecessary, TCA too many SE

Question 22

55M with DM, HTN, neuropathy, anxiety, h/o suicide attempt. Has taken paroxetine, sertraline, bupropion. Treatment?

Answer 22

• Since he has not achieved remission with two SSRIs or a novel agent, try a dual reuptake inhibitor like SNRI. Not venlafaxine d/t HTN. Not TCAs bc (despite neuropathy and depression), bad SE and lethal OD.
• Try duloxetine (neuropathy, depression, anxiety). But potential drug-drug interactions (2D6 and 1A2 inhibitor)