Know this Antidepressant Agents/ Manic

Question 1

Lithium – Adverse Effects

Answer 1

Related to plasma concentration - narrow therapeutic index**

Fine tremor, GI upset, muscle weakness
Decrease in thyroid function (3-30%); possible weight gain
Polyuria, polydipsia (anti-ADH action) (12%)

Moderate toxicity: Confusion, sedation, lethargy, twitching**

Severe toxicity: Seizures, stupor, coma**

Drug Interaction

Diuretics can decrease renal clearance by 25%***

Increase in lithium levels also seen with NSAIDs

Question 2

Lithium – Pharmacokinetics

Answer 2

Competes with Na+ for reabsorption - Food-Drug Interactions possible

Increase in dietary Na+ –> ↓ Li+ Cp

Na+ restriction –> ↑ Li+ Cp

Question 3

Lithium – Mechanism of Action

Answer 3

Also interference with Gs and Gi (adenylyl cyclase) can lead to side effects

In thyroid –> anti-TSH –> hypothyroidism

In kidney –> anti-ADH –> polyuria-polydipsia

May affect gene regulation for growth factors and neuronal plasticity

Question 4

Lithium – Mechanism of Action

Answer 4

Slow onset (10-21 d) – necessary to accumulate Li+ in cell

Effects greatest on cells with highest level of activity (use-dependence)

Enhance 5HT action and/or diminish NE and DA effect – most favored MOA:

Interference with PIP recycling (Gq protein: IP3 and DAG)

Question 5

Weight Gain

Answer 5

More: TCADs – mirtazapine – paroxetine

Less: fluoxetine – sertraline – venlafaxine

Least: bupropion

Question 6

Sexual Dysfunction

Answer 6

Less with bupropion and mirtazapine

Question 7

Anticholinergic side effects

Answer 7

Concern with TCADs (

Question 8

Arrhythmias

Answer 8

Concern with TCADs (avoid if cardiac disease - ↑ QT)

Question 9

Orthostatic hypotension

Answer 9

Trazodone - TCADs - MAOIs*

Question 10

Hypertension

Answer 10

Venlafaxine-Duloxetine

Question 11

Withdrawal syndrome (flu-like or neurologic symptoms)

Answer 11

Paroxetine and venlafaxine most likely

Fluoxetine least likely

Question 12

Most agents: ______________-

Answer 12

Additive CNS depressant effects when used with other sedatives

Question 13

SSRIs + MAOIs –> serotonin syndrome

Answer 13

Hyperthermia, muscle rigidity, myoclonus

Rapid changes in mental status (confusion / agitation) and vital signs (hypertension and tachycardia)

Also SSRIs + opioids: analgesics [meperidine-tramadol] and antitussive [ dextromethorphan]**

Question 14

SSRI Common Side Effects Acute

Answer 14

Insomnia

Somnolence

Diarrhea

Nausea

Question 15

SSRI Common Side Effects Delayed onset

Answer 15

Sexual dysfunction

Weight gain

Cognitive blunting

Under-appreciated by physicians, but most concerning to patients

Question 16

Summary of Pharmacotherapy for Depression

Answer 16

Generic SSRIs are usually first line

Fluoxetine

Question 17

Summary of Pharmacotherapy for Depression

Equal efficacy

Less weight gain and sexual side effects

Not effective in anxious depression

Answer 17

Bupropion

Question 18

SNRIs (esp. Venlafaxine)

Answer 18

May be more effective

Side effects > SSRIs

HTN, withdrawal symptoms,