Antidepressants and Mood Stabilizers

Question 1

All antidepressant agents are effective, yet may take how long to demonstrate beneficial effects?

This depends on… (2)

Answer 1

3-8+ wks.

Depends on disease severity/duration and dosage of selected agent.

Question 2

If a patient does not respond to a given antidepressant after an 8-week trial on an adequate dose, what is a reasonable action?

If there is partial response, what can be done?

Answer 2

Another antidepressant with a different MOA.

Adding another drug to the initail agent (including ‘antipsychotics’).

Question 3

Mono-therapy with antidepressants is only indicated for…

Answer 3

Unipolar depression - not depressive phase of bipolar disorder.

Question 4

All antidepressants are associated with which side-effects?

What is recommended when prescribing?

Answer 4

Withdrawal syndrome:
Flu-like symptoms
Insomnia
Nausea
Imbalance
Sensory disturbances
Hyperarousal

Slow titration downward (deprescribing).

Question 5

What are other (non-mental health) indications for antidepressants and which drug is used? (4)

Answer 5

Nicotine withdrawal (Bupropion)

Enuresis/bedwetting (Imipramine)

Diabetic peripheral neuropathy, fibromyalgia and chronic MSK pain (Duloxetine)

Stress incontinence (Duloxetine)

Question 6

SSRI MOA

Answer 6

Selectively inhibits pre-synaptic reuptake of serotonin (via SERT), which results in enhanced, prolonged serotonergic neurotransmission to post-synaptic receptors.

Question 7

What are the major side-effects of SSRIs?

Answer 7

Acute withdrawal reactions**

Serotonin syndrome (increased risk when other agents given in addition): sweating, hyperreflexia, akathisia/myoclonus, shivering/tremors

Suicidality (highest risk in younger ages)

Question 8

Which SSRI is has the greatest risk of drug-drug interaction?

Which one have the least? (2)

Answer 8

Greatest risk = Fluoxetine

Least risk = Vortioxetine and Escitalopram

Question 9

MOA of SNRIs (including TCAs):

In general for the TCAs, tertiary amine TCAs inhibit:
Secondary amines inhibit:

Answer 9

Selectively inhibit the pre-synaptic reuptake of serotonin (via SERT) and NE (via NET).

3-amine: inhibit both NE/5-HT relatively equally
2-amine: inhibit NE > 5-HT

Question 10

Which other receptors can TCAs block and which side-effects can ensue? (3)

Answer 10

Histamine (H1): CNS

• sedation, fatigue
• dizziness, seizures

Muscarinic (cholinergic): anti-cholinergic

• dry mouth
• urinary retention, constipation
• blurred vision

alpha-1: CV

• tachycardia
• orthostatic hypotension
• dysrhythmias

Question 11

What are signs of toxic ingestion of TCAs?

Answer 11

3 Cs

• coma
• cardiotoxicity (conduction abnormalities): ‘quinidine-like’ effect
• convulsions

Question 12

What are the major side-effects of non-TCA SNRIs?

Answer 12

Relatively similar to SSRIs, but less risk of of sexual dysfunction.

Question 13

What is the MOA of Trazodone and Nefazodone?

What else can they cause?

Answer 13

(SARA): Acts like SSRIs and also block post-synaptic a1 receptors on NE neurons and post-synaptic 5HT2 receptors.

Cause blockade of H1 - sedation.

Question 14

What is the MOA of Mirtazapine?

What else can it cause?

Answer 14

(SARA): Blocks pre-synaptic a2 receptors on NE and 5HT neurons and blocks post-synaptic 5HT2/3 receptors.

Causes blockade of H1 - sedation.
*no SERT/NET activity

Question 15

What is the major side-effect(s) of Trazodone and Mirtazapine?

Answer 15

Trazodone: CNS sedation, orthostatic hypotension

Mirtazapine: CNS sedation, weight gain

Question 16

What is the MOA of NDRIs?

How do they release effects?

Answer 16

Selectively inhibits pre-synaptic reuptake of NE (via (NET) and DA (via DAT). Results in prolonged stimulation by these NTs.

VMAT2 transporter

Question 17

What are the side-effects of NDRIs? (3)

Answer 17

Seizures*

Agitation/insomnia (simulating)
-HTN, tachy, tremors

Weight loss

Question 18

What is the MOA of MAOIs?

All oral agents are considered…

All agents are non-selective, except:

What is unique of Tranylcypromine?

Answer 18

Inhibition of MAO (A/B subtypes) increases levels of monoamines in neuronal vesicles and increase amounts of NE, 5-HT and DA release.

All oral agents are irreversible MAOIs.

All are non-selective (A/B subtypes), except Selegine (B-selective, but non-selective at high doses).

It is a stimulant analog.

Question 19

What are the major side-effects of MAOIs?

What are the major drug interactions? What must be done?

What are the risks if this does ensue?

Answer 19

Orthostatic hypotension, sexual dysfunction, weight gain, insomnia/agitation/nervousness.

Interactions with 5HT/NE affecting drugs (anti-hypertensives, amphetamines, SSRIs/TCAs/SNRIs).
*2-week washout period! 5-weeks for fluoxetine.

Risk of serotonin syndrome and HTN crisis.

Question 20

HTN crisis is the major risk for which class?

How does it occur molecularly?

Which drug has a dose-dependent relationship w/ this effect?

Answer 20

MAOIs

Increased tyrmaine can induce significant catecholamine release and HTN crisis.

Selegine.

Question 21

What is the MOA of Esketamine?

Where is it indicated?

What is the route of administration? What must be done after?

Answer 21

It is an NDMA-receptor (glutamate) antagonist.

Treatment-resistant depression in conjunction w/ ongoing anti-depressant therapy.

Nasal administration and patient observed for 2-hrs. post-dose due to concern of BP and cognitive impairment.

Question 22

What 2 drugs are considered “miscellaneous anti-depressants”?

Answer 22

Esketamine

Brexanolone

Question 23

What is the MOA of Brexanolone?

What is the indication?

Answer 23

A GABA-A-receptor positive allosteric modulator (identical to alloprogesterone).

Post-partum depression.

Question 24

What are the 3 major actions of Lithium?

Answer 24

Brain structure - neuroprotective/neuroproliferative.

NT modulation - inhibits DA neurotransmission, downregulates NMDA receptor, promotes GABAergic neurtransmission.

Intracellular changes - inhibits IPPase and IMPase, inhibits PKC, MARCKS, and GSK-3.

Question 25

How is Li+ treated by the kidneys?

It competes with…

Answer 25

Similarly to Na+/K+

Na+ for kidney reabsorption

Question 26

What is the major side-effect of Li+?

Answer 26

Resistance to ADH resulting in polyuria and polydipsia.

-nephrogenic DI

Question 27

What are 3 other drug classes that may interact with Lithium?

Answer 27

Diuretics (esp. Thiazides)

ACEIs (esp. Lisinopril)

NSAIDs

Question 28

Which drug is know to be a “narrow therapeutic agent”?

What range should be limited to normally?
In refractory cases?
In the elderly?

Answer 28

Li+

Normally: 0.6-1.2 mEq/L
Refractory cases: up to 1.5 mEq/L
Elderly: 0.4-0.8 mEq/L

Question 29

What are the indications for Lithium? (2)

What is an off-label use of Li+?

Answer 29

Acute and maintenance treatment of mania/bipolar disorder I.

Augmentation in unipolar depressive in patients w/ inadequate response to anti-depressive therapy.

Reduced risk of suicide.

Question 30

What is the indication of Valproic acid/Divalproex? Dose?

What is the indication of Lamotrigine?

What is the indication of Carbamazepine?

Answer 30

Valproic acid/Divalproex: Acute bipolar I. 50-125 mcg/mL.

Lamotrigine: Maintenance of bipolar disorder I and II.

Carbamazepine: Acute and maintenance treatment of acute mania and mixed episodes (bipolar I).

Question 31

What is the major CYP450 inducer?

Answer 31

Carbamazepine (anti-seizure agent)