Antidepressants & Mood Stabilizers

Question 1

phenelzine (Nardil)

tranylcypromine (Parnate)

Answer 1

Monoamine oxidase inhibitors (MAOIs)
Non-selective MAO-A and MAO-B inhibitors–irreversible

MOA: inhibit monoamine oxidase enzymes
Reduced catabolsim of synaptic monoamines–>increased synaptic 5-HT and NE
MAO-A: targets tyramine, NE, 5HT, DA
MAO-B: targets mainly DA

Use: last line treatment for depression (no response to SSRIs or SNRIs)
Rarely used due to toxicity, lethal dose with food and drug interactions

Adverse effects: orthostatic hypotension, weight gain, sexual effects, discontinuation syndrome if used after SSRIs

Avoid foods with tyramine (wine and cheese): enhance NE effects–>vasoconstriction and increased BP–>stroke or myocardial infarction

Question 2

selegiline (Deprenyl)

Answer 2

Monoamine oxidase inhibitors (MAOIs)
MAO-B inhibitor–irreversible (non-selective at high dose)

MOA: inhibit monoamine oxidase enzymes
Reduced catabolsim of synaptic monoamines–>increased synaptic 5-HT and NE
MAO-A: targets tyramine, NE, 5HT, DA
MAO-B: targets mainly DA

Use: last line treatment for depression (no response to SSRIs or SNRIs)
Used for tx of Parkinson’s disease–>increase DA levels
Rarely used due to toxicity, lethal dose with food and drug interactions

Adverse effects: orthostatic hypotension, weight gain, sexual effects, discontinuation syndrome if used after SSRIs

Avoid foods with tyramine (wine and cheese): enhance NE effects–>vasoconstriction and increased BP–>stroke or myocardial infarction

Question 3

moclobemide (Aurorix)

Answer 3

Monoamine oxidase inhibitors (MAOIs)
MAO-A competitive inhibitor–reversible

MOA: inhibit monoamine oxidase enzymes
Reduced catabolsim of synaptic monoamines–>increased synaptic 5-HT and NE
MAO-A: targets tyramine, NE, 5HT, DA
MAO-B: targets mainly DA

Use: last line treatment for depression (no response to SSRIs or SNRIs)
Not available in US

Adverse effects: orthostatic hypotension, weight gain, sexual effects, discontinuation syndrome if used after SSRIs

Avoid foods with tyramine (wine and cheese): enhance NE effects–>vasoconstriction and increased BP–>stroke or myocardial infarction

Question 4

imipramine
desipramine
amitriptyline

Answer 4

Tricyclics (TCAs)

MOA: inhibit 5HT transporter (SERT) and NE transporter (NET)

Use: 2nd or 3rd line tx for MDD (if no response to SSRIs or SNRIs), chronic pain, enuresis, insomnia
Declined in used due to severe side effects

Metabolism: metabolized by liver via CYP2D6 (serotonin syndrome if taken with fluoxetine)

Adverse effects: anticholinergic (dry mouth, constipation, blurred vision, urinary retention, confusion), antihistamine (sedation, weight gain), anti-alpha-adrenergic (orthostatic hypotension), CNS toxicity (delirium, seizure, tremor), sexual dysfunction (aorgasmia, loss of libido), cardiac toxicity (lethal cardiac arrhythmia)

Overdose: 3 C’s–convulsions, coma, cardiac arrhythmias

Drug interactions: MAOIs, SSRIs

Question 5

fluoxetine (Prozac)
sertraline (Zoloft)
paroxetine (Paxil)
citalopram (Celexa) 
escitalopram (Lexapro)
fluvoxamine (Luvox)

Answer 5

Selective serotonin reuptake inhibitors (SSRIs)

MAO: inhibit 5HT transporter (SERT)
Little affinity for histamine, ACh, and adrenergic receptors

Use: depression, anxiety, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder, panic disorders, pre-menstrual dysphoric disorder, bulimia

Adverse effects: GI disturbances, diminished sexual function, headaches, sleep alterations
Discontinuation syndrome–1 or 2 days after sudden discontinuation of drug and persisting for 1 week or longer
Serotonin syndrome–fluoxetine has to be discontinued >4 wks before MAOIs can be used; discontinue for at least 2 wks prior to switching meds

Fluoxetine and paroxetine are potent CYP2D6 inhibitors–>drug interactions

Question 6

venlafaxine (Effexor)

duloxetine (Cymbalta)

Answer 6

Atypical antidepressant
Serotonin-norepinephrine reuptake inhibitors (SNRIs)

MOA: inhibit SERT and NET
Block reuptake of 5HT and NE
Not much affinity for other receptors

Use: MDD, anxiety, stress urinary incontinence, vasomotor symptoms of menopause, chronic pain (fibromyalgia)

Adverse effects: sertonergic (GI, sexual dysfunction) and NE effect (increased BP and HR, CNS activation–>insomnia, anxiety, agitation)

Question 7

trazodone (Desyrel)

Answer 7

Atypical antidepressant
5-HT2 antagonist

MOA: inhibit 5HT2 receptors

Use: insomnia without tolerance, dependence, depression, or anxiety

Bound to protein and readily metabolized

Adverse effects: sedation, GI disturbances

Question 8

bupropion (Wellbutrin, Zyban)

Answer 8

Atypical antidepressant
Resembles amphetamines

MOA: blocks DA and NE reuptake and increases presynaptic release of catecholamines

Uses: depression, smoking cessation

Adverse effects: agitation, insomnia, anorexia

Question 9

mirtazapine (Remeron)

Answer 9

Atypical antidepressant

MOA:
Blocks synaptic alpha-2 adrenergic autoreceptors
Increases synaptic release of 5HT and NE
Antagonist of 5HT3 and 5HT2 receptors

Use: MDD pts unresponsive to other Tx, anti-emetic agent

Question 10

lithium

Answer 10

Treatment of Bipolar disorder

MOA:
Reduction of NE release
Inhibit 5HT1a/1b autoreceptors
Reduce synaptic glutamate by enhancing reuptake
Inhibit glycogen synthase kinase-3 (GSK-3)–>increased activation of beta-catenin

Use: maintenance tx of bipolar disorder

Depressive phase: require antidepressant

Adverse effects: tremor, flu-like symptoms, seizures, edema, wight gain, GI upset, hypothyroidism, nephrogenic insipidus (blocks vasopressin/ADH response), skin reactions

Drug interactions: thiazide and loop diuretics diminish Li clearance–>Li toxicity ( sweating, dilutional hypoatremia)

Question 11

valproic acid

carbamazepine

Answer 11

Bipolar disorder tx

Treatment of acute mania
Anticonvulsants and antipsychotics

Used alone or in combination with lithium