BM Pharm: Major Depressive Disorder

What are the PHQ2 questions and what score is concerning?

“Over the past two weeks, have you felt down, depressed, or hopeless?”

“Over the past two weeks, have you felt little pleasure or interest in doing things?”

With a score of 2 or greater, you should do a more in-depth screening.

What are two non-pharmacological Tx for major depressive disorder

Psychotherapy and electroconvulsive therapy (ECT)

ECT is extreme, reserve for pts w/ multiple suicide attempts, pregnancy, treatment resistive MDD, etc.

SSRI indications, S.E., half life

Indications: initial Tx of unipolar depression

S.E.: sexual dysfunction, nervousness, insomnia, emotional blunting, minimal anticholinergic activity, low toxicity in overdose (low potential for abuse

Longest half life is fluoxetine, shortest is paroxetine. The shorter the half life, the bigger a problem it is to miss a dose.

SSRI examples

Citalopram, Escitalopram (Lexapro, S-enantiomer of citalopram), Fluoxetine (Prozac), Fluvoxamine, Paroxetine, Sertraline (Zoloft)

SNRI indications, S.E., half life

Indications: may be first line, more important as second line if SSRIs fail

S.E.: venlafaxine and desvenlafaxine can cause HTN (avoid with vasoconstrictors), more GI effects than SSRIs, nausea is common

Half life: longest are duloxetine and levomilnacipran (12 hours), shortest is venlafaxine (5 hours)

SNRI examples

Venlafaxine, Desvenlafaxine (S enantiomer of venlafaxine), Duloxetine, Milnacipran, Levomilnacipran

What are the classes of “atypical” antidepressants?

NDRIs and NaSSA

Bupropion (Wellbutrin) MOA, S.E.

MOA: norepinephrine and dopamine reuptake inhibitor (NDRI)

S.E.: less sexual dysfunction and weight gain, lowers seizure threshold (C.I. in those with seizure risk)

Mirtazapine/Remeron MOA, S.E.

MOA: noradrenergic and specific serotonergic antidepressant (NaSSA)

S.E.: dry mouth, sedation, weight gain, less sexual dysfunction

SARI MOA, S.E., example, partial agonist example

MOA: serotonin antagonist and reuptake inhibitor that blocks 5HT2a receptors which allows more 5HT to interact at 5HT1a (anti-depressant activity) sites

S.E.: Sedation, priapism, serotonin syndrome

Example: Trazodone/Oleptro

Partial agonist: Vilazodone/Viibryd

Tricyclic antidepressants MOA, S.E., other uses

MOA: 1st gen antidepressants, serotonin and NE reuptake inhibitors. Also blocks muscarinic cholinergic receptors (“dirty slutty receptors”)

S.E.: sedation (blockage of histamine receptors), orthostatic HoTN, lowers seizure threshold, toxicity in overdose (heart block and QT prolongation, death, avoid in suicidal patients)

Other uses: anxiety disorders, chronic neuropathic pain, migraine prevention

Tricyclic antidepressant examples

Amitriptyline, Nortriptyline, Desipramine, Imipramine, Doxepin

MAO inhibitors MOA, S.E.,

MOA: 1st gen antidepressant, irreversibly blocks monoamine oxidase → blocks breakdown of 5HT, NE, and dopamine

S.E.: HoTN, diziness, dry mouth, HA, myoclonic jerks, pts require low tyramine diet to avoid hypertensive crisis

NOT 1st line due to risks

MAO examples

Phenelzine, Selegiline, Tranylcypromine

Steps for treatment resistant depression

-Second gen (atypical) antipsychotic

-Lithium

-Add another antidepressant from another class

-Thyroid hormone

What can occur if MAO are mixed with any of the following: TCA, NE releasers, a1-agonists, L-dopa, tyramine

Hypertensive crisis

(avoid foods like aged cheese, marmite, sauerkraut → releases NE which cannot be destroyed by MAO)

An SSRI plus any of the following: meperidine, dextramethorphan (in nyquil), TCA will cause…

Serotonin syndrome

MAO plus SSRI or TCA will cause what

Serotonin syndrome

Serotonin syndrome Sx and Tx

Sx: rapid onset of autonomic stimulation (hyperthermia, tachycardia, diaphoresis), neuromuscular excitation, altered mental status

Tx: sedation with benzodiazepines, then give serotonin antagonist (cyproheptaine)

SSRIs safe in pregnancy

Sertraline/Zoloft, Citalopram, Escitalopram/Lexapro

antidepressants safe for the elderly, what to avoid

SSRIs safe, avoid TCAs due to anticholinergic activity, cardiovascular and sedative properties.

Antidepressants safe for children

SSRIs specifically Fluoxetine/Prozac, assess suicide risk first