Overview

BZD	??? ??, TDI ? GABA, Cl channel? ???? GABA ?? ?
Buspirone	????? ?? ??????, ??, ??? X, BZD ??? ??? ? ??.
Propranolol	?????? TOC

Comparison

Class	Block	Benefits & indications	Analgesic	Sleep	Weight	Adverse effects	Contraindications
TCA	S, NE, α1, M		O	O		??? ???? ??.
SSRIs	S			X
MAOI	MAO (S, E, NE)	MDD+atypical feature, or TCA?			Gain	Hypertensive crisis, serotonin syndrome
SNRI	S, NE	Duloxetine	O			A/N/V
		Venlafaxine				A/N/V, HTN
NDRI	NE, D	Bupropion – stimulant		O	Loss	Tachycardia, insomnia	Seizure disorders, bulimia/anorexia nervosa.
NaSSA	S(5-HT2, 3), H1	Mirtazapine –		O	Gain
SARI	S, α1	Nefazodone Trazodone		O

Augmentation strategies
When a patient has experienced a partial response to an adequate trial of monotherapy.
Adding aripiprazole or bupropion

<Strategy>

• SSRI: assessment of response in 6-12 weeks after initial treatment
  • If response is minimal or significant S/E occurred -> cross-tapering
  • Lethargy, difficult concentrating, weight gain -> bupropion (NDRI)
  • Insomnia -> trazodone (SARI)

TCA

NE, 5-HT? amine NT ?? – ?? ?, REM ?? ?? – ? ??.
Imipramine, nortriptyline, desipramine? ???? ??.

Indication
???? imipramine (S/E: Torsa de pointes)
???? clomipramine (S/E: anti cholinergic)
????, ??? ?

• Anticholinergic (M)
  • Tachycardia, urinary retention, dry mouth
  • Tertiary > Secondary
  • Confusion, hallucination in the elderly – nortriptyline is better.
• Antihistamine (H1)
  • ???, ??
• ?1-blocking effect
  • ??? ???
• Presynaptic (NE & 5-HT) neurotransmitter reuptake
  • Antidepressant & anxiolytic effects, seizures, tremors
• Blockade of cardiac fast Na+ channels
  • Prolonged PR/QT interval, arrhythmias (eg, ventricular tachycardia, fibrillation)
  • Widened QRS interval (like Ic group)
• Convulsion, Coma

3? ??: imipramine(?????), amitriptyline(????)
2? ??: desipramine, nortriptyline
New: Clomipramine, trazodone(???)

Management of intoxication

• Tintinalli

SSRI

Indication

MDD ??? anxiety, sexual disorders ??? ????.
REM ??? ????? ??? X, (?????) ????? ?

Characteristics

• ?? ????? 4-8? ??. ??? ???? ??? mania? ??.
• ?? ??? ??? washout period? ????. Fluoxetine? 5?, ???? 2?.
• Stimulating effect
  • SSRI-induced activation of presynaptic 5HT1A ? inhibition of serotonin release and a net ? in serotonin levels before the full effects of the medication.
  • Temporary dose reduction with the goal of improving tolerability.
• Treatment-resistant
  • Failure to respond to at least 2 adequate antidepressant trials
• Continuation-phase treatment
  • Achieved remission after acute-phase treatment with sertraline.
  • To decrease the risk of depressive relapse, recommend continuing antidepressant treatment for an additional 6 months in patients with remitted single-episode, unipolar major depression. The dose should not be reduced.
• Maintenance-phase treatment
  • Maintenance for 1-3 years is appropriate for patient with a high risk of recurrence (eg, >2 episodes, persistent residual depressive symptoms)
• Complete remission
  • Maintained at the end of the continuation phase, the antidepressant can then be tapered gradually and discontinued.

• Fluoxetine
  • ‘???’ ?? ? ???
  • ??? ?? SSRI? ?? ?? ?? ??, ????? ?? ???? ???, ??? ???? ??? ???? ??? ??? ??. ?? ?? ?? ? ?? ??? ?? ?????
• Sertraline
• Paroxetine
  • ?? ??????, ??? ?? ??.
• Fluvoxamine
• Citalopram
  • ?? SSRI ??? ?? ????? ??????? ?? ?? ???. ?? ???? ???????? ???? ??? ? ?? ???? ???.
• Escitalopram
  • ?????? ???? ????? ????? s-????? ??? ????. ??????? ????? ?????? ? ???? ? ?? ???. ????? ???(?????)? ??? ?? ?? ???? ?? ?? ? ????. ???, ???? ?? ?? ???? ???? ?? ????[3] ???? NICE??? ???? 1? ???? ?? ???? ??.
• Vilazodone
  • Inhibits 5-HT reuptake, 5-HT1A receptor partial agonist.
• Vortioxetine
  • Inhibits 5-HT reuptake, 5-HT1A receptor agonist, 5-HT3 antagonist.

Side effects

Sexual dysfunction
In > 50%, ????/????(+sildenafil or bupropion)
Weight gain, headaches, GI complaints, ??

Serotonin syndrome

• Etiology
  • Associated with high doses, MAOI/SSRI combo, MAOI/synthetic narcotic combination.
  • Or serotonergic medication combination with non-antidepressant with MAOI activity (e.g., linezolid)

• Clinical features
  • Similar symptoms with NMS, but onset <1 day, hyper-reflexia, clonus (not rigidity)
  • General restlessness, sweating, insomnia, nausea, diarrhea, cramps, delirium, myoclonus.
• Treatment
  • Removal of the causative agent, stopping the SSRI, and administering cyproheptadine (5-HT2 receptor antagonist)
• Prevention
  • Most antidepressants should be discontinued 2 weeks before beginning an MAOI.
  • The SSRI fluoxetine is an exception d/t its long half-life and must be stopped 5 weeks before initiating an MAOI.

Withdrawal

• Discontinuation syndrome; ???, NV, ??, ??? ? ? 3? ? ?? ??

MAO

Clinical use

• Major depressive disorder(MDD)
  • Treatment-resistant MDD
  • MDD with atypical features
• Anxiety
• Parkinson disease (selegiline)

Phenelzine, selegiline

Adverse effects

• D/t CNS stimulation
• Hypertensive crisis
  • Problem foods: aged cheese, dried fish, sauerkraut, sausage, chocolate, avocados, red wine.
  • Safe foods: cottage cheese, some wine (mostly white)
• Serotonin syndrome
  • CIx with SSRIs, TCAs, St.John?s wort, meperidine, dextromethorphan
  • ?? serotonergic drug? ?????? 2?? ?????.

SNRI

Duloxetine

???? ???? ??, ??? ???? ??. A/N/V
Also indicated for fibromyalgia

Venlafaxine

??? ??? A/N/V ????, ?????

Side effects

• Hypertension
  • Dose-dependent. BP should be monitored regularly
  • Especially significant at doses >300mg daily, in which the incidence may be >10%
• Stimulant effects, blurry vision (common)

NDRI – bupropion

Mechanism

Relatively weak inhibitor of the re-uptake of NE and D
Does not inhibit the re-uptake of serotonin
Stimulates 5-HT1A receptors
?? ?????? 1-2? ??

Activating antidepressant; could increase anxiety and insomnia.

Toxicity

? Stimulant effects
? Tachycardia, insomnia
? Headache, seizures in anorexic/bulimic patients
? Barbiturate, BZD?? ?? alcohol? interact ??.

NaSSA – mirtazapine

Mechanism

? Alpha 2 antagonist
? Stimulates NE and 5-HT release
? Blocks 5-HT2, 5-HT3, H1

???? – ??? ??? ???
?????, ??????

SARIs – nefazodone and trazodone

5-HT2, ?1, H1 blocker
?? ??? ??.

Side effects

Almost no anticholinergic adverse effects.
Priapism -> used to treat erectile dysfunction.
Can cause sexual dysfunction like SSRI.
Sedation is common.