Table 1.

Clinical and pharmacological characteristics of newer antidepressants.

Name	Class	Indication	Half-Life Hours	Dose mg/day	Route	PK Drug-Drug Interactions	Gene-Drug Interactions	Molecular Targets	Clinical Utility	Common AEs
Vilazodone	SPARI	Adult MDD	25	40	Oral	Concurrent use of CYP3A4 substrates, Inhibitors, or Inducers	CYP3A4 polymorphisms are clinically insignificant	-SERT, inhibitor -5HT1A receptor partial agonist	Compared to SSRIs: -Lower sexual dysfunction -Lesser initial anxiety -Lesser emotional blunting -Faster onset of efficacy, -Lower risk for long-term loss or decrease in efficacy	Frequent GI upset, dizziness, insomnia, fatigue, jitteriness
Levomilnacipran	SNRI	Adult MDD & Fibromyalgia	12	40–120	Oral	Concurrent use of CYP3A4 substrates, Inhibitors, or Inducers	CYP3A4 polymorphisms are clinically insignificant	-NET inhibition more than SET inhibition	Activating, less emotional and cognitive blunting, improves fatigue, low weight gain,	Nausea, headache, dry mouth, hyperhidrosis, tachycardia, hypertension
Vortioxetine	MMA	Adult MDD	57	5–20	Oral	Concurrent use of CYP2D6 substrates or Inhibitors	CYP2D6 polymorphisms are clinically significant	-5-HT3, 5HT7, & 5HT1D receptor antagonist, -5-HT1B receptor partial agonist -5-HT1A receptor agonist -SERT inhibitor	Minimal sleep effects, improved psychomotor speed, fewer discontinuation symptoms	Less GI upset, minimal sexual dysfunction
Esketamine	GRA	-Adult TRD -Augmentation treatment	7–12	-Day 1—56 mg -Wk. 1–8—56 or 84 mg twice/wk. -Wk. 9—56 or 84 mg once or twice/wk.	Intranasal spray	Concurrent use of CYP2A6, CYP2B6, CYP2C9, or CYP3A4 substrates, inhibitors, or inducers	Polymorphisms in CYP2B6 can be clinically significant	-NMDA receptor antagonism, -mu-opioid receptor blockade	Rapid antidepressant and antisuicidal effects	Dissociation, dizziness, nausea, sleepiness, vertigo, headache, dysgeusia, numbness, anxiety, flushing, hypertension
Dextromethorphan (DXM) -Bupropion (BUP)	GRA	Adult MDD	22	DXM = 45 mg plus BUP = 105 mg. 1 tab once/day × 3 days, then -1 tab two times a day	Oral	Concurrent use of CYP2D6 substrates or inhibtors for DXM Concurrent use of CYP2B6, substrates, inhibitors, or inducers for BUP	Polymorphisms in CYP2D6 and CYP2B6 are clinically significant	-DXM - NMDA receptor antagonism -BUP – NE and DA reuptake pump blockade	Rapid antidepressant effects	Anxiety, psychosis, hypomania, confusion, decreased concentration, seizures, hypertension
Brexanolone	GPAM	PPD	9	90 mcg/kg/h	60-h IV infusion	Concurrent use of substrate inhibitors, or inducers of phase II enzymes ketoreductase, Glucuronyl transferase, and sulfatase	Polymorphisms of ketoreductase, glucuronyl transferase, and sulfatase)	-PAM for GABA-A receptors	Rapid antidepressant effects	Sedation, injection site discomfort/erythema, pain/rash, dizziness, flushing, oropharyngeal pain, increased TSH, loss of or altered consciousness