Table 1.

Enantiomer-specific behavioral effects of (S)-ketamine and (R)-ketamine.

			(S)-ketamine	(R)-ketamine
Prophylactic Effects	Preclinical	Despair-like behaviors (FST, TST)	[57]a,b	[57]a,b [61–63]
		Anhedonic-like behaviors (SPT)	none	[63]
		Other depression-like behaviors	[57]a,b	[57]a,b (fear response) [69] (cognitive impairment)
	Clinical	No enantiomer-specific clinical research prophylactic antidepressant effects
Immediate	Preclinical	Despair-like behaviors (FST, TST)	[76,79,80,92,93,100]	[76,92,93,100] [80] a,*
		Anhedonic-like behaviors (SPT)	[76,77,92,100] [80]a [93]*	[76,77,80,92,93,100] [80] a,*
		Other depression-like behaviors	[77] (self-grooming) [93]* (self-grooming)	[77,93]
	Clinical	Depression	FDA approval for intranasal esketamine, [102–106,108,109]	[111] [110,112]*
Sustained	Preclinical	Despair-like behaviors (FST, TST)	[118,119] [117]*	[117–120]
		Anhedonic-like behaviors (SPT)	[77,116,119]	[77,119,120]
		Other depression-like behaviors	[116] (OFT) [122]* (cognitive deficits)	[122] (cognitive deficits)
	Clinical	Depression	FDA approval for intranasal esketamine, [18,104,105,108,125–128] [123,124]*	No clinical research on the sustained antidepressant effects of (R)-ketamine

^aenantiomer-specific metabolites used (hydroxynorketamine or norketamine)

^bsex-dependent results

^*negative results

In studies [76,77,100,119], (R)-ketamine performed better than (S)-ketamine on behavioral measures.

FDA: US Food and Drug Administration; FST: Forced Swim Test; OFT: Open Field Test; SPT: Sucrose Preference Test; TST: Tail Suspension Test