Table I.

Clinical trials evaluating pharmacological compounds targeting negative symptoms in schizophrenia.

Neurotransmitter system	Study, year	Agent	Mechanism	Duration (weeks)	No. of subjects	Negative symptom instrument	Findings	(Refs.)
Dopamine system	Buchanan et al, 1998	Clozapine	D2, 5-HT2A antagonist	10 + extension 1 year	75	SANS	No benefit PNS	(10)
	Liang and Yu, 2017	Amisulpride	Partial agonist D2/D3, antagonist 5-HT7	8	26	PANSS	Efficient for NS/SNS	(14)
	Potkin et al, 2013	Asenapine	D2, 5HT2A α2 adrenoceptors antagonist	25 + additional 52	502	PANSS, NSA-16	Efficient for NS	(21)
	Fleischhacker et al, 2019	Cariprazine	D2/D3, 5-HT1A partial agonist	26	227	PANSS	Efficient for PNS	(22)
Glutamate system	Umbricht et al, 2014	Bitopertin	Glycine reuptake inhibitor	8	323	PANSS	Efficient for NS	(28)
	Mazinani et al, 2017	Memantine	NMDA receptor antagonist	12	46	PANSS	Efficient for PNS	(30)
Inflammatory pathway	Laan et al, 2010	Aspirin	Anti-inflammatory drug	36	70	PANSS	No benefit for PNS	(36)
	Zang et al, 2018	Minocyclin	Tetracycline	12	75	PANSS	Efficient for NS	(44)
	Sepehrmanesh et al, 2018	NAC	Anti-inflammatory and glutamatergic excitotoxicity	12	84	PANSS	Efficient for PNS	(42)
Serotonin system	Davidson et al, 2017	MIN-101	5-HT2A antagonist	12	244	PANSS, BNSS	Efficient for PNS	(49)
	Samadi et al, 2017	Ondansetron	5-HT3 antagonist	12	38	PANSS	Efficient for PNS	(47)
Cholinergic system	Conley et al, 2009	Galantamine	Acetylcholinesterase inhibitor	12	84	SANS	Efficient for alogia	(60)
Hormones	Modabbernia et al, 2013	Oxytocin		8	37	PANSS	No benefit PNS	(66)

D2, dopamine D2 receptors; 5-HT, 5 hydroxytryptamine receptors; NMDA, N-methyl-D-aspartate; NAC, N-acetylcysteine. PANSS, Positive and Negative Syndrome Scale. NSA-16, Negative Symptoms Assessment Scale-16 items. SANS, Scale for the Assessment of Negative Symptoms. BNSS, Brief Negative Symptom Scale. PNS, primary negative symptoms. NS, negative symptoms. SNS, secondary negative symptoms.