Table 1:

Drugs with Potential to be Repurposed for AUD

Drug Name	Target	Original Indication	Novel Indication	Clinical Trial	Refs
Quetiapine (Seroquel)	Atypical Antipsychotic Antagonist: D1 and D2 dopamine receptors, alpha 1 and alpha 2 adrenoreceptors, and 5-HT1A and 5-HT2 serotonin receptors, histamine H1 receptor (and others)	Schizophrenia (Scz) Bipolar disorder (BD) Major depressive disorder (MDD) (along with an SSRI)	AUD and Bipolar; Sleep disturbances in abstinence; Schizophrenia and SUD; AUD and anxiet	NCT00457197 NCT00114686 NCT00223249 NCT00550394 NCT00434876 NCT00156715 NCT00352469	(Jensen et al. 2008; Schotte et al. 1996) (Litten et al. 2012)
Aripiprazole (Abilify)	Atypical antipsychotic Antagonist: D1 and D2 dopamine receptors, alpha 1 and alpha 2 adrenoreceptors, and 5-HT1A and 5-HT2 serotonin receptors, histamine H1 receptor (and others)	Scz BD MDD (along with an SSRI)	AUD and Bipolar	NCT02918370	(Anton et al. 2008; Kenna et al. 2009; Martinotti et al. 2009; Martinotti et al. 2007; Shapiro et al. 2003; Voronin et al. 2008)
Duloxetine (Cymbalta)	Serotonin–norepinephrine reuptake inhibitor (SNRI)	MDD GAD Muscle pain Peripheral neuropathy	AUD	NCT00929344	(Bymaster et al. 2001)
Venlafaxine (Effexor)	SNRI	MDD GAD Panic disorder Social anxiety disorder	AUD and anxiety	NCT00248612	(Bymaster et al. 2001; Ciraulo et al. 2013; Upadhyaya et al. 2001)
Rolipram	Phosphodiesteras e-4 inhibitor	Shelved compound; Phase 3 for MDD (Fleischhacker et al, 1992)	AUD		(Bell et al. 2017; Dominguez et al. 2016; Gong et al. 2017; Hu et al. 2011; Liu et al. 2017; Ray et al. 2014; Wen et al. 2012)
Ibudilast	Phosphodiesterase inhibitor	Asthma (Japan)	AUD	NCT02025998	(Bell et al. 2015; Crews et al. 2017; Ray et al. 2017; Ray et al. 2014)
Fenofibrate (Tricor)	Fibrate PPARα agonist	Hypercholesterolemia Hypertriglyceridemia	AUD	NCT02158273	(Blednov et al. 2015; Blednov et al. 2016a; b; Ferguson et al. 2014; Haile and Kosten 2017; Karahanian et al. 2014; Rivera-Meza et al. 2017)
Gabapentin (Neurontin)	Anticonvulsant binds to the α2δ subunit of the voltagedependent calcium channels (Pregabalin is structurally related to gabapentin)	Seizures Restless leg syndrome Postherpetic neuralgia Shingles	AUD; Abstinence initiation in AUD; AUD (in combination with naltrexone); Sleep disturbances in AUD; AUD (in combination with flumazenil for withdrawal and relapse prevention); AUD (in combination with lorazepam for withdrawal); Comorbid alcohol and opioid abuse	NCT02771925 NCT01141049 NCT00391716 NCT00183196 NCT01014533 NCT00262639 NCT03274167 NCT00011297 NCT03205423 NCT02252536	(Geisler and Ghosh 2014; Guglielmo et al. 2012; Litten et al. 2016; Mason et al. 2014a; Mason et al. 2014b; Nunes 2014)
Pregabalin (Lyrica)	Anticonvulsant binds to the α2δ subunit of the voltagedependent calcium channels	Epilepsy Neuropathic pain Fibromyalgia Generalized anxiety disorder (GAD)	AUD; AUD and PTSD	NCT03256253 NCT02884908 NCT00929344	(Guglielmo et al. 2012; Li et al. 2011)
Topiramate (Topamax)	Anticonvulsant Blocks voltagegated Na+ Channels, PAMs of subunits of the GABAA Receptor Modulates AMPA/kainite glutamate receptors. Blocks carbonic anhydrase (CA) CA I1 and CA IV	Epilepsy Migraines	AUD; AUD and PTSD; AUD and Borderline Personality Disorder; AUD and BD; AUD and cocaine dependence; AUD and nicotine dependence	NCT01135602 NCT01145677 NCT01749215 NCT00769158 NCT00463775 NCT00210925 NCT00572117 NCT00223639 NCT00884884 NCT00006205 NCT00571246 NCT03120468 NCT00802412 NCT00448825 NCT00329407 NCT00862563 NCT01182766 NCT00300742 NCT00167245 NCT02371889 NCT01764685 NCT01087736 NCT01408641 NCT00550394 NCT03018704	(Guglielmo et al. 2015; Ray and Bujarski 2016; Shank et al. 2000)
Varenicline (Chantix and Champix)	α7 nicotinic acetylcholine receptor agonist α4β2, α3β4, and α6β2 subtype s partial agonist weak agonist on the α3β2 containing receptors	Smoking cessation	AUD; AUD and tobacco dependence; AUD and cocaine dependence; AUD, SCZ and nicotine dependence	NCT01071187 NCT01146613 NCT00705523 NCT00846859 NCT00873535 NCT01553136 NCT01347112 NCT01151813 NCT01169610 NCT00727103 NCT01011907 NCT01092702 NCT01286584 NCT01592695 NCT02698215	(Falk et al. 2015; Litten et al. 2013)
ABT-436	highly selective vasopressin V1B receptor antagonist	Shelved compound; Phase 2 for MDD (NCT01741142)	AUD	NCT01613014	(Ryan et al. 2017)
Mifepristone (RU-486) (Mifeprex)	glucocorticoid and progesterone receptor antagonist	Abortifacient Hyperglycemia Diabetes mellitus	AUD	NCT02243709 NCT02179749 NCT02989662 NCT01548417	(Donoghue et al. 2016; Howland 2013; Lyon 2017; Vendruscolo et al. 2012; Vendruscolo et al. 2015)
Citicoline (Cebroton, Ceraxon, Cidilin, Citifar, Cognizin, more)	membrane permeability enhancer glutathione transferase stimulant (overthe-counter nutritional supplement)	Stroke Alzheimer’s disease Senile dementia Parkinson’s disease Attentiondeficit/hyperactiv ity disorder (ADHD) Glaucoma	AUD; AUD and BD	NCT02074735 NCT02582905	(Secades and Lorenzo 2006; Wignall and Brown 2014)
Baclofen (Lioresal)	Central nervous system depressant; skeletal muscle relaxant GABAB receptor agonist	Spastic movement disorders (commonly for spinal cord injury, cerebral palsy, and multiple sclerosis)	AUD; Alcohol withdrawal; AUD and Hepatitis C; AUD with liver disease; AUD and anxiety disorders	NCT02596763 NCT03034408 NCT03293017 NCT01008280 NCT02511886 NCT01711125 NCT01751386 NCT00877734 NCT00614328 NCT01266655 NCT01980706 NCT01738282 NCT01002105 NCT00802035 NCT02835365 NCT01604330 NCT02723383 NCT01076283 NCT01937364 NCT00525252 NCT02107352 NCT02771925	(Bell et al. 2017; Borro et al. 2016; Colombo et al. 2004; Farokhnia et al. 2017; Geisel et al. 2016; Imbert et al. 2015; Litten et al. 2016; Liu and Wang 2017; Lyon 2017; Mirijello et al. 2015; Morley et al. 2014; Muller et al.2015; Ponizovsky et al. 2015; Rigal et al. 2015; Rolland et al. 2015a; Rolland et al. 2015b; Weibel et al. 2015)
Nalmefene (Selincro)	Antagonist of the μ-opioid receptor weak partial agonist of the κ-opioid receptor	Antidote for opioid overdose Approved in Europe for AUD	AUD; AUD with cirrhosis; AUD and tobacco dependence; AUD and Borderline Personality Disorder; AUD and opioid use disorder	NCT00811720 NCT01969617 NCT00812461 NCT00811941 NCT02824354 NCT02382276 NCT02364947 NCT02197598 NCT02679469 NCT02372318 NCT02195817 NCT02492581 NCT00000450 NCT00000437 NCT02752503 NCT03034408 NCT03279562	(Litten et al. 2016; Naudet 2016; Naudet et al. 2016; Soyka 2016; Soyka et al. 2016)