Table 4.

Primary outcomes of clinical trials testing drugs for the treatment of AUD.

Medication	Time Abstinent	Treatment Duration/Target Dose	Primary Outcome	References
Disulfiram	0 days	119 weeks (12 week supervised medication, up to 52 week targeted medication, 67 week follow-up period); 100-200 mg q.d. or 2 × 400 mg twice a week	Compared to naltrexone (50 mg q.d.) and acamprosate (2 × 333 mg t.i.d. for people ≥ 60 kg body weight; 1332 mg for people < 60 kg body weight): Increased time to first HDD and time to first drink during the first 12 weeks	(Laaksonen et al., 2008)
	Men; abstinent 19 ± 5 days on average for DSF group; 20 ± 11 for TPM group	9 months/ 250 mg q.d.	Compared to TPM (50 mg t.i.d.): Increased days to first relapse; No effect on days of abstinence, discontinuation of treatment, or drop out rate; Decreased craving severity and GGT	(De Sousa et al., 2008)
Naltrexone	5 days	12 weeks/ 50 mg q.d.	Decreased drinks per drinking day; Increased time to first relapse, and % days abstinent	(Anton et al., 1999)
	AD or Alcohol abusers, 5-30 days abstinent	12 weeks/ 50 mg q.d.	No effect on time to first episode of heavy drinking	(Chick et al., 2000a)
	0 days	24 weeks/ 380 mg or 190 mg long-acting injectable naltrexone administered monthly	380 mg dose decreased event rate of HDD; Treatment effects were greater in subpopulation that were abstinent for 7 days prior to treatment	(Garbutt et al., 2005)
	5- 30 days (19.5 ± 9.4 days on average)	12 weeks/ 50 mg q.d.	No effect on time to first heavy drinking episode	(Gastpar et al., 2002)
	12-15 days	12 weeks/ 50 mg q.d.	Increased time to first relapse and time to first drink	(Kiefer et al., 2003)
	12-15 days	12 weeks/ 50 mg naltrexone q.d.+ 2 × 333 mg t.i.d.	Increased time to first relapse and time to first drink (compared to both placebo and acamprosate alone)	(Kiefer et al., 2003)
	Predominantly male, 5 days abstinent	12 months/ 50 mg q.d. for 12 months; 50 mg q.d. for 3 months + placebo for 9 months	No effect on time to relapse during the first 3 months, % drinking days over the 12 month period or number of drinks per drinking day over the 12 month period	(Krystal et al., 2001)
	3-21 days	12 weeks/ 50 mg q.d.	Compared to both placebo and acamprosate: No effect on number of days to first lapse, days to first relapse, cumulative days abstinent, or drinks per drinking day	(Morley et al., 2006)
	Males; 3-30 days abstinent (8 ± 5 days on average for NTX group; 9 ± 6 for placebo)	12 weeks/ 50 mg q.d.	Decreased relapse to drinking; No effect on maintenance of abstinence	(Morris et al., 2001)
	Non treatment seeking heavy drinkers (63% AD); 0 days abstinent	3 weeks/ 50 mg q.d. (in addition to a 1-week placebo lead-in)	Decreased % drinking days; No effect on drinks per day, drinks per drinking day, % HDD or any subjective effects of alcohol	(Tidey et al., 2008)
	4-21 days	16 weeks/ 50 mg b.i.d.	Increased % days abstinent; Decreased risk of HDD	(Anton et al., 2006)
	Males; 3-30 days abstinent	12 weeks/ 50 mg q.d.	Decreased relapse to heavy drinking	(Ahmadi and Ahmadi, 2002)
	14-28 days	12 weeks/ 50 mg q.d. (in addition to a 1 week placebo run-in and therapy every 4th week from week 12-24)	Decreased HDD	(Balldin et al., 2003)
	Non AD heavy drinkers; 0 days	6 weeks/ 25 mg q.d.; 50 mg q.d. (in addition to a one month post treatment follow-up)	Compared to pre-treatment measures: Decreased number of standard drinks consumed, HDD, and drinks per drinking days; increased number of days abstinent	(Bohn et al., 1994)
	5-30 days	12 weeks/ 50 mg q.d.	Decreased relapse to heavy drinking	(Guardia et al., 2002)
	0 days	12 weeks/ 50 mg q.d. (in addition to a 1 week placebo run-in and 20 week post treatment targeted medication)	Naltrexone + cognitive coping skills decreased relapse to heavy drinking	(Heinala et al., 2001)
	0 days	12 weeks/ 50 mg q.d.	Compared to placebo + treatment as usual and treatment as usual alone: No effect on % days drinking, average drinks per day, average drinks per drinking day, HDD, or time to first heavy drink	(Killeen et al., 2004)
	3 days	8 weeks/ 50 mg PO daily for 2 weeks, followed by a 2-week, no-medication wash out period, a 4-week 206 mg injection (single) period, and a 4-week follow-up period	Compared to placebo injection: Decreased % HDD during injection period; No effect on average drinks per drinking day during injection period; Decreased % HDD and average drinks per day during follow-up period	(Kranzler et al., 1998)
	7-51 days (11.7 day on average)	12 weeks/ 50 mg q.d.	Decreased relapse rate; Increased time to first relapse; No effect on reported side effects	(Latt et al., 2002)
	3 days	12 weeks/ 50 mg b.i.d. (in addition to a one week placebo lead-in)	Decreased number of heavy drinking days	(Monterosso et al., 2001)
Acamprosate	12-15 days	12 weeks/ 2 × 333 mg t.i.d.	Increased time to first relapse and time to first drink	(Kiefer et al., 2003)
	<10 days (must have reduced drinking to no more than 2 (F) or 3 (M) drinks in the 2-10 days pre randomization)	24 weeks/ 2 × 500 mg b.i.d.; 3 × 500 mg b.i.d.	No effect on % days abstinent	(Mason et al., 2006)
	3-21 days	12 weeks/ 2 × 333 mg t.i.d.	Compared to both placebo and NTX: No effect on number of days to first lapse, days to first relapse, cumulative days abstinent, or drinks per drinking day	(Morley et al., 2006)
	Predominantly male; 1 day abstinent	8 weeks/ 1998 mg for people ≥ 60 kg body weight or 1332 mg for people < 60 kg body weight (dosing schedule not specified)	No effect on time to first drink, time to relapse, or % days abstinent	(Namkoong et al., 2003)
	7-28 days (18 days on average)	12 months/ 1332 mg per day (4 × 333 mg per day); 1998 mg per day (6 × 333 mg per day) (in addition to a single-blind 6 month follow-up on placebo)	Dose dependently increased continuous abstinence at 6 months; No effect on continuous abstinence at 12 months	(Paille et al., 1995)
	5 days	24 weeks/ 2 × 333 mg t.i.d. (in addition to a 12 week medication-free follow-up)	Increased abstinence rate, cumulative abstinence duration, period of continued abstinence	(Tempesta et al., 2000)
	4-21 days	16 weeks/ 2 × 500 mg t.i.d.	No effect on mean % days abstinent or time to first HDD	(Anton et al., 2006)
	5 days	360 days/ 2 × 333 mg t.i.d. for people ≥ 60 kg body weight; 1332 mg (2+1+1) for people < 60 kg body weight (in addition to a 360 day follow up period)	Increased cumulative abstinence duration; Decreased relapse rate through assessment day 270	(Besson et al., 1998)
	5 days	24 weeks/ 2 × 333 mg t.i.d.	No effect on continuous abstinence or cumulative abstinence duration	(Chick et al., 2000b)
	5 days	24 weeks/ 2 × 333 mg t.i.d. for people ≥ 60 kg body weight; 1332 mg (333 mg, 2+1+1) for people < 60 kg body weight (in addition to a medication free 6-month follow-up period)	Increased cumulative duration of abstinence, time to first relapse, % abstinent on assessment day 135	(Geerlings et al., 1997)
	0 days	180 days/ 2 × 333 mg t.i.d.	Increased cumulative abstinence duration	(Gual and Lehert, 2001)
	Within 48 h following hospitalization for alcohol withdrawal; 5-30 days abstinent	90 days; 1332 mg (333 mg, 2+1+1)	Decreased GGT	(Lhuintre et al., 1990)
	14 day inpatient detoxification program	90 days/ 1332 mg (333 mg, 2+1+1); 2 × 333 mg t.i.d.	Increased cumulative abstinence duration; Decreased relapse rate	(Pelc et al., 1997)
	5 days	24 weeks/ 2 × 333 mg t.i.d. for people ≥ 60 kg body weight; 1332 mg (333 mg, 2+1+1) for people < 60 kg body weight (in addition to a 24 week follow-up period)	Increased abstinence at month 1, 6, and 12; No effect on abstinence at month 3 and 9	(Poldrugo, 1997)
	5 days	360 days/ 2 × 333 mg t.i.d. for people > 60 kg body weight; 1332 mg (333 mg, 2+1+1) for people ≤ 60 kg body weight (in addition to a 360 day follow-up period)	Increased time to first treatment failure	(Whitworth et al., 1996)
Nalmefene	3 days	12 weeks/ 2 × 2.5 mg q.d.; 2 × 10 mg q.d.; 2 × 20 mg q.d.	No effect of treatment on number of HDD per month	(Anton et al., 2004b)
	0 days	24 weeks/ up to 18 mg per day prn (in addition to a 1-2 week screening period and 4-week double-blind run-out period)	Decreased HDD; No effect on monthly total alcohol consumption	(Gual et al., 2013)
	0 days	24 weeks/ up to 18 mg per day prn (in addition to a 1-2 week screening period and 4-week double-blind run-out period)	Decreased number of HDD and total alcohol consumption	(Mann et al., 2013)
	2 weeks on average	12 weeks/ 10 mg b.i.d.; 40 mg b.i.d. (in addition to a 2-week single-blind placebo period)	Decreased relapse to heavy drinking; No effect on drinks per drinking day or % days abstinent	(Mason et al.)
	0 days	12 weeks/ 20 mg b.i.d; 5 mg b.i.d. (in addition to a 2-week single-blind placebo lead-in)	40 mg dose compared to 10 mg and placebo: Decreased relapse to heavy drinking; Increased change mean abstinence days/week from single-blind placebo phase to treatment phase	(Mason et al., 1994)
			Both doses compared to placebo: Decreased change in number of drinks per drinking day from single-blind placebo phase to treatment phase; No effect on craving or retention in treatment	(Mason et al., 1994)
Ondansetron	0 days	11 weeks/ 1 μg/kg b.i.d.; 4 μg/kg b.i.d.; 16 μg/kg b.i.d. (in addition to a 1 week placebo lead-in)	All doses in early onset alcoholics: Decreased drinks per day and drinks per drinking day	(Johnson et al., 2000)
			4 μg/kg b.i.d. in early onset alcoholics: Increased % days abstinent and total day abstinent per study week	(Johnson et al., 2000)
	0 days	8 weeks/ 4 μg/kg/ml b.i.d.	In early onset alcoholics: Decreased drinks per day and drinks per drinking day compared to late onset alcoholics; No effect on % days abstinent or number of HDD between groups	(Kranzler et al., 2003)
	Non severely AD males; 0 days	6 weeks/ 0.25 mg b.i.d.; 2 mg b.i.d. (in addition to a 2 week baseline period)	In all patients: No effects on number of standard drinks per drinking day between baseline and treatment	(Sellers et al., 1994)
			In light drinkers: Decreased number of drinks per drinking day compared to baseline	(Sellers et al., 1994)
Topiramate	0 days	12 weeks/ escalating dose of 25-300 mg per day (weeks 8-12 100 mg + 2 × 25 mg b.i.d.)	Decreased drinks per day, drinks per drinking day, % HDD and plasma GGT; Increased % days abstinent	(Johnson et al., 2003)
	0 days	14 weeks/ 300 mg per day (100 q.a.m. + 2 × 100 mg q.p.m.)	Decreased % HDD	(Johnson et al., 2007)
	Men; abstinent 19 ± 5 days on average for DSF group; 20 ± 11 for TPM group	9 months/ 50 mg t.i.d.	Compared to DSF (250 mg q.d.): Decreased days to first relapse; No effect on days of abstinence, discontinuation of treatment, or drop out rate; Increased craving severity and GGT	(De Sousa et al., 2008)
Zonisamide	0 days	12 weeks/ 100-500 mg q.d. (increased 100 mg every 2 weeks for 8 weeks)	Medications × Treatment week interaction: Decreased HDD per week and drinks per week; No effect on abstinent days per week	(Arias et al., 2010)
	Detoxified or present mild symptoms of abstinence (scores on the CIWA for Alcohol-Revised of <6)	12 weeks/ 50-300 mg per day (flexible-dose schedule with average of 220 mg per day ± 50)	Compared to baseline: Decreased number of drinks per week, craving severity and GGT levels	(Rubio et al., 2010)
Levetiracetam	Heavy social drinkers; 0 days abstinent	2, 14 day treatment periods (one cycle with placebo and the other with low or high dose Levetiracetam)/ 250-500 g b.i.d.; 500-1000 g b.i.d. (in addition to a 3-day drug taper and 7 day washout period)	No effect on number of drinks consumed	(Mitchell et al., 2012a)
	0 days	6 days/ fixed dose schedule (days: 1-3: 1000-0-1000 mg; 4: 500-0-1000 mg; 5: 500-0-500 mg; 6: 0-0-500 mg)	No effect on dose of diazepam as a rescue medication or the severity of withdrawal symptoms	(Richter et al., 2010)
	0 days	10 weeks/ titrated up to 1000 mg b.i.d. over the first 3 weeks to a total of 2000 mg (in addition to 1 week of screening and 2 weeks taper)	Decreased standard drinks per day	(Sarid-Segal et al., 2008)
	0 days	16 weeks/ titrated for the first 4 weeks from 500 to 2000 mg/day week 5-14 followed by a 2 week taper (in addition to a follow-up interview week 19)	No effect on percent HDD and percent subjects with no HDD	(Fertig et al., 2012)
Gabapentin	3 days	12 weeks/ 2 × 150 mg t.i.d.; 2 × 300 mg t.i.d.	Dose dependently increased rates of complete abstinence and no heavy drinking	(Mason et al., 2014)
	Patients with moderate-severe AWS; 0 days	2 days/ 400 mg q.i.d. (data on safety and tolerability continued to be measured until day 7)	No effect on amount of CLO required in the first 24 hours (no psychosocial component specified)	(Bonnet et al., 2003)
Pregabalin	5-10 days	16 weeks/ flexible dose of 150-450 mg per day (mean 262.5 mg per day ± 117.9)	Half (n=10) were completely abstinent for duration of the study; One quarter (n=5) relapsed	(Martinotti et al., 2008)
	0 days	14 days; up to 450 mg per day	Compared to both tiapride and lorazepam: Increased abstinence; Decreased CIWA-Ar scores on items regarding headache and orientation Compared to tiapride only: Increased time to dropout	(Martinotti et al., 2010)
Baclofen	12-24 h	30 days/ 10 mg t.i.d.	Increased % abstinent and number of cumulative abstinent days	(Addolorato et al., 2002)
	3 days	12 weeks/ 10 mg t.i.d.; 20 mg t.i.d.	Compared to baseline: Decreased number of drinks per day	(Addolorato et al., 2011)
	AD with liver cirrhosis, 3-4 days abstinent	12 weeks/ 10 mg t.i.d.	Increased % abstinent and cumulative abstinent duration	(Addolorato et al., 2007)
	3 days	12 weeks/ 30 mg per day (dosing schedule not specified)	No effect on % HDD	(Garbutt et al., 2010)
	3 days	12 weeks/ 10 mg t.i.d.	Compared to baseline measures: Decreased number of drinks per drinking day and HDD; Increased number of abstinent days	(Flannery et al., 2004)
Varenicline	0 days	13 weeks/ 1 mg b.i.d.	Decreased weekly % HDD	(Litten et al., 2013)
	Heavy drinking smokers seeking treatment for smoking only; 0 days abstinent	12 weeks/ 1 mg b.i.d. (in addition to 2 follow-up visits at week 14 and 16)	Decreased drinks and cigarettes per week from weeks 3-11; No effect on craving per week	(Mitchell et al., 2012c)
	0 days	12 weeks/ 1 mg b.i.d.	No effect on alcohol use	(Plebani et al., 2013)
Oxytocin	0 days	3 days/ 24 IU/dose b.i.d.	Required less total lorazepam to complete detoxification	(Pedersen et al., 2013)
Memantine	0 days	12 weeks/ 20 mg b.i.d. (in addition to a 2 week placebo lead-in and a 2 week placebo lead-out)	Increased % HDD; Decreased % days abstinent; No effect on average drinks per day or drinks per drinking day	(Evans et al., 2007)
Prazosin	0 days	6 weeks/ 4 mg q.a.m. + 4 mg q.p.m. + 8 mg q.h.s.	No effect on mean drinks per week or mean drinking days per week; Decreased drinking days per week in the final 3 weeks	(Simpson et al., 2009)
			In men only in the final 3 weeks: Decreased drinking days per week, average total number of drinking days, drinks per week, average number of total drinks	(Simpson et al., 2009)
Doxazosin	0 days	10 weeks/ titrated during the first 4 weeks up to 16 mg per day and a 1-week downward titration at week 10 (in addition to a follow-up week 12)	In AD patients with high family history density of alcoholism (FHDA): Reduced drinks per week and HDD per week In AD patients with low FHDA: Increased drinks per week, No effect on HDD per week	(Kenna et al., 2015)
Rimonabant	7-28 days	12 weeks/ 20 mg q.d.	No effect on time to first drink or time to first HDD	(Soyka et al., 2008)

Note: All results are compared to placebo unless otherwise stated; Population was AD males and females unless otherwise stated. All treatment included a psychosocial/medical management component.