lorazepam and Substance Withdrawal Syndrome studies

Lorazepam: A benzodiazepine used as an anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent.

Substance Withdrawal Syndrome: Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.

Research Excerpts

Excerpt	Relevance	Reference
"Treatment with intravenous lorazepam is associated with a significant reduction in the risk of recurrent seizures related to alcohol."	9.09	Lorazepam for the prevention of recurrent seizures related to alcohol. ( D'Onofrio, G; Fish, SS; Freedland, ES; Rathlev, NK; Ulrich, AS, 1999)
"Hypnotic efficacy and safety of 3 weeks of daily doses of 2 mg lorazepam or 30 mg flurazepam were compared in a double-blind cross-over study in eight chronic insomniacs between the ages of 29 and 60 years."	9.06	Comparison of lorazepam and flurazepam as hypnotic agents in chronic insomniacs. ( Chang, H; McClure, DJ; Olah, A; Pecknold, JC; Walsh, J; Wilson, R, 1988)
" The patient was diagnosed with catatonia due to benzodiazepine withdrawal and had gradual return to baseline with administration of lorazepam 1 mg intravenous three times per day."	7.88	Catatonia due to alprazolam withdrawal. ( Abdelmalak, F; Bornmann, C; Iyengar, S; LaRocca, T, 2018)
"The aim of this report is to describe the clinical and electroencephalographic findings seen in an elderly woman without previous history of seizures who developed a nonconvulsive generalized status epilepticus following acute withdrawal of lorazepam."	7.71	De novo absence status of late onset following withdrawal of lorazepam: a case report. ( Fernández-Torre, JL, 2001)
"A 53-year-old man with a 3-month addiction to approximately 5 mg/day of triazolam experienced psychosis and delirium following relatively abrupt withdrawal from the drug."	7.67	A case of psychosis and delirium following withdrawal from triazolam. ( Capwell, R; Heritch, AJ; Roy-Byrne, PP, 1987)
"Benzodiazepine withdrawal-induced catatonia is a rare phenomenon in the adult population and has never been reported in a pediatric patient."	5.46	Case Report of Midazolam Withdrawal-Induced Catatonia in a 9-Year-Old Patient. ( Duncan-Azadi, CR; Gormley, A; Johnson, PN, 2017)
"Catatonia is a rare manifestation of benzodiazepine withdrawal in elderly patients who have used it for a long time."	5.39	Lorazepam withdrawal catatonia: a case report. ( Khandelwal, SK; Sivakumar, T; Sood, M; Yadav, A, 2013)
"To perform a randomized evaluation of lorazepam and ethanol/lorazepam to evaluate the safety and efficacy of these 2 strategies for preventing alcohol withdrawal syndrome in patients with acute coronary syndromes."	5.17	Alcohol withdrawal prevention: a randomized evaluation of lorazepam and ethanol--a pilot study. ( Bride, W; Fullwood, JE; Granger, BB; Granger, CB; Mostaghimi, Z; Washam, JB; Zhao, Y, 2013)
" The primary objective of this study was to compare the efficacy of gabapentin to lorazepam in alleviating sleep disturbances and daytime sleepiness during an episode of alcohol withdrawal."	5.12	Self-reported sleep, sleepiness, and repeated alcohol withdrawals: a randomized, double blind, controlled comparison of lorazepam vs gabapentin. ( Boyle, E; Malcolm, R; Myrick, LH; Randall, PK; Veatch, LM, 2007)
"Treatment with intravenous lorazepam is associated with a significant reduction in the risk of recurrent seizures related to alcohol."	5.09	Lorazepam for the prevention of recurrent seizures related to alcohol. ( D'Onofrio, G; Fish, SS; Freedland, ES; Rathlev, NK; Ulrich, AS, 1999)
"Hypnotic efficacy and safety of 3 weeks of daily doses of 2 mg lorazepam or 30 mg flurazepam were compared in a double-blind cross-over study in eight chronic insomniacs between the ages of 29 and 60 years."	5.06	Comparison of lorazepam and flurazepam as hypnotic agents in chronic insomniacs. ( Chang, H; McClure, DJ; Olah, A; Pecknold, JC; Walsh, J; Wilson, R, 1988)
"The effects of 3 mg lorazepam on polysomnographic recordings, performance, anxiety, and perceived sleep were examined."	5.05	Effects of lorazepam and its withdrawal on sleep, performance, and subjective state. ( Parwatikar, S; Schweitzer, PK; Walsh, JK, 1983)
"While some case reports indicate that high doses of propylene glycol (PG) may result in metabolic acidosis, there has been no large-scale study that evaluated the risk of metabolic acidosis in patients receiving PG-containing benzodiazepines for acute alcohol withdrawal."	3.88	Assessing Propylene Glycol Toxicity in Alcohol Withdrawal Patients Receiving Intravenous Benzodiazepines: A One-Compartment Pharmacokinetic Model. ( Bodreau, C; Elbarbry, F; Farthing, K; Jahn, A, 2018)
" The patient was diagnosed with catatonia due to benzodiazepine withdrawal and had gradual return to baseline with administration of lorazepam 1 mg intravenous three times per day."	3.88	Catatonia due to alprazolam withdrawal. ( Abdelmalak, F; Bornmann, C; Iyengar, S; LaRocca, T, 2018)
"Pretreatment with R121919 attenuated the subsequent HPA axis activation, behavioral measures of anxiety, and expression of the CRF gene in the paraventricular nucleus of the hypothalamus, as measured by CRF heteronuclear RNA, which occurs after flumazenil-precipitation of withdrawal from the BZ, lorazepam."	3.74	The CRF1 receptor antagonist R121919 attenuates the neuroendocrine and behavioral effects of precipitated lorazepam withdrawal. ( Gutman, DA; Nemeroff, CB; Owens, MJ; Skelton, KH; Thrivikraman, KV, 2007)
"The aim of this report is to describe the clinical and electroencephalographic findings seen in an elderly woman without previous history of seizures who developed a nonconvulsive generalized status epilepticus following acute withdrawal of lorazepam."	3.71	De novo absence status of late onset following withdrawal of lorazepam: a case report. ( Fernández-Torre, JL, 2001)
" Three cases of convulsive status epilepticus (CSE) following abrupt discontinuation of long-term use of 25 mg of lorazepam in one patient and more than 20 mg of flunitrazepam in two patients are presented; they were non-epileptics and free of other high-risk factors for seizures."	3.70	Convulsive status epilepticus following abrupt high-dose benzodiazepine discontinuation. ( Angelopoulos, EK; Chioni, A; Daskalopoulou, EG; Gatzonis, SD; Mantouvalos, V; Siafakas, A; Zournas, C, 2000)
"QUESTIONOne of my patients suffers from anxiety and was using lorazepam to treat it."	3.70	Can we use anxiolytics during pregnancy without anxiety? ( Addis, A; Dolovich, LR; Einarson, TR; Koren, G, 2000)
"In this study, we present five cases of seizures following withdrawal of flunitrazepam, lorazepam, or triazolam, representing 3% of a sample consisting of 153 patients dependent on benzodiazepines."	3.69	Benzodiazepine withdrawal syndrome seizures. ( de Iceta, M; Martínez-Cano, H; Martínez-Gras, I; Pomalima, R; Vela-Bueno, A, 1995)
"Sodium phenobarbitone (20 and 70 mg/kg) had a significant anticonvulsant action against pentylenetetrazole-induced seizures, which persisted for 21 days of treatment."	3.68	Changes in seizure threshold and aggression during chronic treatment with three anticonvulsants and on drug withdrawal. ( File, SE; Wilks, LJ, 1990)
"A 53-year-old man with a 3-month addiction to approximately 5 mg/day of triazolam experienced psychosis and delirium following relatively abrupt withdrawal from the drug."	3.67	A case of psychosis and delirium following withdrawal from triazolam. ( Capwell, R; Heritch, AJ; Roy-Byrne, PP, 1987)
" Non-BZD adverse events warrant further investigation."	3.01	Beyond benzodiazepines: a meta-analysis and narrative synthesis of the efficacy and safety of alternative options for alcohol withdrawal syndrome management. ( Fluyau, D; Kailasam, VK; Pierre, CG, 2023)
"Lorazepam was used as rescue medication."	2.82	A randomized, open-label, standard controlled, parallel group study of efficacy and safety of baclofen, and chlordiazepoxide in uncomplicated alcohol withdrawal syndrome. ( Girish, K; Manjunatha, R; Nagraj, M; Pandit, LV; Pundarikaksha, HP; Shruthi, R; Vasundara, K; Vijendra, R; Vikram Reddy, K, 2016)
"High-dose and low-dose groups were combined as a single dexmedetomidine group for primary analysis with secondary analysis exploring a dose-response relationship."	2.79	A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal. ( Fish, DN; Kiser, TH; Lavelle, JC; MacLaren, R; Malkoski, SP; Mueller, SW; Preslaski, CR, 2014)
"Lorazepam treated group showed a significant difference in the rate of improvement over 48 h compared to chlordiazepoxide group (70."	2.78	A double blind randomised comparison of chlordiazepoxide and lorazepam in alcohol withdrawal. ( Mohandas, E; Rajmohan, V; Sushil, K, 2013)
"Phenobarbital and LZ were similarly effective in the treatment of mild/moderate alcohol withdrawal in the ED and at 48 hours."	2.76	A prospective, randomized, trial of phenobarbital versus benzodiazepines for acute alcohol withdrawal. ( Barnes, RL; Dery, RA; Hendey, GW; Mentler, P; Snowden, B, 2011)
"One hundred consecutive consenting male inpatients in a state of moderately severe, uncomplicated alcohol withdrawal at screening were randomized to receive either lorazepam (8 mg/day) or chlordiazepoxide (80 mg/day) with dosing down-titrated to zero in a fixed-dose schedule across 8 treatment days."	2.74	A randomized, double-blind comparison of lorazepam and chlordiazepoxide in patients with uncomplicated alcohol withdrawal. ( Andrade, C; Kumar, CN; Murthy, P, 2009)
"Post-treatment, gabapentin-treated participants had less probability of drinking during the follow-up post-treatment period (p = 0."	2.74	A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal. ( Anton, RF; Becker, HC; Boyle, E; Malcolm, R; Myrick, H; Randall, CL; Randall, PK, 2009)
"The lorazepam dosage was tapered in a uniform fashion over 6 days by decreasing the total daily dose by 50% every other day on 3 occasions; it was then discontinued."	2.72	Withdrawal from lorazepam in critically ill children. ( Coleman, DM; Crowley, MR; Dominguez, KD; Katz, RW; Kelly, HW; Wilkins, DG, 2006)
"The severity of withdrawal symptoms was measured using the Clinical Institute Withdrawal Assessment-Benzodiazepines (CIWA-B) questionnaire."	2.71	Impaired hypothalamic-pituitary-adrenocortical (HPA) system is related to severity of benzodiazepine withdrawal in patients with depression. ( Brunner, H; Friess, E; Holsboer, F; Ising, M; Pedrosa Gil, F; Wichniak, A, 2004)
"Carbamazepine and lorazepam were equally effective at decreasing the symptoms of alcohol withdrawal."	2.70	The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. ( Anton, RF; Ballenger, JC; Malcolm, R; Myrick, H; Roberts, J; Wang, W, 2002)
"Lormetazepam or placebo were randomly assigned and given in a double-blind fashion."	2.70	Fast withdrawal from benzodiazepines in geriatric inpatients: a randomised double-blind, placebo-controlled trial. ( Afschrift, M; Mariman, A; Petrovic, M; Pevernagie, D; Van Maele, G, 2002)
" The percentage of reduction of benzodiazepine daily dosage at all time points in the treatment trial was similar for the ondansetron and placebo groups."	2.69	A controlled trial of ondansetron, a 5-HT3 antagonist, in benzodiazepine discontinuation. ( Busto, UE; Kaplan, HL; Romach, MK; Sellers, EM; Somer, G, 1998)
"Benzodiazepine use in the treatment of insomnia may cause benzodiazepine dependence, especially in opiate users."	2.69	Amitriptyline vs. lorazepam in the treatment of opiate-withdrawal insomnia: a randomized double-blind study. ( Jarusuraisin, N; Srisurapanont, M, 1998)
"Withdrawal symptoms were detected after discontinuation of therapeutic doses of lorazepam."	2.69	Safety of ipsapirone treatment compared with lorazepam: discontinuation effects. ( Bologa, M; Bremner, KE; Busto, UE; Naranjo, CA; Peachey, JE, 1998)
" After four weeks the dosage was reduced in 25% quantities until no further benzodiazepines were taken."	2.67	A double-blind comparison of the effects of gradual withdrawal of lorazepam, diazepam and bromazepam in benzodiazepine dependence. ( Murphy, SM; Tyrer, P, 1991)
"Flumazenil did not precipitate withdrawal symptoms in subjects who received a single administration of lorazepam."	2.67	Intravenous flumazenil following acute and repeated exposure to lorazepam in healthy volunteers: antagonism and precipitated withdrawal. ( Evans, SM; Furman, WR; Griffiths, RR; Guarino, JJ; Liebson, I; Roache, JD; Schwam, EM, 1993)
"Some withdrawal symptoms were distinct from those of anxiety (e."	2.66	Withdrawal reaction after long-term therapeutic use of benzodiazepines. ( Busto, U; Cappell, H; Naranjo, CA; Sanchez-Craig, M; Sellers, EM; Sykora, K, 1986)
" This was also reflected in the spectral analyzed EEG, which showed, after one single dosage of both drugs, a typical anxiolytic profile which was more pronounced after lopirazepam than prazepam, while after the chronic administration (12 h after the evening medication) only prazepam showed an anxiolytic profile."	2.65	Clinical symptomatology and computer analyzed EEG before, during and after anxiolytic therapy of alcohol withdrawal patients. ( Grünberger, J; Karobath, M; Mader, R; Saletu, B; Saletu, M, 1983)
"40 patients seen in general practice and psychiatric outpatient clinics who had taken lorazepam or diazepam alone in regular dosage for a mean period of 3."	2.65	Benzodiazepine withdrawal symptoms and propranolol. ( Huggett, T; Rutherford, D; Tyrer, P, 1981)
" Guidelines recommend dosing based on objectively measured symptoms (symptom-triggered therapy) rather than fixed dose regimens."	2.61	Symptom-Triggered Therapy for Alcohol Withdrawal Syndrome: a Systematic Review and Meta-analysis of Randomized Controlled Trials. ( Gunderson, CG; Holleck, JL; Merchant, N, 2019)
"Lorazepam alone was not effective in massive doses in these cases."	2.42	Propofol combined with lorazepam for severe poly substance misuse and withdrawal states in intensive care unit: a case series and review. ( Gowda, RM; Jani, K; Subramaniam, K; Ute, R; Zewedie, W, 2004)
"Lorazepam is an excellent first choice because of its intermediate half-life, absence of active metabolites, and high bioavailability that can be achieved with a number of routes of administration."	2.37	Emerging treatment options in the alcohol withdrawal syndrome. ( Rosenbloom, A, 1988)
"However, withdrawal symptoms may occur in patients receiving recommended doses and/or short-term therapy."	2.36	Benzodiazepine withdrawal syndrome: a literature review and evaluation. ( MacKinnon, GL; Parker, WA, 1982)
"Phenobarbital has been shown to be an effective adjunctive therapy for AWS, reducing benzodiazepine use, in the emergency department."	1.56	Phenobarbital and symptom-triggered lorazepam versus lorazepam alone for severe alcohol withdrawal in the intensive care unit. ( Lam, SW; Nguyen, TA, 2020)
"The few in-ED seizures occurred before medication administration."	1.56	Lorazepam Versus Diazepam in the Management of Emergency Department Patients With Alcohol Withdrawal. ( Barbic, D; Chiu, I; Duley, S; Grafstein, E; Grunau, B; Innes, G; Kestler, A; Lane, DJ; Miles, I; Moe, J; Nolan, S; Scheuermeyer, FX; Slaunwhite, A; Sljivic, I; Ti, L; Yan, A, 2020)
" Caution should be exercised regarding the long-term use of benzodiazepines in older adults (aged ≥65 years)."	1.51	Complicated Withdrawal Phenomena During Benzodiazepine Cessation in Older Adults. ( Kamal, A; Reeves, RR, 2019)
"Severe AWS can develop into delirium tremens (DT), which is potentially life-threatening."	1.51	Lorazepam versus chlordiazepoxide for the treatment of alcohol withdrawal syndrome and prevention of delirium tremens in general medicine ward patients. ( Bergeron, JB; March, KL; Reaves, AB; Sakaan, SA; Self, TH; Slayton, MM; Twilla, JD, 2019)
"Benzodiazepine withdrawal-induced catatonia is a rare phenomenon in the adult population and has never been reported in a pediatric patient."	1.46	Case Report of Midazolam Withdrawal-Induced Catatonia in a 9-Year-Old Patient. ( Duncan-Azadi, CR; Gormley, A; Johnson, PN, 2017)
"Treatment with carisoprodol and phenobarbital provided additional benefit and can be considered in cases of severe carisoprodol withdrawal."	1.46	Severe Carisoprodol Withdrawal After a 14-Year Addiction and Acute Overdose. ( Benowitz, NL; Horng, H; Smollin, CG; Vo, KT, 2017)
" A protocol incorporating SAS scoring and symptom-triggered benzodiazepine dosing was implemented in place of a protocol that utilized the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale and fixed benzodiazepine dosing."	1.46	A Symptom-Triggered Benzodiazepine Protocol Utilizing SAS and CIWA-Ar Scoring for the Treatment of Alcohol Withdrawal Syndrome in the Critically Ill. ( Dargin, J; Gray, A; Grgurich, P; Lei, Y; Sen, S; Smith-Freedman, A; Tulolo, A, 2017)
"Catatonia is a severe motor syndrome found in approximately 10% of all acute psychiatric hospital admissions."	1.43	Catatonia and cannabis withdrawal: A case report. ( Amad, A; Caudron, M; Deheul, S; Geoffroy, PA; Rolland, B; Thomas, P, 2016)
"Catatonia is a rare manifestation of benzodiazepine withdrawal in elderly patients who have used it for a long time."	1.39	Lorazepam withdrawal catatonia: a case report. ( Khandelwal, SK; Sivakumar, T; Sood, M; Yadav, A, 2013)
"However in those cases withdrawal symptoms were distinct and the medical intervention was needed."	1.38	[Description of a patient with schizophrenia and coexisting megadose lorazepam dependence with slightly expressed withdrawl symptoms during drug reduction. A case report]. ( Badura-Brzoza, K; Pasierb, N; Schylla, A; Scisło, P, 2012)
"Both lorazepam and MK-801 treatment conditions resulted in enhanced BSE activity during the entire fourth (untreated) withdrawal episode."	1.33	Lorazepam and MK-801 effects on behavioral and electrographic indices of alcohol withdrawal sensitization. ( Becker, HC; Veatch, LM, 2005)
"Alcohol abuse is common in patients with squamous cell cancer of the head and neck."	1.33	Alcohol withdrawal prophylaxis in patients undergoing surgical treatment of head and neck squamous cell carcinoma. ( Gourin, CG; Neyman, KM; Terris, DJ, 2005)
" In the specific case of acute catatonia brought on by benzodiazepine withdrawal the recommended dosage is the same as for acute catatonia caused by something other than benzodiazepine withdrawal."	1.33	[Benzodiazepines in the treatment of catatonia]. ( Sabbe, BG; Van Dalfsen, AN; Van Den Bossche, B; Van Den Eede, F, 2006)
"Withdrawal from the endogenous steroid progesterone (P) after chronic administration increases anxiety and seizure susceptibility via declining levels of its potent GABA-modulatory metabolite 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alphaTHP)."	1.32	Progesterone withdrawal reduces paired-pulse inhibition in rat hippocampus: dependence on GABA(A) receptor alpha4 subunit upregulation. ( Hsu, FC; Smith, SS, 2003)
"We report a case of gamma-hydroxybutyrate (GHB) withdrawal resulting in severe agitation, mental status changes, elevated blood pressure, and tachycardia hours after stopping chronic use of GHB."	1.31	Severe gamma-hydroxybutyrate withdrawal: a case report and literature review. ( Bania, TC; Craig, K; Gomez, HF; McManus, JL, 2000)
"Withdrawal from the neurosteroid 3alpha,5alpha-allopregnanolone after chronic administration of progesterone increases anxiety in female rats and up-regulates the alpha4 subunit of the GABA(A) receptor (GABA(A)-R) in the hippocampus."	1.31	Progesterone withdrawal increases the alpha4 subunit of the GABA(A) receptor in male rats in association with anxiety and altered pharmacology - a comparison with female rats. ( Gong, QH; Gulinello, M; Smith, SS, 2002)
"Lorazepam was administered 1 hr into each of the first three withdrawal cycles (or equivalent times); no drug injections were given during the final (fourth) withdrawal cycle."	1.31	Effects of lorazepam treatment for multiple ethanol withdrawals in mice. ( Becker, HC; Veatch, LM, 2002)
"Isradipine inhibited lorazepam withdrawal symptoms, the effect being accompanied in the 24-h withdrawal group by significant decreases in the noradrenaline and dopamine content of the thalamus and hypothalamus and in the noradrenaline content of the mid-brain."	1.30	Influence of certain calcium-channel blockers on some aspects of lorazepam-dependence in mice. ( Attia, AS; Khayyal, MT; Saad, ES; Saad, SF, 1997)
"Diphenhydramine was administered orally in the dose schedules of once daily (10, 20 and 40 mg/kg) and twice daily (5, 10 and 20 mg/kg) in separate groups during the withdrawal period."	1.30	Evaluation of inhibitory effect of diphenhydramine on benzodiazepine dependence in rats. ( Gupta, MB; Nath, C; Patnaik, GK; Saxena, RC, 1997)
"] upon abrupt discontinuation after chronic administration of its parent compound, progesterone (P), in a manner similar to other GABA-modulatory drugs."	1.30	Progesterone withdrawal. II: insensitivity to the sedative effects of a benzodiazepine. ( Goldberg, M; Moran, MH; Smith, SS, 1998)
" The switch to oral agents must take into consideration the differences in potency, half-life, and oral bioavailability between the agents."	1.29	Outpatient therapy of iatrogenic drug dependency following prolonged sedation in the pediatric intensive care unit. ( Deshpande, JK; Gregory, DF; Tobias, JD, 1994)
" The symptoms 'loss of body weight' and 'decrease in food intake' appeared to be more sensitive in benzodiazepine withdrawal: they were dose dependently present over the whole dosage range (2."	1.29	Tolerance and withdrawal after chronic lorazepam treatment in rats. ( de Groot, G; Jansen van't Land, C; van der Laan, JW, 1993)
" Drug was most often given on a fixed dosing schedule with additional medication "as needed" (52% of the programs)."	1.29	Alcohol withdrawal: a nationwide survey of inpatient treatment practices. ( Friedman, LS; Mayo-Smith, MF; Saitz, R, 1995)
"Lorazepam therapy was initiated in anticipation of alcohol withdrawal."	1.29	Polyethylene glycol nephrotoxicity secondary to prolonged high-dose intravenous lorazepam. ( Adams, SC; Hossain, SM; Laine, GA; Solis, RT, 1995)
"Audiogenic seizures were completely blocked by 20 mg/kg dose of verapamil and nimodipine while nifedipine was partially effective."	1.29	Effect of calcium channel blockers on withdrawal syndrome of lorazepam in rats. ( Gupta, MB; Nath, C; Patnaik, GK; Saxena, RC, 1996)
" Dose-response curves for stimulation of phosphoinositide (PI) hydrolysis by the selective metabotropic glutamate receptor (mGluR) agonist, (1S,3R)-1-aminocyclopentane dicarboxylic acid [(1S,3R)-ACPD] were performed with cortical slices from mice treated with lorazepam or vehicle for 7 days and subject to 0, 1, 2, 3, 4 and 7 days of withdrawal."	1.29	The effect of lorazepam tolerance and withdrawal on metabotropic glutamate receptor function. ( Mortensen, M; Suzdak, PD; Thomsen, C, 1995)
"Alcohol withdrawal (especially delirium tremens) poses significant potential morbidity to postsurgical patients."	1.29	Trends in the management of alcohol withdrawal syndrome. ( Moore, M; Newman, JP; Terris, DJ, 1995)
" Chronic administration of lorazepam reduces the coupling between the benzodiazepine agonist site and the chloride channel and concomitantly increases coupling between the channel and the inverse agonist site, while withdrawal resets the receptor coupling back to control response levels."	1.28	Effects of lorazepam tolerance and withdrawal on GABAA receptor operated chloride channels in mice selected for differences in ethanol withdrawal severity. ( Allan, AM; Baier, LD; Zhang, X, 1992)
"3."	1.28	Lorazepam discontinuation promotes 'inverse agonist' effects of benzodiazepines. ( Greenblatt, DJ; Lopez, F; Miller, LG; Schatzki, A; Shader, RI, 1989)
"A case of Gilles de la Tourette's syndrome (TS) is described, in which a state of akinesia developed during an attempt to withdraw lorazepam by diazepam substitution."	1.28	Gilles de la Tourette's syndrome. Amelioration following acute akinesia during lorazepam withdrawal. ( Peet, M; Wright, S, 1989)
"Lorazepam-treated baboons displayed precipitated withdrawal signs following the administration of Ro 15-1788 (5 mg/kg), and displayed mild to moderate spontaneous withdrawal signs following termination of drug treatment."	1.27	Precipitated and spontaneous withdrawal in baboons after chronic dosing with lorazepam and CGS 9896. ( Griffiths, RR; Lamb, RJ, 1984)
"Dogs, surgically implanted with a gastric fistula, were chronically dosed with diazepam or lorazepam."	1.27	Physical dependence on diazepam and lorazepam in the dog. ( Cherian, S; Martin, WR; McNicholas, LF, 1983)
" Caution should be exercised in long-term use of benzodiazepines in susceptible individuals."	1.27	Delusional depression following benzodiazepine withdrawal. ( Eales, M; Joyce, E; Keshavan, MS; Moodley, P; Yeragani, VK, 1988)
"The benzodiazepine withdrawal symptoms are presented here."	1.27	Manic-like reaction induced by lorazepam withdrawal. ( Labelle, A; Lapierre, YD, 1987)
"Dogs, surgically implanted with a chronic gastric fistula, were chronically dosed with N-desmethyldiazepam (32 mg/kg/day) in four divided doses to attain N-desmethyldiazepam plasma levels comparable to those observed in dogs dependent on diazepam (60 mg/kg/day)."	1.27	N-desmethyldiazepam physical dependence in dogs. ( Martin, WR; McNicholas, LF; Pruitt, TA, 1985)
"Lorazepam is a new member of a constantly growing benzodiazepine family."	1.26	Lorazepam-related withdrawal seizures. ( de la Fuente, JR; Martin, HR; Niven, RG; Rosenbaum, AH, 1980)

Research

Studies (206)

Authors

Clinical Trials (10)

Trial Overview

Trial Outcomes

Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 12

Timeframe	Studies, this research(%)	All Research%
pre-1990	60 (29.13)	18.7374
1990's	55 (26.70)	18.2507
2000's	43 (20.87)	29.6817
2010's	41 (19.90)	24.3611
2020's	7 (3.40)	2.80

Authors	Studies
Gonzalez, J	1
Upadhyaya, VD	1
Manna, ZT	1
Sharma, AR	1
Christopher, J	1
Douedi, S	1
Sen, S	2
Fluyau, D	1
Kailasam, VK	1
Pierre, CG	1
Andaluz, A	1
DeMoss, D	1
Claassen, C	1
Blair, S	1
Hsu, J	1
Bakre, S	1
Khan, M	1
Atem, F	1
Rush, AJ	1
Scheuermeyer, FX	1
Miles, I	1
Lane, DJ	1
Grunau, B	1
Grafstein, E	1
Sljivic, I	1
Duley, S	1
Yan, A	1
Chiu, I	1
Kestler, A	1
Barbic, D	1
Moe, J	1
Slaunwhite, A	1
Nolan, S	1
Ti, L	1
Innes, G	1
Mahmoud, S	1
Anderson, E	1
Vosooghi, A	1
Herring, AA	1
Muzyk, AJ	1
Rogers, RE	1
Dighe, G	1
Hartung, J	1
Musser, RC	1
Stillwagon, MJ	1
Rivelli, S	1
Jahn, A	1
Bodreau, C	1
Farthing, K	1
Elbarbry, F	1
Shah, P	1
McDowell, M	1
Ebisu, R	1
Hanif, T	1
Toerne, T	1
Warrington, SE	1
Collier, HK	1
Himebauch, AS	1
Wolfe, HA	1
Amirnovin, R	1
Sanchez-Pinto, LN	1
Okuhara, C	1
Lieu, P	1
Koh, JY	1
Rodgers, JW	1
Nelson, LP	1
Leandre, F	1
Ginory, A	1
Hardman, MI	1
Sprung, J	1
Weingarten, TN	1
Iyengar, S	1
Bornmann, C	1
Abdelmalak, F	1
LaRocca, T	1
Ibarra, F	1
Holleck, JL	1
Merchant, N	1
Gunderson, CG	1
Morrison, M	1
Udeh, E	1
Burak, M	1
Reeves, RR	1
Kamal, A	1
March, KL	1
Twilla, JD	1
Reaves, AB	1
Self, TH	1
Slayton, MM	1
Bergeron, JB	1
Sakaan, SA	1
Nguyen, TA	1
Lam, SW	1
Schylla, A	1
Scisło, P	1
Badura-Brzoza, K	1
Pasierb, N	1
Fullwood, JE	1
Mostaghimi, Z	1
Granger, CB	1
Washam, JB	1
Bride, W	1
Zhao, Y	1
Granger, BB	1
Rajmohan, V	1
Sushil, K	1
Mohandas, E	1
Sivakumar, T	1
Yadav, A	1
Sood, M	1
Khandelwal, SK	1
Huang, MC	2
Chen, CH	2
Pan, CH	1
Lin, SK	1
Kasper, S	1
Iglesias-García, C	1
Schweizer, E	3
Wilson, J	1
DuBrava, S	1
Prieto, R	1
Pitman, VW	1
Knapp, L	1
Mueller, SW	1
Preslaski, CR	1
Kiser, TH	1
Fish, DN	1
Lavelle, JC	1
Malkoski, SP	1
MacLaren, R	1
Sohraby, R	1
Attridge, RL	1
Hughes, DW	1
Hoch, HJ	1
Gehring, C	1
Prakash, S	1
Mandal, P	1
Savel, RH	1
Kupfer, Y	1
Crispo, AL	1
Daley, MJ	1
Pepin, JL	1
Harford, PH	1
Brown, CV	1
Guru, S	1
Vanamoorthy, U	1
Loganathan, S	1
Varghese, M	1
Caudron, M	1
Rolland, B	1
Deheul, S	1
Geoffroy, PA	1
Thomas, P	1
Amad, A	1
Stewart, R	1
Perez, R	1
Musial, B	1
Lukens, C	1
Adjepong, YA	1
Manthous, CA	1
Girish, K	1
Vikram Reddy, K	1
Pandit, LV	1
Pundarikaksha, HP	1
Vijendra, R	1
Vasundara, K	1
Manjunatha, R	1
Nagraj, M	1
Shruthi, R	1
Grgurich, P	1
Tulolo, A	1
Smith-Freedman, A	1
Lei, Y	1
Gray, A	1
Dargin, J	1
Vo, KT	1
Horng, H	1
Smollin, CG	1
Benowitz, NL	1
Duncan-Azadi, CR	1
Johnson, PN	1
Gormley, A	1
Kumar, CN	1
Andrade, C	1
Murthy, P	1
Brantley, E	1
Cohn, J	1
Babu, K	1
Myrick, H	4
Malcolm, R	5
Randall, PK	2
Boyle, E	2
Anton, RF	4
Becker, HC	3
Randall, CL	1
Martinotti, G	1
di Nicola, M	1
Frustaci, A	1
Romanelli, R	1
Tedeschi, D	1
Guglielmo, R	1
Guerriero, L	1
Bruschi, A	1
De Filippis, R	1
Pozzi, G	1
Di Giannantonio, M	1
Bria, P	1
Janiri, L	1
Hendey, GW	1
Dery, RA	1
Barnes, RL	1
Snowden, B	1
Mentler, P	1
Liu, HC	1
Chen, CC	1
Ho, CC	1
Leu, SJ	1
Keys, VA	1
Narayanaswamy, JC	1
Viswanath, B	1
Jose, SP	1
Chakraborty, V	1
Subodh, BN	1
Benegal, V	1
Kashyap, GL	1
Patel, AG	1
da Silva, PS	1
Passos, RM	1
Waisberg, DR	1
Wang, BZ	1
Gupta, A	1
Bastiampillai, T	1
Sani, F	1
Amos, JJ	1
Müller, H	1
Seifert, F	1
Maler, JM	1
Kornhuber, J	1
Sperling, W	1
Gulinello, M	1
Gong, QH	1
Smith, SS	4
Hsu, FC	1
Maccioli, GA	1
Multz, AS	1
Rosenberg, MH	1
Deerfield, LJ	1
Baruch, EM	1
Devi, G	1
Stanley, KM	2
Amabile, CM	1
Simpson, KN	2
Couillard, D	1
Norcross, ED	1
Worrall, CL	2
Wichniak, A	1
Brunner, H	1
Ising, M	1
Pedrosa Gil, F	1
Holsboer, F	1
Friess, E	1
Subramaniam, K	1
Gowda, RM	1
Jani, K	1
Zewedie, W	1
Ute, R	1
Stewart, SA	1
Neyman, KM	1
Gourin, CG	1
Terris, DJ	2
Mendhekar, DN	1
Jiloha, RC	1
Veatch, LM	3
Moeller, KE	1
Barnes, BJ	1
Lunsford, SL	1
Miller, JG	1
Spencer, AP	1
Dominguez, KD	1
Crowley, MR	1
Coleman, DM	1
Katz, RW	1
Wilkins, DG	1
Kelly, HW	1
Van Dalfsen, AN	1
Van Den Eede, F	1
Van Den Bossche, B	1
Sabbe, BG	1
McMahon, LR	1
Javors, MA	1
France, CP	1
Skelton, KH	1
Gutman, DA	1
Thrivikraman, KV	1
Nemeroff, CB	1
Owens, MJ	1
Myrick, LH	1
Hartsell, Z	1
Drost, J	1
Wilkens, JA	1
Budavari, AI	1
Carroll, BT	2
Thomas, C	1
Tugrul, KC	1
Coconcea, C	1
Goforth, HW	1
Pizon, AF	1
Lovecchio, F	1
Kwon, P	1
Lefkowitz, W	1
Einarson, TR	2
de la Fuente, JR	1
Rosenbaum, AH	1
Martin, HR	1
Niven, RG	1
Howe, JG	1
Stewart, RB	1
Salem, RB	1
Springer, PK	1
Khan, A	1
Joyce, P	1
Jones, AV	1
Linnoila, M	1
Viukari, M	1
Lamminsivu, U	1
Auvinen, J	1
van Hiele, LJ	1
Tyrer, P	2
Rutherford, D	1
Huggett, T	1
Lapierre, YD	2
Barton, DF	1
de Figueiredo, R	1
Franchini, A	1
Martinho, A	1
Hindmarch, I	1
MacKinnon, GL	1
Parker, WA	1
Shader, RI	3
Greenblatt, DJ	5
McNicholas, LF	2
Martin, WR	2
Cherian, S	1
Griffiths, RR	5
Ator, NA	2
Lukas, SE	1
Lamb, RJ	3
Brady, JV	1
Olajide, D	1
Lader, M	1
Scharf, MB	1
Feil, P	1
Saletu, M	1
Saletu, B	1
Grünberger, J	1
Mader, R	1
Karobath, M	1
Solomon, J	1
Rouck, LA	1
Koepke, HH	1
Kahan, BB	1
Haskett, RF	1
Walsh, JK	1
Schweitzer, PK	1
Parwatikar, S	1
Miller, WC	1
McCurdy, L	1
Adam, K	1
Oswald, I	1
Cumin, R	1
Bonetti, EP	1
Scherschlicht, R	1
Haefely, WE	1
Naranjo, CA	3
Sellers, EM	3
Chater, K	1
Iversen, P	1
Roach, C	1
Sykora, K	2
Kemper, N	1
Poser, W	1
Poser, S	1
Costa, AM	1
Spence, KT	1
ffrench-Mullen, JM	1
Zimbroff, DL	1
Mortensen, M	1
Suzdak, PD	1
Thomsen, C	1
Romach, M	1
Busto, U	2
Somer, G	2
Kaplan, HL	2
Sellers, E	1
Louvel, D	1
Delvaux, M	1
Larrue, V	1
Moreau, J	1
Bonnafous, C	1
Bueno, L	1
Frexinos, J	1
Cohen, SI	2
Newman, JP	1
Moore, M	1
Galynker, II	1
Rosenthal, RN	1
Perkel, C	1
Shwartz, A	1
Cutler, NR	1
Sramek, JJ	1
Keppel Hesselink, JM	2
Krol, A	1
Roeschen, J	2
Rickels, K	4
Deckert, J	1
Przuntek, H	1
Gleiter, CH	1
Tobias, JD	1
Deshpande, JK	1
Gregory, DF	1
Sannerud, CA	1
van der Laan, JW	1
Jansen van't Land, C	1
de Groot, G	1
Bird, RD	1
Makela, EH	1
Byrnes, JJ	1
Miller, LG	4
Perkins, K	1
Kanofsky, JF	1
Lindenmayer, JP	1
Konafsky, D	1
Evans, SM	1
Guarino, JJ	1
Roache, JD	1
Furman, WR	1
Liebson, I	1
Schwam, EM	1
Saitz, R	1
Friedman, LS	1
Mayo-Smith, MF	1
Laine, GA	1
Hossain, SM	1
Solis, RT	1
Adams, SC	1
de Angelis, L	1
Bhattacharya, SK	1
Chakrabarti, A	1
Sandler, M	1
Glover, V	1
Bourin, M	1
Malinge, M	1
Gupta, MB	4
Nath, C	4
Patnaik, GK	2
Saxena, RC	3
Mandos, LA	1
Cutler, N	1
Martínez-Cano, H	1
Vela-Bueno, A	1
de Iceta, M	1
Pomalima, R	1
Martínez-Gras, I	1
Gerra, G	1
Giucasto, G	1
Zaimovic, A	1
Fertonani, G	1
Chittolini, B	1
Avanzini, P	1
Caccavari, R	1
Delsignore, R	1
Saad, SF	1
Khayyal, MT	1
Attia, AS	1
Saad, ES	1
Koff, JM	1
Pritchard, GA	1
Volkow, ND	1
Wang, GJ	1
Fowler, JS	1
Hitzemann, R	1
Gatley, SJ	1
Dewey, SS	1
Pappas, N	1
Busto, UE	2
Bremner, KE	1
Peachey, JE	1
Bologa, M	1
Srisurapanont, M	1
Jarusuraisin, N	1
Romach, MK	1
Moran, MH	1
Goldberg, M	1
Naassila, M	1
Legrand, E	1
d'Alche-Birée, F	1
Daoust, M	1
D'Onofrio, G	1
Rathlev, NK	1
Ulrich, AS	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Auricular Acupressure as an Adjunct Treatment for Opioid Tapering in a Pediatric Cardiac Intensive Care Unit: A Pilot Feasibility Study[NCT05025384]		40 participants (Actual)	Interventional	2021-10-25	Completed
Phenobarbital Versus Ativan for Refractory Alcohol Withdrawal Treatment in the Intensive Care Unit[NCT04156464]	Phase 4	142 participants (Anticipated)	Interventional	2020-07-06	Recruiting
Long Term Safety And Efficacy Study Of Pregabalin (Lyrica) In Subjects With Generalized Anxiety Disorder[NCT00624780]	Phase 4	615 participants (Actual)	Interventional	2009-05-31	Completed
A Randomized, Double-Blind, Placebo Controlled, Dose Escalation Study of Dexmedetomidine as Adjunctive Therapy for Alcohol Withdrawal[NCT00936377]		24 participants (Actual)	Interventional	2009-09-30	Completed
Imaging Framework for Testing GABAergic/Glutamatergic Drugs in Bipolar Alcoholics[NCT03220776]	Phase 2	54 participants (Actual)	Interventional	2017-08-07	Completed
The Effect of N-acetylcysteine (NAC) on Treatment of Alcohol and Cocaine Use Disorders: A Double-Blind Randomized Controlled Trial.[NCT03018236]	Phase 4	100 participants (Anticipated)	Interventional	2017-01-31	Recruiting
A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Dexmedetomidine (Precedex®), With Lorazepam Rescue, for the Management of Severe Alcohol Withdrawal Syndrome (AWS) and Alcohol Withdrawal Delirium (AWD)[NCT01362205]	Phase 4	49 participants (Actual)	Interventional	2012-03-31	Terminated (stopped due to DSMB recommendation for slow enrollment)
Neurocognitive Functioning Following The PROMETA® Treatment Protocol In Subjects With Alcohol Dependence[NCT00570388]		120 participants (Anticipated)	Interventional	2007-03-31	Recruiting
Evaluation of the Standardised Nurse-led Approach for Risk Screening and Decrease of Alcohol Withdrawal Among Adult Inpatients With Alcohol Dependence in an Ear, Nose, Throat and Jaw Surgery Department[NCT02782156]		89 participants (Actual)	Observational	2014-11-30	Completed
The Impact of a Pharmacist Intervention on Post-discharge Hypnotic Drug Discontinuation in Geriatric Inpatients: a Before-after Study[NCT05521971]		173 participants (Actual)	Interventional	2016-10-11	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. (NCT00624780)
Timeframe: Baseline, Week 12

Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Week 24

Intervention	units on a scale (Mean)
Pregabalin High Dose	-2.3
Pregabalin Low Dose	-2.1
Lorazepam	-2.1

Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2

Intervention	units on a scale (Mean)
Pregabalin High Dose, Pregabalin High Dose	-2.4
Pregabalin High Dose, Placebo	-2.3
Pregabalin Low Dose, Pregabalin Low Dose	-2.4
Pregabalin Low Dose, Placebo	-2.0
Lorazepam, Lorazepam	-2.5
Lorazepam, Placebo	-2.2

HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. (NCT00624780)
Timeframe: Baseline, Week 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)

Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2

Intervention	units on a scale (Mean)
Pregabalin High Dose	-12.0
Pregabalin Low Dose	-5.9
Lorazepam	-9.7

Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2

Intervention	units on a scale (Mean)
Pregabalin High Dose	-15.6
Pregabalin Low Dose	-14.9
Lorazepam	-16.0

HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected. (NCT00624780)
Timeframe: Baseline, Week 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)

Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 12

Intervention	units on a scale (Mean)
Pregabalin High Dose, Pregabalin High Dose	-16.6
Pregabalin High Dose, Placebo	-19.1
Pregabalin Low Dose, Pregabalin Low Dose	-18.3
Pregabalin Low Dose, Placebo	-16.0
Lorazepam, Lorazepam	-16.7
Lorazepam, Placebo	-18.7

Change From Baseline in Hamilton Anxiety Scale (HAM-A) Score at Week 24

Intervention	units on a scale (Mean)
Pregabalin High Dose	-17.4
Pregabalin Low Dose	-16.0
Lorazepam	-16.7

Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 2

Intervention	units on a scale (Mean)
Pregabalin High Dose, Pregabalin High Dose	-18.7
Pregabalin High Dose, Placebo	-17.5
Pregabalin Low Dose, Pregabalin Low Dose	-18.2
Pregabalin Low Dose, Placebo	-14.9
Lorazepam, Lorazepam	-19.0
Lorazepam, Placebo	-17.5

PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. (NCT00624780)
Timeframe: Last visit on treatment, Week 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)

Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 2

Intervention	units on a scale (Mean)
Pregabalin High Dose	-2.0
Pregabalin Low Dose	-2.7
Lorazepam	-3.2

Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 2

Intervention	units on a scale (Mean)
Pregabalin High Dose	2.1
Pregabalin Low Dose	2.0
Lorazepam	1.6

Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 1

Intervention	units on a scale (Mean)
Pregabalin High Dose, Pregabalin High Dose	2.8
Pregabalin High Dose, Placebo	-1.0
Pregabalin Low Dose, Pregabalin Low Dose	1.7
Pregabalin Low Dose, Placebo	1.8
Lorazepam, Lorazepam	2.2
Lorazepam, Placebo	-0.1

CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. (NCT00624780)
Timeframe: Week 12

Clinical Global Impression - Improvement (CGI-I) Score at the End of Period 2

Intervention	units on a scale (Mean)
Pregabalin High Dose	1.9
Pregabalin Low Dose	1.9
Lorazepam	1.9

Number of Participants With Rebound Anxiety for Cohort 1 (Less Than 3-Month Last Visit)

Intervention	units on a scale (Mean)
Pregabalin High Dose, Pregabalin High Dose	1.7
Pregabalin High Dose, Placebo	1.9
Pregabalin Low Dose, Pregabalin Low Dose	1.6
Pregabalin Low Dose, Placebo	2.3
Lorazepam, Lorazepam	1.5
Lorazepam, Placebo	2.0

Rebound anxiety was defined as a rapid return of the participant's original symptoms following drug discontinuation, that were worse compared to baseline. This was characterized by a HAM-A score at the Discontinuation Week 1 or Week 2 greater than or equal to the baseline value. (NCT00624780)
Timeframe: 2 weeks post-treatment discontinuation (discontinuation occurred prior to Week 9)

Number of Participants With Rebound Anxiety for Cohort 2 (3-Month Last Visit)

Intervention	participants (Number)
Pregabalin High Dose	1
Pregabalin Low Dose	5
Lorazepam	1

Number of Participants With Rebound Anxiety for Cohort 3 (6-Month Last Visit)

Intervention	participants (Number)
Pregabalin High Dose	3
Pregabalin Low Dose	1
Lorazepam	2

Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1

Intervention	participants (Number)
Pregabalin High Dose, Pregabalin High Dose	4
Pregabalin High Dose, Placebo	0
Pregabalin Low Dose, Pregabalin Low Dose	0
Pregabalin Low Dose, Placebo	1
Lorazepam, Lorazepam	6
Lorazepam, Placebo	0

HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. (NCT00624780)
Timeframe: Baseline, Week 1 post-treatment discontinuation (discontinuation occurred prior to Week 9)

Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1

Intervention	units on a scale (Mean)
	Baseline (n=15,19,21)	Change at Discontinuation Week 1 (n=15,19,18)
Lorazepam	24.4	-9.9
Pregabalin High Dose	25.8	-7.7
Pregabalin Low Dose	24.9	-5.9

HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. (NCT00624780)
Timeframe: Baseline, Week 1 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)

Change From Baseline in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1

Intervention	units on a scale (Mean)
	Baseline	Change at Discontinuation Week 1
Lorazepam	24.6	-15.8
Pregabalin High Dose	25.0	-15.3
Pregabalin Low Dose	24.7	-15.3

HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. (NCT00624780)
Timeframe: Baseline, Week 1 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)

Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2

Intervention	units on a scale (Mean)
	Baseline	Change at Discontinuation Week 1
Lorazepam, Lorazepam	24.6	-16.2
Lorazepam, Placebo	24.9	-19.1
Pregabalin High Dose, Placebo	24.2	-18.7
Pregabalin High Dose, Pregabalin High Dose	25.5	-17.6
Pregabalin Low Dose, Placebo	24.9	-16.5
Pregabalin Low Dose, Pregabalin Low Dose	24.7	-18.4

PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. (NCT00624780)
Timeframe: Baseline, Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)

Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2

Intervention	units on a scale (Mean)
	Baseline (n=14,19,21)	Change at Discontinuation Week 1 (n=14,19,18)	Change at Discontinuation Week 2 (n=13,15,16)
Lorazepam	16.4	-5.9	-5.4
Pregabalin High Dose	13.6	-3.4	-4.7
Pregabalin Low Dose	17.6	-3.3	-2.7

PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. (NCT00624780)
Timeframe: Baseline, Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)

Change From Baseline in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2

Intervention	units on a scale (Mean)
	Baseline (n=57,51,52)	Change at Discontinuation Week 1 (n=57,51,49)	Change at Discontinuation Week 2 (n=53,48,44)
Lorazepam	14.8	-7.6	-8.0
Pregabalin High Dose	17.4	-8.5	-8.3
Pregabalin Low Dose	17.1	-9.3	-8.7

PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. (NCT00624780)
Timeframe: Baseline, Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24)

Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1 and 2

Intervention	units on a scale (Mean)
	Baseline (n=109,30,94,29,99,30)	Change at DC Week 1 (n=109,30,94,29,99,30)	Change at DC Week 2 (n=106,29,84,26,92,30)
Lorazepam, Lorazepam	16.8	-8.7	-9.6
Lorazepam, Placebo	14.9	-10.4	-10.3
Pregabalin High Dose, Placebo	17.8	-12.9	-13.8
Pregabalin High Dose, Pregabalin High Dose	17.8	-11.0	-9.8
Pregabalin Low Dose, Placebo	17.4	-9.9	-10.2
Pregabalin Low Dose, Pregabalin Low Dose	16.1	-11.0	-10.8

HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. (NCT00624780)
Timeframe: Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)

Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1 and 2

Intervention	units on a scale (Mean)
	Last visit on treatment (n=15,18,20)	Change at Discontinuation Week 1 (n=15,18,18)	Change at Discontinuation Week 2 (n=14,15,16)
Lorazepam	16.1	-2.4	-2.2
Pregabalin High Dose	16.1	2.0	-2.3
Pregabalin Low Dose	21.6	-2.3	-3.5

HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected. (NCT00624780)
Timeframe: Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)

Change From Last Visit of Treatment in Hamilton Anxiety Scale (HAM-A) for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1 and 2

Intervention	units on a scale (Mean)
	Last visit on treatment (n=58,52,50)	Change at Discontinuation Week 1 (n=58,52,48)	Change at Discontinuation Week 2 (n=54,49,44)
Lorazepam	6.7	2.3	1.5
Pregabalin High Dose	8.0	1.7	1.5
Pregabalin Low Dose	8.5	0.9	1.5

HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. (NCT00624780)
Timeframe: Last visit on treatment, Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24)

Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit) at Discontinuation Week 1

Intervention	units on a scale (Mean)
	Last visit on treatment (n=109,30,93,29,100,30)	Change at DC Week 1 (n=109,30,93,28,99,30)	Change at DC Week 2 (n=107,29,84,26,94,30)
Lorazepam, Lorazepam	5.6	3.0	2.2
Lorazepam, Placebo	5.5	0.3	0.6
Pregabalin High Dose, Placebo	5.5	-0.0	-0.8
Pregabalin High Dose, Pregabalin High Dose	6.3	1.6	2.5
Pregabalin Low Dose, Placebo	8.3	0.6	1.5
Pregabalin Low Dose, Pregabalin Low Dose	5.6	0.7	1.2

PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. (NCT00624780)
Timeframe: Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred prior to Week 9)

Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit) at Discontinuation Week 1

Intervention	units on a scale (Mean)
	Last visit on treatment (n=15,18,20)	Change at Discontinuation Week 1 (n=15,18,18)
Lorazepam	13.1	-4.2
Pregabalin High Dose	10.1	0.1
Pregabalin Low Dose	16.8	-2.8

PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. (NCT00624780)
Timeframe: Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)

Change From Last Visit on Treatment in Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit) at Discontinuation Week 1

Intervention	units on a scale (Mean)
	Last visit on treatment	Change at Discontinuation Week 1
Lorazepam	5.0	2.3
Pregabalin High Dose	7.2	1.9
Pregabalin Low Dose	6.5	1.4

PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. (NCT00624780)
Timeframe: Last visit on treatment, Week 1 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)

Clinical Global Impression - Severity (CGI-S) Score for Period 1

Intervention	units on a scale (Mean)
	Last visit on treatment	Change at Discontinuation Week 1
Lorazepam, Lorazepam	5.3	3.0
Lorazepam, Placebo	4.7	-0.1
Pregabalin High Dose, Placebo	4.9	0.0
Pregabalin High Dose, Pregabalin High Dose	5.2	1.7
Pregabalin Low Dose, Placebo	6.5	1.0
Pregabalin Low Dose, Pregabalin Low Dose	3.9	1.1

Clinical Global Impression - Severity (CGI-S) Score for Period 2

Intervention	units on a scale (Mean)
	Baseline	Week 12
Lorazepam	4.4	2.3
Pregabalin High Dose	4.6	2.3
Pregabalin Low Dose	4.5	2.5

Hamilton Anxiety Scale (HAM-A) for Cohort 1 (Less Than 3-Month Last Visit)

Intervention	units on a scale (Mean)
	Baseline	Week 24
Lorazepam, Lorazepam	4.4	1.9
Lorazepam, Placebo	4.5	2.4
Pregabalin High Dose, Placebo	4.5	2.2
Pregabalin High Dose, Pregabalin High Dose	4.7	2.3
Pregabalin Low Dose, Placebo	4.5	2.5
Pregabalin Low Dose, Pregabalin Low Dose	4.5	2.1

HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. (NCT00624780)
Timeframe: Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)

Hamilton Anxiety Scale (HAM-A) for Cohort 2 (3-Month Last Visit)

Intervention	units on a scale (Mean)
	Discontinuation Week 1 (n=15,19,18)	Discontinuation Week 2 (n=14,15,16)
Lorazepam	14.1	14.6
Pregabalin High Dose	18.1	13.9
Pregabalin Low Dose	19.0	18.6

HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected. (NCT00624780)
Timeframe: Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)

Hamilton Anxiety Scale (HAM-A) Score for Cohort 3 (6-Month Last Visit)

Intervention	units on a scale (Mean)
	Discontinuation Week 1 (n=58,52,48)	Discontinuation Week 2 (n=54,49,44)
Lorazepam	8.8	8.3
Pregabalin High Dose	9.6	9.0
Pregabalin Low Dose	9.4	9.9

HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); total possible range 0 to 56. Lower score indicates less affected. (NCT00624780)
Timeframe: Week 1, 2 post-treatment discontinuation (discontinuation [DC] occurred after Week 15 to Week 24)

Hamilton Anxiety Scale (HAM-A) Score for Period 1

Intervention	units on a scale (Mean)
	Discontinuation Week 1 (n=109,30,94,28,99,30)	Discontinuation Week 2 (n=107,29,84,26,94,30)
Lorazepam, Lorazepam	8.4	7.9
Lorazepam, Placebo	7.07	6.1
Pregabalin High Dose, Placebo	5.5	5.0
Pregabalin High Dose, Pregabalin High Dose	7.9	8.9
Pregabalin Low Dose, Placebo	8.4	9.2
Pregabalin Low Dose, Pregabalin Low Dose	6.3	6.5

Hamilton Anxiety Scale (HAM-A) Score for Period 2

Intervention	units on a scale (Mean)
	Baseline	Week 12
Lorazepam	24.5	7.9
Pregabalin High Dose	25.3	8.0
Pregabalin Low Dose	24.9	8.9

Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 1 (Less Than 3-Month Last Visit)

Intervention	units on a scale (Mean)
	Baseline	Week 24
Lorazepam, Lorazepam	24.7	5.7
Lorazepam, Placebo	24.1	6.6
Pregabalin High Dose, Placebo	24.6	7.1
Pregabalin High Dose, Pregabalin High Dose	25.6	7.0
Pregabalin Low Dose, Placebo	25.1	10.2
Pregabalin Low Dose, Pregabalin Low Dose	24.8	6.5

DESS adverse events, a subset of Treatment Emergent Signs and Symptoms (TESS), were defined as those spontaneously reported adverse events that developed or existed prior to but worsened during Discontinuation Week 1 and 2. (NCT00624780)
Timeframe: 2 weeks post-treatment discontinuation (discontinuation occurred prior to Week 9)

Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 2 (3-Month Last Visit)

Intervention	participants (Number)
	Newly developed DESS	Worsened DESS
Lorazepam	3	0
Pregabalin High Dose	6	0
Pregabalin Low Dose	0	0

Number of Participants With Discontinuation-Emergent Signs and Symptoms (DESS) for Cohort 3 (6-Month Last Visit)

Intervention	participants (Number)
	Newly developed DESS	Worsened DESS
Lorazepam	36	1
Pregabalin High Dose	40	1
Pregabalin Low Dose	38	2

Number of Participants With Treatment-Emergent Adverse Events (AEs)

Intervention	participants (Number)
	Newly developed DESS	Worsened DESS
Lorazepam, Lorazepam	50	5
Lorazepam, Placebo	7	0
Pregabalin High Dose, Placebo	5	0
Pregabalin High Dose, Pregabalin High Dose	78	2
Pregabalin Low Dose, Placebo	17	1
Pregabalin Low Dose, Pregabalin Low Dose	35	2

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and Week 12, for period 1, and between Week 13 and Week 24, for period 2, that were absent before treatment or that worsened relative to pretreatment state. (NCT00624780)
Timeframe: Baseline up to Week 12 (period 1), Week 13 up to Week 24 (period 2)

Physician's Withdrawal Checklist (PWC) Score for Cohort 1 (Less Than 3-Month Last Visit)

Intervention	participants (Number)
	Period 1 (n=154,52,154,52,153,50)	Period 2 (n=121,39,112,38,114,39)
Lorazepam, Lorazepam	95	52
Lorazepam, Placebo	35	20
Pregabalin High Dose, Placebo	37	26
Pregabalin High Dose, Pregabalin High Dose	103	62
Pregabalin Low Dose, Placebo	40	18
Pregabalin Low Dose, Pregabalin Low Dose	100	62

PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. (NCT00624780)
Timeframe: Week 1, 2 post-treatment discontinuation (discontinuation occurred prior to Week 9)

Physician's Withdrawal Checklist (PWC) Score for Cohort 2 (3-Month Last Visit)

Intervention	units on a scale (Mean)
	Discontinuation Week 1 (n=15,19,18)	Discontinuation Week 2 (n=14,15,16)
Lorazepam	9.1	10.6
Pregabalin High Dose	10.2	8.2
Pregabalin Low Dose	14.3	14.1

PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. (NCT00624780)
Timeframe: Week 1, 2 post-treatment discontinuation (discontinuation occurred from Week 9 to Week 15)

Physician's Withdrawal Checklist (PWC) Score for Cohort 3 (6-Month Last Visit)

Intervention	units on a scale (Mean)
	Discontinuation Week 1 (n=58,52,49)	Discontinuation Week 2 (n=54,49,44)
Lorazepam	7.3	6.9
Pregabalin High Dose	9.1	8.9
Pregabalin Low Dose	8.0	8.3

PWC: 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected. (NCT00624780)
Timeframe: Week 1, 2 post-treatment discontinuation (discontinuation occurred after Week 15 to Week 24)

Change in 12-Hour Lorazepam Requirement Pre- and Post-Treatment

Intervention	units on a scale (Mean)
	Discontinuation Week 1 (n=109,30,94,29,99,30)	Discontinuation Week 2 (n=106,29,84,26,93,30)
Lorazepam, Lorazepam	8.0	7.1
Lorazepam, Placebo	4.6	4.6
Pregabalin High Dose, Placebo	4.9	4.1
Pregabalin High Dose, Pregabalin High Dose	6.8	7.9
Pregabalin Low Dose, Placebo	7.4	7.1
Pregabalin Low Dose, Pregabalin Low Dose	5.1	5.7

(NCT00936377)
Timeframe: 12 hours before treatment, 12 hours after treatment on first day of starting study drug

Change in 24-Hour Lorazepam Requirement Pre- and Post-Treatment

Intervention	mg (Median)
Dexmedetomidine, Low Dose	-42.5
Dexmedetomidine, High Dose	-34.3
Placebo	-17.5

(NCT00936377)
Timeframe: 24 hours before treatment, 24 hours after treatment on first day of starting study drug

Cumulative Lorazepam Dose Over the First Seven Days of Alcohol Withdrawal

Duration of Study Drug Administration

Intervention	mg (Median)
Dexmedetomidine, Low Dose	-62.1
Dexmedetomidine, High Dose	-45
Placebo	-8

Intervention	mg (Median)
Dexmedetomidine, Low Dose	180.5
Dexmedetomidine, High Dose	112.5
Placebo	109.1

(NCT00936377)
Timeframe: The duration of study drug in hours as measured when the subject was discharged from the ICU, for up to 24 weeks

ICU Length of Stay

Intervention	hours (Median)
Dexmedetomidine, Low Dose	53.1
Dexmedetomidine, High Dose	78
Placebo	70.3

(NCT00936377)
Timeframe: The duration of ICU stay in days as measured at time of hospital discharge, for up to 24 weeks

Plasma Epinephrine Concentrations Across Groups Over Time

Intervention	days (Median)
Dexmedetomidine, Low Dose	5.5
Dexmedetomidine, High Dose	3.8
Placebo	4

Plasma epinephrine concentrations (NCT00936377)
Timeframe: Four days with samples measured prior to study drug and 48 and 96 hours after starting study drug

The Degree of Alcohol Withdrawal Assessed by Clinical Institute Withdrawal Assessment (CIWA) Scores

Proportion of clinical institute withdrawal assessment (CIWA) Scores listed as severe or moderate 24 Hours after Starting Study Drug. All subjects had at least four CIWA assessments.The CIWA is a ten item scale with each item on the scale scored independently on a 0-7 or 0-4 scale, and the summation of the scores yielding an aggregate value that correlates to the severity of alcohol withdrawal. Ranges of scores are from 0 to 67. Mild alcohol withdrawal is defined with a score less than or equal to 15, moderate with scores of 16 to 20, and severe with any score greater than 20. The ten items evaluated include nausea and vomiting, tremor, sweats, anxiety, agitation, tactile disturbances, auditory disturbances, visual disturbances, headache, and orientation. (NCT00936377)
Timeframe: Every 2-4 hours for 24 hours after starting study drug

The Occurrence of Adverse Events.

Occurrence of hypotension or bradycardia while on study drug (NCT00936377)
Timeframe: Seven days

Prefrontal GABA+ Concentrations

Concentrations of GABA+, referenced to unsuppressed water and corrected for within-voxel CSF proportion, in dorsal anterior cingulate cortex measured via Proton Magnetic Resonance Spectroscopy (i.e., MEGA-PRESS). (NCT03220776)
Timeframe: Day 5 of each experimental condition

Prefrontal Glx Concentrations

Concentrations of Glx (i.e., glutamate + glutamine), referenced to unsuppressed water and corrected for within-voxel CSF proportion, in dorsal anterior cingulate cortex measured via Proton Magnetic Resonance Spectroscopy. (NCT03220776)
Timeframe: Day 5 of each experimental condition

Average MINDS Score

Minnesota Detoxification Scale (MINDS) min score 0, max score 46. The higher the score, the worse the symptoms of AWS/AWD. (NCT01362205)
Timeframe: up to 28 days

Number of Ventilator Free Days After Randomization.

A ventilator day is counted for any use of invasive mechanical ventilation during a calendar day (NCT01362205)
Timeframe: up to 28 days

Resource Utilization Costs Associated With This Hospitalization Billed by Facility.

Resource Utilization Costs Associated With This Hospitalization Billed by Physicians.

Scores at Hospital Discharge on the Beck Anxiety Inventory

The Beck Anxiety Inventory is a validated questionnaire used to measure severity of anxiety (min score 0, max score 63). The higher the score the greater the severity of anxiety. A score of 30-63 indicates severe anxiety, 17-29 moderate anxiety, 10-16 mild anxiety and 0-9 minimal anxiety. (NCT01362205)
Timeframe: Up to 28 days.

Scores at Hospital Discharge on the Beck Depression Inventory.

The Beck Depression Inventory is a validated questionnaire used to measure severity of depression (min score 0, max score 63). The higher the score the greater the severity of depression. A score of 30-63 indicates severe depression, 19-29 moderate depression, 10-18 mild depression and 0-9 minimal depression. (NCT01362205)
Timeframe: Up to 28 days.

Scores at Hospital Discharge on the Mini Mental Exam.

The Mini Mental State Examination or Folstein test is a validated 30-point questionnaire used to measure cognitive impairment (min score 0, max score 30). A score of 24 points (out of a max of 30) indicates normal cognition, less than or equal to 9 points indicates severe impairment, 10-18 indicates moderate impairment and 19-23 mild impairment. (NCT01362205)
Timeframe: up to 28 days

Scores at Hospital Discharge on the PTSD Civilian Checklist

PTSD checklist consists of 17 questions graded on a scale of 1 to 5. The PTSD score is comprised from the sum of the scores 17 questions. The PTSD score has possible values from to 17 to 85 with higher values indicating greater symptom severity. (NCT01362205)
Timeframe: Up to 28 days

The Length in Days of the Hospital Stay

A hospital day is counted for any time on a calendar day the patient is admitted to the hospital. Hospital days are inclusive of ICU days. (NCT01362205)
Timeframe: up to 28 days

The Length of ICU Stay Defined as the Time Between Randomization and ICU Transfer Orders.

The Number of CAM-ICU Negative Days After Randomization.

The Confusion Assessment Method (CAM)-ICU is a validated instrument used to detect the presence or absence of delirium in the ICU. A delirium free day is counted for any day a patient is negative by the CAM-ICU. The higher the number of CAM-ICU negative days indicates the more days a patient was able to think clearly. (NCT01362205)
Timeframe: up to 28 days

Intervention	ng/mL (Mean)
	Baseline	Time 48 hours	Time 96 hours
Dexmedetomidine, High Dose	0.29	0.21	0.27
Dexmedetomidine, Low Dose	0.27	0.27	0.26
Placebo	0.31	0.27	0.3

Intervention	percentage of ciwa assessment (Number)
	severe	moderate
Dexmedetomidine, High Dose	15	24
Dexmedetomidine, Low Dose	11	31
Placebo	25	22

Intervention	participants (Number)
	Hypotension	Bradycardia
Dexmedetomidine, High Dose	2	3
Dexmedetomidine, Low Dose	1	1
Placebo	0	0

Intervention	mmol/kg (Mean)
N-Acetylcysteine	21.59
Gabapentin	21.69
Placebo Oral Tablet	22.25

Article	Year
Paradoxical Excitation Following Intravenous Lorazepam Administration for Alcohol Withdrawal - A Case Presentation and Literature Review. Journal of pharmacy practice, 2023, Volume: 36, Issue:5 Topics: Alcoholism; Benzodiazepines; Humans; Infusions, Intravenous; Lorazepam; Male; Middle Aged; Substance	2023
Beyond benzodiazepines: a meta-analysis and narrative synthesis of the efficacy and safety of alternative options for alcohol withdrawal syndrome management. European journal of clinical pharmacology, 2023, Volume: 79, Issue:9 Topics: Alcoholism; Benzodiazepines; Ethanol; Humans; Lorazepam; Randomized Controlled Trials as Topic; Subs	2023
Acute phenibut withdrawal: A comprehensive literature review and illustrative case report. Bosnian journal of basic medical sciences, 2019, May-20, Volume: 19, Issue:2 Topics: Akathisia, Drug-Induced; Baclofen; Cyproheptadine; Dexmedetomidine; Diphenhydramine; GABA-A Receptor	2019
Symptom-Triggered Therapy for Alcohol Withdrawal Syndrome: a Systematic Review and Meta-analysis of Randomized Controlled Trials. Journal of general internal medicine, 2019, Volume: 34, Issue:6 Topics: Alcoholism; Benzodiazepines; Humans; Lorazepam; Randomized Controlled Trials as Topic; Substance Wit	2019
Propofol combined with lorazepam for severe poly substance misuse and withdrawal states in intensive care unit: a case series and review. Emergency medicine journal : EMJ, 2004, Volume: 21, Issue:5 Topics: Adult; Anesthetics, Intravenous; Critical Care; Drug Therapy, Combination; Female; Humans; Hypnotics	2004
The effects of benzodiazepines on cognition. The Journal of clinical psychiatry, 2005, Volume: 66 Suppl 2 Topics: Activities of Daily Living; Anti-Anxiety Agents; Anxiety Disorders; Benzodiazepines; Cognition; Cogn	2005
Managing alcohol withdrawal in hospitalized patients. JAAPA : official journal of the American Academy of Physician Assistants, 2007, Volume: 20, Issue:9 Topics: Alcohol-Induced Disorders; Anti-Anxiety Agents; Benzodiazepines; Diazepam; Hospitalization; Humans;	2007
Benzodiazepine withdrawal syndrome: a literature review and evaluation. The American journal of drug and alcohol abuse, 1982, Volume: 9, Issue:1 Topics: Anti-Anxiety Agents; Chlordiazepoxide; Diazepam; Dose-Response Relationship, Drug; Humans; Lorazepam	1982
The use of benzodiazepines in clinical practice. British journal of clinical pharmacology, 1981, Volume: 11 Suppl 1 Topics: Anti-Anxiety Agents; Chlordiazepoxide; Clorazepate Dipotassium; Diazepam; Humans; Kinetics; Lorazepa	1981
Alcohol withdrawal: what is the benzodiazepine of choice? The Annals of pharmacotherapy, 1994, Volume: 28, Issue:1 Topics: Alcohol Withdrawal Delirium; Benzodiazepines; Chlordiazepoxide; Clinical Trials as Topic; Diazepam;	1994
Chronic benzodiazepine administration: from the patient to the gene. Journal of clinical pharmacology, 1991, Volume: 31, Issue:6 Topics: Alprazolam; Animals; Benzodiazepines; Clonazepam; Down-Regulation; Drug Tolerance; Flumazenil; Human	1991
Rebound insomnia and elimination half-life: assessment of individual subject response. Journal of clinical pharmacology, 1985, Volume: 25, Issue:2 Topics: Adult; Anti-Anxiety Agents; Benzodiazepines; Clinical Trials as Topic; Dose-Response Relationship, D	1985
Emerging treatment options in the alcohol withdrawal syndrome. The Journal of clinical psychiatry, 1988, Volume: 49 Suppl Topics: Adrenergic beta-Antagonists; Alcohol Withdrawal Delirium; Benzodiazepines; Drug Therapy, Combination	1988

Article	Year
Alcohol withdrawal prevention: a randomized evaluation of lorazepam and ethanol--a pilot study. American journal of critical care : an official publication, American Association of Critical-Care Nurses, 2013, Volume: 22, Issue:5 Topics: Acute Coronary Syndrome; Adult; Alcoholism; Central Nervous System Depressants; Drug Therapy, Combin	2013
A double blind randomised comparison of chlordiazepoxide and lorazepam in alcohol withdrawal. Asian journal of psychiatry, 2013, Volume: 6, Issue:5 Topics: Adult; Alcoholism; Analysis of Variance; Chlordiazepoxide; Double-Blind Method; Humans; Hypnotics an	2013
Lack of efficacy of dextromethorphan in managing alcohol withdrawal: a preliminary report of a randomized, double-blind, placebo-controlled trial. Journal of clinical psychopharmacology, 2014, Volume: 34, Issue:1 Topics: Adult; Alcohol Abstinence; Alcohol Drinking; Alcoholism; Brain; Dextromethorphan; Double-Blind Metho	2014
Pregabalin long-term treatment and assessment of discontinuation in patients with generalized anxiety disorder. The international journal of neuropsychopharmacology, 2014, Volume: 17, Issue:5 Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Anxiety Disorders; Dose-Response Relationship, Drug; D	2014
A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal. Critical care medicine, 2014, Volume: 42, Issue:5 Topics: Adult; Anticonvulsants; Dexmedetomidine; Dose-Response Relationship, Drug; Double-Blind Method; Drug	2014
A randomized, open-label, standard controlled, parallel group study of efficacy and safety of baclofen, and chlordiazepoxide in uncomplicated alcohol withdrawal syndrome. Biomedical journal, 2016, Volume: 39, Issue:1 Topics: Adult; Alcohol Drinking; Baclofen; Chlordiazepoxide; Diazepam; Humans; Lorazepam; Male; Middle Aged;	2016
A randomized, double-blind comparison of lorazepam and chlordiazepoxide in patients with uncomplicated alcohol withdrawal. Journal of studies on alcohol and drugs, 2009, Volume: 70, Issue:3 Topics: Adolescent; Adult; Alcohol-Induced Disorders; Alcoholism; Chlordiazepoxide; Drug Administration Sche	2009
A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal. Alcoholism, clinical and experimental research, 2009, Volume: 33, Issue:9 Topics: Adult; Alcohol Drinking; Amines; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Doub	2009
Pregabalin, tiapride and lorazepam in alcohol withdrawal syndrome: a multi-centre, randomized, single-blind comparison trial. Addiction (Abingdon, England), 2010, Volume: 105, Issue:2 Topics: Adolescent; Adult; Aged; Alcoholism; Analgesics; Female; gamma-Aminobutyric Acid; Humans; Lorazepam;	2010
A prospective, randomized, trial of phenobarbital versus benzodiazepines for acute alcohol withdrawal. The American journal of emergency medicine, 2011, Volume: 29, Issue:4 Topics: Administration, Oral; Alcohol-Related Disorders; Chlordiazepoxide; Female; GABA Modulators; Humans;	2011
Impaired hypothalamic-pituitary-adrenocortical (HPA) system is related to severity of benzodiazepine withdrawal in patients with depression. Psychoneuroendocrinology, 2004, Volume: 29, Issue:9 Topics: Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; Antidepressive Agents; Benzodiazepines;	2004
Withdrawal from lorazepam in critically ill children. The Annals of pharmacotherapy, 2006, Volume: 40, Issue:6 Topics: Child, Preschool; Critical Illness; Dose-Response Relationship, Drug; Endpoint Determination; Female	2006
Self-reported sleep, sleepiness, and repeated alcohol withdrawals: a randomized, double blind, controlled comparison of lorazepam vs gabapentin. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2007, Feb-15, Volume: 3, Issue:1 Topics: Adult; Aged; Alcoholism; Amines; Cyclohexanecarboxylic Acids; Disorders of Excessive Somnolence; Dou	2007
Efficacy and side effects of lorazepam, oxazepam, and temazepam as sleeping aids in psychogeriatric inpatients. International pharmacopsychiatry, 1980, Volume: 15, Issue:2 Topics: Aged; Anti-Anxiety Agents; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Lorazepam;	1980
Benzodiazepine withdrawal symptoms and propranolol. Lancet (London, England), 1981, Mar-07, Volume: 1, Issue:8219 Topics: Anti-Anxiety Agents; Diazepam; Humans; Lorazepam; Placebos; Propranolol; Substance Withdrawal Syndro	1981
Differences in the effect of two benzodiazepines in the treatment of anxious outpatients. International pharmacopsychiatry, 1981, Volume: 16, Issue:1 Topics: Adult; Ambulatory Care; Anti-Anxiety Agents; Anxiety; Benzodiazepines; Benzodiazepinones; Clinical T	1981
Clinical symptomatology and computer analyzed EEG before, during and after anxiolytic therapy of alcohol withdrawal patients. Neuropsychobiology, 1983, Volume: 9, Issue:2-3 Topics: Adult; Alcoholism; Clinical Trials as Topic; Computers; Double-Blind Method; Electroencephalography;	1983
Double-blind comparison of lorazepam and chlordiazepoxide in the treatment of the acute alcohol abstinence syndrome. Clinical therapeutics, 1983, Volume: 6, Issue:1 Topics: Acute Disease; Adult; Aged; Chlordiazepoxide; Clinical Trials as Topic; Double-Blind Method; Drug Ad	1983
Effects of lorazepam and its withdrawal on sleep, performance, and subjective state. Clinical pharmacology and therapeutics, 1983, Volume: 34, Issue:4 Topics: Adult; Anxiety; Female; Humans; Lorazepam; Male; Psychomotor Performance; Sleep Initiation and Maint	1983
Nonpharmacologic intervention in acute alcohol withdrawal. Clinical pharmacology and therapeutics, 1983, Volume: 34, Issue:2 Topics: Adult; Alcoholism; Double-Blind Method; Female; Humans; Lorazepam; Male; Middle Aged; Substance With	1983
A double-blind, placebo-controlled study comparing the efficacy and safety of ipsapirone versus lorazepam in patients with generalized anxiety disorder: a prospective multicenter trial. Journal of clinical psychopharmacology, 1993, Volume: 13, Issue:6 Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Double-Blind Method; Female; Humans; Lorazepam; Male;	1993
Intravenous flumazenil following acute and repeated exposure to lorazepam in healthy volunteers: antagonism and precipitated withdrawal. The Journal of pharmacology and experimental therapeutics, 1993, Volume: 265, Issue:3 Topics: Adolescent; Adult; Drug Interactions; Flumazenil; Hemodynamics; Humans; Injections, Intravenous; Lor	1993
Controlled comparison of the effects and abrupt discontinuation of buspirone and lorazepam. Progress in neuro-psychopharmacology & biological psychiatry, 1995, Volume: 19, Issue:4 Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Anxiety Disorders; Buspirone; Double-Blind Method; Fem	1995
Placebo-controlled comparison of the clinical effects of rapid discontinuation of ipsapirone and lorazepam after 8 weeks of treatment for generalized anxiety disorder. International clinical psychopharmacology, 1995, Volume: 10, Issue:4 Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Female; Humans; Lorazepam; Male; Placebo Effect; Psyc	1995
Intravenous flumazenil following prolonged exposure to lormetazepam in humans: lack of precipitated withdrawal. International clinical psychopharmacology, 1996, Volume: 11, Issue:2 Topics: Adult; Anti-Anxiety Agents; Benzodiazepines; Double-Blind Method; Flumazenil; GABA Modulators; Human	1996
Safety of ipsapirone treatment compared with lorazepam: discontinuation effects. Journal of psychiatry & neuroscience : JPN, 1998, Volume: 23, Issue:1 Topics: Adult; Anti-Anxiety Agents; Double-Blind Method; Humans; Lorazepam; Male; Prospective Studies; Pyrim	1998
Amitriptyline vs. lorazepam in the treatment of opiate-withdrawal insomnia: a randomized double-blind study. Acta psychiatrica Scandinavica, 1998, Volume: 97, Issue:3 Topics: Adult; Amitriptyline; Anti-Anxiety Agents; Antidepressive Agents, Tricyclic; Double-Blind Method; Fe	1998
A controlled trial of ondansetron, a 5-HT3 antagonist, in benzodiazepine discontinuation. Journal of clinical psychopharmacology, 1998, Volume: 18, Issue:2 Topics: Alprazolam; Anti-Anxiety Agents; Anxiety; Double-Blind Method; Female; Humans; Lorazepam; Male; Midd	1998
Lorazepam for the prevention of recurrent seizures related to alcohol. The New England journal of medicine, 1999, Mar-25, Volume: 340, Issue:12 Topics: Adult; Alcoholism; Anticonvulsants; Double-Blind Method; Ethanol; Female; Humans; Injections, Intrav	1999
Butorphanol agonist effects and acute physical dependence in opioid abusers: comparison with morphine. Drug and alcohol dependence, 1998, Dec-01, Volume: 53, Issue:1 Topics: Adult; Arousal; Brain; Butorphanol; Dose-Response Relationship, Drug; Double-Blind Method; Euphoria;	1998
Fast withdrawal from benzodiazepines in geriatric inpatients: a randomised double-blind, placebo-controlled trial. European journal of clinical pharmacology, 2002, Volume: 57, Issue:11 Topics: Aged; Aged, 80 and over; Alcoholism; Anti-Anxiety Agents; Benzodiazepines; Double-Blind Method; Fema	2002
The differential effects of medication on mood, sleep disturbance, and work ability in outpatient alcohol detoxification. The American journal on addictions, 2002,Spring, Volume: 11, Issue:2 Topics: Adult; Affect; Alcoholism; Anti-Anxiety Agents; Anticonvulsants; Anxiety; Carbamazepine; Double-Blin	2002
The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. Journal of general internal medicine, 2002, Volume: 17, Issue:5 Topics: Adult; Alcoholism; Ambulatory Care; Anti-Anxiety Agents; Anticonvulsants; Carbamazepine; Double-Blin	2002
A double-blind comparison of the effects of gradual withdrawal of lorazepam, diazepam and bromazepam in benzodiazepine dependence. The British journal of psychiatry : the journal of mental science, 1991, Volume: 158 Topics: Adult; Anti-Anxiety Agents; Bromazepam; Diazepam; Dose-Response Relationship, Drug; Double-Blind Met	1991
Agitation in the demented elderly: a role for benzodiazepines? International clinical psychopharmacology, 1991,Winter, Volume: 6, Issue:3 Topics: Aged; Alprazolam; Dementia; Double-Blind Method; Female; Humans; Lorazepam; Male; Motor Activity; Ps	1991
[Benzodiazepine withdrawal syndrome. Problems of differential diagnosis against depression, panic attacks and generalized anxiety]. La Clinica terapeutica, 1991, May-15, Volume: 137, Issue:3 Topics: Anxiety; Benzodiazepines; Depression; Diagnosis, Differential; Double-Blind Method; Humans; Lorazepa	1991
Efficacy and withdrawal of two potent benzodiazepines: bromazepam and lorazepam. Psychopharmacology bulletin, 1985, Volume: 21, Issue:1 Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Bromazepam; Clinical Trials as Topic; Double-Blind Me	1985
Rebound insomnia and elimination half-life: assessment of individual subject response. Journal of clinical pharmacology, 1985, Volume: 25, Issue:2 Topics: Adult; Anti-Anxiety Agents; Benzodiazepines; Clinical Trials as Topic; Dose-Response Relationship, D	1985
Clorazepate and lorazepam: clinical improvement and rebound anxiety. The American journal of psychiatry, 1988, Volume: 145, Issue:3 Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Clinical Trials as Topic; Clorazepate Dipotassium; Do	1988
Withdrawal reaction after long-term therapeutic use of benzodiazepines. The New England journal of medicine, 1986, Oct-02, Volume: 315, Issue:14 Topics: Adolescent; Adult; Aged; Anxiety; Benzodiazepines; Diazepam; Double-Blind Method; Female; Flurazepam	1986
Comparison of lorazepam and flurazepam as hypnotic agents in chronic insomniacs. Journal of clinical pharmacology, 1988, Volume: 28, Issue:1 Topics: Adult; Arousal; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Electroencephalograp	1988
Comparison of two benzodiazepines in the treatment of alcohol withdrawal: effects on symptoms and cognitive recovery. Drug and alcohol dependence, 1986, Volume: 18, Issue:4 Topics: Adult; Cognition; Diazepam; Ethanol; Female; Humans; Lorazepam; Male; Middle Aged; Psychological Tes	1986
Indications and contraindications for chronic anxiolytic treatment: is there tolerance to the anxiolytic effect? Advances in biochemical psychopharmacology, 1985, Volume: 40 Topics: Anxiety; Chronic Disease; Clinical Trials as Topic; Clorazepate Dipotassium; Diazepam; Double-Blind	1985

lorazepam and Substance Withdrawal Syndrome