gamma-aminobutyric acid and Anxiety Neuroses studies

gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.
gamma-aminobutyric acid : A gamma-amino acid that is butanoic acid with the amino substituent located at C-4.

Research Excerpts

Excerpt	Relevance	Reference
"Pregabalin was generally well tolerated in the long-term treatment of anxiety disorders."	9.17	Long-term treatment of anxiety disorders with pregabalin: a 1 year open-label study of safety and tolerability. ( Emir, B; Haswell, H; Montgomery, S; Prieto, R, 2013)
"We will include all randomised controlled trials (RCTs) reported as double-blind and comparing gabapentin or pregabalin with placebo or any other active pharmacological treatment (any preparation, dose, frequency, route of delivery or setting) in patients with bipolar disorder, anxiety or insomnia."	8.95	Biological rationale and potential clinical use of gabapentin and pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis. ( Atkinson, LZ; Awad, A; Cipriani, A; Forrest, A; Geddes, JR; Harrison, PJ; Houghton, KT; Stockton, S, 2017)
" Gabapentin and pregabalin, a very similar drug with the same mechanism of action, bind to a subunit of voltage-dependent calcium channels which are implicated in the aetiopathogenesis of bipolar disorder, anxiety and insomnia."	8.95	Biological rationale and potential clinical use of gabapentin and pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis. ( Atkinson, LZ; Awad, A; Cipriani, A; Forrest, A; Geddes, JR; Harrison, PJ; Houghton, KT; Stockton, S, 2017)
"Data from the MEDLINE database were searched using algorithms to identify relevant economic evaluations published in English or Spanish on pregabalin for the management of neuropathic pain, generalized anxiety disorder (GAD), and epilepsy in Spanish patients over the last 10 years."	8.90	Pharmacoeconomic outcomes for pregabalin: a systematic review in neuropathic pain, generalized anxiety disorder, and epilepsy from a Spanish perspective. ( Álvarez, E; Darbà, J; Kaskens, L; Navarro-Artieda, R; Pérez, C; Sicras-Mainar, A, 2014)
"The majority of published evidence supports the possibility that pregabalin could be a cost-effective and/or cost-saving alternative for the treatment of refractory epilepsy, GAD, and neuropathic pain, in both treatment-naïve patients and in those who have demonstrated inadequate response or intolerance to previous therapy."	8.90	Pharmacoeconomic outcomes for pregabalin: a systematic review in neuropathic pain, generalized anxiety disorder, and epilepsy from a Spanish perspective. ( Álvarez, E; Darbà, J; Kaskens, L; Navarro-Artieda, R; Pérez, C; Sicras-Mainar, A, 2014)
"Pregabalin appears to be an effective therapy in patients with diabetic peripheral neuropathy, postherpetic neuralgia, and adults with refractory partial-onset seizures."	8.84	Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. ( Boyce, E; Guyer, J; Nuzum, D; Tassone, DM, 2007)
"The US Food and Drug Administration (FDA) approved pregabalin in December 2004 for the treatment of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia."	8.84	Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. ( Boyce, E; Guyer, J; Nuzum, D; Tassone, DM, 2007)
" The search terms included pregabalin, Lyrica, S-(+)-3 isobutyl-gaba, PN, DPN, diabetic peripheral neuropathy, PHN, postherpetic neuralgia, partial seizures, epilepsy, generalized anxiety disorder, and CI-1008."	8.84	Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. ( Boyce, E; Guyer, J; Nuzum, D; Tassone, DM, 2007)
"Pregabalin was mainly used as a second-line drug for the treatment of GAD or neuropathic pain and to a lesser extent as add-on therapy in epilepsy."	7.80	Pregabalin is increasingly prescribed for neuropathic pain, generalised anxiety disorder and epilepsy but many patients discontinue treatment. ( Bodén, R; Brandt, L; Kieler, H; Wettermark, B, 2014)
"Dizziness and drowsiness are cited as being predictors of dropout from clinical trials for the medicine pregabalin."	7.75	Joint modeling of dizziness, drowsiness, and dropout associated with pregabalin and placebo treatment of generalized anxiety disorder. ( Frame, B; Hutmacher, MM; Miller, R, 2009)
"To describe the pregabalin exposure-adverse event (AE) (dizziness) relationship in patients with generalized anxiety disorder, separate models were developed for the incidence of AE and for the conditional severity of AE, given that an AE has occurred using patient data from six clinical studies."	7.74	Exposure-response analysis for spontaneously reported dizziness in pregabalin-treated patient with generalized anxiety disorder. ( Frame, B; Hutmacher, M; Ito, K; Liu, J; Miller, R; Qiu, R, 2008)
"We evaluated effectiveness and predictors of response of gabapentin (GBP) as adjunctive treatment in a sample of 43 subjects with DSM-III-R bipolar disorder who were resistant to standard mood stabilizers."	7.71	Effectiveness of adjunctive gabapentin in resistant bipolar disorder: is it due to anxious-alcohol abuse comorbidity? ( Akiskal, HS; Frare, F; Moretti, L; Perugi, G; Ruffolo, G; Toni, C; Torti, C, 2002)
"Low levels of gamma-aminobutyric acid (GABA) in plasma have been associated with the presence of mood disorders in patients with major depressive disorder."	7.69	Plasma levels of gamma-aminobutyric acid and panic disorder. ( Davis, LL; Germine, M; Goddard, AW; Kramer, GL; Narayan, M; Petty, F; Woods, SW, 1996)
"5%) was the only treatment-related adverse event (AE) occurring ≥10%."	6.78	Long-term treatment of anxiety disorders with pregabalin: a 1 year open-label study of safety and tolerability. ( Emir, B; Haswell, H; Montgomery, S; Prieto, R, 2013)
"Gabapentin has been extensively prescribed off-label for psychiatric indications, with little established evidence of efficacy."	6.55	Biological rationale and potential clinical use of gabapentin and pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis. ( Atkinson, LZ; Awad, A; Cipriani, A; Forrest, A; Geddes, JR; Harrison, PJ; Houghton, KT; Stockton, S, 2017)
" Overall, pregabalin was well tolerated with no new adverse events emerging that have not been reported with its use in other indications."	6.44	Pregabalin: its efficacy, safety and tolerability profile in fibromyalgia syndrome. ( Owen, RT, 2007)
"We included 41 adult patients with focal epilepsy in a monocentric, noncontrolled open-label study adding up to 600 mg of PGB to an antiepileptic baseline medication."	5.39	Efficacy and safety of pregabalin in refractory focal epilepsy with and without comorbid anxiety disorders - results of an open-label, parallel group, investigator-initiated, proof-of-concept study. ( Brandt, C; Fueratsch, N; May, TW; Pohlmann-Eden, B; Schoendienst, M; Schrecke, M; Trentowska, M; Witte-Boelt, K, 2013)
" Endpoints were responder rate, seizure frequency, adverse events, and anxiety symptoms."	5.39	Efficacy and safety of pregabalin in refractory focal epilepsy with and without comorbid anxiety disorders - results of an open-label, parallel group, investigator-initiated, proof-of-concept study. ( Brandt, C; Fueratsch, N; May, TW; Pohlmann-Eden, B; Schoendienst, M; Schrecke, M; Trentowska, M; Witte-Boelt, K, 2013)
" Mean dosage +/- SD at week 8 was 1270 +/- 561."	5.31	Effectiveness of adjunctive gabapentin in resistant bipolar disorder: is it due to anxious-alcohol abuse comorbidity? ( Akiskal, HS; Frare, F; Moretti, L; Perugi, G; Ruffolo, G; Toni, C; Torti, C, 2002)
"Pregabalin was generally well tolerated in the long-term treatment of anxiety disorders."	5.17	Long-term treatment of anxiety disorders with pregabalin: a 1 year open-label study of safety and tolerability. ( Emir, B; Haswell, H; Montgomery, S; Prieto, R, 2013)
"The aims of the present study were to investigate the main demographic and clinical characteristics, comorbidity patterns, use in association and tolerability of pregabalin in a sample of patients with affective disorders, and to compare demographic and clinical variables of the groups divided, according to the treatment pregabalin was associated with."	5.16	Tolerability and use in co-administration of pregabalin in affective patients: a 6-month prospective naturalistic study. ( Altamura, AC; Arici, C; Buoli, M; Camuri, G; Dell'Osso, B; Dobrea, C, 2012)
"One hundred and fourteen consecutive outpatients, with anxiety and/or depressive disorders with or without comorbidity, were started on pregabalin, assessed and interviewed and their demographic data, associated therapy, tolerability and side effects collected over an observational period of 6 months."	5.16	Tolerability and use in co-administration of pregabalin in affective patients: a 6-month prospective naturalistic study. ( Altamura, AC; Arici, C; Buoli, M; Camuri, G; Dell'Osso, B; Dobrea, C, 2012)
"Abnormalities in brain gamma-aminobutyric acid (GABA) and glutamate may be relevant to the underlying pathophysiology of anxiety disorders including social anxiety disorder (SAD)."	5.13	High-field MRS study of GABA, glutamate and glutamine in social anxiety disorder: response to treatment with levetiracetam. ( Jensen, JE; Kaufman, RE; Pollack, MH; Renshaw, PF; Simon, NM, 2008)
"Pregabalin is a novel compound under development for the treatment of several types of anxiety disorders."	5.10	A randomized, double-blind, placebo-controlled, fixed-dose, multicenter study of pregabalin in patients with generalized anxiety disorder. ( Carter, CM; Cohn, CK; Crockatt, JG; Dubovsky, SJ; Feltner, DE; Liu-Dumaw, M; Pande, AC; Shrivastava, RK; Targum, SD, 2003)
"The acute effects of diazepam on plasma GABA were determined in 18 patients with panic disorder, 13 patients with generalized anxiety disorder and 20 healthy controls."	5.07	Effect of acute and chronic benzodiazepines on plasma GABA in anxious patients and controls. ( Cowley, DS; Greenblatt, DJ; Hommer, D; Kramer, GL; Petty, F; Roy-Byrne, PP, 1992)
"We will include all randomised controlled trials (RCTs) reported as double-blind and comparing gabapentin or pregabalin with placebo or any other active pharmacological treatment (any preparation, dose, frequency, route of delivery or setting) in patients with bipolar disorder, anxiety or insomnia."	4.95	Biological rationale and potential clinical use of gabapentin and pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis. ( Atkinson, LZ; Awad, A; Cipriani, A; Forrest, A; Geddes, JR; Harrison, PJ; Houghton, KT; Stockton, S, 2017)
" Gabapentin and pregabalin, a very similar drug with the same mechanism of action, bind to a subunit of voltage-dependent calcium channels which are implicated in the aetiopathogenesis of bipolar disorder, anxiety and insomnia."	4.95	Biological rationale and potential clinical use of gabapentin and pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis. ( Atkinson, LZ; Awad, A; Cipriani, A; Forrest, A; Geddes, JR; Harrison, PJ; Houghton, KT; Stockton, S, 2017)
"The majority of published evidence supports the possibility that pregabalin could be a cost-effective and/or cost-saving alternative for the treatment of refractory epilepsy, GAD, and neuropathic pain, in both treatment-naïve patients and in those who have demonstrated inadequate response or intolerance to previous therapy."	4.90	Pharmacoeconomic outcomes for pregabalin: a systematic review in neuropathic pain, generalized anxiety disorder, and epilepsy from a Spanish perspective. ( Álvarez, E; Darbà, J; Kaskens, L; Navarro-Artieda, R; Pérez, C; Sicras-Mainar, A, 2014)
"Data from the MEDLINE database were searched using algorithms to identify relevant economic evaluations published in English or Spanish on pregabalin for the management of neuropathic pain, generalized anxiety disorder (GAD), and epilepsy in Spanish patients over the last 10 years."	4.90	Pharmacoeconomic outcomes for pregabalin: a systematic review in neuropathic pain, generalized anxiety disorder, and epilepsy from a Spanish perspective. ( Álvarez, E; Darbà, J; Kaskens, L; Navarro-Artieda, R; Pérez, C; Sicras-Mainar, A, 2014)
"A search of PubMed (1966-December 2011) and International Pharmaceutical Abstracts (1970-December 2011) was conducted using the MeSH and free-text terms pregabalin, anxiety disorders, and anxiety."	4.88	Pregabalin for the treatment of generalized anxiety disorder. ( Cates, ME; Powe, KW; Wensel, TM, 2012)
"Pregabalin appears to be an effective therapy in patients with diabetic peripheral neuropathy, postherpetic neuralgia, and adults with refractory partial-onset seizures."	4.84	Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. ( Boyce, E; Guyer, J; Nuzum, D; Tassone, DM, 2007)
" The search terms included pregabalin, Lyrica, S-(+)-3 isobutyl-gaba, PN, DPN, diabetic peripheral neuropathy, PHN, postherpetic neuralgia, partial seizures, epilepsy, generalized anxiety disorder, and CI-1008."	4.84	Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. ( Boyce, E; Guyer, J; Nuzum, D; Tassone, DM, 2007)
"The US Food and Drug Administration (FDA) approved pregabalin in December 2004 for the treatment of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia."	4.84	Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. ( Boyce, E; Guyer, J; Nuzum, D; Tassone, DM, 2007)
"Pregabalin is a gamma-aminobutyric acid analog that is under development by Pfizer for the potential treatment of central nervous system disorders, including epilepsy, neuropathic pain, fibromyalgia and generalized anxiety disorder."	4.82	Pregabalin (Pfizer). ( Huckle, R, 2004)
"There is growing evidence for GABA and glutamate-glutamine dysfunction in the pathogenesis of mood and anxiety disorders."	3.91	Association between prefrontal glutamine levels and neuroticism determined using proton magnetic resonance spectroscopy. ( Brechbühl, S; Buchmann, A; Ghisleni, C; Hasler, G; Haynes, M; Müller, ST; Tuura, R, 2019)
"Pregabalin was mainly used as a second-line drug for the treatment of GAD or neuropathic pain and to a lesser extent as add-on therapy in epilepsy."	3.80	Pregabalin is increasingly prescribed for neuropathic pain, generalised anxiety disorder and epilepsy but many patients discontinue treatment. ( Bodén, R; Brandt, L; Kieler, H; Wettermark, B, 2014)
"Dizziness represents a major determinant of dropout in the treatment of generalized anxiety disorder with pregabalin."	3.77	Modeling dropout from adverse event data: impact of dosing regimens across pregabalin trials in the treatment of generalized anxiety disorder. ( Frame, B; Hutmacher, M; Lalovic, B; Miller, R, 2011)
"Impaired function of the central gamma-aminobutyric acid (GABA) system, which provides the brain's major inhibitory pathways, is thought to play an important role in the pathophysiology of anxiety disorders."	3.76	Effect of acute psychological stress on prefrontal GABA concentration determined by proton magnetic resonance spectroscopy. ( Drevets, WC; Grillon, C; Hasler, G; Shen, J; van der Veen, JW, 2010)
"Dizziness and drowsiness are cited as being predictors of dropout from clinical trials for the medicine pregabalin."	3.75	Joint modeling of dizziness, drowsiness, and dropout associated with pregabalin and placebo treatment of generalized anxiety disorder. ( Frame, B; Hutmacher, MM; Miller, R, 2009)
"To describe the pregabalin exposure-adverse event (AE) (dizziness) relationship in patients with generalized anxiety disorder, separate models were developed for the incidence of AE and for the conditional severity of AE, given that an AE has occurred using patient data from six clinical studies."	3.74	Exposure-response analysis for spontaneously reported dizziness in pregabalin-treated patient with generalized anxiety disorder. ( Frame, B; Hutmacher, M; Ito, K; Liu, J; Miller, R; Qiu, R, 2008)
" One promising pharmacological agent in BDZ discontinuation might be the newer anti-epileptic pregabalin, already successfully tested in the treatment of anxiety disorders."	3.74	Pregabalin in the discontinuation of long-term benzodiazepines' use. ( Karakatsanis, NA; Karapoulios, E; Konstantakopoulos, G; Kontoangelos, KA; Kouzoupis, AV; Masdrakis, VG; Oulis, P; Papadimitriou, GN, 2008)
"We evaluated effectiveness and predictors of response of gabapentin (GBP) as adjunctive treatment in a sample of 43 subjects with DSM-III-R bipolar disorder who were resistant to standard mood stabilizers."	3.71	Effectiveness of adjunctive gabapentin in resistant bipolar disorder: is it due to anxious-alcohol abuse comorbidity? ( Akiskal, HS; Frare, F; Moretti, L; Perugi, G; Ruffolo, G; Toni, C; Torti, C, 2002)
"Low levels of gamma-aminobutyric acid (GABA) in plasma have been associated with the presence of mood disorders in patients with major depressive disorder."	3.69	Plasma levels of gamma-aminobutyric acid and panic disorder. ( Davis, LL; Germine, M; Goddard, AW; Kramer, GL; Narayan, M; Petty, F; Woods, SW, 1996)
" Study treatments were dosed incrementally over a three week period, to reach daily doses of 150 mg venlafaxine and 200mg pregabalin by the CO(2) challenge test day."	2.78	Evaluation of the effects of venlafaxine and pregabalin on the carbon dioxide inhalation models of Generalised Anxiety Disorder and panic. ( Bailey, JE; Craig, K; Dawson, GR; Diaper, A; Dourish, CT; Nutt, DJ; Osman-Hicks, V; Rich, AS, 2013)
"5%) was the only treatment-related adverse event (AE) occurring ≥10%."	2.78	Long-term treatment of anxiety disorders with pregabalin: a 1 year open-label study of safety and tolerability. ( Emir, B; Haswell, H; Montgomery, S; Prieto, R, 2013)
"A 'high-insomnia' subgroup was defined by a baseline HAM for Depression (HAM-D) insomnia factor score greater than 3 (maximum = 6)."	2.74	The efficacy of pregabalin and benzodiazepines in generalized anxiety disorder presenting with high levels of insomnia. ( Herman, BK; Mandel, FS; Montgomery, SA; Schweizer, E, 2009)
" Pregabalin was well-tolerated, with almost all adverse events in the mild-to-moderate range, and self-limiting (median duration of 4-16 days)."	2.73	Efficacy and safety of pregabalin in elderly people with generalised anxiety disorder. ( Baldinetti, F; Chatamra, K; Montgomery, S; Pauer, L; Whalen, E, 2008)
"Pregabalin, in doses of 150-600 mg/day, was a safe and effective treatment of generalised anxiety disorder in patients 65 years and older."	2.73	Efficacy and safety of pregabalin in elderly people with generalised anxiety disorder. ( Baldinetti, F; Chatamra, K; Montgomery, S; Pauer, L; Whalen, E, 2008)
" Pregabalin in both dosage treatment groups (400 mg/day, p < ."	2.72	Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder: a 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine. ( Kasper, S; Montgomery, SA; Pande, AC; Tobias, K; Zornberg, GL, 2006)
"Gamma-aminobutyric acid (GABA) plays a key role in the pathophysiology and treatment of depression and anxiety."	2.72	Open-label tiagabine monotherapy for major depressive disorder with anxiety. ( Carpenter, LL; Haggarty, R; Mello, AF; Mello, MF; Price, LH; Schecter, JM; Tyrka, AR, 2006)
" Discontinuation rates due to associated adverse events were greatest in the venlafaxine treatment group: venlafaxine, 20."	2.72	Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder: a 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine. ( Kasper, S; Montgomery, SA; Pande, AC; Tobias, K; Zornberg, GL, 2006)
" More studies are needed to determine the best dosing regimen to optimize efficacy and tolerability."	2.71	A randomized, double-blind, placebo-controlled, fixed-dose, multicenter study of pregabalin in patients with generalized anxiety disorder. ( Carter, CM; Cohn, CK; Crockatt, JG; Dubovsky, SJ; Feltner, DE; Liu-Dumaw, M; Pande, AC; Shrivastava, RK; Targum, SD, 2003)
" The current study evaluated the anxiolytic efficacy of BID versus TID dosing of pregabalin in patients with generalized anxiety disorder."	2.71	Efficacy of pregabalin in the treatment of generalized anxiety disorder: double-blind, placebo-controlled comparison of BID versus TID dosing. ( Feltner, DE; Fieve, RR; Pande, AC; Pohl, RB, 2005)
"Tiagabine was initiated at 4 mg/day and then flexibly dosed twice a day to a maximum dose of 16 mg/day."	2.71	The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study. ( Brown, C; Ondrasik, J; Pollack, MH; Rickels, K; Roy-Byrne, PP; Snyder, H; Van Ameringen, M, 2005)
"Tiagabine was generally well tolerated and not associated with changes in sexual functioning or depressive status."	2.71	The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study. ( Brown, C; Ondrasik, J; Pollack, MH; Rickels, K; Roy-Byrne, PP; Snyder, H; Van Ameringen, M, 2005)
" Tiagabine was initiated at 4 mg/day and then flexibly dosed twice a day to a maximum dose of 16 mg/day."	2.71	The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study. ( Brown, C; Ondrasik, J; Pollack, MH; Rickels, K; Roy-Byrne, PP; Snyder, H; Van Ameringen, M, 2005)
"Forty adult patients with partial epilepsy were studied in a prospective, non-randomized fashion with interviewer-rated and self-rated scales of mood and anxiety: the Cornell Dysthymia Rating Scale (CDRS), Beck Depression Inventory (BDI), and Hamilton Depression (Ham-D) and Anxiety (Ham-A) Scales."	2.69	A beneficial effect on mood in partial epilepsy patients treated with gabapentin. ( Carson, D; Goldstein, MA; Harden, CL; Kocsis, JH; Labar, DR; Lazar, LM; Nikolov, B; Pick, LH; Ravdin, LD, 1999)
"Mood disorders and Major Depressive Disorder, in particular, appear to be some of the most common psychiatric disorders with a high rate of comorbidity most frequently of anxiety or substance abuse disorders (alcohol use disorder)."	2.66	Immunological Disturbances and Neuroimaging Findings in Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) Comorbid Patients. ( Kakanakova, A; Maes, M; Popov, S, 2020)
"Gabapentin has been extensively prescribed off-label for psychiatric indications, with little established evidence of efficacy."	2.55	Biological rationale and potential clinical use of gabapentin and pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis. ( Atkinson, LZ; Awad, A; Cipriani, A; Forrest, A; Geddes, JR; Harrison, PJ; Houghton, KT; Stockton, S, 2017)
"This review aims to analyze pharmacokinetic profile, plasma level variations so as the metabolism, interactions and possible relation to clinical effect of several drugs which are used primarily as anxiolytics."	2.49	Understanding the pharmacokinetics of anxiolytic drugs. ( Altamura, AC; Bareggi, S; Maffini, M; Mauri, MC; Moliterno, D; Paletta, S, 2013)
"There is a need for a more balanced assessment of the benefits and risks associated with benzodiazepine use, particularly considering pharmacokinetic profile of the drugs to ensure that patients, who would truly benefit from these agents, are not denied appropriate treatment."	2.49	Understanding the pharmacokinetics of anxiolytic drugs. ( Altamura, AC; Bareggi, S; Maffini, M; Mauri, MC; Moliterno, D; Paletta, S, 2013)
"As somnolence and dizziness are common adverse effects, caution should be used in elderly patients."	2.48	Pregabalin for the treatment of generalized anxiety disorder. ( Cates, ME; Powe, KW; Wensel, TM, 2012)
"Although drug-resistant partial epilepsy is associated with a higher probability of developing vestibulo-cerebellar AEs, the risk for PGB toxicity does not differ across distinct disorders."	2.48	The adverse event profile of pregabalin across different disorders: a meta-analysis. ( Gangemi, PF; Perucca, P; Zaccara, G, 2012)
"Ataxia was more common in drug-resistant partial epilepsy compared to fibromyalgia."	2.48	The adverse event profile of pregabalin across different disorders: a meta-analysis. ( Gangemi, PF; Perucca, P; Zaccara, G, 2012)
"In a recent meta-analysis of 38 double-blind randomized controlled trials (RCTs) comparing pregabalin (PGB) to placebo, we found 20 adverse events (AEs) to be significantly associated with PGB treatment."	2.48	The adverse event profile of pregabalin across different disorders: a meta-analysis. ( Gangemi, PF; Perucca, P; Zaccara, G, 2012)
"Pediatric epilepsy is a common, chronic, and challenging physical illness for children and their families."	2.46	Psychiatric concerns in pediatric epilepsy. ( Bujoreanu, IS; DeMaso, DR; Ibeziako, P, 2010)
" Overall, pregabalin was well tolerated with no new adverse events emerging that have not been reported with its use in other indications."	2.44	Pregabalin: its efficacy, safety and tolerability profile in fibromyalgia syndrome. ( Owen, RT, 2007)
"Gamma-aminobutyric acid is a major inhibitory neurotransmitter in the central nervous system."	2.44	[Gamma-aminobutyric acid--metabolism and its disorders]. ( Kowalski, A; Rebas, E; Zylińska, L, 2007)
" Four of the available six placebo-controlled trials were found acceptable for a pooled analysis of dose-response relationship."	2.44	Dose-response relationship of pregabalin in patients with generalized anxiety disorder. A pooled analysis of four placebo-controlled trials. ( Bech, P, 2007)
" The most frequently reported adverse events were dizziness and somnolence, although tolerance to these developed within a few weeks."	2.44	Pregabalin: its efficacy, safety and tolerability profile in generalized anxiety. ( Owen, RT, 2007)
" In this article, we examine issues related to the long-term use of benzodiazepines, including concerns about the development of therapeutic tolerance, dose escalation, and adverse cognitive effects."	2.43	Benzodiazepines in clinical practice: consideration of their long-term use and alternative agents. ( Pollack, MH; Stevens, JC, 2005)
" In healthy volunteers, it is rapidly absorbed with peak blood concentrations within 1 h and it has a bioavailability of approximately 90%."	2.42	Pregabalin: a new anxiolytic. ( Lauria-Horner, BA; Pohl, RB, 2003)
"Among psychiatric disorders the acute symptoms of schizophrenia are exacerbated by enhanced GABA-ergic function."	2.36	Pharmacology of GABA. ( Meldrum, B, 1982)
"camara leaves on seizures induced by kainate in mice, and possible mechanisms of action."	1.72	An aqueous extract of Lantana camara attenuates seizures, memory impairment, and anxiety in kainate-treated mice: Evidence of GABA level, oxidative stress, immune and neuronal loss modulation. ( Kandeda, AK; Mabou, ST; Moutchida, C, 2022)
"Thirty patients with atypical facial pain were treated with noophen."	1.42	[Emotional and personality disorders in atypical facial pain]. ( Maximova, MY; Suanova, ET, 2015)
"We included 41 adult patients with focal epilepsy in a monocentric, noncontrolled open-label study adding up to 600 mg of PGB to an antiepileptic baseline medication."	1.39	Efficacy and safety of pregabalin in refractory focal epilepsy with and without comorbid anxiety disorders - results of an open-label, parallel group, investigator-initiated, proof-of-concept study. ( Brandt, C; Fueratsch, N; May, TW; Pohlmann-Eden, B; Schoendienst, M; Schrecke, M; Trentowska, M; Witte-Boelt, K, 2013)
" Endpoints were responder rate, seizure frequency, adverse events, and anxiety symptoms."	1.39	Efficacy and safety of pregabalin in refractory focal epilepsy with and without comorbid anxiety disorders - results of an open-label, parallel group, investigator-initiated, proof-of-concept study. ( Brandt, C; Fueratsch, N; May, TW; Pohlmann-Eden, B; Schoendienst, M; Schrecke, M; Trentowska, M; Witte-Boelt, K, 2013)
"Depression, epilepsy, post traumatic stress disorder (PTSD), and chronic pain exemplify medical conditions that are exacerbated by stress, have low heart rate variability (HRV) and low GABAergic activity, respond to pharmacologic agents that increase activity of the GABA system, and show symptom improvement in response to yoga-based interventions."	1.38	Effects of yoga on the autonomic nervous system, gamma-aminobutyric-acid, and allostasis in epilepsy, depression, and post-traumatic stress disorder. ( Brown, RP; Ciraulo, DA; Gerbarg, PL; Saper, RB; Streeter, CC, 2012)
" The objective of the current study was to examine the dose-response relationship for treatment of GAD with pregabalin."	1.38	Pregabalin: dose-response relationship in generalized anxiety disorder. ( Boschen, MJ, 2012)
"The current study pools results from previous fixed-dose treatment trials of GAD with pregabalin and uses curve-fitting statistical procedures to generate curvilinear regression lines as a synthesis of previous dose-response information."	1.38	Pregabalin: dose-response relationship in generalized anxiety disorder. ( Boschen, MJ, 2012)
" Dropout is an important treatment failure endpoint, which can be analyzed using time-to-event models that incorporate daily dosing or other time-varying information."	1.37	Modeling dropout from adverse event data: impact of dosing regimens across pregabalin trials in the treatment of generalized anxiety disorder. ( Frame, B; Hutmacher, M; Lalovic, B; Miller, R, 2011)
" Titration (dose escalation) regimens based on clinical judgment were implemented to mitigate this adverse event and reduce patient dropout across clinical trials."	1.37	Modeling dropout from adverse event data: impact of dosing regimens across pregabalin trials in the treatment of generalized anxiety disorder. ( Frame, B; Hutmacher, M; Lalovic, B; Miller, R, 2011)
" A dose-response effect was evident for PGB that reached a plateau at a dose of 300 mg/d."	1.36	Comparative efficacy of pregabalin and benzodiazepines in treating the psychic and somatic symptoms of generalized anxiety disorder. ( Feltner, DE; Herman, B; Lydiard, RB; Rickels, K, 2010)
"Tolerance, dependence, and adverse effects on cognitive functions are well-known consequences of long-term use of benzodiazepines (BDZ), especially at high doses, raising thorny therapeutic problems in their discontinuation."	1.35	Pregabalin in the discontinuation of long-term benzodiazepines' use. ( Karakatsanis, NA; Karapoulios, E; Konstantakopoulos, G; Kontoangelos, KA; Kouzoupis, AV; Masdrakis, VG; Oulis, P; Papadimitriou, GN, 2008)
" The experiments demonstrate that the most consistent finding following chronic administration of antidepressants is an increase in GABAB receptor function, with or without a change in receptor binding or subunit expression."	1.33	GABAergic hypotheses of anxiety and depression: focus on GABA-B receptors. ( Nowak, G; Pilc, A, 2005)
" Additionally, pregabalin (initial dosage 450 mg/day) was effective for the prevention of relapse of GAD over 34 weeks."	1.33	Pregabalin: in the treatment of generalised anxiety disorder. ( Foster, RH; Frampton, JE, 2006)
" Mean dosage +/- SD at week 8 was 1270 +/- 561."	1.31	Effectiveness of adjunctive gabapentin in resistant bipolar disorder: is it due to anxious-alcohol abuse comorbidity? ( Akiskal, HS; Frare, F; Moretti, L; Perugi, G; Ruffolo, G; Toni, C; Torti, C, 2002)

Research

Studies (181)

Authors

Clinical Trials (12)

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	17 (9.39)	18.7374
1990's	16 (8.84)	18.2507
2000's	73 (40.33)	29.6817
2010's	66 (36.46)	24.3611
2020's	9 (4.97)	2.80

Authors	Studies
Kandeda, AK	1
Mabou, ST	1
Moutchida, C	1
Gallo, AT	1
Hulse, GK	1
Zhong, H	1
Rong, J	1
Yang, Y	1
Liang, M	1
Li, Y	1
Zhou, R	1
Ulrich, M	1
Pollali, E	1
Çalışkan, G	2
Stork, O	2
Albrecht, A	1
Amaro, A	1
Sousa, D	1
Sá-Rocha, M	1
Ferreira-Junior, MD	1
Rosendo-Silva, D	1
Saavedra, LPJ	1
Barra, C	1
Monteiro-Alfredo, T	1
Gomes, RM	1
de Freitas Mathias, PC	1
Baptista, FI	1
Matafome, P	1
Richards, A	1
Kanady, JC	1
Neylan, TC	1
Kakanakova, A	1
Popov, S	1
Maes, M	1
Felice, D	1
Cryan, JF	1
O'Leary, OF	1
Colijn, MA	1
Houghton, KT	1
Forrest, A	1
Awad, A	1
Atkinson, LZ	1
Stockton, S	1
Harrison, PJ	1
Geddes, JR	1
Cipriani, A	1
Zhang, C	1
Kalueff, AV	2
Song, C	1
Hasler, G	2
Buchmann, A	1
Haynes, M	1
Müller, ST	1
Ghisleni, C	1
Brechbühl, S	1
Tuura, R	1
Papazisis, G	1
Garyfallos, G	1
Sardeli, C	1
Kouvelas, D	1
Montgomery, S	2
Emir, B	1
Haswell, H	1
Prieto, R	5
Wettermark, B	1
Brandt, L	1
Kieler, H	1
Bodén, R	1
Brandt, C	1
Schoendienst, M	1
Trentowska, M	1
Schrecke, M	1
Fueratsch, N	1
Witte-Boelt, K	1
Pohlmann-Eden, B	1
May, TW	1
Roth, T	1
Arnold, LM	1
Garcia-Borreguero, D	1
Resnick, M	1
Clair, AG	1
Sarro, EC	1
Sullivan, RM	1
Barr, G	1
Kasper, S	5
Brasser, M	1
Schweizer, E	6
Lyndon, G	2
Both, C	1
Kojda, G	1
Lange-Asschenfeldt, C	1
Iglesias-García, C	1
Wilson, J	1
DuBrava, S	1
Pitman, VW	1
Knapp, L	1
Darbà, J	1
Kaskens, L	1
Pérez, C	1
Álvarez, E	2
Navarro-Artieda, R	1
Sicras-Mainar, A	1
Dias, GP	1
Bevilaqua, MC	1
da Luz, AC	1
Fleming, RL	1
de Carvalho, LA	1
Cocks, G	1
Beckman, D	1
Hosken, LC	1
de Sant'Anna Machado, W	1
Corrêa-e-Castro, AC	1
Mousovich-Neto, F	1
de Castro Gomes, V	1
Bastos, Gde N	1
Kubrusly, RC	1
da Costa, VM	1
Srivastava, D	1
Landeira-Fernandez, J	1
Nardi, AE	1
Thuret, S	1
Gardino, PF	1
Almeida-Suhett, CP	1
Prager, EM	1
Pidoplichko, V	1
Figueiredo, TH	1
Marini, AM	1
Li, Z	2
Eiden, LE	1
Braga, MF	2
Frampton, JE	2
Müller, I	1
Marseglia, L	1
D'Angelo, G	1
Manti, S	1
Aversa, S	1
Arrigo, T	1
Reiter, RJ	1
Gitto, E	1
Wong, A	1
Little, M	1
Caldicott, D	1
Easton, C	1
Andres, D	1
Greene, SL	1
Skórzewska, A	2
Lehner, M	2
Wisłowska-Stanek, A	2
Turzyńska, D	2
Sobolewska, A	2
Krząścik, P	1
Płaźnik, A	2
Smulevich, AB	1
Volel, BA	1
Ternovaya, ES	1
Nikitina, YM	1
Maximova, MY	1
Suanova, ET	1
Hartmann, J	1
Dedic, N	1
Pöhlmann, ML	1
Häusl, A	1
Karst, H	1
Engelhardt, C	1
Westerholz, S	1
Wagner, KV	1
Labermaier, C	1
Hoeijmakers, L	1
Kertokarijo, M	1
Chen, A	1
Joëls, M	1
Deussing, JM	1
Schmidt, MV	1
Yamashita, PS	1
Spiacci, A	1
Hassel, JE	1
Lowry, CA	1
Zangrossi, H	1
dos Reis, LM	1
Canto-de-Souza, A	1
Chatamra, K	1
Pauer, L	1
Whalen, E	1
Baldinetti, F	3
Kowalski, A	1
Rebas, E	1
Zylińska, L	1
Domschke, K	1
Zwanzger, P	1
Davies, SJ	1
Esler, M	1
Nutt, DJ	6
Schönfeldt-Lecuona, C	1
Wolf, RC	1
Osterfeld, ND	1
Vasic, N	1
Connemann, BJ	1
Schmid, M	1
Freudenmann, RW	1
Vera-Llonch, M	1
Dukes, E	1
Rejas, J	2
Sofrygin, O	1
Mychaskiw, M	1
Oster, G	1
Cunningham, MG	1
Connor, CM	1
Carlezon, WA	1
Meloni, E	1
Montgomery, SA	3
Herman, BK	1
Mandel, FS	3
Lydiard, RB	3
Rickels, K	4
Herman, B	2
Feltner, DE	6
Frame, B	3
Miller, R	3
Hutmacher, MM	1
Zoberi, K	1
Pollard, CA	1
Bujoreanu, IS	1
Ibeziako, P	1
DeMaso, DR	1
Krüger, S	1
Lindstaedt, M	1
Englisch, S	2
Esser, A	1
Enning, F	1
Hohmann, S	1
Schanz, H	1
Zink, M	2
Nikolaus, S	1
Antke, C	1
Beu, M	1
Müller, HW	1
van der Veen, JW	1
Grillon, C	1
Drevets, WC	1
Shen, J	1
Lalovic, B	1
Hutmacher, M	2
Taracha, E	1
Maciejak, P	1
Szyndler, J	1
Hamed, A	1
Bidziński, A	1
Magsalin, RM	1
Khan, AY	1
Poleszak, E	1
Socała, K	1
Szopa, A	1
Wróbel, A	1
Szewczyk, B	1
Kasperek, R	1
Blicharska, E	1
Nowak, G	2
Wlaź, P	1
Durant, C	1
Christmas, D	1
Nutt, D	1
Bobes, J	1
Rubio, G	1
Terán, A	1
Cervera, G	1
López-Gómez, V	1
Vilardaga, I	1
Pérez, M	1
Liu-Dumaw, M	3
Bielski, R	1
Nivoli, G	1
Van Ameringen, M	3
Petralia, A	1
Bandelow, B	4
Hadley, SJ	1
Baldwin, DS	2
Xu, Y	1
Boschen, MJ	2
Allgulander, C	1
Ferre, F	1
Pallanti, S	1
Trincavelli, ML	1
Da Pozzo, E	1
Daniele, S	1
Martini, C	1
Alm, B	1
Meyer-Lindenberg, A	1
Zaccara, G	1
Perucca, P	1
Gangemi, PF	1
Shiovitz, TM	1
Ramey, TS	1
Weaver, JJ	1
Knapp, LE	1
Miceli, JJ	1
Streeter, CC	1
Gerbarg, PL	1
Saper, RB	1
Ciraulo, DA	1
Brown, RP	1
Wensel, TM	1
Powe, KW	1
Cates, ME	1
Steiger, A	1
Karaiskos, D	1
Pappa, D	1
Tzavellas, E	1
Siarkos, K	1
Katirtzoglou, E	1
Papadimitriou, GN	3
Politis, A	1
Diaper, A	1
Osman-Hicks, V	1
Rich, AS	1
Craig, K	1
Dourish, CT	1
Dawson, GR	1
Bailey, JE	1
Sher, L	1
Bunevicius, R	1
Hollander, E	1
Zohar, J	1
Möller, HJ	1
Martinotti, G	1
Sommer, C	1
Häuser, W	1
Alten, R	1
Petzke, F	1
Späth, M	1
Tölle, T	1
Uçeyler, N	1
Winkelmann, A	1
Winter, E	1
Bär, KJ	1
Micó, JA	1
Dobrea, C	1
Buoli, M	1
Arici, C	1
Camuri, G	1
Dell'Osso, B	1
Altamura, AC	2
Bondarenko, II	1
Kissin, MIa	1
Huang, R	1
Chen, H	1
Huang, Y	1
Ding, L	1
Holsboer-Trachsler, E	1
De Salas-Cansado, M	1
Olivares, JM	1
Carrasco, JL	1
Ferro, MB	1
Moliterno, D	1
Paletta, S	1
Maffini, M	1
Mauri, MC	1
Bareggi, S	1
Crawford, LK	1
Rahman, SF	1
Beck, SG	1
Stahl, SM	3
Kent, JM	1
Mathew, SJ	1
Gorman, JM	1
Perugi, G	1
Toni, C	1
Frare, F	1
Ruffolo, G	1
Moretti, L	1
Torti, C	1
Akiskal, HS	1
Pande, AC	6
Crockatt, JG	2
Janney, CA	1
Smith, WT	1
Weisler, R	1
Londborg, PD	1
Bielski, RJ	2
Zimbroff, DL	2
Davidson, JR	1
Nemeroff, CB	1
Chang, L	1
Cloak, CC	1
Ernst, T	1
Kalin, NH	1
Lauria-Horner, BA	1
Pohl, RB	2
Dubovsky, SJ	1
Cohn, CK	1
Shrivastava, RK	1
Targum, SD	1
Carter, CM	1
Maeda, H	1
Yanagimoto, K	1
Blanco, C	1
Schneier, FR	1
Schmidt, A	1
Blanco-Jerez, CR	1
Marshall, RD	1
Sánchez-Lacay, A	1
Liebowitz, MR	1
Freund, TF	1
Pigott, TA	1
Huckle, R	1
Barenbaum, RD	1
Rilla Manta, L	1
Kaufman, KR	1
Fieve, RR	1
Stevens, JC	1
Pollack, MH	5
Ameli, R	1
Snow, J	1
Rakocevic, G	1
Dalakas, MC	1
Tobias, K	2
Brock, JD	1
Zornberg, GL	2
Pilc, A	1
Roy-Byrne, PP	2
Snyder, H	1
Brown, C	1
Ondrasik, J	1
Carpenter, LL	1
Schecter, JM	1
Tyrka, AR	1
Mello, AF	1
Mello, MF	1
Haggarty, R	1
Price, LH	1
Keck, ME	1
Ströhle, A	1
Mataix-Cols, D	1
van den Heuvel, OA	1
Harro, J	1
Lauer, D	1
Hölzel, L	1
Hornyak, M	1
Foster, RH	1
Möhler, H	2
Barros, VG	1
Rodríguez, P	1
Martijena, ID	1
Pérez, A	1
Molina, VA	1
Antonelli, MC	1
Schwartz, TL	1
Nihalani, N	1
Aroniadou-Anderjaska, V	1
Qashu, F	1
Hashemi, E	1
Sahbaie, P	1
Davies, MF	1
Clark, JD	1
DeLorey, TM	1
Liu, GX	1
Cai, GQ	1
Cai, YQ	1
Sheng, ZJ	1
Jiang, J	1
Mei, Z	1
Wang, ZG	1
Guo, L	1
Fei, J	1
Hasnie, FS	1
Breuer, J	1
Parker, S	1
Wallace, V	1
Blackbeard, J	1
Lever, I	1
Kinchington, PR	1
Dickenson, AH	1
Pheby, T	1
Rice, AS	1
Giachino, C	1
Canalia, N	1
Capone, F	1
Fasolo, A	1
Alleva, E	1
Riva, MA	1
Cirulli, F	1
Peretto, P	1
Tassone, DM	1
Boyce, E	1
Guyer, J	1
Nuzum, D	1
Wedekind, D	1
Leon, T	1
Bech, P	1
Owen, RT	2
Biermann, T	1
Bleich, S	1
Kornhuber, J	1
Hillemacher, T	1
Nymdelger, S	1
Nieber, K	1
Feltner, D	1
Wittchen, HU	1
Kavoussi, R	1
Brock, J	1
Jensen, JE	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A 1-Year Open-Label Safety Extension Study of Pregabalin in Patients With Anxiety Disorders[NCT00150449]	Phase 3	511 participants	Interventional	2001-01-31	Completed
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
An 8-Week Multicenter, Randomized, Double-Blind, Placebo-Controlled, Flexible Dose Study Of Pregabalin (300-600 Mg/Day) And Venlafaxine XR (75-225 Mg/Day) For The Acute Treatment Of DSM-IV Generalized Anxiety Disorder In Outpatients[NCT00151450]	Phase 3	390 participants	Interventional	2005-03-31	Completed
An 8-Week, Double-Blind, Placebo-Controlled, Phase 3 Trial of Pregabalin (150-600 mg/Day) in the Adjunctive Treatment of Patients With Generalized Anxiety Disorder (GAD) Who Have Not Optimally Responded to Existing Therapies(GAD)[NCT00413010]	Phase 3	356 participants (Actual)	Interventional	2006-12-31	Completed
Application of Vagal Stimulation by Cold Face Mask in Exposure and Response Prevention for Obsessive Compulsive Disorder[NCT02196090]		10 participants (Anticipated)	Interventional	2014-07-31	Recruiting
Pharmacogenetic Treatment With Anti-Glutaminergic Agents for Comorbid PTSD & AUD[NCT02884908]	Phase 3	252 participants (Anticipated)	Interventional	2016-09-30	Active, not recruiting
Preoperative Anxiety's Incidence and Related Factors in Surgical Patients[NCT03162692]		2,000 participants (Anticipated)	Observational	2017-04-01	Recruiting
Remote Effects of Stroke on Cerebral Metabolism. Evaluation With Positron Emission Tomography and Proton Magnetic Resonance Spectroscopy[NCT00063180]		70 participants	Observational	2003-06-19	Completed
Role of the Gut Microbiome as Determinant of Depression in Multiple Sclerosis Subjects[NCT05808101]		120 participants (Anticipated)	Observational	2022-01-27	Recruiting
Opioid-Induced Hyperalgesia in Prescription Opioid Abusers: Effects of Pregabalin[NCT01821430]	Phase 2	4 participants (Actual)	Interventional	2013-03-31	Terminated (stopped due to poor recruitment)
Efficacy of Pregabalin and Duloxetine in Patients With Painful Diabetic Peripheral Neuropathy (PDPN): the Effect of Pain on Cognitive Function, Sleep and Quality of Life (BLOSSOM)[NCT04246619]	Phase 4	254 participants (Actual)	Interventional	2019-11-12	Terminated (stopped due to The statistical analysis will still provide relevant results with the same statistical power as initially planned.COVID-19 pandemic prolonged the recruiting period and consequently affected the costs of the clinical trial.)
A Phase II, Placebo-controlled, Double-blind, Randomized Crossover Trial of Pregabalin for the Prophylaxis of Pegfilgrastim-induced Bone Pain[NCT03407430]	Phase 2	11 participants (Actual)	Interventional	2016-01-27	Terminated (stopped due to Low patient accrual)
[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 Hamilton Anxiety Rating Scale (HAM-A) Total Scores

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

Change from baseline: average across visit weeks using mixed model. HAM-A=clinician-rated interview measuring presence of anxiety-related symptoms in 14 areas including anxiety, tension, depressed mood, palpitations, breathing difficulties, sleep disturbances, & restlessness. Total score ranges from 0 to 56; higher score indicates greater anxiety. (NCT00413010)
Timeframe: Baseline, 8 weeks

Time to Onset of Sustained Hamilton Anxiety Rating Scale (HAM-A) Improvement

Intervention	score on scale (Least Squares Mean)
Pregabalin	-7.6
Placebo	-6.4

Time to sustained improvement was defined as time to 50% or greater reduction in HAM-A total score from Baseline, which was sustained for the remainder of the study. HAM-A is a clinician-rated interview measuring the presence of anxiety-related symptoms in 14 areas. Total score ranges from 0 to 56; a higher score indicates greater anxiety. (NCT00413010)
Timeframe: Week 8

Change in HAM-A Total Score at Weekly Visits

Intervention	days (Median)
Pregabalin	57

Change: score at each study week minus score at baseline. HAM-A, a clinician-rated interview, measures presence of anxiety-related symptoms in 14 areas including anxiety, tension, depressed mood, palpitations, breathing difficulties, sleep disturbances, & restlessness. Total score ranges from 0 to 56; higher score indicates greater anxiety. (NCT00413010)
Timeframe: Baseline, Weeks 1 through Week 8

Change in Hamilton Depression Rating Scale (HAM-D) Total Score

Intervention	score on scale (Least Squares Mean)
	Week 1 (n=164;n=169)	Week 2 (n=166;n=163)	Week 3 (n=157;n=160)	Week 4 (n=153;n=150)	Week 5 (n=135;n=130)	Week 6 (n=122;n=125)	Week 8 (n=126;n=127)
Placebo	-3.1	-5.2	-5.5	-7.0	-7.6	-8.0	-8.0
Pregabalin	-4.4	-6.3	-7.0	-8.3	-8.4	-9.2	-9.3

Change: score at each study week minus score at baseline. HAM-D, clinician-rated interview, measures presence of depressive symptoms in 17 areas (symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, & weight loss). Total score ranges from 0 to 52; higher scores indicate more depression. (NCT00413010)
Timeframe: Weeks 1 through Week 8

Clinical Global Impression of Severity (CGI-S) Score

Intervention	score on scale (Least Squares Mean)
	Week 1 n=165,168	Week 2 n=165,164	Week 3 n=156,160	Week 4 n=153, 149	Week 5 n=135, 130	Week 6 n=122, 125	Week 8 n= 126, 127
Placebo	-1.3	-2.4	-2.8	-3.3	-3.9	-3.8	-3.8
Pregabalin	-2.1	-3.1	-3.5	-4.7	-4.3	-4.7	-4.8

CGI-S is a clinician-rated instrument measuring the severity of a subject's symptoms on a 7-point categorical scale. Scores range from 1 (not at all ill) to 7 (among the most extremely ill patients). Higher score indicates that the subject is more ill. (NCT00413010)
Timeframe: Week 8

Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score

Intervention	participants (Number)
	Normal, not ill at all	Borderline, mentally ill	Mildly ill	Moderately ill	Markedly ill	Severely ill	Among the most extremely ill	Not assessed
Placebo	18	37	63	48	8	1	0	1
Pregabalin	28	49	49	46	2	2	0	0

Responders = YES using CGI-I if score indicated much improved or very much improved at the last study week. CGI-I is a clinician-rated instrument that measures change in subject's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). (NCT00413010)
Timeframe: Week 1 through Week 8

Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A)

Responders = YES if subjects achieved a >= 50% decrease in HAM-A total score from Baseline to respective study week. HAM-A is a clinician-rated interview measuring the presence of anxiety-related symptoms in 14 areas. Total score ranges from 0 to 56; higher score indicates greater anxiety. (NCT00413010)
Timeframe: Weeks 1 through Week 8

Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score

Participant in remission defined as HAM-A total score of <= 7. HAM-A=clinician-rated interview measuring presence of anxiety-related symptoms in 14 areas including anxiety, tension, depressed mood, palpitations, breathing difficulties, sleep disturbances, & restlessness. Total score ranges 0 - 56; higher score indicates greater anxiety. (NCT00413010)
Timeframe: Week 1 through Week 8

Maximum Change in Pain Score From Baseline Between Pregabalin and Placebo Across the 2 Cycles

"Compare the maximum change in pain score from baseline between pregabalin and placebo within cycle 1 and across the 2 cycles.~The ten-point numerical scale is scored from 0 to 10. They will use this scale to rate their pain (and separately bone/joint pain) with 0 signifying no pain and 10 signifying the worst pain you can imagine. Each patient will be assessed regularly, including: before therapeutic intervention (i.e. at consent/screening), first day of chemotherapy administration (during cycles 1 & 2), 4 days after pegfilgrastim administration (during cycles 1 & 2), and 8 days after pegfilgrastim administration (during cycles 1 & 2)." (NCT03407430)
Timeframe: Up to 12 weeks

Maximum Neuropathic Pain Score Between Pregabalin and Placebo Across the 2 Cycles

"Compare the maximum neuropathic pain score between pregabalin and placebo within cycle 1 and across the 2 cycles.~The ID Pain scale (also know as the Identify Pain scale) is a 6-item, participant-completed screening tool designed to help differentiate nociceptive and neuropathic pain. This pain score also helps to evaluate the presence/absence of neuropathic pain at a given point of time.~Did the pain feel like pins and needles?~Did the pain feel hot/burning?~Did the pain feel numb?~Did the pain feel like electrical shocks?~Is the pain made worse with the touch of clothing or bed sheets?~Is the pain limited to your joints?~A yes response to questions 1-5 are scored as 1; for question 6, a yes is scored as -1. As such, higher scores (approaching 5) signify worse outcomes. The scale's total range for a patient is -1 to 5." (NCT03407430)
Timeframe: Up to 12 weeks

Number of Days of Breakthrough Analgesic Use Between Pregabalin and Placebo Across the 2 Cycles

"Compare the number of days of breakthrough analgesic use between pregabalin and placebo within cycle 1 and across the 2 cycles.~The number of days of breakthrough analgesic use (i.e additional pain medication being required) is evaluated based on participant-provided medication logs kept during study treatment. If additional pain medication outside of their normal pain control regimen was reported, this day counts as 1. The total days for each patient are then reported, with a total range from zero to 14 (for patients with breast cancer) or zero to 21 (for patients with a lymphoma)." (NCT03407430)
Timeframe: Up to 12 weeks

Number of Patients Who Have an Increase in Pain Score of ≥ 3 From Baseline Through the End of Study Medication in Cycle 1

"Compare the proportion of patients who have an increase in pain score of ≥ 3 from baseline through the end of study medication in cycle 1 between Arm A and Arm B.~The ten-point numerical scale is scored from 0 to 10. They will use this scale to rate their pain (and separately bone/joint pain) with 0 signifying no pain and 10 signifying the worst pain you can imagine." (NCT03407430)
Timeframe: Up to 12 weeks

Number of Subjects That Experienced a Grade 2 or Higher Adverse Events When Taking Pregabalin

CTCAE The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. (NCT03407430)
Timeframe: Up to 12 weeks

Proportion of Patients Who Have an Increase in Bone/Joint Pain Score of ≥ 3 From Baseline Through the End of Study Medication in Cycle 1

"Compare the proportion of patients who have an increase in bone/joint pain score of ≥ 3 from baseline through the end of study medication in cycle 1 between Arm A and Arm B.~The ten-point numerical scale is scored from 0 to 10. They will use this scale to rate their pain (and separately bone/joint pain) with 0 signifying no pain and 10 signifying the worst pain you can imagine." (NCT03407430)
Timeframe: Up to 12 weeks

Proportion of Patients Who Have an Increase in Pain Score of ≥ 3 From Baseline Between Pregabalin and Placebo Across the 2 Cycles

"Compare the proportion of patients who have an increase in pain score of ≥ 3 from baseline between pregabalin and placebo across the 2 cycles.~The ten-point numerical scale is scored from 0 to 10. They will use this scale to rate their pain (and separately bone/joint pain) with 0 signifying no pain and 10 signifying the worst pain you can imagine." (NCT03407430)
Timeframe: Up to 12 weeks

Proportion of Patients With Severe Pain Between Pregabalin and Placebo Across the 2 Cycles

"Compare the proportion of patients with severe pain between pregabalin and placebo within cycle 1 and across the 2 cycles.~The ten-point numerical scale is scored from 0 to 10. They will use this scale to rate their pain (and separately bone/joint pain) with 0 signifying no pain and 10 signifying the worst pain you can imagine." (NCT03407430)
Timeframe: Up to 12 weeks

Intervention	participants (Number)
	Week 1: Yes	Week 1: No	Week 2: Yes	Week 2: No	Week 3: Yes	Week 3: No	Week 4: Yes	Week 4: No	Week 5: Yes	Week 5: No	Week 6: Yes	Week 6: No	Week 8: Yes	Week 8: No	Week 8 (LOCF): Yes	Week 8 (LOCF): No
Placebo	49	120	74	89	76	86	88	61	81	50	76	49	82	45	110	66
Pregabalin	62	101	94	72	93	62	97	55	89	45	83	38	80	43	113	61

Intervention	participants (Number)
	Week 1 Responder: Yes	Week 1 Responder: No	Week 2 Responder: Yes	Week 2 Responder: No	Week 3 Responder: Yes	Week 3 Responder: No	Week 4 Responder: Yes	Week 4 Responder: No	Week 5 Responder: Yes	Week 5 Responder: No	Week 6 Responder: Yes	Week 6 Responder: No	Week 8 Responder: Yes	Week 8 Responder: No	Week 8 (LOCF) Responder: Yes	Week 8 (LOCF) Responder: No
Placebo	8	161	26	137	23	137	46	104	46	84	48	77	47	80	62	114
Pregabalin	21	143	39	127	51	106	64	89	58	77	57	65	63	63	84	93

Intervention	participants (Number)
	Week 1 Remission: Yes	Week 1 Remission: No	Week 2 Remission: Yes	Week 2 Remission: No	Week 3 Remission: Yes	Week 3 Remission: No	Week 4 Remission: Yes	Week 4 Remission: No	Week 5 Remission: Yes	Week 5 Remission: No	Week 6 Remission: Yes	Week 6 Remission: No	Week 8 Remission: Yes	Week 8 Remission: No	Week 8 (LOCF) Remission: Yes	Week 8 (LOCF) Remission: No
Placebo	5	164	15	148	18	142	29	121	30	100	32	93	31	96	42	134
Pregabalin	12	152	22	144	32	125	43	110	39	96	37	85	40	86	55	122

Intervention	units on a scale (Mean)
First Intervention = Pregabalin	0.4
Second Intervention = Placebo	2
First Intervention = Placebo	0
Second Intervention = Pregabalin	1.67

Intervention	days (Mean)
First Intervention = Pregabalin	1.4
Second Intervention = Placebo	3.25
First Intervention = Placebo	0.67
Second Intervention = Pregabalin	0

Intervention	proportion (Number)
First Intervention = Pregabalin	0.4
Second Intervention = Placebo	0.25
First Intervention = Placebo	0.67
Second Intervention = Pregabalin	0

Article	Year
Long-term treatment of anxiety disorders with pregabalin: a 1 year open-label study of safety and tolerability. Current medical research and opinion, 2013, Volume: 29, Issue:10 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anxiety Disorders; Calcium Channel Blockers; Double-Blin	2013
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
[Pantogam activ (D-, L-hopantenic acid) in the treatment of cognitive and anxiety disorders in patients with arterial hypertension]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 2015, Volume: 115, Issue:12 Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Anxiety Disorders; Blood Pressure Monitoring, Ambu	2015
Efficacy and safety of pregabalin in elderly people with generalised anxiety disorder. The British journal of psychiatry : the journal of mental science, 2008, Volume: 193, Issue:5 Topics: Aged; Aged, 80 and over; Anti-Anxiety Agents; Anxiety Disorders; Double-Blind Method; Female; gamma-	2008
The efficacy of pregabalin and benzodiazepines in generalized anxiety disorder presenting with high levels of insomnia. International clinical psychopharmacology, 2009, Volume: 24, Issue:4 Topics: Adult; Anxiety Disorders; Benzodiazepines; Double-Blind Method; Female; gamma-Aminobutyric Acid; Hum	2009
Efficacy of pregabalin in generalized social anxiety disorder: results of a double-blind, placebo-controlled, fixed-dose study. International clinical psychopharmacology, 2011, Volume: 26, Issue:4 Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Double-Blind Method; Female; gamma-Aminobutyric Acid;	2011
Efficacy of pregabalin and venlafaxine-XR in generalized anxiety disorder: results of a double-blind, placebo-controlled 8-week trial. International clinical psychopharmacology, 2009, Volume: 24, Issue:2 Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Cyclohexanols; Diagnostic and Statistical Manual of M	2009
Switching from long-term benzodiazepine therapy to pregabalin in patients with generalized anxiety disorder: a double-blind, placebo-controlled trial. Journal of psychopharmacology (Oxford, England), 2012, Volume: 26, Issue:4 Topics: Adult; Alprazolam; Anxiety Disorders; Cognition; Double-Blind Method; Female; gamma-Aminobutyric Aci	2012
Does early improvement predict endpoint response in patients with generalized anxiety disorder (GAD) treated with pregabalin or venlafaxine XR? European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2012, Volume: 22, Issue:2 Topics: Adult; Analgesics; Anxiety Disorders; Cyclohexanols; Delayed-Action Preparations; Double-Blind Metho	2012
Adjunctive therapy with pregabalin in generalized anxiety disorder patients with partial response to SSRI or SNRI treatment. International clinical psychopharmacology, 2012, Volume: 27, Issue:3 Topics: Adrenergic Uptake Inhibitors; Adult; Antidepressive Agents; Anxiety Disorders; Citalopram; Cyclohexa	2012
Evaluation of the effects of venlafaxine and pregabalin on the carbon dioxide inhalation models of Generalised Anxiety Disorder and panic. Journal of psychopharmacology (Oxford, England), 2013, Volume: 27, Issue:2 Topics: Administration, Inhalation; Adult; Anxiety Disorders; Blood Pressure; Carbon Dioxide; Cyclohexanols;	2013
Tolerability and use in co-administration of pregabalin in affective patients: a 6-month prospective naturalistic study. Expert opinion on drug safety, 2012, Volume: 11, Issue:6 Topics: Adult; Aged; Anticonvulsants; Antidepressive Agents; Anxiety Disorders; Benzodiazepines; Depressive	2012
Pregabalin in generalized anxiety disorder: a placebo-controlled trial. The American journal of psychiatry, 2003, Volume: 160, Issue:3 Topics: Adult; Anticonvulsants; Anxiety Disorders; Dizziness; Drug Administration Schedule; Female; gamma-Am	2003
A randomized, double-blind, placebo-controlled, fixed-dose, multicenter study of pregabalin in patients with generalized anxiety disorder. Journal of clinical psychopharmacology, 2003, Volume: 23, Issue:3 Topics: Adolescent; Adult; Aged; Analysis of Variance; Anxiety Disorders; Double-Blind Method; Female; gamma	2003
Efficacy of pregabalin in the treatment of generalized anxiety disorder: double-blind, placebo-controlled comparison of BID versus TID dosing. Journal of clinical psychopharmacology, 2005, Volume: 25, Issue:2 Topics: Adult; Anxiety Disorders; Double-Blind Method; Drug Administration Schedule; Female; gamma-Aminobuty	2005
Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam. Archives of general psychiatry, 2005, Volume: 62, Issue:9 Topics: Adult; Alprazolam; Anti-Anxiety Agents; Anticonvulsants; Anxiety Disorders; Dizziness; Double-Blind	2005
The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study. The Journal of clinical psychiatry, 2005, Volume: 66, Issue:11 Topics: Adult; Aged; Anxiety Disorders; Data Interpretation, Statistical; Double-Blind Method; Drug Administ	2005
Open-label tiagabine monotherapy for major depressive disorder with anxiety. The Journal of clinical psychiatry, 2006, Volume: 67, Issue:1 Topics: Adult; Ambulatory Care; Anxiety Disorders; Comorbidity; Depressive Disorder, Major; Drug Administrat	2006
Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder: a 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine. The Journal of clinical psychiatry, 2006, Volume: 67, Issue:5 Topics: Adult; Anticonvulsants; Anxiety Disorders; Cyclohexanols; Disorders of Excessive Somnolence; Dizzine	2006
Long-term efficacy of pregabalin in generalized anxiety disorder. International clinical psychopharmacology, 2008, Volume: 23, Issue:1 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Anxiety Agents; Anxiety Disorders; Double-Blind Met	2008
High-field MRS study of GABA, glutamate and glutamine in social anxiety disorder: response to treatment with levetiracetam. Progress in neuro-psychopharmacology & biological psychiatry, 2008, Apr-01, Volume: 32, Issue:3 Topics: Adolescent; Adult; Aged; Anxiety Disorders; Female; gamma-Aminobutyric Acid; Glutamic Acid; Glutamin	2008
Baclofen administration for the treatment of affective disorders in alcoholic patients. Drug and alcohol dependence, 1993, Volume: 33, Issue:2 Topics: Administration, Oral; Adult; Alcoholism; Amitriptyline; Anxiety Disorders; Baclofen; Blood Platelets	1993
Gabapentin: long-term antianxiety and hypnotic effects in psychiatric patients with comorbid anxiety-related disorders. Canadian journal of psychiatry. Revue canadienne de psychiatrie, 1998, Volume: 43, Issue:3 Topics: Acetates; Adult; Aged; Amines; Anti-Anxiety Agents; Anticonvulsants; Anxiety Disorders; Behavioral S	1998
A beneficial effect on mood in partial epilepsy patients treated with gabapentin. Epilepsia, 1999, Volume: 40, Issue:8 Topics: Acetates; Adult; Affect; Aged; Amines; Anticonvulsants; Anxiety Disorders; Comorbidity; Cyclohexanec	1999
Effect of acute and chronic benzodiazepines on plasma GABA in anxious patients and controls. Psychopharmacology, 1992, Volume: 109, Issue:1-2 Topics: Adult; Alprazolam; Anti-Anxiety Agents; Anxiety Disorders; Diazepam; gamma-Aminobutyric Acid; Humans	1992
The administration of transcranial electric treatment for affective disturbances therapy in alcoholic patients. Drug and alcohol dependence, 1991, Volume: 27, Issue:1 Topics: Adult; Alcoholism; Alpha Rhythm; Anxiety Disorders; Arousal; Depressive Disorder; Electric Stimulati	1991
Role of gamma-aminobutyric acid in antipanic drug efficacy. The American journal of psychiatry, 1989, Volume: 146, Issue:3 Topics: Anxiety Disorders; Baclofen; Clinical Trials as Topic; Double-Blind Method; Fear; gamma-Aminobutyric	1989

gamma-aminobutyric acid and Anxiety Neuroses