gamma-aminobutyric acid and Sleep Initiation and Maintenance Disorders 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.

Sleep Initiation and Maintenance Disorders: Disorders characterized by impairment of the ability to initiate or maintain sleep. This may occur as a primary disorder or in association with another medical or psychiatric condition.

Research Excerpts

Excerpt	Relevance	Reference
"Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design."	9.19	Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study. ( Arnold, LM; Arsenault, P; Chew, ML; Clair, AG; Huffman, C; Messig, M; Patrick, JL; Pauer, L; Sanin, L; Scavone, JM, 2014)
"Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response."	9.19	Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study. ( Arnold, LM; Arsenault, P; Chew, ML; Clair, AG; Huffman, C; Messig, M; Patrick, JL; Pauer, L; Sanin, L; Scavone, JM, 2014)
"To evaluate the efficacy and safety of pregabalin in the treatment of postherpetic neuralgia (PHN)."	9.10	Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. ( Bockbrader, H; Corbin, AE; Dworkin, RH; Garofalo, EA; LaMoreaux, L; Poole, RM; Sharma, U; Young, JP, 2003)
"The efficacy of a new drug, pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg), was studied on 100 patients affected by insomnia, associated with mood disorders."	9.08	Evaluation of the efficacy of pivagabine on insomnia associated with mood disorders. ( Negri, L, 1997)
" 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)
"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)
"We studied the effects of low-dose ozone therapy on the sleep quality of patients with coronary heart disease (CHD) and insomnia by measuring the levels of brain-derived neurotrophic factor (BDNF) and GABA in blood serum."	8.02	Low-Dose Ozone Therapy Improves Sleep Quality in Patients with Insomnia and Coronary Heart Disease by Elevating Serum BDNF and GABA. ( Feng, X; Huang, H; Li, Y; Ren, H; Wang, Y; Yu, S, 2021)
"Forty chronic insomnia participants were randomized to either real or sham rTMS group."	7.11	Alteration of gamma-aminobutyric acid in the left dorsolateral prefrontal cortex of individuals with chronic insomnia: a combined transcranial magnetic stimulation-magnetic resonance spectroscopy study. ( Huang, X; Liang, K; Wang, C; Zhang, H, 2022)
" Given the maximal dosage studied, pregabalin had acceptable tolerability compared to placebo despite a greater incidence of side effects, which were generally mild to moderate in intensity."	6.71	Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. ( Bockbrader, H; Corbin, AE; Dworkin, RH; Garofalo, EA; LaMoreaux, L; Poole, RM; Sharma, U; Young, JP, 2003)
"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)
"Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response."	5.19	Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study. ( Arnold, LM; Arsenault, P; Chew, ML; Clair, AG; Huffman, C; Messig, M; Patrick, JL; Pauer, L; Sanin, L; Scavone, JM, 2014)
"Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design."	5.19	Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study. ( Arnold, LM; Arsenault, P; Chew, ML; Clair, AG; Huffman, C; Messig, M; Patrick, JL; Pauer, L; Sanin, L; Scavone, JM, 2014)
"Pregabalin 150 to 600 mg/day was effective in relieving central neuropathic pain, improving sleep, anxiety, and overall patient status in patients with spinal cord injury."	5.12	Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial. ( Chambers, R; Cousins, MJ; Griesing, T; Murphy, TK; Otte, A; Siddall, PJ, 2006)
"To evaluate the efficacy and safety of pregabalin in the treatment of postherpetic neuralgia (PHN)."	5.10	Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. ( Bockbrader, H; Corbin, AE; Dworkin, RH; Garofalo, EA; LaMoreaux, L; Poole, RM; Sharma, U; Young, JP, 2003)
"The efficacy of a new drug, pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg), was studied on 100 patients affected by insomnia, associated with mood disorders."	5.08	Evaluation of the efficacy of pivagabine on insomnia associated with mood disorders. ( Negri, L, 1997)
"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)
"We studied the effects of low-dose ozone therapy on the sleep quality of patients with coronary heart disease (CHD) and insomnia by measuring the levels of brain-derived neurotrophic factor (BDNF) and GABA in blood serum."	4.02	Low-Dose Ozone Therapy Improves Sleep Quality in Patients with Insomnia and Coronary Heart Disease by Elevating Serum BDNF and GABA. ( Feng, X; Huang, H; Li, Y; Ren, H; Wang, Y; Yu, S, 2021)
"Considerable evidence implicates the neurotransmitter gamma-aminobutyric acid (GABA) in the biochemical pathophysiology of mood disorders."	3.70	GABAA alpha-1 subunit gene not associated with depressive symptomatology in mood disorders. ( Catalano, M; Cusin, C; Di Bella, D; Lattuada, E; Lilli, R; Macciardi, F; Serretti, A; Smeraldi, E, 1998)
"After 21-day sleep deprivation (SD) in platform water environment, CSD mice model was prepared."	3.54	Effects of BXSMD on ESR1 and ESR2 expression in CSD female mice. ( Liang, S; Liu, L; Liu, X; Wang, S; Yang, J; Zhang, Y, 2024)
"Forty chronic insomnia participants were randomized to either real or sham rTMS group."	3.11	Alteration of gamma-aminobutyric acid in the left dorsolateral prefrontal cortex of individuals with chronic insomnia: a combined transcranial magnetic stimulation-magnetic resonance spectroscopy study. ( Huang, X; Liang, K; Wang, C; Zhang, H, 2022)
"Both AB+AA and AA can relieve insomnia symptoms, but a stronger long-term effect were observed for AB+AA."	3.11	Effect of Auricular Acupoint Bloodletting plus Auricular Acupressure on Sleep Quality and Neuroendocrine Level in College Students with Primary Insomnia: A Randomized Controlled Trial. ( Chen, H; Huo, YX; Liu, DN; She, YF; Shi, XL; Sun, H; Wu, JA; Yuan, XR; Zhang, MJ, 2022)
"One hundred and thirty patients with insomnia were randomized into an observation group and a control group, 65 cases in each one."	2.79	[Clinical observation on the neurotransmitters regulation in patients of insomnia differentiated as yang deficiency pattern treated with warm acupuncture and auricular point sticking therapy]. ( Du, L; Liu, XC; Yang, JL; Yang, YS; Zhang, R, 2014)
"Individuals with major depressive disorder (MDD) often use hypnotics like zolpidem (Ambien(®)) to improve sleep in addition to their selective serotonin reuptake inhibitor (SSRI) regimen."	2.79	Zolpidem increases GABA in depressed volunteers maintained on SSRIs. ( Conn, NA; Jensen, JE; Licata, SC; Lukas, SE; Winer, JP, 2014)
"Aside from treating insomnia, using zolpidem in the presence of SSRIs may have some unidentified therapeutic effects for depressed individuals."	2.79	Zolpidem increases GABA in depressed volunteers maintained on SSRIs. ( Conn, NA; Jensen, JE; Licata, SC; Lukas, SE; Winer, JP, 2014)
"Gabapentin was associated with significantly higher values of KSD Sleep Quality Index and reported TST versus placebo; no other reported outcomes were significant."	2.79	A randomized, double-blind, single-dose, placebo-controlled, multicenter, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance. ( Furey, SA; Hull, SG; Jayawardena, S; Lankford, DA; Mayleben, DW; Rosenberg, RP; Roth, T; Seiden, DJ, 2014)
" The starting dosage of pregabalin was 75 mg/day and was increased up to as much as 300 mg/day, depending on the individual patient's condition, while tapering off hypnotics."	2.79	Effects of pregabalin in patients with hypnotic-dependent insomnia. ( Cho, YW; Song, ML, 2014)
"Gabapentin was associated with less %stage1 on Day 1, and greater %REM on Day 28, versus placebo."	2.79	A randomized, double-blind, placebo-controlled, multicenter, 28-day, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance. ( Furey, SA; Hull, SG; Jayawardena, S; Leibowitz, MT; Roth, T, 2014)
" Using plasma gabapentin concentration data obtained after administration of GEn in 12 phase 1 to 3 GEn studies in healthy adults or patients with RLS (dose range, 300-2400 mg/d), a population pharmacokinetic (PK) model was developed by nonlinear mixed-effect modeling using NONMEM."	2.78	Population pharmacokinetics and pharmacodynamics of gabapentin after administration of gabapentin enacarbil. ( Cundy, KC; Lal, R; Lassauzet, ML; Luo, W; Sukbuntherng, J; Tovera, J, 2013)
"Insomnia is a common phenomenon particularly in patients with epilepsy."	2.77	Pregabalin increases slow-wave sleep and may improve attention in patients with partial epilepsy and insomnia. ( Bazil, CW; Cole, J; Dave, J; Drake, E; Stalvey, J, 2012)
"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)
"To evaluate pregabalin in central neuropathic pain associated with spinal cord injury."	2.72	Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial. ( Chambers, R; Cousins, MJ; Griesing, T; Murphy, TK; Otte, A; Siddall, PJ, 2006)
"Dizziness was the most common side effect."	2.71	Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial. ( Bockbrader, H; Knapp, LE; Lamoreaux, L; Portenoy, R; Richter, RW; Sharma, U, 2005)
"Two hundred forty-six men and women with painful diabetic neuropathy received pregabalin (150 or 600 mg/day by mouth) or placebo."	2.71	Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial. ( Bockbrader, H; Knapp, LE; Lamoreaux, L; Portenoy, R; Richter, RW; Sharma, U, 2005)
" Given the maximal dosage studied, pregabalin had acceptable tolerability compared to placebo despite a greater incidence of side effects, which were generally mild to moderate in intensity."	2.71	Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. ( Bockbrader, H; Corbin, AE; Dworkin, RH; Garofalo, EA; LaMoreaux, L; Poole, RM; Sharma, U; Young, JP, 2003)
"Gabapentin is a calcium channel GABAergic modulator that is widely used for pain."	2.58	Gabapentin for the treatment of alcohol use disorder. ( Mason, BJ; Quello, S; Shadan, F, 2018)
"Expert opinion: Alcohol use disorder represents a challenge and large, unmet medical need."	2.58	Gabapentin for the treatment of alcohol use disorder. ( Mason, BJ; Quello, S; Shadan, F, 2018)
"Behavioral therapies for insomnia include the following: sleep hygiene, cognitive behavioral therapy for insomnia, multicomponent behavioral therapy or brief behavioral therapy for insomnia, relaxation strategies, stimulus control, and sleep restriction."	2.55	An update of management of insomnia in patients with chronic orofacial pain. ( Almoznino, G; Benoliel, R; Haviv, Y; Sharav, Y, 2017)
"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)
"Chronic orofacial pain can greatly improve following treatment of the underlying insomnia, and therefore, re-evaluation of COFP is advised after 1 month of treatment."	2.55	An update of management of insomnia in patients with chronic orofacial pain. ( Almoznino, G; Benoliel, R; Haviv, Y; Sharav, Y, 2017)
"Sleep disorders are treated using anti-insomnia drugs that target ionotropic and G protein-coupled receptors (GPCRs), including γ-aminobutyric acid (GABA) agonists, melatonin agonists, and orexin receptor antagonists."	2.53	Sleep Control, GPCRs, and Glucose Metabolism. ( Sakurai, T; Sasaoka, T; Tsuneki, H, 2016)
"The consequences of insomnia, including issues with mood, behavior, and cognition, are discussed."	2.53	Pediatric Insomnia. ( Brown, KM; Malow, BA, 2016)
"Chronic insomnia is a common condition that affects people worldwide and has negative effects on patients' health and wellbeing."	2.53	Advances in the management of chronic insomnia. ( Attarian, H; Kay-Stacey, M, 2016)
"Therefore, insomnia and alcohol dependence might be best thought of as co-occurring disorders, each of which requires its own treatment."	2.52	Assessment and treatment of insomnia in adult patients with alcohol use disorders. ( Brower, KJ, 2015)
"Insomnia in patients with alcohol dependence has increasingly become a target of treatment due to its prevalence, persistence, and associations with relapse and suicidal thoughts, as well as randomized controlled studies demonstrating efficacy with behavior therapies and non-addictive medications."	2.52	Assessment and treatment of insomnia in adult patients with alcohol use disorders. ( Brower, KJ, 2015)
"Neuroimaging studies in primary insomnia remain relatively few, considering the important prevalence of this disorder in the general population."	2.50	Neuroimaging findings in primary insomnia. ( Berman Rosa, M; Dang-Vu, TT; Gouin, JP; O'Byrne, JN, 2014)
"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)
"Suvorexant is a dual orexin antagonist currently in Phase III clinical trials for the modulation of sleep and is being developed by Merck."	2.48	ACS chemical neuroscience molecule spotlight on Suvorexant. ( Hopkins, CR, 2012)
"Therefore, exploring the anti-insomnia effects of volatile oils from HAD is of great importance."	2.44	Effects of aqueous extracts and volatile oils prepared from Huaxiang Anshen decoction on p-chlorophenylalanine-induced insomnia mice. ( Chen, D; He, C; Li, X; Pu, Y; Shen, M; Wang, M; Zhang, T; Zhou, J, 2024)
"It is hard to define what ratio of insomnia and daytime hypersomnia is caused by the antiparkinsonian treatment, by the somatic and mental-emotional symptoms of the neurodegenerative disease and by the neurodegenerative brain process itself."	2.44	[Sleep disorders in Parkinson syndromes]. ( Kovács, GG; Lalit, N; Péter, H; Szucs, A, 2007)
"Sleep-onset and maintenance insomnia is a characteristic feature of schizophrenic patients regardless of either their medication status (drug-naive or previously treated) or the phase of the clinical course (acute or chronic)."	2.43	Sleep disturbance in schizophrenia. ( Monti, D; Monti, JM, 2005)
"Chronic insomnia affects a significant proportion of young adult and elderly populations."	2.43	Treating insomnia: Current and investigational pharmacological approaches. ( Deacon, S; Ebert, B; Wafford, KA, 2006)
"Insomnia is a common symptom in schizophrenia, although it is seldom the predominant complaint."	2.43	Sleep disturbance in schizophrenia. ( Monti, D; Monti, JM, 2005)
"Some correlates of insomnia in alcoholic patients are identical to those observed in non-alcoholic insomniacs, including anxiety and depression, tobacco smoking, and the use of alcohol to aid sleep."	2.42	Insomnia, alcoholism and relapse. ( Brower, KJ, 2003)
" The safety and tolerability of GABA-BZ receptor agonists and SUX were high, and no serious adverse effects were observed after switching to LEM."	1.91	Efficacy and safety of lemborexant as an alternative drug for patients with insomnia taking gamma-aminobutyric acid-benzodiazepine receptor agonists or suvorexant. ( Inamoto, A; Iwanami, A; Kawai, K; Okino, K; Sanada, K; Suzuki, H; Tomioka, H, 2023)
"Insomnia is the most common sleep disorder and is often comorbid with mental and physical diseases."	1.91	Electroacupuncture of the cymba concha alleviates p-chlorophenylalanine-induced insomnia in mice. ( Peng, Q; Tang, L; Zhang, F; Zhang, X, 2023)
"AA have certain therapeutic effects on insomnia."	1.91	The Effect of Chinese Agarwood Essential Oil with Cyclodextrin Inclusion against PCPA-Induced Insomnia Rats. ( Chen, J; Hua, L; Lai, Y; Li, J; Shi, S; Xu, J; Yang, J; Zhang, S; Zhu, S, 2023)
"Although gamma-aminobutyric acid-benzodiazepine (GABA-BZ) receptor agonists are used to treat insomnia, their long-term or high-dosage use causes adverse events."	1.91	Efficacy and safety of lemborexant as an alternative drug for patients with insomnia taking gamma-aminobutyric acid-benzodiazepine receptor agonists or suvorexant. ( Inamoto, A; Iwanami, A; Kawai, K; Okino, K; Sanada, K; Suzuki, H; Tomioka, H, 2023)
"The novel dual orexin receptor antagonist lemborexant (LEM) has fewer adverse effects than GABA-BZ receptor agonists."	1.91	Efficacy and safety of lemborexant as an alternative drug for patients with insomnia taking gamma-aminobutyric acid-benzodiazepine receptor agonists or suvorexant. ( Inamoto, A; Iwanami, A; Kawai, K; Okino, K; Sanada, K; Suzuki, H; Tomioka, H, 2023)
"That meets the main mechanism of insomnia in traditional Chinese medicine."	1.72	Jiaotaiwan increased GABA level in brain and serum, improved sleep via increasing NREM sleep and REM sleep, and its component identification. ( ChongLiang, L; LuFeng, H; Ren, Y; SiSi, L; Yuan, F; ZhengZhong, Y, 2022)
"In the caffeine-induced insomnia model, the administration of a Saaz-Saphir mixture increased the sleep time compared to Saaz or Saphir administration alone, which was attributed to the increase in NREM sleep time by the δ-wave increase."	1.62	GABA ( Ahn, Y; Cho, HJ; Jo, K; Kwak, WK; Min, B; Suh, HJ, 2021)
"In this study, PCPA-induced insomnia model was used to explore the sleep-promoting mechanism of enzymolysis peptides from PMM, and its main composition and chemical structure were analyzed."	1.62	Enzymolysis peptides from Mauremys mutica plastron improve the disorder of neurotransmitter system and facilitate sleep-promoting in the PCPA-induced insomnia mice. ( Luo, LS; Lv, YB; Yan, JX; Zhang, JL; Zhou, Q, 2021)
"Established the PCPA insomnia model of mice, The open field test, pentobarbital-induced falling asleep rate, latency of sleeping time, and duration of sleeping time experiments were used to evaluate the behavior of mice, the enzyme-linked immunosorbent assay was used to analyze the content of 5-HT and GABA in hypothalamus and cerebral cortex."	1.62	Sedative and hypnotic effects of Perilla frutescens essential oil through GABAergic system pathway. ( Du, Q; Guo, Y; Hu, P; Huang, X; Li, J; Li, W; Liu, S; Ren, G; Shuai, S; Wu, L; Xiao, S; Yang, M; Zhang, K; Zhang, M; Zheng, Q; Zhong, Y; Zhu, L, 2021)
"Insomnia is a common health problem in modern societies."	1.56	Beneficial effect of GABA-rich fermented milk on insomnia involving regulation of gut microbiota. ( Cen, S; Chen, W; Duan, H; Feng, S; Han, X; Tian, F; Xue, Y; Yu, L; Zhai, Q; Zhang, H; Zhao, J, 2020)
"The extent to which comorbid insomnia contributes to GABAergic or glutamatergic deficiencies in MDD remains unclear."	1.56	( Baer, L; Benson, KL; Bottary, R; Eric Jensen, J; Gonenc, A; Schoerning, L; Winkelman, JW, 2020)
"Both Major Depressive Disorder (MDD) and Primary Insomnia (PI) have been linked to deficiencies in cortical γ-aminobutyric acid (GABA) and glutamate (Glu) thus suggesting a shared neurobiological link between these two conditions."	1.56	( Baer, L; Benson, KL; Bottary, R; Eric Jensen, J; Gonenc, A; Schoerning, L; Winkelman, JW, 2020)
"Chronic insomnia is defined as a persistent difficulty with sleep initiation maintenance or non-restorative sleep."	1.46	The dual orexin receptor antagonist, DORA-22, lowers histamine levels in the lateral hypothalamus and prefrontal cortex without lowering hippocampal acetylcholine. ( Coleman, PJ; Fox, SV; Gotter, AL; Hodgson, R; Ramirez, AD; Renger, JJ; Roecker, AJ; Smith, SM; Uslaner, JM; Winrow, CJ; Yao, L, 2017)
"Chronic insomnia is one of the most prevalent central nervous system disorders."	1.43	Magnetic Resonance Spectroscopy in Patients with Insomnia: A Repeated Measurement Study. ( Baglioni, C; Feige, B; Hennig, J; Lange, T; Nissen, C; Regen, W; Riemann, D; Spiegelhalder, K, 2016)
"The findings have implications for PTSD treatment approaches."	1.40	Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality. ( Metzler, T; Meyerhoff, DJ; Mon, A; Neylan, TC, 2014)
"As expected, PTSD+ had higher depressive and anxiety symptom scores and a higher Insomnia Severity Index (ISI) score."	1.40	Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality. ( Metzler, T; Meyerhoff, DJ; Mon, A; Neylan, TC, 2014)
" Before dosing and at 30, 60, 120, 240 min, general behaviors within 5 min were recorded."	1.40	[Mechanism of Bailemian capsules in the treatment of insomnia in mice]. ( Bian, Y; Tang, X, 2014)
"In middle and high-dose groups, insomnia symptoms improved significantly."	1.40	[Mechanism of Bailemian capsules in the treatment of insomnia in mice]. ( Bian, Y; Tang, X, 2014)
"Insomnia is a prominent modern disease that affects an increasing population."	1.40	Discovery of novel insomnia leads from screening traditional Chinese medicine database. ( Chan, YC; Chang, SS; Chen, CY; Chen, HY, 2014)
"Twenty-seven patients with PTSD (PTSD+) and 18 trauma-exposed controls without PTSD (PTSD-), recruited from United States Army reservists, Army National Guard, and mental health clinics."	1.40	Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality. ( Metzler, T; Meyerhoff, DJ; Mon, A; Neylan, TC, 2014)
"Insomnia is prevalent in pediatrics, particularly in those with neurodevelopmental disorders."	1.39	Gabapentin shows promise in treating refractory insomnia in children. ( Malow, BA; Robinson, AA, 2013)
"The model of insomnia rats were established by PCPA intraperitoneal injection, after the modeling, all the therapeutic group were treated with corresponding drug for one week."	1.39	[Effects of extracts from ziziphi spinosae semen and schisandrae chinensis fructus on amino acid neurotransmitter in rats with insomnia induced by PCPA]. ( Chen, JF; Gao, JR; Ji, WB; Jiang, H, 2013)
"We report a case with refractory insomnia."	1.39	Treatment-resistant insomnia treated with pregabalin. ( Di Iorio, G; Di Tizio, L; Martinotti, G; Matarazzo, I, 2013)
"Gabapentin has shown promise in treating insomnia in adults."	1.39	Gabapentin shows promise in treating refractory insomnia in children. ( Malow, BA; Robinson, AA, 2013)
"Increased GABA levels in persons with insomnia may reflect an allostatic response to chronic hyperarousal."	1.38	Cortical GABA levels in primary insomnia. ( Fasula, M; Forselius, E; Mason, GF; Morgan, PT; Pace-Schott, EF; Sanacora, G; Valentine, GW, 2012)
"Acupuncture can effectively suppress insomnia induced down-regulation of hypothalamic GABA and GABA(A)R in rats and lengthen pole-climbing time, which may contribute to its effect in relieving insomnia."	1.38	[Effect of acupuncture at different acupoints on expression of hypothalamic GABA and GABA(A) receptor proteins in insomnia rats]. ( Gao, XY; Ren, S; Wang, PY; Zhou, YL, 2012)
"Insomnia is closely related to major depressive disorder (MDD) both cross-sectionally and longitudinally, and as such, offers potential opportunities to refine our understanding of the neurobiology of both sleep and mood disorders."	1.38	Reduced γ-aminobutyric acid in occipital and anterior cingulate cortices in primary insomnia: a link to major depressive disorder? ( Jensen, JE; Plante, DT; Schoerning, L; Winkelman, JW, 2012)
"Non-medicated persons with primary insomnia (N = 16) and no sleep complaints (N = 17)."	1.38	Cortical GABA levels in primary insomnia. ( Fasula, M; Forselius, E; Mason, GF; Morgan, PT; Pace-Schott, EF; Sanacora, G; Valentine, GW, 2012)
"The primary insomnia group was distinguished from persons with no sleep complaints on self-reported and polysomnographically measured sleep."	1.38	Cortical GABA levels in primary insomnia. ( Fasula, M; Forselius, E; Mason, GF; Morgan, PT; Pace-Schott, EF; Sanacora, G; Valentine, GW, 2012)
"Human transmissible spongiform encephalopathies (TSEs) or prion diseases are neurodegenerative disorders of infectious, inherited or sporadic origin and include Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), kuru and fatal familial insomnia (FFI)."	1.30	Selective neuronal vulnerability in human prion diseases. Fatal familial insomnia differs from other types of prion diseases. ( Budka, H; Flicker, H; Guentchev, M; Voigtländer, T; Wanschitz, J, 1999)

Research

Studies (91)

Authors

Clinical Trials (12)

Trial Overview

Trial Outcomes

Change From Baseline in Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 6- Quantity of Sleep

Timeframe	Studies, this research(%)	All Research%
pre-1990	2 (2.20)	18.7374
1990's	6 (6.59)	18.2507
2000's	22 (24.18)	29.6817
2010's	39 (42.86)	24.3611
2020's	22 (24.18)	2.80

Authors	Studies
Hong, JSW	1
Atkinson, LZ	2
Al-Juffali, N	1
Awad, A	2
Geddes, JR	2
Tunbridge, EM	1
Harrison, PJ	2
Cipriani, A	2
SiSi, L	1
Yuan, F	1
LuFeng, H	1
ChongLiang, L	1
Ren, Y	1
ZhengZhong, Y	1
Min, B	1
Ahn, Y	2
Cho, HJ	1
Kwak, WK	1
Suh, HJ	2
Jo, K	1
Zhang, H	2
Huang, X	3
Wang, C	2
Liang, K	1
Zuo, CS	1
Davis, KA	1
Lukas, SE	2
Kim, H	1
Park, I	1
Park, K	1
Park, S	1
Kim, YI	1
Park, BG	1
Wang, Y	2
Gong, B	1
Wu, Y	1
Chen, X	1
Liu, Y	1
Wei, J	1
Chen, H	1
Zhang, MJ	1
Wu, JA	1
She, YF	1
Yuan, XR	1
Huo, YX	1
Sun, H	1
Liu, DN	1
Shi, XL	1
Mu, K	3
Zhang, J	3
Feng, X	4
Zhang, D	3
Li, K	3
Li, R	3
Yang, P	3
Mao, S	3
Lai, Y	1
Hua, L	1
Yang, J	2
Xu, J	1
Chen, J	1
Zhang, S	1
Zhu, S	1
Li, J	3
Shi, S	1
Okino, K	1
Suzuki, H	1
Tomioka, H	1
Sanada, K	1
Kawai, K	1
Iwanami, A	1
Inamoto, A	1
Yan, LD	1
Zhou, P	1
Lai, MQ	1
Wu, M	1
Zhang, Y	2
Tang, RD	1
Sun, R	1
Luo, Y	1
Li, M	1
Sun, JL	1
Fu, WB	1
Zhang, F	1
Zhang, X	1
Peng, Q	1
Tang, L	1
Park, CW	1
Hong, KB	1
Wang, S	1
Liu, L	1
Liang, S	1
Liu, X	1
Li, X	1
He, C	1
Shen, M	1
Wang, M	1
Zhou, J	1
Chen, D	1
Zhang, T	1
Pu, Y	1
Zhong, Y	2
Zheng, Q	2
Hu, P	2
Yang, M	2
Ren, G	2
Du, Q	2
Luo, J	1
Zhang, K	2
Wu, H	1
Guo, Y	2
Liu, S	2
Yu, L	1
Han, X	1
Cen, S	1
Duan, H	1
Feng, S	1
Xue, Y	1
Tian, F	1
Zhao, J	1
Zhai, Q	1
Chen, W	1
Benson, KL	2
Bottary, R	1
Schoerning, L	2
Baer, L	1
Gonenc, A	1
Eric Jensen, J	1
Winkelman, JW	4
Wu, L	1
Zhu, L	1
Li, W	1
Xiao, S	1
Shuai, S	1
Zhang, M	1
Li, Y	1
Ren, H	1
Huang, H	1
Yu, S	1
Lv, YB	1
Zhou, Q	1
Yan, JX	1
Luo, LS	1
Zhang, JL	1
Lee, S	1
Jung, W	1
Eom, S	1
Yeom, HD	1
Park, HD	1
Lee, JH	1
Houghton, KT	1
Forrest, A	1
Stockton, S	1
Yao, L	1
Ramirez, AD	1
Roecker, AJ	1
Fox, SV	1
Uslaner, JM	1
Smith, SM	1
Hodgson, R	1
Coleman, PJ	1
Renger, JJ	1
Winrow, CJ	1
Gotter, AL	1
Mason, BJ	1
Quello, S	1
Shadan, F	1
Feng, J	1
Zhang, Q	1
Zhang, C	1
Wen, Z	1
Zhou, X	1
Peplow, M	1
Chen, HY	1
Chang, SS	1
Chan, YC	1
Chen, CY	2
Di Iorio, G	1
Matarazzo, I	1
Di Tizio, L	1
Martinotti, G	1
Krystal, AD	1
Benca, RM	1
Kilduff, TS	1
Gao, JR	1
Ji, WB	1
Jiang, H	1
Chen, JF	1
Meyerhoff, DJ	1
Mon, A	1
Metzler, T	1
Neylan, TC	1
Cho, YW	1
Song, ML	1
Arnold, LM	1
Arsenault, P	1
Huffman, C	1
Patrick, JL	1
Messig, M	1
Chew, ML	1
Sanin, L	1
Scavone, JM	1
Pauer, L	1
Clair, AG	1
Licata, SC	1
Jensen, JE	4
Conn, NA	1
Winer, JP	1
O'Byrne, JN	1
Berman Rosa, M	1
Gouin, JP	1
Dang-Vu, TT	1
Rosenberg, RP	1
Hull, SG	2
Lankford, DA	1
Mayleben, DW	1
Seiden, DJ	1
Furey, SA	2
Jayawardena, S	2
Roth, T	2
Leibowitz, MT	1
Bian, Y	1
Tang, X	1
Yang, JL	1
Zhang, R	1
Du, L	1
Yang, YS	1
Liu, XC	1
Brower, KJ	5
Brown, KM	1
Malow, BA	2
Luppi, PH	1
Peyron, C	1
Fort, P	1
Spiegelhalder, K	1
Regen, W	1
Nissen, C	1
Feige, B	1
Baglioni, C	1
Riemann, D	1
Hennig, J	1
Lange, T	1
Kay-Stacey, M	1
Attarian, H	1
Tsuneki, H	1
Sasaoka, T	1
Sakurai, T	1
Erden, V	1
Abitağaoğlu, S	1
Güler, C	1
Doğan, Z	1
Kırgezen, Ş	1
Abut, Y	1
Almoznino, G	1
Haviv, Y	1
Sharav, Y	1
Benoliel, R	1
Chen, YF	1
Tsai, HY	1
Myra Kim, H	1
Strobbe, S	1
Karam-Hage, MA	1
Consens, F	1
Zucker, RA	1
Buxton, OM	1
O'Connor, SP	1
Wang, W	1
Renshaw, PF	1
Kushida, CA	1
Becker, PM	1
Ellenbogen, AL	1
Canafax, DM	1
Barrett, RW	1
Russell, IJ	1
Crofford, LJ	1
Leon, T	1
Cappelleri, JC	2
Bushmakin, AG	2
Whalen, E	1
Barrett, JA	1
Sadosky, A	1
Konno, M	1
Uchiyama, M	1
Cheng, TC	1
Tsai, JF	1
McDermott, AM	1
Sadosky, AB	1
Petrie, CD	1
Martin, S	1
Montgomery, SA	1
Herman, BK	1
Schweizer, E	1
Mandel, FS	1
Lucey, BP	1
Noetzel, MJ	1
Duntley, SP	1
Plante, DT	2
Bazil, CW	1
Dave, J	1
Cole, J	1
Stalvey, J	1
Drake, E	1
Guttuso, T	1
Morgan, PT	1
Pace-Schott, EF	1
Mason, GF	1
Forselius, E	1
Fasula, M	1
Valentine, GW	1
Sanacora, G	1
Hopkins, CR	1
Robinson, AA	1
Zhou, YL	1
Gao, XY	1
Wang, PY	1
Ren, S	1
Ganguly, G	1
Altamura, AC	1
Moliterno, D	1
Paletta, S	1
Maffini, M	1
Mauri, MC	1
Bareggi, S	1
Lal, R	1
Sukbuntherng, J	1
Luo, W	1
Tovera, J	1
Lassauzet, ML	1
Cundy, KC	1
Dworkin, RH	1
Corbin, AE	1
Young, JP	1
Sharma, U	2
LaMoreaux, L	2
Bockbrader, H	2
Garofalo, EA	1
Poole, RM	1
Karam-Hage, M	2
Staner, L	1
Luthringer, R	1
Macher, JP	1
Richter, RW	1
Portenoy, R	1
Knapp, LE	1
Monti, JM	1
Monti, D	1
Baghdoyan, HA	2
Ebert, B	1
Wafford, KA	1
Deacon, S	1
Siddall, PJ	1
Cousins, MJ	1
Otte, A	2
Griesing, T	1
Chambers, R	1
Murphy, TK	1
Szucs, A	1
Kovács, GG	1
Lalit, N	1
Péter, H	1
de Haas, S	1
de Weerd, A	1
van Erp, G	1
Cohen, A	1
van Gerven, J	1
Watson, CJ	1
Soto-Calderon, H	1
Lydic, R	1
Study, RE	1
Barker, JL	1
Sack, RL	1
Hughes, RJ	1
Edgar, DM	1
Lewy, AJ	1
Negri, L	1
Stotz-Potter, E	1
Benarroch, E	1
Serretti, A	1
Macciardi, F	1
Cusin, C	1
Lattuada, E	1
Lilli, R	1
Di Bella, D	1
Catalano, M	1
Smeraldi, E	1
Manber, R	1
Armitage, R	1
Guentchev, M	1
Wanschitz, J	1
Voigtländer, T	1
Flicker, H	1
Budka, H	1
Fratta, W	1
Collu, M	1
Martellotta, MC	1
Pichiri, M	1
Muntoni, F	1
Gessa, GL	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase 3 Double-blind, Randomized, Placebo-controlled, Safety And Efficacy Study Of Once Daily Controlled Release Pregabalin In The Treatment Of Patients With Fibromyalgia (Protocol A0081245)[NCT01271933]	Phase 3	441 participants (Actual)	Interventional	2011-03-31	Completed
A Randomized, Double-Blind, Single-Dose, Placebo-Controlled, Multicenter, Polysomnographic Study Of Gabapentin 250 mg And 500 mg In Transient Insomnia Induced By A Sleep Phase Advance[NCT00674752]	Phase 3	377 participants (Actual)	Interventional	2006-03-31	Completed
Impact of Gabapentin on Slow Wave Sleep in Adult Critically Ill Patient.[NCT04818450]		60 participants (Actual)	Interventional	2021-04-19	Completed
A Randomized, Double-Blind, Placebo-Controlled, Multicenter, 28-day, Polysomnographic Study of Gabapentin 250 mg in Transient Insomnia Induced by a Sleep Phase Advance[NCT00163046]	Phase 3	256 participants (Actual)	Interventional	2005-10-31	Completed
Comparison of Plasma Orexin-A Levels and Awakening Time From Anesthesia in Patients With and Without Insomnia Who Had Laparoscopic Cholecystectomy Under General Anesthesia[NCT05664295]		60 participants (Actual)	Observational [Patient Registry]	2022-12-30	Completed
A Placebo-controlled, Double -Blind Randomised Trial of Suvorexant in the Management Comorbid Sleep Disorder and Alcohol Dependence[NCT03897062]	Phase 2	22 participants (Actual)	Interventional	2019-08-26	Terminated (stopped due to Recruitment problems during covid lockdowns resulted in Merck ceasing supply of suvorexant/placebo)
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.)
Comparison of Oral Gabapentin and Pregabalin in Postoperative Pain Control After Photorefractive Keratectomy: a Prospective, Randomized Study.[NCT00954187]		8 participants (Actual)	Interventional	2009-11-30	Terminated (stopped due to PI left institution)
Phase IV Study of Ramelteon as an Adjunct Therapy in Non-Diabetic Patients With Schizophrenia[NCT00595504]	Phase 4	25 participants (Actual)	Interventional	2008-01-31	Completed
Prolonged-release Melatonin Versus Placebo for Benzodiazepine Discontinuation in Patients With Schizophrenia: a Randomized Clinical Trial[NCT01431092]	Phase 4	86 participants (Actual)	Interventional	2011-10-31	Completed
The Emergence of Abstract Structure Knowledge Across Learning and Sleep[NCT05746299]		250 participants (Anticipated)	Interventional	2023-03-29	Recruiting
Cannabinoids and an Anti-inflammatory Diet for the Treatment of Neuropathic Pain After Spinal Cord Injury[NCT04057456]	Phase 3	140 participants (Anticipated)	Interventional	2023-03-01	Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

The MOS-SS is a validated self-administered questionnaire consisting of 12 items that assess key constructs of sleep. Instrument scoring yields 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) and two overall sleep problems indices assessing sleep over the past week. Score range for Sleep Disturbance (SD), sleep adequacy (SA), snoring, somnolence, awakening short of breath/headache was 0-100, where higher score=greater SD; greater SA; greater snoring; greater somnolence; greater shortness of breath/headache respectively. Quantity of Sleep (range-0 to 24 hours; higher scores/hours=greater quantity of sleep). Sleep Problem Index I and II: Score Range=0 to 100; higher scores =greater sleep problems. Optimal Sleep (assessed as yes or no), 'Yes' =optimal sleep (average 7-8 hours/night); 'No' =not optimal sleep. (NCT01271933)
Timeframe: Baseline, Week 6

Double-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Minutes of Interrupted Sleep at Double Blind End Point Visit (Week 19)

Intervention	hours (Mean)
Pregabalin (Single Blind Phase)	0.7

Double-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Percent Sedentary at Double Blind End Point Visit (Week 19)

Intervention	Minutes (Least Squares Mean)
Pregabalin (Double Blind Phase)	-3.5
Placebo (Double Blind Phase)	-2.3

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Percent sedentary = percent of daytime spent in sedentary activities as determined by the activity counts measured each minute. (NCT01271933)
Timeframe: Baseline, Double blind end point visit (Week 19)

Double-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Sleep Fragmentation Index at Double Blind End Point Visit (Week 19)

Intervention	Percent of daytime (Least Squares Mean)
Pregabalin (Double Blind Phase)	-1.4
Placebo (Double Blind Phase)	-2.0

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Sleep fragmentation index = a measure of sleep relatedness. Sleep fragmentation index calculated from analysis of the periods that participant was not moving (immobile bouts). It is number of immobile bouts that were exactly 1 minute long divided by total number of immobile bouts. Value ranges from 0-100 percent, with low number representing more restful sleep. (NCT01271933)
Timeframe: Baseline, Double blind end point visit (Week 19)

Double-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Total Daytime Activity at Double Blind End Point Visit (Week 19)

Intervention	Percentage of immobile bouts (Least Squares Mean)
Pregabalin (Double Blind Phase)	-2.5
Placebo (Double Blind Phase)	-0.6

"Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Total daytime activity = total activity counts during the day." (NCT01271933)
Timeframe: Baseline, Double blind end point visit (Week 19)

Double-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment- Total Sleep Time at Double Blind End Point Visit (Week 19)

Intervention	Counts of total daytime activity (Least Squares Mean)
Pregabalin (Double Blind Phase)	-182.7
Placebo (Double Blind Phase)	-6672.2

Double-Blind Phase: Change From Baseline in Average Daily Tiredness Score at Double Blind Endpoint Visit

Intervention	Hours (Least Squares Mean)
Pregabalin (Double Blind Phase)	0.5
Placebo (Double Blind Phase)	0.1

The tiredness assessment in the daily IVRS diary consists of an 11-point NRS ranging from zero (not tired) to 10 (extremely tired). Participants rate their tiredness due to fibromyalgia during the past 24 hours by choosing the appropriate number between 0 (not tired) and 10 (extremely tired). (NCT01271933)
Timeframe: Baseline, Double blind endpoint visit (Week 19)

Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Sleep Quality at Double Blind Endpoint Visit

Intervention	Units on a scale (Least Squares Mean)
Pregabalin (Double Blind Phase)	-2.6
Placebo (Double Blind Phase)	-2.5

Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Number of Awakenings After Sleep Onset at Double Blind Endpoint Visit

Intervention	Units on a scale (Least Squares Mean)
Pregabalin (Double Blind Phase)	1.9
Placebo (Double Blind Phase)	1.4

Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Total Sleep Time at Double Blind Endpoint Visit

Intervention	Number of times the participant awakened (Least Squares Mean)
Pregabalin (Double Blind Phase)	-0.5
Placebo (Double Blind Phase)	-0.8

Double-Blind Phase: Change From Baseline in Mean Daily Pain Score at Double Blind Endpoint Visit

Intervention	Hours (Least Squares Mean)
Pregabalin (Double Blind Phase)	0.6
Placebo (Double Blind Phase)	0.4

Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 NRS: 0 (no pain) to 10 (worst possible pain). (NCT01271933)
Timeframe: Baseline, Double blind endpoint visit (Week 19)

Double-Blind Phase: Change From Baseline in Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 19- Quantity of Sleep

Intervention	Units on a scale (Least Squares Mean)
Pregabalin (Double Blind Phase)	-2.9
Placebo (Double Blind Phase)	-2.5

Double-Blind Phase: Change From Baseline in Weekly Pain Score at Week 19 (1 Week Recall Period)

Intervention	hours (Least Squares Mean)
Pregabalin (Double Blind Phase)	0.7
Placebo (Double Blind Phase)	0.5

Weekly pain scores were calculated from the daily pain diary. Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 NRS: 0 (no pain) to 10 (worst possible pain). (NCT01271933)
Timeframe: Baseline, Week 19

Double-Blind Phase: Number of Participants With Loss of Therapeutic Response (LTR) Event

Intervention	Units on a scale (Least Squares Mean)
Pregabalin (Double Blind Phase)	-3.1
Placebo (Double Blind Phase)	-2.4

Participants who did not maintain at least 30% pain response during the DB phase relative to baseline or were discontinued during DB due to lack of efficacy or an adverse event were considered to have a loss of therapeutic response. (NCT01271933)
Timeframe: Randomization to Week 19

Double-Blind Phase: Time to Loss of Therapeutic Response (LTR)

Intervention	Participants (Count of Participants)
Pregabalin (Double Blind Phase)	34
Placebo (Double Blind Phase)	41

The time to loss of therapeutic response (LTR) is the time to loss of pain response (<30% pain response relative to the single-blind (SB) baseline mean pain) or withdrawal due to lack of efficacy or adverse events (in the double blind phase). (NCT01271933)
Timeframe: Randomization to Week 19

Single-Blind Phase: Change From Baseline in Weekly Pain Score at Week 6 (1 Week Recall Period)

Intervention	Days (Median)
Pregabalin (Double Blind Phase)	58
Placebo (Double Blind Phase)	23

Change From Baseline in Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 6 - Sleep Disturbance, Snoring, Awakening Short of Breath or With a Headache, Sleep Adequacy, Somnolence, Sleep Problems Index I and Sleep Problems Index II

Intervention	Units on a scale (Mean)
Pregabalin (Single Blind Phase)	-1.6

Double-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Minutes of Interrupted Sleep at Weeks 11, 12, 13, 14 and 15

Intervention	Units on a scale (Mean)
	Sleep disturbance	Snoring	Awakening Short of Breath/with a Headache	Sleep adequacy	Somnolence	Sleep Problems Index I	Sleep Problems Index II
Pregabalin (Single Blind Phase)	-21.8	-1.0	-11.0	18.9	-3.6	-16.1	-15.9

Double-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Percent Sedentary at Weeks 11, 12, 13, 14 and 15

Intervention	Minutes (Mean)
	Minutes of Interrupted Sleep (Week 11)	Minutes of Interrupted Sleep (Week 12)	Minutes of Interrupted Sleep (Week 13)	Minutes of Interrupted Sleep (Week 14)	Minutes of Interrupted Sleep (Week 15)
Placebo (Double Blind Phase)	2.5	-1.7	0.4	-1.8	-0.5
Pregabalin (Double Blind Phase)	-9.0	-3.0	-3.0	-3.2	-0.4

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Percent sedentary = percent of daytime spent in sedentary activities as determined by the activity counts measured each minute. (NCT01271933)
Timeframe: Baseline, Weeks 11, 12, 13, 14 and 15

Double-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Sleep Fragmentation Index at Weeks 11, 12, 13, 14 and 15

Intervention	Percent of daytime (Mean)
	Percent Sedentary (Week 11)	Percent Sedentary (Week 12)	Percent Sedentary (Week 13)	Percent Sedentary (Week 14)	Percent Sedentary (Week 15)
Placebo (Double Blind Phase)	1.1	-1.4	-0.9	-1.1	-1.4
Pregabalin (Double Blind Phase)	-0.7	-0.8	-1.3	-2.1	-1.5

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Sleep fragmentation index = a measure of sleep relatedness. Sleep fragmentation index calculated from analysis of the periods that participant was not moving (immobile bouts). It is number of immobile bouts that were exactly 1 minute long divided by total number of immobile bouts. Value ranges from 0-100 percent, with low number representing more restful sleep. (NCT01271933)
Timeframe: Baseline, Weeks 11, 12, 13, 14 and 15

Double-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Total Daytime Activity at Weeks 11, 12, 13, 14 and 15

Intervention	Percentage of immobile bouts (Mean)
	Sleep Fragmentation Index (Week 11)	Sleep Fragmentation Index (Week 12)	Sleep Fragmentation Index (Week 13)	Sleep Fragmentation Index (Week 14)	Sleep Fragmentation Index (Week 15)
Placebo (Double Blind Phase)	0.1	-0.4	-0.3	-0.6	-0.9
Pregabalin (Double Blind Phase)	-4.4	-2.8	-2.2	-2.4	-0.9

Double-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Total Sleep Time at Weeks 11, 12, 13, 14 and 15

Intervention	Counts of total daytime activity (Mean)
	Total daytime activity (Week 11)	Total daytime activity ((Week 12)	Total daytime activity ((Week 13)	Total daytime activity ((Week 14)	Total daytime activity ((Week 15)
Placebo (Double Blind Phase)	-2083.9	-6691.1	521.8	-4523.8	-4649.4
Pregabalin (Double Blind Phase)	-1894.1	-50.7	-4362.4	-179.7	-4138.3

Double-Blind Phase: Change From Baseline in Average Daily Tiredness Score at Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Intervention	Hours (Mean)
	Total Sleep Time (Week 11)	Total Sleep Time (Week 12)	Total Sleep Time (Week 13)	Total Sleep Time (Week 14)	Total Sleep Time (Week 15)
Placebo (Double Blind Phase)	0.0	0.1	0.1	0.1	0.3
Pregabalin (Double Blind Phase)	0.5	0.5	0.4	0.4	0.2

Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Sleep Quality at Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Intervention	Units on a scale (Mean)
	Week 7	Week 8	Week 9	Week 10	Week 11	Week 12	Week 13	Week 14	Week 15	Week 16	Week 17	Week 18	Week 19	Week 20
Placebo (Double Blind Phase)	-3.0	-2.8	-2.9	-2.6	-2.5	-2.5	-2.6	-2.5	-2.6	-2.7	-2.5	-2.4	-2.4	-4.9
Pregabalin (Double Blind Phase)	-3.4	-3.3	-3.2	-3.2	-3.1	-3.4	-3.2	-3.2	-3.4	-3.1	-3.4	-3.2	-3.1	-2.7

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night. Participants rated quality of sleep during the past night by selecting a number between 0 (very poor) and 10 (excellent). Mean sleep quality was calculated as the mean of the last seven days, the potential range of responses at each week was therefore 0 (very poor) -10 (excellent), where higher scores indicated better quality of sleep. (NCT01271933)
Timeframe: Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Number of Awakenings After Sleep Onset at Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Intervention	Units on a scale (Mean)
	Sleep Quality (Week 7)	Sleep Quality (Week 8)	Sleep Quality (Week 9)	Sleep Quality (Week 10)	Sleep Quality (Week 11)	Sleep Quality (Week 12)	Sleep Quality (Week 13)	Sleep Quality (Week 14) N=48,43	Sleep Quality (Week 15)	Sleep Quality (Week 16)	Sleep Quality (Week 17)	Sleep Quality (Week 18)	Sleep Quality (Week 19)	Sleep Quality (Week 20)
Placebo (Double Blind Phase)	1.9	1.7	1.8	1.7	1.7	1.7	1.9	2.1	2.0	1.9	1.9	1.8	1.5	3.3
Pregabalin (Double Blind Phase)	1.9	2.0	2.1	2.2	2.3	2.1	1.9	2.2	2.2	1.9	2.2	2.1	2.0	3.1

Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Total Sleep Time at Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Intervention	Number of times the participant awakened (Mean)
	Subjective No.of Awakenings after Sleep (Week 7)	Subjective No.of Awakenings after Sleep (Week 8)	Subjective No.of Awakenings after Sleep (Week 9)	Subjective No.of Awakenings after Sleep (Week 10)	Subjective No.of Awakenings after Sleep (Week 11)	Subjective No.of Awakenings after Sleep (Week 12)	Subjective No.of Awakenings after Sleep (Week 13)	Subjective No.of Awakenings after Sleep (Week 14)	Subjective No.of Awakenings after Sleep (Week 15)	Subjective No.of Awakenings after Sleep (Week 16)	Subjective No.of Awakenings after Sleep (Week 17)	Subjective No.of Awakenings after Sleep (Week 18)	Subjective No.of Awakenings after Sleep (Week 19)	Subjective No.of Awakenings after Sleep (Week 20)
Placebo (Double Blind Phase)	-1.0	-0.8	-1.1	-0.9	-0.9	-0.8	-1.0	-1.1	-1.1	-1.0	-0.9	-1.0	-0.9	-1.5
Pregabalin (Double Blind Phase)	-1.1	-1.2	-1.2	-1.2	-1.1	-1.1	-1.0	-1.0	-0.8	-1.0	-1.2	-1.1	-0.7	-1.5

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night. Subjective total sleep time was the subjective estimate of the total amount of time the participant was asleep after lights out until final awakening. (NCT01271933)
Timeframe: Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Wake After Sleep Onset and Subjective Latency to Sleep Onset at Double Blind Endpoint Visit

Intervention	Hours (Mean)
	Subjective Total Sleep Time (Week 7)	Subjective Total Sleep Time (Week 8)	Subjective Total Sleep Time (Week 9)	Subjective Total Sleep Time (Week 10)	Subjective Total Sleep Time (Week 11)	Subjective Total Sleep Time (Week 12)	Subjective Total Sleep Time (Week 13)	Subjective Total Sleep Time (Week 14)	Subjective Total Sleep Time (Week 15)	Subjective Total Sleep Time (Week 16)	Subjective Total Sleep Time (Week 17)	Subjective Total Sleep Time (Week 18)	Subjective Total Sleep Time (Week 19)	Subjective Total Sleep Time (Week 20)
Placebo (Double Blind Phase)	0.5	0.6	0.5	0.5	0.6	0.5	0.6	0.7	0.7	0.7	0.7	0.5	0.6	0.5
Pregabalin (Double Blind Phase)	0.7	0.9	0.8	0.9	0.9	0.8	0.7	0.9	0.7	0.7	0.7	0.6	0.5	-0.1

Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Wake After Sleep Onset and Subjective Latency to Sleep Onset at Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Intervention	Minutes (Least Squares Mean)
	Subjective Wake after Sleep Onset	Subjective Latency to Sleep Onset
Placebo (Double Blind Phase)	-20.6	-11.9
Pregabalin (Double Blind Phase)	-26.2	-10.6

Double-Blind Phase: Change From Baseline in FIQ Score at Week 19

Intervention	Minutes (Mean)
	Subjective Wake after Sleep Onset (Week 7)	Subjective Wake after Sleep Onset (Week 8)	Subjective Wake after Sleep Onset (Week 9)	Subjective Wake after Sleep Onset (Week 10)	Subjective Wake after Sleep Onset (Week 11)	Subjective Wake after Sleep Onset (Week 12)	Subjective Wake after Sleep Onset (Week 13)	Subjective Wake after Sleep Onset (Week 14)	Subjective Wake after Sleep Onset (Week 15)	Subjective Wake after Sleep Onset (Week 16)	Subjective Wake after Sleep Onset (Week 17)	Subjective Wake after Sleep Onset (Week 18)	Subjective Wake after Sleep Onset (Week 19)	Subjective Wake after Sleep Onset (Week 20)	Subjective Latency to Sleep Onset (Week 7)	Subjective Latency to Sleep Onset (Week 8)	Subjective Latency to Sleep Onset (Week 9)	Subjective Latency to Sleep Onset (Week 10)	Latency to Sleep Onset (Week 11)	Subjective Latency to Sleep Onset (Week 12)	Subjective Latency to Sleep Onset (Week 13)	Subjective Latency to Sleep Onset (Week 14)	Subjective Latency to Sleep Onset (Week 15)	Subjective Latency to Sleep Onset (Week 16)	Subjective Latency to Sleep Onset (Week 17)	Subjective Latency to Sleep Onset (Week 18)	Subjective Latency to Sleep Onset (Week 19)	Subjective Latency to Sleep Onset (Week 20)
Placebo (Double Blind Phase)	-32.0	-28.0	-33.2	-26.2	-37.4	-31.0	-31.4	-43.3	-35.1	-35.0	-36.2	-37.3	-23.1	-7.1	-19.1	-12.3	-16.0	-18.0	-18.0	-18.8	-16.8	-21.8	-19.1	-20.9	-20.9	-18.7	-19.5	-28.7
Pregabalin (Double Blind Phase)	-27.8	-27.4	-27.0	-26.9	-29.0	-26.0	-22.8	-27.0	-31.7	-25.9	-31.5	-32.4	-27.3	-22.5	-15.6	-19.1	-18.4	-19.5	-18.5	-16.3	-17.5	-20.8	-19.4	-15.8	-23.1	-16.3	-16.7	23.0

The FIQ is a 20-item self-administered questionnaire. FIQ contains 10 subscales, which are combined to yield a total score. There are 11 questions that are related specifically to physical functioning (item 1). The remaining questions assess pain, fatigue, stiffness, difficulty working, and symptoms of anxiousness and depression. The FIQ is scored from 0 to 100, with higher scores indicating more impairment. (NCT01271933)
Timeframe: Baseline, Week 19

Double-Blind Phase: Change From Baseline in HADS Score at Week 19

Intervention	Units on a scale (Least Squares Mean)
	Item 1: Physical activities	Item 2: feel good	Item 3: Work missed	Item 4: Do job	Item 5: Pain	Item 6: Fatigue	Item 7: Rested	Item 8: Stiffness	Item 9: Anxiety	Item 10: Depression	Total Score
Placebo (Double Blind Phase)	-1.3	-3.2	-1.0	-2.2	-2.2	-2.4	-2.2	-2.2	-1.7	-0.7	-19.1
Pregabalin (Double Blind Phase)	-1.0	-3.0	-1.2	-2.1	-2.7	-2.3	-2.6	-2.4	-1.8	-0.7	-19.6

HADS: participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. (NCT01271933)
Timeframe: Baseline, Week 19

Double-Blind Phase: Change From Baseline in Mean Daily Pain Score at Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Intervention	Units on a scale (Least Squares Mean)
	HADS-A Anxiety scale	HADS-D Depression scale
Placebo (Double Blind Phase)	-1.6	-1.1
Pregabalin (Double Blind Phase)	-0.7	-1.4

Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 NRS: 0 (no pain) to 10 (worst possible pain). (NCT01271933)
Timeframe: Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Double-Blind Phase: Change From Baseline in Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 19-Sleep Disturbance, Snoring, Awakening Short of Breath or With a Headache, Sleep Adequacy, Somnolence, Sleep Problems Index I and Sleep Problems Index II

Intervention	Units on a scale (Mean)
	Week 7	Week 8	Week 9	Week 10	Week 11	Week 12	Week 13	Week 14	Week 15	Week 16	Week 17	Week 18	Week 19	Week 20
Placebo (Double Blind Phase)	-3.0	-2.7	-2.8	-2.4	-2.6	-2.6	-2.6	-2.5	-2.6	-2.6	-2.5	-2.5	-2.4	-4.9
Pregabalin (Double Blind Phase)	-3.9	-3.7	-3.6	-3.7	-3.7	-3.7	-3.6	-3.5	-3.6	-3.4	-3.6	-3.4	-3.4	-3.0

Double-Blind Phase: Change From Baseline in MFI Score at Week 19

Intervention	Units on a scale (Least Squares Mean)
	Sleep disturbance	Snoring	Awakening Short of Breath/with a Headache	Sleep adequacy	Somnolence	Sleep Problems Index I	Sleep Problems Index II
Placebo (Double Blind Phase)	-15.5	-2.9	-4.2	17.1	-6.6	-13.7	-14.0
Pregabalin (Double Blind Phase)	-25.4	-2.4	-8.1	23.9	-11.9	-19.5	-19.7

The MFI is a 20-item, self-administered questionnaire designed to measure the following dimensions of fatigue: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Items are summed to form subscale scores; there is no overall score. The score range is from 4 to 20, where higher scores indicate greater dysfunction. (NCT01271933)
Timeframe: Baseline, Week 19

Double-Blind Phase: Change From Baseline in SF-36 Score at Week 19

Intervention	Units on a scale (Least Squares Mean)
	General fatigue	Physical fatigue	Reduced activity	Reduced motivation	Mental fatigue
Placebo (Double Blind Phase)	-0.1	0.2	-0.3	0.3	0.1
Pregabalin (Double Blind Phase)	0.1	-0.1	0.0	1.0	-0.1

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100. Higher scores indicated a better health-related quality of life. (NCT01271933)
Timeframe: Baseline, Week 19

Double-Blind Phase: Change From Baseline WPAI Questionnaire at Week 19

Intervention	Units on a scale (Least Squares Mean)
	SF-36 Physical Functioning	SF-36 Role-Physical	SF-36 Pain Index	SF-36 General Health Perceptions	SF-36 Vitality	SF-36 Social Functioning	SF-36 Role-Emotional	SF-36 Mental Health Index	Physical Component Score	Mental Component Score
Placebo (Double Blind Phase)	13.7	16.2	16.0	9.3	15.7	13.5	2.2	5.2	7.2	2.4
Pregabalin (Double Blind Phase)	12.4	18.9	19.2	3.3	12.2	13.3	3.8	6.6	6.8	2.6

WPAI: 6 question participant rated questionnaire to determine the degree to which disease state affected work productivity while at work and affected activities outside of work. Subscale scores include percent work time missed due to the health problem; percent impairment while working due to problem; percent overall work impairment due to problem; and percent activity impairment due to problem. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. (NCT01271933)
Timeframe: Baseline, Week 19

Double-Blind Phase: Number of Participants Who Reported Global Impression of Change (PGIC) at Week 19

Intervention	Units on a scale (Least Squares Mean)
	Percent Work Time Missed	Percent Impairment While Working	Percent Activity Impairment	Percent Overall Work Impairment
Placebo (Double Blind Phase)	-26.7	-15.0	-19.6	-17.5
Pregabalin (Double Blind Phase)	-7.3	-14.0	-16.4	-15.9

PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). (NCT01271933)
Timeframe: Week 19

Double-Blind Phase: Number of Participants With Benefit, Satisfaction, and Willingness (BSW) to Continue Data at Visit 9 (3 Component Questions) at Week 19

Intervention	Participants (Number)
	Very Much Improved	Much Improved	Minimally Improved	No Change	Minimally Worse	Much Worse	Very Much Worse
Placebo (Double Blind Phase)	7	11	12	11	6	8	2
Pregabalin (Double Blind Phase)	7	15	14	9	7	7	1

The questionnaire consists of 3 single-item measures designed to captures the participant's perception of the effect of treatment in terms of the relative benefit, their satisfaction, and their intention or willingness to continue on therapy. (NCT01271933)
Timeframe: Week 19

Number of Participants With Suicidal Ideation Throughout the Study Assessed by Columbia Classification Algorithm of Suicide Assessment (C-CASA)

Intervention	Participants (Number)
	Benefit from treatment-No	Benefit from treatment-Little benefit	Benefit from treatment-much benefit	Satisfaction from treatment-very dissatisfied	Satisfaction from treatment-a little dissatisfied	Satisfaction from treatment-a little satisfied	Satisfaction from treatment-very satisfied	Willing to continue treatment-very unwilling	Willing to continue treatment-little unwilling	Willing to continue treatment-little bit willing	Willing to continue treatment-very willing
Placebo (Double Blind Phase)	11	16	30	6	8	13	30	4	8	11	34
Pregabalin (Double Blind Phase)	3	15	41	4	10	10	36	8	6	9	37

C-CASA was used to categorize and summarize results from the Sheehan Suicidality Tracking Scale (S-STS) and the Columbia Suicidality Severity Rating Scale (C-SSRS). S-STS was an 8-item prospective rating scale that tracked treatment-emergent suicidal ideation and behaviors. Items 1a, 2 to 6, 7a, 8 were scored on a 5-point Likert scale (ranges 0 [not at all] to 4 [extremely]). Items 1, 1b, and 7 required yes or no responses. S-STS total score range 0-30. Lower score=reduced suicidal tendency. C-SSRS was a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Responses on S-STS or C-SSRS were mapped to C-CASA categories as: Completed suicide; suicide attempt; preparatory acts; suicide ideation; self-injurious behavior, intent unknown; not enough information; self-injurious behavior, no suicide intent; other, no deliberate self harm. (NCT01271933)
Timeframe: Week 1 to Week 7 and Week 11 to Week 20

Number of Participants With Suicidal Ideation Throughout the Study Assessed by Columbia Classification Algorithm of Suicide Assessment (C-CASA)

Intervention	Participants (Number)
	Week 11	Week 15	Week 19	Week 20
Placebo (Double Blind Phase)	0	1	3	1
Pregabalin (Double Blind Phase)	3	1	1	1

Single-Blind Phase: Change From Baseline at in Actigraphy Functional/Sleep Assessment - Sleep Fragmentation Index Weeks 3, 4, 5, 6 and 7

Intervention	Participants (Number)
	Week 1	Week 2	Week 3	Week 6	Week 7
Pregabalin (Single Blind Phase)	5	6	4	16	10

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Sleep fragmentation index = a measure of sleep relatedness. Sleep fragmentation index calculated from analysis of the periods that participant was not moving (immobile bouts). It is number of immobile bouts that were exactly 1 minute long divided by total number of immobile bouts. Value ranges from 0-100 percent, with low number representing more restful sleep. (NCT01271933)
Timeframe: Baseline, Weeks 3, 4, 5, 6 and 7

Single-Blind Phase: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Week 6

Intervention	Percentage of immobile bouts (Mean)
	Sleep Fragmentation Index (Week 3)	Sleep Fragmentation Index (Week 4)	Sleep Fragmentation Index (Week 5)	Sleep Fragmentation Index (Week 6)	Sleep Fragmentation Index (Week 7)
Pregabalin (Single Blind Phase)	-0.8	-2.5	-2.8	-2.6	0.7

Single-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Minutes of Interrupted Sleep at Weeks 3, 4, 5, 6 and 7

Intervention	Units on a scale (Mean)
	SF-36 Physical Functioning	SF-36 Role-Physical	SF-36 Pain Index	SF-36 General Health Perceptions	SF-36 Vitality	SF-36 Social Functioning	SF-36 Role-Emotional	SF-36 Mental Health Index	Physical Component Score	Mental Component Score
Pregabalin (Single Blind Phase)	14.0	17.8	20.7	8.5	18.2	12.9	8.6	7.9	7.2	4.5

Single-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Percent Sedentary at Weeks 3, 4, 5, 6 and 7

Intervention	Minutes (Mean)
	Minutes of Interrupted Sleep (Week 3)	Minutes of Interrupted Sleep (Week 4)	Minutes of Interrupted Sleep (Week 5)	Minutes of Interrupted Sleep (Week 6)	Minutes of Interrupted Sleep (Week 7)
Pregabalin (Single Blind Phase)	-5.3	-5.9	-7.0	-6.6	0.7

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Percent sedentary = percent of daytime spent in sedentary activities as determined by the activity counts measured each minute. (NCT01271933)
Timeframe: Baseline, Weeks 3, 4, 5, 6 and 7

Single-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Total Daytime Activity at Weeks 3, 4, 5, 6 and 7

Intervention	Percent of daytime (Mean)
	Percent Sedentary (Week 3)	Percent Sedentary (Week 4)	Percent Sedentary (Week 5)	Percent Sedentary (Week 6)	Percent Sedentary (Week 7)
Pregabalin (Single Blind Phase)	0.7	0.7	0.6	0.3	0.2

Single-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Total Sleep Time at Weeks 3, 4, 5, 6 and 7

Intervention	Counts of total daytime activity (Mean)
	Total daytime activity (Week 3)	Total daytime activity (Week 4)	Total daytime activity (Week 5)	Total daytime activity (Week 6)	Total daytime activity (Week 7)
Pregabalin (Single Blind Phase)	10264.3	10588.1	8635.8	7134.2	18420.7

Single-Blind Phase: Change From Baseline in Average Daily Tiredness Score at Weeks 1, 2, 3, 4, 5, 6

Intervention	Hours (Mean)
	Total Sleep Time (Week 3)	Total Sleep Time (Week 4)	Total Sleep Time (Week 5)	Total Sleep Time (Week 6)	Total Sleep Time (Week 7)
Pregabalin (Single Blind Phase)	-0.1	0.4	0.3	0.3	0.6

The tiredness assessment in the daily interactive voice response system (IVRS) diary consists of an 11-point NRS ranging from zero (not tired) to 10 (extremely tired). Participants rate their tiredness due to fibromyalgia during the past 24 hours by choosing the appropriate number between 0 (not tired) and 10 (extremely tired). (NCT01271933)
Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6

Single-Blind Phase: Change From Baseline in Daily SSQ - Subjective Number of Awakenings After Sleep Onset at Weeks 1, 2, 3, 4, 5, 6

Intervention	Units on a scale (Mean)
	Week 1	Week 2	Week 3	Week 4	Week 5	Week 6
Pregabalin (Single Blind Phase)	-0.7	-1.2	-1.6	-2.0	-2.2	-2.3

Single-Blind Phase: Change From Baseline in Daily SSQ - Subjective Total Sleep Time at Weeks 1, 2, 3, 4, 5, 6

Single-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Sleep Quality at Weeks 1, 2, 3, 4, 5, 6

Single-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Wake After Sleep and Subjective Latency to Sleep Onset at Weeks 1, 2, 3, 4, 5, 6

Single-Blind Phase: Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) at Week 6

Single-Blind Phase: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) at Week 6

Single-Blind Phase: Change From Baseline in Mean Daily Pain Score at Weeks 1, 2, 3, 4, 5, 6

Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain). (NCT01271933)
Timeframe: Baseline, Weeks 1, 2, 3, 4, 5, 6

Single-Blind Phase: Change From Baseline in Multidimensional Fatigue Inventory (MFI) at Week 6

Single-Blind Phase: Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire at Week 6

Single-Blind Phase: Number of Participants Who Reported Global Impression of Change (PGIC) at Week 6

PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). (NCT01271933)
Timeframe: Week 6

Single-Blind Phase: Number of Participants With Benefit, Satisfaction, Willingness to Continue Measure (BSW) at Week 6

Change in Abdominal Fat (DEXA).

A comparison between the ramelteon group and the placebo group of change in abdominal fat measured by a DEXA scan, assessed at Baseline and Week 8. (NCT00595504)
Timeframe: Baseline and Week 8

Change in Insulin Resistance as Measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).

A comparison between the ramelteon group and the placebo group of change in insulin resistance measured by the homeostatic model assessment of insulin resistance (HOMA-IR), assessed at Baseline and Week 8. (NCT00595504)
Timeframe: Baseline and Week 8

Change in Waist Circumference

A comparison between the ramelteon group and the placebo group in change in waist circumference (measured in cm) measured at Baseline and Week 8. (NCT00595504)
Timeframe: Baseline and Week 8

Reviews

23 reviews available for gamma-aminobutyric acid and Sleep Initiation and Maintenance Disorders

Trials

23 trials available for gamma-aminobutyric acid and Sleep Initiation and Maintenance Disorders

Other Studies

45 other studies available for gamma-aminobutyric acid and Sleep Initiation and Maintenance Disorders

Intervention	Hours (Mean)
	Subjective Total Sleep Time (Week 1)	Subjective Total Sleep Time (Week 2)	Subjective Total Sleep Time (Week 3)	Subjective Total Sleep Time (Week 4)	Subjective Total Sleep Time (Week 5)	Subjective Total Sleep Time (Week 6)
Pregabalin (Single Blind Phase)	0.6	0.6	0.6	0.7	0.7	0.7

Intervention	Units on a scale (Mean)
	Sleep quality (Week 1)	Sleep quality (Week 2)	Sleep quality (Week 3)	Sleep quality (Week 4)	Sleep quality (Week 5)	Sleep quality (Week 6)
Pregabalin (Single Blind Phase)	1.0	1.2	1.5	1.6	1.7	1.7

Article	Year
Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale. Molecular psychiatry, 2022, Volume: 27, Issue:3 Topics: Amines; Anxiety; Bipolar Disorder; Calcium Channels; Cyclohexanecarboxylic Acids; Gabapentin; gamma-	2022
Effects of BXSMD on ESR1 and ESR2 expression in CSD female mice. Journal of ethnopharmacology, 2024, Jan-10, Volume: 318, Issue:Pt B Topics: Animals; Estrogen Receptor alpha; Estrogen Receptor beta; Female; gamma-Aminobutyric Acid; Mice; RNA	2024
Biological rationale and potential clinical use of gabapentin and pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis. BMJ open, 2017, 03-27, Volume: 7, Issue:3 Topics: Amines; Anti-Anxiety Agents; Anxiety Disorders; Bipolar Disorder; Cyclohexanecarboxylic Acids; Doubl	2017
Gabapentin for the treatment of alcohol use disorder. Expert opinion on investigational drugs, 2018, Volume: 27, Issue:1 Topics: Alcohol Drinking; Alcoholism; Amines; Animals; Calcium Channel Blockers; Cyclohexanecarboxylic Acids	2018
Understanding the sleep-wake cycle: sleep, insomnia, and the orexin system. The Journal of clinical psychiatry, 2013, Volume: 74 Suppl 1 Topics: Animals; Benzodiazepines; Brain; Brain Mapping; Circadian Rhythm; Cognitive Behavioral Therapy; Comb	2013
Neuroimaging findings in primary insomnia. Pathologie-biologie, 2014, Volume: 62, Issue:5 Topics: Affective Symptoms; Arousal; Cerebral Cortex; Comorbidity; gamma-Aminobutyric Acid; Hippocampus; Hum	2014
Assessment and treatment of insomnia in adult patients with alcohol use disorders. Alcohol (Fayetteville, N.Y.), 2015, Volume: 49, Issue:4 Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Amines; Anti-Anxiety Agents; Anticonvulsants; Antipsych	2015
Pediatric Insomnia. Chest, 2016, Volume: 149, Issue:5 Topics: Actigraphy; Adolescent; Amines; Anti-Anxiety Agents; Autism Spectrum Disorder; Central Nervous Syste	2016
Not a single but multiple populations of GABAergic neurons control sleep. Sleep medicine reviews, 2017, Volume: 32 Topics: Animals; Brain; GABAergic Neurons; gamma-Aminobutyric Acid; Humans; Rats; Receptors, GABA; Sleep; Sl	2017
Advances in the management of chronic insomnia. BMJ (Clinical research ed.), 2016, 07-06, Volume: 354 Topics: Cognitive Behavioral Therapy; GABA Agents; gamma-Aminobutyric Acid; Humans; Prevalence; Relaxation T	2016
Sleep Control, GPCRs, and Glucose Metabolism. Trends in endocrinology and metabolism: TEM, 2016, Volume: 27, Issue:9 Topics: Animals; gamma-Aminobutyric Acid; Glucose; Humans; Melatonin; Receptors, G-Protein-Coupled; Sleep; S	2016
An update of management of insomnia in patients with chronic orofacial pain. Oral diseases, 2017, Volume: 23, Issue:8 Topics: Amines; Anticonvulsants; Antidepressive Agents; Benzodiazepines; Chronic Pain; Cognitive Behavioral	2017
[Update on the treatment of restless legs syndrome]. Brain and nerve = Shinkei kenkyu no shinpo, 2009, Volume: 61, Issue:5 Topics: Amines; Analgesics, Opioid; Anticonvulsants; Baths; Benzodiazepines; Cyclohexanecarboxylic Acids; Do	2009
ACS chemical neuroscience molecule spotlight on Suvorexant. ACS chemical neuroscience, 2012, Sep-19, Volume: 3, Issue:9 Topics: Animals; Azepines; Clinical Trials, Phase I as Topic; Clinical Trials, Phase III as Topic; gamma-Ami	2012
Understanding the pharmacokinetics of anxiolytic drugs. Expert opinion on drug metabolism & toxicology, 2013, Volume: 9, Issue:4 Topics: Adrenergic beta-Antagonists; Amines; Anti-Anxiety Agents; Anticonvulsants; Anxiety Disorders; Atenol	2013
[Development of compounds active in insomnia: recent developments and methodological aspects]. Revue neurologique, 2003, Volume: 159, Issue:11 Suppl Topics: Benzodiazepines; Circadian Rhythm; Clinical Trials as Topic; Drug Design; GABA Agonists; GABA-A Rece	2003
Insomnia, alcoholism and relapse. Sleep medicine reviews, 2003, Volume: 7, Issue:6 Topics: Acetylcholine; Adenosine; Alcoholism; Dopamine; gamma-Aminobutyric Acid; Glutamic Acid; Humans; Nore	2003
Sleep disturbance in schizophrenia. International review of psychiatry (Abingdon, England), 2005, Volume: 17, Issue:4 Topics: Brain; Dopamine; gamma-Aminobutyric Acid; Humans; Schizophrenia; Sleep Initiation and Maintenance Di	2005
Sleep disturbance in schizophrenia. International review of psychiatry (Abingdon, England), 2005, Volume: 17, Issue:4 Topics: Brain; Dopamine; gamma-Aminobutyric Acid; Humans; Schizophrenia; Sleep Initiation and Maintenance Di	2005
Sleep disturbance in schizophrenia. International review of psychiatry (Abingdon, England), 2005, Volume: 17, Issue:4 Topics: Brain; Dopamine; gamma-Aminobutyric Acid; Humans; Schizophrenia; Sleep Initiation and Maintenance Di	2005
Sleep disturbance in schizophrenia. International review of psychiatry (Abingdon, England), 2005, Volume: 17, Issue:4 Topics: Brain; Dopamine; gamma-Aminobutyric Acid; Humans; Schizophrenia; Sleep Initiation and Maintenance Di	2005
Sleep disturbance in schizophrenia. International review of psychiatry (Abingdon, England), 2005, Volume: 17, Issue:4 Topics: Brain; Dopamine; gamma-Aminobutyric Acid; Humans; Schizophrenia; Sleep Initiation and Maintenance Di	2005
Sleep disturbance in schizophrenia. International review of psychiatry (Abingdon, England), 2005, Volume: 17, Issue:4 Topics: Brain; Dopamine; gamma-Aminobutyric Acid; Humans; Schizophrenia; Sleep Initiation and Maintenance Di	2005
Sleep disturbance in schizophrenia. International review of psychiatry (Abingdon, England), 2005, Volume: 17, Issue:4 Topics: Brain; Dopamine; gamma-Aminobutyric Acid; Humans; Schizophrenia; Sleep Initiation and Maintenance Di	2005
Sleep disturbance in schizophrenia. International review of psychiatry (Abingdon, England), 2005, Volume: 17, Issue:4 Topics: Brain; Dopamine; gamma-Aminobutyric Acid; Humans; Schizophrenia; Sleep Initiation and Maintenance Di	2005
Sleep disturbance in schizophrenia. International review of psychiatry (Abingdon, England), 2005, Volume: 17, Issue:4 Topics: Brain; Dopamine; gamma-Aminobutyric Acid; Humans; Schizophrenia; Sleep Initiation and Maintenance Di	2005
Treating insomnia: Current and investigational pharmacological approaches. Pharmacology & therapeutics, 2006, Volume: 112, Issue:3 Topics: Animals; Electroencephalography; GABA-A Receptor Agonists; gamma-Aminobutyric Acid; Humans; Hypnotic	2006
[Sleep disorders in Parkinson syndromes]. Ideggyogyaszati szemle, 2007, May-30, Volume: 60, Issue:5-6 Topics: Acetylcholine; Antidepressive Agents; Antiparkinson Agents; Diagnosis, Differential; Disorders of Ex	2007
Pontine reticular formation (PnO) administration of hypocretin-1 increases PnO GABA levels and wakefulness. Sleep, 2008, Volume: 31, Issue:4 Topics: Animals; Arousal; Body Temperature; gamma-Aminobutyric Acid; Injections; Intracellular Signaling Pep	2008
Sleep-promoting effects of melatonin: at what dose, in whom, under what conditions, and by what mechanisms? Sleep, 1997, Volume: 20, Issue:10 Topics: Adult; Aged; Body Temperature Regulation; Circadian Rhythm; gamma-Aminobutyric Acid; Humans; Hypnoti	1997
Sex, steroids, and sleep: a review. Sleep, 1999, Aug-01, Volume: 22, Issue:5 Topics: Animals; Depressive Disorder; Female; gamma-Aminobutyric Acid; Gonadal Steroid Hormones; Humans; Hyp	1999

Article	Year
Jiaotaiwan increased GABA level in brain and serum, improved sleep via increasing NREM sleep and REM sleep, and its component identification. Journal of ethnopharmacology, 2022, Mar-01, Volume: 285 Topics: Animals; Brain; Drugs, Chinese Herbal; gamma-Aminobutyric Acid; Male; Mice; Rats; Rats, Sprague-Dawl	2022
GABA Molecules (Basel, Switzerland), 2021, Nov-24, Volume: 26, Issue:23 Topics: Acids; Animals; Bicuculline; Caffeine; Cyclohexenes; Disease Models, Animal; Electroencephalography;	2021
Lower dACC glutamate in cannabis users during early phase abstinence. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2022, Volume: 47, Issue:11 Topics: Cannabinoid Receptor Agonists; Cannabis; Dronabinol; gamma-Aminobutyric Acid; Glutamic Acid; Gyrus C	2022
The Positive Effects of International journal of environmental research and public health, 2022, 05-29, Volume: 19, Issue:11 Topics: Animals; Caffeine; gamma-Aminobutyric Acid; Mice; Mice, Inbred ICR; Plant Extracts; Quality of Life;	2022
Effective Components and Molecular Mechanism of Agarwood Essential Oil Inhalation and the Sedative and Hypnotic Effects Based on GC-MS-Qtof and Molecular Docking. Molecules (Basel, Switzerland), 2022, May-28, Volume: 27, Issue:11 Topics: Animals; Fenclonine; gamma-Aminobutyric Acid; Gas Chromatography-Mass Spectrometry; Glutamic Acid; H	2022
Sedative-hypnotic effects of Boropinol-B on mice via activation of GABAA receptors. The Journal of pharmacy and pharmacology, 2023, Jan-31, Volume: 75, Issue:1 Topics: Animals; gamma-Aminobutyric Acid; Hypnotics and Sedatives; Mice; Pentobarbital; Rats; Receptors, GAB	2023
Sedative-hypnotic effects of Boropinol-B on mice via activation of GABAA receptors. The Journal of pharmacy and pharmacology, 2023, Jan-31, Volume: 75, Issue:1 Topics: Animals; gamma-Aminobutyric Acid; Hypnotics and Sedatives; Mice; Pentobarbital; Rats; Receptors, GAB	2023
Sedative-hypnotic effects of Boropinol-B on mice via activation of GABAA receptors. The Journal of pharmacy and pharmacology, 2023, Jan-31, Volume: 75, Issue:1 Topics: Animals; gamma-Aminobutyric Acid; Hypnotics and Sedatives; Mice; Pentobarbital; Rats; Receptors, GAB	2023
Sedative-hypnotic effects of Boropinol-B on mice via activation of GABAA receptors. The Journal of pharmacy and pharmacology, 2023, Jan-31, Volume: 75, Issue:1 Topics: Animals; gamma-Aminobutyric Acid; Hypnotics and Sedatives; Mice; Pentobarbital; Rats; Receptors, GAB	2023
Sedative-hypnotic effects of Boropinol-B on mice via activation of GABAA receptors. The Journal of pharmacy and pharmacology, 2023, Jan-31, Volume: 75, Issue:1 Topics: Animals; gamma-Aminobutyric Acid; Hypnotics and Sedatives; Mice; Pentobarbital; Rats; Receptors, GAB	2023
Sedative-hypnotic effects of Boropinol-B on mice via activation of GABAA receptors. The Journal of pharmacy and pharmacology, 2023, Jan-31, Volume: 75, Issue:1 Topics: Animals; gamma-Aminobutyric Acid; Hypnotics and Sedatives; Mice; Pentobarbital; Rats; Receptors, GAB	2023
Sedative-hypnotic effects of Boropinol-B on mice via activation of GABAA receptors. The Journal of pharmacy and pharmacology, 2023, Jan-31, Volume: 75, Issue:1 Topics: Animals; gamma-Aminobutyric Acid; Hypnotics and Sedatives; Mice; Pentobarbital; Rats; Receptors, GAB	2023
Sedative-hypnotic effects of Boropinol-B on mice via activation of GABAA receptors. The Journal of pharmacy and pharmacology, 2023, Jan-31, Volume: 75, Issue:1 Topics: Animals; gamma-Aminobutyric Acid; Hypnotics and Sedatives; Mice; Pentobarbital; Rats; Receptors, GAB	2023
Sedative-hypnotic effects of Boropinol-B on mice via activation of GABAA receptors. The Journal of pharmacy and pharmacology, 2023, Jan-31, Volume: 75, Issue:1 Topics: Animals; gamma-Aminobutyric Acid; Hypnotics and Sedatives; Mice; Pentobarbital; Rats; Receptors, GAB	2023
The Effect of Chinese Agarwood Essential Oil with Cyclodextrin Inclusion against PCPA-Induced Insomnia Rats. Molecules (Basel, Switzerland), 2023, Jan-07, Volume: 28, Issue:2 Topics: Animals; Cyclodextrins; Fenclonine; gamma-Aminobutyric Acid; Neurotransmitter Agents; Oils, Volatile	2023
Efficacy and safety of lemborexant as an alternative drug for patients with insomnia taking gamma-aminobutyric acid-benzodiazepine receptor agonists or suvorexant. Human psychopharmacology, 2023, Volume: 38, Issue:3 Topics: gamma-Aminobutyric Acid; Humans; Receptors, GABA-A; Retrospective Studies; Sleep Initiation and Main	2023
Electroacupuncture of the cymba concha alleviates p-chlorophenylalanine-induced insomnia in mice. Acupuncture in medicine : journal of the British Medical Acupuncture Society, 2023, Volume: 41, Issue:6 Topics: Animals; Electroacupuncture; Fenclonine; gamma-Aminobutyric Acid; Hypothalamus; Mice; Sleep Initiati	2023
Sleep-promoting activity of amylase-treated Ashwagandha (Withania somnifera L. Dunal) root extract via GABA receptors. Journal of food and drug analysis, 2023, 06-15, Volume: 31, Issue:2 Topics: Amylases; gamma-Aminobutyric Acid; Pentobarbital; Plant Extracts; Receptors, GABA; Sleep; Sleep Init	2023
Effects of aqueous extracts and volatile oils prepared from Huaxiang Anshen decoction on p-chlorophenylalanine-induced insomnia mice. Journal of ethnopharmacology, 2024, Jan-30, Volume: 319, Issue:Pt 3 Topics: Animals; beta-Cyclodextrins; Dopamine; Fenclonine; gamma-Aminobutyric Acid; Hypnotics and Sedatives;	2024
Sedative and hypnotic effects of compound Anshen essential oil inhalation for insomnia. BMC complementary and alternative medicine, 2019, Nov-11, Volume: 19, Issue:1 Topics: Administration, Inhalation; Animals; Aromatherapy; Brain; Citrus sinensis; Female; gamma-Aminobutyri	2019
Beneficial effect of GABA-rich fermented milk on insomnia involving regulation of gut microbiota. Microbiological research, 2020, Volume: 233 Topics: Animals; Cultured Milk Products; Fatty Acids, Volatile; gamma-Aminobutyric Acid; Gastrointestinal Mi	2020
Journal of affective disorders, 2020, 09-01, Volume: 274 Topics: Adult; Depression; Depressive Disorder, Major; gamma-Aminobutyric Acid; Glutamic Acid; Gyrus Cinguli	2020
Sedative and hypnotic effects of Perilla frutescens essential oil through GABAergic system pathway. Journal of ethnopharmacology, 2021, Oct-28, Volume: 279 Topics: Administration, Inhalation; Animals; Disease Models, Animal; Female; gamma-Aminobutyric Acid; Gas Ch	2021
Low-Dose Ozone Therapy Improves Sleep Quality in Patients with Insomnia and Coronary Heart Disease by Elevating Serum BDNF and GABA. Bulletin of experimental biology and medicine, 2021, Volume: 170, Issue:4 Topics: Brain-Derived Neurotrophic Factor; Catalase; Coronary Disease; Depression; gamma-Aminobutyric Acid;	2021
Enzymolysis peptides from Mauremys mutica plastron improve the disorder of neurotransmitter system and facilitate sleep-promoting in the PCPA-induced insomnia mice. Journal of ethnopharmacology, 2021, Jun-28, Volume: 274 Topics: Animals; Brain; Brain-Derived Neurotrophic Factor; Dopamine; gamma-Aminobutyric Acid; Hypnotics and	2021
Molecular Regulation of Betulinic Acid on α3β4 Nicotinic Acetylcholine Receptors. Molecules (Basel, Switzerland), 2021, May-01, Volume: 26, Issue:9 Topics: Acetylcholine; Animals; Betulinic Acid; Binding Sites; Cattle; Electrophysiology; gamma-Aminobutyric	2021
The dual orexin receptor antagonist, DORA-22, lowers histamine levels in the lateral hypothalamus and prefrontal cortex without lowering hippocampal acetylcholine. Journal of neurochemistry, 2017, Volume: 142, Issue:2 Topics: Acetylcholine; Animals; gamma-Aminobutyric Acid; Hippocampus; Histamine; Hypothalamic Area, Lateral;	2017
The Effect of sequential bilateral low-frequency rTMS over dorsolateral prefrontal cortex on serum level of BDNF and GABA in patients with primary insomnia. Brain and behavior, 2019, Volume: 9, Issue:2 Topics: Adult; Brain-Derived Neurotrophic Factor; Correlation of Data; Female; gamma-Aminobutyric Acid; Huma	2019
Structure: the anatomy of sleep. Nature, 2013, May-23, Volume: 497, Issue:7450 Topics: Adolescent; Adult; Child; gamma-Aminobutyric Acid; Humans; Infant, Newborn; Sleep; Sleep Initiation	2013
Discovery of novel insomnia leads from screening traditional Chinese medicine database. Journal of biomolecular structure & dynamics, 2014, Volume: 32, Issue:5 Topics: Binding Sites; Caffeic Acids; Citric Acid; Coumaric Acids; Databases, Chemical; Drugs, Chinese Herba	2014
Treatment-resistant insomnia treated with pregabalin. European review for medical and pharmacological sciences, 2013, Volume: 17, Issue:11 Topics: Female; gamma-Aminobutyric Acid; Humans; Middle Aged; Pregabalin; Restless Legs Syndrome; Sleep Init	2013
[Effects of extracts from ziziphi spinosae semen and schisandrae chinensis fructus on amino acid neurotransmitter in rats with insomnia induced by PCPA]. Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials, 2013, Volume: 36, Issue:10 Topics: Animals; Disease Models, Animal; Drugs, Chinese Herbal; Female; Fenclonine; Fruit; gamma-Aminobutyri	2013
Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality. Sleep, 2014, May-01, Volume: 37, Issue:5 Topics: Arousal; Aspartic Acid; Cerebral Cortex; gamma-Aminobutyric Acid; Glutamic Acid; Gyrus Cinguli; Huma	2014
[Mechanism of Bailemian capsules in the treatment of insomnia in mice]. Zhonghua yi xue za zhi, 2014, Dec-16, Volume: 94, Issue:46 Topics: Animals; Capsules; gamma-Aminobutyric Acid; Injections, Intraperitoneal; Mice; Serotonin; Sleep; Sle	2014
Magnetic Resonance Spectroscopy in Patients with Insomnia: A Repeated Measurement Study. PloS one, 2016, Volume: 11, Issue:6 Topics: Adult; Brain; Brain Chemistry; Case-Control Studies; Female; gamma-Aminobutyric Acid; Glutamic Acid;	2016
Insomnia may increase anesthetic requirement. Journal of clinical anesthesia, 2016, Volume: 34 Topics: Abdominal Pain; Adult; Anesthetics, Inhalation; Carbon Dioxide; Cholecystectomy, Laparoscopic; Consc	2016
What is the effective component in suanzaoren decoction for curing insomnia? Discovery by virtual screening and molecular dynamic simulation. Journal of biomolecular structure & dynamics, 2008, Volume: 26, Issue:1 Topics: Binding Sites; Blood-Brain Barrier; Brain; Computer Simulation; Drugs, Chinese Herbal; gamma-Aminobu	2008
Reduced brain GABA in primary insomnia: preliminary data from 4T proton magnetic resonance spectroscopy (1H-MRS). Sleep, 2008, Volume: 31, Issue:11 Topics: Adult; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Brain; Cross-Sectional Studies; Dia	2008
GABA tea helps sleep. Journal of alternative and complementary medicine (New York, N.Y.), 2009, Volume: 15, Issue:7 Topics: Adult; Camellia sinensis; gamma-Aminobutyric Acid; Humans; Male; Phytotherapy; Plant Extracts; Sleep	2009
Paroxysmal arousals and myoclonic movements associated with interictal epileptiform discharges in NREM and REM sleep. Clinical neurology and neurosurgery, 2011, Volume: 113, Issue:5 Topics: Adolescent; Amines; Antiparkinson Agents; Arousal; Chromosome Disorders; Chromosome Inversion; Chrom	2011
Reduced γ-aminobutyric acid in occipital and anterior cingulate cortices in primary insomnia: a link to major depressive disorder? Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012, Volume: 37, Issue:6 Topics: Actigraphy; Adult; Brain Mapping; Case-Control Studies; Creatine; Depressive Disorder, Major; Female	2012
Nighttime awakenings responding to gabapentin therapy in late premenopausal women: a case series. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2012, Apr-15, Volume: 8, Issue:2 Topics: Adult; Amines; Anti-Anxiety Agents; Cyclohexanecarboxylic Acids; Estradiol; Female; Follicle Stimula	2012
The role of GABA in primary insomnia. Sleep, 2012, Jun-01, Volume: 35, Issue:6 Topics: Brain Chemistry; Female; gamma-Aminobutyric Acid; Humans; Male; Sleep Initiation and Maintenance Dis	2012
Cortical GABA levels in primary insomnia. Sleep, 2012, Jun-01, Volume: 35, Issue:6 Topics: Adult; Brain Chemistry; Case-Control Studies; Female; gamma-Aminobutyric Acid; Humans; Magnetic Reso	2012
Gabapentin shows promise in treating refractory insomnia in children. Journal of child neurology, 2013, Volume: 28, Issue:12 Topics: Adolescent; Amines; Anticonvulsants; Child; Child, Preschool; Cyclohexanecarboxylic Acids; Female; F	2013
[Effect of acupuncture at different acupoints on expression of hypothalamic GABA and GABA(A) receptor proteins in insomnia rats]. Zhen ci yan jiu = Acupuncture research, 2012, Volume: 37, Issue:4 Topics: Acupuncture Points; Acupuncture Therapy; Animals; Disease Models, Animal; gamma-Aminobutyric Acid; H	2012
Gabapentin efficacy in reducing nighttime awakenings in premenopausal women: a class effect of GABAergic medications or unique property of gabapentin only? Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2012, Dec-15, Volume: 8, Issue:6 Topics: Amines; Anti-Anxiety Agents; Cyclohexanecarboxylic Acids; Female; gamma-Aminobutyric Acid; Humans; P	2012
Hyperalgesia induced by REM sleep loss: a phenomenon in search of a mechanism. Sleep, 2006, Volume: 29, Issue:2 Topics: Acetylcholine; Adenosine; Anxiety; Chronic Disease; Depression; Drug Therapy; Drug-Related Side Effe	2006
Cellular mechanisms of benzodiazepine action. JAMA, 1982, Apr-16, Volume: 247, Issue:15 Topics: Animals; Anti-Anxiety Agents; Anxiety; Benzodiazepines; gamma-Aminobutyric Acid; Humans; Mice; Model	1982
Removal of GABAergic inhibition in the mediodorsal nucleus of the rat thalamus leads to increases in heart rate and blood pressure. Neuroscience letters, 1998, May-15, Volume: 247, Issue:2-3 Topics: Animals; Autonomic Nervous System Diseases; Bicuculline; Blood Pressure; GABA Antagonists; GABA-A Re	1998
GABAA alpha-1 subunit gene not associated with depressive symptomatology in mood disorders. Psychiatric genetics, 1998,Winter, Volume: 8, Issue:4 Topics: Adult; Anxiety; Bipolar Disorder; Delusions; Depression; DNA; Female; gamma-Aminobutyric Acid; Genet	1998
Selective neuronal vulnerability in human prion diseases. Fatal familial insomnia differs from other types of prion diseases. The American journal of pathology, 1999, Volume: 155, Issue:5 Topics: Adult; Brain; Female; gamma-Aminobutyric Acid; Humans; Immunohistochemistry; Male; Middle Aged; Neur	1999
Stress-induced insomnia: opioid-dopamine interactions. European journal of pharmacology, 1987, Oct-27, Volume: 142, Issue:3 Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Antipsychotic Agents; Appetite	1987