gabapentin and Disorders of Excessive Somnolence studies

Gabapentin: A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of PARTIAL SEIZURES; NEURALGIA; and RESTLESS LEGS SYNDROME.
gabapentin : A gamma-amino acid that is cyclohexane substituted at position 1 by aminomethyl and carboxymethyl groups. Used for treatment of neuropathic pain and restless legs syndrome.

Disorders of Excessive Somnolence: Disorders characterized by hypersomnolence during normal waking hours that may impair cognitive functioning. Subtypes include primary hypersomnia disorders (e.g., IDIOPATHIC HYPERSOMNOLENCE; NARCOLEPSY; and KLEINE-LEVIN SYNDROME) and secondary hypersomnia disorders where excessive somnolence can be attributed to a known cause (e.g., drug affect, MENTAL DISORDERS, and SLEEP APNEA SYNDROME). (From J Neurol Sci 1998 Jan 8;153(2):192-202; Thorpy, Principles and Practice of Sleep Medicine, 2nd ed, p320)

Research Excerpts

Excerpt	Relevance	Reference
"The goal of this study was to evaluate the efficacy and safety of gastroretentive gabapentin (G-GR) for the treatment of moderate-to-severe menopausal hot flashes."	9.19	Phase 3 randomized controlled study of gastroretentive gabapentin for the treatment of moderate-to-severe hot flashes in menopause. ( Kagan, R; Pinkerton, JV; Portman, D; Sathyanarayana, R; Sweeney, M, 2014)
"Treatment options for postherpetic neuralgia (PHN), a complication of herpes zoster, are commonly unsatisfactory and associated with adverse events."	6.78	Once-daily gastroretentive gabapentin for postherpetic neuralgia: integrated efficacy, time to onset of pain relief and safety analyses of data from two phase 3, multicenter, randomized, double-blind, placebo-controlled studies. ( Irving, GA; Rauck, RL; Sweeney, M; Vanhove, GF; Wallace, MS, 2013)
"Gabapentin was effective for the prevention of HAH and had satisfactory tolerability."	6.73	Gabapentin for prevention of hypobaric hypoxia-induced headache: randomized double-blind clinical trial. ( Abolfazli, R; Gorouhi, F; Jafarian, S; Lotfi, J; Rezaie, S, 2008)
"The goal of this study was to evaluate the efficacy and safety of gastroretentive gabapentin (G-GR) for the treatment of moderate-to-severe menopausal hot flashes."	5.19	Phase 3 randomized controlled study of gastroretentive gabapentin for the treatment of moderate-to-severe hot flashes in menopause. ( Kagan, R; Pinkerton, JV; Portman, D; Sathyanarayana, R; Sweeney, M, 2014)
" The primary objective of this study was to compare the efficacy of gabapentin to lorazepam in alleviating sleep disturbances and daytime sleepiness during an episode of alcohol withdrawal."	5.12	Self-reported sleep, sleepiness, and repeated alcohol withdrawals: a randomized, double blind, controlled comparison of lorazepam vs gabapentin. ( Boyle, E; Malcolm, R; Myrick, LH; Randall, PK; Veatch, LM, 2007)
"Treatment options for postherpetic neuralgia (PHN), a complication of herpes zoster, are commonly unsatisfactory and associated with adverse events."	2.78	Once-daily gastroretentive gabapentin for postherpetic neuralgia: integrated efficacy, time to onset of pain relief and safety analyses of data from two phase 3, multicenter, randomized, double-blind, placebo-controlled studies. ( Irving, GA; Rauck, RL; Sweeney, M; Vanhove, GF; Wallace, MS, 2013)
"Gabapentin was effective for the prevention of HAH and had satisfactory tolerability."	2.73	Gabapentin for prevention of hypobaric hypoxia-induced headache: randomized double-blind clinical trial. ( Abolfazli, R; Gorouhi, F; Jafarian, S; Lotfi, J; Rezaie, S, 2008)
"Gabapentin is a new adjunctive medication to antiseizure therapies."	2.69	Gabapentin as an adjunct to standard mood stabilizers in outpatients with mixed bipolar symptomatology. ( DeMet, EM; Green, C; Maris, DE; Sokolski, KN, 1999)
"Donepezil was started at 3-5 mg/day upon experiencing gabapentinoid-induced somnolence."	1.46	Donepezil, an Acetylcholinesterase Inhibitor, Can Attenuate Gabapentinoid-Induced Somnolence in Patients with Neuropathic Pain: A Retrospective Chart Review. ( Abe, H; Hozumi, J; Ikegami, K; Inoue, R; Kawahara, K; Kogure, T; Sumitani, M; Yamada, Y, 2017)
" A substantially lower median seizure frequency was observed at all gabapentin dosing periods (visit I - 2."	1.37	[Efficacy and tolerability of dose-escalation with generic gabapentin--a multicenter, non-interventional study]. ( Kaczyński, K; Lipa, A; Rejdak, K; Stelmasiak, Z, 2011)

Research

Studies (8)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Frequency of Moderate to Severe Hot Flashes at Week 24 of the Efficacy Treatment Period, Compared With Baseline.

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	1 (12.50)	18.2507
2000's	3 (37.50)	29.6817
2010's	4 (50.00)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Pinkerton, JV	1
Kagan, R	1
Portman, D	1
Sathyanarayana, R	1
Sweeney, M	2
Kogure, T	1
Sumitani, M	1
Ikegami, K	1
Abe, H	1
Hozumi, J	1
Inoue, R	1
Kawahara, K	1
Yamada, Y	1
Kushida, CA	1
Becker, PM	1
Ellenbogen, AL	1
Canafax, DM	1
Barrett, RW	1
Rejdak, K	1
Lipa, A	1
Kaczyński, K	1
Stelmasiak, Z	1
Rauck, RL	1
Irving, GA	1
Wallace, MS	1
Vanhove, GF	1
Malcolm, R	1
Myrick, LH	1
Veatch, LM	1
Boyle, E	1
Randall, PK	1
Jafarian, S	1
Abolfazli, R	1
Gorouhi, F	1
Rezaie, S	1
Lotfi, J	1
Sokolski, KN	1
Green, C	1
Maris, DE	1
DeMet, EM	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety and Efficacy of Gabapentin Extended Release (G-ER_ Tablets in the Treatment of Vasomotor Symptoms in Postmenopausal Women[NCT01080300]	Phase 3	600 participants (Actual)	Interventional	2010-08-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

G-ER dosed at 1800mg daily(600mg AM, 1200mg PM), compared with placebo in reducing the average daily frequency of moderate to severe hot flashes in post menopausal women at Week 24 of the efficacy treatment period compared with Baseline. (NCT01080300)
Timeframe: Baseline, Week 24

G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Severity Score of Moderate to Severe Hot Flashes at Week 24 of the Efficacy Treatment Period, Compared With Baseline.

Intervention	hot flashes (Least Squares Mean)
G-ER 1800 mg	-8.99
Sugar Pill	-7.91

"G-ER dosed at 1800mg daily(600mg AM, 1200mg PM), compared with placebo in reducing the average daily severity score of moderate to severe hot flashes in post menopausal women (score defined as Mild (1), Moderate (2), and Severe (3)) at Week 24 of the efficacy treatment period compared with Baseline." (NCT01080300)
Timeframe: Baseline, Week 24

Change From Baseline to Weeks 4, Week 12, and Week 24 in Average Daily Sleep Interference Score.

Intervention	scores on a scale (Least Squares Mean)
G-ER 1800 mg	-0.86
Sugar Pill	-0.64

Sleep Interference Score Range: Minimum value = 0, maximum value = 10 Lower scores indicate better outcome (ie, less interference) (NCT01080300)
Timeframe: Baseline, Week 4, Week 12, and Week 24

Changes From Baseline in Quality of Life Scores, Measured by the Menopause-Specific Quality of Life Questionnaire (MENQOL) to Weeks, 4, 12, 24 of the Efficacy Treatment Period.

Intervention	units on a scale (Least Squares Mean)
	Change from Baseline to Week 4: LOCF daily rating	Change from Baseline to Week 12: LOCF daily rating	Change from Baseline to Week 24: LOCF daily rating
G-ER 1800 mg	-2.67	-3.09	-3.15
Sugar Pill	-1.31	-2.17	-2.20

"4 sub-categories each scored individually: Minimum value = 1, maximum value = 8.~Overall summary score was mean of the 4 sub-category scores (minimum = 1 and maximum = 8).~Lower scores indicate better outcome (ie, less severity)" (NCT01080300)
Timeframe: Baseline, Week 4, Week 12, and Week 24

Changes From Baseline in Sleep Quality Scores, Measured by the Insomnia Severity Index (ISI) to Week 4, Week 12, and Week 24 of the Efficacy Treatment Period.

Intervention	scores on a scale (Least Squares Mean)
	Baseline LOCF MENQOL score at Week 4	Baseline LOCF MENQOL score at Week 12	Baseline LOCF MENQOL score at Week 24
G-ER 1800 mg	-0.91	-1.01	-1.01
Sugar Pill	-0.71	-0.87	-0.96

Insomnia Severity Index (ISI) scored on 4-point Likert-scales ('0' not at all - '4' extremely) for 7 sub-categories. Final score is sum of each sub-category generating a total sleep quality score (0-28). Minimum value = 0, maximum value = 28 (Lower scores indicate better outcome (ie, less severity)). (NCT01080300)
Timeframe: Baseline, Week 4, Week 12, and Week 24

Clinical Global Impression of Change (CGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period.

Intervention	scores on a scale (Least Squares Mean)
	Change from Baseline to Week 4: LOCF ISI rating	Change from Baseline to Week 12: LOCF ISI rating	Change from Baseline to Week 24: LOCF ISI rating
G-ER 1800 mg	-6.47	-7.02	-6.71
Sugar Pill	-4.13	-5.17	-4.95

"Proportion of patients who were categorized as very much or much improved in CGIC at Week 12 and Week 24. Scale range is 6 categories: minimum value = very much worse to maximum value = very much improved." (NCT01080300)
Timeframe: Week 12 and Week 24

G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Frequency of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline.

Intervention	Participants (Count of Participants)
	Baseline LOCF Proportion at Week 12	Baseline LOCF Proportion at Week 24
G-ER 1800 mg	173	159
Sugar Pill	122	124

G-ER dosed at 1800mg daily(600mg AM, 1200mg PM), compared with placebo in reducing the average daily frequency of moderate to severe hot flashes in post menopausal women at Week 4 of the efficacy treatment period compared with Baseline and at Week 12 of the efficacy treatment period compared with Baseline. (NCT01080300)
Timeframe: Baseline, Week 4, and Week 12

G-ER at 1800mg Daily Compared With Placebo in Reducing the Average Daily Severity Score of Moderate to Severe Hot Flashes at Weeks 4 & 12 of the Efficacy Treatment Period, Compared With Baseline.

Intervention	hot flashes (Least Squares Mean)
	Baseline LOCF Average Daily Frequency at Week 4	Baseline LOCF Average Daily Frequency at Week 12
G-ER 1800 mg	-6.72	-7.64
Sugar Pill	-5.01	-6.50

"G-ER dosed at 1800mg daily(600mg AM, 1200mg PM), compared with placebo in reducing the average daily severity score of moderate to severe hot flashes in post menopausal women (score defined as Mild (1), Moderate (2), and Severe (3)) at Week 4 of the efficacy treatment period compared with Baseline and at Week 12 of the efficacy treatment period compared with Baseline." (NCT01080300)
Timeframe: Baseline, Week 4, and Week 12

Patient Global Impression of Change (PGIC) Scales at Weeks 12 and 24 of the Efficacy Treatment Period.

Intervention	scores on a scale (Least Squares Mean)
	Baseline LOCF Average Daily Severity at Week 4	Baseline LOCF Average Daily Severity at Week 12
G-ER 1800 mg	-0.42	-0.65
Sugar Pill	-0.22	-0.46

"Proportion of patients who were categorized as very much or much improved for PGIC at Week 12 and Week 24. Scale range is 6 categories: minimum value = very much worse to maximum value = very much improved." (NCT01080300)
Timeframe: Week 12 and Week 24

Percent of Patients With 75% or Greater Reduction in Average Daily Frequency of Moderate to Severe Hot Flashes

Percent of Patients With 75% or Greater Reduction in Average Daily Severity Score of Moderate to Severe Hot Flashes

Safety of G-ER Measuring Columbia-Suicide Severity Rating Scale (C-SSRS).

Intervention	Participants (Count of Participants)
	Baseline LOCF Proportion at Week 12	Baseline LOCF Proportion at Week 24
G-ER 1800 mg	173	156
Sugar Pill	130	114

Intervention	Participants (Count of Participants)
	Baseline LOCF Proportion at Week 12	Baseline LOCF Proportion at Week 24
G-ER 1800 mg	125	146
Sugar Pill	101	122

Intervention	Participants (Count of Participants)
	Baseline LOCF Average Daily Score at Week 12	Baseline LOCF Average Daily Score at Week 24
G-ER 1800 mg	48	62
Sugar Pill	36	48

"Columbia-Suicide Severity Rating Scale (C-SSRS). Subjects were classified as 0=no suicidal ideation or 1=suicidal ideation. Outcome Measure is number of participants with or without suicidal ideation.~Higher counts without suicidal ideation = better outcome." (NCT01080300)
Timeframe: Week 4, Week 12, Week 24/Early Termination, Week 28

Intervention	Participants (Count of Participants)
	Patients Taking C-SSRS at Week 472302449		Patients Taking C-SSRS at Week 472302448	Patients Taking C-SSRS at Week 1272302448	Patients Taking C-SSRS at Week 1272302449	Patients Taking C-SSRS at Week 24/EarlyTermination72302448	Patients Taking C-SSRS at Week 24/EarlyTermination72302449	Patients Taking C-SSRS at Week 2872302448	Patients Taking C-SSRS at Week 2872302449
	Without Suicidal Ideation	With Suicidal Ideation
Gabapentin Extended Release	260
Placebo	257
Placebo	0
Gabapentin Extended Release	224
Placebo	215
Gabapentin Extended Release	0
Placebo	1
Gabapentin Extended Release	271
Placebo	266
Gabapentin Extended Release	1
Gabapentin Extended Release	256
Placebo	243

Article	Year
Phase 3 randomized controlled study of gastroretentive gabapentin for the treatment of moderate-to-severe hot flashes in menopause. Menopause (New York, N.Y.), 2014, Volume: 21, Issue:6 Topics: Adult; Aged; Amines; Calcium Channel Blockers; Cyclohexanecarboxylic Acids; Delayed-Action Preparati	2014
Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS. Neurology, 2009, Feb-03, Volume: 72, Issue:5 Topics: Adult; Amines; Anti-Anxiety Agents; Carbamates; Central Nervous System; Cyclohexanecarboxylic Acids;	2009
Once-daily gastroretentive gabapentin for postherpetic neuralgia: integrated efficacy, time to onset of pain relief and safety analyses of data from two phase 3, multicenter, randomized, double-blind, placebo-controlled studies. Journal of pain and symptom management, 2013, Volume: 46, Issue:2 Topics: Amines; Analgesics; Causality; Comorbidity; Cyclohexanecarboxylic Acids; Disorders of Excessive Somn	2013
Self-reported sleep, sleepiness, and repeated alcohol withdrawals: a randomized, double blind, controlled comparison of lorazepam vs gabapentin. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2007, Feb-15, Volume: 3, Issue:1 Topics: Adult; Aged; Alcoholism; Amines; Cyclohexanecarboxylic Acids; Disorders of Excessive Somnolence; Dou	2007
Gabapentin for prevention of hypobaric hypoxia-induced headache: randomized double-blind clinical trial. Journal of neurology, neurosurgery, and psychiatry, 2008, Volume: 79, Issue:3 Topics: Adolescent; Adult; Aged; Altitude Sickness; Amines; Cyclohexanecarboxylic Acids; Disorders of Excess	2008
Gabapentin as an adjunct to standard mood stabilizers in outpatients with mixed bipolar symptomatology. Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists, 1999, Volume: 11, Issue:4 Topics: Acetates; Adult; Affect; Aged; Ambulatory Care; Amines; Antidepressive Agents; Bipolar Disorder; Cyc	1999

Article	Year
Donepezil, an Acetylcholinesterase Inhibitor, Can Attenuate Gabapentinoid-Induced Somnolence in Patients with Neuropathic Pain: A Retrospective Chart Review. Journal of pain & palliative care pharmacotherapy, 2017, Volume: 31, Issue:1 Topics: Adult; Aged; Aged, 80 and over; Amines; Cholinesterase Inhibitors; Cyclohexanecarboxylic Acids; Diso	2017
[Efficacy and tolerability of dose-escalation with generic gabapentin--a multicenter, non-interventional study]. Wiadomosci lekarskie (Warsaw, Poland : 1960), 2011, Volume: 64, Issue:2 Topics: Adult; Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Disorders of Excessive Somnolence; Dizz	2011

gabapentin and Disorders of Excessive Somnolence