lamotrigine and Aging studies

Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.

Research Excerpts

Excerpt	Relevance	Reference
"To determine the relative tolerability and efficacy of two newer antiepileptic drugs, lamotrigine (LTG) and gabapentin (GBP), as compared to carbamazepine (CBZ) in older patients with epilepsy."	9.11	New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. ( Boardman, KD; Carter, GS; Collins, JF; Felicetta, J; Frederick, T; Marks, W; Pryor, F; Ramsay, RE; Rowan, AJ; Spitz, M; Tomyanovich, ML; Towne, A; Uthman, BM, 2005)
" However, there were no associations between NAA/Cr, Glu/Cr, or Gln/Cr and either depression severity or lamotrigine treatment."	7.91	Lamotrigine Therapy and Biomarkers of Cerebral Energy Metabolism in Older Age Bipolar Depression. ( Forester, BP; Harper, DG; Jensen, E; Mellen, EJ; Ravichandran, C; Silveri, M, 2019)
"Recent findings of antidystonic effects of NMDA and non-NMDA receptor antagonists in an inbred line of Syrian hamsters with primary generalized dystonia prompted us to investigate the effects of lamotrigine, an inhibitor of veratrine-induced glutamate release, on the severity of dystonia in mutant hamsters."	7.69	The novel antiepileptic drug, lamotrigine, exerts prodystonic effects in a mutant hamster model of generalized dystonia. ( Löscher, W; Löschmann, PA; Richter, A, 1994)
"To determine the relative tolerability and efficacy of two newer antiepileptic drugs, lamotrigine (LTG) and gabapentin (GBP), as compared to carbamazepine (CBZ) in older patients with epilepsy."	5.11	New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. ( Boardman, KD; Carter, GS; Collins, JF; Felicetta, J; Frederick, T; Marks, W; Pryor, F; Ramsay, RE; Rowan, AJ; Spitz, M; Tomyanovich, ML; Towne, A; Uthman, BM, 2005)
"Subjects were 85 men with localization-related epilepsy (25 on carbamazepine [CBZ], 25 on phenytoin [PHT], 25 on lamotrigine [LTG], and 10 untreated for at least 6 months [no AED]) and 25 controls."	5.11	Differential effects of antiepileptic drugs on sexual function and hormones in men with epilepsy. ( Bromfield, EB; Drislane, FW; Dworetzky, BA; Farina, EL; Frye, CA; Herzog, AG; Pennell, PB; Schomer, DL, 2005)
" However, there were no associations between NAA/Cr, Glu/Cr, or Gln/Cr and either depression severity or lamotrigine treatment."	3.91	Lamotrigine Therapy and Biomarkers of Cerebral Energy Metabolism in Older Age Bipolar Depression. ( Forester, BP; Harper, DG; Jensen, E; Mellen, EJ; Ravichandran, C; Silveri, M, 2019)
" To test whether glucuronidation reactions supported by UDP-glucuronosyltransferases are differentially affected in such conditions, we investigated the in vitro glucuronidation of four selected drugs and xenobiotics (zidovudine, oxazepam, lamotrigine, and umbelliferone) by using microsomes from human healthy and unhealthy (cirrhosis, hepatitis) livers as enzyme sources."	3.70	Glucuronidation of drugs by hepatic microsomes derived from healthy and cirrhotic human livers. ( Bourdon, O; Demirdjian, S; Furlan, V; Magdalou, J; Taburet, AM, 1999)
"Recent findings of antidystonic effects of NMDA and non-NMDA receptor antagonists in an inbred line of Syrian hamsters with primary generalized dystonia prompted us to investigate the effects of lamotrigine, an inhibitor of veratrine-induced glutamate release, on the severity of dystonia in mutant hamsters."	3.69	The novel antiepileptic drug, lamotrigine, exerts prodystonic effects in a mutant hamster model of generalized dystonia. ( Löscher, W; Löschmann, PA; Richter, A, 1994)
"The anticonvulsant actions of lamotrigine and phenytoin against pentylenetetrazol-induced seizures were compared in laboratory rats during ontogenesis."	3.68	Anticonvulsant action of lamotrigine during ontogenesis in rats. ( Kubová, H; Mares, P; Stanková, L, 1992)
" The goal of this study is to determine the pharmacokinetic parameters, such as clearance, and the factors that have a significant effect on these parameters to provide evidence-based information that can be used to dose elderly patients taking lamotrigine."	2.73	Population pharmacokinetics of lamotrigine in elderly patients. ( Birnbaum, AK; Brundage, RC; Collins, JF; Macias, FM; Punyawudho, B; Ramsay, RE; Rowan, AJ, 2008)
"Epilepsy is one of the most common neurological conditions in the elderly, and the incidence of de novo geriatric epilepsy is rising."	2.49	[Epilepsy in the elderly]. ( Lossius, MI; Markhus, R; Nakken, KO; Sætre, E, 2013)
"The neurodegenerative disorders (Parkinson's disease, Alzheimer's dementia, Huntington's disease, cerebellar degeneration) are common medical and social problems."	2.40	[Neurodegeneration: aging and dementia. Etiopathogenic role of electron transport disorders. Therapeutic possibilities]. ( Klivényi, P; Vécsei, L, 1997)
"An allometrically scaled pharmacokinetic model was developed using adolescent and adult data, taking into account the effect of comedications."	1.48	Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and Potential Implications for Maintenance Dose Optimisation in Future Clinical Trials. ( Danhof, M; de Jager, NCB; Della Pasqua, O; Rauwé, WM; van Dijkman, SC, 2018)
" Age was a significant factor contributing to pharmacokinetic variability in individuals using LTG, OXC, and CBZ with increasing clearance as a function of bioavailability (Cl/F) over age 18, a maximum Cl/F at 33years (CBZ) and 36 years (LTG and OXC), and a gradual decrease of Cl/F towards older age."	1.39	The impact of age on lamotrigine and oxcarbazepine kinetics: a historical cohort study. ( Lindhout, D; Sander, JW; Wegner, I; Wilhelm, AJ, 2013)
"Epilepsy was confirmed in 58 cases."	1.37	[Epilepsy in elderly]. ( Kotov, AS; Rudakova, IG, 2011)
"Lamotrigine is a commonly used anticonvulsant with a relatively good adverse-effects profile."	1.36	Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster. ( Avanesian, A; Felgner, JS; Jafari, M; Khodayari, B, 2010)

Research

Studies (18)

Authors

Clinical Trials (4)

Trial Overview

Trial Outcomes

58-week Retention Rate Measured by the Number of Drop Outs Due to Adverse Events or Seizures From Day 1 of Treatment

Percentage of Patients Remaining Seizure Free at Week 58 (Visit 6)

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	6 (33.33)	18.2507
2000's	5 (27.78)	29.6817
2010's	7 (38.89)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
van Dijkman, SC	1
de Jager, NCB	1
Rauwé, WM	1
Danhof, M	1
Della Pasqua, O	1
Mellen, EJ	1
Harper, DG	1
Ravichandran, C	1
Jensen, E	1
Silveri, M	1
Forester, BP	1
Nakken, KO	1
Sætre, E	1
Markhus, R	1
Lossius, MI	1
Wegner, I	1
Wilhelm, AJ	1
Sander, JW	1
Lindhout, D	1
Avanesian, A	1
Khodayari, B	1
Felgner, JS	1
Jafari, M	1
Forcelli, PA	1
Gale, K	1
Kondratyev, A	1
Kotov, AS	1
Rudakova, IG	1
Aulakh, JS	1
Hawkins, JW	1
Athwal, HS	1
Sheikh, JI	1
Yesavage, J	1
Tinklenberg, JR	1
Rowan, AJ	2
Ramsay, RE	2
Collins, JF	2
Pryor, F	1
Boardman, KD	1
Uthman, BM	1
Spitz, M	1
Frederick, T	1
Towne, A	1
Carter, GS	1
Marks, W	1
Felicetta, J	1
Tomyanovich, ML	1
Herzog, AG	1
Drislane, FW	1
Schomer, DL	1
Pennell, PB	1
Bromfield, EB	1
Dworetzky, BA	1
Farina, EL	1
Frye, CA	1
Punyawudho, B	1
Macias, FM	1
Brundage, RC	1
Birnbaum, AK	1
Richter, A	1
Löschmann, PA	1
Löscher, W	1
Gillham, R	1
Baker, G	1
Thompson, P	1
Birbeck, K	1
McGuire, A	1
Tomlinson, L	1
Eckersley, L	1
Silveira, C	1
Brown, S	1
Klivényi, P	1
Vécsei, L	1
Furlan, V	1
Demirdjian, S	1
Bourdon, O	1
Magdalou, J	1
Taburet, AM	1
Armijo, JA	1
Bravo, J	1
Cuadrado, A	1
Herranz, JL	1
Reith, DM	1
Andrews, J	1
Parker-Scott, S	1
Eadie, MJ	1
Stanková, L	1
Kubová, H	1
Mares, P	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Multicenter, Double-Blind, Randomized, Parallel-group Evaluation of LAMICTAL Extended-release Adjunctive Therapy in Subjects With Partial Seizures[NCT00113165]	Phase 3	244 participants (Actual)	Interventional	2004-10-31	Completed
An Open-label, Double Conversion Study to Characterize the Pharmacokinetics of Lamotrigine When Switching Patients With Epilepsy on LAMICTAL Immediate-release to Extended-release Formulation and Vice Versa[NCT00264615]	Phase 3	45 participants	Interventional	2005-10-31	Completed
A Multicentre, Double-blind, Randomized, Phase IV Clinical Trial Comparing the Safety, Tolerability and Efficacy of Levetiracetam Versus Lamotrigine and Carbamazepine in the Oral Antiepileptic Therapy of Newly Diagnosed Elderly Patients With Focal Epileps[NCT00438451]	Phase 4	361 participants (Actual)	Interventional	2007-01-31	Completed
An Open-label, Randomised Pilot Study Comparing the Efficacy, Safety and Tolerability of Raltegravir With Protease Inhibitor-based Therapy in Treatment-naïve, HIV/Hepatitis C Co-infected Injecting Drug Users Receiving Methadone[NCT01105611]	Phase 4	40 participants (Anticipated)	Interventional	2010-08-31	Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Intervention	proportion of participants (Mean)
Levetiracetam	0.61
Carbamazepine	0.46
Lamotrigine	0.56

Percentage of patients experiencing no seizures until week 58 (Visit 6) and did not discontinue the study until week 58. (NCT00438451)
Timeframe: week 58

Percentage of Patients Remaining Seizure-free at Week 30 (Visit 4)

Intervention	percentage of participants (Number)
Levetiracetam	43
Carbamazepine	33
Lamotrigine	38

Percentage of patients experiencing no seizures until week 30 (Visit 4) and did not discontinue the study until week 30. (NCT00438451)
Timeframe: Week 30

Proportion of Seizure-free Days During the Maintenance Phase for Subjects Who Enter the Maintenance Phase

Results of Cognitive Testing (EpiTrack© by UCB) - Score at V6

Intervention	percentage of participants (Number)
Levetiracetam	48
Carbamazepine	39
Lamotrigine	49

Intervention	proportion of seizure-free days (Number)
Levetiracetam	0.99
Carbamazepine	0.99
Lamotrigine	0.99

EPITrack-Score shows the performance of attention and executive functions. Higher values indicate a better performance. The results of EPITrack Score ranges between 7 and 45. (NCT00438451)
Timeframe: week 58

The Absolute Seizure Frequency During the Maintenance Phase (Weeks 7 - 58)

Intervention	units on a scale (Mean)
Levetiracetam	26.0
Carbamazepine	26.0
Lamotrigine	25.4

"Seizure frequency was assessed by investigators in the CRF at the Visits V3, V4, V5 and V6.~The absolute seizure frequency during the maintenance phase was defined as the sum of those entries." (NCT00438451)
Timeframe: over 52 weeks

The Time (in Days) to First Break-through Seizure (From Day 1 of Treatment)

Time to Drop Out

Intervention	number of seizures (Number)
Levetiracetam	168
Carbamazepine	131
Lamotrigine	130

Intervention	days (Median)
Levetiracetam	NA
Carbamazepine	NA
Lamotrigine	NA

number of days between randomization and premature discontinuation of the study (NCT00438451)
Timeframe: 58 weeks

Portland Neurotoxicity Scale (PNS) at V6

Intervention	days (Median)
Levetiracetam	NA
Carbamazepine	265
Lamotrigine	NA

"The PNS is a 15-item scale. Each item can be scored from 1 to 9. There are a total score (includes all items, range:15 to 135) and two subscores: The cognitive toxicity subscore (10 items: Energy Level, Memory, Interest, Concentration, Forgetfulness, Sleepliness, Moodiness, Alertness, Attention Span, Motivation, range:10 to 90) and the somatomoto subscore (5 items: Vision, Walking, Coordination, Tremor, Speech, range:5-45). The score is calculated by taking the mean of all non-missing values times the number of items.~Lower values indicate better quality of life." (NCT00438451)
Timeframe: at week 58

QOLIE-31 (Quality Of Life In Epilepsy) Results at V6

Intervention	units on a scale (Mean)
	Cognitive toxicity subscore	Somatomotor subscore	Total Score
Carbamazepine	27.3	11.4	38.7
Lamotrigine	23.7	10.8	34.5
Levetiracetam	22.2	10.5	32.7

The QOLIE-31 is a 31 item score that measures the quality of life in epilepsy (each item with a range of 0 to 100). There are 7 sub-scores seizure worry (items 11,21,22,23,25), overall quality of life (items 1,14), emotional well-being (items 3,4,5,7,9), energy/fatigue (items 2,6,8,10), cognitive functioning (items 12,15,16,17,18,26), medication effects (items 24,29,30) and social functioning (13,19,20,27,28). These scores were combined to a total score by Total score = seizure worry*0.08 + overall quality of life*0.14 + emotional well-being*0.15 + energy/fatigue*0.12 + cognitive functioning*0.27 + medication effects*0.03 + social functioning*0.21 For all scores, higher values indicate better quality of life. Each score has a possible range from 0 to 100. (NCT00438451)
Timeframe: 58 weeks, final visit

Intervention	units on a scale (Mean)
	Seizure worry	Overall quality of life	Emotional well-being	Energy/fatigue	Cognitive functioning	Medication effects	Social functioning	Total Score	Health Scale
Carbamazepine	75.4	65.0	69.8	54.5	68.9	70.6	76.3	68.9	65.7
Lamotrigine	75.0	67.1	67.4	59.8	68.0	72.6	76.7	69.1	67.5
Levetiracetam	85.1	67.2	72.0	60.8	75.1	77.6	81.1	73.9	69.5

"Evaluation of current testing at V6:~≥29 score points: Inconspicuous; 26 to 28 score points: Borderline;~≤25 score points: Impaired" (NCT00438451)
Timeframe: 58 weeks

Intervention	participants (Number)
	Without pathological findings	Borderline	Impaired
Carbamazepine	34	17	33
Lamotrigine	31	15	39
Levetiracetam	38	10	36

"Evaluation of Changes~Changes in the EpiTrack® Score were categorized as follows:~≥5 score points: Improved;~-3 to 4 score points: Unchanged;~≤-4 score points: Worsened" (NCT00438451)
Timeframe: week 58

Article	Year
[Epilepsy in the elderly]. Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 2013, Mar-05, Volume: 133, Issue:5 Topics: Age Factors; Aged; Aging; Anticonvulsants; Dose-Response Relationship, Drug; Epilepsy; Humans; Isoxa	2013
[Neurodegeneration: aging and dementia. Etiopathogenic role of electron transport disorders. Therapeutic possibilities]. Orvosi hetilap, 1997, Feb-09, Volume: 138, Issue:6 Topics: Aged; Aging; Alzheimer Disease; Calcium Channel Blockers; Cerebellar Diseases; Dementia; Electron Tr	1997

Article	Year
New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology, 2005, Jun-14, Volume: 64, Issue:11 Topics: Aged; Aging; Amines; Anticonvulsants; Carbamazepine; Cerebral Infarction; Cyclohexanecarboxylic Acid	2005
Differential effects of antiepileptic drugs on sexual function and hormones in men with epilepsy. Neurology, 2005, Oct-11, Volume: 65, Issue:7 Topics: Adolescent; Adult; Age Factors; Aging; Anticonvulsants; Carbamazepine; Cross-Sectional Studies; Down	2005
Population pharmacokinetics of lamotrigine in elderly patients. Journal of clinical pharmacology, 2008, Volume: 48, Issue:4 Topics: Aged; Aged, 80 and over; Aging; Alcohol Drinking; Algorithms; Anticonvulsants; Body Weight; Double-B	2008
Standardisation of a self-report questionnaire for use in evaluating cognitive, affective and behavioural side-effects of anti-epileptic drug treatments. Epilepsy research, 1996, Volume: 24, Issue:1 Topics: Adolescent; Adult; Affect; Aging; Anticonvulsants; Behavior; Carbamazepine; Cognition Disorders; Dou	1996
Urinary excretion of valproate metabolites in children and adolescents. Biopharmaceutics & drug disposition, 2000, Volume: 21, Issue:8 Topics: Adolescent; Aging; Anticonvulsants; Biotransformation; Child; Child, Preschool; Chromatography, Gas;	2000

Article	Year
Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and Potential Implications for Maintenance Dose Optimisation in Future Clinical Trials. Clinical pharmacokinetics, 2018, Volume: 57, Issue:8 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Algorithms; Body Weight; Child; Child, Preschool;	2018
Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and Potential Implications for Maintenance Dose Optimisation in Future Clinical Trials. Clinical pharmacokinetics, 2018, Volume: 57, Issue:8 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Algorithms; Body Weight; Child; Child, Preschool;	2018
Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and Potential Implications for Maintenance Dose Optimisation in Future Clinical Trials. Clinical pharmacokinetics, 2018, Volume: 57, Issue:8 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Algorithms; Body Weight; Child; Child, Preschool;	2018
Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and Potential Implications for Maintenance Dose Optimisation in Future Clinical Trials. Clinical pharmacokinetics, 2018, Volume: 57, Issue:8 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Algorithms; Body Weight; Child; Child, Preschool;	2018
Lamotrigine Therapy and Biomarkers of Cerebral Energy Metabolism in Older Age Bipolar Depression. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2019, Volume: 27, Issue:8 Topics: Aged; Aging; Antipsychotic Agents; Aspartic Acid; Biomarkers; Bipolar Disorder; Cerebral Cortex; Cre	2019
The impact of age on lamotrigine and oxcarbazepine kinetics: a historical cohort study. Epilepsy & behavior : E&B, 2013, Volume: 29, Issue:1 Topics: Adult; Aged; Aging; Anticonvulsants; Carbamazepine; Cohort Studies; Dose-Response Relationship, Drug	2013
Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster. Biogerontology, 2010, Volume: 11, Issue:1 Topics: Aging; Animals; Calcium Channel Blockers; Dose-Response Relationship, Drug; Drosophila melanogaster;	2010
Early postnatal exposure of rats to lamotrigine, but not phenytoin, reduces seizure threshold in adulthood. Epilepsia, 2011, Volume: 52, Issue:4 Topics: Aging; Animals; Anticonvulsants; Disease Models, Animal; Epilepsy; Female; Lamotrigine; Male; Phenyt	2011
[Epilepsy in elderly]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 2011, Volume: 111, Issue:7 Topics: Aged; Aged, 80 and over; Aging; Anticonvulsants; Carbamazepine; Electroencephalography; Epilepsies,	2011
Tolerability and effectiveness of lamotrigine in complex elderly patients. Journal of geriatric psychiatry and neurology, 2005, Volume: 18, Issue:1 Topics: Aged; Aged, 80 and over; Aging; Antimanic Agents; Female; Humans; Lamotrigine; Male; Mental Disorder	2005
The novel antiepileptic drug, lamotrigine, exerts prodystonic effects in a mutant hamster model of generalized dystonia. European journal of pharmacology, 1994, Nov-03, Volume: 264, Issue:3 Topics: Administration, Oral; Aging; Animals; Anticonvulsants; Cricetinae; Disease Models, Animal; Dose-Resp	1994
Glucuronidation of drugs by hepatic microsomes derived from healthy and cirrhotic human livers. The Journal of pharmacology and experimental therapeutics, 1999, Volume: 289, Issue:2 Topics: Adolescent; Adult; Aging; Aryl Hydrocarbon Hydroxylases; Biotransformation; Child; Child, Preschool;	1999
Lamotrigine serum concentration-to-dose ratio: influence of age and concomitant antiepileptic drugs and dosage implications. Therapeutic drug monitoring, 1999, Volume: 21, Issue:2 Topics: Adolescent; Adult; Aged; Aging; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship	1999
Anticonvulsant action of lamotrigine during ontogenesis in rats. Epilepsy research, 1992, Volume: 13, Issue:1 Topics: Aging; Animals; Anticonvulsants; Epilepsy, Tonic-Clonic; Injections, Intraperitoneal; Lamotrigine; M	1992

lamotrigine and Aging