lamotrigine and Cognition Disorders studies

Cognition Disorders: Disorders characterized by disturbances in mental processes related to learning, thinking, reasoning, and judgment.

Research Excerpts

Excerpt	Relevance	Reference
"Several placebo controlled studies investigating lamotrigine augmentation of clozapine in schizophrenia patients with partial response have shown varying results."	9.17	Lamotrigine augmentation in patients with schizophrenia who show partial response to clozapine treatment. ( Anıl Yağcıoğlu, AE; Gürel, SC; Karahan, S; Karcı, O; Vayısoğlu, S; Yağcıoğlu, S; Yazıcı, MK, 2013)
"This meta-analysis suggests that lamotrigine augmentation may be an effective treatment for patients with clozapine-resistant schizophrenia."	8.85	The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. ( Kiviniemi, V; Tiihonen, J; Wahlbeck, K, 2009)
"Lamotrigine (LTG) has shown benefits in animal models of cerebral ischemia, but the mechanism involved was not fully studied."	7.81	Lamotrigine attenuates cerebral ischemia-induced cognitive impairment and decreases β-amyloid and phosphorylated tau in the hippocampus in rats. ( Han, H; Qian, Q; Sun, G; Yu, Y; Zhao, D, 2015)
"Several placebo controlled studies investigating lamotrigine augmentation of clozapine in schizophrenia patients with partial response have shown varying results."	5.17	Lamotrigine augmentation in patients with schizophrenia who show partial response to clozapine treatment. ( Anıl Yağcıoğlu, AE; Gürel, SC; Karahan, S; Karcı, O; Vayısoğlu, S; Yağcıoğlu, S; Yazıcı, MK, 2013)
"This meta-analysis suggests that lamotrigine augmentation may be an effective treatment for patients with clozapine-resistant schizophrenia."	4.85	The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. ( Kiviniemi, V; Tiihonen, J; Wahlbeck, K, 2009)
"To review and summarize the currently available data on the use of anticonvulsant mood stabilizers (carbamazepine, valproic acid, gabapentin, lamotrigine, topiramate) in the treatment of behavioral and psychological symptoms of dementia (BPSD); to determine whether these medications can be recommended for routine clinical use."	4.84	Anticonvulsants for the treatment of behavioral and psychological symptoms of dementia: a literature review. ( Konovalov, S; Muralee, S; Tampi, RR, 2008)
"Lamotrigine (LTG) has shown benefits in animal models of cerebral ischemia, but the mechanism involved was not fully studied."	3.81	Lamotrigine attenuates cerebral ischemia-induced cognitive impairment and decreases β-amyloid and phosphorylated tau in the hippocampus in rats. ( Han, H; Qian, Q; Sun, G; Yu, Y; Zhao, D, 2015)
"An 8-year-old boy developed tremor, unsteadiness, chorea, and eye movement abnormalities on starting lamotrigine for myoclonic jerks."	3.72	Unusual side effects of lamotrigine therapy. ( Cross, JH; Das, KB; Harris, C; Smyth, DP, 2003)
"The aim of our study was to examine the influence of long term lamotrigine (LTG) add-on therapy on higher nervous function in patients at the developmental age with epilepsy and to analyse the correlation between changes in EEG and cognitive parameters as a consequence of applying LTG in bi- or polytherapy with conventional antiepileptic drugs (AEDs)."	3.70	[Neuropsychological aspects of cognitive functioning in epileptic children and adolescents treated with lamotrigine]. ( Galas-Zgorzalewicz, B; Mojs, E; Steinborn, B, 2000)
"Treatment with lamotrigine as monotherapy and as adjunctive therapy was associated with improved cognitive functioning and reduced neurocognitive side effects, regardless of index mood polarity."	2.71	Effect of lamotrigine on cognitive complaints in patients with bipolar I disorder. ( Adams, BE; Asnis, GM; Davis, KH; Ginsberg, LD; Goodwin, FK; Khan, A; Krishnan, AA, 2004)
"Attempts to control the seizure disorder by resection of apparently epileptogenic mesial temporal or other cortical structures have failed consistently."	2.70	Resection of the lesion in patients with hypothalamic hamartomas and catastrophic epilepsy. ( Andermann, F; Aronyk, K; Chandler, C; Costa Da Costa, J; Coutinho, L; Farmer, JP; Martínez, JV; Montes, J; Paglioli, E; Paglioli-Neto, E; Palmini, A; Polkey, C; Portuguez, M; Raupp, S; Rosenblatt, B; Sinclair, B, 2002)
"Lamotrigine is a new antiepileptic drug that may possess unique cognitive and behavioral characteristics."	2.40	Behavioral and cognitive effects of lamotrigine. ( Baker, GA; Meador, KJ, 1997)
" To conclude, long term administration of topiramate impairs cognitive functions during experimental epilepsy while lamotrigine and oxcarbazepine are safer."	1.37	Effect of lamotrigine, oxcarbazepine and topiramate on cognitive functions and oxidative stress in PTZ-kindled mice. ( Agarwal, NB; Agarwal, NK; Mediratta, PK; Sharma, KK, 2011)
"Lamotrigine treatment had no effect on oxidative stress parameters alone, while it significantly decreased oxidative stress in the pentylenetetrazole-kindled group as compared to the pentylenetetrazole-kindled carbamazepine-treated group."	1.36	Effect of carbamazepine and lamotrigine on cognitive function and oxidative stress in brain during chemical epileptogenesis in rats. ( Arora, T; Banerjee, BD; Garg, GR; Mediratta, PK; Mehta, AK; Sharma, AK; Sharma, KK, 2010)
"Epilepsy is often the most important clinical manifestation of the syndrome, even if its appearance is not constantly precocious."	1.35	Ring chromosome 20 syndrome: a link between epilepsy onset and neuropsychological impairment in three children. ( Canevini, MP; Dalla Bernardina, B; Darra, F; Fiorini, E; La Selva, L; Lazzarotto, F; Piazzini, A; Vignoli, A; Zucca, C, 2009)
"Lamotrigine was used concurrently in four of the 11 children with behavioral or cognitive abnormalities but in only seven of the 64 children without abnormalities (P = 0."	1.31	Factors associated with behavioral and cognitive abnormalities in children receiving topiramate. ( Connolly, MB; Farrell, K; Gerber, PE; Hamiwka, L, 2000)

Research

Studies (36)

Authors

Clinical Trials (7)

Trial Overview

Trial Outcomes

A Secondary Analysis Will Examine the Possible Sustained Benefit of Continued Memantine Use.

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	4 (11.11)	18.2507
2000's	17 (47.22)	29.6817
2010's	15 (41.67)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Pocsay, G	1
Gazdag, A	1
Engelhardt, J	1
Szaniszló, I	1
Szolnoki, Z	1
Forczek, G	1
Mikló, L	1
Verrotti, A	1
Scaparrotta, A	1
Cofini, M	1
Chiarelli, F	1
Tiboni, GM	1
Fagan, CS	1
Carmody, TJ	1
McClintock, SM	1
Suris, A	1
Nakamura, A	1
Jeon-Slaughter, H	1
Lo, A	1
Brown, ES	1
Omrani, A	1
van der Vaart, T	1
Mientjes, E	1
van Woerden, GM	1
Hojjati, MR	1
Li, KW	1
Gutmann, DH	1
Levelt, CN	1
Smit, AB	1
Silva, AJ	1
Kushner, SA	1
Elgersma, Y	1
Anderson, M	1
Egunsola, O	1
Cherrill, J	1
Millward, C	1
Fakis, A	1
Choonara, I	1
Han, H	1
Qian, Q	1
Yu, Y	1
Zhao, D	1
Sun, G	1
Wang, K	1
Fernandez-Escobar, A	1
Han, S	1
Zhu, P	1
Wang, JH	1
Sun, Y	1
Tiihonen, J	1
Wahlbeck, K	1
Kiviniemi, V	1
Bonnín, CM	1
Martínez-Arán, A	1
Torrent, C	1
Pacchiarotti, I	1
Rosa, AR	1
Franco, C	1
Murru, A	1
Sanchez-Moreno, J	1
Vieta, E	1
Vignoli, A	1
Canevini, MP	1
Darra, F	1
La Selva, L	1
Fiorini, E	1
Piazzini, A	1
Lazzarotto, F	1
Zucca, C	1
Dalla Bernardina, B	1
Arora, T	1
Mehta, AK	1
Sharma, KK	2
Mediratta, PK	2
Banerjee, BD	1
Garg, GR	1
Sharma, AK	1
Cumbo, E	1
Ligori, LD	1
Cavanna, AE	1
Ali, F	1
Rickards, HE	1
McCorry, D	1
Kálmán, J	2
Agarwal, NB	1
Agarwal, NK	1
Cretin, B	1
Davanture, C	1
Longato, N	1
Philippi, N	1
Blanc, F	1
Vayısoğlu, S	1
Anıl Yağcıoğlu, AE	1
Yağcıoğlu, S	1
Karahan, S	1
Karcı, O	1
Gürel, SC	1
Yazıcı, MK	1
Das, KB	1
Harris, C	1
Smyth, DP	1
Cross, JH	1
Holzer, L	1
Halfon, O	1
Khan, A	1
Ginsberg, LD	1
Asnis, GM	1
Goodwin, FK	1
Davis, KH	1
Krishnan, AA	1
Adams, BE	1
Meador, KJ	3
Loring, DW	1
Vahle, VJ	1
Ray, PG	2
Werz, MA	1
Fessler, AJ	1
Ogrocki, P	1
Schoenberg, MR	1
Miller, JM	1
Kustra, RP	1
Smith, ME	1
Gevins, A	1
McEvoy, LK	1
Gilliam, F	2
Kilaru, S	1
Bergqvist, AGC	1
Konovalov, S	1
Muralee, S	1
Tampi, RR	1
Pavlovic, ZM	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
Bouman, WP	1
Pinner, G	1
Johnson, H	1
Baker, GA	1
Martin, R	1
Kuzniecky, R	1
Ho, S	1
Hetherington, H	1
Pan, J	1
Sinclair, K	1
Faught, E	1
Anand, A	1
Charney, DS	1
Oren, DA	1
Berman, RM	1
Hu, XS	1
Cappiello, A	1
Krystal, JH	1
Gerber, PE	1
Hamiwka, L	1
Connolly, MB	1
Farrell, K	1
Mojs, E	1
Galas-Zgorzalewicz, B	1
Steinborn, B	1
Aldenkamp, AP	1
Goldberg, JF	1
Burdick, KE	1
Palmini, A	1
Chandler, C	1
Andermann, F	1
Costa Da Costa, J	1
Paglioli-Neto, E	1
Polkey, C	1
Rosenblatt, B	1
Montes, J	1
Martínez, JV	1
Farmer, JP	1
Sinclair, B	1
Aronyk, K	1
Paglioli, E	1
Coutinho, L	1
Raupp, S	1
Portuguez, M	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase IIA, Prospective, Randomized, Double-blind, Multiple-dose Study of NW-3509A in Chronic Schizoprhenia Patients Not Responding to Their Current Anti-psychotic Medication[NCT02624167]	Phase 2	90 participants (Actual)	Interventional	2015-12-31	Completed
L-Arginine add-on Treatment for Schizophrenia: A Randomized, Double Blind, Placebo Controlled, Cross Over Study[NCT02398279]		12 participants (Actual)	Interventional	2011-06-30	Completed
Does Memantine Improve Verbal Memory Task Performance in Subjects With Localization-related Epilepsy and Memory Dysfunction? A Randomized, Double-Blind, Placebo-Controlled Trial[NCT01054599]		29 participants (Actual)	Interventional	2009-01-31	Completed
Cognitive Effects of Treatment of Interictal Discharges[NCT00916149]		31 participants (Actual)	Interventional	2007-01-31	Completed
A Randomized, Pilot Study to Evaluate the Tolerability of OnabotulinumtoxinA Plus Topiramate vs. OnabotulinumtoxinA Plus Placebo and Long Term Effect of Treatment on Cognitive Efficiency and Continuation of Care[NCT01700387]	Phase 4	20 participants (Actual)	Interventional	2012-10-31	Completed
Medications After Adolescent Bariatric Surgery Protocol for Inadequate Weight Loss Following Sleeve Gastrectomy in Adolescents and Young Adults: A Pilot Feasibility Study[NCT04572217]	Phase 2	0 participants (Actual)	Interventional	2022-06-30	Withdrawn (stopped due to No available funding)
An Investigation of the Antidepressant Efficacy and Safety of an AMPAkine (Org 24448) in Major Depressive Disorder, A Double-Blind, Placebo-Controlled, Randomized Study[NCT00113022]	Phase 2	9 participants (Actual)	Interventional	2005-05-31	Terminated (stopped due to Terminated due to concerns about adverse events in separate study.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

SRT-CLTR (range 0-72; higher scores indicate better memory), and 7-24 Spatial Memory Test (range 0-35; scores are summed across the 5 learning trials, with higher scores indicating better memory) scores will be assessed across the first (baseline) and third (post-open label memantine) testing sessions. These measures are considered to be scores on a scale, rather than standard units. The hypothesis was that subjects randomized to memantine would demonstrate sustained improvement from baseline, while the placebo group would demonstrate improvements after taking open label memantine (compared to baseline). (NCT01054599)
Timeframe: 26 weeks

The Change Scores in Memory Measures From Baseline to Post-treatment/Placebo Will be Compared Between the Memantine Treatment and Placebo Groups.

Intervention	scores on a scale (Mean)
	SRT CLTR Baseline	SRT CLTR Post-Open Label	7-24 Total Learning Baseline	7-24 Total Learning Post-Open Label
Memantine	32.67	40.33	30.33	31.67
Sugar Pill	22.71	40.29	28.14	32.43

Change scores from pre- to post-treatment/placebo were calculated for the primary outcome measures, the Selective Reminding Test Continuous Long-Term Retrieval (range 0-72; higher scores indicate better memory) and 7-24 Spatial Recall Test Total Learning (range 0-35; total correct across 5 learning trials are summed, with higher scores indicating better memory) scores. These measures are scores on a scale, rather than representing standard units. (NCT01054599)
Timeframe: 13 weeks

Mean Change in Focal Interictal Discharges (IEDs) Per Hour, Pre to Post Treatment

Intervention	scores on a scale (Mean)
	7-24 Spatial Recall Tests Learning Change Score	SRT Continuous Long-Term Retrieval Change Score
Memantine	1.00	4.38
Sugar Pill	1.78	8.11

This descriptive analysis examined the change in interictal discharge rates pre to post-treatment with levetiracetam in subjects with epilepsy and with no treatment in healthy controls. (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Adverse Events Profile (AEP)

Intervention	IEDs/hour (Mean)
No Treatment	-28.8
Levetiracetam	.54

Change in Adverse Events Profile score (scores range from 19-76; higher scores indicate greater side effects) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Delayed Recall

Intervention	scores on a scale (Mean)
No Treatment	-1.27
Levetiracetam	1

Change in Brief Visuospatial Memory Test-Revised (BVMT-R) Delayed Recall score (the score ranges from 0-6, reflecting the number of shapes recalled after a 25 minute delay) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Learning

Intervention	number recalled (Mean)
No Treatment	.36
Levetiracetam	.33

Change in Brief Visuospatial Memory Test-Revised (BVMT-R) Learning score (the score ranges from 0-6, reflecting the number of shapes recalled on the initial learning trial) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Total Learning

Intervention	number recalled (Mean)
No Treatment	.45
Levetiracetam	.33

Change in Brief Visuospatial Memory Test-Revised (BVMT-R) Total Learning score (the score is summed across 3 learning trials, score range 0-18, reflecting the total number of shapes recalled) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Choice Accuracy

Intervention	number recalled (Mean)
No Treatment	1.09
Levetiracetam	.17

Change in Choice Accuracy Score (indicate if red or blue stimulus; accuracy 0-100%) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Choice Reaction Time

Intervention	percentage of correct responses (Mean)
No Treatment	.02
Levetiracetam	.1

Change in Choice Reaction Time Score, with reaction time measured in seconds (indicate if red or blue stimulus; lower reaction time suggests better performance) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CPT Accuracy

Intervention	seconds (Mean)
No Treatment	34.96
Levetiracetam	.45

Change in Continuous Performance Test Score - Accuracy (CPT; score ranges from 0-100% correct) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CPT Reaction Time (CPT RT)

Intervention	percentage of correct responses (Mean)
No Treatment	-0.01
Levetiracetam	.01

Change in Continuous Performance Test Score - Reaction Time, measured in seconds (CPT RT; less time reflects better performance) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Long Delay

Intervention	seconds (Mean)
No Treatment	1.04
Levetiracetam	-11.33

Change in California Verbal Learning Test (CVLT) Long Delay Recall score (the score ranges from 0-16, reflecting the number of words recalled) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Short Delay

Intervention	number recalled (Mean)
No Treatment	1.55
Levetiracetam	2.67

Change in California Verbal Learning Test (CVLT) Short Delay Recall Score (the score ranges from 0-16, reflecting the number of words recalled) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Total Learning

Intervention	number recalled (Mean)
No Treatment	1.27
Levetiracetam	-0.4

Change in California Verbal Learning Test (CVLT) Total Learning Score (the total learning score is summed across 5 learning trials, range 0-80). Higher scores indicate better memory. Scores on the CVLT reflect the number of words recalled. (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Trial 1 Learning Score

Intervention	number recalled (Mean)
No Treatment	8.09
Levetiracetam	5.5

Change in California Verbal Learning Test (CVLT) Trial 1 learning score (range 0-16; higher score indicates better memory) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Design Fluency

Intervention	scores on a scale (Mean)
No Treatment	2.45
Levetiracetam	2.5

Change in Design Fluency score (Score range: lowest score = 0; there is no upper limit. A higher score reflects more designs generated, hence better performance.) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Digit Span

Intervention	scores on a scale (Mean)
No Treatment	2.8
Levetiracetam	.83

Change in Digit Span score (score ranges from 0-30; higher scores indicate better performance). Scores indicate the number of digit sequences correctly recalled, forwards and backwards. (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Digit Symbol

Intervention	number recalled (Mean)
No Treatment	.73
Levetiracetam	-.33

Change in Digit Symbol Score (The score is the number of items completed. A higher score reflects better performance.) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Facial Recognition Accuracy

Intervention	scores on a scale (Mean)
No Treatment	3.2
Levetiracetam	1.5

Change in Facial Recognition Accuracy Score (accuracy ranges from 0-100%) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Facial Recognition Reaction Time

Intervention	percentage of correct responses (Mean)
No Treatment	.01
Levetiracetam	.03

Change in Facial Recognition Reaction Time Score (indicates processing speed, with reaction time measured in seconds) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Grooved Pegboard

Intervention	seconds (Mean)
No Treatment	-66.76
Levetiracetam	.61

Change in Grooved Pegboard Score (The score is the time for completion. A lower score reflects better performance.) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: LNS

Intervention	seconds (Mean)
No Treatment	-4.73
Levetiracetam	-4.36

Change in Letter-Number Sequencing score (LNS; score ranges from 0-21; higher scores indicate better performance). The score reflects the number of items that the subject can correctly recall and place in proper alphabetical and numerical sequence. (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: NDDIE

Intervention	scores on a scale (Mean)
No Treatment	.18
Levetiracetam	-0.5

Change in Neurological Disorders Depression Inventory for Epilepsy (NDDIE) score (scores range from 0-24; higher scores indicate greater depressive symptoms) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Non-verbal Working Memory Accuracy

Intervention	scores on a scale (Mean)
No Treatment	0.18
Levetiracetam	1.5

Change in Non-verbal Working Memory Accuracy Score (accuracy ranges from 0-100%) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Non-verbal Working Memory Reaction Time

Intervention	percentage of correct responses (Mean)
No Treatment	-.01
Levetiracetam	0

Change in Non-verbal Working Memory Reaction Time Score (indicates processing speed, with reaction time measured in seconds) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: QOLIE

Intervention	seconds (Mean)
No Treatment	-31.99
Levetiracetam	-25.54

Change in Quality of Life Inventory in Epilepsy-89 score (QOLIE; score ranges from 0-100; higher scores reflect better quality of life) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Spatial Span

Intervention	scores on a scale (Mean)
Levetiracetam	19.6

Change in Spatial Span score (score ranges from 0-32; higher scores indicate better performance). Scores indicate the number of spatial sequences correctly recalled, forwards and backwards. (NCT00916149)
Timeframe: 1 and 11 Weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Stroop

Intervention	number recalled (Mean)
No Treatment	.36
Levetiracetam	-1.67

Change in Stroop score (The score is the time for completion in seconds; less time reflects better performance.) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Trails Test

Intervention	seconds (Mean)
No Treatment	.98
Levetiracetam	-7.3

Change in Trails Test score (The score is the time for completion in seconds. A lower score reflects better performance.) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Fluency

Intervention	seconds (Mean)
No Treatment	-9.51
Levetiracetam	11.29

Change in Verbal Fluency score (Score range: lowest score = 0, with no upper limit, reflecting total number of words generated. Higher scores indicate better performance.) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Recognition Accuracy

Intervention	scores on a scale (Mean)
No Treatment	-1.55
Levetiracetam	-.83

Change in Verbal Recognition Accuracy Score (accuracy ranges from 0-100%) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Recognition Reaction Time

Intervention	percentage of correct responses (Mean)
No Treatment	.02
Levetiracetam	.14

Change in Verbal Recognition Reaction Time Score (indicates processing speed, with reaction time measured in seconds) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Working Memory Accuracy

Intervention	seconds (Mean)
No Treatment	2.98
Levetiracetam	-6.1

Change in Verbal Working Memory Accuracy Score (range 0-100%) (NCT00916149)
Timeframe: 1 and 11 weeks

Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Working Memory Reaction Time

Intervention	percentage of correct responses (Mean)
No Treatment	0
Levetiracetam	-.02

Change in Verbal Working Memory Reaction Time Score, with reaction time measured in seconds (indicates processing speed) (NCT00916149)
Timeframe: 1 and 11 weeks

Number of Non-Serious Adverse Events Between Groups

Headache Impact Test (HIT-6) Scores at Visits 2-6 to Measure Effect of Headache in Subject's Life

Intervention	seconds (Mean)
No Treatment	-54.76
Levetiracetam	-9.36

Intervention	Adverse Events (Mean)
OnabotulinumtoxinA + Topiramate	8.60
OnabotulinumtoxinA + Placebo	4.60

The Headache Impact Test (HIT-6) is a tool used to measure the impact headaches have on an individual's ability to function on the job, at school, at home and in social situations. The HIT-6 score range is from 36 to 78 with higher scores indicating greater impact (worse outcome). (NCT01700387)
Timeframe: Collected on Visit 2 (Day 29), 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)

MEWT Matching to Sample Sub-test Score Percent Change Compared From Baseline to Visits 3-6

Intervention	units on a scale (Mean)
	Visit 2	Visit 3	Visit 4	Visit 5	Visit 6
OnabotulinumtoxinA + Placebo	66.50	59.9	60.44	58.71	54.17
OnabotulinumtoxinA + Topiramate	66.40	61.89	54.5	52.83	52.57

The Mental Efficiency Workload Test (MEWT) is a cognitive functioning scale with four sub-scales (Simple Reaction Time, Running Memory Continuous Performance Task, Matching to Sample, and Mathematical Processing). Each sub-scale has a minimum and maximum values of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. MEWT sub-scale score percent change from baseline will be reported. Positive change scores represent better cognitive functioning compared to baseline. (NCT01700387)
Timeframe: Baseline, Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)

MEWT Mathematical Processing Sub-test Score Percent Change Compared From Baseline to Visits 3-6

Intervention	percentage of change from baseline score (Mean)
	Visit 3	Visit 4	Visit 5	Visit 6
OnabotulinumtoxinA + Placebo	21.74	8.59	12.72	24.75
OnabotulinumtoxinA + Topiramate	19.06	15.04	18.49	40.86

MEWT Running Memory Continuous Performance Task Sub-test Score Percent Change Compared From Baseline to Visits 3-6

Intervention	percentage of change from baseline score (Mean)
	Visit 3	Visit 4	Visit 5	Visit 6
OnabotulinumtoxinA + Placebo	17.74	16.43	28.61	29.44
OnabotulinumtoxinA + Topiramate	-11.23	-22.90	-23.81	1.52

MEWT Simple Reaction Time Sub-test Score Percent Change Compared From Baseline to Visits 3-6

Intervention	percentage of change from baseline score (Mean)
	Visit 3	Visit 4	Visit 5	Visit 6
OnabotulinumtoxinA + Placebo	1.13	4.39	18.81	2.2
OnabotulinumtoxinA + Topiramate	-15.66	-1.20	-3.96	-6.99

Number of Headache Days

Intervention	percentage of change from baseline score (Mean)
	Visit 3	Visit 4	Visit 5	Visit 6
OnabotulinumtoxinA + Placebo	14.22	4.76	-4.17	2.31
OnabotulinumtoxinA + Topiramate	-8.90	-3.20	-3.87	-3.16

Number of Headache Days reported in 30-day Baseline Period and Treatment Period Months 1-12 (NCT01700387)
Timeframe: Baseline and Months 1-12

Physician Global Impression of Change (PGIC)

Intervention	Headache days (Mean)
	Baseline	Month 1	Month 2	Month 3	Month 4	Month 5	Month 6	Month 7	Month 8	Month 9	Month 10	Month 11	Month 12
OnabotulinumtoxinA + Placebo	23.77	21.67	17.54	18.37	14.39	13.47	16.58	12.54	11.5	9.96	8.02	8.51	8.06
OnabotulinumtoxinA + Topiramate	22.95	18.41	16.50	16.83	15.74	11.34	15.18	12.64	12.36	12.02	6.93	8.36	7.51

Score on Physician Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better. (NCT01700387)
Timeframe: Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)

Subject Attrition Post Randomization

Intervention	units on a scale (Mean)
	Visit 3	Visit 4	Visit 5	Visit 6
OnabotulinumtoxinA + Placebo	5.30	5.89	5.83	5.83
OnabotulinumtoxinA + Topiramate	5.25	5.40	6.67	6.83

Count of subject attrition following randomization and reason for attrition (Consent withdrawn, Withdrawn due to adverse event, Lost to follow up) (NCT01700387)
Timeframe: Collected on Visit 2 (Day 29) through Visit 6 (Day 365)

Subject Estimation of Compliance With Daily Study Drug

Intervention	participants (Number)
	Consent Withdrawn	Withdrawn Due to Adverse Event	Lost to Follow Up
OnabotulinumtoxinA + Placebo	2	1	1
OnabotulinumtoxinA + Topiramate	1	1	2

Subject estimation of compliance with daily study drug during the study period. Compliance ranges from 0% to 100% with higher percentages indicating greater compliance with study drug. (NCT01700387)
Timeframe: Collected on Visit 2 (Day 29), 3 (Day 113), Visit 4 (Day 197), and Visit 5 (281)

Subject Global Impression of Change (SGIC)

Intervention	percentage of compliance (Mean)
	Visit 2	Visit 3	Visit 4	Visit 5
OnabotulinumtoxinA + Placebo	99.73	99.73	97.65	99.63
OnabotulinumtoxinA + Topiramate	100	99.84	99.55	98.69

Score on Subject Global Impression of Change at Visits 3-6 (Day 113 and 365). Likert scale ranging from 1-7, where 1 = extremely worse and 7 = extremely better. (NCT01700387)
Timeframe: Collected on Visit 3 (Day 113), Visit 4 (Day 197), Visit 5 (281), and Visit 6 (Day 365)

Subject's Controlled Oral Word Association Test (COWAT) Score Percent Change Compared From Baseline to Visits 3-6

Intervention	units on a scale (Mean)
	Visit 3	Visit 4	Visit 5	Visit 6
OnabotulinumtoxinA + Placebo	5.30	5.77	6.17	6.00
OnabotulinumtoxinA + Topiramate	5.38	6.33	6.66	7.00

The Controlled Oral Word Association Test (COWAT) is a measure of verbal fluency. Raw COWAT scores have a lower bound of 0 with no upper bound. Higher scores indicate better verbal fluency. COWAT score percent change from baseline will be reported. Positive change scores represent better verbal fluency compared to baseline. (NCT01700387)
Timeframe: Baseline, Visit 3 (Day 113) through Visit 6 (Day 365)

Subject's Migraine Specific Quality of Life Questionnaire (MSQ) Scores at Baseline, 3, 6, 9 and 12 Months to Measure Subject's Quality of Life

Intervention	percentage of change from baseline score (Mean)
	Visit 3	Visit 4	Visit 5	Visit 6
OnabotulinumtoxinA + Placebo	-3.50	-8.93	1.48	-4.99
OnabotulinumtoxinA + Topiramate	-17.06	-17.93	-12.63	-5.05

The Migraine-Specific Quality of Life Questionnaire (MSQ) is a scale that measures the impact of migraine across three aspects: role function-restrictive (RR), role function-preventive (RP), and emotional function (EF). Possible scores on each sub-scale range from a 0 to 100 scale such that higher scores indicate better quality of life. (NCT01700387)
Timeframe: Baseline, Months: 3, 6, 9 and 12

Montgomery-Asberg Depression Rating Scale (MADRS)

The MADRS is a measure of depression severity examined on a weekly basis. The minimum score on the 10 item scale is 0 indicating no depression. The maximum score is 60 indicating a very severe depression. Scores of 18 and above are generally considered to suggest significant levels of depression. (NCT00113022)
Timeframe: 8 weeks

Intervention	score on a scale (Mean)
	Role Function-Restrictive - Baseline	Role Function-Restrictive - Month 3	Role Function-Restrictive - Month 6	Role Function-Restrictive - Month 9	Role Function-Restrictive - Month 12	Role Function-Preventive - Baseline	Role Function-Preventive - Month 3	Role Function-Preventive - Month 6	Role Function-Preventive - Month 9	Role Function-Preventive - Month 12	Emotional Function - Baseline	Emotional Function - Month 3	Emotional Function - Month 6	Emotional Function - Month 9	Emotional Function - Month 12
OnabotulinumtoxinA + Placebo	29.71	56.29	59.37	60.41	72.38	46.50	65.00	72.22	72.86	80.83	22.67	56.67	56.30	70.48	78.89
OnabotulinumtoxinA + Topiramate	32.14	56.51	77.14	79.52	81.90	56.50	72.78	90.00	88.33	96.67	39.33	57.78	88.89	92.22	95.56

Article	Year
Developmental neurotoxicity and anticonvulsant drugs: a possible link. Reproductive toxicology (Elmsford, N.Y.), 2014, Volume: 48 Topics: Animals; Anticonvulsants; Breast Feeding; Carbamazepine; Cognition Disorders; Developmental Disabili	2014
The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. Schizophrenia research, 2009, Volume: 109, Issue:1-3 Topics: Age Factors; Anticonvulsants; Antipsychotic Agents; Clozapine; Cognition Disorders; Drug Resistance;	2009
Behavioral and cognitive effects of anti-epileptic drugs. Discovery medicine, 2010, Volume: 9, Issue:45 Topics: Amines; Anticonvulsants; Antidepressive Agents; Behavior; Cognition; Cognition Disorders; Cyclohexan	2010
[Sense and sensibility: bipolar affective disorder as a battlefield of cognitions and emotions--lamotrigine therapy as a peacekeeper]. Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet lapja = official journal of the Hungarian Association of Psychopharmacology, 2010, Volume: 12, Issue:2 Topics: Adolescent; Adult; Affect; Aged; Antimanic Agents; Bipolar Disorder; Cerebral Cortex; Child; Clinica	2010
Anticonvulsants for the treatment of behavioral and psychological symptoms of dementia: a literature review. International psychogeriatrics, 2008, Volume: 20, Issue:2 Topics: Aggression; Amines; Anticonvulsants; Carbamazepine; Cognition Disorders; Cyclohexanecarboxylic Acids	2008
Behavioral and cognitive effects of lamotrigine. Journal of child neurology, 1997, Volume: 12 Suppl 1 Topics: Adult; Anticonvulsants; Child; Cognition Disorders; Epilepsy; Female; Humans; Intellectual Disabilit	1997
Cognitive side effects of anticonvulsants. The Journal of clinical psychiatry, 2001, Volume: 62 Suppl 14 Topics: Acetates; Amines; Anticonvulsants; Bipolar Disorder; Carbamazepine; Cognition Disorders; Cyclohexane	2001

Article	Year
Levetiracetam, lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer's disease. Epilepsy & behavior : E&B, 2010, Volume: 17, Issue:4 Topics: Aged; Aged, 80 and over; Alzheimer Disease; Analysis of Variance; Anticonvulsants; Case-Control Stud	2010
Lamotrigine augmentation in patients with schizophrenia who show partial response to clozapine treatment. Schizophrenia research, 2013, Volume: 143, Issue:1 Topics: Adolescent; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Calcium Channel Blockers; Chi-S	2013
Effect of lamotrigine on cognitive complaints in patients with bipolar I disorder. The Journal of clinical psychiatry, 2004, Volume: 65, Issue:11 Topics: Adult; Anticonvulsants; Bipolar Disorder; Cognition Disorders; Diagnostic and Statistical Manual of	2004
Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology, 2005, Jun-28, Volume: 64, Issue:12 Topics: Adult; Anticonvulsants; Brain; Cognition Disorders; Cross-Over Studies; Dose-Response Relationship,	2005
Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology, 2005, Jun-28, Volume: 64, Issue:12 Topics: Adult; Anticonvulsants; Brain; Cognition Disorders; Cross-Over Studies; Dose-Response Relationship,	2005
Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology, 2005, Jun-28, Volume: 64, Issue:12 Topics: Adult; Anticonvulsants; Brain; Cognition Disorders; Cross-Over Studies; Dose-Response Relationship,	2005
Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology, 2005, Jun-28, Volume: 64, Issue:12 Topics: Adult; Anticonvulsants; Brain; Cognition Disorders; Cross-Over Studies; Dose-Response Relationship,	2005
Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology, 2005, Jun-28, Volume: 64, Issue:12 Topics: Adult; Anticonvulsants; Brain; Cognition Disorders; Cross-Over Studies; Dose-Response Relationship,	2005
Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology, 2005, Jun-28, Volume: 64, Issue:12 Topics: Adult; Anticonvulsants; Brain; Cognition Disorders; Cross-Over Studies; Dose-Response Relationship,	2005
Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology, 2005, Jun-28, Volume: 64, Issue:12 Topics: Adult; Anticonvulsants; Brain; Cognition Disorders; Cross-Over Studies; Dose-Response Relationship,	2005
Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology, 2005, Jun-28, Volume: 64, Issue:12 Topics: Adult; Anticonvulsants; Brain; Cognition Disorders; Cross-Over Studies; Dose-Response Relationship,	2005
Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology, 2005, Jun-28, Volume: 64, Issue:12 Topics: Adult; Anticonvulsants; Brain; Cognition Disorders; Cross-Over Studies; Dose-Response Relationship,	2005
Distinct cognitive neurophysiologic profiles for lamotrigine and topiramate. Epilepsia, 2006, Volume: 47, Issue:4 Topics: Adult; Anticonvulsants; Cognition; Cognition Disorders; Cortical Synchronization; Cross-Over Studies	2006
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
Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Neurology, 1999, Jan-15, Volume: 52, Issue:2 Topics: Acetates; Adult; Affect; Amines; Anticonvulsants; Cognition Disorders; Cyclohexanecarboxylic Acids;	1999
Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists. Archives of general psychiatry, 2000, Volume: 57, Issue:3 Topics: Adult; Affect; Brief Psychiatric Rating Scale; Cognition Disorders; Double-Blind Method; Excitatory	2000
Resection of the lesion in patients with hypothalamic hamartomas and catastrophic epilepsy. Neurology, 2002, May-14, Volume: 58, Issue:9 Topics: Adolescent; Adult; Brain; Child; Child, Preschool; Cognition Disorders; Electroencephalography; Epil	2002

Article	Year
[Hashimoto encephalopathy]. Orvosi hetilap, 2013, Aug-18, Volume: 154, Issue:33 Topics: Adrenal Cortex Hormones; Adult; Anticonvulsants; Antipsychotic Agents; Autoantibodies; Brain Disease	2013
The effect of cognitive functioning on treatment attendance and adherence in comorbid bipolar disorder and cocaine dependence. Journal of substance abuse treatment, 2015, Volume: 49 Topics: Adult; Bipolar Disorder; Cocaine-Related Disorders; Cognition Disorders; Diagnosis, Dual (Psychiatry	2015
HCN channels are a novel therapeutic target for cognitive dysfunction in Neurofibromatosis type 1. Molecular psychiatry, 2015, Volume: 20, Issue:11 Topics: Animals; Cognition Disorders; Disease Models, Animal; Excitatory Amino Acid Antagonists; Excitatory	2015
A prospective study of adverse drug reactions to antiepileptic drugs in children. BMJ open, 2015, Jun-01, Volume: 5, Issue:6 Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Cognition Disorders; Drug Thera	2015
Lamotrigine attenuates cerebral ischemia-induced cognitive impairment and decreases β-amyloid and phosphorylated tau in the hippocampus in rats. Neuroreport, 2015, Aug-19, Volume: 26, Issue:12 Topics: Amyloid beta-Peptides; Animals; Brain Ischemia; Cognition Disorders; Hippocampus; Lamotrigine; Male;	2015
Lamotrigine Reduces Inflammatory Response and Ameliorates Executive Function Deterioration in an Alzheimer's-Like Mouse Model. BioMed research international, 2016, Volume: 2016 Topics: Alzheimer Disease; Animals; Brain; Cognition Disorders; Cytokines; Disease Models, Animal; Gene Expr	2016
Clinical and neurocognitive predictors of functional outcome in bipolar euthymic patients: a long-term, follow-up study. Journal of affective disorders, 2010, Volume: 121, Issue:1-2 Topics: Adult; Affect; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Cognition Disorders; Female; Fol	2010
Ring chromosome 20 syndrome: a link between epilepsy onset and neuropsychological impairment in three children. Epilepsia, 2009, Volume: 50, Issue:11 Topics: Adult; Age of Onset; Anticonvulsants; Child; Chromosomes, Human, Pair 20; Cognition Disorders; Comor	2009
Effect of carbamazepine and lamotrigine on cognitive function and oxidative stress in brain during chemical epileptogenesis in rats. Basic & clinical pharmacology & toxicology, 2010, Volume: 106, Issue:5 Topics: Animals; Anticonvulsants; Avoidance Learning; Brain; Carbamazepine; Catalase; Cognition; Cognition D	2010
Effect of lamotrigine, oxcarbazepine and topiramate on cognitive functions and oxidative stress in PTZ-kindled mice. Seizure, 2011, Volume: 20, Issue:3 Topics: Animals; Anticonvulsants; Carbamazepine; Catalase; Cognition Disorders; Disease Models, Animal; Drug	2011
[Syndrome of transient epileptic amnesia and epileptic amnesic syndrome: the same entity?]. Revue neurologique, 2013, Volume: 169, Issue:1 Topics: Abdominal Pain; Aged, 80 and over; Amnesia, Transient Global; Anticonvulsants; Cognition Disorders;	2013
Unusual side effects of lamotrigine therapy. Journal of child neurology, 2003, Volume: 18, Issue:7 Topics: Anticonvulsants; Child; Child Behavior Disorders; Chorea; Cognition Disorders; Epilepsy, Absence; Hu	2003
Normalization of impaired cognitive functions failed to improve clinical symptomatology in a schizophrenic patient. European psychiatry : the journal of the Association of European Psychiatrists, 2004, Volume: 19, Issue:6 Topics: Acute Disease; Adolescent; Antipsychotic Agents; Benzodiazepines; Brain; Cognition Disorders; Electr	2004
Current treatment of myoclonic astatic epilepsy: clinical experience at the Children's Hospital of Philadelphia. Epilepsia, 2007, Volume: 48, Issue:9 Topics: Age of Onset; Anticonvulsants; Child; Cognition Disorders; Dietary Fats; Electroencephalography; Epi	2007
Lamotrigine for the treatment of impulsive aggression and affective symptoms in a patient with borderline personality disorder comorbid with body dysmorphic disorder. The Journal of neuropsychiatry and clinical neurosciences, 2008,Winter, Volume: 20, Issue:1 Topics: Adult; Affective Symptoms; Aggression; Anticonvulsants; Borderline Personality Disorder; Cognition D	2008
Cognitive impairment associated with lamotrigine. The British journal of psychiatry : the journal of mental science, 1997, Volume: 170 Topics: Aged; Anticonvulsants; Cognition Disorders; Female; Humans; Lamotrigine; Triazines	1997
Factors associated with behavioral and cognitive abnormalities in children receiving topiramate. Pediatric neurology, 2000, Volume: 22, Issue:3 Topics: Adolescent; Anticonvulsants; Child; Child Behavior Disorders; Child, Preschool; Cognition Disorders;	2000
[Neuropsychological aspects of cognitive functioning in epileptic children and adolescents treated with lamotrigine]. Neurologia i neurochirurgia polska, 2000, Volume: 34 Suppl 1 Topics: Adolescent; Anticonvulsants; Attention; Child; Cognition Disorders; Dose-Response Relationship, Drug	2000
Valproate and other anticonvulsants for psychiatric disorders. The Medical letter on drugs and therapeutics, 2000, Dec-11, Volume: 42, Issue:1094 Topics: Abnormalities, Drug-Induced; Acetates; Adult; Amines; Anti-Anxiety Agents; Anticonvulsants; Bipolar	2000
Effects of antiepileptic drugs on cognition. Epilepsia, 2001, Volume: 42 Suppl 1 Topics: Acetates; Amines; Anticonvulsants; Carbamazepine; Cognition; Cognition Disorders; Cyclohexanecarboxy	2001

lamotrigine and Cognition Disorders