Cognitive Functioning in Bipolar Patients Receiving Lamotrigine

Daban, Claire; Martínez‐Arán, Anabel; Torrent, Carla; Sánchez-Moreno, José; Goikolea, José Manuel; Benabarre, Antonio; Comes, Mercè; Colom, Francesc; Vieta, Eduard

doi:10.1097/01.jcp.0000204332.64390.f3

Cited by 49 publications

(25 citation statements)

References 26 publications

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“…In healthy controls (Aldenkamp et al, 2002) and in animal models (Shannon and Love, 2004) lamotrigine appears to be associated with no significant changes in cognitive performance. In patients with bipolar disorder, both improvement (Daban et al, 2006) and worsening of cognitive performance (Osuji et al, 2007, in press) have been reported with lamotrigine. A study in HIV-positive patients with cocaine use reported no change in RAVLT performance with lamotrigine (Margolin et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Attenuation of the Effects of Corticosteroids on Declarative Memory with Lamotrigine

Brown

Wolfshohl

Shad

et al. 2007

Neuropsychopharmacol

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An extensive animal literature suggests that excessive corticosteroid exposure is associated with changes in memory and the hippocampus. Agents that decrease glutamate attenuate corticosteroid effects on the hippocampus. Minimal data are available on preventing or reversing corticosteroid effects on the human hippocampus. We previously reported that open-label lamotrigine was associated with significant improvement in declarative memory in corticosteroid-treated patients. We now examine the impact of 24 weeks of randomized, placebo-controlled lamotrigine therapy on declarative memory (primary aim) and hippocampal volume (secondary aim) in 28 patients (n ¼ 16 for lamotrigine, n ¼ 12 for placebo) taking prescription corticosteroids. All participants with data from at least one postbaseline assessment (n ¼ 9 for lamotrigine, n ¼ 11 for placebo) were included in the analysis. Declarative memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT) at baseline and weeks 12 and 24. Hippocampal and total brain volumes were manually traced from MRI scans obtained at baseline and week 24. On the basis of an ANCOVA analysis, total words learned on the RAVLT at exit were significantly greater in the lamotrigine group (n ¼ 8, missing data or dropouts n ¼ 8) compared to the placebo group (n ¼ 11, dropout n ¼ 1). RAVLT scores in the lamotrigine group increased from mildly impaired to average range. Hippocampal volume changes were small in both lamotrigine (n ¼ 7) and placebo (n ¼ 7) groups during the 24-week assessment period and between-group differences were not significant. Results suggest that lamotrigine may improve declarative memory in patients taking prescription corticosteroids although differential dropout rate in the two groups is a concern.

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Section: Discussionmentioning

confidence: 99%

Attenuation of the Effects of Corticosteroids on Declarative Memory with Lamotrigine

Brown

Wolfshohl

Shad

et al. 2007

Neuropsychopharmacol

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“…Lamotrigine appears to be cognitively benign 41 , whereas topiramate, which is not indicated for bipolar disorder but may be prescribed for prevention of migraine headaches or weight control, is associated with extensive adverse cognitive effects 37 .…”

Section: Challenges and Recommendations For Trial Design In Bipolar Dmentioning

confidence: 99%

Assessing Cognitive Function in Bipolar Disorder: Challenges and Recommendations for Clinical Trial Design

Burdick¹,

Ketter

Goldberg³

et al. 2015

J. Clin. Psychiatry

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OBJECTIVE Neurocognitive impairment in schizophrenia has been recognized for more than a century. In contrast, only recently have significant neurocognitive deficits been recognized in bipolar disorder. Converging data suggest the importance of cognitive problems in relation to quality of life in bipolar disorder, highlighting the need for treatment and prevention efforts targeting cognition in bipolar patients. Future treatment trials targeting cognitive deficits will be met with methodological challenges due to the inherent complexity and heterogeneity of the disorder, including significant diagnostic comorbidities, the episodic nature of the illness, frequent use of polypharmacy, cognitive heterogeneity, and a lack of consensus regarding measurement of cognition and outcome in bipolar patients. Guidelines for use in designing future trials are needed. PARTICIPANTS The members of the consensus panel (each of the bylined authors) were selected based upon their expertise in bipolar disorder. Dr. Burdick is a neuropsychologist who has studied cognition in this illness for 15 years; Drs. Ketter, Calabrese, and Goldberg each bring considerable expertise in the treatment of bipolar disorder both within and outside of controlled clinical trials. This consensus statement was derived from work together at scientific meetings (e.g. symposium presention at the 2014 Annual meeting of the American Society of Clinical Psychopharmacology, among others) and ongoing discussions by conference call. With the exception of the public presentations on this topic, these meetings were closed to outside participants. EVIDENCE A literature review was undertaken by the authors to identify illness-specific challenges relevant to the design and conduct of treatment trials targeting neurocognition in bipolar disorder. Expert opinion from each of the authors guided the consensus recommendations. CONSENSUS PROCESS Consensus recommendations, reached by unanimous opinion of the authors, are provided here as a preliminary guide for future trial design. Recommendations comprise exclusion of certain syndromal level comorbid diagnoses and current affective instability, restrictions on numbers and types of medications, and use of pre-screening assessment to ensure enrollment of subjects with adequate objective evidence of baseline cognitive impairment. CONCLUSIONS Clinical trials to address cognitive deficits in bipolar disorder face distinctive design challenges. As such trials move from proof-of-concept to confirmation of clinical efficacy, it will be important to incorporate distinctive design modifications to adequately address these challenges and increase the likelihood of demonstrating cognitive remediation effects. The field is now primed to address these challenges and a comprehensive effort to formalize best practice guidelines will be a critically important next step.

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“…Changes in brain activation during working memory and facial recognition tasks in patients with bipolar disorder with LMG monotherapy have been reported (Haldane et al, 2008). Preliminary results suggest a safer neurocognitive profile of LMG on bipolar patients, as compared with other anticonvulsants (Daban et al, 2006).…”

Section: Discussionmentioning

confidence: 96%

Lamotrigine, a mood stabilizer, may have beneficial effects on memory acquisition and retrieval in mice

et al. 2012

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Cognitive Functioning in Bipolar Patients Receiving Lamotrigine

Cited by 49 publications

References 26 publications

Attenuation of the Effects of Corticosteroids on Declarative Memory with Lamotrigine

Attenuation of the Effects of Corticosteroids on Declarative Memory with Lamotrigine

Assessing Cognitive Function in Bipolar Disorder: Challenges and Recommendations for Clinical Trial Design

Lamotrigine, a mood stabilizer, may have beneficial effects on memory acquisition and retrieval in mice

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