Divalproex Sodium in Nursing Home Residents With Possible or Probable Alzheimer Disease Complicated by Agitation: A Randomized, Controlled Trial

Tariot, Pierre N.; Raman, Rema; Jakimovich, Laura; Schneider, Lon S.; Porsteinsson, Anton P.; Thomas, Ronald G.; Mintzer, Jacobo; Brenner, Ronald; Schafer, Kimberly; Thal, Leon J.

doi:10.1176/appi.ajgp.13.11.942

Cited by 57 publications

(54 citation statements)

References 19 publications

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“…These results are consistent with previous RCTs that showed no statistically significant benefits for valproate on primary outcome measures [11][12][13]19] , though 3 [11][12][13] showed efficacy for some secondary measures. Despite potential benefits of modulating GABA to treat BPSD [20,21] , our study adds to the mounting evidence suggesting lack of efficacy for valproate in AD patients with agitation and aggression.…”

Section: Discussionsupporting

confidence: 92%

A Placebo-Controlled Trial of Valproate for Agitation and Aggression in Alzheimer’s Disease

Herrmann

Lanctôt²,

Rothenburg³

et al. 2006

Dement Geriatr Cogn Disord

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Background/Aims: To assess the efficacy and tolerability of valproate for the treatment of agitation and aggression in moderate-to-severe Alzheimer’s disease (AD). Methods: This was a randomized, double-blind, placebo-controlled crossover trial of valproate in institutionalized AD patients. Patients were assessed with the Neuropsychiatric Inventory (NPI) and Cohen-Mansfield Agitation Inventory at baseline and after 6 weeks of treatment with valproate and placebo, with 2 weeks between phases to allow for placebo washout and tapering. Results: Fourteen patients (8 male/6 female) aged 85.6 ± 4.5 years with baseline Mini Mental State Examination scores of 4.5 ± 4.6 and NPI agitation/aggression scores of 6.4 ± 3.5 were randomized to treatment. NPI agitation/aggression treatment change scores significantly worsened during valproate treatment compared with placebo (Z = –2.03, p = 0.04). Tolerability of valproate was also poor, with patients experiencing a significantly greater mean number of adverse events during valproate therapy compared to placebo (Z = –2.82, p = 0.005). Conclusion: Valproate is not effective for the management of agitation in moderate-to-severe AD, and may be poorly tolerated in this population.

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Section: Discussionsupporting

confidence: 92%

A Placebo-Controlled Trial of Valproate for Agitation and Aggression in Alzheimer’s Disease

Herrmann

Lanctôt²,

Rothenburg³

et al. 2006

Dement Geriatr Cogn Disord

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“…The excluded articles referred to 6 clinical studies on mood stabilizers in all types of dementia but not limited to the Alzheimer type [7][8][9][10][11][12] , 2 open studies [13,14] , and 2 studies with insufficient data for analysis [15,16] . Five studies met our inclusion criteria [17][18][19][20][21] . One of these trials originated from Canada [17] , one from England [18] , and the other three originated from the United States [19][20][21] .…”

Section: Study Descriptionmentioning

confidence: 99%

“…Five studies met our inclusion criteria [17][18][19][20][21] . One of these trials originated from Canada [17] , one from England [18] , and the other three originated from the United States [19][20][21] . With regard to drug, there were one trial of valproate [17] , two of divalproex sodium [20,21] , one of carbamazepine [19] , and one of lithium [18] .…”

Section: Study Descriptionmentioning

confidence: 99%

A meta-analysis of mood stabilizers for Alzheimer’s disease

Xiao

Cao

et al. 2010

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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The objective of this study was to assess the clinical evidence for or against mood stabilizers as a treatment for Alzheimer's disease (AD). We searched 5 databases from their inception to January 2010. Five randomized clinical trials of mood stabilizers to treat human patients suffering from AD were included. These trials assessed the effectiveness of mood stabilizers as an adjunct treatment to conventional anti-dementia drugs on behavioral and psychological symptoms, especially on agitation. Methodological quality was assessed using the Jadad score. The results suggested a significant effect in favor of placebo on the Mini-Mental Status Examination [n=270, weight mean difference (WMD), -0.89; 95% confidence intervals (CIs) -1.69 to -0.09, P=0.03] and on the Neuropsychiatric Inventory total (NPI total) (n=51, WMD, 3.71; 95% CIs 0.15 to 7.26, P=0.04). There were no significant differences in change scores on total Brief Psychiatric Rating Scale (BPRS total), NPI/BPRS agitation, Cohen-Mansfield Agitation Inventory total and Physical Self Maintenance Scale between mood stabilizers and placebo. Only one of these studies was free of methodological limitations (Jadad score=5). In conclusion, based on the existing evidence, mood stabilizers are ineffective or even harmful as a treatment for AD.

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“…It has also been studied for possible anti-agitation effects in Alzheimer disease (AD). 1 There are no widely accepted or clearly effective drug therapies for behavioral management in AD.…”

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confidence: 99%

Chronic divalproex sodium use and brain atrophy in Alzheimer disease

et al. 2011

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Objective:We evaluated the effect of the divalproex sodium formulation of valproic acid on brain volumes using MRI in people with mild to moderate Alzheimer disease (AD) and assessed for changes associated with behavioral and cognitive effects.Methods: Eighty-nine of 313 participants randomized to divalproex or placebo in a 24-month, parallel-group trial received MRI scans at baseline and 12 months. Interval MRI annual percent changes in whole brain, ventricular, and hippocampal volumes were the primary outcomes of interest. Change from baseline in clinical outcomes was assessed at 6-month intervals.Results: There were no baseline differences between active treatment and placebo groups in age, education, brain volumes, clinical rating scores, or APOE ⑀4 carrier status. The group treated with divalproex showed a greater rate of decline in left and right hippocampal and brain volumes (Ϫ10.9% and Ϫ12.4% vs Ϫ5.6% and Ϫ6.3%, and Ϫ3.5% vs Ϫ1.4%, respectively), and a greater rate of ventricular expansion (24.5% vs 9.9%) (p Ͻ 0.001). Mini-Mental State Examination scores showed a more rapid decline with divalproex through month 12 (placebo ϭ Ϫ2.0 Ϯ 4.3, divalproex ϭ Ϫ3.9 Ϯ 4.0) (p ϭ 0.037), although there were no changes on other cognitive, behavioral, or functional ratings at 12 and 24 months.

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Divalproex Sodium in Nursing Home Residents With Possible or Probable Alzheimer Disease Complicated by Agitation: A Randomized, Controlled Trial

Cited by 57 publications

References 19 publications

A Placebo-Controlled Trial of Valproate for Agitation and Aggression in Alzheimer’s Disease

A Placebo-Controlled Trial of Valproate for Agitation and Aggression in Alzheimer’s Disease

A meta-analysis of mood stabilizers for Alzheimer’s disease

Chronic divalproex sodium use and brain atrophy in Alzheimer disease

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