Divalproex Sodium in Nursing Home Residents With Possible or Probable Alzheimer Disease Complicated by Agitation

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:10.1097/00019442-200511000-00004

Cited by 25 publications

(20 citation statements)

References 18 publications

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“…The 29 studies meeting inclusion criteria encompassed 19 studies of antipsychotics (Barnes et al ., 1982; Cantillon et al ., 1996; De Deyn et al ., 1999; 2004; Katz et al ., 1999; Street et al ., 2000; Gaber et al ., 2001; Brodaty et al ., 2003; Fontaine et al ., 2003; Ballard et al ., 2005; Mintzer et al ., 2006; 2007; Tariot et al ., 2006; Verhey et al ., 2006; Holmes et al ., 2007; Huertas et al ., 2007; Zhong et al ., 2007; Streim et al ., 2008; Rappaport et al ., 2009) (15 studies of atypical antipsychotics (De Deyn et al ., 1999; 2004; Katz et al ., 1999; Street et al ., 2000; Brodaty et al ., 2003; Fontaine et al ., 2003; Ballard et al ., 2005; Mintzer et al ., 2006; 2007; Tariot et al ., 2006; Verhey et al ., 2006; Holmes et al ., 2007; Zhong et al ., 2007; Streim et al ., 2008; Rappaport et al ., 2009) and seven of typical antipsychotics (Barnes et al ., 1982; Cantillon et al ., 1996; De Deyn et al ., 1999; Gaber et al ., 2001; Tariot et al ., 2006; Verhey et al ., 2006; Huertas et al ., 2007)), three studies of cholinesterase inhibitors (Tariot et al ., 2001; Ballard et al ., 2005; Holmes et al ., 2007), four studies of anticonvulsants (Tariot et al ., 1998; 2005; Porsteinsson et al ., 2001; Sommer et al ., 2009), one study of antidepressants (Gaber et al ., 2001), and seven studies evaluating medications from other classes (Cantillon et al ., 1996; Kyomen et al ., 1999; Hall et al ., 2005; Peskind et al ., 2005; Huertas et al ., 2007; Gehrman et al ., 2009; Wang et al ., 2009) (Table 1). Of these studies, 20 were placebo-controlled (Barnes et al ., 1982; Tariot et al ., 1998; 2001; 2005; De Deyn et al ., 1999; …”

Section: Resultsmentioning

confidence: 99%

Pharmacological treatments for neuropsychiatric symptoms of dementia in long-term care: a systematic review

Seitz

Gill

Herrmann

et al. 2012

Int. Psychogeriatr.

109

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Background: Medications are frequently prescribed for neuropsychiatric symptoms (NPS) associated with dementia, although information on the efficacy and safety of medications for NPS specifically in long-term care (LTC) settings is limited. The objective of this study was to provide a current review of the efficacy and safety of pharmacological treatments for NPS in LTC.Methods: We searched MEDLINE, EMBASE, PsychINFO, and the Cochrane Library for randomized controlled trials comparing medications with either placebo or other interventions in LTC. Study quality was described using the Cochrane collaboration risk of bias tool. The efficacy of medications was evaluated using NPS symptom rating scales. Safety was evaluated through rates of trial withdrawals, trial withdrawals due to adverse events, and mortality.Results: A total of 29 studies met inclusion criteria. The most common medications evaluated in studies were atypical antipsychotics (N = 15), typical antipsychotics (N = 7), anticonvulsants (N = 4), and cholinesterase inhibitors (N = 3). Statistically significant improvements in NPS were noted in some studies evaluating risperidone, olanzapine, and single studies of aripiprazole, carbamazepine, estrogen, cyproterone, propranolol, and prazosin. Study quality was difficult to rate in many cases due to incomplete reporting of details. Some studies reported higher rates of trial withdrawals, adverse events, and mortality associated with medications.Conclusions: We conclude that there is limited evidence to support the use of some atypical antipsychotics and other medications for NPS in LTC populations. However, the generally modest efficacy and risks of adverse events highlight the need for the development of safe and effective pharmacological and non-pharmacological interventions for this population.

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Section: Resultsmentioning

confidence: 99%

Pharmacological treatments for neuropsychiatric symptoms of dementia in long-term care: a systematic review

Seitz

Gill

Herrmann

et al. 2012

Int. Psychogeriatr.

109

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“…Studies have linked anticonvulsant use in the elderly with fracture [22], somnolence and thrombocytopenia [23]. In addition, although valproic acid and its derivatives have been touted for behavioral stabilization and even as potentially neuroprotective, the evidence has been lacking for such efficacy [24, 25]. …”

Section: Discussionmentioning

confidence: 99%

Risk of Mortality Among Individual Antipsychotics in Patients With Dementia

Kales¹,

Kim²,

Zivin³

et al. 2012

AJP

328

222

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Objective The use of antipsychotics to treat the behavioral symptoms of dementia is associated with increased mortality. However, there remains limited information regarding individual agents’ risks. Method This was a retrospective cohort study using national data from the US Department of Veterans Affairs (fiscal years 1999–2008) for patients ≥65 years old with dementia, beginning outpatient treatment with an antipsychotic (risperidone, olanzapine, quetiapine, and haloperidol) or valproic acid and its derivatives (as a non-antipsychotic comparison). The total sample included 33,604 patients. Individual drug groups were compared for 180-day mortality rates. Potential confounding was addressed using multivariate models and propensity adjustments. Results In covariate-adjusted intent to treat analyses, haloperidol users had the highest mortality rates (relative risk 1.54, 95% confidence interval 1.38–1.73) followed by risperidone (reference), olanzapine (RR 0.99, 95% CI 0.89–1.10), valproic acid and its derivatives (RR 0.91, 95% CI 0.78–1.06) and quetiapine (RR 0.73, 95% CI 0.67–0.80). Propensity-stratified and propensity-weighted models as well as analyses controlling for site of care and medication dosage showed similar patterns. Haloperidol risk was highest in the first 30 days and then significantly and sharply decreased. Among the other agents, mortality risk differences were most significant in the first 120 days and declined in the subsequent 60 days during 180-day follow-up. Conclusions There may be differences in mortality risks among individual antipsychotic agents. Further, the use of valproic acid and its derivatives as alternative agents to address the neuropsychiatric symptoms of dementia may carry associated risks as well.

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“…Similarly, a Cochrane Database review (Basan et al, 2004) that examined the effectiveness of valproate as an adjunct to antipsychotic medications in mixed age schizophrenia populations noted no significant effect of using valproate as an adjunct to antipsychotic therapy. Randomized, controlled trials with valproate semisodium have also been conducted to evaluate effects on behavioral symptoms in elderly dementia populations (Porsteinsson et al, 2001;Sival et al, 2002;Tariot et al, 2005). However, the findings are consistent with the relatively unpromising results across varying psychotropic compounds for symptoms of dementia (Sink et al, 2005).…”

Section: Discussionmentioning

confidence: 77%