Transdermal estrogen patches for aggressive behavior in male patients with dementia: a randomized, controlled trial

Abstract

Objectives:To investigate the efficacy and tolerability of transdermal estrogen patches for the adjunctive treatment of aggressive behavior in male patients with advanced dementia. Methods:The study was designed as an 8-week, randomized, controlled trial in acute aged psychiatry inpatient units and specialized nursing homes in Melbourne, Australia, between 1998 and 1999. The participants were 27 men with established dementia, identified as displaying aggressive behavior not responding to treatment for at least 2 weeks prior to referral. The instruments used to measure aggressive behavior were the Rating Scale for Aggressive Behavior in the Elderly (RAGE), the Cornell Scale for Depression in Dementia (CSDD) and the Mini-mental State Examination (MMSE). Physical examination was performed and biochemistry and serum hormone concentrations were measured at baseline and at 8 weeks. Concomitant psychotropic medication use was recorded and analyzed.Results: There was no significant difference in aggressive behavior at 8 weeks, but significant "rebound" in aggressive behavior (change in scores between week 8 and week 10, p < 0.009) and benzodiazepine use in the estrogen group (p < 0.03), following removal of the patches. Only behavioral items of the CSDD improved in the experimental group (p = 0.031). The use of patches was associated with a significant rise in serum estrogen (p < 0.001) but not with a significant decrease in serum testosterone (p = 0.077). There were no adverse effects associated with their use. Conclusions:The use of transdermal estrogen yielding up to 100 µg per day was not associated with discernable improvement in aggressive behavior in men 165 166 K. A. Hall et al.with advanced dementia. Small subject numbers, multiple variables and a lack of statistical power impair interpretation of these results. However, the tolerability and apparent rebound effect on removal of patches indicate the need for larger studies in this area.

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

“…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; …”

“…Of these studies, 20 were placebo-controlled (Barnes et al ., 1982; Tariot et al ., 1998; 2001; 2005; De Deyn et al ., 1999; 2004; Katz et al ., 1999; Kyomen et al ., 1999; Street et al ., 2000; Porsteinsson et al ., 2001; Brodaty et al ., 2003; Ballard et al ., 2005; Hall et al ., 2005; Peskind et al ., 2005; Mintzer et al ., 2006; 2007; Tariot et al ., 2006; Zhong et al ., 2007; Streim et al ., 2008; Gehrman et al ., 2009; Rappaport et al ., 2009; Sommer et al ., 2009; Wang et al ., 2009), and 11 compared two medications within the same trial (Barnes et al ., 1982; Cantillon et al ., 1996; De Deyn et al ., 1999; Gaber et al ., 2001; Fontaine et al ., 2003; Ballard et al ., 2005; Tariot et al ., 2006; Verhey et al ., 2006; Holmes et al ., 2007; Huertas et al ., 2007). All of the studies used oral formulations of medications except for one trial that utilized intramuscular aripiprazole (Rappaport et al ., 2009) and one study of transdermal estrogen (Hall et al ., 2005). A total of 4,954 individuals were included with a median study sample size of 76 (range = 14–625 participants per trial).…”

“…The median trial duration was 56 days (range = 1–90 days). A variety of outcome measures were reported in studies including composite measures of NPS (Barnes et al ., 1982; Cantillon et al ., 1996; Tariot et al ., 1998; 2001; 2005; 2006; De Deyn et al ., 1999; 2004; Katz et al ., 1999; Street et al ., 2000; Porsteinsson et al ., 2001; Fontaine et al ., 2003; Peskind et al ., 2005; Gehrman et al ., 2009; Sommer et al ., 2009; Wang et al ., 2009), agitation (Gaber et al ., 2001; Ballard et al ., 2005; Verhey et al ., 2006; Holmes et al ., 2007; Zhong et al ., 2007; Rappaport et al ., 2009,), aggression (Kyomen et al ., 1999; Brodaty et al ., 2003; Hall et al ., 2005; Huertas et al ., 2007), or psychosis (Mintzer et al ., 2006; 2007; Streim et al ., 2008). …”

“…A total of 24 studies reported on trial withdrawals due to any cause (Tariot et al ., 1998; 2001; 2005; 2006; De Deyn et al ., 1999; 2004; Katz et al ., 1999; Kyomen et al ., 1999; Street et al ., 2000; Porsteinsson et al ., 2001; Brodaty et al ., 2003; Fontaine et al ., 2003; Ballard et al ., 2005; Peskind et al ., 2005; Mintzer et al ., 2006; 2007; Huertas et al ., 2007; Streim et al ., 2008; Gehrman et al ., 2009; Rappaport et al ., 2009; Sommer et al ., 2009; Wang et al ., 2009), 21 studies reported on trial withdrawals due to adverse events (Tariot et al ., 1998; 2001; 2005; 2006; Katz et al ., 1999; Kyomen et al ., 1999; Street et al ., 2000; Porsteinsson et al ., 2001; Brodaty et al ., 2003; Fontaine et al ., 2003; De Deyn et al ., 2004; Ballard et al ., 2005; Peskind et al ., 2005; Mintzer et al ., 2006; 2007; Huertas et al ., 2007; Zhong et al ., 2007; Streim et al ., 2008; Gehrman et al ., 2009; Rappaport et al ., 2009; Sommer et al ., 2009), and 23 studies reported mortality rates (Tariot et al ., 1998; 2001; 2005; 2006; Katz et al ., 1999; Kyomen et al ., 1999; Street et al ., 2000; Porsteinsson et al ., 2001; Brodaty et al ., 2003; Fontaine et al ., 2003; De Deyn et al ., 2004; Ballard et al ., 2005; Hall et al ., 2005; Peskind et al ., 2005; Mintzer et al ., 2006; 2007; Huertas et al ., 2007; Zhong et al ., 2007; Streim et al ., 2008; Gehrman et al ., 2009; Rappaport et al ., 2009; Sommer et al ., 2009; Wang et al ., 2009) (Table 1). Tr...…”

The study protocol of a cluster-randomised controlled trial of family-mediated personalised activities for nursing home residents with dementia

“…However, in cases where the causes of BPSD are less obvious, medications have variable efficacy and can lead to adverse effects such as worsened confusion and falls [4,5]. More attention is being paid, therefore, to non-pharmacological interventions that better address the needs that underpin BPSD.…”