Citalopram, in European studies, has shown some early promise for treatment of poststroke depression and behavioral complications of dementia. An open pilot study of citalopram was conducted in 16 patients with dementia and behavioral disturbances. Citalopram was well tolerated by 13 of the patients, and 9 had a clinically impressive response. A significant overall mean reduction in disruptive vocalizations was observed by means of a novel technique of computer-assisted real-time observation. The mean citalopram plasma level-to-dose ratio was found to be twice that previously reported in younger patients. These pilot findings should encourage future placebo concentration-controlled trials.
"Evidence to support the use of alternative agents remains scarce. Our group has reported on the efficacy of the selective serotonin reuptake inhibitor (SSRI) citalopram in one open (Pollock et al., 1997) and two double-blind randomized trials: one placebo-controlled (Pollock et al., 2002) and one with risperidone as the active comparator (Pollock et al., 2007). However, the clinical utility of SSRIs has yet to be confirmed. "
[Show abstract][Hide abstract] ABSTRACT: The risk/benefit ratio of pharmacotherapy for behavioral symptoms of dementia is questionable: second-generation antipsychotics are poorly tolerated, and the efficacy of alternative treatments, for example, selective serotonin-reuptake inhibitors (SSRIs), is uncertain. Biomarkers of treatment response may improve this risk/benefit ratio. The length polymorphism of the serotonin transporter promoter gene (5-HTTLPR/SLC6A4) may moderate tolerability of SSRIs and expression of behavioral symptoms in dementia. We assessed the effect of 5-HTTLPR on tolerability and efficacy of citalopram and risperidone in a 12-week randomized controlled trial, which included nondepressed patients with dementia hospitalized for behavioral or psychotic symptoms. Genotypes including the A/G polymorphism of the L allele (rs25531) were determined in 92 of 103 participants. We used pattern-mixture models to account for dropout. Low-expression alleles (S and Lg) predicted greater early and overall side effects of citalopram and early treatment discontinuation. These results remained unchanged after excluding African-American participants and in covariate analyses. Unexpectedly, low-expression alleles seemed to predict greater early side effects of risperidone (but not early discontinuation) and poorer early response of psychosis symptoms to risperidone. In conclusion, 5-HTTLPR may be a useful biomarker of SSRI intolerance in dementia. Our findings of intolerance of a second-generation antipsychotics and persistence of psychosis in patients with low-expression alleles needs to be replicated.
International clinical psychopharmacology 01/2010; 25(1):37-45. DOI:10.1097/YIC.0b013e328333ee10 · 2.46 Impact Factor
"There are some reports showed serotoninergic psychotropic agents like trazadone, citalopram, or paroksetin could be useful in treatment of agitation (Pollock et al 1997; Ramadan 2000). In our opinion, mirtazapine could make a step forward for previously studied agents. "
[Show abstract][Hide abstract] ABSTRACT: Agitation is one of the most devastating behavioral symptoms in demented patients but there is little evidence about effective and safe pharmacotherapy. We aimed to determine the effectiveness and safety of mirtazapine in treatment of agitated patients with Alzheimer's disease (AD). The consecutive patients with AD who have significant agitation were assigned to a 12-week open-label, prospective study. Patients received mirtazapine 15-30 mg/day. The changes in Cohen-Mansfield Agitation Inventory-Short form (CMAI-SF) scores were primary outcome measurement. The change in Clinical Global Impression-Severity scale (CGI-S) scores and tolerability-safety profile were the secondary efficacy variables. Thirteen of 16 (81.25%) patients completed the study. There was a significant reduction in CMAI-SF and CGI-S between the pre- and post-treatment with mirtzapaine (p < 0.001). The mean baseline score was 26.54 ( +/- 5.4) and mean reduction was 10.6 ( +/- 7.5) in CMAI-SF. There was no significant side effect and cognitive deterioration. The results of this open-label pilot study suggest that mirtazapine may be an effective choice for treatment of agitated patients with AD.
"The in vivo functional significance of underlying dysfunctions in serotonergic neurotransmission with respect to behaviors and their potential for treatment is unknown. Open label trial treatment with selective serotonin reuptake inhibitors (SSRIs) such as alaproclate (Bergman et al. 1983), sertraline (Burke et al. 1997; Burke et al. 1994) and citalopram (Pollock et al. 1997), and the 5-HT 1A partial agonist buspirone (Herrmann and Eryavec 1993) have been associated with improvements in BPSD in a high proportion of patients. Randomized controlled trials with the SSRIs (Auchus and Bissey-Black 1997; Burke et al. 1994; Cutler et al. 1985; Dehlin et al. 1985; Katona et al. 1998; Lanctôt et al. 2002; Nyth and Gottfries 1990; Olafsson et al. 1992; Pollock et al. 2002; Taragano et al. 1997), buspirone (Cantillon et al. 1996; Lawlor et al. 1994) and the serotonin norepinephrine reuptake inhibitor trazodone (Lawlor et al. 1994; Sultzer et al. 1997) have also been performed for the treatment of BPSD with more equivocal results. "
[Show abstract][Hide abstract] ABSTRACT: The clinical correlates of reduced serotonin (5-HT) in Alzheimer's disease (AD) remain unknown. The hypothesis of this study was that altered central serotonergic activity is related to aggression in AD. Twenty-two institutionalized, nondepressed elderly (12 M/10 F, mean age +/- SD: 82.2 +/- 6.4) with probable AD, severe cognitive impairment (MMSE = 4.1 +/- 4.7) and significant behavioral disturbance (Neuropsychiatric Inventory (NPI) score > or = 8) were studied. The prolactin (PRL) response to d,l-fenfluramine (60 mg p.o.) was used as an index of central serotonergic function. The NPI aggression score, NPI irritability score, and Behavioral Pathology in AD aggression score were positively correlated to prolactin concentrations following fenfluramine challenge (r(S) =.61, p =.003; r(S) =.53, p =.012; and r(S) =.47, p =.029 respectively). In addition, aggressive patients showed a greater mean PRL increase (% baseline) (215 +/- 60, n = 11) than nonaggressive subjects (123 +/- 54, n = 11) (p =.01, 2-tailed t-test). The change in PRL concentration depended on level of cognitive impairment (p =.0004) and the gender x aggression interaction (p =.015) with the overall regression model accounting for 74% of the variance (r = 0.86, F = 11.9, p =.0001). Female aggressive subjects with less cognitive impairment had the largest response to fenfluramine challenge. These results suggest a complex link between aggression in AD and central serotonergic dysfunction having interactions with gender and cognitive impairment.
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