Cognitive effects with rivastigmine augmentation of risperidone: A 12-month, randomized, double-blind, placebo-controlled study in schizophrenia

Abstract

Objective:An important challenge in schizophrenia therapeutics is to develop an efficacious treatment for cognitive impairment. Acetylcholinesterase inhibitors, such as rivastigmine, have been studied for improving cognitive performance in these patients.Materials and Methods:Rivastigmine (uptitrated to 6 mg/day) was given as an add-on therapy to risperidone-treated stable schizophrenia patients in a randomized, double-blind, placebo-controlled design. Of 67 patients who met eligibility criteria, 55 were recruited into the study. Twenty-eight were assigned to rivastigmine and 27 to placebo. These patients completed tests of attention, executive functioning, verbal skills, verbal and visuospatial working memory, and psychomotor speed on five occasions: at baseline, and at the end of the 1st, 3rd, 6th, and 12th months.Results:The groups were similar in terms of sociodemographic profile and baseline clinical characteristics (Positive and Negative Syndrome Scale and Clinical Global Impression-Severity). Contrary to expectations, rivastigmine patients showed poorer outcomes on several cognitive measures. Rivastigmine patients experienced also more psychological as well as neurological side effects. Core psychopathology ratings, however, did not differ between rivastigmine and placebo groups.Conclusions:Our study does not support the long-term use of rivastigmine as an augmentation agent in schizophrenia. Rivastigmine may be associated with higher incidence of psychological and neurological side effects in patients with schizophrenia.

Cognitive improvement of acetylcholinesterase inhibitors in schizophrenia

“…There was no statistical heterogeneity among effect estimates (Chi 2 =9.12 on 7 d.f., p value=0.24, I 2 =23%) (Figure 3(c)). The most conservative pooled effect size (SMD −0.33, 95% CI −0.64 to −0.02, p value=0.02) was obtained after deleting the study of Kumar et al (2017). The prediction interval of the effect was −1.05–0.20.…”

“…We included in this systematic review nine studies that compared antipsychotics plus AChE inhibitors versus antipsychotics plus placebo. Five studies used donepezil (Akhondzadeh et al, 2008; Freudenreich et al, 2005; Lee et al, 2007; Tuğal et al, 2004; Zhu et al, 2014), three studies used galantamine (Buchanan et al, 2008; Dyer et al, 2008; Lee and Kim, 2005) and one study used rivastigmine (Kumar et al, 2017). The sample size of the studies ranges from 12–86 participants, with a median of 30 participants for study.…”

“…Overall, the risk of bias was rated as unclear for all outcomes. Finally, we considered Kumar et al (2017) presented an unclear risk of bias. This study did not show imbalance at baseline in clinical prognostic variables (illness and treatment duration), but comparison groups differed in the mean age that was higher for the rivastigmine intervention (42.8 years) than for the placebo intervention (37.3 years).…”

“…Moreover, the majority of trials did not present a length of treatment beyond 12 weeks, thus the evidence gathered represents the likely effects of the intervention in acute treatment but not in chronic administration conditions that are more relevant regarding a chronic disease such as schizophrenia. Only one study provided information beyond 12 weeks on treatment (Kumar et al, 2017). It provided information at 12, 24 and 48 weeks.…”

“…Of the nine studies included in this review, three were included in Chouinard et al (2007) review, six were included in Ribeiz et al (2010) review, six were included in Choi et al (2013) review, and seven were included in Singh et al (2012) review. Our review has updated the set of trials by including two trials published after the date of publication of previous reviews (Kumar et al, 2017; Zhu et al, 2014). The overall results with and without these two trials are quite similar: speed of processing (all outcomes) SMD=−0.52, p value=0.0002 versus SMD=−0.51, p value=0.001 without the study of Zhu et al (2014); speed of processing (TMT-A) MD=−9.59 s, p value=0.02 versus MD=−13.78 s, p value=0.03 without the study of Zhu et al (2014).…”