Adjunctive Varenicline Treatment with Antipsychotic Medications for Cognitive Impairments in People with Schizophrenia: A Randomized Double-Blind Placebo-Controlled Trial

Abstract

The aim of this study is to examine the effects of treatment with varenicline, a partial agonist at the a4b2 and full agonist at the a7 nicotine acetylcholine receptor, on cognitive impairments in people with schizophrenia. In all, 120 clinically stable people with schizophrenia participated in randomized, double-blind, placebo-controlled 8-week trial. Antipsychotic and concomitant medication doses remained fixed throughout the study. Varenicline was titrated up to 1 mg twice daily for weeks 2-8. Neuropsychological, clinical, and safety assessments were administered at baseline and weeks 1, 2, 4, and 8. In the primary analyses of neurocognitive differences at week 8, no varenicline-placebo differences were significant. In secondary longitudinal analyses, varenicline improved compared with placebo on the Digital Symbol Substitution Test (p ¼ 0.013) and the Wisconsin Card Sorting Test non-perseverative errors (p ¼ 0.043). Some treatment effects were different between smokers and non-smokers. In smokers, Continuous Performance Test hit reaction time (p ¼ 0.008) and Stroop Interference (p ¼ 0.004) were reduced for varenicline compared with placebo, while there were no treatment differences in non-smokers. No significant treatment main effects or interactions were noted for total scores on the Positive and Negative Syndrome Scale or the Scale for the Assessment for Negative Symptoms. Our findings suggest beneficial effects of adjunctive varenicline treatment with antipsychotics for some cognitive impairments in people with schizophrenia. In some cases, effects of treatment varied between smokers and non-smokers. Further study is required to assess the functional significance of these changes.

Precursors of cognitive impairments in psychotic disorders: A population-based study

“…The literature suggests that both severity of positive and negative symptoms (Hughes et al, 2003) and longer durations of untreated psychoses (Amminger et al, 2002;Lappin et al, 2007) are linked to poorer cognitive performance in first episode psychosis. Effects of antipsychotic drugs on cognitive performance in patients with schizophrenia are not entirely clear: while some studies found positive effects (Selva-Vera et al, 2010;Shim et al, 2012) others found either no effects (Remillard et al, 2008;Kelly et al, 2009) or effects varying by type of medication (conventional/atypical) (Müller et al, 2005). Fourth, the individuals in our sample were all males.…”

Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders

“…Indeed, the α4β2 nAChR agonist, AZD3480, is in Phase II clinical trials for Alzheimer's disease (http://clinicaltrials.gov/show/NCT01466088). The partial α4β2 nAChR agonist and full α7 nAChR agonist varenicline was shown to have a beneficial effects on cognition in patients with schizophrenia when used in addition to antipsychotic drug treatment (Shim et al, 2012). …”

Varenicline for smoking cessation and reduction in people with severe mental illnesses: systematic review and meta-analysis

“…Full-text assessments of the remaining 11 potentially relevant articles excluded a further three studies [37][38][39]. A total of eight studies (398 participants) met the selection criteria and were included in the analysis [40][41][42][43][44][45][46][47]. The included studies were published between 2011 and 2014.…”

“…Three studies explored the effectiveness of varenicline alone, and the remaining studies evaluated varenicline in combination with individual behavioural interventions [42, 44,47]. The duration of the varenicline treatment varied between eight and twelve weeks, and 81% of participants treated with varenicline completed the treatment, compared with 82% in placebo groups.…”

“…Amongst the studies included in this review, a majority of studies reported no significant difference between varenicline and control groups in terms of neuropsychiatric events in people with SMIs [40][41][42][44][45]47]. Only one study reported a significantly increased risk of suicidal ideation in the varenicline group (one case) compared with the placebo group (no cases) [43].…”