РКИ варениклина при шизофрении

The aim of this study is to examine the effects of treatment with varenicline, a partial agonist at the α4β2 and full agonist at the α7 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=0.013) and the Wisconsin Card Sorting Test non-perseverative errors (p=0.043). Some treatment effects were different between smokers and non-smokers. In smokers, Continuous Performance Test hit reaction time (p=0.008) and Stroop Interference (p=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.

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

Нейропсихиатрические побочные эффекты варениклина

Background

Varenicline is an α4β2 partial nicotinic agonist approved for smoking cessation. There have been spontaneous postmarketing reports of neuropsychiatric adverse events (NPAEs) in smokers without a history of psychiatric illness quitting with varenicline.

Methods

One hundred ten smokers without history of psychiatric illness (screened by Structured Clinical Interview for DSM-IV) were randomized to 12 weeks of varenicline 1 mg twice daily (n = 55) or placebo. Adverse events were solicited systematically. Depressive symptoms, anxiety, aggression, and irritability were measured at baseline and weekly using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Hamilton Anxiety Scale (HAM-A), and the Overt Aggression Scale—Modified (OAS-M). The Profile of Mood States (POMS) was administered daily. Mixed-model analysis of repeated measures was conducted to compare mean changes in scores between groups across study periods.

Results

Participants' mean baseline characteristics were 33 years of age, 22 cigarettes/day and Fagerström Test for Nicotine Dependence score > 7. Reported NPAEs were similar between groups. No suicidal events were reported. There were no significant differences between groups for the MADRS (treatment difference vs. placebo = .03, 95% confidence interval [CI] −.68–.73; NS), HAM-A (treatment difference [TD] = .14, 95% CI −.62–.90; NS), OAS-M Aggression subscale (TD = .5, 95% CI −1.18–2.18; NS), OAS-M Irritability subscale (TD = .08, 95% CI −.17–.34; NS), and the POMS total scores (TD = .5, 95% CI −.52–1.53; NS).

Conclusions

There were no significant differences between groups on measures of depressive symptoms, anxiety, or aggression/hostility. Systematically solicited NPAEs were similar between the varenicline and placebo groups.

A Double-Blind Randomized Placebo-Controlled Pilot Study of Neuropsychiatric Adverse Events in Abstinent Smokers Treated with Varenicline or Placebo

Hallucinations in the Context of Varenicline Withdrawal

"Mr. A" was a 43-year-old, well-educated, healthy man with no current or previous medical or psychiatric history, including no past alcohol dependence or drug abuse. Notably, his family history was positive for schizophrenia, with one brother suffering from the illness. The patient reported smoking 10 cigarettes daily for more than 20 years. Varenicline was administered at a dose of 0.5 mg once daily for an initial period of 3 days, followed by 0.5 mg twice daily for the next 4 days. The drug was then administered at a dose of 1.0 mg twice daily.

The patient reported headaches shortly after starting varenicline. However, he was able to stop smoking after 2 weeks of treatment and therefore reduced the dose of the drug during the third week of treatment, taking only 0.5 mg once daily for 4 days. He then discontinued treatment. After taking the last tablet of varenicline on the following day, the patient began experiencing symptoms of derealization. His symptoms then progressed to visual hallucinations of unknown, distressing people who he "shooed" away. At that point, Mr. A suspected that he was having a "realistic dream." He also perceived that he had a conversation with a deceased rock star while being conscious that the person in question was actually dead. He became distressed and presented to his general practitioner, and he was started on quetiapine (50 mg at bedtime) for 10 days. The symptoms of hallucinosis rapidly disappeared. When interviewed by a psychiatrist 1 month later, the patient showed no symptoms of any psychiatric disorder, and he was not taking any medication. He had also managed to remain smoke-free.

http://ajp.psychiatryonline.org/cgi/content/short/166/5/619-a?rss=1