Annotated Abstracts of Journal Articles
2014, 1st Quarter
Annotations by Lydia Chwastiak, MD, MPH, FAPM and Oliver Freudenreich, MD, FAPM
Evins AE, Cather C, Pratt SA, Pachas GN, Hoeppner SS, Goff DC, et al
JAMA 2014 Jan 8; 311(2):145-54
ANNOTATION (Chwastiak & Freudenreich)
The Finding: This double-blind, placebo controlled RCT demonstrated the efficacy of 52 weeks of varenicline for relapse prevention among adults with serious mental illness who had stopped smoking after an initial 12 weeks of treatment with varenicline and CBT. The point prevalence of abstinence at 1 year was 3 times higher among those assigned to maintenance varenicline treatment (60%) than among those assigned to placebo (19%).
Strength and Weaknesses: A major strength of the study was the generalizability of the findings: the trial was conducted at 10 community mental health centers in several states. Also, there was exclusion criteria based on antipsychotic pharmacotherapy (all were included) and few based on the severity of mental illness (those with imminent suicidality or homicidality were excluded). Approximately 60% of the sample had severe nicotine dependence (more than 20 cigarettes daily) at baseline.
A potential limitation is the relatively small sample size, as 203 patients entered the open-label 12-week treatment trial, and 87 participants achieved abstinence at 12 weeks and were randomized to the relapse prevention RCT. 26 randomized participants dropped out before the end of the relapse prevention phase (but in the analyses, these were considered to have relapsed—so findings are quite robust).
Weaknesses of the study include its cross-sectional design, which provides no information about temporal relationship between exposure and outcome. The relatively small numbers of patients on specific medications provided limited statistical power to detect associations with long QT, and precluded the evaluation of dose-related effects. Finally, associations based on data collected from inpatients may not reflect associations in the general population.
Relevance: Standard courses of pharmacotherapy (12 weeks) are effective for smoking cessation among patients with serious mental illness, but most patients who attain abstinence after 12 weeks relapse rapidly after discontinuation of pharmacotherapy. This is the first RCT of maintenance pharmacotherapy for the prevention of relapse to smoking among patients with SMI. This suggests a change is needed in the approach to smoking cessation treatment among patients with SMI.
Importance: It is estimated that more than half of those with serious mental illness smoke tobacco regularly. Standard courses of pharmacotherapeutic cessation aids improve short-term abstinence, but most who attain abstinence relapse rapidly after discontinuation of pharmacotherapy.
Objective: To determine whether smokers diagnosed with schizophrenia and bipolar disease have higher rates of prolonged tobacco abstinence with maintenance pharmacotherapy than with standard treatment.
Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, parallel-group, relapse-prevention clinical trial conducted in 10 community mental-health centers. Of 247 smokers with schizophrenia or bipolar disease recruited from March 2008-April 2012, 203 received 12-weeks’ open-label varenicline and cognitive behavioural therapy and 87 met abstinence criteria to enter the relapse prevention intervention.
Interventions: Participants who had 2 weeks or more of continuous abstinence at week 12 of open treatment were randomly assigned to receive cognitive behavioral therapy and double-blind varenicline (1 mg, 2 per day) or placebo from weeks 12 to 52. Participants then discontinued study treatment and were followed up to week 76.
Main Outcomes and Measures: Seven-day rate of continuous abstinence at study week 52, the end of the relapse-prevention phase, confirmed by exhaled carbon monoxide. Secondary outcomes were continuous abstinence rates for weeks 12 through 64 based on biochemically verified abstinence and weeks 12 through 76, based on self-reported smoking behavior.
Results: Sixty-one participants completed the relapse-prevention phase; 26 discontinued participation (7 varenicline, 19 placebo) and were considered to have relapsed for the analyses; 18 of these had relapsed prior to dropout. At week 52, point-prevalence abstinence rates were 60% in the varenicline group (24 of 40) vs 19% (9 of 47) in the placebo group (odds ratio [OR], 6.2; 95%CI, 2.2-19.2; P < .001). From weeks 12 through 64, 45%(18 of 40) among those in the varenicline group vs 15%(7 of 47) in the placebo group were continuously abstinent (OR, 4.6; 95%CI, 1.5-15.7; P = .004), and from weeks 12 through 76, 30% (12 of 40) in the varenicline group vs 11% (5 of 47) in the placebo group were continuously abstinent (OR, 3.4; 95%CI, 1.02-13.6; P = .03). There were no significant treatment effects on psychiatric symptom ratings or psychiatric adverse events.
Conclusions and Relevance: Among smokers with serious mental illness who attained initial abstinence with standard treatment, maintenance pharmacotherapy with varenicline and cognitive behavioral therapy improved prolonged tobacco abstinence rates compared with cognitive behavioral therapy alone after 1 year of treatment and at 6 months after treatment discontinuation.
ANNOTATION (Chwastiak & Freudenreich)
The Finding: Personal health records shift the ownership and the locus of health information from being scattered across multiple providers to the patient. An increasing number of studies suggest that personal health records can improve rates of routine preventive services in general medical populations. This study demonstrates that clinically complex and socially disadvantaged patients with serious mental illness can derive similar benefits.
Strength and Weaknesses: Strengths of the study include that the intervention (My Health Record) was based on a widely-used community-based personal health record, that was carefully adapted for the unique needs of patients with SMI (e.g., adding a section on mental health goals and a mental health advanced directive). Limitations of the study include that it was conducted at a single community mental health center, and that it was only included the subset of patients who had a regular mental health and medical provider.
Relevance: Personal health records may provide a relatively low-cost strategy for improving the medical care for patients with serious mental illness who have comorbid chronic medical illnesses. Recent advances in rapidly evolving health care technology may provide even more useful and scalable technology than the personal health record evaluated in this study.
Objective: The authors evaluated the effect of an electronic personal health record on the quality of medical care in a community mental health setting.
Method: A total of 170 individuals with a serious mental disorder and a comorbid medical condition treated in a community mental health center were randomly assigned to either a personal health record or usual care. One-year outcomes assessed quality of medical care, patient activation, service use, and health-related quality of life.
Results: Patients used the personal health record a mean of 42.1 times during the 1-year intervention period. In the personal health record group, the total proportion of eligible preventive services received increased from 24% at baseline to 40% at the 12-month follow-up, whereas it declined in the usual care group, from 25% to 18%. In the subset of patients with one or more cardiometabolic conditions (N=118), the total proportion of eligible services received improved by 2 percentage points in the personal health record group and declined by 11 percentage points in the usual care group, resulting in a significant difference in change between the two groups. There was an increase in the number of outpatient medical visits, which appeared to explain many of the significant differences in the quality of medical care.
Conclusions: Having a personal health record resulted in significantly improved quality of medical care and increased use of medical services among patients. Personal health records could provide a relatively low-cost scalable strategy for improving medical care for patients with comorbid medical and serious mental illnesses.
ANNOTATION (Chwastiak & Freudenreich)
The Finding: This survival analysis of a Danish nationwide cohort which included 40,000 individuals with schizophrenia, followed 4 million people from 1987 until 2010, death, emigration from Denmark, or onset of an autoimmune disease. Individuals with schizophrenia had 53% increase in the risk of subsequent diagnosis of one or more autoimmune disease. For individuals with schizophrenia who also had hospital contact for infections, the risk of autoimmune disease was 2.70.
Strength and Weaknesses: The major strength of the paper is the dataset, which is from the Danish Civil Registration System. The sample for the study was very large (including a large number of individuals with schizophrenia), and nationally representative.
A limitation is that some unmeasured factors may also be at play. Smoking and alcohol use, increased among individuals with schizophrenia, may increase risk of autoimmune disorders. Psychological stress may also be a trigger. The paper raises the interesting suggestion of a biological interaction between schizophrenia and infectious disease in increasing the risk of developing an autoimmune disease, but these analyses cannot determine the nature of this (i.e., whether infection might be a common risk factor for both schizophrenia and autoimmune disorders).
Relevance: Previous studies have demonstrated an increased risk of psychotic disorders among individuals with autoimmune disorders. This study used large population-based national registries from Denmark to demonstrate the reverse temporal direction: patients with schizophrenia are at increased risk of incident autoimmune disorders.
Objective: Previous research has found an increased risk of schizophrenia in individuals with autoimmune diseases and smaller but significant associations with a family history of autoimmune diseases. This study investigates, for the first time, the association between schizophrenia and subsequent autoimmune diseases (the reverse temporality) and also considers the effect of infections, a possible risk factor for both schizophrenia and autoimmune diseases.
Method: Danish nationwide registers were linked to establish a cohort of 3.83 million people, identifying 39,364 individuals with schizophrenia-like psychosis and 142,328 individuals with autoimmune disease. Data were analyzed using survival analysis and adjusted for calendar year, age, and sex.
Results: Individuals with schizophrenia had an elevated risk of subsequent autoimmune diseases, with an incidence rate ratio of 1.53 (95% CI=1.46–1.62). Among persons without hospital contacts for infections, the effect of having schizophrenia was smaller, with an increased incidence rate ratio of 1.32 (95% CI=1.22–1.43) for autoimmune diseases. For individuals with schizophrenia as well as hospital contacts for infections, the combined risk of autoimmune diseases was 2.70 (95% CI=2.51–2.89). A family history of schizophrenia slightly increased the overall risk of developing autoimmune diseases (incidence rate ratio=1.06, 95% CI=1.02–1.09). Autoimmune diseases developed subsequently in 3.6% of people with schizophrenia, and 3.1% of people with autoimmune diseases had a family history of schizophrenia.
Conclusions: The increased risk of subsequent autoimmune diseases in individuals with schizophrenia may involve neuropsychiatric manifestations from the undiagnosed autoimmune disease, medical treatment or lifestyle associated with schizophrenia, or common etiological mechanisms, such as infections and shared genetic factors.