Marcia Valenstein

The expert consensus guideline series

Abstract Over the past decade, many new epilepsy treatments have been approved in the United States, promising better quality of life for many with epilepsy. However, clinicians must now choose among a growing number of treatment options and possible combinations. Randomized clinical trials (RCTs) form the basis for evidence-based decision making about best treatment options, but they rarely compare active therapies, making decisions difficult. When medical literature is lacking, expert opinion is helpful, but may contain potential biases. The expert consensus method is a new approach for statistically analyzing pooled opinion to minimize biases inherent in other systems of summarizing expert opinion. We used this method to analyze expert opinion on treatment of three epilepsy syndromes (idiopathic generalized epilepsy, symptomatic localization-related epilepsy, and symptomatic generalized epilepsy) and status epilepticus. For all three syndromes, the experts recommended the same general treatment strategy. As a first step, they recommend monotherapy. If this fails, a second monotherapy should be tried. Following this, the experts are split between additional trials of monotherapy and a combination of two therapies. If this fails, most agree the next step should be additional trials of two therapies, with less agreement as to the next best step after this. One exception to these recommendations is that the experts recommend an evaluation for epilepsy surgery after the third failed step for symptomatic localization-related epilepsies. The results of the expert survey were used to develop user-friendly treatment guidelines concerning overall treatment strategies and choice of specific medications for different syndromes and for status epilepticus.

Pharmacy data identify poorly adherent patients with schizophrenia at increased risk for admission.

Background. Health care organizations may be able to use pharmacy data to identify patients with schizophrenia and poor antipsychotic adherence. Objective. To determine whether a pharmacy-based measure of outpatient adherence, the medication possession ratio (MPR), is associated with adverse outcomes among patients with schizophrenia, as evidenced by increased psychiatric admission. Research Design. Cohort study linking pharmacy and utilization data for veterans with schizophrenia. MPRs were calculated by dividing the number of days’ supply of antipsychotic medication the veteran had received by the number of days’ supply they needed to receive to take their antipsychotic continuously. Using multivariate regression, the relationship between MPRs and psychiatric admission was examined. Subjects. Sixty-seven thousand seventy-nine veterans who received a diagnosis of schizophrenia and had outpatient antipsychotic medication fills between October 1, 1998 and September 30, 1999. Results. Patients with MPRs close to 1.0 had the lowest rates of admission. As patients secured progressively smaller proportions of required antipsychotic medication (and had smaller MPRs), rates of admission climbed. Among patients on one antipsychotic (n = 49,003), patients with poor adherence (MPRs < 0.8) were 2.4 times as likely to be admitted as patients with good adherence (MPRs from 0.8–1.1). 23% of poorly adherent patients but only 10% of adherent patients were admitted. Once admitted, poorly adherent patients had more hospital days. Patients who received excess medication also had higher admission rates. Conclusions. Many health care systems may be able to use pharmacy data to identify poorly adherent patients with schizophrenia. These patients are at-risk for admission and may benefit from intervention.

Risk of mortality among individual antipsychotics in patients with dementia.

OBJECTIVE The use of antipsychotics to treat the behavioral symptoms of dementia is associated with greater mortality. The authors examined the mortality risk of individual agents to augment the limited information on individual antipsychotic risk. METHOD The authors conducted a retrospective cohort study using national data from the U.S. Department of Veterans Affairs (fiscal years 1999-2008) for dementia patients age 65 and older who began outpatient treatment with an antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) or valproic acid and its derivatives (as a nonantipsychotic comparison). The total sample included 33,604 patients, and individual drug groups were compared for 180-day mortality rates. The authors analyzed the data using multivariate models and propensity adjustments. RESULTS In covariate-adjusted intent-to-treat analyses, haloperidol was associated with the highest mortality rates (relative risk=1.54, 95% confidence interval [CI]=1.38-1.73) followed by risperidone (reference), olanzapine (relative risk=0.99, 95% CI=0.89-1.10), valproic acid and its derivatives (relative risk=0.91, 95% CI=0.78-1.06), and quetiapine (relative risk=0.73, 95% CI=0.67-0.80). Propensity-stratified and propensity-weighted models as well as analyses controlling for site of care and medication dosage revealed similar patterns. The mortality risk with haloperidol was highest in the first 30 days but decreased significantly and sharply thereafter. Among the other agents, mortality risk differences were most significant in the first 120 days and declined in the subsequent 60 days during follow-up. CONCLUSIONS There may be differences in mortality risks among individual antipsychotic agents used for treating patients with dementia. The use of valproic acid and its derivatives as alternative agents to address the neuropsychiatric symptoms of dementia may carry associated risks as well.

Suicide mortality among patients receiving care in the veterans health administration health system.

Understanding and reducing mortality from suicide among veterans is a national priority, particularly for individuals receiving care from the US Veterans Health Administration (VHA). This report examines suicide rates among VHA patients and compares them with rates in the general population. Suicide mortality was assessed in fiscal year 2001 for patients alive at the start of that fiscal year and with VHA use in fiscal years 2000-2001 (n = 4,692,034). Deaths from suicide were identified by using National Death Index data. General population rates were identified by use of the Web-based Injury Statistics Query and Reporting System. VHA rates were 43.13/100,000 person-years for men and 10.41/100,000 person-years for women. For male patients, the age-adjusted standardized mortality ratio was 1.66; for females, it was 1.87. Male patients aged 30-79 years had increased risks relative to men in the general population; standardized mortality ratios ranged from 2.56 (ages 30-39 years) to 1.33 (ages 70-79 years). Female patients aged 40-59 years had greater risks than did women in the general population, with standardized mortality ratios of 2.15 (ages 40-49 years) and 2.36 (ages 50-59 years). Findings offer heretofore unavailable comparison points for health systems. Prior to the conflicts in Afghanistan and Iraq and before recent VHA initiatives, rates were higher among VHA patients than in the general population. Female patients had particularly high relative risks.

Effect of smoking, alcohol, and depression on the quality of life of head and neck cancer patients

This pilot study examined the relationship between smoking, alcohol intake, depressive symptoms and quality of life (QoL) in head and neck cancer patients. A questionnaire on smoking, alcohol, depressive symptoms and QoL was distributed to head and neck cancer patients (N=81). Over one-third (35%) of the respondents had smoked within the last 6 months, 46% had drunk alcohol within the last 6 months and 44% screened positive for significant depressive symptoms. About one-third (32%) of smokers were interested in smoking cessation services and 37% of patients with depressive symptoms were interested in depression services. However, only 9% of those who drank alcohol expressed interest in alcohol services. Smoking was negatively associated with five scales of the SF-36V including Physical Functioning, General Health, Vitality, Social Functioning, and Role-Emotional Health. Depressive symptoms were negatively associated with all eight scales on the SF-36V and all four scales of the Head and Neck Quality of Life instrument. Surprisingly, alcohol was not found to be associated with any of the QoL scales. While smoking, alcohol intake and depression may be episodically treated, standardized protocols and aggressive intervention strategies for systematically addressing these highly prevalent disorders are needed in this population.

Efficacy of peer support interventions for depression: A meta-analysis

OBJECTIVE To assess the efficacy of peer support for reducing symptoms of depression. METHODS Medline, PsycINFO, CINAHL and CENTRAL databases were searched for clinical trials published as of April 2010 using Medical Subject Headings and free text terms related to depression and peer support. Two independent reviewers selected randomized controlled trials (RCTs) that compared a peer support intervention for depression to usual care or a psychotherapy control condition. Meta-analyses were conducted to generate pooled standardized mean differences (SMD) in the change in depressive symptoms between study conditions. RESULTS Seven RCTs of peer support vs. usual care for depression involving 869 participants were identified. Peer support interventions were superior to usual care in reducing depressive symptoms, with a pooled SMD of -0.59 (95% CI, -0.98 to -0.21; P=.002). Seven RCTs with 301 total participants compared peer support to group cognitive behavioral therapy (CBT). There was no statistically significant difference between group CBT and peer interventions, with a pooled SMD of 0.10 (95% CI, -0.20 to 0.39, P=.53). CONCLUSION Based on the available evidence, peer support interventions help reduce symptoms of depression. Additional studies are needed to determine effectiveness in primary care and other settings with limited mental health resources.

A Tailored Smoking, Alcohol, and Depression Intervention for Head and Neck Cancer Patients

Background: Smoking, alcohol use, and depression are interrelated and highly prevalent in patients with head and neck cancer, adversely affecting quality of life and survival. Smoking, alcohol, and depression share common treatments, such as cognitive behavioral therapy and antidepressants. Consequently, we developed and tested a tailored smoking, alcohol, and depression intervention for patients with head and neck cancer. Methods: Patients with head and neck cancer with at least one of these disorders were recruited from the University of Michigan and three Veterans Affairs medical centers. Subjects were randomized to usual care or nurse-administered intervention consisting of cognitive behavioral therapy and medications. Data collected included smoking, alcohol use, and depressive symptoms at baseline and at 6 months. Results: The mean age was 57 years. Most participants were male (84%) and White (90%). About half (52%) were married, 46% had a high school education or less, and 52% were recruited from Veterans Affairs sites. The sample was fairly evenly distributed across three major head and neck cancer sites and over half (61%) had stage III/IV cancers. Significant differences in 6-month smoking cessation rates were noted with 47% quitting in the intervention compared with 31% in usual care (P < 0.05). Alcohol and depression rates improved in both groups, with no significant differences in 6-month depression and alcohol outcomes. Conclusion: Treating comorbid smoking, problem drinking, and depression may increase smoking cessation rates above that of usual care and may be more practical than treating these disorders separately. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2203–8)

Pain and suicidal thoughts, plans and attempts in the United States ☆

OBJECTIVE This study examined the association between pain and suicidality in the general US population. METHOD Using data from the National Comorbidity Survey-Replication, we assessed relationships between four measures of pain (back and neck, headache, other nonarthritic pain and a summary score of the count of these conditions) and 12-month suicidal thoughts, plans and attempts using chi-square tests and logistic regression models. Multivariate logistic regression models controlled for demographic characteristics, chronic health conditions, mood, anxiety and substance use disorders. RESULTS In multivariate models adjusting for concurrent psychiatric disorders and other chronic medical conditions, suicidal ideation was associated with head pain (OR 1.9, 95% CI: 1.2, 3.0) and the pain summary score (OR 1.2, 95% CI: 1.0, 1.4). Suicide attempt was also associated with head pain (OR 2.3, 95% CI: 1.2, 4.4) and pain summary score (OR 1.7, 95% CI: 1.1, 2.6). Other nonarthritic pain was associated with suicide attempts (OR4.0, 95% CI: 1.8, 9.1). CONCLUSIONS These findings highlight the importance of pain as a potentially independent risk factor for suicide, particularly among those with head pain or multiple forms of co-occurring pain. Individuals suffering from chronic pain may be particularly appropriate for suicide screening and intervention efforts.

Trends in Antipsychotic Use in Dementia 1999-2007

CONTEXT Use of atypical antipsychotics for neuropsychiatric symptoms of dementia increased markedly in the 1990s. Concerns about their use began to emerge in 2002, and in 2005, the US Food and Drug Administration warned that use of atypical antipsychotics in dementia was associated with increased mortality. OBJECTIVE To examine changes in atypical and conventional antipsychotic use in outpatients with dementia from 1999 through 2007. DESIGN Time-series analyses estimated the effect of the various warnings on atypical and conventional antipsychotic usage using national Veterans Affairs data across 3 periods: no warning (1999-2003), early warning (2003-2005), and black box warning (2005-2007). SUBJECTS Patients aged 65 years or older with dementia (n = 254 564). MAIN OUTCOME MEASURES Outpatient antipsychotic use (percentage of patients, percentage of quarterly change, and difference between consecutive study periods). RESULTS In 1999, 17.7% (95% confidence interval [CI], 17.2-18.1) of patients with dementia were using atypical or conventional antipsychotics. Overall use began to decline during the no-warning period (rate per quarter, -0.12%; 95% CI, -0.16 to -0.07; P < .001). Following the black box warning, the decline continued (rate, -0.26%; 95% CI, -0.34 to -0.18; P < .001), with a significant difference between the early and black box warning periods (P = .006). Use of atypical antipsychotics as a group increased during the no-warning period (rate, 0.23; 95% CI, 0.17-0.30; P < .001), started to decline during the early-warning period (rate, -0.012; 95% CI, -0.14 to 0.11; P = .85), and more sharply declined during the black box warning period (rate, -0.27; 95% CI, -0.36 to -0.18; P < .001). Olanzapine and risperidone showed declining rates and quetiapine showed an increase during the early-warning period, but rates of use for all 3 antipsychotics declined during the black box warning period. In the black box warning period, there was a small but significant increase in anticonvulsant prescriptions (rate, 0.117; 95% CI, 0.08-0.16; P < .001). CONCLUSIONS Use of atypical antipsychotics began to decline significantly in 2003, and the Food and Drug Administration advisory was temporally associated with a significant acceleration in the decline.

Sleep problems and suicidality in the National Comorbidity Survey Replication

OBJECTIVE Links between sleep problems and suicidality have been frequently described in clinical samples; however, this issue has not been well-studied in the general population. Using data from a nationally representative survey, we examined the association between self-reported sleep difficulties and suicidality in the United States. METHODS The WHO Composite International Diagnostic Interview was used to assess sleep problems and suicidality in the National Comorbidity Survey Replication (NCS-R). Relationships between three measures of sleep (difficulty initiating sleep, maintaining sleep, early morning awaking), and suicidal thoughts, plans, and attempts were assessed in logistic regression analyses, while controlling for demographic characteristics, 12-month diagnoses of mood, anxiety and substance use disorders, and chronic health conditions. RESULTS In multivariate models, the presence of any of these sleep problems was significantly related to each measure of suicidality, including suicidal ideation (OR=2.1), planning (OR=2.6), and suicide attempt (OR=2.5). Early morning awakening was associated with suicidal ideation (OR=2.0), suicide planning (OR=2.1), and suicide attempt (OR=2.7). Difficulty initiating sleep was a significant predictor of suicidal ideation and planning (ORs: 1.9 for ideation; 2.2 for planning), while difficulty maintaining sleep during the night was a significant predictor of suicidal ideation and suicide attempts (ORs: 2.0 for ideation; 3.0 for attempt). CONCLUSIONS Among community residents, chronic sleep problems are consistently associated with greater risk for suicidality. Efforts to develop comprehensive models of suicidality should consider sleep problems as potentially independent indicators of risk.