Sue M. Marcus

A comparision between responses from a propensity-weighted web survey and an identical RDD survey

The authors conducted a large-scale survey about health care twice, once as a web and once as a random digit dialing (RDD) phone survey. The web survey used a statistical technique, propensity scoring, to adjust for selection bias. Comparing the weighted responses from both surveys, there were no significant response differences in 8 of 37 questions. Web survey responses were significantly more likely to agree with RDD responses when the question asked about the respondent’s personal health (9 times more likely), was a factual question (9 times more likely), and only had two as opposed to multiple response categories (17 times more likely). For three questions, significant differences turned insignificant when adjacent categories of multicategory questions were combined. Factual questions tended to also be questions with two rather than multiple response categories. More study is needed to isolate the effects of these two factors more clearly.

Relationship between antidepressants and suicide attempts: an analysis of the Veterans Health Administration data sets.

OBJECTIVE In late 2006, a U.S. Food and Drug Administration advisory committee recommended that the 2004 black box warning regarding suicidality in pediatric patients receiving antidepressants be extended to include young adults. This study examined the relationship between antidepressant treatment and suicide attempts in adult patients in the Veterans Administration health care system. METHOD The authors analyzed data on 226,866 veterans who received a diagnosis of depression in 2003 or 2004, had at least 6 months of follow-up, and had no history of depression from 2000 to 2002. Suicide attempt rates overall as well as before and after initiation of antidepressant therapy were compared for patients who received selective serotonin reuptake inhibitors (SSRIs), new-generation non-serotonergic-specific (non-SSRI) antidepressants (bupropion, mirtazapine, nefazodone, and venlafaxine), tricyclic antidepressants, or no antidepressant. Age group analyses were also performed. RESULTS Suicide attempt rates were lower among patients who were treated with antidepressants than among those who were not, with a statistically significant odds ratio for SSRIs and tricyclics. For SSRIs versus no antidepressant, this effect was significant in all adult age groups. Suicide attempt rates were also higher prior to treatment than after the start of treatment, with a significant relative risk for SSRIs and for non-SSRIs. For SSRIs, this effect was seen in all adult age groups and was significant in all but the 18-25 group. CONCLUSIONS These findings suggest that SSRI treatment has a protective effect in all adult age groups. They do not support the hypothesis that SSRI treatment places patients at greater risk of suicide.

Adolescent Substance Use in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (ADHD) (MTA) as a Function of Childhood ADHD, Random Assignment to Childhood Treatments, and Subsequent Medication

OBJECTIVE To determine long-term effects on substance use and substance use disorder (SUD), up to 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the multisite Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA; n = 436); to test whether medication at follow-up, cumulative psychostimulant treatment over time, or both relate to substance use/SUD; and to compare substance use/SUD in the ADHD sample to the non-ADHD childhood classmate comparison group (n = 261). METHOD Mixed-effects regression models with planned contrasts were used for all tests except the important cumulative stimulant treatment question, for which propensity score matching analysis was used. RESULTS The originally randomized treatment groups did not differ significantly on substance use/SUD by the 8-year follow-up or earlier (mean age = 17 years). Neither medication at follow-up (mostly stimulants) nor cumulative stimulant treatment was associated with adolescent substance use/SUD. Substance use at all time points, including use of two or more substances and SUD, were each greater in the ADHD than in the non-ADHD samples, regardless of sex. CONCLUSIONS Medication for ADHD did not protect from, or contribute to, visible risk of substance use or SUD by adolescence, whether analyzed as randomized treatment assignment in childhood, as medication at follow-up, or as cumulative stimulant treatment over an 8-year follow-up from childhood. These results suggest the need to identify alternative or adjunctive adolescent-focused approaches to substance abuse prevention and treatment for boys and girls with ADHD, especially given their increased risk for use and abuse of multiple substances that is not improved with stimulant medication. Clinical trial registration information-Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA); http://clinical trials.gov/; NCT00000388.

Cognitive-Behavioral Therapy vs Risperidone for Augmenting Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder: A Randomized Clinical Trial

IMPORTANCE Obsessive-compulsive disorder (OCD) is one of the worlds most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP). OBJECTIVE To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial. INTERVENTIONS While continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks. MAIN OUTCOME AND MEASURE The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity. RESULTS Patients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vs risperidone: mean [SE], -9.72 [1.38]; P < .001 vs placebo: mean [SE], -10.10 [1.68]; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean [SE], -0.38 [1.72]; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life. CONCLUSIONS AND RELEVANCE Adding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00389493.

Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept

Serotonin reuptake inhibitors (SRIs), the first-line pharmacological treatment for obsessive-compulsive disorder (OCD), have two limitations: incomplete symptom relief and 2–3 months lag time before clinically meaningful improvement. New medications with faster onset are needed. As converging evidence suggests a role for the glutamate system in the pathophysiology of OCD, we tested whether a single dose of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, could achieve rapid anti-obsessional effects. In a randomized, double-blind, placebo-controlled, crossover design, drug-free OCD adults (n=15) with near-constant obsessions received two 40-min intravenous infusions, one of saline and one of ketamine (0.5 mg/kg), spaced at least 1-week apart. The OCD visual analog scale (OCD-VAS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess OCD symptoms. Unexpectedly, ketamine’s effects within the crossover design showed significant (p<0.005) carryover effects (ie, lasting longer than 1 week). As a result, only the first-phase data were used in additional analyses. Specifically, those receiving ketamine (n=8) reported significant improvement in obsessions (measured by OCD-VAS) during the infusion compared with subjects receiving placebo (n=7). One-week post-infusion, 50% of those receiving ketamine (n=8) met criteria for treatment response (⩾35% Y-BOCS reduction) vs 0% of those receiving placebo (n=7). Rapid anti-OCD effects from a single intravenous dose of ketamine can persist for at least 1 week in some OCD patients with constant intrusive thoughts. This is the first randomized, controlled trial to demonstrate that a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an SRI and is consistent with a glutamatergic hypothesis of OCD.

Time-dependent changes in positively biased self-perceptions of children with attention-deficit/hyperactivity disorder: A developmental psychopathology perspective

This study examined changes in the degree of positive bias in self-perceptions of previously diagnosed 8- to 13-year-old children with attention-deficit/hyperactivity disorder (ADHD; n = 513) and comparison peers (n = 284) over a 6-year period. The dynamic association between biased self-perceptions and dimensional indices of depressive symptoms and aggression also were considered. Across the 6-year time span, comparison children exhibited less bias than children with ADHD, although a normative bolstering of social self-views during early adolescence was observed. Decreases in positive biases regarding social and behavioral competence were associated with increases in depressive symptoms over time, whereas increases in levels of positively biased self-perceptions in the behavioral (but not social) domain were predictive of greater aggression over time. ADHD status moderated the dynamic association between biases and adjustment. Finally, evidence indicated that there was a bidirectional relationship between biases and aggression, whereas depressive symptoms appeared to inversely predict later bias.

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

Suicide is a major public health problem with ∼1 million victims each year worldwide. Up to 90% of adults who commit suicide have at least one psychiatric diagnosis such as major depression, bipolar disorder (BPD), schizophrenia (SZ), substance abuse or dependence. A question that has remained unanswered is whether the biological substrates of suicide are distinct from those of the psychiatric disorders in which it occurs. The serotonin 2C receptor (5-HT2CR) has been implicated in depression and suicide. We, therefore, compared the frequencies of its mRNA editing variants in postmortem prefrontal cortical specimens from subjects who committed suicide or who died from other causes. All suicides occurred in the context of either SZ or BPD. The non-suicide cases included subjects with either SZ or BPD as well as subjects with no psychiatric diagnosis. We identified 5-HT2CR mRNA editing variations that were associated with suicide but not with the comorbid psychiatric diagnoses, and were not influenced by demographic characteristics (age and sex) and alcohol or drug use. These variations consisted of a significant increase in the pool of mRNA variants (ACD and ABCD) that encode one of the most prevalent and highly edited isoforms of 5-HT2CR, that is, VSV (Val156–Ser158–Val160). Because the VSV isoform of 5-HT2CR exhibits low functional activity, an increase in its expression frequency may significantly influence the serotonergic regulation of the brain. Thus, at least in patients with SZ or BPD, overexpression of the VSV isoform in the prefrontal cortex may represent an additional risk factor for suicidal behavior.

Intent-to-Treat vs. Non-Intent-to-Treat Analyses under Treatment Non-Adherence in Mental Health Randomized Trials.

FULL DISCLOSURE POLICY In accordance with the Accreditation Council for Continuing Medical Education’s Standards for Commercial Support, all CME providers are required to disclose to the activity audience the relevant financial relationships of the planners, teachers, and authors involved in the development of CME content. An individual has a relevant financial relationship if he or she has a financial relationship in any amount occurring in the last 12 months with a commercial interest whose products or services are discussed in the CME activity content over which the individual has control. Relationship information appears at the beginning of each CME-accredited article in this issue.

Factors associated with home environmental problems among community-living older people

PURPOSE This paper describes the types of difficulties older people have with their home environments and the factors associated with having such difficulties. METHOD Data were used from 296 study participants of the University at Buffalos Consumer Assessments Study that examines the home modification needs and environmental difficulties of older people. A combination of socio-demographic variables, health and functional status indicators and measures of psychosocial well-being were used to predict environmental problems. RESULTS An average of 13 problems with the environment that posed as a barrier to safe and independent performance was observed in homes. It was found that most difficulties occurred in bathrooms, kitchens, bedrooms and access to entryways and rooms. Hierarchical multiple regression analysis showed that having home environmental problems was most strongly associated with younger age, being female, being of minority status, having pain, and greater physical disability. CONCLUSION The findings show that a combination of conditions that include demographic and functional conditions place older people at risk for problems with the home environment that impede performance of daily living activities.Purpose : This paper describes the types of difficulties older people have with their home environments and the factors associated with having such difficulties. Method : Data were used from 296 study participants of the University at Buffalos Consumer Assessments Study that examines the home modification needs and environmental difficulties of older people. A combination of socio-demographic variables, health and functional status indicators and measures of psychosocial well-being were used to predict environmental problems. Results : An average of 13 problems with the environment that posed as a barrier to safe and independent performance was observed in homes. It was found that most difficulties occurred in bathrooms, kitchens, bedrooms and access to entryways and rooms. Hierarchical multiple regression analysis showed that having home environmental problems was most strongly associated with younger age, being female, being of minority status, having pain, and greater physical disability. Conclusion : The findings show that a combination of conditions that include demographic and functional conditions place older people at risk for problems with the home environment that impede performance of daily living activities.

Risk of venous thromboembolism from oral contraceptives containing gestodene and desogestrel versus levonorgestrel: a meta-analysis and formal sensitivity analysis.

Controversy exists regarding whether oral contraceptives (OCs) containing desogestrel and gestodene are associated with an increased risk of venous thromboembolism (VTE) versus OCs containing levonorgestrel. We were interested in synthesizing the available data, exploring explanations for mixed results, and characterizing the degree of uncontrolled confounding that could have produced a spurious association. We performed a meta-analysis and formal sensitivity analysis of studies that examined the relative risk of VTE for desogestrel and gestodene versus levonorgestrel. Twelve studies, all observational, were included. The summary relative risk (95% CI) was 1.7 (1.3-2.1; heterogeneity p = 0.09). If real, the incremental risk of VTE would be about 11 per 100,000 women per year. An association was present when accounting for duration of use and when restricted to the first year of use in new users. However, in the sensitivity analysis, the association abated in many, but not all, scenarios in which an unmeasured confounding factor increased the risk of VTE three to fivefold and in nearly all examined scenarios in which the factor increased the risk 10-fold. The summary relative risk of 1.7 does not appear to be caused by depletion of susceptibles, but is sensitive to a modest degree of unmeasured confounding. Whether such confounding occurred is unknown. However, given this sensitivity, this issue probably cannot be settled unequivocally with observational data. In the absence of a definitive answer, this apparent increased risk, together with its uncertainty and small magnitude and its important consequences, should be considered when selecting an OC for a given woman.