Recommendations for selection and adaptation of rating scales for clinical studies of rapid-acting antidepressants.

The novel mechanisms of action (MOA) derived from some recently introduced molecular targets have led to regulatory approvals for rapid acting antidepressants (RAADs) that can generate responses within hours or days, rather than weeks or months. These novel targets include the N-methyl-D-glutamate receptor antagonist ketamine, along with its enantiomers and various derivatives, and the allosteric modulators of gamma-aminobutyric acid (GABA) receptors. There has also been a strong resurgence in interest in psychedelic compounds that impact a range of receptor sites including D1, 5-HT7, KOR, 5-HT5A, Sigma-1, NMDA, and BDNF. The RAADs developed from these novel targets have enabled successful treatment for difficult to treat depressed individuals and has generated a new wave of innovation in research and treatment. Despite the advances in the neurobiology and clinical treatment of mood disorders, we are still using rating instruments that were created decades ago for drugs from a different era (e.g., The Hamilton and Montgomery-Åsberg depression rating scales, HDRS, and MADRS) continue to be used. These rating instruments were designed to assess mood symptoms over a 7-day time frame. Consequently, the use of these rating instruments often requires modifications to address items that cannot be assessed in short time frames, such as the sleep and appetite items. This review describes the adaptative approaches that have been made with the existing scales to meet this need and examines additional domains such as daily activities, side effects, suicidal ideation and behavior, and role functioning. Recommendations for future studies are described, including the challenges related to implementation of these adapted measures and approaches to mitigation.

Consistency checks to improve measurement with the Hamilton Rating Scale for Anxiety (HAM-A).

BACKGROUND: Mitigating rating inconsistency can improve measurement fidelity and detection of treatment response. METHODS: The International Society for CNS Clinical Trials and Methodology convened an expert Working Group that developed consistency checks for ratings of the Hamilton Anxiety Rating Scale (HAM-A) and Clinical Global Impression of Severity of anxiety (CGIS) that are widely used in studies of mood and anxiety disorders. Flags were applied to 40,349 HAM-A administrations from 15 clinical trials and to Monte Carlo-simulated data as a proxy for applying flags under conditions of inconsistency. RESULTS: Thirty-three flags were derived these included logical consistency checks and statistical outlier-response pattern checks. Twenty-percent of the HAM-A administrations had at least one logical scoring inconsistency flag, 4 % had two or more. Twenty-six percent of the administrations had at least one statistical outlier flag and 11 % had two or more. Overall, 35 % of administrations had at least one flag of any type, 19 % had one and 16 % had 2 or more. Most of administrations in the Monte Carlo- simulated data raised multiple flags. LIMITATIONS: Flagged ratings may represent less-common presentations of administrations done correctly. Conclusions-Application of flags to clinical ratings may aid in detecting imprecise measurement. Flags can be used for monitoring of raters during an ongoing trial and as part of post-trial evaluation. Appling flags may improve reliability and validity of trial data.

Consistency checks to improve measurement with the Hamilton Rating Scale for Depression (HAM-D).

BACKGROUND: Symptom manifestations in mood disorders can be subtle. Cumulatively, small imprecisions in measurement can limit our ability to measure treatment response accurately. Logical and statistical consistency checks between item responses (i.e., cross-sectionally) and across administrations (i.e., longitudinally) can contribute to improving measurement fidelity. METHODS: The International Society for CNS Clinical Trials and Methodology convened an expert Working Group that assembled flags indicating consistency/inconsistency ratings for the Hamilton Rating Scale for Depression (HAM-D17), a widely-used rating scale in studies of depression. Proposed flags were applied to assessments derived from the NEWMEDS data repository of 95,468 HAM-D administrations from 32 registration trials of antidepressant medications and to Monte Carlo-simulated data as a proxy for applying flags under conditions of known inconsistency. RESULTS: Two types of flags were derived: logical consistency checks and statistical outlier-response pattern checks. Almost thirty percent of the HAMD administrations had at least one logical scoring inconsistency flag. Seven percent had flags judged to suggest that a thorough review of rating is warranted. Almost 22% of the administrations had at least one statistical outlier flag and 7.9% had more than one. Most of the administrations in the Monte Carlo- simulated data raised multiple flags. LIMITATIONS: Flagged ratings may represent less-common presentations of administrations done correctly. CONCLUSIONS: Application of flags to clinical ratings may aid in detecting imprecise measurement. Reviewing and addressing these flags may improve reliability and validity of clinical trial data.

An interactive web-based method of outreach to college students at risk for suicide.

OBJECTIVE AND PARTICIPANTS: From 2002 to 2005, the authors tested an interactive, Web-based method to encourage college students at risk for suicide to seek treatment. METHODS: The authors invited students at 2 universities to complete an online questionnaire that screened for depression and other suicide risk factors. Respondents received a personalized assessment and were able to communicate anonymously with a clinical counselor online. At-risk students were urged to attend in-person evaluation and treatment. RESULTS: A total of 1,162 students (8% of those invited) completed the screening questionnaire; 981 (84.4%) were designated as at high or moderate risk. Among this group, 190 (19.4%) attended an in-person evaluation session with the counselor, and 132 (13.5%) entered treatment. Students who engaged in online dialogues with the counselor were 3 times more likely than were those who did not to come for evaluation and enter treatment. CONCLUSIONS: The method has considerable promise for encouraging previously untreated, at-risk college students to get help.

Group processes and process evaluations in a new treatment setting: inpatient group psychotherapy followed by internet-chat aftercare groups.

Little is known about processes characterizing therapeutic Internet-chat groups, which offer a novel way of providing group therapy over distances. In this study group processes and group evaluations were examined in a treatment setting where face-to-face inpatient groups are followed by chat aftercare groups. For a sample of 121 patients who participated in both treatment modalities, group processes and group evaluations were modeled using hierarchical linear modeling. The group evaluations followed a consistent upward course from the beginning of therapy until the end of chat aftercare. For the process measures Activity and Emotional Reactivity, the initial scores at the beginning of the chat groups were lower than at the end of the inpatient treatment, but higher than at admission. During chat aftercare, Activity and Emotional Reactivity scores increased less than during the inpatient phase, but on average Activity and Emotional Reactivity were higher during Internet-chat aftercare. The predictive value of the acquaintance of the therapist from inpatient treatment and the course of group evaluations during inpatient treatment on the course of group evaluations during chat aftercare were examined.

Psychological and educational factors: better predictors of work status than FEV1 in adults with cystic fibrosis.

Now that more individuals with cystic fibrosis (CF) are living into adulthood, vocational attainment is an increasingly important consideration. Work is a key factor in quality of life. The purpose of the present paper was to evaluate the factors that are associated with work status in 183 adults with CF. Approximately half of the participants were working at the time of evaluation, an impressive figure given that the mean forced expired volume in 1 sec (FEV1) was 31.9%. The average number of hours worked was 32.7 hr/week. The majority of individuals were employed in professional, technical, or managerial occupations (accounting, teaching, law, or social work). A third were employed in clerical and sales occupations, and the remaining individuals were employed in a wide range of other occupations (hotel manager, undercover shopper, artist, or dental technician). Interestingly, FEV1 and age did not differentiate between subjects who were working and those who were not. Individuals who were working had significantly lower depression scores and a higher educational level than those who were not working. Future research is needed to determine whether it is the increased socialization and the resulting social support that may come from a work environment, or a reduction in financial stress because of better income and health benefits that helps to explain this difference. Alternatively, work may serve as a distraction from the symptoms of CF. It is likely that those with higher educational levels had more professional jobs that were more easily modified as health declined. Future research needs to assess how career choices are made, and what factors into a patient's decision to keep working.

Appraisal and coping as predictors of psychological distress and self-reported physical disability before lung transplantation.

CONTEXT: Certain appraisals and coping strategies have been associated with increased levels of psychological distress and disability in other medical populations, but no study has examined this relationship with patients who are awaiting lung transplantation. OBJECTIVE: To describe the cognitive appraisal and coping strategies used by patients who are pursuing lung transplantation and to evaluate the extent to which these processes are associated with depression, anxiety, and disability. METHODS: This is a cross-sectional design with 160 participants (42.5% men) who have end-stage lung disease and were evaluated for lung transplantation at a large medical center. MEASURES: The outcome variables of depression, anxiety, and physical disability were assessed using the Beck Depression Inventory, Spielberger Trait Anxiety Inventory, and the Sickness Impact Profile, respectively. The predictor variables, coping and appraisal styles, were measured using the COPE and the Stress Threat Questionnaire, respectively. Demographic variables were also assessed. RESULTS: Patients used a variety of adaptive problem- and emotion-focused coping strategies. Hierarchical multiple regressions demonstrated that harm appraisals and the use of particular types of coping styles; namely, disengagement, avoidance, ruminating and venting emotions, low solicitation of emotional support, and suppressing other activities are maladaptive and were uniquely related to psychological distress and disability. CONCLUSIONS: Maladaptive appraisal and coping styles can serve as markers of emotional distress and disability that may help the transplant team identify patients who may benefit from counseling and psychological interventions.

Linguistic analyses of natural written language: unobtrusive assessment of cognitive style in eating disorders.

OBJECTIVE: Linguistic style analysis is introduced as a method of nonreactive measurement of cognitive style in individuals with eating disorders (ED). METHOD: A journaling exercise was implemented on an ED inpatient unit. Thirty-four written essays collected from an unselected sample of 11 patients were analysed with the Linguistic Inquiry and Word Count, with regard to predefined text categories. At each session, self-report of participant well-being and session impact were assessed. RESULTS: Compared to essays from a student control group, and message-board entries of individuals who had recovered from an anorexia nervosa (AN), the inpatient journals displayed the highest rates of self-related words, negative emotion words, and the lowest rate of positive emotion words. Inpatients used more anxiety words and fewer words that refer to social processes and eating concerns than individuals who had recovered from an AN. Associations were found between linguistic categories, prewriting well-being, and postwriting evaluation. CONCLUSION: Linguistic style analysis offers insights into cognitive styles, and provides a promising approach for their unobtrusive measurement in ED.

Binge eating disorder treatment: a systematic review of randomized controlled trials.

OBJECTIVE: The Research Triangle Institute-University of North Carolina Evidence Based Practice Center (RTI-EPC) systematically reviewed evidence on efficacy of treatment for binge eating disorder (BED), harms associated with treatments, factors associated with treatment efficacy, and differential outcome by sociodemographic characteristics. METHOD: We searched six major databases for studies on the treatment of BED published from 1980 to September, 2005, in all languages against a priori inclusion/exclusion criteria and focused on eating, psychiatric or psychological, or biomarker outcomes. RESULTS: Twenty-six studies, including medication-only, medication plus behavioral intervention, and behavioral intervention only designs, met inclusion criteria. The strength of the evidence for medication and behavioral interventions was moderate, for self-help and other interventions was weak, for treatment-related harms was strong, for factors associated with efficacy of treatment was weak, and for differential outcome by sociodemographic factors was nonexistent. Individual or group CBT reduces binge eating and improves abstinence rates for up to 4 months after treatment but does not lead to weight loss. Medications may play a role in treating BED patients. CONCLUSION: The literature regarding treatment efficacy for BED is variable. Future directions include the identification of optimal interventions that are associated with both sustained abstinence from binge eating and permanent weight loss.

Anorexia nervosa treatment: a systematic review of randomized controlled trials.

OBJECTIVE: The RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center (RTI-UNC EPC) systematically reviewed evidence on efficacy of treatment for anorexia nervosa (AN), harms associated with treatments, factors associated with treatment efficacy, and differential outcome by sociodemographic characteristics. METHOD: We searched six major databases for studies on the treatment of AN from 1980 to September 2005, in all languages against a priori inclusion/exclusion criteria focusing on eating, psychiatric or psychological, or biomarker outcomes. RESULTS: Thirty-two treatment studies involved only medications, only behavioral interventions, and medication plus behavioral interventions for adults or adolescents. The literature on medication treatments and behavioral treatments for adults with AN is sparse and inconclusive. Cognitive behavioral therapy may reduce relapse risk for adults with AN after weight restoration, although its efficacy in the underweight state remains unknown. Variants of family therapy are efficacious in adolescents, but not in adults. CONCLUSION: Evidence for AN treatment is weak; evidence for treatment-related harms and factors associated with efficacy of treatment are weak; and evidence for differential outcome by sociodemographic factors is nonexistent. Attention to sample size and statistical power, standardization of outcome measures, retention of patients in clinical trials, and developmental differences in treatment appropriateness and outcome is required.

Bulimia nervosa treatment: a systematic review of randomized controlled trials.

OBJECTIVE: The RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center systematically reviewed evidence on efficacy of treatment for bulimia nervosa (BN), harms associated with treatments, factors associated with treatment efficacy, and differential outcome by sociodemographic characteristics. METHOD: We searched six major databases published from 1980 to September 2005 in all languages against a priori inclusion/exclusion criteria; we focused on eating, psychiatric or psychological, and biomarker outcomes. RESULTS: Forty-seven studies of medication only, behavioral interventions only, and medication plus behavioral interventions for adults or adolescents met our inclusion criteria. Fluoxetine (60 mg/day) decreases the core symptoms of binge eating and purging and associated psychological features in the short term. Cognitive behavioral therapy reduces core behavioral and psychological features in the short and long term. CONCLUSION: Evidence for medication or behavioral treatment for BN is strong, for self-help is weak; for harms related to medication is strong but either weak or nonexistent for other interventions; and evidence for differential outcome by sociodemographic factors is nonexistent. Attention to sample size, standardization of outcome measures, attrition, and reporting of abstinence from target behaviors are required. Longer follow-up intervals, innovative treatments, and attention to sociodemographic factors would enhance the literature.

Management of eating disorders.

OBJECTIVES: The RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center (RTI-UNC EPC) systematically reviewed evidence on efficacy of treatment for anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED), harms associated with treatments, factors associated with the treatment efficacy and with outcomes of these conditions, and whether treatment and outcomes for these conditions differ by sociodemographic characteristics. DATA SOURCES: We searched MEDLINE, the Cumulative Index to Nursing and Applied Health (CINAHL), PSYCHINFO, the Educational Resources Information Center (ERIC), the National Agricultural Library (AGRICOLA), and Cochrane Collaboration libraries. REVIEW METHODS: We reviewed each study against a priori inclusion/exclusion criteria. For included articles, a primary reviewer abstracted data directly into evidence tables; a second senior reviewer confirmed accuracy. We included studies published from 1980 to September 2005, in all languages. Studies had to involve populations diagnosed primarily with AN, BN, or BED and report on eating, psychiatric or psychological, or biomarker outcomes. RESULTS: We report on 30 treatment studies for AN, 47 for BN, 25 for BED, and 34 outcome studies for AN, 13 for BN, 7 addressing both AN and BN, and 3 for BED. The AN literature on medications was sparse and inconclusive. Some forms of family therapy are efficacious in treating adolescents. Cognitive behavioral therapy (CBT) may reduce relapse risk for adults after weight restoration. For BN, fluoxetine (60 mg/day) reduces core bulimic symptoms (binge eating and purging) and associated psychological features in the short term. Individual or group CBT decreases core behavioral symptoms and psychological features in both the short and long term. How best to treat individuals who do not respond to CBT or fluoxetine remains unknown. In BED, individual or group CBT reduces binge eating and improves abstinence rates for up to 4 months after treatment; however, CBT is not associated with weight loss. Medications may play a role in treating BED patients. Further research addressing how best to achieve both abstinence from binge eating and weight loss in overweight patients is needed. Higher levels of depression and compulsivity were associated with poorer outcomes in AN; higher mortality was associated with concurrent alcohol and substance use disorders. Only depression was consistently associated with poorer outcomes in BN; BN was not associated with an increased risk of death. Because of sparse data, we could reach no conclusions concerning BED outcomes. No or only weak evidence addresses treatment or outcomes difference for these disorders. CONCLUSIONS: The literature regarding treatment efficacy and outcomes for AN, BN, and BED is of highly variable quality. In future studies, researchers must attend to issues of statistical power, research design, standardized outcome measures, and sophistication and appropriateness of statistical methodology.

Religious and non-religious coping in lung transplant candidates: does adding god to the picture tell us more?

Individuals use many non-religious coping (NRC) and religious coping (RC) strategies to cope with stress. In previous studies with lung transplant candidates, we found that NRC and RC predicted depression, anxiety, and disability. The present study aimed to (a) assess whether RC and NRC contributed uniquely to the prediction of distress and disability, or whether they were redundant and offered no additional information, and (b) evaluate the unique contribution of each subscale to determine the strongest associations with outcomes. Participants were 81 patients with end-stage lung disease being evaluated for lung transplant. Our findings suggest that RC and NRC are not functionally redundant. The best RC predictor was reappraising the situation as a punishment from God, and the best NRC predictors were mental disengagement and denial. Our findings suggest that NRC and RC are independent components of psychological functioning, and measuring both coping styles provides more information than studying each alone.

Tobacco and alcohol use in lung transplant candidates and recipients.

Tobacco and alcohol use among lung transplant candidates and recipients is unknown. Our first goal was to describe tobacco and alcohol use before and after lung transplant in patients with cystic fibrosis (CF) and other pulmonary diseases (non-CF). Our second goal was to determine whether demographic variables, depression, anxiety and social support predicted tobacco and alcohol use. Self-report data from transplant candidates and recipients, and transplant nurse coordinator ratings of post-transplant smoking and drinking were utilized. Data from two samples were analyzed. Sample 1 comprised 219 patients being evaluated for lung transplant, and sample 2 comprised 45 transplant recipients who were 1-7 yrs post-transplant. The results from analyzing sample 1 indicated that 72% of non-CF patients and 16% of CF patients had a history of smoking cigarettes, and the majority of patients in both groups had consumed alcohol in the past. For CF patients, past smoking was related to higher depression scores, and past drinking was related to higher education and lower social support. For non-CF patients, a history of smoking was associated with being Caucasian and older. For CF patients, a history of drinking was associated with being older and less depressed, and for non-CF patients a history of drinking was associated with higher education and lower social support. Post-transplant 100% of recipients reported abstinence from tobacco, and over 60% reported abstinence from alcohol. Transplant coordinator ratings corroborated that no transplant recipients were using tobacco products or consuming alcohol in an excessive or problematic manner. For both groups, consuming alcohol after transplant was related to lower levels of social support. In conclusion, lung recipients remain abstinent from tobacco, and although over 30% of patients consume alcohol after transplant, it is not at problematic levels. Smoking and drinking behaviors were related to demographic variables, depression, and low social support.