Biomedical subjects

A John Rush

Publications and source records attributed to A John Rush.

At least 19 recordsLinked to original sources

PubMed2008

Symptom features of postpartum depression: are they distinct?

The clinical features of postpartum depression and depression occurring outside of the postpartum period have rarely been compared. The 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR(16)) provides a means to assess core depressive symptoms. Item response theory and classical test theory analyses were conducted to examine differences between postpartum (n=95) and nonpostpartum (n=50) women using the QIDS-SR(16). The two groups of females were matched on the basis of age. All met DSM-IV criteria for nonpsychotic major depressive disorder. Low energy level and restlessness/agitation were major characteristics of depression in both groups. The nonpostpartum group reported more sad mood, more suicidal ideation, and more reduced interest. In contrast, for postpartum depression sad mood was less prominent, while psychomotor symptoms (restlessness/agitation) and impaired concentration/decision-making were most prominent. These symptomatic differences between postpartum and other depressives suggest the need to include agitation/restlessness and impaired concentration/decision-making among screening questions for postpartum depression.

Adult↗

PubMed2006

Methodological challenges in constructing effective treatment sequences for chronic psychiatric disorders.

Psychiatric disorders are often chronic conditions that require sequential decision making to achieve the best clinical outcomes. Sequential decisions are necessary to accommodate treatment response heterogeneity, a variable course of illness, and the often heavy burden associated with intensive or longer-term treatment. Yet, only a few studies in this field have been designed to address sequential decisions. Most of the experimental designs and data analytic methods that are best suited for improving sequential clinical decision making are often found in nonmedical fields such as engineering, computer science, and statistics. Promising designs and methods are surveyed with a focus on those areas most immediately useful for informing clinical decision making.

Chronic Disease↗

PubMed2006

Dropouts versus completers among chronically depressed outpatients.

BACKGROUND: Premature termination is common among patients treated for depression with either pharmacotherapy or psychotherapy. Yet little is known about factors associated with premature treatment termination among depressed patients. METHODS: This study examines predictors of, time to, and reasons for dropout from the 12-week acute phase treatment of nonpsychotic adult outpatients, age 18-75, with chronic major depression who were randomly assigned to nefazadone alone (MED), cognitive behavioral analysis system of psychotherapy alone (CBASP) or both treatments (COMB). RESULTS: Of 681 randomized study participants, 156 were defined as dropouts. Dropout rates were equivalent across the three treatments. Among dropouts, those in COMB remained in treatment (Mean=40 days) significantly longer than those in either MED (Mean=27 days) or CBASP (Mean=28 days). Dropouts attributed to medication side-effects were significantly lower in COMB than in MED, suggesting that the relationship with the psychotherapist may increase patient willingness to tolerate side-effects associated with antidepressant medications. Ethnic or racial minority status, younger age, lower income, and co-morbid anxiety disorders significantly predicted dropout in the full sample. Within treatments, differences between completers and dropouts in minority status and the prevalence of anxiety disorders were most pronounced in MED. Among those receiving CBASP, dropouts had significantly lower therapeutic alliance scores than completers. LIMITATIONS: The sample included only individuals with chronic depression. CONCLUSIONS: Predictors of dropout included baseline patient characteristics, but not early response to treatment. Ethnic and racial minorities and those with comorbid anxiety are at higher risk of premature termination, particularly in pharmacotherapy, and may require modified treatment strategies.

Adolescent↗

PubMed2006

Clinical differences among depressed patients with and without a history of suicide attempts: findings from the STAR*D trial.

BACKGROUND: This study sought to determine whether a history of suicide attempts among outpatients diagnosed with nonpsychotic major depressive disorder (MDD) is correlated with any difference in clinical presentation that should influence patient care. METHODS: Baseline data from the Sequenced Treatment Alternatives to Relieve Depression (STAR()D) trial on outpatients with MDD treated in primary and specialty care settings were used to model significant demographic and clinical correlates of suicide attempter status. RESULTS: Altogether, 16.5% of participants (n=667) reported prior suicide attempts. Controlling for age, gender, and depressive symptom severity, previous attempters had more current general medical conditions (micro=3.2 vs. 2.9, p<.0001), more current alcohol/substance abuse (p<.0001), and more work hours missed in the past week (26.2% vs. 18.2%, p<.0001) than non-attempters. On average, for the previously suicidal, the onset of MDD occurred 8.9 years earlier in life (p<.0001) and had included 1.2 additional depressive episodes (p=0.001) compared to those without prior suicidal behavior. Previous attempters also reported more current suicidal ideation (61.3% of previous attempters, adjusted OR 1.6, vs. 45.5% of nonattempters, p<.0001). LIMITATIONS: Presence or absence of a history of suicide attempts was determined only through self report. CONCLUSIONS: Those with a history of suicidal behavior suffer a greater burden of depressive illness. Earlier intervention and ongoing, aggressive care, including maintenance-phase pharmacotherapy, may be critical to mitigating the long-term consequences associated with this increased disease burden.

Absenteeism↗

PubMed2006

Report by the ACNP Task Force on response and remission in major depressive disorder.

This report summarizes recommendations from the ACNP Task Force on the conceptualization of remission and its implications for defining recovery, relapse, recurrence, and response for clinical investigators and practicing clinicians. Given the strong implications of remission for better function and a better prognosis, remission is a valid, clinically relevant end point for both practitioners and investigators. Not all depressed patients, however, will reach remission. Response is a less desirable primary outcome in trials because it depends highly on the initial (often single) baseline measure of symptom severity. It is recommended that remission be ascribed after 3 consecutive weeks during which minimal symptom status (absence of both sadness and reduced interest/pleasure along with the presence of fewer than three of the remaining seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved, remission can only be lost if followed by a relapse. Recovery is ascribed after at least 4 months following the onset of remission, during which a relapse has not occurred. Recovery, once achieved, can only be lost if followed by a recurrence. Day-to-day functioning and quality of life are important secondary end points, but they were not included in the proposed definitions of response, remission, recovery, relapse, or recurrence. These recommendations suggest that symptom ratings that measure all nine criterion symptom domains to define a major depressive episode are preferred as they provide a more certain ascertainment of remission. These recommendations were based largely on logic, the need for internal consistency, and clinical experience owing to the lack of empirical evidence to test these concepts. Research to evaluate these recommendations empirically is needed.

Clinical Trials as Topic↗

PubMed2006

The Montgomery Asberg and the Hamilton ratings of depression: a comparison of measures.

The 17-item Hamilton Rating Scale for Depression (HRSD(17)) and the Montgomery Asberg Depression Rating Scale (MADRS) are two widely used clinician-rated symptom scales. A 6-item version of the HRSD (HRSD(6)) was created by Bech to address the psychometric limitations of the HRSD(17). The psychometric properties of these measures were compared using classical test theory (CTT) and item response theory (IRT) methods. IRT methods were used to equate total scores on any two scales. Data from two distinctly different outpatient studies of nonpsychotic major depression: a 12-month study of highly treatment-resistant patients (n=233) and an 8-week acute phase drug treatment trial (n=985) were used for robustness of results. MADRS and HRSD(6) items generally contributed more to the measurement of depression than HRSD(17) items as shown by higher item-total correlations and higher IRT slope parameters. The MADRS and HRSD(6) were unifactorial while the HRSD(17) contained 2 factors. The MADRS showed about twice the precision in estimating depression as either the HRSD(17) or HRSD(6) for average severity of depression. An HRSD(17) of 7 corresponded to an 8 or 9 on the MADRS and 4 on the HRSD(6). The MADRS would be superior to the HRSD(17) in the conduct of clinical trials.

Adolescent↗

PubMed2006

Algorithms and collaborative-care systems for depression: are they effective and why? A systematic review.

BACKGROUND: Treatment algorithms and collaborative-care systems are systematic treatment approaches that are designed to improve outcomes by enhancing the quality of care. During the last decade, algorithm research has evolved as a new branch of clinical research that evaluates the clinical and economic impact of algorithm-guided treatment in primary and psychiatric care of patients with depressive disorders. METHODS: This article discusses the rationale of algorithm development, their risks and limitations, and important elements in their implementation in clinical practice. It further reviews the available studies that have evaluated algorithm-guided treatment for depression. RESULTS: Recent studies show that compared with treatment as usual, the use of algorithms and collaborative-care approaches in the care of depressed patients enhances treatment outcomes by modifying practice procedures and treatment processes. CONCLUSIONS: Treatment algorithms and collaborative-care systems clearly increase the efficacy of applied treatments in the care of depressed patients. However, to what extent the enhanced outcomes are a result of diligent measurement-based care or of the specific treatment steps that are used remains to be resolved. Valid clinical or pharmacogenetic predictors of response are needed to further tailor specific algorithms to individual patients.

Algorithms↗

PubMed2006

Sexual dysfunction associated with second-generation antipsychotics in outpatients with schizophrenia or schizoaffective disorder: an empirical evaluation of olanzapine, risperidone, and quetiapine.

OBJECTIVE: Evaluate sexual dysfunction, as measured by the Arizona Sexual Experience Scale (ASEX), in olanzapine-, quetiapine-, and risperidone-treated outpatients with schizophrenia or schizoaffective disorder. METHOD: The sexual functioning of 238 outpatients (age> or =18 years) with diagnoses of schizophrenia or schizoaffective disorder who took quetiapine (n=57), olanzapine (n=94), or risperidone (n=87) was evaluated with a one-time rating of the ASEX. The dose range for each treatment group was 5 to 40 mg/day (M=16.6 mg/day, SD=7.4) for olanzapine; 1 to 8 mg/day (M=3.9 mg/day, SD=1.6) for risperidone; and 50 to 900 mg/day (M=376.8 mg/day, SD=213.4) for quetiapine. Antipsychotic group designation was based on medication treatment at study entry (i.e., non-random assignment). Participant characteristics were collected to test for treatment group differences and for potential associations with severity of sexual dysfunction. The primary data analysis was a mixed linear model analysis of covariance with age, gender, and presence/absence of antidepressant known to cause sexual dysfunction included as covariates. RESULTS: There was a significant treatment effect on severity of sexual dysfunction, as measured by ASEX total scores (p=.04). The adjusted average ASEX total scores were lower in the quetiapine (M=17.80) than in the risperidone (M=19.69) or olanzapine (M=20.34) groups. Individual comparisons of the treatments on adjusted average ASEX total scores indicated a significant difference between olanzapine and quetiapine (p=.04), but no difference between risperidone and quetiapine (p=.17) or olanzapine and risperidone (p=.76). CONCLUSIONS: Quetiapine was associated with less severe sexual dysfunction than olanzapine and risperidone (albeit the effect between risperidone and quetiapine was not statistically significant). Olanzapine and risperidone were associated with a comparable degree of sexual dysfunction. Patients in all three treatment groups, nonetheless, experienced a moderately high degree of sexual dysfunction. Because the patients were not randomized, conclusions must be interpreted within the context of the quasi-experimental design.

Adolescent↗

PubMed2006

Clinical vs. self-report versions of the quick inventory of depressive symptomatology in a public sector sample.

OBJECTIVES: Recent work using classical test theory (CTT) and item response theory (IRT) has found that the self-report (QIDS-SR(16)) and clinician-rated (QIDS-C(16)) versions of the 16-item quick inventory of depressive symptomatology were generally comparable in outpatients with nonpsychotic major depressive disorder (MDD). This report extends this comparison to a less well-educated, more treatment-resistant sample that included more ethnic/racial minorities using IRT and selected classical test analyses. METHODS: The QIDS-SR(16) and QIDS-C(16) were obtained in a sample of 441 outpatients with nonpsychotic MDD seen in the public sector in the Texas Medication Algorithm Project (TMAP). The Samejima graded response IRT model was used to compare the QIDS-SR(16) and QIDS-C(16). RESULTS: The nine symptom domains in the QIDS-SR(16) and QIDS-C(16) related well to overall depression. The slopes of the item response functions, a, which index the strength of relationship between overall depression and each symptom, were extremely similar with the two measures. Likewise, the CTT and IRT indices of symptom frequency (item means and locations of the item response functions, b(i) were also similar with these two measures. For example, sad mood and difficulty with concentration/decision making were highly related to the overall depression severity with both the QIDS-C(16) and QIDS-SR(16). Likewise, sleeping difficulties were commonly reported, even though they were not as strongly related to overall magnitude of depression. CONCLUSION: In this less educated, socially disadvantaged sample, differences between the QIDS-C(16) and QIDS-SR(16) were minor. The QIDS-SR(16) is a satisfactory substitute for the more time-consuming QIDS-C(16) in a broad range of adult, nonpsychotic, depressed outpatients.

Adult↗

PubMed2006

Making clinicians lives easier: guidance on use of the QIDS self-report in place of the MADRS.

BACKGROUND: The ability to convert total scores from one scale to another facilitates the interpretation of research findings and facilitates the use of systematic measurement in clinical practice. METHODS: Item Response Theory methods were used to convert total scores between the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16) and the Montgomery Asberg Depression Rating Scale (MADRS) total scores. Data were obtained from a sample of 233 outpatients with highly treatment-resistant, nonpsychotic major depressive episodes participating in a one-year open label study of vagus nerve stimulation to augment psychotropic medication treatment. RESULTS: MADRS total scores averaged 31.9 (SD = 6.7) at baseline and 21.9 (SD = 11.0) at one year. QIDS-SR16 total scores averaged 17.6 (SD = 3.6) at baseline and 12.5 (SD = 5.8) at one year. Based on one-year data (or exit if the patient did not complete one year), corresponding QIDS-SR16 and MADRS total scores were presented for each possible QIDS-SR16 and MADRS total score. A QIDS-SR16 total score of 5 was comparable to a MADRS total score of 7 or 8 (7.5). LIMITATION: The degree to which these results generalize to less treatment-resistant samples is unknown. CONCLUSION: The conversion of QIDS-SR16 and MADRS total scores provides a basis for clinicians who wish to use the QIDS-SR16 to understand what MADRS total scores reported in clinical trials approximate QIDS-SR16 total scores obtained with their patients.

Adult↗

PubMed2006

Family history of mood disorder and characteristics of major depressive disorder: a STAR*D (sequenced treatment alternatives to relieve depression) study.

INTRODUCTION: Clinicians routinely ask patients with major depressive disorder (MDD) about their family history. It is unknown, however, if patients who report a positive family history differ from those who do not. This study compared the demographic and clinical features of a large cohort of treatment-seeking outpatients with non-psychotic MDD who reported that they did or did not have at least one first-degree relative who had either MDD or bipolar disorder. METHODS: Subjects were recruited for the STAR( *)D multicenter trial. Differences in demographic and clinical features for patients with and without a family history of mood disorders were assessed after correcting for age, sex, race, and ethnicity. RESULTS: Patients with a family history of mood disorder (n=2265; 56.5%) were more frequently women and had an earlier age of onset of depression, as compared to those without such a history (n=1740; 43.5%). No meaningful differences were found in depressive symptoms, severity, recurrence, depressive subtype, or daily function. CONCLUSIONS: Women were twice as likely as men to report a positive family history of mood disorder, and a positive family history was associated with younger age of onset of MDD in the proband. Consistent with prior research, early age of onset appears to define a familial and, by extension, genetic subtype of major depressive disorder.

Adolescent↗

PubMed2006

Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.

BACKGROUND: After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor (SSRI), it is not known whether switching to one antidepressant is more effective than switching to another. METHODS: We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks: sustained-release bupropion (239 patients) at a maximal daily dose of 400 mg, sertraline (238 patients) at a maximal daily dose of 200 mg, or extended-release venlafaxine (250 patients) at a maximal daily dose of 375 mg. The study was conducted in 18 primary and 23 psychiatric care settings. The primary outcome was symptom remission, defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of the study. Scores on the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16), obtained at treatment visits, determined secondary outcomes, including remission (a score of 5 or less at exit) and response (a reduction of 50 percent or more on baseline scores). RESULTS: Remission rates as assessed by the HRSD-17 and the QIDS-SR-16, respectively, were 21.3 percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent for extended-release venlafaxine. These treatments did not differ significantly with respect to outcomes, tolerability, or adverse events. CONCLUSIONS: After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression. (ClinicalTrials.gov number, NCT00021528.).

Adult↗

PubMed2006

Medication augmentation after the failure of SSRIs for depression.

BACKGROUND: Although clinicians frequently add a second medication to an initial, ineffective antidepressant drug, no randomized controlled trial has compared the efficacy of this approach. METHODS: We randomly assigned 565 adult outpatients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy (mean final dose, 55 mg per day) to receive sustained-release bupropion (at a dose of up to 400 mg per day) as augmentation and 286 to receive buspirone (at a dose of up to 60 mg per day) as augmentation. The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of this study; scores were obtained over the telephone by raters blinded to treatment assignment. The 16-item Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR-16) was used to determine the secondary outcomes of remission (defined as a score of less than 6 at the end of this study) and response (a reduction in baseline scores of 50 percent or more). RESULTS: The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission (29.7 percent and 30.1 percent, respectively), QIDS-SR-16 remission (39.0 percent and 32.9 percent), and QIDS-SR-16 response (31.8 percent and 26.9 percent). Sustained-release bupropion, however, was associated with a greater reduction (from baseline to the end of this study) in QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1 percent, P<0.04), a lower QIDS-SR-16 score at the end of this study (8.0 vs. 9.1, P<0.02), and a lower dropout rate due to intolerance (12.5 percent vs. 20.6 percent, P<0.009). CONCLUSIONS: Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have certain advantages, including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events. (ClinicalTrials.gov number, NCT00021528.).

Adult↗

PubMed2006

Remissions in maternal depression and child psychopathology: a STAR*D-child report.

CONTEXT: Children of depressed parents have high rates of anxiety, disruptive, and depressive disorders that begin early, often continue into adulthood, and are impairing. OBJECTIVE: To determine whether effective treatment with medication of women with major depression is associated with reduction of symptoms and diagnoses in their children. DESIGN: Assessments of children whose depressed mothers were being treated with medication as part of the multicenter Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial conducted (between December 16, 2001 and April 24, 2004) in broadly representative primary and psychiatric outpatient practices. Children were assessed by a team of evaluators not involved in maternal treatment and unaware of maternal outcomes. Study is ongoing with cases followed at 3-month intervals. SETTING AND PATIENTS: One hundred fifty-one mother-child pairs in 8 primary care and 11 psychiatric outpatient clinics across 7 regional centers in the United States. Children were aged 7 to 17 years. MAIN OUTCOME MEASURES: Child diagnoses based on the Kiddie Schedule for Affective Disorders and Schizophrenia; child symptoms based on the Child Behavior Checklist; child functioning based on the Child Global Assessment Scale in mothers whose depression with treatment remitted with a score of 7 or lower or whose depression did not remit with a score higher than 7 on the Hamilton Rating Scale for Depression. RESULTS: Remission of maternal depression after 3 months of medication treatment was significantly associated with reductions in the children's diagnoses and symptoms. There was an overall 11% decrease in rates of diagnoses in children of mothers whose depression remitted compared with an approximate 8% increase in rates of diagnoses in children of mothers whose depression did not. This rate difference remained statistically significant after controlling for the child's age and sex, and possible confounding factors (P = .01). Of the children with a diagnosis at baseline, remission was reported in 33% of those whose mothers' depression remitted compared with only a 12% remission rate among children of mothers whose depression did not remit. All children of mothers whose depression remitted after treatment and who themselves had no baseline diagnosis for depression remained free of psychiatric diagnoses at 3 months, whereas 17% of the children whose mothers remained depressed acquired a diagnosis. Findings were similar using child symptoms as an outcome. Greater level of maternal response was associated with fewer current diagnoses and symptoms in the children, and a maternal response of at least 50% was required to detect an improvement in the child. CONCLUSIONS: Remission of maternal depression has a positive effect on both mothers and their children, whereas mothers who remain depressed may increase the rates of their children's disorders. These findings support the importance of vigorous treatment for depressed mothers in primary care or psychiatric clinics and suggest the utility of evaluating the children, especially children whose mothers continue to be depressed.

Adult↗

PubMed2006

Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment.

Depressive disorders account for a large and increasing global burden of disease. Although the condition of many patients improves with medication, only a minority experience full remission, and patients whose condition responds to one medication may not have a response to others. Individual variation in antidepressant treatment outcome is, at present, unpredictable but may have a partial genetic basis. We searched for genetic predictors of treatment outcome in 1,953 patients with major depressive disorder who were treated with the antidepressant citalopram in the Sequenced Treatment Alternatives for Depression (STAR*D) study and were prospectively assessed. In a split-sample design, a selection of 68 candidate genes was genotyped, with 768 single-nucleotide-polymorphism markers chosen to detect common genetic variation. We detected significant and reproducible association between treatment outcome and a marker in HTR2A (P range 1 x 10(-6) to 3.7 x 10(-5) in the total sample). Other markers in HTR2A also showed evidence of association with treatment outcome in the total sample. HTR2A encodes the serotonin 2A receptor, which is downregulated by citalopram. Participants who were homozygous for the A allele had an 18% reduction in absolute risk of having no response to treatment, compared with those homozygous for the other allele. The A allele was over six times more frequent in white than in black participants, and treatment was less effective among black participants. The A allele may contribute to racial differences in outcomes of antidepressant treatment. Taken together with prior neurobiological findings, these new genetic data make a compelling case for a key role of HTR2A in the mechanism of antidepressant action.

Adult↗

PubMed2006

Lamotrigine for bipolar disorder and comorbid cocaine dependence: a replication and extension study.

BACKGROUND: Bipolar disorder (BPD) is associated with high rates of substance abuse. We previously reported favorable results with lamotrigine in 30 patients with BPD and cocaine dependence. This report examines lamotrigine therapy in an additional 32 cocaine dependent patients. Data on these 32 participants are presented as a replication study. In addition, we extend the previous findings by combining data from both groups, and by exploring predictors of response. METHOD: Participants received a baseline evaluation and assessment for up to 36weeks with the 17-item Hamilton Rating Scale for Depression (HRSD(17)), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS(18)), and Cocaine Craving Questionnaire (CCQ). Urine samples were obtained, and participants reported drug use during the previous week. RESULTS: In the replication sample (n=32), significant improvements were observed in HRSD(17), YMRS, BPRS(18), and CCQ (baseline to exit), as well as on dollars/week spent on cocaine. In the extension study, the original sample (n=30) and the replication sample (n=32) were combined for a total of 62 participants in the intent-to-treat sample. HRSD(17), YMRS, BPRS(18), and CCQ scores, as well as dollars spent on cocaine, decreased significantly. LIMITATIONS: The study has an open-label, uncontrolled design. CONCLUSION: Lamotrigine treatment was associated with significant improvements in mood, drug craving, and drug use. Controlled trials are needed.

Adult↗

PubMed2006

Effect of two prednisone exposures on mood and declarative memory.

Corticosteroids are essential for life and an integral part of the stress response. However, in excess, corticosteroids can be associated with a variety of effects on the brain including hippocampal atrophy and even neuronal death, mood changes, and declarative memory impairment. The magnitude of mood change in patients receiving prednisone is reportedly associated with previous lifetime corticosteroid exposure, consistent with a sensitization or kindling process whereby greater effects are observed with repeated exposure. To our knowledge, the effect of multiple corticosteroid exposures on mood and memory has not been previously examined prospectively in animals or humans. In this study, 30 human volunteers, with no history of systemic prescription corticosteroid therapy, were given (in random order using a crossover design) two 3-day exposures of prednisone (60 mg/day) and one of identical placebo, with 11-day washouts between each medication exposure. Before and after each 3-day prednisone/placebo exposure, declarative memory was assessed using different versions of the Rey Auditory Verbal Learning Test (RAVLT) to minimize practice or learning effects, while mood was assessed with the 21-item Hamilton Rating Scale for Depression, Young Mania Rating Scale and Internal State Scale. No significant mood changes were found. However, a significant decrease in aspects of RAVLT performance was observed after the first prednisone exposure consistent with a decline in declarative memory performance. The decline in RAVLT performance was significantly smaller after the second prednisone exposure as compared to the initial prednisone exposure. Thus, a second prednisone exposure was associated with an attenuated prednisone-effect on declarative memory. These data suggest tolerance or habituation, rather than sensitization, to prednisone effects on declarative memory during a second exposure. Implications and possible explanations for the findings are discussed.

Adult↗

PubMed2006

Enrolling research subjects from clinical practice: ethical and procedural issues in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial is a multi-site effectiveness study funded by the National Institute of Mental Health (NIMH) with the aim of identifying successful, acceptable and cost-effective treatment strategies for outpatients with unremitted depression. With enrollment of 4,041 adults with major depressive disorder (MDD), it is the largest controlled psychiatric treatment study ever undertaken. In the course of developing procedures to ensure that ambitious enrollment goals were met, a number of ethical and practical issues became apparent that underscore the conflicts between effectiveness research and human subject protections. These are delineated as they relate to study design; eligibility criteria; incentives to subjects; investigators and clinical sites; the complementary roles of clinical research coordinators (CRCs) and study clinicians; and recruitment and consent procedures. The STAR*D trial exemplifies the interplay and tension between those strategies that integrate research and clinical aims and roles in the service of enhancing external validity, site participation, and recruitment and retention versus those strategies that differentiate research and clinical treatment in the service of research integrity and human subject protections. We hope that a discussion of these key challenges and dilemmas and how they have been addressed will help inform future discussions concerning design and conduct of ethical effectiveness trials designed to optimize care in real world clinical settings.

Adolescent↗