Advancing the Wisconsin idea.
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Administrative Personnel↗
Biomedical subjects
Robert N Golden
Publications and source records attributed to Robert N Golden.
Mood disorders in the medically ill: scientific review and recommendations.
OBJECTIVE: The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research. DATA SOURCES: Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors. STUDY SELECTION/DATA EXTRACTION: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed. CONCLUSIONS: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.
Acquired Immunodeficiency Syndrome↗
The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence.
OBJECTIVE: The purpose of this study was to assess the evidence base for the efficacy of light therapy in treating mood disorders. METHOD: The authors systematically searched PubMed (January 1975 to July 2003) to identify randomized, controlled trials of light therapy for mood disorders that fulfilled predefined criteria. These articles were abstracted, and data were synthesized by disease and intervention category. RESULTS: Only 13% of the studies met the inclusion criteria. Meta-analyses revealed that a significant reduction in depression symptom severity was associated with bright light treatment (eight studies, having an effect size of 0.84 and 95% confidence interval [CI] of 0.60 to 1.08) and dawn simulation in seasonal affective disorder (five studies; effect size=0.73, 95% CI=0.37 to 1.08) and with bright light treatment in nonseasonal depression (three studies; effect size=0.53, 95% CI=0.18 to 0.89). Bright light as an adjunct to antidepressant pharmacotherapy for nonseasonal depression was not effective (five studies; effect size=-0.01, 95% CI=-0.36 to 0.34). CONCLUSIONS: Many reports of the efficacy of light therapy are not based on rigorous study designs. This analysis of randomized, controlled trials suggests that bright light treatment and dawn simulation for seasonal affective disorder and bright light for nonseasonal depression are efficacious, with effect sizes equivalent to those in most antidepressant pharmacotherapy trials. Adopting standard approaches to light therapy's specific issues (e.g., defining parameters of active versus placebo conditions) and incorporating rigorous designs (e.g., adequate group sizes, randomized assignment) are necessary to evaluate light therapy for mood disorders.
Adult↗
The relationship between psychiatry residency applicant evaluations and subsequent residency performance.
OBJECTIVE: The goal of this study was to measure the predictive value of applicant evaluations for a psychiatry residency in terms of the subsequent performance of those who matriculated in the program. METHOD: The match lists for resident cohorts beginning their course of training over 4 years were divided into thirds, which served as our primary, preresidency measure of expected performance. The preresidency applicant evaluations of those residents who entered were compared to their postresidency evaluations. RESULTS: There was no significant association between preresidency selection evaluations and postresidency final evaluations in any of the four cohorts of trainees. CONCLUSIONS: The overall results of this study of four cohorts of residents indicate only a small, nonsignificant association between pre- and postresidency evaluations. Further efforts to predict residency performance in applicants may help identify those trainees who might benefit from additional monitoring and supervision.
Education↗
Making advances where it matters: improving outcomes in mood and anxiety disorders.
Mood and anxiety disorders are among the most prevalent psychiatric illnesses and are associated with considerable morbidity and mortality. Selective serotonin reuptake inhibitors (SSRIs) are safe and effective treatments for major depression and anxiety disorders, and have become the most widely prescribed antidepressants worldwide. However, several issues limit SSRI treatment outcomes. Although SSRIs have a wider therapeutic margin and a milder side-effect profile compared to earlier antidepressants, even minor SSRI side effects can have a major impact on treatment outcomes by interfering with patient compliance. Nausea is one of the most common early SSRI side effects, and advances in SSRI delivery systems can diminish this. A controlled-release formulation of paroxetine targets the site of absorption for a more distal region of the small intestine, thereby avoiding the stimulation of upper gastrointestinal serotonin receptors that mediate nausea. The sustained-release characteristics also reduce the amplitude in blood level peaks and troughs, which may lead to diminished side effects and enhanced efficacy. Sexual side effects and weight gain are important sustained SSRI side effects, which affect compliance during continuation and maintenance phases of treatment. Several strategies address SSRI sexual side effects, including the use of adjunctive medication and/or manipulations in the scheduling of drug administration. Depression negatively impacts the management of many medical illnesses, including cardiovascular disease, cancer, and infectious diseases. The recognition and treatment of depression leads to improved outcomes in the management of breast cancer. Prophylactic SSRI treatment significantly reduces the incidence of interferon-associated depression and enhances completion rates in malignant melanoma.
Acquired Immunodeficiency Syndrome↗
Changes in neuropsychological functioning with progression of HIV-1 infection: results of an 8-year longitudinal investigation.
Despite the advent of more effective treatments for HIV-1 infection, cognitive impairment is still frequent and questions remain regarding which areas of impairment are more common in the different disease stages. This study investigated cognitive performance over an 8-year period of time in 59 HIV-1 seropositive (HIV-1+) men who were clinically asymptomatic at study entry, in comparison to a cohort of 55 HIV-1 seronegative (HIV-1-) men. Every 6 months we examined cognitive functioning in 5 domains-fine motor speed, attention, verbal memory, executive functioning, and speed of information processing. We found that patients with AIDS scored significantly worse on fine motor speed and speed of information processing than HIV-1- individuals and the HIV-1+ non-AIDS patients. In addition, the HIV-1+ non-AIDS patients performed more poorly than the HIV-1- group on speed of information processing. Depressive symptoms were also associated with diminished performance on measures of attention, executive functioning, and speed of information processing. Further research is needed to examine the effects of disease stage and depression on cognitive impairment in the era of new HIV treatments.
AIDS Dementia Complex↗
Effect of stress on pregnancy outcome among women undergoing assisted reproduction procedures.
BACKGROUND: This study was performed to examine the effect of stress on pregnancy outcome in women who underwent assisted reproductive technology (ART) procedures. METHODS: In a controlled clinical study of healthy volunteers in an academic research environment, stress was measured subjectively by administering patient questionnaires and biochemically by examining urinary excretion of cortisol and 6-sulfatoxy-melatonin (6-SM), the primary metabolite of melatonin and a marker of peripheral stress response. A total of 42 women who underwent ART procedures during an 18-month period agreed to participate in the study and were enrolled consecutively. The women collected 24-hour urine specimens on the day after human chorionic gonadotropin administration and concurrently completed the State-Trait Anxiety Inventory questionnaire. We measured the cortisol and 6-SM levels in the urine collection for each of the 42 women and for 10 oocyte donors who served as controls. Pregnancy tests were performed 14 days after embryo transfer. Analysis of covariance was used to compare the relationship of stress ratings to urinary cortisol and 6-SM levels among the women who became pregnant, the women who did not, and the women who served as controls. Other variables were explored by performing chi2 analysis and Fisher's exact test. RESULTS: Neither self-ratings of acute anxiety, nor total daily 6-SM value, nor cortisol levels were associated with pregnancy outcome in the ART procedures. CONCLUSION: Biochemical markers of stress failed to support a deleterious effect of stress on pregnancy outcome in women who underwent ART procedures. Subjective measurement of stress levels did not differ between women who became pregnant and those who did not.
Adolescent↗
The effects of mirtazapine on plasma lipid profiles in healthy subjects.
BACKGROUND: The novel antidepressant mirtazapine has been linked to elevated random plasma total cholesterol (TC) levels. The purpose of this study was to evaluate in a more controlled and precise approach the putative effects of mirtazapine on plasma lipids. METHOD: In a double-blind design, 50 healthy subjects (30 women and 20 men) were randomized to receive either mirtazapine (N = 28) or placebo (N = 22) for a 4-week period. The study was conducted from June 1997 to September 1998. The initial dose for the mirtazapine group was 15 mg daily, which was increased to 30 mg daily at the beginning of the second week. Body weight and plasma lipoprotein profiles, including TC, low-density lipoproteins (LDL), high-density lipoproteins (HDL), and triglycerides, were determined at baseline and at weekly intervals throughout the study period. RESULTS: At baseline, there were no group differences in any of the measures. There was a statistically significant increase of 2.5% in mean body weight over the course of the study in the mirtazapine group that appeared to reach a plateau at 3 weeks, while no increase was observed in the placebo group. Mirtazapine subjects also showed significantly increased TC at week 4 (p =.016) and a transient rise in triglycerides that normalized by week 4. No significant changes in any of the other lipid parameters, including HDL, LDL, and TC/HDL ratios, were observed within either group. Changes in TC were significantly and positively correlated with changes in weight (p <.01). CONCLUSION: These results suggest that while mirtazapine may be associated with increased TC, it does not increase LDL levels or affect the ratio of TC to HDL.
Adult↗
Efficacy and tolerability of controlled-release paroxetine.
Paroxetine controlled-release (CR) was developed with the objective of minimizing the occurrence and severity of selective serotonin reuptake inhibitor (SSRI)-associated adverse events, thereby improving clinical outcomes. Paroxetine CR delays the onset and controls the rate of absorption of medication. Multicenter controlled clinical trials have found lower rates of early-onset, treatment-associated nausea and lower dropout rates from adverse events in depressed patients treated with paroxetine CR compared with those treated with the conventional, immediate-release formulation. At the same time, clinical response and remission rates are favorable. Other studies have demonstrated the efficacy and tolerability of paroxetine CR in geriatric depression, panic disorder, and social anxiety disorder. The CR formulation of paroxetine appears to represent an effective pharmacokinetic approach to minimizing SSRI adverse events and thereby enhancing clinical outcomes.
Adult↗
A longitudinal study of serotonergic function in depression.
Several reports have described abnormal neuroendocrine responses to serotonergic challenge tests in depression, but few have studied depressed patients followed longitudinally. In order to determine whether blunted prolactin responses to clomipramine challenge is a "state" vs. "trait" marker in depression, we applied this challenge paradigm to 20 patients with Major Depression prior to treatment and at three additional time points following response to desipramine: at the completion of acute treatment; at the end of the continuation phase of treatment; and after a minimum of three weeks "washout" following the discontinuation of treatment. The prolactin response to clomipramine challenge was blunted in depressed patients compared with matched healthy control subjects, at each time point over the longitudinal course of their illness and recovery. Challenge test results in depressed patients did not change after response to acute desipramine therapy, at the conclusion of the continuation phase of treatment, or while in a medication-free state of remission. Blunted prolactin response to clomipramine challenge persists in depressed patients after recovery from acute illness, and may reflect an underlying biological vulnerability.
Adult↗
Efficacy and tolerability of controlled-release and immediate-release paroxetine in the treatment of depression.
BACKGROUND: Antidepressant efficacy may be compromised by early discontinuation of treatment secondary to common, treatment-emergent side effects, including nausea, agitation, and somnolence. Paroxetine controlled-release (CR) was developed to improve general tolerability and, in particular, gastrointestinal tolerability. OBJECTIVE: To determine the antidepressant efficacy and tolerability of paroxetine CR in adult patients 18 to 65 years of age with DSM-IV major depressive disorder. METHOD: Paroxetine CR (25-62.5 mg/day; N = 212) and paroxetine immediate-release (IR; 20-50 mg/day; N = 217) were compared with placebo (N = 211) in the pooled dataset from 2 identical, double-blind, 12-week clinical trials. RESULTS: Both paroxetine CR and paroxetine IR exhibited efficacy in major depressive disorder as assessed by the reduction in 17-item Hamilton Rating Scale for Depression total score compared with placebo. Moreover, depressed mood and psychic anxiety symptoms improved as early as treatment week 1 in the paroxetine CR group compared with the placebo group. After 6 weeks of treatment, response and remission rates were 41.5% and 20.5% for placebo, 52.8% and 29.6% for paroxetine IR, and 58.9% and 34.4% for paroxetine CR, respectively. After 12 weeks of treatment, response and remission rates were 61.2% and 44.0% for placebo, 72.9% and 52.5% for paroxetine IR, and 73.7% and 56.2% for paroxetine CR, respectively. Rates of nausea were significantly lower for paroxetine CR (14%) than for paroxetine IR (23%; p < or = .05) during week 1. Rates of dropout due to adverse events were comparable between paroxetine CR and placebo, while significantly (p = .0008) more patients treated with paroxetine IR withdrew from the study prematurely compared with those treated with placebo. CONCLUSION: Paroxetine CR is an effective and well-tolerated antidepressant exhibiting symptomatic improvement as early as week 1. Paroxetine CR is associated with low rates of early-onset nausea and dropout rates due to adverse events comparable to those of placebo. The clinical improvement seen with paroxetine CR, coupled with its favorable adverse event profile, suggests a benefit for therapeutic outcome with paroxetine CR.
Adolescent↗
A direct comparison of presenting characteristics of depressed outpatients from primary vs. specialty care settings: preliminary findings from the STAR*D clinical trial.
PURPOSE: No study has directly compared the clinical features of depression for patients entering clinical trials using identical enrollment criteria at primary care (PC) and specialty care (SC) settings. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (http://www.star-d.org) provides a unique opportunity to provide this comparison for patients with a major depressive disorder (MDD) requiring treatment. SUBJECTS AND METHODS: We report baseline data for the first 1500 patients enrolled in this trial involving 41 clinic sites (18 PC, 23 SC). Broadly inclusive eligibility criteria required that patients have a DSM-IV diagnosis of nonpsychotic MDD, have not failed an adequate medication trial during their current episode and score>or=14 on the 17-item Hamilton Rating Scale for Depression (HAM-D17). Primary outcomes included the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) and the HAM-D17. RESULTS: Specialty care and PC patients had equivalent degrees of depressive severity (IDS-C30=35.8; HAM-D17=20.4). Specialty care patients were almost twice as likely to report a prior suicide attempt than PC patients (21% vs. 12%, P<.0001) and slightly less likely to endorse suicidal ideation in the past week (45.0% vs. 50.8%, P=.006). The only other distinguishing core symptoms were a slightly lower likelihood of PC patients endorsing depressed mood (95.2% vs. 97.7%, P=.032) or anhedonia (66.3% vs. 70.7%, P=.042, IDS-C30) and a lower likelihood of PC patients endorsing weight loss (IDS-C30). HAM-D17 results were identical. CONCLUSION: Depressive severity was not different, and symptomatic presentations did not differ substantially. Major depressive disorder is more similar than different among patients at SC and PC settings. Thus, similar clinical and research methods for screening, detecting and measuring treatment outcomes can be applied in both settings.
Ambulatory Care↗
ENRICHD and SADHART: implications for future biobehavioral intervention efforts.
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Clinical Trials as Topic↗
Predicting fatigue and depression in HIV-positive gay men.
HIV-related fatigue is a prevalent and troubling symptom for HIV-positive people. The purpose of the study was to develop a model for predicting fatigue and depression among HIV-positive gay men as a function of history of fatigue and depression in the previous year and to determine whether psychological and psychosocial variables or physiologic variables better predict fatigue. Data from 96 HIV-positive gay men followed longitudinally for up to 7.5 years were used to develop logistic regression models for predicting fatigue and depression. Fatigue was predicted by both physiologic and psychological risk factors, whereas depression was predicted by only psychological risk factors.
Adult↗