Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. A meta-analysis.

BACKGROUND: Questions have been raised regarding the relative efficacy and tolerability of the different serotonin transport inhibitors in the treatment of obsessive-compulsive disorder. We compared the results from four large multicenter placebo-controlled trials of the serotonin transport inhibitors clomipramine hydrochloride (N = 520), fluoxetine hydrochloride (N = 355), fluvoxamine maleate (N = 320), and sertraline hydrochloride (N = 325) for the treatment of obsessive-compulsive disorder. METHODS: Effect size was calculated by subtracting the end-point drug treatment mean change from the end-point placebo mean change and dividing by the end-point pooled change standard deviation. A test for overall differences between effect sizes was conducted, followed by all possible pairwise comparisons. The Yale-Brown Obsessive Compulsive Scale was the primary outcome measure for all four studies. RESULTS: All four agents were significantly more effective than placebo, with clomipramine significantly more effective than the other three treatments, which did not differ in effect size. A significantly greater percentage of patients treated with clomipramine were rated much or very much improved than were patients treated with fluoxetine, fluvoxamine, or sertraline. CONCLUSION: While the results of this meta-analysis support the superiority of clomipramine, head-to-head, double-blind comparisons of these compounds would be the best test of comparative efficacy and tolerability.

Medical costs attributed to depression among patients with a history of high medical expenses in a health maintenance organization.

BACKGROUND: While previous studies have compared medical utilization between depressed and nondepressed patients, we conducted a study that focused specifically on patients who had a history of high medical expenditures. METHODS: This study was designed to determine whether a positive screen for depression is predictive of continued high medical expenditures. Medical utilization data were obtained on 50,000 patients enrolled in the DeanCare health maintenance organization for 2 consecutive years. Consistent high utilizers were identified based on the medical utilization costs (paid by the health maintenance organization) for those 2 consecutive years, 1992 and 1993. A depression screen based on the Medical Outcomes Survey was mailed to 786 high utilizers. Their costs were determined for 1994. Regression analyses identified 1994 costs associated with depression, adjusting for age, sex, benefits package, and medical comorbidity. RESULTS: Depressed high utilizers were more likely than nondepressed high utilizers to have higher medical costs in 1994. Among high utilizers, depressed patients' 1994 costs were significantly higher ($5764 vs $4227; P < .001), although expenditures for depressed and nondepressed high utilizers were similar for the previous 2 years. The total medical cost associated with depression in 1994, adjusted for age, sex, benefits package, and medical comorbidity, was $1498 per patient. CONCLUSIONS: In the third year (1994), a positive Medical Outcomes Survey screen for depression in high utilizers was associated with $1498 in higher medical costs. The average actual amount spent on depression treatment accounted for only a small portion of total medical costs for depressed high utilizers in the third year.

Cost-effectiveness of systematic depression treatment for high utilizers of general medical care.

BACKGROUND: Expanding access to high-quality depression treatment will depend on the balance of incremental benefits and costs. We examine the incremental cost-effectiveness of an organized depression management program for high utilizers of medical care. METHODS: Computerized records at 3 health maintenance organizations were used to identify adult patients with outpatient medical visit rates above the 85th percentile for 2 consecutive years. A 2-step screening process identified patients with current depressive disorders, who were not in active treatment. Eligible patients were randomly assigned to continued usual care (n = 189) or to an organized depression management program (n = 218). The program included patient education, antidepressant pharmacotherapy initiated in primary care (when appropriate), systematic telephone monitoring of adherence and outcomes, and psychiatric consultation as needed. Clinical outcomes (assessed using the Hamilton Depression Rating Scale on 4 occasions throughout 12 months) were converted to measures of "depression-free days." Health services utilization and costs were estimated using health plan-standardized claims. RESULTS: The intervention program led to an adjusted increase of 47.7 depression-free days throughout 12 months (95% confidence interval [CI], 28.2-67.8 days). Estimated cost increases were $1008 per year (95% CI, $534-$1383) for outpatient health services, $1974 per year for total health services costs (95% CI, $848-$3171), and $2475 for health services plus time-in-treatment costs (95% CI, $880-$4138). Including total health services and time-in-treatment costs, estimated incremental cost per depression-free day was $51.84 (95% CI, $17.37-$108.47). CONCLUSIONS: Among high utilizers of medical care, systematic identification and treatment of depression produce significant and sustained improvements in clinical outcomes as well as significant increases in health services costs.

Sertraline for social phobia: a double-blind, placebo-controlled crossover study.

OBJECTIVE: The authors examined the efficacy of sertraline in the treatment of social phobia. METHOD: In a double-blind crossover study, 12 outpatients were randomly assigned to 10 weeks of sertraline (50-200 mg/day, flexible dosing) and 10 weeks of placebo. RESULTS: A statistically significant improvement in scores on the Liebowitz Social Anxiety Scale was found with sertraline but not with placebo. There was no significant difference between scores obtained with computer- and clinician-administered versions of the Liebowitz Social Anxiety Scale, and the majority of patients preferred to be interviewed by the computer. CONCLUSIONS: Sertraline seems a safe and effective treatment for social phobia, and computer administration may be a preferable mode of assessment with socially phobic patients.

Impact of generalized social anxiety disorder in managed care.

OBJECTIVE: The authors determined the costs associated with generalized social anxiety disorder in a managed care setting. METHOD: A three-phase mail and telephone survey was conducted from July to October 1998 in two outpatient clinics of a large health maintenance organization (HMO). The survey assessed direct costs, indirect costs, health-related quality of life, and clinical severity associated with generalized social anxiety disorder, both alone and with comorbid psychopathology. RESULTS: The weighted prevalence rate of current generalized social anxiety disorder was 8.2%. In the past year, only 0.5% of subjects with generalized social anxiety disorder had been accurately diagnosed. Yet 44.1% had a mental health specialty visit or had been prescribed an antidepressant, and psychiatric comorbidity was found in 43.6%. Noncomorbid generalized social anxiety disorder was associated with significantly lower health-related quality of life, work productivity, and earnings and greater utilization of health services; generalized social anxiety disorder with comorbid psychopathology was even more disabling. Suicide was attempted by 21.9% of subjects with noncomorbid generalized social anxiety disorder. Persons with average-severity generalized social anxiety disorder had probabilities of graduating from college that were 10 percentage points lower, earned wages that were 10% lower, and had probabilities of holding a technical, professional, or managerial job that were 14 percentage points lower than the comparison group. CONCLUSIONS: In a community cohort of HMO members, generalized social anxiety disorder was rarely diagnosed or treated despite being highly prevalent and associated with significant direct and indirect costs, comorbid depression, and impairment.

Social anxiety disorder: an unrecognized problem in primary care.

Social anxiety disorder, or social phobia, is one of the most common mental disorders, yet it remains underrecognized and undertreated. Individuals with social anxiety disorder frequently have psychiatric comorbidity, including mood, anxiety, and substance abuse disorders, that can further impair a person's ability to function. This article reviews the literature on social anxiety disorder and explores questions regarding its prevalence, rates of recognition and treatment, and natural history. The association between social anxiety disorder and psychiatric comorbidity and suicide is reviewed, as well as quality-of-life issues, including the impact of social anxiety disorder on educational attainment, occupational functioning and financial dependency, marital status, and health care utilization. There is a need for further study and greater awareness among primary health care providers about the prevalence and treatment of social anxiety disorder.

Computer-administered clinical rating scales. A review.

While clinician-administered symptom rating scales are the most commonly used outcome measures in pharmaceutical research, error variance due to poor inter-rater reliability increases the risk of type II errors in multi-center clinical trials. Such error variance could obscure true differences between active drug and placebo, or between two comparator compounds. Computer-administered versions of symptom rating scales originally designed to be administered by trained clinicians offer a solution to this problem. This paper reviews the empirical data on the reliability, validity and equivalence of computer-administered rating scales. Computer-administered versions of clinician-administered scales are now available for the assessment of depression, anxiety, obsessive-compulsive disorder, and social phobia. Validation studies support the reliability, validity and equivalence of these scales. Patient reaction has been positive, with patients generally more honest with and often preferring the computer for assessing sensitive areas such as suicide, alcohol or drug abuse, sexual behavior, or HIV related symptoms. Applications using Interactive Voice Response (IVR) technology facilitate longitudinal monitoring of patients without requiring office visits to collect data, increase the accessibility of information to the clinician, and the quality of patient care through more informed decision making. When used in accordance with established ethical guidelines, computers offer a reliable, inexpensive, accessible, and time-efficient means of assessing psychiatric symptoms.

Behavioral versus pharmacological treatments of obsessive compulsive disorder: a meta-analysis.

The goal of the study was to provide a quantitative analysis of the relative efficacy of all five currently available serotonin reuptake inhibitors (SRIs) and behavior therapy [exposure and response prevention (ERP)] for obsessive compulsive disorder. The relationship between effect size and methodological characteristics was also empirically examined. A search was conducted of several computerized databases covering the dates from 1973 to 1997. Seventy-seven studies were identified, yielding 106 treatment comparisons involving 4641 patients. Effect sizes were analyzed between individual interventions and between intervention class [SRI, ERP or the combined treatment of an SRI with ERP(ERP/SRI)]. Data were analyzed both before and after controlling for methodological variables. The effect size for clomipramine (CMI) was significantly greater than the other SRIs, with the exception of fluoxetine (FLX). CMI was not significantly greater than ERP or ERP/SRI. As a class, ERP was significantly greater than SRIs as a whole. Effect sizes were larger for studies without a control group or random assignment, for self-reported outcome measures, and varied significantly by method of effect size calculation. Year of publication was significantly related to effect size. When controlling for these methodological variables, CMI was not significantly greater than FLX or fluvoxamine (FLV), and ERP was no longer significantly greater than the SRIs as a whole. No significant difference was found between CMI and the other SRIs as a group in head to head trials. No differences in drop-out rates were found. CMI stands out from the other SRIs. This difference is probably not clinically significant enough to warrant first choice treatment, given CMI's greater lethality in overdose. The choice between an SRI or ERP is dominated primarily by the infrequent availability of ERP and to a lesser degree by personal preference. Methodological differences significantly impact effect size.

Depression, use of medical services and cost-offset effects.

This review considers evidence that depression is associated with increased use of general medical services and that more intensive treatment of depression might be expected to reduce medical expenditures. Cross-sectional studies strongly support an association between depression and medical utilization, but cannot establish a causal relationship. Available longitudinal studies lack the sample size and duration of follow-up necessary to examine how changes in depression influence utilization. Some quasi-experimental and experimental studies support a "cost-offset" effect due to mental health treatment, but no experimental data directly address the specific impact of depression treatment on medical utilization. The available data identify the potential for large cost savings through improved treatment of depression but do not clearly establish that such savings can be realized. Definitive proof of a cost-offset due to depression treatment will require a new generation of experimental studies adapted to assess economic outcomes.

Effect of primary care treatment of depression on service use by patients with high medical expenditures.

OBJECTIVE: The study examined the impact of identifying and treating depression among patients who had a history of high medical expenditures. Effects on service use, disability, and quality of life were measured. METHODS: A total of 786 high users of services from two primary care clinics and an equal number of randomly selected patients who were not high users were screened for depression using the Medical Outcomes Study (MOS) depression screen. High-user patients who screened positive were subsequently seen by their primary care physician for a diagnostic interview. The 20 patients with a confirmed diagnosis of depression were offered open-label antidepressant treatment by their primary care physician for six months. RESULTS: All 20 patients completed the six-month study. Treatment resulted in significant reductions in depression and significant improvements in quality of life in the areas of social functioning, general health, mental health, physical functioning, emotional role functioning, and vitality. Days of missed work per month were reduced, and the percentage of patients who reported not being at all impaired by their depression at work increased. Costs for service use fell from $13.28 to $6.75 per day; when costs for the treatment study were added, the daily service use cost was $12.55. CONCLUSIONS: Identification and treatment of depression among patients with a history of high medical expenditures improved depression and increased work productivity and quality of life. Service use decreased with treatment. A larger sample and control group are needed to determine if treatment is associated with a statistically significant decrease in medical expenditures.

Computerized screening for psychiatric disorders in an outpatient community mental health clinic.

OBJECTIVE: This study examined the validity and utility of two types of computer-administered versions of a screening interview, PRIME-MD (Primary Care Evaluation of Mental Disorders), in a mental health setting: one administered by desktop computer and one by computer using a touch-tone telephone and interactive voice response (IVR) technology. METHODS: Fifty-one outpatients at a community mental health clinic were given both IVR and desktop PRIME-MD and the Structured Clinical Interview for DSM-IV (SCID-IV), which was administered by a clinician, in a counterbalanced order. Diagnoses were also obtained from charts. RESULTS: Prevalence rates found by both computer interviews were similar to those obtained by the SCID-IV for the presence of any diagnosis, any affective disorder, and any anxiety disorder. Prevalence rates for specific diagnoses were also similar to those found by the SCID-IV except for dysthymia, obsessive-compulsive disorder, and panic disorder; the first two conditions were found to be more prevalent by the computer, and panic disorder was more prevalent by the SCID. Compared with the prevalence rates in the charts, the rates found by the computer were higher for anxiety disorders, particularly for obsessive-compulsive disorder and social phobia. Using the SCID-IV as the criterion, both computer-administered versions of PRIME-MD had high sensitivity, specificity, and positive predictive value for most diagnoses. No significant difference was found in how well patients liked each form of interview. CONCLUSIONS: Results support the validity and utility of both desktop and IVR PRIME-MD for gathering information from mental health patients about certain diagnoses.

Reversibility of psychiatric symptoms in a chronic solvent abuser: a case report.

The acute mental status changes associated with inhaled solvent use have been well described. The potential long-term neuropsychiatric sequelae of inhaled solvent use are not as well characterized. We present here the case of a 20-year-old male with a 7-year history of inhaled solvent (toluene) use whose neurological and psychiatric status were followed closely over a 1-month period on an inpatient psychiatric unit.

Does physician education on depression management improve treatment in primary care?

OBJECTIVE: To assess the effect of physician training on management of depression. DESIGN: Primary care physicians were randomly assigned to a depression management intervention that included an educational program. A before-and-after design evaluated physician practices for patients not enrolled in the intervention trial. SETTING: One hundred nine primary care physicians in 2 health maintenance organizations located in the Midwest and Northwest regions of the United States. PATIENTS/PARTICIPANTS: Computerized pharmacy and visit data from a group of 124,893 patients who received visits or prescriptions from intervention and usual care physicians. INTERVENTIONS: Primary care physicians received education on diagnosis and optimal management of depression over a 3-month training period. Methods of education included small group interactive discussions, expert demonstrations, role-play, and academic detailing of pharmacotherapy, criteria for urgent psychiatric referrals, and case reviews with psychiatric consultants. MEASUREMENTS AND MAIN RESULTS: Pharmacy and visit data provided indicators of physician management of depression: rate of newly diagnosed depression, new prescription of antidepressant medication, and duration of pharmacotherapy. One year after the training period, intervention and usual care physicians did not differ significantly in the rate of new depression diagnosis (P =.95) or new prescription of antidepressant medicines (P =.10). Meanwhile, patients of intervention physicians did not differ from patients of usual care physicians in adequacy of pharmacotherapy (P =.53) as measured by 12 weeks of continuous antidepressant treatment. CONCLUSIONS: After education on optimal management of depression, intervention physicians did not differ from their usual care colleagues in depression diagnosis or pharmacotherapy.

Teaching psychiatric residents to teach.

Teaching other residents and medical students is one of the primary activities of psychiatric residents, yet most receive minimal or no formal training or supervision on how to teach. This report describes a Teaching Day Workshop, designed and implemented by residents at the Massachusetts General Hospital with the support of their faculty and an educational consultant, as one model to introduce the concepts and techniques of teaching to psychiatric residents. The participating residents were unanimous in their positive appraisal of the workshop, and they recommended that additional seminars on teaching be integrated into the residency's core curriculum. Ways that the Teaching Day Workshop can be adapted for use by other residency training programs are discussed. The authors believe that teaching residents to be better teachers can have an impact on recruitment of medical students into psychiatry and psychiatric residents into careers in academic psychiatry.

Depression among high utilizers of medical care.

OBJECTIVE: To determine the prevalence of unrecognized or unsuccessfully treated depression among high utilizers of medical care, and to describe the relation between depression, medical comorbidities, and resource utilization. DESIGN: Survey. SETTING: Three HMOs located in different geographic regions of the United States. PATIENTS: A total of 12,773 HMO members were identified as high utilizers. Eligibility criteria for depression screening were met by 10,461 patients. MEASUREMENTS AND MAIN RESULTS: Depression status was assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition. Depression screening was completed in 7,203 patients who were high utilizers of medical care, of whom 1,465 (20.3%) screened positive for current major depression or major depression in partial remission. Among depressed patients, 621 (42.4%) had had a visit with a mental health specialist or a diagnosis of depression or both within the previous 2 years. The prevalence of well-defined medical conditions was the same in patients with and patients without evidence of depression (41.5% vs 41.5%, p = .87). However, high-utilizing patients who had not made a visit for a nonspecific complaint during the previous 2 years were at significantly lower risk of depression (13.1% vs 22.4%, p < .001). Patients with current depression or depression in partial remission had significantly higher numbers of annual office visits and hospital days per 1,000 than patients without depression. CONCLUSIONS: Although there was evidence that mental health problems had previously been recognized in many of the patients, a large percentage of high utilizers still suffered from active depression that either went unrecognized or was not being treated successfully. Patients who had not made visits for nonspecific complaints were at significantly lower risk of depression. Depression among high utilizers was associated with higher resource utilization.

Computerized assessment of depression and anxiety over the telephone using interactive voice response.

We examined the reliability and validity of computer-administered versions of the Hamilton Depression (HAMD) and Hamilton Anxiety (HAMA) Rating Scales that were administered over the telephone using Interactive Voice Response (IVR). In two identical studies (HAMD: N = 113, HAMA: N = 74), both the IVR- and clinician-administered versions were administered in a counterbalanced order to a heterogeneous sample of subjects with psychiatric disorders and controls. Both the IVR HAMD and HAMA demonstrated adequate internal-consistency reliability (.90 and .93, respectively) and test-retest reliability (.74 and .97, respectively). The correlation between the IVR and clinician was high (HAMD = .96; HAMA = .65). The mean score difference between the IVR and clinician versions was less than one point for both the HAMD (.69 of a point) and HAMA (.60 of a point). It took subjects 12.23 minutes to complete the IVR HAMD, compared to 15.21 minutes for the clinician version; and 11.27 minutes for the IVR HAMA, compared to 15.33 minutes for the clinician (p < .001 for both comparisons). Subjects rated the clinician better in the areas of how much they liked being interviewed and how well they were able to describe their feelings. However, they were significantly more embarrassed with the clinician than with the IVR. Results support the psychometric properties of the IVR versions of the HAMD and HAMA scales. IVR technology presents new opportunities for expanding the utility of computerized clinical assessment.

Computer-administered rating scales for social anxiety in a clinical drug trial.

Computer-administered versions of two clinician-administered symptom rating scales for social anxiety (the Liebowitz Social Anxiety Scale [LSAS] and the Brief Social Phobia Scale [BSPS]) and one paper-and-pencil scale (the Fear Questionnaire) were developed and utilized in a clinical trial for social phobia. The reliability and validity of the computer versions were examined, as were their equivalence to the traditional versions. Correlations between the computer and original versions were high at baseline, and remained high throughout the study. The internal consistency reliability of the computer scales was also high, and almost identical to the original versions. Mean score differences between computer and original versions were not significant at baseline, and no significant differences were found between computer and traditional versions on the amount of change detected from baseline to endpoint. Seventy-seven percent of subjects felt that the computer did not interfere with their visit at baseline and a plurality (36%) preferred the computer, with 30% preferring the clinician and 34% having no preference. By the end of the study, the plurality (41%) had no preference, with 27% preferring the computer and 32% preferring the clinician. Results support the use of these computer-administered symptom rating scales of social anxiety as a viable alternative to the clinician-administered versions with this subset of patients, which should offer researchers and clinicians a reliable and cost-effective method for evaluating social phobia.

Treatment of social phobia with gabapentin: a placebo-controlled study.

A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate the efficacy and safety of gabapentin in relieving the symptoms of social phobia. Sixty-nine patients were randomly assigned to receive double-blind treatment with either gabapentin (dosed flexibly between 900 and 3,600 mg daily in three divided doses) or placebo for 14 weeks. A significant reduction (p < 0.05) in the symptoms of social phobia was observed among patients on gabapentin compared with those on placebo as evaluated by clinician- and patient-rated scales. Results were similar for the intent-to-treat and week-2 completer populations. Adverse events were consistent with the known side effect profile of gabapentin. Dizziness (p = 0.05), dry mouth (p = 0.05), somnolence, nausea, flatulence, and decreased libido occurred at a higher frequency among patients receiving gabapentin than among those receiving placebo. No serious adverse events or deaths were reported. On the basis of these limited data, it seems that gabapentin offers a favorable risk-benefit ratio for the treatment of patients with social phobia. Further studies are required to confirm this effect and to determine whether a dose-response relationship exists.

Administration of the Hamilton Depression Rating Scale using interactive voice response technology.

We compared the reliability and equivalence of scores on the Hamilton rating scale for depression obtained by an interactive voice response (IVR) system and by human raters among 367 subjects 18 to 79 years old. Structured clinical interviews indicated that 93 of these subjects met the DSM-IV criteria for current major depression. We also examined short forms using the IVR data. The results obtained with the long (17-item) IVR interview correlated with those of the face-to-face interview, as did the results of the short (six- and eight-item) IVR interviews. In a random sample of 264 subjects, linear transformations of IVR results produced scores equivalent to clinical scores in the validation sample. We conclude that computerized assessment of the severity of depression by touch-tone telephone presents expanded opportunities for outcome research.

Brofaromine for social phobia: a multicenter, placebo-controlled, double-blind study.

The safety and efficacy of brofaromine, a reversible and selective monoamine oxidase inhibitor, were examined in a multicenter trial of 102 outpatients with social phobia. After a 1-week placebo washout, subjects were randomly assigned to 10 weeks of treatment with either brofaromine (N = 52) or placebo (N = 50). Brofaromine dosage began at 50 mg/day and was titrated to a maximum of 150 mg/day, depending on treatment response. Brofaromine produced a significantly greater change from baseline in Liebowitz Social Anxiety Scale (LSAS) scores compared with placebo, F(1) = 6.01, p < 0.016. Mean LSAS scores decreased from 81.8 at baseline to 62.6 at endpoint for brofaromine, t = 5.41,p < 0.001, and from 79.8 to 70.7 for placebo, t = 3.66, p < 0.001. Eleven of the 14 brofaromine early terminators discontinued because of adverse experiences, as did 4 of the 17 placebo early terminators. Side effects more common with brofaromine than placebo included insomnia, dizziness, dry mouth, anorexia, tinnitus, and tremor. No clinically significant variations in vital signs or laboratory values were found. The findings are consistent with the clinical efficacy for the treatment of social phobia.