John H. Greist

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.

Obsessive-Compulsive Symptom Dimensions as Predictors of Compliance with and Response to Behaviour Therapy: Results from a Controlled Trial

Background: Recent factor-analytic studies in obsessive-compulsive disorder (OCD) identified consistent symptom dimensions. Support for the validity of these dimensions comes from studies of psychiatric comorbidity, functional brain imaging, genetic transmission, and treatment response to medications. This study examined whether previously identified OCD symptom dimensions are associated with treatment compliance and response to behaviour therapy (BT) for OCD. Methods: One hundred and fifty-three OCD outpatients who participated in a multi-centre randomised controlled trial of computer- versus clinician-guided BT for OCD were included in the study. Logistic and multiple regression models tested for significant predictors of compliance with and response to BT and relaxation. Results: The patients studied were phenomenologically comparable (including the presence of ‘pure’ obsessions and mental rituals) to those in previous serotonin reuptake inhibitor (SRI) trials and those in clinical epidemiology studies. High scorers on the ‘hoarding’ dimension were more likely to drop out prematurely from the study and tended to improve less. For those completing treatment, the strongest predictor of outcome was pre-treatment severity. Initial depression scores were unrelated to outcome. After controlling for symptom severity, higher scores on the ‘sexual/religious obsessions’ factor predicted poorer outcome with BT, especially when computer-guided. Conclusions: BT is especially indicated for OCD patients with aggressive/checking, contamination/cleaning and symmetry/ordering symptoms. Previous accounts of unsuccessful BT in patients with hoarding symptoms may be due in part to their propensity to drop out earlier from treatment. Patients with sexual/religious obsessions, but not those with mental rituals, might respond less well to traditional BT techniques. Existing treatments need to be refined and/or new treatments developed to improve these patients’ adherence and response to treatment.

Running as treatment for depression.

Abstract For centuries, Man has had strong opinions about the importance of exercise in the maintenance of physical and mental health. Unfortunately, very little systematic study has been conducted to determine whether there is a relationship between exercise and mental health and, if a positive relationship exists, what specific factors under the broader rubric of “exercise” are responsible for its effectiveness in the maintenance and restoration of health.

Clomipramine hydrochloride in childhood and adolescent obsessive-compulsive disorder―a multicenter trial

Children and adolescents with obsessive compulsive disorder were studied in an 8-week, multicenter, double-blind, parallel groups trial of clomipramine hydrochloride (CMI) versus placebo. Efficacy assessments included the child version of the Yale-Brown Obsessive Compulsive Scale and the National Institute of Mental Health Global rating scale. At the end of 8 weeks, CMI-treated patients showed a mean reduction in Yale-Brown Obsessive Compulsive Scale score of 37% compared to 8% in the placebo group. Side effects were typical of tricyclic antidepressants. In a 1-year open label treatment, CMI continued to be effective and well tolerated.

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

Abstract 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.

A Comparative Outcome Study of Group Psychotherapy vs. Exercise Treatments for Depression

Depression is the most common mental disorder. Careful studies done in American communities have found that about 5 % of the population can be diagnosed as major depressive at any one time [1], and that 10%-25 % of the population will experience a major depression during their lifetime [2]. Studies in many countries and cultures and across all social classes show a similar frequency of depression [3]. People with histories of serious depression average about five episodes during their lifetime, although this number varies greatly. At most, only half of those with the disorder will receive treatment, despite the fact that 15 % of major depressives will end their lives by suicide [4]. Therefore, the availability and use of effective antidepressant treatments should lower both morbidity and mortality associated with depression. Because of the prevalence of depression and because many people have recurrent episodes, it is important to develop a range of effective treatment and prevention options. Many people are reluctant to take psychotropic medications for fear of developing negative side effects. Others are unwilling to participate in psychotherapy, cannot afford it, or do not have access to therapists who are versed in techniques that are

Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study

ABSTRACT Objective: The goal of a non-inferiority study is to test whether a new treatment has at least as much efficacy as an established treatment1. The purpose of this non-inferiority study was to compare the speed of onset of antidepressant efficacy for duloxetine (a dual serotonin and norepinephrine reuptake inhibitor) and escitalopram (a selective serotonin reuptake inhibitor). Research design and methods: This was a randomized, double-blind, placebo- and active comparator-controlled study, in which patients (≥ 18 years) meeting DSM‑IV criteria for Major Depressive Disorder (MDD) received duloxetine 60 mg once daily (QD; N = 273), escitalopram 10 mg QD (N = 274), or placebo (N = 137) for 8 weeks. The primary objective was to compare the onset of antidepressant efficacy, by testing the hypothesis that the percentage of duloxetine-treated patients achieving onset criteria at Week 2 was not inferior to that in the escitalopram group. Main outcome measures: Onset of efficacy was defined as a 20% decrease from baseline on the 17‑item Hamilton Rating Scale for Depression (HAMD17) Maier subscale that was maintained or exceeded at all subsequent visits. Results: Probabilities of meeting onset criteria at Week 2 for duloxetine- and escitalopram-treated patients were 42.6% versus 35.2%, respectively (treatment difference = 7.4%; 95% confidence interval, –1.3% to 16.2%; p = 0.097). Both drugs showed significant improvement compared with placebo ( p ≤ 0.05) on the primary efficacy measure (Maier subscale) at Week 1 and endpoint (Week 8). No differences were found between duloxetine, escitalopram, and placebo rates of remission or response at 8 weeks. Adverse events that occurred significantly more frequently among duloxetine-treated patients when compared with those receiving escitalopram were nausea, dry mouth, vomiting, yawning, and irritability. The rate of discontinuation due to adverse events did not differ significantly between treatment groups. Limitations: Given the difficulties in constructing appropriate dose comparisons, the results of this study should be interpreted specific to the doses tested and not extrapolated to the drug as a whole. This study employed a fixed-dose design; flexible-dose designs are more likely to find a difference between antidepressants and placebo. Conclusion: In this study, both duloxetine and escitalopram showed significantly greater improvement on the primary efficacy measure than placebo over the 8‑week acute treatment period, while no differences were observed between drugs or between drugs and placebo on response and remission rates at 8 weeks. Escitalopram at a starting dose of 10 mg QD was better tolerated than duloxetine at a starting dose of 60 mg QD. This study met its pre-defined primary objective of assessing if duloxetine was non-inferior to escitalopram in antidepressant onset efficacy, and the results show that duloxetine is at least as fast as (non-inferior to) escitalopram. Trial registration: ClinicalTrials.gov identifier: NCT00073411.

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.

Computer-administered clinical rating scales A review

Abstract 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.

Performance of two forms of a computer psychiatric screening interview: Version I of the DISSI

This study reports on the performance of two forms of version I of the Diagnostic Interview Schedule (DIS) computer screening interview, using the traditional interviewer-administered DIS (T-DIS) as the standard. The screening interview was either self-administered (called the S-DISSI) with the subject keying in responses, or interviewer-administered (I-DISSI), with the interviewer keying in the subjects responses. Sensitivity and specificity for both forms were ample (excluding antisocial personality), ranging from 60% to 100% for sensitivity and 54% to 95% for specificity. Concordances with the T-DIS were similar for both forms of the screening interview, ranging from .10 to .87 and compared favorably to those reported by other investigators. The I-DISSI took on average 30 min less than either the T-DIS and S-DISSI. Since the performances of both versions were equivalent, the decision to use either may be based on available resources and characteristics of the study population.