Duloxetine in the treatment of irritable bowel syndrome: an open-label pilot study.

OBJECTIVE: To assess the efficacy of duloxetine for irritable bowel syndrome (IBS). METHODS: We conducted an open-label 12-week trial of duloxetine 60 mg daily in 15 patients with IBS without concurrent major depressive disorder. The primary outcome measure was average abdominal pain. Secondary measures included IBS symptoms, Clinical Global Impression-Severity, Hamilton Anxiety Rating Scale, IBS Quality-of-Life Scale, and Sheehan Disability Scale. We analyzed changes using random regression and one-sample t-tests. RESULTS: Fourteen patients completed at least one post-baseline evaluation; eight completed the study. Duloxetine was associated with significant improvement (p < 0.05) in pain, severity of illness, quality of life, loose stool, work and family disability, and anxiety. However, duloxetine did not improve hard stool. Although we found no evidence of serious duloxetine toxicity, seven participants withdrew over the course of the study because of adverse drug events. CONCLUSIONS: In this small, open-label study, duloxetine appeared to be effective for many features of IBS, but its adverse effects, most notably constipation, limited its use. Since our study excluded individuals with concurrent major depression, it appears that duloxetine may benefit IBS independently of its antidepressant effects. These encouraging but preliminary open-label findings support further investigation of duloxetine treatment in placebo-controlled trials of IBS.

Memantine in the treatment of binge eating disorder: an open-label, prospective trial.

OBJECTIVE: To assess preliminarily the efficacy of memantine in binge eating disorder. METHOD: This was an open-label, 12-week, flexible-dose (5-20 mg/day) trial of memantine in binge eating disorder. The primary outcome was frequency of binge days. Secondary outcomes included frequency of binge episodes, body-mass index (BMI), weight, Clinical Global Impressions Severity (CGI-S), Three Factor Eating Questionnaire (TFEQ), Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), and Sheehan Disability Scale (SDS). Longitudinal random regression analysis was performed for frequency of binge days and episodes, BMI, weight, and CGI-S; analysis of baseline to endpoint change was performed for all outcomes. RESULTS: Sixteen individuals received memantine; 15 completed at least one postbaseline evaluation, 9 completed the study. Mean dose at endpoint was 18.3 mg/day. Memantine was associated with significant reductions in frequency of binge days and episodes, severity of illness (p < .001 for both analyses), disinhibition on the TFEQ (p = .015), and disability on the SDS (p < .05 for three subscales). There was no significant change in BMI, weight, MADRS, HAM-A, and TFEQ cognitive restraint and hunger. CONCLUSION: In this open-label trial, memantine was well tolerated and effective in reducing binge eating, severity of illness, and disability, but had little effect on BMI and weight.

Rapid enhancement of glutamatergic neurotransmission in bipolar depression following treatment with riluzole.

Glutamatergic abnormalities may underlie bipolar disorder (BD). The glutamate-modulating drug riluzole may be efficacious in bipolar depression, but few in vivo studies have examined its effect on glutamatergic neurotransmission. We conducted an exploratory study of the effect of riluzole on brain glutamine/glutamate (Gln/Glu) ratios and levels of N-acetylaspartate (NAA). We administered open-label riluzole 100-200 mg daily for 6 weeks to 14 patients with bipolar depression and obtained imaging data from 8-cm(3) voxels in the anterior cingulate cortex (ACC) and parieto-occipital cortex (POC) at baseline, day 2, and week 6 of treatment, using two-dimensional J-resolved proton magnetic resonance spectroscopy at 4 T. Imaging data were analyzed using the spectral-fitting package, LCModel; statistical analysis used random effects mixed models. Riluzole significantly reduced Hamilton Depression Rating Scale (HAM-D) scores (d=3.4; p<0.001). Gln/Glu ratios increased significantly by day 2 of riluzole treatment (Cohen's d=1.2; p=0.023). NAA levels increased significantly from baseline to week 6 (d=1.2; p=0.035). Reduction in HAM-D scores was positively associated with increases in NAA from baseline to week 6 in the ACC (d=1.4; p=0.053), but was negatively associated in the POC (d=9.6; p<0.001). Riluzole seems to rapidly increase Gln/Glu ratios-suggesting increased glutamate-glutamine cycling, which may subsequently enhance neuronal plasticity and reduce depressive symptoms. Further investigation of the Gln/Glu ratio as a possible early biomarker of response to glutamate-modulating therapies is warranted.

Co-occurrence of binge eating disorder with psychiatric and medical disorders.

BACKGROUND: Prior studies suggest that certain psychiatric and medical disorders co-occur with binge eating disorder (BED). However, there has been no large, community-based study with diagnoses made by clinician interviewers. We used data from that type of study to assess the co-occurrence of various psychiatric and medical disorders with DSM-IV BED and with subthreshold BED. METHOD: From October 2002 to July 2004, we interviewed 150 probands with BED, 150 probands without BED, and 888 of their first-degree relatives (135 of whom had BED, and 54 of whom met specific partial criteria for BED that we defined as subthreshold BED). Study participants were interviewed using the Structured Clinical Interview for DSM-IV to assess BED and other psychiatric disorders and a supplemental structured interview to assess certain medical disorders; participants also completed a self-report questionnaire, the Bad Things Scale. For each psychiatric and medical disorder, we calculated the age- and sex-adjusted co-occurrence odds ratio: the odds of having that disorder in one's lifetime among individuals with (full or subthreshold) lifetime BED compared to individuals without lifetime BED. We also used subjects' responses to the Bad Things Scale to adjust for adversity over-reporting, a type of response bias that could result in spurious findings of co-occurrence. RESULTS: Full BED co-occurred significantly with bipolar disorder, major depressive disorder, bulimia nervosa but not anorexia nervosa, most anxiety disorders, substance use disorders, body dysmorphic disorder, kleptomania, irritable bowel syndrome, and fibromyalgia. These results changed little after correcting for adversity over-reporting. Subthreshold BED co-occurred significantly with many, but not all, of the significantly co-occurring disorders for full BED. CONCLUSION: BED and, to a lesser degree, subthreshold BED exhibit substantial lifetime co-occurrence with psychiatric and medical disorders.