Self-guided digital acceptance and commitment therapy for fibromyalgia management: results of a randomized, active-controlled, phase II pilot clinical trial.

Although empirically validated for fibromyalgia (FM), cognitive and behavioral therapies, including Acceptance and Commitment Therapy (ACT), are inaccessible to many patients. A self-guided, smartphone-based ACT program would significantly improve accessibility. The SMART-FM study assessed the feasibility of conducting a predominantly virtual clinical trial in an FM population in addition to evaluating preliminary evidence for the safety and efficacy of a digital ACT program for FM (FM-ACT). Sixty-seven patients with FM were randomized to 12 weeks of FM-ACT (n = 39) or digital symptom tracking (FM-ST; n = 28). The study population was 98.5% female, with an average age of 53 years and an average baseline FM symptom severity score of 8 out of 11. Endpoints included the Fibromyalgia Impact Questionnaire-Revised (FIQ-R) and the Patient Global Impression of Change (PGIC). The between-arm effect size for the change from baseline to Week 12 in FIQ-R total scores was d = 0.44 (least-squares mean difference, - 5.7; SE, 3.16; 95% CI, - 11.9 to 0.6; P = .074). At Week 12, 73.0% of FM-ACT participants reported improvement on the PGIC versus 22.2% of FM-ST participants (P < .001). FM-ACT demonstrated improved outcomes compared to FM-ST, with high engagement and low attrition in both arms. Retrospectively registered at ClinicalTrials.gov (NCT05005351) on August 13, 2021.

Placebo-controlled study of quetiapine monotherapy in ambulatory bipolar spectrum disorder with moderate-to-severe hypomania or mild mania.

BACKGROUND: There are no randomized, placebo-controlled data for quetiapine in outpatients with bipolar spectrum disorder (ambulatory BSD) and moderate-to-severe hypomanic or mild manic symptoms (hypomania/mild mania). METHODS: An 8-week, randomized, double-blind, placebo-controlled trial of quetiapine in ambulatory BSD with hypomanic/mild manic symptoms, defined operationally as a score of >or=3 but <5 on the mania subscale of the Clinical Global Impressions Scale Modified for Bipolar Illness (CGI-BP) at baseline and one prior study visit, at least 3 days but no more than 2 weeks apart. The primary outcome measure was the rate of change in the Young Mania Rating Scale score (YMRS). RESULTS: During the 8-week study period, patients receiving quetiapine (average daily dose=232mg) had a marginally greater rate of reduction in mean total YMRS score than patients receiving placebo (p=0.06). Additionally, CGI-BP mania (p=0.01) and the CGI-BP overall (p<0.001) scores were significantly reduced and the CGI-depression score (p=0.08) was marginally reduced in the quetiapine group. Six (32%) quetiapine patients and 8 (40%) placebo patients did not complete the trial. LIMITATIONS: Small sample size and high attrition (36%). CONCLUSION: Quetiapine was marginally more effective than placebo in reducing hypomanic/mild manic symptoms in ambulatory BSD as assessed by the YMRS. It was more effective than placebo in reducing manic symptoms and global bipolar symptoms as assessed by the CGI-BP. The drug's discontinuation rate was similar to placebo's. Controlled trials of quetiapine and other compounds with mood stabilizing properties in larger groups of ambulatory BSD patients with hypomanic/mild manic symptoms appear warranted.

Long-term safety of divalproex sodium extended-release in children and adolescents with bipolar I disorder.

OBJECTIVE: The objective of this open-label study was to assess the safety of divalproex sodium extended-release in the treatment of children and adolescents with acute mania associated with bipolar I disorder. METHODS: This was a 6-month, Phase 3, open-label study in healthy subjects aged 9-17 years with a current Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition, Text Revision (DSM-IV-TR) diagnosis of bipolar I disorder manic or mixed episode. Divalproex sodium extended-release (DVPX-ER) was initiated at 15 mg/kg per day on day 1 (not to exceed 750 mg/day) with increases allowed to a maximum of 35 mg/kg per day. Study visits were conducted on day 1 and at months 1, 2, 3, and 6. Assessments included standard safety evaluations and appropriate rating scales for clinical effect. RESULTS: A total of 226 subjects were enrolled; 109 subjects completed the study. The most common adverse events were weight gain (16%), nausea (9%), and increased appetite (8%). Nonsymptomatic elevations of mean ammonia levels in plasma were observed. The mean Young Mania Rating Scale (YMRS) decreased 12.4 from baseline to final visit; small improvements were seen in behavior and caregiver stress ratings. CONCLUSIONS: DVPX-ER was generally well tolerated in children and adolescents with acute mania, with a side-effect profile similar to that observed in adults.

Are mood disorders and obesity related? A review for the mental health professional.

OBJECTIVE: We reviewed evidence regarding a possible relationship between mood disorders and obesity to better inform mental health professionals about their overlap. METHOD: We performed a MEDLINE search of the English-language literature for the years 1966-2003 using the following terms: obesity, overweight, abdominal, central, metabolic syndrome, depression, mania, bipolar disorder, binge eating, morbidity, mortality, cardiovascular, diabetes, cortisol, hypertriglyceridemia, sympathetic, family history, stimulant, sibutramine, antiobesity, antidepressant, topiramate, and zonisamide. We evaluated studies of obesity (and related conditions) in persons with mood disorders and of mood disorders in persons with obesity. We also compared studies of obesity and mood disorders regarding phenomenology, comorbidity, family history, biology, and pharmacologic treatment response. RESULTS: The most rigorous clinical studies suggest that (1). children and adolescents with major depressive disorder may be at increased risk for developing overweight; (2). patients with bipolar disorder may have elevated rates of overweight, obesity, and abdominal obesity; and (3). obese persons seeking weight-loss treatment may have elevated rates of depressive and bipolar disorders. The most rigorous community studies suggest that (1). depression with atypical symptoms in females is significantly more likely to be associated with overweight than depression with typical symptoms; (2). obesity is associated with major depressive disorder in females; and (3). abdominal obesity may be associated with depressive symptoms in females and males; but (4). most overweight and obese persons in the community do not have mood disorders. Studies of phenomenology, comorbidity, family history, biology, and pharmacologic treatment response of mood disorders and obesity show that both conditions share many similarities along all of these indices. CONCLUSION: Although the overlap between mood disorders and obesity may be coincidental, it suggests the two conditions may be related. Clinical and theoretical implications of this overlap are discussed, and further research is called for.

Heart disease and depression: don't ignore the relationship.

Evidence is mounting that depression is a risk factor for the development of cardiovascular disease and portends a worse outcome in cardiac patients. Depression can be easily diagnosed and safely treated in cardiac patients, but it is undertreated.

Citalopram in the treatment of binge-eating disorder: a placebo-controlled trial.

BACKGROUND: Binge-eating disorder is a newly recognized eating disorder characterized by recurrent episodes of binge eating without compensatory weight loss behaviors. It commonly co-occurs with depressive disorders and obesity. Citalopram is a highly selective serotonin reuptake inhibitor antidepressant. The purpose of this study was to assess the efficacy and safety of citalopram in the treatment of binge-eating disorder. METHOD: Thirty-eight outpatients with a DSM-IV diagnosis of binge-eating disorder were enrolled in the study between August 2000 and July 2001 and were randomly assigned to receive either citalopram (N = 19) or placebo (N = 19) in a 6-week, double-blind, flexible-dose (20-60 mg/day) study. The primary measure of efficacy was frequency of binge-eating episodes. Secondary measures included frequency of binge days, body mass index (BMI), weight, Clinical Global Impressions-Severity of Illness scale scores, Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (YBOCS-BE) scores, Hamilton Rating Scale for Depression (HAM-D) scores, and response categories. The outcome measures were analyzed using 2 random regression methods, with a time trend analysis (primary analysis) and an endpoint analysis. In addition, response categories were analyzed using an exact trend test. RESULTS: Compared with placebo-treated subjects, subjects receiving citalopram (mean dose of 57.9 mg/day) had a significantly greater rate of reduction in frequency of binge eating (p =.003), frequency of binge days (p <.001), BMI (p <.001), weight (p <.001), severity of illness (p =.028), and YBOCS-BE score (p =.007) and a marginally significant rate of reduction in HAM-D score (p =.053). Differences between groups in response categories were marginally significant (p =.068 for intent-to-treat analysis). CONCLUSION: In a 6-week, placebo-controlled, flexible-dose trial, citalopram was efficacious in reducing binge-eating frequency, weight, and severity of illness and was generally well tolerated in subjects with binge-eating disorder.

Venlafaxine treatment of binge-eating disorder associated with obesity: a series of 35 patients.

BACKGROUND: Binge-eating disorder is a newly recognized eating disorder characterized by recurrent episodes of binge eating without extreme weight loss behaviors. It commonly co-occurs with overweight and obesity. To preliminarily explore the effectiveness and tolerability of venlafaxine in binge-eating disorder, we retrospectively reviewed the response of 35 consecutive overweight or obese outpatients with binge-eating disorder presenting at the University of Cincinnati Physicians Weight Management Program, Cincinnati, Ohio, to clinical treatment with venlafaxine. METHOD: The medical charts of 35 consecutive outpatients with binge-eating disorder (DSM-IV criteria) and overweight (body mass index [BMI] = 25.0-29.9) or obesity (BMI > or = 30.0) who received clinical treatment with venlafaxine at a weight management program were reviewed. Response of binge-eating disorder symptoms was assessed by weekly binge frequency (the number of binges reported by the patient the week before the clinic appointment), the Clinical Global Impressions-Severity of Illness (CGI-S) scale, and categorical response (no response, mild, moderate, marked, or remission). Weight, BMI, waist circumference, comorbid Axis I diagnoses, vital signs, and side effects also were collected. RESULTS: Twenty-nine patients (83%) received venlafaxine as monotherapy and 6 (17%) received the drug adjunctively for a median of 120 days (range, 28-300 days). The mean +/- SD venlafaxine treatment dose was 222 +/- 63 mg/day (range, 75-300 mg/day). In the 33 patients who were actively binge eating at the time venlafaxine was begun, weekly binge frequency, severity of binge-eating and mood symptoms as measured by the CGI-S scale, weight, BMI, waist circumference, and diastolic blood pressure all showed statistically significant decreases over time (p < .05). Of these 33 patients, 29 (88%) displayed a moderate (50% reduction) or better response of binge-eating episodes. Fifteen (43%) of the 35 patients lost 5% or more of their baseline weight. In general, venlafaxine was well tolerated, with dry mouth, sexual dysfunction, insomnia, and nausea being the most frequently reported side effects. Sustained increases in blood pressure seen in 6 patients (17%) were considered clinically insignificant. No patients discontinued the drug. CONCLUSION: Venlafaxine may be an effective treatment for binge-eating disorder associated with overweight or obesity. Controlled studies of venlafaxine in binge-eating disorder appear warranted.

Medical management of obesity associated with mental disorders.

Obesity and mental disorders are major public health problems that co-occur to a significant degree. They also significantly overlap in phenomenology and response to medications. However, many psychotropic agents have adverse effects on appetite, binge eating, and weight. In this review, we aim to improve understanding of the relationship between obesity and mental illness and provide practical clinical guidelines for the management of obesity associated with mental disorders.