Med Check

A brief behavioral intervention targeting insomnia in patients with major depressive disorder improved not only sleep but also depressive symptoms.

Norio Watanabe, M.D., Ph.D., of the Nagoya City University in Japan and colleagues randomly assigned 37 adult patients who had depression with mood symptoms and insomnia to either treatment as usual (n=17) or a brief behavioral therapy focused on insomnia (n=20). The behavioral intervention was given in one-hour individual sessions weekly for four weeks. Blinded raters rated patients' clinical outcomes at four and eight weeks.

At eight weeks, patients who received the behavioral therapy had significantly lower scores on the Insomnia Severity Index and higher sleep efficiency than patients under usual care (p<0.05 for both comparisons). Behavioral therapy–treated patients also had significantly lower Hamilton Rating Scale for Depression (HAM-D) total scores and HAM-D scores after excluding sleep-related questions (p<0.05 for both comparisons).

In a phase 3, randomized, double-blind, controlled clinical trial of vilazodone, the investigational antidepressant was compared with placebo in 481 adult patients with a diagnosis of major depressive disorder. After eight weeks of treatment, vilazodone-treated patients (n=231) had a mean reduction of 13.9 points in Montgomery-Asberg Depression Rating Scale (MADRS) total score, the primary outcome. Placebo-treated patients had a mean reduction of 10.8 points. The difference was statistically significant (p=0.009). The rate of response, defined as at least 50 percent reduction in MADRS score from baseline, was 44 percent in the vilazodone group and 30 percent in the placebo group (p=0.002). The rates of remission, defined as a MADRS score of less than 10, were 27 percent and 20 percent, respectively, which was not statistically significant. The most common vilazodone-associated adverse events were diarrhea, nausea, headache, dry mouth, dizziness, and insomnia.

Vilazodone is being developed by Clinical Data Inc., and the study was funded by the company. The drug is both a selective serotonin reuptake inhibitor and a partial agonist of the serotonin 5HT_1A receptor. A new drug application for vilazodone was submitted to the Food and Drug Administration (FDA) in May.

A randomized, double-blind, placebo-controlled clinical trial was conducted in Europe to study the efficacy of levomilnacipran to treat patients with major depressive disorder. Enrolled patients were titrated up to 75 mg to 100 mg of levomilnacipran (or equivalent placebo) during the first two weeks and then continued for another eight weeks. At the end of 10 weeks, the reductions in MADRS and HAM-D scores from baseline were statistically significantly higher in the levomilnacipran group (n=276) than the placebo group. The mean reduction in actual scores was not presented. The levomilnacipran group also had statistically significantly greater reduction in functional impairment, as measured by the Sheehan Disability Scale score, than the placebo group. The most common adverse events associated with levomilnacipran were nausea, headache, dizziness, and excessive sweating.

The study was funded by Forest Laboratories and Pierre-Fabre Medicament, which are studying the drug in phase 3 clinical trials. Levomilnacipran is an enantiomer of milnacipran, a drug approved in the United States to treat fibromyalgia, and selectively inhibits norepinephrine and serotonin reuptake.

Partam Manalai, M.D., of the Mood and Anxiety Program in the University of Maryland Psychiatry Department and colleagues identified an association between allergy related to seasonal pollen exposure and depressive mood symptoms during the peak pollen season.

Among the 100 recruited study participants with a prior diagnosis of either major depressive disorder or bipolar disorder, approximately half had positive allergen-specific immunoglobulin E (IgE) in blood samples, indicating an allergic reaction to airborne pollen. Their allergy symptoms were measured with the Allergy Symptom Severity Assessment (ASSA) scale, and their mood symptoms were assessed using the questionnaire Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders Version (SIGH-SAD).

After controlling for various confounding factors with multiple regression analysis, the researchers found that the participants' score change in the typical depression portion of the SIGH-SAD was statistically associated with worse ASSA score (p=0.008), and the change in the atypical depression portion of the SIGH-SAD was associated with IgE positivity (p=0.033). “The relationship between … [the] allergen-specific IgE and changes in mood supports a biological … mediation of the association between allergy and depression,” the authors wrote.

In a randomized, placebo-controlled trial, asenapine outperformed placebo as an adjunctive therapy to mood stabilizers in patients with bipolar I disorder. Adult patients in a current manic or mixed episode who had been on lithium and valproate for at least two weeks were randomly assigned to receive either asenapine or placebo as an add-on treatment. Changes in Young Mania Rating Scale (YMRS) scores from baseline showed a statistically significant reduction in the asenapine group (n=155) compared with the placebo group (n=163) at week 3 and week 12.

The 116 patients who completed the 12-week study phase continued on their treatment in a blinded manner for another 40 weeks while being maintained on the mood stabilizers. Patients on asenapine (n=41) and on placebo (n=36) did not differ significantly in YMRS score at the end of the 40-week extension.

Asenapine is currently approved for acute treatment of mania or mixed episode and for schizophrenia. The study was supported by Schering-Plough, now part of Merck.

The proportion of patients discharged from hospitals with a diagnosis of bipolar disorder increased, on average, by 10 percent per year, while the average length of hospital stay decreased from 14 days to 6.4 days between 1979 and 2006, according to a large epidemiological study.

Natalya Weber, M.D., M.P.H., of the Department of Epidemiology in the Division of Preventive Medicine at the Walter Reed Army Institute of Research analyzed hospital-discharge records of patients aged 13 to 64 using data from the National Hospital Discharge Survey (NHDS). The NHDS is a nationally representative survey of hospital records collected by the Centers for Disease Control and Prevention and contains up to seven ICD-9 diagnoses.

Compared with discharged patients without bipolar disorder, the types of nonpsychiatric comorbidities significantly more common in bipolar patients included diseases of sebaceous glands, extrapyramidal disease and abnormal-movement disorders, poisoning by psychotropic agents, dermatophytosis, open wound of elbow, forearm, or wrist, acquired hypothyroidism, psoriasis and similar disorders, and contact dermatitis and other eczema. Although many of these comorbidities have well-known links to bipolar disorder or its treatment, some “warrant additional investigation to determine any commonality” in etiology, the authors said. The study was funded by the Stanley Medical Research Institute.

John Olsen, M.D., and colleagues at the University of Utah School of Medicine conducted a retrospective review of the records of 1,002 patients who received a first series of electroconvulsive therapy (ECT) treatments in the decade from 1999 to 2009 and analyzed the reported somatic side effects in adolescent and adult patients. About three-fourths of the patients (n=744) had a diagnosis of depression, and one-fourth (n=239) had bipolar disorder. The incidences of headache, nausea, and myalgia within one to seven days after ECT were 39.9 percent, 15.6 percent, and 13.3 percent of the patients, respectively. These side effects showed a diminishing trend after the first ECT session in subsequent treatments. Patients aged 60 or older appeared to have lower rates of these somatic side effects than did patients younger than 60.