SOURCE: Healio - Psychiatric Annals
September 20, 2016

Erythropoietin, commonly used as a performance-enhancing drug in sports, improved cognitive functioning among individuals with unipolar or bipolar depression, according to findings presented at the European College of Neuropsychopharmacology Congress.
“Erythropoietin (EPO) treated patients showed a five times greater cognitive improvement from their individual baseline levels compared with placebo treated patients. EPO-treated patients showed 11% improvement while placebo treated patients improved only by 2%. This effect of EPO on cognition was maintained 6 weeks after patients had completed their treatment,” study researcher Kamilla Miskowiak, PhD, of Copenhagen University Hospital, Denmark, said in a press release.
To assess effects of EPO on speed of complex cognitive processing in individuals with unipolar or bipolar depression, researchers randomly assigned individuals to 8 weekly EPO (n = 40) or saline (n = 39) infusions. Speed of complex cognitive processing and mood symptoms were assessed at baseline, week 9 and week 14.
Participants who received EPO had improved speed of complex cognitive processing at weeks 9 and 14 (P .05).
Objective cognitive baseline deficits increased likelihood of achieving clinically relevant improvement in cognition by 9.7 (95% CI, 1.2-81.1) at week 9 and 9.9 (95% CI, 1.1-88.4) at week 14 among participants who received EPO.
Cognitive improvement associated with EPO was correlated with reduced subjective cognitive complaints at week 9 (P = .01), which was mediated by lower depressive symptom severity.
However, the significant correlation persisted independently of change in depressive symptoms at week 14 (P < .01).
Improved objective cognition was not associated with change in quality of life or socio-occupational function.
“The results of this study, albeit preliminary, give hope to people suffering from mood disorders and associated neurocognitive symptoms. Those symptoms are now recognized as a core part of affective disorders and are not appropriately tackled by the currently available pharmacological armamentarium, despite their close association with relevant clinical outcomes such as the ability to return to work,” Eduard Vieta, PhD, treasurer of the European College of Neuropsychopharmacology, said in the release. – by Amanda Oldt
Reference
Ott CV, et al. The effect of erythropoietin on cognition in affective disorders — associations with baseline deficits and change in subjective cognitive complaints. Presented at: European College of Neuropsychopharmacology Congress; September 17-20, 2016; Vienna.

SOURCE: MPR
​September 26, 2016 | ​Debra Hughes, MS

During the initial 2 weeks of treatment with first-line fluoxetine, patients with major depressive disorder (MDD) who spent 8 hours in bed had significantly lower depression severity and an earlier onset of remission when compared with those who spent only 6 hours in bed, one of the first studies to examine adequate sleep and antidepressant treatment response has found.

Among those who slept only 6 hours, no difference was observed between those who went to bed 2 hours later versus arising 2 hours earlier, reported J. Todd Arnedt, PhD, associate professor of psychiatry and neurology at the Sleep and Circadian Research Laboratory, University of Michigan Medical School, Ann Arbor, MI, and colleagues in the Journal of Clinical Psychiatry.

“Effective and practical clinical strategies are critically needed to improve response and remission rates to first-line antidepressant medications,” the study authors wrote. MDD affects approximately 16.5% of US adults in their lifetime.
Although one night of total sleep deprivation is shown to improve mood in 60% of patients with MDD, in those who are unmedicated, relapse in up to 80% is observed after recovery sleep. Recent studies have investigated combining sleep deprivation with medication, light therapy, and sleep schedule adjustments. Also explored as an alternative to total sleep deprivation in a laboratory setting is single-night partial sleep deprivation (4–5 hours of sleep), with repetition “during the initial 1-4 weeks of antidepressant therapy” accelerating treatment response, Dr Arnedt noted.

However, “to date, no study has assessed the effects of a modest repeated restriction of time in bed on treatment response in outpatients with depression initiating an antidepressant treatment trial.”

From September 2009 to December 2012, the investigators recruited 68 adults with DSM-IV–diagnosed MDD. Mean age was 25.4 years and 34 were women. Mean age at onset of MDD was 16.6 years and the current MDD episode, a mean of 11.6 months.

Participants were excluded if they had lifetime psychotic disorder, substance or alcohol dependence, eating disorder, posttraumatic stress disorders, and obsessive-compulsive disorder, and those post 6-month substance or alcohol abuse. The 8-hour time in bed group had more years of education than the other 2 groups (P<.005). The majority of the patients were white, unmarried, employed part-time or unemployed, and had a positive family history of MDD. About one-third of the patients had no history of prior MDD treatment; the others had received medication, psychotherapy, or both.

Each subject received 8 weeks of open-label fluoxetine 20 to 40mg and, for the first 2 weeks, was randomly assigned to 1 of 3 nightly “time in bed” conditions as adjunctive therapy: 19 adults were restricted to 8 hours in bed; 24 to 6 hours in bed, with a 2-hour bedtime delay (“late bedtime”); and 25 to 6 hours in bed with a 2-hour rise time advance (“early rise time).”

The initial dose of fluoxetine 20mg was taken after the first time in bed condition night, followed by fluoxetine 20mg/day for 8 weeks. Based on clinician-rated response, dose could be increased to 40mg after week 4.

Symptom severity was rated at baseline and then weekly by clinicians blinded to the time in bed condition. Primary outcome measures, as rated by the 17-item Hamilton Depression Rating Scale, were symptom severity, remission rates, and remission onset. Compliance was evaluated by pill count at each in-laboratory visit.

Study subjects also completed depression scales at baseline and at weeks 1, 2, 4, and 8; quality-of-life ratings were completed at baseline and weeks 4 and 8.
A total of 58 subjects (85.2%) completed the 2-week time in bed condition and 54 (79.4%) completed the 8-week study. Among those randomly assigned, 11 (16.2%) discontinued participation, 3 in the 8-hour, 5 in the late bedtime, and 3 in the early rise time groups; in addition, 4 subjects were discontinued for protocol violations.

When the 8-hour time in bed group was compared with both 6-hour time in bed groups, lower depression severity was observed in the 8-hour group (P<.05). Among those in the 8-hour group, 63.2% remitted by week 8, compared to 32.6% of subjects in the 6-hour groups, and this remission occurred earlier (hazard ratio = 0.43; 95% CI, 0.20-0.91; P<.03). No difference in remission onset was seen between the 6-hour time in bed conditions.
The Self-Rated 12-Item Short-Form Health Survey indicated a significant difference between the 8-hour time in bed and 6-hour time in bed groups in the mental composite score at Week 8 compared to baseline (–7.9; P = .04).
These findings “raise the possibility that adequate time in bed duration may positively impact treatment response,” they reported, adding that “these effects were not due to better medication compliance or to a higher medication dose in the 8-hour time in bed group. Importantly, objective compliance monitoring indicated that subjects were compliant with the 8-hour time in bed schedule, but subjects assigned to the 6-hour time in bed schedule were not. To our knowledge, this study is the first to evaluate experimentally a modest repeated time in bed restriction in antidepressant treatment response.”
Needed to confirm these finding are studies that “optimize or extend sleep duration while initiating antidepressant therapy,” including in “larger, more ethnically diverse, and older samples.” In addition, diurnal mood variation and circadian preference or insomnia, potentially important clinical and sleep-related moderators, respectively, should be systematically included in studies to measure treatment response and evaluate mechanisms of adjunctive treatments for depression.
The authors concluded: “Patients initiating a new trial of antidepressant medication should be cautioned against restricting their time in bed.”

Reference
1. Arnedt JT, Swanson LM, Dopp RR, et al. Effects of restricted time in bed on antidepressant treatment response: A randomized controlled trial. J Clin Psychiatry. Dx.doi.org/10.4088/JCP.15m09879.

SOURCE: MPR
​September 27, 2016 | Da Hee Han, PharmD

Insomnia-specific treatment proved effective at improving daytime and psychological functioning in the short-term, and maintenance therapy added further value to optimizing long-term outcomes, according to a study published in Behaviour Research and Therapy.
 
Few studies have examined the clinical impact of insomnia therapies on daytime outcomes though daytime functioning impairment is typically the main reason for seeking treatment. Researchers from Canada and Spain evaluated the impact of cognitive-behavior therapy (CBT) alone and in combination with medication, on various outcomes of daytime and psychological functioning.
 
A total of 160 individuals with chronic insomnia received CBT alone or CBT + zolpidem for an initial 6 weeks followed by an extended 6-month therapy. Patients in the CBT group received maintenance CBT or no additional treatment; those in the combination treatment group continued with CBT + intermittent medication or CBT without medication (taper).
 
Researchers measured patients' anxiety and depressive symptoms, fatigue, quality of life, and perceived impact of sleep difficulties on various indices of daytime functioning at baseline, after each treatment stage, and at 6-month follow-up.
 
They found that after acute treatment, significant improvements of fatigue, quality of life (mental component), anxiety, and depression were obtained in the CBT alone group but not in the CBT + medication group. After extended treatment, more improvements were seen for the subcohort receiving extended CBT with no additional treatment and for the subcohort receiving CBT with intermittent medication vs. CBT alone. These improvements were sustained through the 6-month follow-up.