The US Food and Drug Administration (FDA) today approved a first-in-class insomnia drug called suvorexant (Belsomra, Merck) after the manufacturer lowered the dosages to satisfy the agency’s safety concerns. Merck announced that the FDA had declined to approve suvorexant until the starting dose for most patients was 10 mg. The agency also said that proposed upper-limit doses of 30 mg for elderly patients and 40 mg for nonelderly patients were unsafe. In a news release today, the FDA said it had approved suvorexant at 4 different strengths — 5 mg, 10 mg, 15 mg, and 20 mg. The total dosage in 1 day should not exceed 20 mg. Merck noted in its own news release today that the recommended dose is 10 mg for most patients, just as the FDA insisted. Suvorexant, an orexin receptor antagonist, is the first drug of its kind to be approved for patients with insomnia. It alters the signaling of orexins, neurotransmitters responsible for regulating the sleep-wake cycle. The FDA determined that suvorexant was effective based on 3 clinical trials involving more than 500 participants. Those receiving suvorexant nodded off more quickly and spent less time awake for the rest of the night compared with participants given a placebo. Drowsiness was the most commonly reported adverse event for clinical trial participants taking suvorexant, which is classified as a Sche
Investigators at Dalhousie University in Halifax, Canada, found that CRP, an “easily accessible biomarker of systemic inflammation,” predicted response to the antidepressants escitalopram (Lexapro, Forest Laboratories, Inc) and nortriptyline. “While there have been other biomarkers identified [to predict response to antidepressants], CRP has the major advantage of being ‘differential’ ― it predicts response to one drug in one direction and response to an alternative drug in the opposite direction,” lead author Rudolf Uher, MD, PhD, told Medscape Medical News. Low CRP, Better Response . With previous evidence showing an association between systemic inflammation and depression, the researchers wanted to investigate the hypothesis that a similar relationship might exist between CRP and response to treatment for depression, using the 2 different antidepressants ― escitalopram, a selective serotonin reuptake inhibitor, and nortriptyline, a selective norepinephrine reuptake inhibitor. The study involved 241 adults with major depressive disorder who were enrolled in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study, a multicenter, randomized clinical trial. Patients were randomly assigned to receive 12 weeks of treatment with escitalopram (N = 115) or nortriptyline (N = 126), and their CRP levels were measured at baseline. Patients wit
Stimulation with a low-strength electromagnetic field device immediately improves mood in patients with major depressive disorder (MDD) and bipolar disorder (BPD), new research shows. Results from a randomized, double-blind, sham-controlled study are exciting, especially because the effects were so rapid, lead author Michael L. Rohan, PhD, a physicist at McLean Hospital and Harvard Medical School, Belmont, Massachusetts, told Medscape Medical News. The device holds “great potential” as a clinical tool for psychiatrists, Dr. Rohan added. The ability of the rapidly oscillating electromagnetic field, called low-field magnetic stimulation (LFMS), to improve mood was discovered “serendipitously” about a decade ago. Researchers who were carrying out experimental MRI scans to assess brain chemistry noticed changes in depressed bipolar patients. After further research, Dr. Rohan designed and built the portable tabletop device that is now being studied. It consists of a magnetic coil, an amplifier, a waveform generator, and a computer. The US Food and Drug Administration (FDA) has determined that the device carries a nonsignificant risk. Dr. Rohan described the LFMS device as being similar in size and shape to “an old-fashioned mailbox.” Patients lie on a bed with a padded headrest. The top of their head fits into the device, leaving the rest of the
A simple test examining involuntary eye movements may provide an objective way to tell whether individuals have attention-deficit/hyperactive disorder (ADHD) and whether stimulant medication will be an effective treatment, new research suggests. Investigators from Tel Aviv University in Tel Hashomer, Israel, observed increased microsaccades and blink rates in adults with ADHD, which normalized with methylphenidate treatment. “Striking” Predictive Effect “The rationale behind our study was following recent studies ― of ours and others ― which found that the rate of microsaccades is inversely correlated with the level of attention,” Dr. Fried told Medscape Medical News. In this latest study, the investigators recorded involuntary eye movements in 22 adults with ADHD with and without methylphenidate and 22 control individuals while they performed the test of variables of attention (TOVA). They found that unmedicated ADHD patients had significantly higher rates of eye blinks and microsaccades compared with control participants. This effect was largest in the peristimulus period, “where eye movements should be suppressed because they could interfere with the task,” the researchers write. In addition, stimulant medication had a “striking effect” on involuntary eye movements, with full normalization of the
Alterations in a gene linked to stress reactions may eventually help clinicians identify patients at increased risk for suicidal behavior, including attempts, potentially by way of a simple blood test, new research shows. Investigators at the Johns Hopkins University School of Medicine in Baltimore, Maryland, examined postmortem brains and found a genetic and epigenetic link between suicide and the single- nucleotide polymorphism (SNP) rs7208505 “within the 3′ untranslated region of the SKA2 gene.” The investigators were able to then replicate this finding in 2 other postmortem brain cohorts and in blood draws from 3 live participant cohorts. They found a significantly lower SKA2 gene expression in those with suicidal behavior and an association with variations of rs7208505. A final analysis, this time of salivary cortisol, showed that SKA2 variations may modulate cortisol suppression. The study was published July 30 in the American Journal of Psychiatry.
Although the risk of developing dementia doubles in older adults diagnosed with major depression vs those without the disorder, the mechanism is unclear. Most previous studies have examined 1 or 2 biomarkers when investigating this question. However, in the current study, the investigators tested 242 blood-based proteins and also examined structural brain abnormalities. A total of 80 adults with remitted late-life depression were enrolled; 36 had MCI (67% women; mean age, 73.4 years), and 44 had normal cognitive function (87% women; mean age, 72.4 years). Whole-blood samples were taken from all participants and tested for the proteins associated with pathways for cancer, cardiovascular disease, metabolic syndrome, psychiatric disorders, and neurodegenerative disorders.
In addition, positron emission tomography using Pittsburgh compound B (PiB-PET) was used to measure brain amyloid-beta (Aβ) deposition, thought to be involved in Alzheimer’s disease, and MRI scans were used to measure white matter hyperintensity and whole-brain gray matter atrophy volumes. Results showed that the participants who had both depression and MCI had significant “differential expression” of 24 proteins used in the regulation of immune-inflammatory activity (including higher levels of CCL13-MCP-4 and CXCL11-interferon-inducible T-
Una prueba que se realiza a través de las fosas nasales podría diagnosticar con mayor rapidez y precisión la enfermedad de Creutzfeldt-Jakob (ECJ). Para la investigación, se analizaron las muestras nasales de 31 pacientes con ECJ y 43 participantes con otras enfermedades neurológicas o sin ninguna patología. Las muestras de las neuronas olfativas se recogieron con un nuevo procedimiento accediendo por la parte interna de la nariz. Las muestras se analizaron y se identificó a 30 de los 31 pacientes con ECJ (sensibilidad del 97%; IC 95% = 82-100%): 15 de 15 con ECJ esporádica definida, 13 de 14 con ECJ esporádica probable y 2 de 2 con ECJ adquirida. Además, se detectaron resultados negativos en los 43 pacientes que no presentaban la enfermedad (especificidad del 100% (IC 95% = 90-100%). En comparación, el análisis de las muestras de líquido cefalorraquídeo del mismo grupo de pacientes dio una sensibilidad del 77% (IC 95% = 57-89%) y una especificidad del 100% (IC 95% = 90-100%). [N Engl J Med 2014] Orrú CD, Bongianni M, Tonoli G, Ferrari S, Hughson AG, Groveman BR, et al.
Commenting on the study for Medscape Medical News, Heather Snyder, PhD, director, medical and scientific relations, Alzheimer’s Association, Chicago, Illinois, said a number of studies have shown that lifestyle interventions can attenuate the progressive decline in cognitive function in older individuals.
Most recently, the FINGER study (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability), which was presented earlier this year at the Alzheimer’s Association International Conference 2014 and was reported by Medscape Medical News at that time, showed that a multipronged lifestyle intervention had a significant beneficial effect on overall cognitive performance, including memory, executive function, and psychomotor speed, in a large cohort of older participants at high risk for cognitive decline.
“The FINGER study certainly suggests that this is the kind of study we need to do in translating what Dr Bredesen did to a much larger clinical trial,” Dr Snyder said.
Dr Snyder also noted that it is clear the underlying pathology driving AD is already changing well before patients manifest overt memory loss
The interventions used in the 10 patients involved in the UCLA pilot project were tailored to each individual, but they shared similar elements. Typically, patients were asked to eliminate all simple carbohydrates from their diet.
They were also asked to increase consumption of fruit, vegetables, and nonfarmed fish and to follow a strict meal pattern with specifically timed interludes of fasting.
Exercise was a key component of all interventions, and participants were counseled on ways to reduce stress through practices such as yoga and meditation.
Participants also took a large variety of daily supplements, including vitamin D3, fish oil, coenzyme Q10, melatonin, and methylcobalamin.
And where appropriate, practitioners counseled their female patients to resume previously discontinued hormone replacement therapy.
“The program is not easy to follow,” Dr Bredesen acknowledged. (None of the patients in this pilot project were able to fully follow the program).
“But what this program says is that we are all contributing to our own AD by the diet we chose to eat; by the way we sleep; by the stress we hav
In studies of transgenic mice, Dr Bredesen and colleagues found that beta-amyloid precursor protein (APP) signaling can be manipulated to inhibit the underlying pathophysiology that causes AD.
However, many different metabolic factors contribute to APP signaling, including hormones, inflammatory mediators, and exercise.
This suggests that the pathobiology of AD must be approached at different points of intervention and not with a single targeted agent.
“Just as for other chronic illnesses such as atherosclerotic cardiovascular disease, the goal is not simply to normalize metabolic parameters, but rather to optimize them,” the investigators write.
“Based on the hypothesis that AD results from an imbalance in an extensive plasticity network, the therapy should address as many network components as possible, with the idea that a combination approach may create an effect that is more than the sum of the effects of many monotherapeutics,” the researchers add.
Critical to the success of this hypothesis is the idea that there is a “threshold” at which multiple interventions will start to reverse the pathology leading to memory loss.