Long-term usage of antidepressant medications may protect from dementia

Long-term treatment with certain antidepressants appeared associated with reduced dementia incidence, according to results of a case-control study published in Journal of Clinical Psychiatry.

“Depression could represent one of these potentially modifiable risk factors for all-cause dementia,” Claudia Bartels, PhD, of the department of psychiatry and psychotherapy at University Medical Center Goettingen in Germany, and colleagues wrote. “Numerous studies have concordantly demonstrated a strong association between depression and an increased risk [for] subsequent dementia. Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat depressive symptoms in [Alzheimer’s disease] dementia.

“Preclinical research in recent years has suggested that SSRIs reduce amyloid plaque burden in transgenic mouse models of [Alzheimer’s disease] and in cognitively healthy humans, attenuate amyloid-[beta]1-42–induced tau hyperphosphorylation in cell culture and improve cognition in mice.”

However, the effects of SSRIs on cognition in Alzheimer’s disease dementia were linked mostly to negative results in randomized clinical trials; research is sparse regarding which antidepressants may influence risk for developing dementia; and evidence is particularly rare for treatment duration effects on this risk. Thus, Bartels and colleagues sought to determine the effects of antidepressant drug classes and individual compounds with various treatment durations on the risk for developing dementia. The researchers analyzed data of 62,317 individuals with an incident dementia diagnosis who were included in the German Disease Analyzer database, and they compared outcomes to those of controls matched by age, sex and physician. They conducted logistic regression analyses, which were adjusted for health insurance status and comorbid diseases linked to dementia or antidepressant use, to evaluate the association between dementia incidence and treatment with four major classes of antidepressant drug, as well as 14 of the most commonly prescribed individual antidepressants.

Results showed an association between treatment for 2 years or longer with any antidepressant and a lower risk for dementia vs. short-term treatment among 17 of 18 comparison. Particularly for long-term treatment, herbal and tricyclic antidepressants were linked to a decrease in incidence of dementia. Long-term treatment with escitalopram (OR = 0.66; 95% CI, 0.5-0.89) and Hypericum perforatum (OR = 0.6; 95% CI, 0.51-0.7) were associated with the lowest risks for dementia on an individual antidepressant basis.

“Clinical trials — although well acknowledged as the gold standard procedure — have debunked numerous promising compounds and become increasingly challenging with longer treatment durations,” Bartels and colleagues wrote. “Thus, and in awareness of the controversy of this suggestion, analyzing data from registries in a naturalistic setting may be an attractive and feasible alternative. If individual datasets could be combined in a multinational effort, even more powerful analyses of merged big databases could be performed and an additive contribution with naturalistic data could be made.”

https://www.healio.com/news/psychiatry/20200828/longterm-treatment-with-certain-antidepressants-may-reduce-dementia-incidence

New study identifies potential new class of more rapidly acting antidepressant medications

A new study by researchers at University of Maryland School of Medicine has identified promising compounds that could successfully treat depression in less than 24 hours while minimizing side effects. Although they have not yet been tested in people, the compounds could offer significant advantages over current antidepressant medications.

The research, led by Scott Thompson, PhD, Professor and Chair of the Department of Physiology at the University of Maryland School of Medicine (UM SOM), was published this month in the journal Neuropsychopharmacology.

“Our results open up a whole new class of potential antidepressant medications,” said Dr. Thompson. “We have evidence that these compounds can relieve the devastating symptoms of depression in less than one day, and can do so in a way that limits some of the key disadvantages of current approaches.”

Currently, most people with depression take medications that increase levels of the neurochemical serotonin in the brain. The most common of these drugs, such as Prozac and Lexapro, are selective serotonin reuptake inhibitors, or SSRIs. Unfortunately, SSRIs are effective in only a third of patients with depression. In addition, even when these drugs work, they typically take between three and eight weeks to relieve symptoms. As a result, patients often suffer for months before finding a medicine that makes them feel better. This is not only emotionally excruciating; in the case of patients who are suicidal, it can be deadly. Better treatments for depression are clearly needed.

Dr. Thompson and his team focused on another neurotransmitter besides serotonin, an inhibitory compound called GABA. Brain activity is determined by a balance of opposing excitatory and inhibitory communication between brain cells. Dr. Thompson and his team argue that in depression, excitatory messages in some brain regions are not strong enough. Because there is no safe way to directly strengthen excitatory communication, they examined a class of compounds that reduce the inhibitory messages sent via GABA. They predicted that these compounds would restore excitatory strength. These compounds, called GABA-NAMs, minimize unwanted side effects because they are precise: they work only in the parts of the brain that are essential for mood.

The researchers tested the compounds in rats that were subjected to chronic mild stress that caused the animals to act in ways that resemble human depression. Giving stressed rats GABA-NAMs successfully reversed experimental signs of a key symptom of depression, anhedonia, or the inability to feel pleasure. Remarkably, the beneficial effects of the compounds appeared within 24 hours – much faster than the multiple weeks needed for SSRIs to produce the same effects.

“These compounds produced the most dramatic effects in animal studies that we could have hoped for,” Dr. Thompson said. “It will now be tremendously exciting to find out whether they produce similar effects in depressed patients. If these compounds can quickly provide relief of the symptoms of human depression, such as suicidal thinking, it could revolutionize the way patients are treated.”

In tests on the rats’ brains, the researchers found that the compounds rapidly increased the strength of excitatory communication in regions that were weakened by stress and are thought to be weakened in human depression. No effects of the compound were detected in unstressed animals, raising hopes that they will not produce side effects in human patients.

“This work underscores the importance of basic research to our clinical future,” said Dean E. Albert Reece, MD, PhD, MBA, who is also the vice president for Medical Affairs, University of Maryland, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean of the School of Medicine. “Dr. Thompson’s work lays the crucial groundwork to transform the treatment of depression and reduce the tragic loss of lives to suicide.”

http://www.news-medical.net/news/20150714/New-study-identifies-potential-antidepressant-medications-with-few-side-effects.aspx

Blueberries may be effective in the treatment for post-traumatic stress disorder (PTSD)

Researchers from Louisiana State University have found that blueberries may be effective in the treatment for post-traumatic stress disorder (PTSD). Findings from the study have been presented at the Experimental Biology Meeting in Boston, MA.

Presently, the only therapy approved by the Food and Drug Administration (FDA) for PTSD is selective serotonin reuptake inhibitors (SSRIs) such as sertraline and paroxetine. Study authors have previously shown that SSRIs increase the level of serotonin (5-HT) and norepinephrine, and that the increased norepinephrine be a possible reason for the reduced efficacy of SSRI therapy.

For this study, the team studied the ability of blueberries to modulate neurotransmitter levels in a rat model of PTSD. Some of the rats received a 2% blueberry-enriched supplement diet and others received a control diet. A third control group consisted of rats without PTSD and received a standard diet without blueberries. Scientists used high-performance liquid chromatography to to measure monoamines and related metabolite levels.

Rats with PTSD who did not receive blueberries showed a predictable increase in 5-HT and norepinephrine level compared with the control group. But rats with PTSD that received blueberries showed a beneficial increase in 5-HT levels with no impact on norepinephrine levels, which suggest that blueberries can alter neurotransmitter levels in PTSD. More studies are needed to understand the protective effects of blueberries and its potential target as a treatment for PTSD.

http://www.empr.com/benefits-of-blueberries-for-post-traumatic-stress-disorder-explored-in-study/article/405810/