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Single Bouts of HIIT Exercise Boost Brain Power - Neuroscience News
New research finds that even single bouts of intense exercise can improve cognitive performance in young adults, particularly in memory, attention, and executive functioning. High-intensity interval training (HIIT) and cycling yielded the most substantial cognitive benefits, especially when lasting under 30 minutes. While the cognitive boost was modest, it suggests that brief, vigorous exercise may have a more immediate effect on brain function than previously thought.
Should I Leave My Husband? The Lure of Divorce
To cope with the stress, I asked my psychiatrist to increase the dosage of the antidepressant I’d been on for years. Sometime around then, I started talking too fast and drinking a lot.
Why are antidepressants so overprescribed? And what to do about it? - HealthSense
Withdrawal symptoms are most likely to occur when medications are stopped abruptly, after prolonged use, and at higher doses. Withdrawal can be very unpleasant and scary, causing lethargy, sadness, anxiety, irritability, trouble concentrating, sleep problems, nightmares, ’flu symptoms, nausea, dizziness, and strange sensations. They can also go on for a long time. Twenty-five per cent of users are still experiencing some symptoms after 3 months, and for some withdrawal can last 6 months.(4) Withdrawal occurs when doctors fail to deprescribe slowly enough or patients stop on their own. Partly because of the widespread misconception that antidepressants don't cause withdrawal, patients and doctors routinely misinterpret the symptoms as relapse – triggering what is often unneeded long term treatment.
Fluvoxamine may prevent serious illness in COVID-19 patients, study suggests: Antidepressant drug repurposed for patients with coronavirus infection -- ScienceDaily
Researchers compared the outcomes of those treated with fluvoxamine to the outcomes of those given an inactive placebo. After 15 days, none of the 80 patients who had received the drug experienced serious clinical deterioration. Meanwhile, six of the 72 patients given placebo (8.3%) became seriously ill, with four requiring hospitalization.
Screening + Drug Treatment = Increase in Veteran Suicides - Mad In America
There is clear evidence that SSRIs and SNRI antidepressants can provoke suicidal impulses and acts in some users, and the reason is well known. SSRIs and other antidepressants can stir extreme restlessness, agitation, insomnia, severe anxiety, mania and psychotic episodes. The agitation and anxiety, which is clinically described as akathisia, may reach “unbearable” levels, and akathisia is known to be associated with suicide and acts of violence, including homicide.
How many of 1829 antidepressant users report withdrawal effects or addiction? - PubMed - NCBI
A total of 1829 New Zealanders who had been prescribed antidepressants completed an online survey; 44% had been taking antidepressants for more than 3 years and were still taking them. Withdrawal effects when stopping medication were reported by 55%, and addiction by 27%. Paroxetine had particularly high rates of withdrawal symptoms.
Efficacy and safety of anti-inflammatory agents for the treatment of major depressive disorder: a systematic review and meta-analysis of randomised controlled trials | Journal of Neurology, Neurosurgery & Psychiatry
Thirty RCTs with 1610 participants were included in the quantitative analysis. The overall analysis pooling from 26 of the RCTs suggested that anti-inflammatory agents reduced depressive symptoms (SMD −0.55, 95% CI −0.75 to −0.35, I2=71%) compared with placebo. Higher response (RR 1.52, 95% CI 1.30 to 1.79, I2=29%) and remission rates (RR 1.79, 95% CI 1.29 to 2.49, I2=41%) were seen in the group receiving anti-inflammatory agents than in those receiving placebo.
Light works, Prozac ties placebo
A total of 122 patients were randomized (light monotherapy, 32; fluoxetine monotherapy, 31; combination therapy, 29; placebo, 30). The mean (SD) changes in MADRS score for the light, fluoxetine, combination, and placebo groups were 13.4 (7.5), 8.8 (9.9), 16.9 (9.2), and 6.5 (9.6), respectively. The combination (effect size [d] = 1.11; 95% CI, 0.54 to 1.64) and light monotherapy (d = 0.80; 95% CI, 0.28 to 1.31) were significantly superior to placebo in the MADRS change score, but fluoxetine monotherapy (d = 0.24; 95% CI, −0.27 to 0.74) was not superior to placebo.
Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins | The BMJ
The medical community strives to make decisions based on evidence, but as this case illustrates we have unfortunately arrived at a point where taking the conclusions of clinical trials at face value is apparently a sign of naivette. Conflicts of interest may play an important role in the reporting of scientific findings. The problem is not limited to just a couple of isolated cases but involves the entire culture of medicine that has developed over the past ten years. Put bluntly, the scientific machinery is broken. There is no easy fix, but surely patients deserve better.
ICER chastises J&J for overpricing depression drug esketamine ‘where there is such need for treatment’ – Endpoints News
Using the esketamine list price of $295 per 28 mg intranasal device, the treatment’s use results in an incremental cost-effectiveness ratio of approximately $198,000 per QALY compared to no additional treatment, exceeding the commonly cited cost-effectiveness thresholds of between $50,000-$150,000 per QALY. Meanwhile, esketamine is estimated to cost approximately $2.6 million per life year gained, ICER found.
Esketamine’s approval was also meant to enhance access to treatment — since ketamine is not covered by health insurers — although there is a concern that there may still be high out-of-pocket expenses through deductibles or non-coverage policies. Indeed, “the place for esketamine may depend on the comparative benefits between esketamine and other available treatments, such as ketamine. Unfortunately, such information is not available at this time,” ICER said.
(So does running) Ketamine reverses neural changes underlying depression-related behaviors in mice: Study sheds light on the neural mechanisms underlying remission of depression -- ScienceDaily
Researchers took high-resolution images of dendritic spines in the prefrontal cortex of mice before and after they experienced a stressor. Dendritic spines are protrusions in the part of neurons that receive communication input from other neurons. The researchers found that mice displaying behaviors related to depression had increased elimination of, and decreased formation of, dendritic spines in their prefrontal cortex compared with mice not exposed to a stressor. This finding replicates prior studies linking the emergence of behaviors related to depression in mice with dendritic spine loss.
In addition to the effects on dendritic spines, stress reduced the functional connectivity and simultaneous activity of neurons in the prefrontal cortex of mice. This reduction in connectivity and activity was associated with behaviors related to depression in response to stressors. Liston's group then found that ketamine treatment rapidly restored functional connectivity and ensemble activity of neurons and eliminated behaviors related to depression
Gut Bacteria Linked to Depression Identified – Neuroscience News
Mireia Valles-Colomer (VIB-KU Leuven): ‘Many neuroactive compounds are produced in the human gut. We wanted to see which gut microbes could participate in producing, degrading, or modifying these molecules. Our toolbox not only allows to identify the different bacteria that could play a role in mental health conditions, but also the mechanisms potentially involved in this interaction with the host. For example, we found that the ability of microorganisms to produce DOPAC, a metabolite of the human neurotransmitter dopamine, was associated with better mental quality of life.’
The cumulative effect of reporting and citation biases on the apparent efficacy of treatments: the case of depression
Figure 1 demonstrates the cumulative impact of reporting and citation biases. Of 105 antidepressant trials, 53 (50%) trials were considered positive by the FDA and 52 (50%) were considered negative or questionable (Fig. 1a). While all but one of the positive trials (98%) were published, only 25 (48%) of the negative trials were published. Hence, 77 trials were published, of which 25 (32%) were negative (Fig. 1b). Ten negative trials, however, became ‘positive’ in the published literature, by omitting unfavorable outcomes or switching the status of the primary and secondary outcomes (Fig. 1c). Without access to the FDA reviews, it would not have been possible to conclude that these trials, when analyzed according to protocol, were not positive. Among the remaining 15 (19%) negative trials, five were published with spin in the abstract (i.e. concluding that the treatment was effective). For instance, one article reported non-significant results for the primary outcome (p = 0.10), yet concluded that the trial ‘demonstrates an antidepressant effect for fluoxetine that is significantly more marked than the effect produced by placebo’ (Rickels et al., 1986). Five additional articles contained mild spin (e.g. suggesting the treatment is at least numerically better than placebo). One article lacked an abstract, but the discussion section concluded that there was a ‘trend for efficacy’. Hence, only four (5%) of 77 published trials unambiguously reported that the treatment was not more effective than placebo in that particular trial (Fig. 1d). Compounding the problem, positive trials were cited three times as frequently as negative trials (92 v. 32 citations in Web of Science, January 2016, p < 0.001, see online Supplementary material for further details) (Fig. 1e). Among negative trials, those with (mild) spin in the abstract received an average of 36 citations, while those with a clearly negative abstract received 25 citations. While this might suggest a synergistic effect between spin and citation biases, where negatively presented negative studies receive especially few citations (de Vries et al., 2016), this difference was not statistically significant (p = 0.50), likely due to the small sample size. Altogether, these results show that the effects of different biases accumulate to hide non-significant results from view.
You Can't Cure Depression By Working Out - Tonic
Our two proven treatment paths for psychiatric illnesses are medication and therapy. People have messed around with the possibility of a third (electroconvulsive therapy, heat therapy) but we don't currently have one, no matter how many people say running eases their nerves better than medication.
SSRIs a 'Double-Edged Sword' in Major Depression?
Investigators led by Igor Branchi, PhD, Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy, explored the hypothesis that SSRIs may not "affect mood per se but [may amplify] the influence of living conditions on mood."
How does helping people affect your brain? Study shows neurobiological effects of giving social support -- ScienceDaily
"Humans thrive off social connections and benefit when they act in the service of others' well-being," according to the authors. A previous study by Dr. Inagaki, also published in Psychosomatic Medicine, found that giving social support has positive effects on brain areas involved in stress and reward responses. That study suggested that providing support -- not just receiving it -- may be an important contributor to the physical and mental health benefits of social support.
In test with rats, cannabidiol showed sustained effects against depression for seven days -- ScienceDaily
"The forced swim test is used to measure the effect of antidepressant drugs because all known antidepressants shorten the duration of immobility and hence lengthen swim time. A reduction in immobility time in this test is interpreted as 'antidepressant-like' behavior."
The researchers found that cannabidiol induced acute and sustained antidepressant-like effects in mice submitted to the forced swim test.
"However, to make sure this result isn't due to the increase in movement caused by a psychostimulant effect leading the animals to swim more vigorously, for example, we performed a separate test to control for locomotor activity," Joca explained.
"To do this we used the open-field test, which consists of putting the animal in a novel arena and letting it explore the new environment freely while its locomotor and exploratory activity is recorded. A drug is said to have potential antidepressant effects if it reduces immobility time and increases swim time in the forced swim test without increasing locomotor activity in the open-field test, showing that the effects observed in the forced swim test aren't secondary to nonspecific alterations in locomotor activity."
Painting a Nuanced Picture of Brain System Regulation Moods and Movements - Neuroscience News
In a series of behavioral tests, the scientists also showed that serotonin neurons from the two groups can respond differently to stimuli. For example, neurons in both groups fired in response to mice receiving rewards like sips of sugar water but they showed opposite responses to punishments like mild foot shocks.
“We now understand why some scientists thought serotonin neurons are activated by punishment, while others thought it was inhibited by punishment. Both are correct – it just depends on which subtype you’re looking at,” Luo said.
Lack of a Single Molecule May Indicate Severe and Treatment Resistant Depression - Neuroscience News
Naturally produced by the body, LAC performs a number of crucial tasks in the brain. For example, the molecule regulates energy metabolism and interacts with DNA to promote the expression of important genes. Specifically, it acts on a gene that controls levels of the neurotransmitter glutamate–a chemical implicated in almost everything that the brain does.
McEwen, the Alfred E. Mirsky Professor, and Nasca, a postdoctoral fellow of the American Foundation for Suicide Prevention, have studied the link between LAC and mood disorders using animal models. In one study, they showed that LAC supplements ameliorate depressive symptoms in mice by reversing brain-cell impairment caused by an excess of glutamate. In a separate rodent study, they observed that LAC treatment reduces depressive behavior and stress-associated neural dysfunction in the medial amygdala, a brain region involved in social interactions. These findings strongly suggest that LAC deficits contribute to a depression-like state in mice, leading the scientists to wonder whether the molecule plays a similar role in humans.
Association of Depressive Symptoms and Heart Rate Variability in Vietnam War–Era Twins: A Longitudinal Twin Difference Study | JAMA Psychiatry | JAMA Network
The association between depression and autonomic dysregulation, indexed by HRV, is bidirectional, with stronger evidence suggesting that autonomic function affects depression risk rather than vice versa.
The immune system and the pathogenesis of depression
There is bidirectional communication between the HPA axis and the immune system. Cytokines activate the HPA axis and thus lead to the release of cortisol, the stress hormone, which ordinarily suppresses the immune response. Cortisol also inhibits its own release and thus the body is able to maintain a stable immune response through a tightly regulated feedback inhibition system. This regulation mechanism seems to be dysfunctional in depressive disorders and is thought to occur because of cytokine mediated receptor resistance to cortisol, thus impairing feedback inhibition. This essentially means that cytokines make cortisol unable to act on the receptors that would inhibit its release. Long story short — the HPA axis is hyperactive because of cytokines, leading to a chronic stress response because cytokines impair the body’s ability to regulate it — thus leading to depressive symptoms.
Ketamine Acts Fast to Treat Depression and Its Effects Last, But How? - Neuroscience News
Ketamine produces rapid and robust antidepressant effects in depressed patients within hours of administration, often when traditional antidepressant compounds have failed to alleviate symptoms. We hypothesized that ketamine would translocate Gαs from lipid rafts to non-raft microdomains, similarly to other antidepressants but with a distinct, abbreviated treatment duration. C6 glioma cells were treated with 10 µM ketamine for 15 min, which translocated Gαs from lipid raft domains to non-raft domains. Other NMDA antagonist did not translocate Gαs from lipid raft to non-raft domains. The ketamine-induced Gαs plasma membrane redistribution allows increased functional coupling of Gαs and adenylyl cyclase to increase intracellular cyclic adenosine monophosphate (cAMP). Moreover, increased intracellular cAMP increased phosphorylation of cAMP response element-binding protein (CREB), which, in turn, increased BDNF expression. The ketamine-induced increase in intracellular cAMP persisted after knocking out the NMDA receptor indicating an NMDA receptor-independent effect. Furthermore, 10 µM of the ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) also induced Gαs redistribution and increased cAMP. These results reveal a novel antidepressant mechanism mediated by acute ketamine treatment that may contribute to ketamine’s powerful antidepressant effect. They also suggest that the translocation of Gαs from lipid rafts is a reliable hallmark of antidepressant action that might be exploited for diagnosis or drug development.
Antidepressants don't work, or depression doesn't exist (as a meaningful category)
The real truth isn't found within the published paper but rather within a busy table on page 142 of the online appendix. It is here where the authors report what we want: the actual difference between drugs and placebo, before and after treatment, on the depression rating scales. Here we see that the Cohen's d standardized mean difference effect sizes range from a low of 0.19 to a high of 0.62 with amitriptyline. Thus, amitriptyline exceeds the clinically meaningful threshold of 0.50, with a traditional meta-analytic method. No other drug does so, with the closest second place being fluvoxamine, with a Cohen's d value of 0.44.
Looking at all of the agents, 10 drugs have Cohen's d values less than 0.30, which is very small and clinically meaningless, whereas four have effect sizes from 0.30 to 0.34. Thus, 74% (14/19) of antidepressants clearly have little or no clinically important benefit in this analysis (for some reason, no data are provided in this table with two of the drugs). Four drugs have effect sizes of 0.37-0.44, and as noted, one agent exceeds the 0.50 threshold (amitriptyline).
Perhaps a clearer conclusion than anything else is the well-proven fact that the tricyclic antidepressants are more effective than newer agents (there were no monoamine oxidase inhibitors in this meta-analysis).
Lessons learned from placebo groups in antidepressant trials
The analysis of ‘nocebo effects’, e.g. adverse effects in placebo groups of antidepressant trials also confirms the impact of expectations: nocebo symptoms reflected the typical side-effect patterns expected in the drug group, with higher symptoms rates in the placebo groups of tricyclic antidepressant trials compared with placebo groups of trials testing selective serotonin reuptake inhibitors.
Antidepressants and bladder medicines linked to dementia in landmark study -- ScienceDaily
"We studied patients with a new dementia diagnosis and looked at what anticholinergic medication they were prescribed between four and 20 years prior to being diagnosed.
"We found that people who had been diagnosed with dementia were up to 30 per cent more likely to have been prescribed specific classes of anticholinergic medications. And the association with dementia increases with greater exposure to these types of medication.
"What we don't know for sure is whether the medication is the cause. It could be that these medications are being prescribed for very early symptoms indicating the onset of dementia.
Antidepressant withdrawal
About half (54%) met their goal of completely discontinuing one or more medications; 46% reported another outcome (use was reduced, use increased, or use stayed the same). Concerns about medications’ effects (for example, long-term effects and side effects) prompted the decision to discontinue for 74% of respondents. They used various strategies to cope with withdrawal symptoms, which 54% rated as severe. Self-education and contact with friends and with others who had discontinued or reduced medications were most frequently cited as helpful. Although more than half rated the initial medication decision with prescribers as largely collaborative, only 45% rated prescribers as helpful during discontinuation. Of respondents who completely discontinued, 82% were satisfied with their decision.
