Health
The Future of Major Depressive Disorder Treatments
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By James Giordano, PhD, as told to Kara Mayer Robinson
Over the last 20 years, we’ve seen major strides in the treatment options for major depressive disorder.
We now understand that depression isn’t the same for everyone. The idea is to identify and diagnose what’s happening in a person’s neurochemistry so we can target our treatment in a way that works specifically for them.
Advances in Evidence-Based Treatment
Drug therapy has come a long way in recent years. We’ve improved the scope and focus of drug therapy by developing more selective or specialized antidepressants and combining them in new ways, with fewer side effects.
Drug therapy today may include newer medications like citalopram (Celexa) and escitalopram (Lexapro) as well as existing medications like fluoxetine (Prozac) and sertraline (Zoloft).
It tends to work best when combined with psychotherapy, as supported by ample evidence. We now know the most effective and efficient types of therapy appear to be cognitive-behavioral and psychodynamic therapy.
For people whose depression is resistant to psychotherapy and drug therapy, doctors may use electroconvulsive therapy (ECT). Today’s version of ECT is much more specific, with lower side effects. It’s usually reserved for people who have severe, drug-resistant depression with bipolar characteristics.
Newer Treatments
Many new therapies have been introduced that have led to major improvement for patients.
Ketamine
A newer therapy involves the drug ketamine, which has been used in the past as an anesthetic and has robust benefits. It’s a relatively new approach. It’s been around for about 5 years.
Ketamine therapy resets your brain node and network connectivity to reduce, if not abolish, many depressive signs and symptoms. Many patients have longstanding relief, and in some cases, recover.
Ketamine therapy may involve as little as a single dose. Or it could be multiple doses over a short period of time. But it must be done under medical supervision. While it’s usually outpatient therapy, proper dosing and support of a patient using ketamine is critical.
It’s not the first drug of choice because it has fairly profound effects on the brain and has to be used with caution. Right now it’s used for severe treatment-resistant depression. But there’s an ongoing discussion that people with severe depression may do well using it earlier in treatment.
I think you’ll see an increased use of ketamine in the future, particularly for those who don’t get help from other treatments.
Psychedelics
There’s building evidence for the use of psychedelic drugs to treat major depression.
Drugs like psilocybin, commonly known as mushrooms, and LSD (lysergic acid diethylamide) can change the properties in your brain chemistry that are involved in depression.
Microdoses or millidoses of these drugs can be very effective, either by themselves or when used with antidepressants. They can improve symptoms, behavior, and function. They tend to be fast-acting, but for some people the effects don’t last long.
Psychedelics are still viewed with relative stigma and they’re a controlled substance. It’s necessary to find the right microdose and schedule for the best effect. Not all clinicians are skilled, comfortable, or willing to provide psychedelic drugs.
Another drawback is that people may try to self-medicate, which is very difficult. This is a very specific method that requires clinical skill.
More research is needed. We need medicine-based evidence for the use and value of psychedelics in treating certain types of depression.
Transcranial Magnetic Stimulation (TMS)
TMS, which involves passing a very weak magnetic current through your skull, is interesting. It works like a dimmer switch to change the electrical activity of your brain and reduce signs and symptoms of depression.
There’s very promising research that repetitive TMS can be very effective in treating certain forms of treatment-resistant depression. It’s very easy to do, can be tailored to each patient’s needs, and often has a rapid and durable response. It can be used by itself or combined with psychotherapy or drug treatment.
But while the effects of TMS are robust, they may taper over time. It may require multiple sessions, and you have to find a clinician who’s trained and skilled to administer TMS.
Deep Brain Stimulation (DBS)
Deep brain stimulation is a new, emerging treatment that involves implanting electrodes to target specific areas of the brain. It can be adjusted for each individual patient to most effectively control their symptoms and signs of depression.
DBS was first tried in 2005. Since then, the science has advanced considerably with the help of the BRAIN Initiative, an NIH program aimed at revolutionizing our understanding of the human brain. Now we have a better understanding of how to target the brain more precisely, which may lead to better results. More research will help even more.
DBS appears to reset the network activities of the brain. Over time, the brain activity involved in depression may be turned off, which means patients stay in remission. There’s evidence to suggest DBS has long-lasting effects.
An interesting effect we’ve seen with some patients is how significantly it changes their outlook. Some people appear more outgoing and ebullient, with a newfound vigor and even changing interests. It’s hard to tell if these changes are a side effect of DBS or if it’s the result of feeling the burden of depression lifted. It’s very interesting.
A downside of DBS is that it’s neurosurgery, so there’s the risk of infection and hemorrhage. It’s rare, but there’s also a risk of misplacement, or electrode drift.
Other cons include side effects and cost. Insurance companies don’t uniformly cover DBS. As the technology gets better, there will be a need for maintenance and upkeep that may be costly.
I believe DBS is the future. When it works, it really works.
On the Horizon
The emerging technology is moving toward minimal or noninvasive DBS.
There’s cutting-edge technology involving nonsurgical implantation of electrodes. A program at DARPA, an agency that supports the BRAIN Initiative, is looking at small transmitters and stimulators that can be delivered into the bloodstream, inhaled, or even swallowed, then guided to the brain.
Other groups are looking at minimally invasive approaches that can be done in a doctor’s office. All it requires is a very small hole in your scalp, where doctors insert fluid electrodes, then guide them to the brain electromagnetically. When they get to the brain, they harden.
I believe this is the future. It may be ready in some form in 5-10 years.
Health
Walmart Is Selling a $300 Power Tower for Just $128, and Shoppers Say It's 'Surprisingly Sturdy'
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When building a home gym, it’s easy to get overwhelmed by all the equipment options, especially when you’re working with limited space and a tight budget. But when you focus on versatile gear and hunt for deals, creating a useful setup is easily doable. Thankfully, Walmart has been slashing prices on a ton of fitness equipment, including its bestselling adjustable dumbbells and even a complete home gym system. Now, it’s reduced the price of a popular power tower by over $170, and it even ships for free.
The Pooboo Body Champ Multifunction Power Tower is on sale for $128, a 57% discount on its normal price of $300. This incredibly versatile workout station has earned nearly 250 five-star ratings from Walmart shoppers who’ve praised its “strong and sturdy” build and “quality fit and finish,” and it’s currently one of the top 5 bestselling models on the site.
Pooboo Body Champ Multifunction Power Tower, $128 (was $300) at Walmart
Don’t let the brand’s bizarre name fool you—this power tower is a well-made piece of gym equipment. It features steel construction and is rated to hold up to 480 pounds (the tower itself weighs 66 pounds). A nearly 42-inch H-shaped base gives it excellent stability, so it won’t wobble or shake when you’re exercising, and anti-slip feet on the bottom keep it securely planted on the floor. It’s also adjustable (from 71.4 inches to 94 inches) to accommodate users of varying heights. And, once it’s set up, you can use it for a huge range of exercises, including dips, pull-ups, chin-ups, push-ups, vertical leg raises, knee raises, and more.
According to Walmart reviewers, the Pooboo Body Champ stands out for its solid build and usefulness. “It’s a surprisingly sturdy piece of equipment,” a shopper said. “Everything about this fitness tower is perfect. I originally purchased this with the intention of only doing pull-ups on it, but after quickly assembling the power tower, I came to realize just how versatile it is. It has cushions for knee and leg raises, it’s sturdy, and the perfect width for dips.” Another shopper agreed, saying, “This was a much-needed addition to my home gym.”
“This thing is amazing and worth every penny,” said another, who added that it’s “easy to install and can hold a lot of weight.”
At just $128, this Pooboo power tower is a screaming deal, and it’s sure to get lots of use during your workouts. But this discount won’t last long, so grab one today before the price pumps back up.
Health
Alzheimer’s Drug May Save Lives Through ‘Suspended Animation’
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By Lindsay Brownell | Wyss Institute Communications | Harvard Gazette
Could buy patients more time to survive critical injuries and diseases, even when disaster strikes far from a hospital
Donepezil, an FDA-approved drug to treat Alzheimer’s, has the potential to be repurposed for use in emergency situations to prevent irreversible organ injury, according to researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University.
Using Donepezil (DPN), researchers report that they were able to put tadpoles of Xenopus laevis frogs into a hibernation-like torpor.
“Cooling a patient’s body down to slow its metabolic processes has long been used in medical settings to reduce injuries and long-term problems from severe conditions, but it can only currently be done in a well-resourced hospital,” said co-author Michael Super, director of immuno-materials at the Wyss Institute. “Achieving a similar state of ‘biostasis’ with an easily administered drug like DNP could potentially save millions of lives every year.”
This research, published Thursday in ACS Nano, was supported as part of the DARPA Biostasis Program, which funds projects that aim to extend the time for lifesaving medical treatment, often referred to as “the Golden Hour,” following traumatic injury or acute infection. The Wyss Institute has been a participant in the Biostasis Program since 2018, and has achieved several important milestones over the last few years.
Using a combination of predictive machine learning algorithms and animal models, the Wyss’ Biostasis team previously identified and tested existing drug compounds that had the potential to put living tissues into a state of suspended animation. Their first successful candidate, SNC80, significantly reduced oxygen consumption (a proxy for metabolism) in both a beating pig heart and in human organ chips, but is known to cause seizures when injected systemically.
In the new study, they once again turned to their algorithm to identify other compounds whose structures are similar to SNC80. Their top candidate was DNP, which has been approved since 1996 to treat Alzheimer’s.
Achieving a similar state of ‘biostasis’ with an easily administered drug like DNP could potentially save millions of lives every year.
–Michael Super
“Interestingly, clinical overdoses of DNP in patients suffering from Alzheimer’s disease have been associated with drowsiness and a reduced heart rate — symptoms that are torpor-like. However, this is the first study, to our knowledge, that focuses on leveraging those effects as the main clinical response, and not as side effects,” said the study’s first author, María Plaza Oliver, who was a postdoctoral fellow at the Wyss Institute when the work was conducted.
The team used X. laevis tadpoles to evaluate DNP’s effects on a whole living organism, and found that it successfully induced a torpor-like state that could be reversed when the drug was removed. The drug, however, did seem to cause some toxicity, and accumulated in all of the animals’ tissues. To solve that problem, the researchers encapsulated DNP inside lipid nanocarriers, and found that this both reduced toxicity and caused the drug to accumulate in the animals’ brain tissues. This is a promising result, as the central nervous system is known to mediate hibernation and torpor in other animals as well.
Although DNP has been shown to protect neurons from metabolic stress in models of Alzheimer’s disease, the team cautions that more work is needed to understand exactly how it causes torpor, as well as scale up production of the encapsulated DNP for use in larger animals and, potentially, humans.
“Donepezil has been used worldwide by patients for decades, so its properties and manufacturing methods are well-established. Lipid nanocarriers similar to the ones we used are also now approved for clinical use in other applications. This study demonstrates that an encapsulated version of the drug could potentially be used in the future to buy patients critical time to survive devastating injuries and diseases, and it could be easily formulated and produced at scale on a much shorter time scale than a new drug,” said senior author Donald Ingber, the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences.
This research was supported by DARPA under Cooperative Agreement Number W911NF-19-2-0027, the Margarita Salas postdoctoral grant co-funded by the Spanish Ministry of Universities, and the University of Castilla-La Mancha (NextGeneration EU UNI/551/2021).
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This story is reprinted with permission from The Harvard Gazette.
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Health
Can Stuff in Rosemary Extract Fight Cocaine Addiction?
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Researchers have discovered that an antioxidant found in rosemary extract can reduce intakes of cocaine by moderating the brain’s reward response, offering a new therapeutic target for treating addiction.
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The study in the journal Neuron describes researchers’ focus on a region of the brain called the globus pallidus externus, which acts as a gatekeeper that regulates how we react to cocaine.
They discovered that within the GPe, parvalbumin-positive neurons are crucial in controlling the response to cocaine by changing the activity neurons releasing the pleasure molecule dopamine.
“There are currently no effective therapeutics for dependence on psychostimulants such as cocaine, which, along with opioids, represent a substantial health burden,” says corresponding author Kevin Beier, an associate professor of physiology and biophysics at the University of California, Irvine.
“Our study deepens our understanding of the basic brain mechanisms that increase vulnerability to substance use disorder-related outcomes and provides a foundation for the development of new interventions.”
Findings in mice revealed that globus pallidus externus parvalbumin-positive cells, which indirectly influence the release of dopamine, become more excitable after being exposed to cocaine. This caused a drop in the expression of certain proteins that encode membrane channels that usually help keep the globus pallidus cell activity in check. The researchers found that carnosic acid, an isolate of rosemary extract, selectively binds to the affected channels, providing an avenue to reduce response to the drug in a relatively specific fashion.
“Only a subset of individuals are vulnerable to developing a substance use disorder, but we cannot yet identify who they are. If globus pallidus cell activity can effectively predict response to cocaine, it could be used to measure likely responses and thus serve as a biomarker for the most vulnerable,” Beier says. “Furthermore, it’s possible that carnosic acid could be given to those at high risk to reduce the response to cocaine.”
The next steps in this research include thoroughly assessing negative side effects of carnosic acid and determining the ideal dosage and timing. The team is also interested in testing its efficacy in reducing the desire for other drugs and in developing more potent and targeted variants.
Scientists from the University of West Virginia and the University of Colorado participated in the study.
Support for this work came from the National Institutes of Health, One Mind, the Alzheimer’s Association, New Vision Research, BrightFocus Foundation, and the Brain & Behavior Research Foundation.
Source: UC Irvine
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Previously Published on futurity.org with Creative Commons License
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