Health - Wellcast

Ketamine or Electroconvulsive Therapy for Resistant Depression

April 25, 2023 By Deborah

An estimated 30% of major depressive disorders are resistant to treatment in the United States. This means a person has tried at least 2 antidepressants for at last 6 weeks each and has not experienced remission or at least a 50% improvement in mood. Two common treatments for this condition are Ketamine or Electroconvulsive therapy for resistant depression. Ketamine has drawn a lot of attention recently. This drug has been studied and administered in controlled, clinical settings to help with treatment-resistant depression and other conditions. Ketamine is an anesthetic and a sedative and has been used to treat suicidal thoughts. . It causes a dissociative experience that makes the brain more malleable and receptive to therapy or alternative ways of thinking. Ketamine influences the neurotransmitter, Glutamate while its causes a cascade of biologic, structural and functional changes in the brain.

Electroconvulsive therapy (ECT) is a medical treatment also used for drug-resistant depression and bipolar disorder. It involves a brief electrical stimulation of the brain to create a generalized cerebral seizure while the person is under anesthesia. Dopamine function is thought to be impaired in people with depression causing impairment in concentration, motivation and pleasure. ECT improves this system while lowering stress hormones and helps feedback regulation.

While both of these treatments have rapid responses (hours to days), is there one better than the other? A meta-analysis was done in which researchers examined 6 studies looking at Ketamine infusions (3 times per week for 2 weeks) and ECT (3 times/week for 4 weeks). Results showed that at 1 month, ECT was significantly more effective than ketamine, with remission rates of 63% versus 43% in the largest study. Both Ketamine and ECT were effective in reducing suicidal ideation. ECT had more cognitive side effects and ketamine was associated with more depersonalization, vertigo and visual disturbance. The effects of both treatments waned over time with comparable outcomes at 3 and 12 months.

There is evidence of long-term maintenance with ECT. Unfortunately, intravenous Ketamine is not reimbursed by insurance companies which is the most bioavailable, precise treatment. Ketamine comes in different forms such as oral, topical, intramuscular, sublingual and intranasal. In the U.S the only FDA-approved form is nasal esketamine (Spravato) but it is only 25-50% bioavailable. Bioavailability means the amount of medication that actually goes to the bodies tissues and the brain. Intravenous treatments are 100% bioavailable. When you take other forms of the drug, parts of the active ingredients don’t go to the bloodstream, but get digested and altered into an unusable form, metabolized and excreted into your body. Although ECT appears to be superior, ketamine might be preferred by those looking for more rapid effects and wanting to avoid ECT’s short-term cognitive effects.

Youth depression rates have risen from 12.9% to 25.2% from pre-pandemic to 2021.

Mental health illness has risen in the United States, with about 20% of people in the country experiencing some form of it. There are many reasons for this sharp increase. The increase can be due to social media, the COVID-19 pandemic, and societal trends resulting in smaller family units, increased financial pressure, social isolation and political and economic stressors. Youth depression rates have risen from 12.9% to 25.2% from pre-pandemic to 2021. More than 50 million Americans struggle with mental illness and most lack access to adequate mental health treatment.

Other brain stimulation treatments include Transcranial magnetic stimulation (TMS) and Vagus nerve stimulation (VNS). Unlike ECT, TMS does not cause a seizure and the patient stays awake through the entire non-invasive process. Rapidly alternating magnetic fields stimulate specific areas of the brain. It is usually administered 4 or 5 times per week for 4-6 weeks. Side effects are usually mild including headaches, twitching and pain at the stimulation site.

Vagus nerve stimulation was originally used to treat seizures but can be effective in treating depression that has not responded to other therapies. It involves implanting an electrical pulse generator under the skin in the patient’s chest that provides intermittent electrical stimulation to the vagus nerve in the neck. Response may take months, so it is not used as a treatment for acute severe depression.

Mental health is so important for our overall health because of its relationship with our physical health. For example, depression raises the risk of diabetes, heart disease and stroke. Similarly, the presence of chronic illnesses can increase the risk of mental illness. Solutions consist of spending time in nature, healthy eating and exercise, connecting with others, reducing stress and getting enough sleep. Other effective treatments include psychotherapy, and many of the above medications or procedures.

Reference: dosomething.org. “11 Facts About Mental Health”. 2023.

Zimmerman, R. Ketamine for depression: What it feels like and who it can help. The Washington Post. 9/12/2022.

The American Psychiatric Association. What is Electroconvulsive therapy? Psychiatry.org

Principium Psychiatry. IV vs Oral Intramuscular vs Intranasal Ketamine: Why route matters. principiumpsychiatry.com

Rhee TG et al. Efficacy and safety of ketamine vs electroconvulsive therapy among patients with major depressive episode: A systemic review and meta-analysis. JAMA Psychiatry 2022. Oct 19; [e-pub]. (https://doi.org/10.1001/jamapsychiatr. 2022.3352)

Brain Therapy TMS: Transcranial magnetic Stimulation. Top 5 treatment-resistant depression statistics you need to know. May 28, 2021.

Postbiotics is Part of the Gut-Brain Axis

March 25, 2023 By Deborah

We have heard the term “probiotics” which refers to the live bacteria and yeast that help maintain or improve the healthy microflora in the gut. We may also be familiar with “prebiotics” which are the fermented foods that FEED these amazing bacteria, as well as viruses and yeast species. But postbiotics are also part of the gut-brain axis that needs to be discussed. All three of these types of “biotics” (from the Greek “bios” meaning “for life”) should be part of the discussion when it comes to our gut, which is the largest organ in the body that holds 70% of our immune system. So it needs to be happy, healthy and well cared for.

So what are “postbiotics’? They are defined as the nonviable bacterial or metabolic products from microorganisms that have biological activity in the host. It is basically the waste left behind by the digestion of pre and probiotics. Some postbiotics from non-viable microorganisms come from Lactobacillus species. These precision probiotics are strains that have precise effects in the body and brain. For instance, there is growing evidence of antidepressant effects of GABA secreted by Lacticaseibacillus rhamnosus and Lacticaseibacillus casei that travels through the nervous system and crosses the blood-brain-barrier altering the expression of GABA receptors that may lead to a reduction in depression. Another GABA secreting bacteria, Levilactobacillus brevis may help with sleep as well as reducing depression.

The fact is that we make more neurotransmitters in our gut than the brain. Certain bacteria can send serotonin, GABA, dopamine and norepinephrine to the brain. Postbiotics are especially helpful in people who are sensitive to probiotics, because they are less likely to cause gas and bloating. It also helps those whom are immune compromised as they pose no risk for infection.

As I mentioned before, postbiotics can include inactivated probiotics or cell wall fragments. This includes metabolites such as short chain fatty acids (SCFA), vitamins (folate, B12, Vitamin K), enzymes and bacterial lysates and more. The most common postbiotics from nonviable organisms come from lactobacillus species, Bifidobacterium species and Saccharomyces (yeast) and bacillus species. The SCFA’s, primarily sodium butyrate are fuel for the microbiota and help regulate GI function, blood pressure and act as intermediaries between the gut and the brain.

Postbiotics have many functions: they strengthen the tight junctions in the gut, improve leaky gut, help with immune modulation, protect from infection and mitigating allergies.

They also help support healthy metabolism by lowering the risk of insulin resistance and the regulation of hemoglobin A1c (blood sugar levels). More and more human studies are being conducted and have observed improvements in irritable bowel syndrome symptoms, immune support (reducing risk of upper respiratory infections and less allergic symptoms), and metabolic support by lowering systolic blood pressure and decreasing elevated liver enzymes as well as total cholesterol and LDL.

Postbiotics are an important addition to gut-brain therapeutics. More research is needed but the existing studies show that dosing varies according to the specific postbiotic and the conditions being used to treat. They are effective in supporting the gut and building foundational health from the gut up.

References: Fidler, M. “Postbiotics: The newest addition to gut-brain therapeutics”. Element by Emerson Ecologics. Issue #6 p. 30-33. 2022.

Lowry, C. “Understanding the Gut Brain: Stress, Appetite, Digestion and Mood”. Conference in Lafayette CO. 3/13/2023.

Golen, T. “What are Postbiotics?” Harvard Health Publishing: Harvard Medical School. Nov. 1 2021.

What You Need To Know About Hormone Replacement Therapy

February 12, 2023 By Deborah

More than 1 million women in the United States experience menopause each year. Yet we are still in the dark about what to do about the troublesome symptoms that embrace this phase of life. Those symptoms can vary for each woman but primarily consist of intrusive hot flushes and night sweats with many hours of lost sleep. Low energy and mood changes that can disrupt work and relationships. Brain fog and difficulty grasping words which cause anxiety around the question of whether you are entering the beginning stages of Alzheimer’s disease. Then there’s the weight gain (especially in the mid-section) along with hair loss, dry skin, dry nails and eyes. The worst part is the fact that these symptoms begin 6 months to 12 years leading up to a woman’s last period, known as peri-menopause. This starts when women reach their late 40’s due to hormonal spikes and dips of estrogen and progesterone as the last eggs of the ovaries start to plummet in number. Irregular menstrual bleeding can also accompany these other symptoms making this time in a women’s life unpredictable. This presents confusion about where to turn for answers and options to get their lives back. Here is what you need to know about hormone replacement therapy (HRT).

Hormone replacement therapy has been around for many years (since 1942) until it took a dramatic turn. The prescriptions for hormone therapy, which was once the most commonly prescribed treatment in the United States suddenly dropped due to a 2002 poorly designed study finding links between hormone therapy and elevated health risks for women of all ages. This single study did women a disservice in how it generalized the use of HRT as opposed to what the study really was about- the unsafe and one-size-fits-all synthetic oral hormone, Prempro. The reasonable thing to do for women who were taking Prempro was to contact their gynecologist and yes, stop that form of HRT but to then discuss other hormone options. But instead, women flushed their pills down the toilet and never looked back. The message was “Hormones are Dangerous”.

It has been a disgrace to see women not even offered the option of HRT when symptoms were quite significant and after they had suffered years of unnecessary discomfort.

Hormone therapy can carry risks as do many other medications that people take to relieve serious symptoms. But dozens of studies since 2002 have provided reassurance for healthy women under the age of 60 or within 10 years of the onset of menopause who are free of contraindications. And the message is that the use of hormone therapy is safe and appropriate. The treatment’s reputation, however has never fully recovered and the consequences have been wide-reaching. It has been a disgrace to see women not even offered the option of HRT when symptoms were quite significant and after they had suffered years of unnecessary discomfort. Instead women are offered a pill for their insomnia, a pill for their depression, a pill for their newly diagnosed osteoporosis, a pill or injection for their diabetes, a pill for their high blood pressure, a pill for achy joints, a pill for their high cholesterol and plaque (caused by endothelial damage). Is it possible that there is a treatment for all these symptoms but has been overlooked by doctors? Yup! And it’s hormone replacement therapy. I am not saying that women would be immune to these conditions if they were on HRT, but it would be significantly less, if at all. This is just another example that reflects the medical culture’s challenges in keeping up with science as well as a representation of a lost opportunity to improve women’s lives.

Rebecca Thurston, a professor of psychiatry at the University of Pittsburgh who studies menopause, believes menopausal women have been underserved- an oversight that she considers one of the great blind spots of medicine. She states “it suggests that we have a high cultural tolerance for women’s suffering. It’s not regarded as important”.

So what does this mean now? Guidelines on hormone therapy from The North American Menopause Society has recently updated their 2022 position statement from 2017. It states that treatment should be individualized using the best available evidence to maximize benefits and minimize risks. Timing is important and the type of hormones are important. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation and whether a progestogen is used. The benefit-risk ratio appears favorable in lowering the risk of coronary heart disease, stroke, venous thromboembolism osteoporosis, depression and dementia for those that initiate treatment younger than 60 years or who are within 10 years of menopause and have no contraindications. Most women start HRT due to bothersome vasomotor symptoms (hot flushes) and genitourinary symptoms. Longer durations of therapy beyond the age of 65 are for persistent symptoms and women should be a part of the decision-making as periodic evaluation continues.

I still have patients tell me that their doctors insist they go off their HRT because they have been “on it for too long”. Do we say the same thing about a man’s testosterone or Viagra prescriptions?! Both women and their providers became very fearful after the 2002 WHI study. It is time to clarify and reassure women that hormone therapy can be given safely and effectively to relieve women’s symptoms and improve their quality of life as long as they are being monitored and the benefits continue to outweigh the risks. We also know that these hormones can delay or prevent many long-term degenerative diseases that are caused by aging. If women are expected to live on average another 30 years after menopause, let’s at least offer them the best quality of life for the years ahead.

We have come a long way…but we’re still not there. Let’s open up the discussion and allow women to voice their concerns and complaints without shame or guilt on whether their discomforts are “significant” enough. They deserve to ask questions and get reliable answers based on current studies with sound guidelines that we currently have, and not a study that was over 20 years old! More research is always needed to help navigate this topic not only for menopausal women now but for our younger generation of women moving forward.

References: Faubion, S, et al. NAMS Position Statement: The 2022 hormone therapy position statement of The North American Menopause Society. Menopause: The Journal of the North American Menopause Society, Vol 29. N0. 7, pp 767-794.

Dominus, S. Women have been misled about menopause. The New York Times magazine. February 1 2023. pp 1-19.

Kaunitz, A. Guidelines on HT have been updated by The North American Menopause Society. OBG Management. June 2017, Vol. 29, N0. 6. pp 18-23.

https://www.nia.nih.gov. Research explores the impact of menopause on women’s health and aging. May 6, 2022.

COVID-19 Is Not Over Yet

July 10, 2022 By Deborah

What we know about SARS-CoV-2, the virus causing COVID, is that it is here to stay. Information is continuing to evolve and research is still on going as new discoveries are being made. What we DO know is that COVID-19 is not over yet. It is still prevalent in many cities, states and countries and the United States remains stuck at an uncomfortable high plateau of pandemic pain and misery while new variants are driving a case surge in Europe.

We used to think that once you were infected and recovered from the virus your odds of dying were very low and both prior infection and immunization showed an even more protective effect against severe disease in certain populations. Age, underlying comorbidities and gender were the main risk factors for illness severity and reinfection. That was based on surveillance information from January 2020 through May 2021. Things have clearly changed.

Last year we thought that reinfections were relatively rare. Now we are seeing people infected 2, 3 or even 4 times after being fully vaccinated and boosted! What gives???

We have to remember that the virus strain that’s circulating now is very different then earlier strains. If we have been infected with COVID-19 or vaccinated, our body creates an immune response and mounts antibodies against future infections. It recognizes the strain that our body was originally in contact with. But as the virus changes as it has with Omicron, it becomes a fuzzier picture for our immune system to recognize the virus and we get re-infected. Omicron by far has been the Hercules of all variants in that it continues to shape-shift into other versions of itself making it more difficult for our antibodies, B cells and T cells to recognize and shut down a growing infection before the next subvariant arrives. What this means is that Omicron infection may have boosted our immunity against earlier variants, but it is less effective against itself and its subvariants (B.1.1.529, BA.4, BA.5, BA.1, BA2, BA.3, BA.2.H78Y). This poor immunogenicity against itself explains the resurgence of reinfections.

The BA.5 and BA.4 subvariants of Omicron account for 70% of all infections in the U.S. “It is the worst version of the virus that we’ve seen” according to Eric Topol, professor of molecular medicine at Scripps Research. He states that it takes “immune escape” to the next level which enhances transmissibility beyond earlier versions of Omicron. Fortunately due to the immunity build up from the winter omicron wave, there has not been a significant increase in hospitalizations or deaths. The BA.5 is different in its biology in that it is able to evade the body’s immune system and go unrecognized by our T-cells.

According to a cohort study in Estonia this year, findings show that an increased risk of death from SARS-CoV-2 is not limited to the acute illness: SARS-CoV-2 infection carries a substantially increased mortality in the following 12 months. This occurs primarily in older people and is driven by a broad array of causes of death. The more times a person gets infected, the higher the risk of long term illnesses effecting the heart and lungs.

Every time our body’s defenses are engaged, it extracts a lot of energy and causes tissue damage. And if our immune system does not have time to heal and repair the damage, then it has less of a chance to help fight the next infection or any other stressor that comes along. Long-term consequences with repeat infections with the virus can lead to a higher likelihood of long-haul COVID than those who have had it just once.

In the meantime…lets continue the familiar mitigation measures: high quality N95 masks when going out in public, stay home and get tested if you feel ill, better air filtration and ventilation http://Air cleaners and COVID-19, avoid exposure in crowded indoor places. COVID-19 is not over yet.

Currently there is a bivalent or two-component vaccine, with old and new Omicron variants as the target. We hope next generation vaccines are more comprehensive in protection and more durable (longer lasting) that can dampen transmission.

The answers are more than alittle murky. Stay tuned…as we wait for more studies and more clear guidance.

References: http://Variants Dampen Immune Protection

http://SARS CoV-2 Reinfection

http://Long Term Mortality Following SARS CoV-2 Infection

The New Wave of Allergens

April 10, 2022 By Deborah

With more than 60 million Americans affected, allergens are an important health issue. We are seeing a new wave of allergens that are effecting more people. Compared to 1990, pollen season occurs 20 days earlier and stays around on average 8 days longer according to a 2021 study. Not only is the season longer, but the symptoms are more severe. Plants, grasses and trees are spraying 21% more pollen than they did 30 years ago. So what gives?

The cause is our ever changing climate. As temperatures go up and the CO2 in the environment increases, plants produce more pollen. The severity depends on where you live and the plant species that proliferate there according to William Anderegg, associate professor of biology at the University of Utah and the lead author of that 2021 study. His study found that Texas and the Midwest have taken the brunt of these increasing pollen hot spots. This new wave of allergens is nothing to sneeze about (sorry.. I had to say it!) Climate change is not in the future…but is here with every breath you take.

If the current trends continue, ragweed and grass pollen concentrations will significantly rise over the next 40 years, says research analyst Hannah Jaffee of the Asthma and Allergy Foundation of America (AAFA). One spokesperson from the AAFA, Neeta Ogden MD, states that allergy symptoms usually improve as we get older because our immune systems become less reactive with age. But climate change is robbing us of this natural protection. Unfortunately, some older adults are actually developing allergies for the first time in their lives. While others are suffering longer and more intense seasons. In many areas, high pollen counts can start in early March and go through late October (even through Halloween!). Microparticles of pollen can continue to linger into the winter season. Treating allergens can also keep you healthier when it comes to warding off viruses. That’s because if you have allergies, your airways are more reactive to viral illnesses. So suppressing flare-ups may improve your overall immunity keeping your defenses up to fight off colds and flu.

Here are some things you can do to help reduce your sneezing, coughing congested symptoms.

Start treatment early: It’s easier to prevent your immune system from getting overwhelmed and overly aroused than it is to calm it down. So for the fall ragweed season, start treatment in August. The dates differ depending on what part of the country you live in. Consider starting with a nasal steroid spray. Over-the-counter nasal sprays include fluticasone (Flonase), triamcinolone (Nasacort) or budesonide (Rhinocort). These nasal sprays reduce nasal swelling and mucous production but can take a week to work so start early. Which one to choose? Some people find Flonase irritating because it contains alcohol so you can start with Nasacort. Anti-histamine nasal sprays are also available that treat itchy, runny nose symptoms and sneezing. These include prescription azelastine (Astelin, Astepro) and olopatadine (Patanase).
Oral antihistamines are also effective. Most over-the-counter medications work well. They include loratadine (Claritin), fexofenadine (Allegra) which are both non-drowsy formulas. Cetirizine (Zyrtec) or levocetirizine (Xyzal) are sedating so they should be taken at night. Natural products that have antihistamine effects include Quercetin, Stinging Nettles and Vitamin C. Still suffering? Consider allergy shots or immunotherapy.
Mask up if you are outdoors on high allergen days. Check the pollen counts daily on apps such as pollen.com, weatherbug.com and weather.com. These resources show counts and ratings for the day. If high, then try to shift outdoor activities indoors. Or you can avoid outside activities when pollen release is at its peak especially on windy and warm days. Those are 5-10AM and after 4 PM to dusk.
Avoid indoor allergens too. The sheer load of allergens can make symptoms worse. Common indoor allergens include pollen, dust mites, dander and mold. Zip up box springs and mattresses with dust mite covers. Vacuum carpets frequently, and keep windows closed while setting up a HEPA air purifier if you are allergic to your pet. Make sure to get roof leaks fixed and keep the indoor humidity to 40% to reduce mold in your home.

Being aware of your allergens is the first step toward taking preventative measures. Speak to your practitioner or see an allergist for testing if you are unsure.

References: Migala, J. Allergies: The next wave. AARP Bulletin April 2022.

Extreme Allergies and Climate Change. Asthma and Allergy Foundation of America. aafa.org