Monday, May 20, 2024

Newest Treatments For Drug Resistant Depression

Scientists Achieve A Remarkable Breakthrough For Treatment

New drug approved for patients with severe depression

Deep brain stimulation for depression has yielded mixed results. These researchers think they’ve fixed the problem.

Being diagnosed with treatment-resistant depression went like this: Somewhere on the internet, I read a story that explained treatment-resistant depression was a diagnosis for people who had routinely failed to respond to antidepressants.

At that time, I was on something like my fifth antidepressant. When I saw my doctor, I asked her if that meant I had treatment-resistant depression. She took a quick look at all the medications Iâd been on and said âyep.â

The initial article Iâd read let me know I wasnât alone, but I didnât yet know how common the condition is. About 30 percent of people with major depressive disorder donât respond to traditional antidepressants â thatâs over half a million people in the United States alone. When the outcomes for people with MDD can include death, the world is in desperate need of effective treatments for the condition.

A proof-of-concept study published Monday in Nature Medicine may indicate a significant breakthrough for researchers trying to find treatments for the stubborn condition.

The study focuses on a promising treatment held back by inconsistent outcomes: deep brain stimulation . In the case of a 36-year-old woman, DBS was administered in a new way â and achieved remarkable results.

How Does Tms Work Where Antidepressants Dont

TMS therapy works in an entirely different way than antidepressants. During a TMS therapy session, the patient is fully awake for the 37-minute session, relaxing in a comfortable chair. A coil is positioned over the scalp, through which magnetic pulses are delivered, targeting the mood center of the brain in the left prefrontal cortex.

As the repetitive pulses induce electrical responses in the brain tissue, the sluggish brain cells are stimulated, increasing their activity over time. As the treatment period of 4-6 weeks proceeds, the brain chemistry is reset and rebalanced, leading to improvements in the symptoms of depression.

TMS therapy is very well tolerated and there is no down time required. Patients are free to drive themselves back to their home or work and immediately resume normal daily activities.

Esketamine Helps The Brain Form New Connections

Research suggests that untreated depression causes long-term brain damage and is a risk factor for dementia. Studies show that people with depression have up to 20% shrinkage of the hippocampus, a region of the brain critical for memory and learning. But esketamine may counteract the harmful effects of depression.

Animal studies indicate that connections between brain cells diminish under chronic stress, but esketamine reverses these stress-related changes. Esketamine is different than any other antidepressant in that it not only prevents the neurotoxic effects of depression on the brain, but it also seems to have a growth-promoting effect, explains Kaplin.

Recommended Reading: Can I Overcome Depression Without Medication

Altering Brain Patterns With Tms

TMS is a noninvasive way of stimulating the brain at specific locations that can relieve the symptoms of depression, Dr. Montie said.

It focuses a magnetic field on the dorsolateral prefrontal cortex of the brain, an area that shows dysfunctional brain patterns on scans of people suffering from depression. The technique is intended to normalize brain function by stimulating that region.

During treatment, a magnetic coil is positioned on the scalp over the part of the brain being stimulated. Most patients report experiencing a tapping sensation in the area of treatment or their forehead.

It sounds a little unbelievable but when we explain and demonstrate it, most patients feel a lot more comfortable, Dr. Montie said. Key points are that it is safe with a very low rate of side effects, has no invasive components, needs no anesthesia and theres no impairment following treatment. Also, people can go back to work afterwards.

A typical course of treatment involves a 30-minute session, five times a week for six weeks. Patients are generally recommended to continue taking an antidepressant, as it increases the likelihood of success.

While its effect is dependent on a variety of factors, it can produce stability for months or years afterwards, Dr. Montie said.

How Do Antidepressants Work

Why the New Ketamine

Research into ketamine as an antidepressant began in the 1990s with Dr. Krystal and his colleagues Dennis Charney, MD, and Ronald Duman, PhD, at the Yale School of Medicine. At the time depression was considered a black box disease, meaning that little was known about its cause.

One popular theory was the serotonin hypothesis, which asserted that people with depression had low levels of a neurotransmitter called serotonin. This hypothesis came about by accidentcertain drugs given to treat other diseases like high blood pressure and tuberculosis seemed to drastically affect peoples moods. Those that lowered serotonin levels caused depression-like symptoms others that raised serotonin levels created euphoric-like feelings in depressed patients. This discovery ushered in a new class of drugs meant to treat depression, known as selective serotonin reuptake inhibitors . The first one developed for the mass market was Prozac.

But eventually it became clear that the serotonin hypothesis didnt fully explain depression. Not only were SSRIs of limited help to more than one-third of people given them for depression, but growing research showed that the neurotransmitters these drugs target account for less than 20 percent of the neurotransmitters in a persons brain. The other 80 percent are neurotransmitters called GABA and glutamate.

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Current Treatments For Treatment Resistant Depression:

  • Allowing more time for medications to become effective
  • Increasing medication dosage, if indicated
  • Switching antidepressants
  • Adding another type of antidepressant
  • Adding medication used for other conditions
  • Consider the cytochrome P450 genotyping test to check for specific genes that indicate how well the body can process a medication

What Is Drug Resistant Depression

When someone experiences the symptoms of depression consistently for more than two weeks he or she should be evaluated by a doctor. After a physical examination rules out any medical issue causing the symptoms, the doctor will prescribe antidepressants, or refer the patient to a psychiatrist for this purpose. The treatment for depression commonly includes both antidepressant therapy and psychotherapy.

When a patient is prescribed an antidepressant they must allow 4-6 weeks for the drug effects to be fully realized. After this trial period, the doctor will assess its effectiveness, and can tweak the dosage or change to an entirely different drug if this first option was ineffective. When this pattern of trialing and subsequent failure to achieve successful reduction in symptoms repeats a couple more times, the patient is then diagnosed as having drug-resistant depression. This might be the point at which the newest treatments for drug resistant depression are explored.

Also Check: Mixing Depressants With Alcohol Can Cause

Principles Of Clinical And Pharmacological Management

Indications for hospitalisation

Hospitalisation is systematically recommended in cases of:

  • High suicidal risk

  • Failure of three unsuccessful attempts of ADT

  • Need for electroconvulsive therapy

Hospitalisation can be considered in cases of:

  • Risk of poor adherence to treatment

  • Failure of two previous ADT

  • Comorbidity with a severe medical condition

  • Co-occurrence with other psychiatric disorders

  • Lack of adequate familial support

  • Intolerance to current medication

  • Need for benzodiazepines withdrawal

  • Need for monoamine oxidase inhibitors, transcranial magnetic stimulation or transcranial direct current stimulation

The need to introduce a tricyclic ADT, lithium, pramipexole or second-generation antipsychotic is not considered as an indication for hospitalisation.

Adjuvant treatments

For patients with anxious features, the adjunctive use of benzodiazepines or hydroxyzine is systematically recommended. The use of buspirone, pregabalin or an ADT belonging to a different pharmacological class is possible in this indication.

The use of an ADT from the same pharmacological class is not recommended.

For patients with sleep disorders, the adjunctive use of hypnotic is systematically recommended. The use of hydroxyzine, benzodiazepines or an ADT with a different pharmacological profile is possible as an alternative therapeutic option.

Treatments with an ADT action

The following classes or medications are recognised as having antidepressant properties:

Minimal duration of ADT

Can Depression Change Your Personality

Ketamine shows new promise for Idahoans suffering from drug-resistant depression

When you dont obtain enough sleep, your depression signs and symptoms will certainly be worse. Sleep deprivation intensifies irritability, grumpiness newest treatments for drug resistant depression, despair, and also fatigue. While some ladies do take antidepressants during their pregnancy, its not clear which ones are the most safe.

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How Do Ketamine And Esketamine Work

Both ketamine and esketamine reduce the symptoms of depression by stimulating different parts of the brain.

Ketamine doesnt stimulate the same area of the brain that SSRIs target. Instead,experts believe that ketamine encourages the regrowth of the connection between neurons. In this way, ketamine helps to rewire the brain.

Esketamine works to restoresynaptic connections in your brain cells. Other antidepressants dont work in this same manner. According tothis press release, Spravato can start to work in just a few hours.

The Barriers To Treating Depression

There are many reasons someone might not get help for depression, and each one could be as unique as every individual.

Researchers got curious and wanted to identify at least some of the potential barriers, so they took a sample of 20,785 adults who had been diagnosed with depression in the last 12 months.

Among those sampled, 30% acknowledged the need for treatment but didnt receive any help.

Those people were provided with a list of 15 potential reasons for not getting the mental health treatment or counseling they needed.

The majority of participants chose only one statement.

The most common justification related to the cost of treatment. About 22% of participants thought they could handle their depression on their own.

Fifteen percent were concerned they would be forced to take medication.

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What Happens In The Brain During Depression

Depression causes the hippocampus to raise its cortisol levels, impeding the development of neurons in your brain. The shrinkage of brain circuits is closely connected to the reduction of the affected parts function. While other cerebral areas shrink due to high levels of cortisol, the amygdala enlarges.

You can help in reducing your risk of cancer cells by making healthy options like consuming right, staying active as well as not smoking. Its also crucial to follow recommended testing guidelines, which can aid find certain cancers cells early. SeeHelping a Friendfor tips for speaking to a good friend regarding depression or various other worries. Light therapy has shown newest treatments for drug resistant depression reliable for Seasonal depression. Rest assists recovery from depression as well as may help stop reappearances. Sign up for our Health Tip of the Day newsletter, and receive day-to-day ideas that will help you live your healthiest life. St. Johns Wort has comparable chemical properties to some SSRIs and works by boosting levels of serotonin.

Recommendations For Clinical Dimensions Of Major Depressive Disorder


No clinical features support the use of different ADT in combination in first-line.

Table 3 Recommendations for clinical dimensions of major depressive disorder

Second-, third-, fourth-, fifth- and sixth-line strategies

In the second-line treatment, in cases of partial response or non-response to ADT treatment, optimising the dose of the initial ADT is systematically recommended with a high priority level.

  • If a patient has a partial response to the first-line ADT: association with an 2-antagonist is recommended irrespective of the class of the initial ADT

  • If a patient has non-response to the first-line ADT: switching strategies is recommended. Association of two ADT is not recommended in first intention.

Strategies recommended in the second-, third-, fourth-, fifth- and sixth-line treatments, which rely on the previous line of treatment, are summarised in Additional file : Figures S1 to S7).

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What Are The Signs And Symptoms Of Treatment

The number one sign of TRD is that youve tried multiple antidepressants as directed and still arent feeling better.

If you havent had an adequate response to antidepressant medication by about 10 weeks of treatment with the optimal dose, its probably worthwhile to request a change in your treatment plan, says John H. Krystal, MD, McNeil Professor and Chair of Psychiatry at Yale. This change might involve adding psychotherapy, an additional medication, switching antidepressants, or starting a neurostimulation treatment.

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Read Also: Medicine Used For Depression And Anxiety

With A Nudge From Ai Ketamine Emerges As A Potential Rare Disease Treatment

The stubbornly high, and steadily increasing, rate of suicides in the U.S. is one factor driving the shift. In April, the National Institute of Mental Health awarded eight grants to test new ways to reduce suicidal thoughts and behaviors in a fast-acting manner, including ketamine and using magnets to activate parts of the brain.

Overall, an unofficial estimate shows the agencys funding for research involving roughly doubled from $34.3 million in the 2007 fiscal year to $68.5 million in FY 2020, based on a search of the National Institutes of Health RePORTER database. A search for transcranial magnetic stimulation for depression reveals an estimated ninefold increase to $21.4 million over the same period.

Nolan Williams, a psychiatrist and neurologist at Stanford University, received one of the new grants as well as another from the NIMH to study magnetic stimulation in treatment-resistant depression. He said there is a push in the field to to think beyond the typical view of depression, and consider new treatments. Were enhancing view to have a multilevel understanding of the problem, he said. Its about incorporating it into a deeper, more dynamic understanding .

The entire thinking of the approach to treating depression is pretty much confined in that little box, said Lisa Harding, a psychiatrist at the Yale School of Medicine.

Strengthening A Weak Connection

Therapy for treatment-resistant depression

The researchers also conjectured that targeting the stimulation more precisely would improve the treatments effectiveness. In transcranial magnetic stimulation, the treatment is aimed at the location where most peoples dorsolateral prefrontal cortex lies. This region regulates executive functions, such as selecting appropriate memories and inhibiting inappropriate responses.

For SAINT, the researchers used magnetic-resonance imaging of brain activity to locate not only the dorsolateral prefrontal cortex, but a particular subregion within it. They pinpointed the subregion in each participant that has a relationship with the subgenual cingulate, a part of brain that is overactive in people experiencing depression.

In people who are depressed, the connection between the two regions is weak, and the subgenual cingulate becomes overactive, said Keith Sudheimer, PhD, clinical assistant professor of psychiatry and a senior author of the study. Stimulating the subregion of the dorsolateral prefrontal cortex reduces activity in the subgenual cingulate, he said.

To test safety, the researchers evaluated the participants cognitive function before and after treatment. They found no negative side effects in fact, they discovered that the participants ability to switch between mental tasks and to solve problems had improved a typical outcome for people who are no longer depressed.

Read Also: Where Can I Get Diagnosed With Depression

There Is Hope For Treatment

Therapy, lifestyle changes, and medication are three tried-and-true depression treatments. Many people find that a combination of these treatments is enough to ease their symptoms. However, for some people, thats not the case. As many as15% of people dont respond to antidepressants, and40% only receive partial relief.

If your depression isnt alleviated with medication, its called treatment-resistant depression. The good news is,Dr. Hadi Estakhri at Allied Psychiatry and Mental Health offers hope for those with this type of condition. Ketamine therapy and Spravato nasal spray are both available at our Newport Beach, California clinic.

In this article, well explore whatketamine treatment is and how it can help treat depression, even if medications arent working.

Ketamine As Well As Depression: Is It A Reason Or A Remedy

Light treatment uses an unique light box to help bring back chemicals in your body as well as reset your bodys biological rhythm, which can improve both your mood and your sleep. This light goes to the very least 10 times stronger than typical light bulbs, is extremely similar to natural daytime, as well as will not damage the eyes. You do not newest treatments for drug resistant depression need a prescription to purchase a light treatment box, however its finest to ask your medical professional if light therapy is a great option for you. This guideline likewise ended that there is insufficient evidence to make suggestions concerning the use of acupuncture, yoga exercise, tai chi, or qi gong for the treatment of depression.

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Building On Success: Whats Next In Ketamine Research

The job is not done for TRD. Ketamine and esketamine work, but both have significant drawbacks. Many patients experience uncomfortable dissociative symptoms, hypertension, or other side effects for a few hours after administration. Because of these symptoms, as well as the potential for abuse, both need to be administered in a doctors office. These arent medications you can pick up at the pharmacy and take on your own. Dr. Zarate and others are hard at work at finding safer alternatives to ketamine by examining the mechanisms by which it works. One such promising compound, a metabolic product of ketamine, was identified through a collaboration between Dr. Zarate and Todd Gould, Ph.D., of the University of Maryland School of Medicine. A cross-institute collaboration between NIMH, National Institute on Aging, and the National Center for Advancing Translational Science is developing this agent in order to test its efficacy in patients with TRD.

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