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Treatment-Resistant Depression


Treatment-Resistant Depression

October 24, 2022

When treating depression, physicians often prescribe a first-line anti-depressant (e.g., Zoloft, Prozac, and Lexapro). While these treatments work for many, a significant portion find that their symptoms remain even after trying several antidepressants. Known as treatment-resistant depression (TRD), this condition affects around 30 percent of adults with major depressive disorder (MDD).

 

Despite its prevalence, many are unaware of treatment-resistant depression, how to determine if they might have it, or what to do about it. 

 

Explore answers to these questions and more below.

When is Depression Treatment Resistant?

Treatment-resistant depression is generally defined as a lack of response to a few adequate trials of antidepressants. However, this leaves several questions open, including:

 

  • What counts as a lack of response?
  • What is an adequate trial?
  • How many antidepressants must a patient have tried?

It’s important to note that there are no universal answers to these questions. Instead of settling them, try answering the following questions:

 

  • Have your treatments failed to make you feel good?
  • Do you still not feel like your old self?
  • Have the side effects been difficult to manage?

Answering yes to any of these questions means you’re not getting the help you need, and it’s time to talk to your physician, who can decide the next best course of action. 

Risk Factors for Treatment-Resistant Depression

Though researchers are still uncovering all traits that can increase the chances of having or developing TRD, we know several factors are associated with the condition. In particular, depression is more likely to be treatment-resistant:

 

  • If it began at an early age
  • The longer one has had depression
  • The more frequent or longer lasting one’s depressive episodes are
  • When there are ongoing stressors
  • If one has other physical or mental health conditions

What to Do About Treatment-Resistant Depression

Treatment-resistant depression is treatable. Below are steps you and your physician can take to alleviate your depressive symptoms that haven’t responded to the first few treatments.

 

  • Confirm your diagnosis: Depression that co-occurs with or is caused by other mental health conditions may require a different treatment protocol. As a result, your physician should confirm your diagnosis if your depression isn’t improving in response to treatment.

 

  • Add on talk therapy: Medications often work best when combined with some form of talk therapy. If you find your depression hasn’t responded adequately to your antidepressants, adding on therapy can give them a boost and help alleviate symptoms.  

 

  • Change your medications: Just because a few medicines haven’t worked doesn’t mean none will. Newer anti-depressants (e.g., Spravato and Auvelity) that act on different neurotransmitters than first-line treatments can provide relief even when the standard solutions haven’t worked.

 

  • Try a non-medication-based intervention: While oral antidepressants are the most common medical treatment for depression, other options exist. For example, transcranial magnetic stimulation (TMS) is a non-invasive procedure where magnetic pulses are used to modulate activity in parts of the brain associated with mood regulation and is FDA approved for treatment-resistant depression.

How We Treat TRD at Heading Health

At Heading, we offer a comprehensive set of solutions to tackle TRD from every angle and provide rapid and sustained relief. We work hard to ensure that cost is not a barrier to accessing the interventions you need. We work with most insurance plans, from United Healthcare to Medicare to Blue Cross Blue Shield, and can provide coverage for all of our services, including ketamine, Spravato, and TMS, for most patients with TRD. Click here for a complete list of participating providers and to schedule a consultation to see whether our solutions are right for you. 

 

 

 

If you need to see a mental health professional or could use help deciding which service is right for you, please call us at 805-204-2502 or fill out an appointment request here. We have a wide variety of providers, including therapists, psychiatrists, nurse practitioners, and nutritional therapists, who can see you in as little as one day via teletherapy.  

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Is Ketamine a Psychedelic? Does it Matter?


Is Ketamine a Psychedelic? Does it Matter?

October 21, 2022

Over the past few years, psychedelics such as LSD and psilocybin mushrooms have garnered much attention as researchers explore their potential use in treating mental health conditions.   

 

Ketamine and its close cousin Spravato (esketamine) are often included in this motley crew of psychedelics due in part to their “mind-altering” effects.  

 

Though many are eager to label ketamine a psychedelic, others are less certain, feeling it would be most appropriate to avoid associating ketamine with psychedelics.  Let’s explore these different viewpoints to get a clearer sense of whether ketamine is genuinely a psychedelic and why the label matters, if it does at all.  

What is a Psychedelic? 

One obvious way of determining whether ketamine is a psychedelic is by comparing its features to those listed in its definition. Unfortunately, there are no agreed-upon criteria for what makes something a psychedelic drug. Experts waver on the importance of three conditions.

#1: Psychedelics Cause Altered States of Consciousness

Though there is much disagreement about what counts as a psychedelic, it’s generally accepted that they must induce specific mind-altering effects. Some argue this is all that is required. In other words, they claim that as long as the substance causes a “psychedelic experience,” then it’s a psychedelic.  

 

But what are psychedelic experiences? While the list is potentially endless, psychedelic experiences are generally thought to impact one’s perception of themselves and the world around them, alter the way they think and reason, and provide insights into how their mind works and the nature of reality. They include experiences like the sense of being at one with the world, distortions of space and time, profound inner peace, ego dissolution, and many more.  

#2: Their Conscious Effects Must Have Therapeutic Benefits

While many agree that psychedelics must cause certain altered states of consciousness, some argue that this isn’t enough. They claim that these changes in thought and perception must have a therapeutic effect on the mind or promote psychological growth. As Dr. Yehuda, director of the Center for Psychedelic Psychotherapy and Trauma Research at Mount Sinai Hospital in New York, notes when discussing ketamine’s status as a psychedelic:

 

The unanswered question in all of this is whether the transpersonal state is what heals you or whether it’s something about the molecule. […] The dissociation or psychoactive effects of ketamine might be incidental. They occur. But that’s not necessarily why the healing is happening.

 

For these experts, if ketamine’s mind-altering effects have nothing to do with its mental health benefits, then it’s not a psychedelic. 

#3: Psychedelics Must Act on Specific Areas in the Brain

In the world of psychedelics, some have been around for longer than others and are more well-studied. For example, mescaline and psilocybin mushrooms have been used since ancient times and were researched heavily in the 1950s and ‘60s. These compounds all appear to affect serotonin (a chemical messenger in the brain) at the “2A” receptor. 

 

Some researchers feel these “classical psychedelics” are the only true ones, and that what really matters when deciding whether to categorize a new agent as a psychedelic is how it works in the brain. As Dr. Yehuda notes:

 

When we talk about chemistry and drug development, we should mostly be defining a psychedelic drug on the basis of the chemistry of the molecule, its pharmacokinetics, and its mechanism of action. 

Does Ketamine Meet These Conditions?

How does ketamine stack up against these criteria? As far as its effects on the brain go, ketamine does not act as the classical psychedelics do. It works on N-methyl-D-aspartate (NMDA) receptors, causing an increase of glutamate and brain-derived neurotrophic factor (BDNF) instead of serotonin.  Under this condition, then, ketamine is not a psychedelic. 

Credit: Yang H. Ku/C&EN

 

However, acting on a specific set of serotonin receptors is not the only way to produce psychedelic experiences. As Dr. Steve Levine, co-founder of Heading Health states:

 

It does appear that subjective psychedelic effects may be induced by a number of stimuli or conditions that also include sensory deprivation, virtual reality, meditation, and suggestibility, among others, and not necessarily mediated through a particular brain receptor.

 

Importantly, many of these psychedelic experiences can be produced by ketamine. It is most commonly associated with dissociative experiences (i.e., the sense that one is separate from their thoughts and body). It can also cause distortions in one’s perception of space and time. Patients have also reported gaining new perspectives and an enhanced ability to make sense of their thoughts. Rarely, ketamine can cause delusions and delirium, otherwise known as psychotomimetic effects. In many ways, then, ketamine seems to have the right sorts of effects on the mind to be considered a psychedelic. 

 

However, it’s worth highlighting that the experiences won’t be identical to “classical psychedelics.” For example, psilocybin appears more likely to cause what’s known as ego dissolution, where one loses their subjective sense of self. Classical psychedelics may also have a greater tendency to induce visual distortions. In general, because they have different effects on the brain, their conscious effects will differ. As Dr. Arif Noorbaksh, Psychiatrist at Heading, states:

 

Ketamine is distinct because it works on a completely different neurotransmitter system (glutamate), exerts an effect in different areas of the brain, and as a result, the perceived effects are different.  They both result in non-ordinary states of consciousness, but the experience a particular person has when exposed to conventional psychedelics versus ketamine will be different.

 

When it comes to the therapeutic effects of the altered states of mind that ketamine puts subjects in, the evidence is mixed. A 2020 review concluded that overall, the evidence does not suggest that ketamine’s dissociative effects are responsible for its antidepressant properties. Others argue that ketamine’s ability to cause a shift in perspective and increase cognitive flexibility and open-mindedness are directly responsible for its therapeutic effects. For example, Celia Morgan, professor of psychopharmacology at the University of Exeter, found in a recent experiment that individuals who underwent ketamine and talk therapy experienced longer-lasting antidepressant effects. Professor Morgan notes that talk therapy “requires that individuals think differently about things and learn new ways of thinking about old problems.” As a result, ketamine’s ability to induce shifts in perspective and open-mindedness may explain why it appears to enhance the effects of therapy alone. 


Where does this leave us? According to some criteria, ketamine seems to be a psychedelic, while on others, it does not. The answer as to whether ketamine is a psychedelic, then, depends on who you ask and which criteria they feel are most essential.

Does it Matter What We Call It?

Some might think this is all just semantics and that there’s no real principle we can use to determine what to call ketamine. 

 

While the dispute may be verbal, how we talk about ketamine matters. As Dr. Noorbaksh notes:

 

I think it matters insofar as the term “psychedelic” comes with preconceived notions for many people, and it also places the emphasis on the acute effects of the agent rather than the potentially longer-term effects these agents can have on neuroplasticity, relation to self and others, and other important contributors to mental health.

 

As a result, it’s important to be mindful of the language we use to describe and categorize ketamine and to avoid clinging to one label or another without regard for how this impacts patients. As Dr. Levine suggests:

 

Ultimately, whether a molecule is “truly” a psychedelic is likely beside the point. […] Let’s not let feeling precious about terminology distract from the real goal, which is improving well-being in a safe and responsible way.  

 

 

 

Talk with your doctor to determine whether this treatment is right for you, or you can schedule an appointment with someone from our team of psychiatrists or therapists to advise you on this or any other potential treatments for depression, including ketamine, Spravato, and TMS. Call us at 805-204-2502 or request an appointment here.

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Ketamine Vs. Esketamine (Spravato) – What’s the Difference?


Ketamine Vs. Esketamine (Spravato) - What’s the Difference?

October 18, 2022
Source: NeuroMend

In 2019, 19 years after researchers first demonstrated ketamine’s therapeutic effects on depression, the Food and Drug Administration (FDA) approved Janssen Pharmaceuticals’ esketamine nasal spray (Spravato) for treatment-resistant depression. In 2020, it was also approved by the FDA for major depressive disorder (MDD) with co-occurring suicidal ideation. With similar names, ingredients, and research-backed mental health benefits, many are likely to wonder whether there are any important differences between the two and if there are any reasons for preferring one over the other. 

 

Let’s explore how they compare. 

What are They Made Of? 

Ketamine, or more specifically racemic ketamine, is made up of two enantiomers (i.e. pairs of molecules that are mirror images of each other), known as r- and s- ketamine (arketamine and esketamine). Esketamine contains only the S enantiomer.

How Do They Work?

Both ketamine and esketamine are thought to work by blocking N-methyl-D-aspartate (NMDA) receptors, which causes a release of glutamate (a chemical messenger in the brain) and, ultimately, brain-derived neurotrophic factor (BDNF), which helps neurons regrow and form new connections. 

 

Though they share this mechanism of action, esketamine has a four-fold higher affinity for the NMDA receptor, which means it is more potent. 

Which is More Effective?

For some drugs, one enantiomer is more “effective” than the other, which raises the question, are ketamine and esketamine equally beneficial?

In the past few years, several randomized controlled trials have directly compared the antidepressant effects of ketamine and esketamine. However, synthesizing their findings can be difficult as the studies utilize different methods of administration, treatment durations, depression-related outcomes, and more. 

 

Despite these obstacles, a team of researchers set out to comb through the data. They analyzed 36 randomized controlled trials comparing the efficacy of ketamine and esketamine on depression in a 2022 meta-analysis. They found that while the racemic mixture was more effective overall, the evidence suggests this is not the case when the same method of administration is used alongside doses that account for differences in potency. For example, one study found that when administered intravenously and in equally potent doses, both formulations had similar remission rates after 24 hours. 

Do They Feel the Same?

Both ketamine and esketamine are psychoactive substances, meaning they can alter one’s normal state of consciousness, affecting one’s thoughts, feelings, and perceptions. For example, ketamine is known for causing feelings of relaxation, dissociation, alterations in the perception of space and time, and more. A natural question, then, is whether the esketamine experience differs from the ketamine one. 

 

Answering this question exhaustively and definitively is challenging for several reasons. To start, ketamine and esketamine can cause a wide range of experiences, so much research needs to be done to demonstrate how likely each drug is to produce each one. Second, because esketamine is more potent, it’s not always clear that researchers have used equivalent doses. 

 

By and large, the experiences appear to be pretty similar. With that said, a few interesting preliminary findings reveal how they might differ. For example, some studies have found that ketamine is more likely to cause feelings of dissociation (i.e, a feeling of being disconnected or separate from one’s thoughts and body). 

 

Another important result has to do with how pleasurable the experiences are. Some studies indicate that the combination of ar- and esketamine is less likely to produce unpleasant reactions like stress and anxiety. For example, one researcher found that:

 

The (R)-enantiomer was able to balance the (S)-enantiomer’s adverse parts of the altered state of consciousness and promote positive psychedelic experiences so that a more coherent state of consciousness is experienced. 

 

It’s important to note that much future research will need to confirm these results and compare the drugs across all their potential subjective effects. It’s also worth pointing out that the therapeutic significance of ketamine and esketamine’s psychoactive effects is currently unclear, so any differences in how they feel may not impact how well they work.

What is the Treatment Like?

Treatments differ by how the drug is administered, the number of sessions needed, and appointment length. 

Esketamine is only available as a nasal spray called Spravato. For this treatment, patients visit their physician’s office twice a week for the first four weeks, once a week for the next four weeks, and then bi-weekly if needed for maintenance. Each appointment lasts two and a half hours.

 

Ketamine is available in several different forms, each with a slightly different protocol. At Heading, we offer intramuscular ketamine. This treatment takes place over three weeks, with three sessions in the first week, two in the second, and one in the third. Patients may continue to receive additional treatments for maintenance if needed. Each appointment lasts around an hour and a half. 

Does Insurance Cover Them?

Several insurance companies cover Spravato for treatment-resistant depression and MDD with suicidal ideation. While ketamine can be more difficult to find coverage for, our team has worked closely with insurance companies to ensure we can secure coverage for most patients.  Click here for a complete list of participating providers.

 

Talk with your doctor to determine whether one of these treatments is right for you, or you can schedule an appointment with one of our team of psychiatrists or therapists to advise you on potential treatments for depression, including ketamine, Spravato, and TMS. Call us at 805-204-2502 or request an appointment here.

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The Surprising Connections Between Caffeine and Mental Health


The Surprising Connections Between Caffeine and Mental Health

October 13, 2022

Between coffee, tea, soft drinks, and energy drinks, caffeine is one of the most commonly consumed psychoactive drugs. According to the Centers for Disease Control and Prevention (CDC), around 80 percent of U.S. adults consume caffeine daily. 

 

Despite its widespread popularity or perhaps because of it, caffeine often goes under the radar as something with no significant effects other than a short boost in attention and alertness. However, caffeine can have important effects on one’s mood and overall mental health that are worth considering when deciding whether to include it in your diet.



Depression

It’s well known that caffeine can provide a short-term elevation in one’s mood. However, it may also have a beneficial effect on depression. A recent meta-analysis of seven studies found that the risk of depression decreased by eight percent per cup of coffee when consumed in moderate amounts.

 

The data only shows that caffeine use is correlated with lower rates of depression, not that it causes it. However, we know that caffeine promotes the release of dopamine and that dopamine deficiencies may contribute to depression. This is why some antidepressants, such as bupropion and phenelzine, modulate dopamine signaling. Additionally, when consumed from natural sources like coffee, caffeine also comes with other ingredients which can reduce inflammation and oxidative stress in the brain (more on this below).

 

Anxiety

Caffeine stimulates the release of cortisol, epinephrine, and norepinephrine, which are associated with feelings of stress and anxiety. This is likely why some feel anxious and jittery after a cup of coffee. Some individuals may even experience anxiety that is severe enough to warrant the diagnosis of a caffeine-induced anxiety disorder, according to the current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V).

 

Several factors may explain why some are more prone to experience anxiety from caffeine. One obvious factor is how anxious they are in general. Studies have found that patients with panic disorder, generalized anxiety disorder, and social anxiety disorder tend to experience stronger anxiety-promoting effects from caffeine. 

 

The source of one’s anxious tendencies may play an important role in determining whether coffee makes them feel more or less nervous. For example, individuals with attention deficit hyperactivity disorder (ADHD) sometimes experience anxiety that stems from difficulties in concentration and executive control. Because caffeine can enhance attention and concentration, it can alleviate stress in individuals with ADHD. 

 

Aside from baseline anxiety symptoms, there may also be a genetic component that explains why some individuals are more likely to experience anxiety from caffeine. Studies have found that specific gene variants for the receptor that caffeine binds to can make one more susceptible to its anxiety-inducing effects. 



Interactions With Antidepressants

Caffeine can alter how our bodies process and respond to certain drugs, including some antidepressants. One way it can do this is by slowing down or speeding up the rate at which our livers break down antidepressants, impacting how much of the drugs build up in our systems. 

 

Some antidepressants can have an activating or energizing effect. When combined with caffeine, some patients might find that the compounds work together to produce feelings of tension and anxiety. Patients should be mindful of how their body reacts to caffeine while on antidepressants and discuss any adverse reactions with their physician. 



Sleep

Caffeine looks similar to a neurotransmitter called adenosine, which is partially responsible for regulating our sleep-wake cycles. When adenosine binds to its receptor, it tells the brain it’s time to sleep. Because of its resemblance to adenosine, caffeine can bind to the same receptor and block adenosine in the process. This prevents adenosine from triggering sleepiness. 

 

Caffeine can interfere with sleep for much longer than one might initially think. This is because several of caffeine’s metabolites (i.e., the chemicals produced as the body breaks down caffeine) can also cause wakefulness. While individual factors affect how long this process takes, caffeine and its metabolites can negatively impact sleep for up to 12 hours.  

 

A poor night’s sleep can lower one’s mood and exacerbate a range of symptoms associated with mental health conditions, so it’s important to be mindful of how caffeine affects your ability to sleep and to avoid consuming it within 12 hours of your bedtime. 



Naturally Occurring Sources of Caffeine Are Better

It’s best to get caffeine from natural sources like coffee and tea instead of synthetic sources like caffeine pills or energy drinks. The reason is that natural sources of caffeine come with other healthy ingredients. For example, tea contains antioxidants that can decrease oxidative stress in the brain, a change associated with improvements in depression. Similarly, caffeine contains chlorogenic acid, an antioxidant and anti-inflammatory. Naturally occurring sources of caffeine may also include a class of compounds known as phenols, which studies have found can work synergistically with caffeine to heal our bodies and minds. 





If you feel you need to see a mental health professional or could use help deciding which service is right for you, please give us a call at 805-204-2502 or fill out an appointment request here. We have a wide variety of providers, including therapists, psychiatrists, nurse practitioners, and nutritional therapists, who can see you in as little as one day via teletherapy. 

 

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TMS for OCD


TMS for OCD

October 11, 2022

Obsessive-compulsive disorder (OCD) is a condition characterized by recurrent, unpleasant intrusive thoughts and repetitive behaviors aimed at reducing anxiety or preventing some undesirable event. It currently afflicts between two to three million U.S. adults.

 

The condition is typically treated with some combination of cognitive-behavioral therapy (CBT) and a type of oral antidepressant called selective serotonin reuptake inhibitors. However, studies indicate that around half of OCD patients fail to respond adequately to the standard treatments. Moreover, many that respond to SSRIs discontinue due to undesirable side effects (e.g., weight gain, sexual dysfunction, emotional numbness, etc.). 

 

Because of this, researchers began to search for novel treatments. Many focused on finding new applications for a non-invasive procedure called transcranial magnetic stimulation (TMS), initially approved by the FDA for treatment-resistant depression in 2008. In 2018, TMS became FDA-approved for OCD. 

 

Here are answers to common questions about this new intervention.  

What is TMS?

TMS is a drug-free and noninvasive procedure used to treat various brain disorders, including several mental health conditions. It uses magnetic coils placed just above the scalp to send magnetic pulses into specific regions of the brain associated with symptoms of the conditions it is being used to treat. For example, in the case of treatment-resistant depression, the pulses are sent toward regions of the brain associated with mood regulation.

By sending repeated pulses to these specific areas of the brain, TMS “trains” neurons in those areas to fire differently and create new, healthier connections.

How Does TMS for OCD Work?

TMS for OCD works in much the same way as TMS for treat-resistant depression, except for two key differences. First, the magnetic pulses are directed at deeper structures in the brain, which are more closely associated with OCD. For example, one of the primary targets is the right orbitofrontal cortex, which studies have found is hyperactive in adults with OCD. It is also thought to be partially responsible for the unending urge to repeat compulsive behaviors that individuals with OCD experience. Other targeted areas include the supplementary motor cortex, medial prefrontal cortex, and anterior cingulate cortex.

 

Unlike treatment-resistant depression, which is associated with underactive neurons in parts of the brain related to mood regulation, OCD is connected with brain regions firing too much. As a result, in addition to targeting different areas of the brain, technicians utilize another type of stimulation called low wave stimulation, which inhibits, rather than activates, regional brain activity.  

 

What are the Advantages of TMS for OCD

TMS has several advantages compared to the first-line oral medications used to treat OCD. 

 

One of the problems with oral medications is that they are often imprecise, spreading throughout the brain and targeting many more areas than are directly implicated in the conditions they are meant to treat. This causes many unwanted side effects, such as weight gain, sexual dysfunction, emotional numbing, and more. TMS can deliver incredibly localized treatments, targeting the very source of the symptoms and avoiding unwanted side effects. 

 

Aside from lacking precision, first-line oral medications often must be taken continuously to cause and maintain their therapeutic effects. After a round of TMS treatments, the benefits can last for a substantial period of time. On average, results last between four to fourteen weeks and can easily be sustained with quick maintenance sessions.  

How Heading Does TMS for OCD Differently

In many cases, TMS is offered as a standalone treatment. While it can be very effective on its own, studies have found its effects can be amplified when combined with other interventions. For example, one experiment found that patients who underwent TMS and CBT experienced nearly a 60 percent drop in their OCD symptoms and that for 80 percent of the subjects, their symptoms decreased by at least 40 percent. 

 

At Heading, patients have access to our integrated team of mental health specialists with wide-ranging expertise to complement their TMS and enhance its therapeutic effects. By combing TMS with other therapies, our patients benefit from the synergistic effects of a holistic approach to mental health.

 

Talk with your doctor to determine whether this treatment is right for you or schedule an appointment with one of our psychiatrists or therapists to advise you on this or any other potential treatments, including ketamine, Spravato, and TMS. Call us at 805-204-2502 or request an appointment here

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