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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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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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Want to find out if Heading is right for you? 

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