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What Is Treatment-Resistant Depression?

In the past decade, the percentage of adults — particularly young adults — experiencing anxiety or depression has increased significantly. Recent analysis shows that in 2023, almost half of all adults ages 18-24 report having experienced symptoms of major depressive disorder. And, each year, over 30% of people with depression develop treatment resistance also known as treatment-resistant depression or TRD.

With so many young people struggling with depression, and with so many patients unable to find relief from depressive symptoms, the demand for effective alternative treatments had increased dramatically. Psychiatrists, researchers, pharmacologists, and other mental health professionals have made great strides in developing new antidepressant medications and alternatives to standard oral antidepressant medications to better treat those with treatment-resistant depression.

What is Treatment-Resistant Depression and How is it Different from Depression?

Treatment-resistant depression (TRD) is a term used to describe a form of major depressive disorder that does not respond adequately to standard treatments. Medication and talk therapy are typically used as first-line treatments for mood and anxiety disorders. Only approximately 50% of people, however, will achieve remission after two medication trials, with each subsequent trial having a higher risk of intolerable side effects and a lower likelihood of achieving remission.

However, in some cases, individuals with depression may not experience significant symptom relief despite these conventional treatments. When patients have tried one or more antidepressant medications or other evidence-based therapies, but their depression symptoms persist or return, they can be diagnosed with treatment-resistant depression.

To recap, treatment-resistant depression (TRD) is commonly defined as the failure to respond or achieve remission after two or more trials of antidepressant medication of adequate dose and duration.

Causes of TRD

There are several reasons why someone may have treatment-resistant depression.

Biological factors

Some individuals may have specific genetic or biological factors that make their depression more resistant to treatment. Research suggests that these risk factors may specifically include older age and fast or slow metabolization speed.

Severe depression

In some cases, when a patient has severe depression, standard treatments aren’t enough to relieve depressive symptoms. Increased severity of the depressive episode and extended duration of the depressive episode are specific risk factors. In these cases, inadequate treatment duration or dose won’t be enough to improve depression symptoms.

Underlying medical conditions

Certain medical conditions, such as thyroid disorders or chronic pain, can contribute to treatment resistance.

Co-occurring mental health disorders

If an individual has other mental health disorders alongside depression, such as anxiety, mood disorders, or substance abuse, it can complicate treatment and make it more challenging to achieve remission.

Incorrect or Inadequate Diagnosis

First, it’s important to confirm a correct diagnosis of depression. A failure to correctly and precisely identify the actual subtype of depression, such as atypical, psychotic, bipolar, or melancholic depression, can impact treatment outcomes. As mentioned above, misdiagnosis may also include failure to identify a comorbid medical condition, including hypothyroidism, anemia, substance abuse disorders, or eating disorders, which can worsen depression or maybe the underlying cause of the treatment-resistant depression.

Other times, a patient may not comply or adhere to their prescribed treatment. Not staying on prescribed antidepressants long enough, skipping doses, unpleasant antidepressant side effects, and drug interactions can all lead to a treatment-resistant depression diagnosis.

Signs and Symptoms

Major depression is a common debilitating disorder affecting 10%–15% of the population per year. Despite advances in the understanding and treatment of major depression and the introduction of several new classes of antidepressants, only 60%–70% of patients with depression respond to antidepressant therapy. Of those who do not respond, 10%–30% exhibit treatment-resistant symptoms which usually include:

  1. Symptoms of depression include tearfulness, loss of interest in normal activities, sleep disturbances, trouble concentrating, or unexplained weight loss/gain
  2. Lack of response to multiple medication trials or various prescribed medicines.
  3. Worsening symptoms of depression or side effects with each failed treatment attempt.

Which risk factors have been associated with treatment-resistant depression?

If you or a loved one suspect you may have TRD, it’s important to confirm a proper diagnosis. Some people with bipolar disorder, substance use disorder, or thyroid disease are misdiagnosed with TRD. A medical evaluation can also rule out important comorbidities including pancreatic cancer, hormonal etiologies like low testosterone and perimenopause or possible deficiencies in Vitamin B12, Folate and Vitamin D.

For those diagnosed with TRD, there is no single cause. However, TRD has been associated with several different risk factors. The following factors may increase a person’s risk of experiencing TRD:

  • Long depressive episode duration
  • Mild or very severe depressive episode
  • High number of stressful life events and traumas
  • Melancholic features including lack of reactivity to positive news and events, feelings of deep despair or worthlessness, weight loss and excess guilt
  • Advanced age
  • Genetic variants including those within the serotonin transporter-lower transporter transcription alleles (SLC6A4)

How Is Treatment-Resistant Depression Treated?

If antidepressants and talk therapy aren’t working for you, you’re not alone and it doesn’t mean you can’t feel better. But, it does mean you should try a different treatment.

Can precision prescribing help treatment-resistant depression?

There are a lot of different antidepressants and it can be difficult to predict how well a particular medication will help an individual. Often, doctors first suggest taking a medication that they consider to be effective and relatively well-tolerated. If it doesn’t help as much as expected, it’s possible to switch to a different medication and sometimes a number of different antidepressants have to be tried before you find one that works. Currently, this trial-and-error prescribing of antidepressants is a contributing factor in treatment failure.

Precision prescribing uses genetic information to help patients avoid the trial-and-error process. With precision prescribing, DNA samples are taken with cheek swabs and sent out to a laboratory. The results may help clinicians and patients rule out medications that, for genetic reasons, will be less effective or that may lead to more side effects.

Studies have shown that patients with treatment-resistant depression are 30% more likely to respond to treatment and 50% more likely to achieve remission when their medication selection is guided by a psychotropic genetic test.

Are there safe and effective treatment alternatives for treatment-resistant depression?

There are many safe and highly effective treatment alternatives for those with TRD. The goal of depression treatment is always to achieve full remission. Patients with TRD should not have to tolerate lingering symptoms or side effects. Treatment alternatives for depression include:

TMS (Transcranial Magnetic Stimulation)

Transcranial magnetic stimulation is a drug-free, FDA-cleared treatment that uses gentle magnetic pulses to treat mood at its source. Unlike medications which can take 6-8 weeks to exert their full effects, most patients experience improvement in 2 weeks with TMS therapy. TMS is not the same thing as electroconvulsive therapy; it’s much safer. TMS utilizes magnetic fields to stimulate nerve cells in specific regions of the brain associated with depression. This non-invasive and repetitive procedure is often recommended when treatment-resistant depression is diagnosed. By delivering focused magnetic pulses to targeted areas, TMS aims to modulate brain activity and alleviate depressive symptoms. When managing treatment-resistant depression, Transcranial Magnetic Stimulation (TMS) therapy emerges as one of the most effective alternative treatments.

MeRT (Magnetic e-Resonance Therapy)

Magnetic Resonance Therapy, MeRT, is a revolutionary technology that combines the latest therapies of TMS (an FDA-cleared therapy), EEG, and EKG to deliver treatments tailored to each individual’s unique brain pattern. By measuring and analyzing your brainwave activity, MeRT assesses the communication quality between the neurons in your brain and custom designs treatment protocols to optimize brain function. 

Spravato Therapy 

Spravato, or esketamine therapy, is a highly effective and rapid-acting treatment. Designated as a ‘breakthrough therapy’ by the FDA, Spravato and other forms of ketamine therapy can rapidly—often within an hour or two—lift the symptoms of treatment-resistant depression and other conditions including anxiety, PTSD, OCD, and chronic pain. After a short series of repeated doses, the antidepressant effect typically extends for weeks to months. Our thoughtfully designed treatment centers ensure a safe, comfortable, and private experience while our therapeutic processing and integration enhance Spravato’s direct effects on the brain and psyche resulting in profound emotional insights and deep inner healing.

Psychiatric Medication Management

Medication management plays a crucial role in the treatment of individuals with treatment-resistant depression. When a patient shows resistance to conventional antidepressant medications, psychiatrists and healthcare providers specializing in mental health can place a patient on a treatment-resistant depression program to closely monitor the patient’s response to different medications, explore various classes of antidepressants, and adjust dosages as needed. Additionally, healthcare professionals ensure that the patient adheres to the prescribed medication schedule, emphasizing the importance of consistency and reporting any side effects or changes in symptoms. Regular follow-up appointments are conducted to assess the effectiveness of the medication and make further adjustments based on the individual’s unique needs. At Neuro Wellness Spa, online and in-person psychiatrists can help with even the toughest cases of treatment-resistant depression.

Treatment-Resistant Depression Treatment in California

Don’t settle for a treatment that’s partially effective at relieving your depression or one that works but causes intolerable side effects. Neuro Wellness Spa can help you or a loved one who may be struggling with treatment-resistant depression. We are proud to offer a full range of mental health services, including psychiatry, talk therapy, and TMS therapy for treatment depression, available both in-person and online. Each of our treatments is designed to correct neurotransmitter deficiencies that cause depressive symptoms and teach you how to change negative thought patterns into healthier, more adaptable ones.

Our psychiatrists will assess your symptoms and determine if medication management and/or TMS therapy is a good fit for you. Individual talk therapy is also available as a supplement to medications and TMS. If you or a loved one is experiencing depression signs or symptoms, please contact us today to find out if any of our treatment-depression treatment options are right for you.

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