Treatment resistant depression (TRD) is a subcategory of Major Depressive Disorder. There are various definitions but, broadly, it is a type of depression that does not respond to traditional therapies. It is quite common; in fact, a 2022 study found that up to 60 percent of psychiatric patients experience treatment resistance. Despite this number, alternative therapies are only recently being explored. In this article, we will explore the criteria for treatment resistant depression and the role alternative therapies, such as ketamine, will have in successfully managing these cases. 

Symptoms of Treatment Resistant Depression

The symptoms of treatment-resistant depression are the same as those of Major Depressive Disorder (MDD), including:

• Enduring feelings of sadness or despair
• Loss of interest in activities previously enjoyed
• Insomnia 
• Excessive fatigue
• Changes in appetite (sometimes resulting in weight loss or weight gain)
• Feelings of worthlessness
• Decreased concentration

The difference between MDD and TRD is the failure to obtain relief of most of or any of these symptoms after traditional therapies have been attempted. 

How is Treatment Resistant Depression Diagnosed?

Again, there are a few different sets of criteria used in defining treatment resistant depression. However, most criteria include an established diagnosis of depression and failure to respond adequately to at least 2 types of antidepressants. 

The duration for each trial of antidepressant varies depending on the treatment model. Two of the most common of these treatment models are known as the American Psychiatric Association (APA) guidelines and the Maudsley guidelines. Both offer evidence-based recommendations for assessing and treating mental health disorders, but these recommendations can differ significantly. 

For example, both Maudsley and the APA recommend at least two attempts at traditional antidepressants before considering treatment-resistant depression as a diagnosis. However, the APA recommends eight weeks per drug, with a review at four weeks and dosage adjustment, if necessary. Maudsley, on the other hand, suggests an initial trial of 3 weeks per medication. 

As we can see, there is quite a discrepancy in the criteria for diagnosing treatment-resistant depression. This raises an important bioethical question: how long is too long for someone to continue to suffer with depressive symptoms when they are actively seeking treatment? 

Given the severely reduced quality of life and increased suicide risk among patients with Major Depressive Disorder, most providers would agree that symptom relief is on the urgent side. Even Maudsley’s 3 week model means, ultimately, six weeks of continued symptoms on the part of the patient. Patients who do not respond to antidepressant therapy have been shown to have higher rates of non-adherence, expressing understandable feelings of frustration, hopelessness, and even a lack of confidence in their healthcare provider. This suggests a dire need for better and faster options for treatment resistant individuals. 

Better Treatment for Resistant Depression

Patient frustration and the general lack of consensus regarding the diagnosis and treatment of TRD has led many providers to explore alternative therapies in order to more effectively help their patients. 

One exciting area of research involves the use of psychedelic and psychedelic-adjacent therapies. Psychedelics, such as LSD and psilocybin, primarily act on the brain’s serotonin receptors to cause feelings of intense well-being and a distorted sense of time and space. Psychedelics are also known as “hallucinogens,” since they can sometimes induce vivid hallucinations. 

Psychedelic-adjacent drugs, such as ketamine, do not usually act on serotonin receptors; rather, they act on different parts of the brain while exerting certain psychedelic properties. For example, ketamine is technically a “dissociative anesthetic” that acts, in part, via the glutamate pathways in the brain. Yet it still produces effects similar to psilocybin, such as feelings of euphoria and a dreamlike state. 

Both psychedelic and psychedelic adjacent drugs are being studied as potential therapies for a wide array of mental health disorders. For example, current studies support the use of low dose ketamine for rapid relief of treatment resistant depression. In fact, ketamine has proved so effective in the treatment of TRD that it is one of only two FDA-approved conditions for its use (along with acute suicidal ideation). 

Research is also underway to evaluate psilocybin as a potential alternative therapy in a wide array of mental health disorders, including TRD, PTSD, and anxiety. 

At the Crane Center, we believe in approaching mental health disorders holistically. We understand that one type of therapy does not work for every patient, which is why we offer a variety of both traditional and non-traditional therapies to help you get better faster. If you are suffering from a treatment resistant psychological disorder, including depression, anxiety, OCD, or PTSD, please contact our office to schedule an appointment.