Living with a mental health condition like major depressive disorder (or depression) is difficult in itself. But the symptoms persisting despite adhering to regular treatment can make it even more tiresome and frustrating. Depression continues to be one of the most common mental disorders across the world. According to the National Mental Health Survey of India, about 5.25% of the Indian population struggles with lifetime prevalence of depression. However, this does not imply that there is no way out. In fact, owing to its most common occurrence, it is also one of the most researched mental health conditions across the globe. If you have been diagnosed with this condition and it does not seem to improve, then knowing more about treatment-resistant depression might help.
What is treatment-resistant depression?
Treatment-resistant depression (TRD) occurs when major depressive disorder (MDD) does not respond to 2 trials of traditional and first-line treatment of pharmacotherapy. This means that if the depressive symptoms persist in intensity even after administering adequate doses of first-line medication (which are often selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors due to their fewer side effects) for the recommended appropriate duration across 2 different trials, then it can be termed as TRD.
Common symptoms of TRD are the same as those of depression, except they are more severe. Some of these are:
- Persistent low or depressive mood throughout the day
- Eating more or less than usual.
- Sleeping more or less than usual.
- Low energy
- Loss of interest or pleasure in activities.
- Low engagement in sexual activities.
- Social withdrawal
- Suicidal ideations
What Could be the Possible Reasons for TRD?
You could be taking treatment for depression for a while without it improving your symptoms. There is no one reason why that could be, but there are several contributing factors that are essential to look into.
1. Genetics or Brain Chemistry
Genetics and brain chemistry can play a major role in determining the success of pharmacotherapy. Every individual’s internal chemistry is different, which is highly influenced by genetics. A family history of mood disorders or other psychiatric conditions can be a contributing factor to resistance to treatment.
2. Misdiagnosis or Comorbid Conditions
Mental health conditions have overlapping symptoms that can be easily misdiagnosed based on the level of information available for diagnosis. Moreover, two or more conditions can coexist in an individual, and this is termed as comorbidities. Depression is known to co-occur most commonly with anxiety disorders, post-traumatic stress disorder, substance-related disorders, obsessive-compulsive disorders, eating disorders and some personality disorders. A misdiagnosis or ignorance of comorbid conditions can lead to improper prescription of medication which may be ineffective and can present as TRD.
3. Absence of Psychotherapy
Psychotherapy is an essential part of treating any mental health condition. While pharmacotherapy takes care of the biochemical imbalance in the body, psychotherapy works on the behavioural and cognitive parts of depression which cause it to persist. Both therapy and medication go hand-in-hand to address all factors and none is better than the other. Absence of psychotherapy can lead to relapse, or resistance to the treatment of depression.
4. Non-Adherence to Medication
Discontinuing medication or therapy by yourself can do more harm than good. While it is understandable that medications may have adverse side effects that feel uncomfortable, not adhering to the prescribed dosage or duration or self-medicating without a proper formal diagnosis can aggravate the symptoms.
5. Other Health Conditions
Often other physical health conditions can contribute resistance to treatment too. Several chronic conditions may have treatments that can cause depressive symptoms as a side effect. Hormonal imbalances and vitamin deficiencies can also contribute just as well to the fluctuations of mood, making depressive symptoms resistant to treatment.
6. Use of Substances or Alcohol
It is a well-known fact that alcohol is a depressant and so it goes without saying that it adds to the severity of depressive symptoms. Substances and alcohol can counter the effects of medication as they alter the biochemistry of the brain. This can aggravate the symptoms, causing resistance to any changes medications bring about.
7. Other Psychosocial Factors
Depression is not a result of just biochemical imbalances, rather several factors interplay to cause the symptoms. Socioeconomic background, stress and its management, living conditions, lifestyle, diet, physical activities, social and familial factors, and the history of an individual, all determine the severity of depressive symptoms. These cannot be addressed with medication alone and so often go unnoticed and therefore, unchanged, causing TRD.
What Can be Done?
In case you notice that your symptoms of depression have not improved or the severity has increased, it is highly recommended that you inform your doctor about this. Here are some of the changes that your doctor may make in your treatment plan.
1. Continue current medication for a little longer
While it ideally takes about 6-8 weeks for medication to show effect, your doctor may recommend continuing your current medication for longer than that to see if it brings about a change. It is not uncommon for biological changes to occur at varied durations across different individuals. The purpose of this can be to observe if the change is only taking a little longer than expected.
2. Increase dosage
If after persisting with the current dosage the symptoms show no effect, then the dosage of these medications may be increased. As mentioned earlier, individual differences lie in the way our bodies respond to simuli and tolerance levels of everyone can vary.
3. Change or add other medication
When it comes to humans, there is no fit-for-all treatment plan. One medication may work on someone but not on someone else. This is why it is common for doctors to change your medication to a different variation of the same class or to a whole other class of medicines. Another approach that helps is adding a medication generally used for treating other conditions such as second-generation antipsychotics, which have been proven to improve TRD.
4. Test for comorbid conditions or get a second opinion
It helps to look at a diagnosis from a different perspective and testing for any other comorbidities that could have been overlooked due to a dominance of depressive symptoms. These conditions may often be underlying, making them easy to miss.
It also helps to get a second opinion on your symptoms as bringing in a fresh perspective may help identify these underlying symptoms that may have been overlooked by your primary doctor.
5. Other medical conditions
Your doctor may look into other acute or chronic medical conditions and treatments that could be hampering or resisting the effects of pharmacotherapy for depression. Further, keeping factors such as vitamins and other essentials under check helps give a comprehensive report of your condition and possible reasons for resistance.
Alternative Treatment Procedures
There are some other procedures except medication that have been supported by research to help improve TRD.
1. Repetitive transcranial magnetic stimulation (rTMS)
This is a non-invasive procedure that involves “waking up” parts of your brain that may have been inactive causing the depressive symptoms. This is done by placing an electromagnetic coil against your scalp and sending tiny electrical pulses in rapid bursts to activate neurons in certain parts of the brain. This procedure takes approximately 30-40 minutes.
2. Electroconvulsive therapy (ECT)
ECT involves controlled electrical current being passed through the brain to briefly trigger a seizure while the patient is under anesthesia. This procedure has been found to effectively treat severe depression and TRD. It helps the brain reset and improve mood. However, there have known to be some side effects such as temporary confusion or memory loss.
3. Vagus nerve stimulation (VNS)
The vagus nerve is the longest cranial nerve that runs the length of the spine. VNS aims to send electrical impulses to the brain via the vagus nerve. In this procedure, a small device is surgically implanted in the chest with a wire connected to the vagus nerve. This device sends out gentle electrical impulses that help regulate the brain’s activity via the vagus nerve.
What Can You Do?
It can be disheartening to reach out for help and barely see any change in your symptoms. The great news is that you are not helpless as there are ways in which you can take matters in your own hands. While the medications do their work internally, here are some of the ways that have proven to be effective in treating depressive symptoms.
1. Be honest with your doctors
Your disclosure of your medical and psychiatric history, the side effects of current medication, the course of your treatment and your adherence tendencies play a vital role in determining your treatment plan. If you have discontinued medication in the past, let your doctor know your reasons so they can take them into consideration. It helps to share your apprehensions regarding pharmacotherapy and getting your doubts clarified to remove foreseeable obstacles from the treatment path.
2. Don’t self-medicate
Adding medication, changing the dosage or duration or making any other changes to your treatment can have a dire impact. It is highly recommended to not take matters in your own hands with regards to medication. Follow the doctor’s directions and in case of concerns, contact them.
3. Take regular therapy and be transparent with your therapist
Psychotherapy takes care of the numerous other symptoms that may be influencing the persistence of depressive symptoms. While therapy is a longer process, it ensures a relapse prevention and works as an additional support in this isolating journey. Several therapeutic modalities, such as Cognitive Behavioural Therapy, Acceptance and Commitment Therapy, Emotion Focused Therapy, Dialectic Behavioural Therapy, etc., can help address different concerns of your life that could be contributing factors.
In case over the course of therapy you notice that the symptoms have not improved, communicate the same to your therapist and discuss a different possible approach. Let your therapist know about your obstacles, your thoughts, and your emotional states, and help them understand what could be bothering you as it is a non-judgmental space meant for you to freely talk about your concerns.
In case a therapist's approach is not working with you, it does not mean the therapy has failed you. Sometimes it can take a while to find a therapist you connect well with, and that is okay. Be open to changing therapists and trying out a different individual.
4. Work on your stress management
Stress is one of the greatest evils and a major cause of almost all mental health conditions. It is therefore crucial to identify different stressors in your life that could be contributing to the maintenance of depressive symptoms. Evaluate your support system and your current coping methods and notice if they need changing. Good stress management techniques can help improve symptoms to a great extent.
5. Good lifestyle is crucial
Regular exercise, balanced diet, and good sleep are essential to healthy living. Regular exercise and physical activity help reduce the release of stress hormones in your body. This need not be an intensive workout. Simple regular walks and easy yoga can also help improve the symptoms. Further, a balanced diet ensures that your vitamin and mineral levels in the body are optimal, therefore reducing the chances of developing chronic conditions. A good sleep ensures that the repair work in your body and other essential biological processes are carried out to maintain internal balance.
6. Avoid drugs or alcohol
As established earlier, drugs and alcohol do not help depressive symptoms but rather counter the effects of the medication and treatment. They may seem like effective short-term coping methods, but in the long term, they encourage TRD. Therefore, avoid drugs and alcohol as they can alter the chemistry of the brain.
7. Do not consult AI
It is very tempting to ask ChatGPT to tell us what we can do next. Avoid consulting AI for any medical or treatment-related concerns. Instead, speak to the professionals who can better understand your history and make use of their educational journey in treating you better.
8. Be patient and don’t lose hope
It is natural to feel impatient and dismayed through the process but it helps to give it time. Treatment– whether biological or psychological– takes time to show effect. What is important to remember is that at no point are you alone, rather, there is help and support at every step of the way for you. All it takes is to reach out.
References
Voineskos, D., Daskalakis, Z. J., & Blumberger, D. M. (2020). Management of treatment-resistant depression: challenges and strategies. Neuropsychiatric disease and treatment, 221-234. doi: 10.2147/NDT.S198774
Schroder, H. S., Patterson, E. H., & Hirshbein, L. (2022). Treatment-resistant depression reconsidered. SSM-Mental Health, 2, 100081. <https://doi.org/10.1016/j.ssmmh.2022.100081>
Mayo Clinic Staff. (2021, April 10). Treatment-resistant depression. Mayo Clinic. <https://www.mayoclinic.org/diseases-conditions/depression/in-depth/treatment-resistant-depression/art-20044324>
Arvind, B. A., et. al. (2019). Prevalence and socioeconomic impact of depressive disorders in India: multisite population-based cross-sectional study. BMJ open, 9(6), e027250. <http://dx.doi.org/10.1136/bmjopen-2018-027250>
