It is currently estimated that almost 9 million Americans have a condition called treatment-resistant depression or “difficult-to-treat” depression. It’s a serious problem that arises when people taking at least two rounds of different antidepressant medications simply don’t work. This may lead to long periods of expensive treatments including inpatient care and lower chances of recovery.
What Is Treatment-Resistant Depression?
Treatment-resistant depression is classified as a form of Major Depressive Disorder and does not respond to either tradition or first-line antidepressants. Technically, this condition may be diagnosed when an individual has tried two different antidepressants for 8 or more weeks each. It can be debilitating and life-threatening and occur anytime throughout the lifespan.
Pseudo-Resistance
Practitioners should be cautious of diagnosing treatment-resistant depression before examining characteristics of pseudo-resistance, which may present for a number of reasons. One of the most common reasons include prescribing suboptimal doses of antidepressants in the beginning of treatment. Some people will stop taking their medication for reasons including intolerable side effects or not taking the medication as prescribed (missing days). Some may have a co-occurring condition such as anxiety, substance-use disorders, or personality disorders. Pseudo-resistance can make the clinical picture rather muddy.
Treatment Options
Although this condition can be challenging to treat and live with, several options exist that can lighten its burden by managing symptoms and promoting quality of life. Treatment options range from changing medications, engaging in psychotherapy, undergoing brain stimulation therapies, and trying some newer, unconventional approaches to treatment-resistant depression.
Pharmacological Approaches
One approach to TRD is augmentation or adjunctive therapy which means adding a second medication other than another traditional antidepressant. Three in particular, are receiving lots of attention in research and include lithium, T3 and second-generation antipsychotics.
Lithium
Lithium has been used to treat mood disorders since the 1960s and has had much success. Some studies show that a combination of lithium with Celexa can cause symptom remission. The American Psychiatric Association (APA) strongly recommends lithium as an effective treatment strategy for TRD and MDD.
T3
T3 is a thyroid hormone that is sometimes prescribed for people with TRD. Thyroid levels are well known to influence mood. T3 not only has been shown to help manage symptoms, but is better tolerated than lithium and requires less clinical monitoring.
Second-Generation Antipsychotics
Research shows that second-generation or “atypical” antipsychotics work with both dopamine and serotonin and include Zyprexa, Abilify, Seroquel, Risperdal, and Latuda. Research has found positive outcomes when these medications are used in combination with SSRIs (Paxil, Prozac, Zoloft) and/or SNRIs including Cymbalta, Meridia, and Effexor.
Optimizing, Combining or Switching Antidepressants
Practitioners generally start treating depression with newer antidepressants including SSRIs and SNRIs. Older classes of antidepressants are used after the newer ones have shown no effect and include tricyclics (Pamelor, Anafranil and Elavil) and Monoamine Oxidase Inhibitors (MAOIs) including Marplan, Parnate and Nardil. These classifications of antidepressants are known to have unpleasant and sometimes dangerous side effects.
Psychotherapy
Mental health professionals will at times suggest use of antidepressants as well as some type of psychotherapy. The rationale behind this is that treatment-resistant depression (or any other type) may have a biological basis, in which case antidepressants may be effective, or a cognitive etiology, in which case psychotherapy may be beneficial. Several types of psychotherapy include:
- Cognitive behavioral therapy
- Acceptance or commitment therapy
- Group therapy
- Mindfulness
- Dialectical behavior therapy
- Interpersonal therapy
- Family or marital therapy
Regardless of which type the practitioner and individual decide to engage in, it has been found that psychotherapy is generally beneficial for various forms of depression, including treatment-resistant depression.
Brain Stimulation Modalities
There are many types of brain stimulation ranging from electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation, theta-burst stimulation, magnetic seizure therapy, deep brain stimulation and vagus nerve stimulation. The general idea behind these forms of treatment is that by stimulating nerve cells in the brain, treatment-resistant depressive symptoms may be improved and quickly.
New and Unconventional Approaches
Researchers and practitioners are looking into alternative ways to help with treatment-resistant depression, including the use of Ketamine, Psilocybin and various anti-inflammatories.
Ketamine
Some experts consider Ketamine a rapid acting antidepressant that has been used to decrease suicidal thinking. The FDA has approved Ketamine as a treatment option for TRD. Some side effects of Ketamine include nausea, confusion, increased heart rate and disassociation or feeling detached from the environment.
Psilocybin
Psilocybin is a psychedelic compound isolated from hallucinogenic mushrooms and appears to interact with serotonin to better manage symptoms of depression. Side effects include psychedelic effects (hallucinations), transient anxiety and mild tachycardia.
Anti-Inflammatories
Inflammation due to elevated C-reactive protein and cytokines have been shown to be elevated in people who have treatment-resistant depression as well as Major Depressive Disorder (MDD). The neurosteroid brexanolone, an intravenous formation allopregnanolone, has been shown to help with symptoms of various forms of depression including MDD, TRD and has been FDA approved for postpartum depression.
Final Thoughts on Treatment-Resistant Depression
Treatment-resistant depression affects enough people in the United States and around the world to pay special attention to various treatment options available to help manage symptoms and improve quality of life. Treatment can be long, expensive and some people may never fully recover. That’s why it’s vital to examine treatments that include medications, brain stimulation, and some newer forms of treatment. It is hoped that one or more of these modalities will make someone’s treatment-resistant depression easier to live with.