For individuals struggling with major depressive disorder (MDD), antidepressants have long been celebrated for their life-changing properties. But when medication suddenly stops working or loses its effectiveness, many struggling individuals are left asking the question, “what is tachyphylaxis and how can I continue on my wellness journey despite it?”
Rates of antidepressant tachyphylaxis impact sizable portions of the affected population. Learn about the definition of tachyphylaxis, what it is, how it’s addressed, and how antidepressant tachyphylaxis symptoms may appear during treatment.
Understanding the Long Term Efficacy of Antidepressants: The Definition of Tachyphylaxis
As the prevalence of antidepressants has continued to increase over the years, the scientific debates concerning antidepressant effectiveness have challenged clinicians and patients. Learning about the definition of tachyphylaxis and how to identify its effects is crucial for both patients and providers in addressing persistent cases of MDD.
What is Tachyphylaxis in MDD?
Tachyphylaxis (otherwise referred to as antidepressant tolerance, “poop out,” or breakthrough Depression), occurs when patients with MDD experience a reduction or total loss in the effectiveness of the medication(s) that once adequately managed their depressive symptoms.
In other words, individuals impacted by tachyphylaxis can experience both relapse and recurrence, finding that their depressive symptoms have returned and that their response to their medications has decreased significantly.
Patients may also encounter the emergence of new symptoms. Using randomized, controlled clinical trials and meta-analyses on antidepressant tachyphylaxis, research published in 2019 found that the prevalence of tachyphylaxis can range anywhere from 9% to 57% in users depending on the patient population and the extent of the follow-up period.
What Causes Antidepressant Tachyphylaxis
Although the exact causes remain both heterogeneous and uncertain, there are several factors that may be culpable for the prevalence of tachyphylaxis in antidepressant users.
One commonly proposed reason for tachyphylaxis is neuroadaptation, which highlights antidepressant long term risks, where the brain’s neurotransmitters adapt to the prolonged use of antidepressants and diminish the medication’s overall effectiveness. Another lies in tolerance, in which the body requires higher doses of a medication in order to cross the same effective therapeutic threshold over time.
Despite these hypotheses, tachyphylaxis has proven rather difficult to study given the obfuscating physical and psychological entanglements from within which it emerges, the interplay of which creates a complex portrait of “tolerance.” The reasons for such tolerance may lie with genetic factors, latent bipolarity, comorbidities, and the psychosocial variables that intrude on clinical research, suggesting a need for further double-blind controlled studies.
“True” tachyphylaxis must also be assessed and differentiated from other potential catalysts involved in re-emergence, such as medication nonadherence, in which patients consume their antidepressants sporadically or stop taking them altogether. There is also the potential that a patient’s underlying MDD is gradually worsening over time. Other nonspecific factors—such as the placebo response—can also challenge and convolute tachyphylaxis studies.
Antidepressant Tachyphylaxis Symptoms
So what is tachyphylaxis and how do the symptoms manifest on a day-to-day basis? Recognizing antidepressant tachyphylaxis can be challenging, as symptoms often mirror those of the original depressive episode.
The hallmark sign of tachyphylaxis is the gradual or sudden return of depressive symptoms despite continued adherence to medication that was previously effective. Patients affected by tachyphylaxis usually experience a noticeable decrease in response to SSRIs—typically occurring without any change to their previously effective dose.
Patients experiencing antidepressant tachyphylaxis symptoms may notice the re-emergence of classic Depression symptoms, including:
- Persistent sadness or low mood
- Loss of interest in activities they once enjoyed
- Fatigue and decreased energy
- Difficulty concentrating or making decisions
- Changes in sleep patterns (either insomnia or sleeping too much)
- Appetite changes
- Feelings of hopelessness or worthlessness
- Social withdrawal.
Tachyphylaxis symptoms can vary widely from person to person. Some patients may find that their returning symptoms feel familiar, while others may notice they present differently than during previous episodes. In some cases, mild to moderate depressive symptoms may become more severe despite the initial dose of antidepressant treatment.
What Distinguishes Antidepressant Tachyphylaxis Symptoms From Other Causes of Returning MDD Symptoms?
Key indicators of antidepressant tachyphylaxis symptoms include a clear period of remission followed by symptom re-emergence while still taking your medication as prescribed, symptoms that develop gradually over weeks or months rather than appearing suddenly, and the absence of major life stressors that might otherwise explain the mood changes.
It is important to differentiate what tachyphylaxis is as opposed to antidepressant discontinuation syndrome, which occurs when patients stop taking their medications. Discontinuation symptoms emerge within days to weeks of stopping the medication or lowering the dose, whereas relapse symptoms develop later and more gradually. The definition of tachyphylaxis is, by contrast, a phenomenon that occurs in patients who continue taking their medication consistently.
If you notice your Depression symptoms returning despite taking your antidepressant as prescribed, consult with your physician. Keeping track of your symptoms and any changes in their severity can help your provider determine whether you may be experiencing true antidepressant tachyphylaxis symptoms and explore the appropriate next steps for your treatment.
How is Antidepressant Tachyphylaxis Treated?
Tachyphylaxis is a persistent and widespread problem that requires new and innovative treatment modalities. When we consider the ways in which the long-term efficacy of antidepressants is subject to a high degree of variability alongside the unfortunate prevalence of treatment-resistant Depression (TRD), the need for effective and sustainable relief is obvious.
A number of treatment strategies for antidepressant tachyphylaxis have emerged, such as increasing a patient’s current antidepressant dose or decreasing the dose in what’s referred to as a “drug holiday” in order to restore receptor sensitivity. Other clinicians might recommend their patients switch antidepressants with different mechanisms of action to combat diminished responses to the former medication.
Another option is to add augmentation/combination medications such as dopaminergic agonists (i.e. bupropion), tricyclic antidepressants, buspirone, mood stabilizers (i.e. lithium, lamotrigine), antipsychotic medications (i.e. quetiapine, aripiprazole), S-adenosylmethionine (SAMe) or methylfolate, thyroid supplementation, or stimulants (e.g., amphetamine, methylphenidate). However, all of these strategies can often have side effects and are variably effective.
Transcranial magnetic stimulation, otherwise known as TMS, is an excellent option to treat MDD and TRD, including for those patients who are experiencing antidepressant tachyphylaxis. This non-invasive treatment delivers magnetic pulses to the brain, regulating over- and under-excitability in areas of the brain associated with MDD, giving those suffering from tachyphylaxis an approach of treating MDD that is much different from medications and achieves lasting wellness.
Sustaining Long-Term Wellness with Mid City TMS
As the research surrounding the long-term efficacy of antidepressants continues to develop, many patients will need to explore the question “what is tachyphylaxis” and seek alternatives to stabilize their mental health. If you’re experiencing a re-emergence of your depressive symptoms despite your medication adherence, it may be time to explore TMS treatment options such as those offered by Mid City TMS.
Tachyphylaxis is challenging but you never have to face it alone. Our experienced physicians will work alongside you to help overcome your MDD and/or TRD. Contact us today to learn more about how we can aid you in the fight against tachyphylaxis.
Sources:
- Bahji, A., Vazquez, G., Zarate, C. A., Bloch, M. H., & Rodriguez, C. I. (2019). Ketamine for depression: A systematic review and meta-analysis of dose and administration. Journal of Affective Disorders, 246, 525-533. https://www.sciencedirect.com/science/article/abs/pii/S0165032718316859?via%3Dihub
- Marcantoni, W. S., Akoumba, B. S., Wassef, M., Mayrand, J., Lai, H., Richard-Devantoy, S., & Beauchamp, S. (2020). A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment-resistant depression: January 2009–January 2019. Journal of Affective Disorders, 277, 1-8. https://pubmed.ncbi.nlm.nih.gov/30439676/
- Wilkinson, S. T., Wright, D., Fasula, M. K., Fenton, L., Griepp, M., Ostroff, R. B., & Sanacora, G. (2018). Cognitive behavior therapy may sustain antidepressant effects of intravenous ketamine in treatment-resistant depression. Psychotherapy and Psychosomatics, 88(1), 62-64. https://pubmed.ncbi.nlm.nih.gov/30385364/
- Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000). Antidepressant effects of ketamine in depressed patients. Biological Psychiatry, 47(4), 351-354. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008298/