For individuals struggling with major depressive disorder (MDD), antidepressants have long been celebrated for their life-changing properties. However, rates of antidepressant “poop out” impact sizable portions of the affected population.
Understanding the Long Term Efficacy of Antidepressants
As the prevalence of antidepressants has continued to increase over the years, the scientific debates concerning antidepressant effectiveness have challenged clinicians and patients.
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 This Antidepressant “Poop Out?”
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 such “poop out” 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.
How is Tachyphylaxis Treated?
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 “poop out.” 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 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.
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.