Efficacy of Antidepressants in MDMA-Assisted Psychotherapy for PTSD

Written by Rena Zhu and Edited by Olivia Cooper

Post-traumatic stress disorder (PTSD) is a chronic condition that may occur in individuals who have experienced a traumatic event, such as murder, violence, or natural disaster. Individuals with PTSD may have very intense, disturbing thoughts related to their past experiences that persist for long periods of time, often causing them to relive the events through flashbacks or nightmares [1]. As a means of alleviating these symptoms, many individuals seek psychotherapy treatment, and psychotherapy has been one of the most popular forms of treatment for mental disorders. In psychotherapy, psychologists use scientifically validated procedures, combined with medications, to help people develop healthier mindsets and habits [2]. It helps build self-esteem, reduce anxiety, improve social and community skills, and strengthen coping mechanisms [3]. However, many individuals with PTSD are resistant to common psychotherapy. Because of this, MDMA-assisted psychotherapy was developed as a novel approach for this particular disorder. 

3,4-Methylenedioxymethamphetamine (MDMA), or commonly known as ecstacy, is a synthetic drug that acts as a stimulant and hallucinogen, and is commonly used to manifest enhanced enjoyment and energizing effects [4]. It causes your brain to release more serotonin, a major neurotransmitter, than normal.  Serotonin plays an important role in regulating neural signals for functions like mood, sleep, appetite, and pain. The excess release of serotonin by MDMA increases neural activity levels and usually enhances enjoyment through sensory experiences [5]. MDMA-assisted psychotherapy allows individuals to lower their defensiveness and anxiety in addition to improving their mood. Additionally, it may also allow for a better relationship between the therapist and the patient. However, MDMA is a potent toxin that can cause serotonergic neurotoxicity—a condition associated with symptoms such as unconsciousness, early neurodegeneration, confusion, depression, or death [6]. Because of its potency, very low dosage levels are used in MDMA-assisted psychotherapy. 

Due to the novelty of MDMA-assisted psychotherapy, the FDA is still investigating and understanding its effectiveness for treating PTSD. Before MDMA-assisted psychotherapy was developed, selective serotonin reuptake inhibitors (SSRIs) were the most commonly prescribed antidepressants for PTSD. SSRIs increase serotonin levels in the brain by blocking the reabsorption of serotonin into the brain, which enables more serotonin to be available [7]. However, when antidepressants like SSRIs are co-administered in MDMA-assisted psychotherapy for PTSD, the psychological effects of the therapy may be reduced. According to a study done by Feduccia, this combination led to a reduced response to psychotherapy and MDMA usage, and it also caused withdrawal symptoms when the medication use was discontinued [8]. This study suggests that there are potential disadvantages of medications when taken together, and that those who take SSRIs medications for PTSD may benefit less from MDMA-assisted psychotherapy. This study also paves the way for future research studies to help explain how certain factors impact response rates and elucidate solutions to  improve treatment outcomes. While there has been some controversy surrounding the effectiveness of psychotherapy, studies have shown that patients who undergo psychotherapy do benefit from treatments in a variety of metrics domains, and future studies can further elaborate on the potential of psychotherapy as a treatment option. 

References

1. “What is Posttraumatic Stress Disorder?”PTSD. American Psychiatric Association. Aug., 2020, https://www.psychiatry.org/patients-families/ptsd/what-is-ptsd.
2. “Understanding psychotherapy and how it works.” Psychology Topics. American Psychological Association. 31 July, 2020, https://www.apa.org/topics/psychotherapy/understanding.
3. “What is Psychotherapy?” American Psychiatric Association, https://www.psychiatry.org/patients-families/psychotherapy#:~:text=It%20helps%20build%20self%2Desteem,the%20rest%20of%20their%20lives.
4. “What is MDMA?” MDMA (Ecstasy) Abuse Research Report. National Institutes on Drug Abuse. Sept., 2017. https://www.drugabuse.gov/publications/research-reports/mdma-ecstasy-abuse/what-mdma
5. “What are MDMA’s effects on the brain?” MDMA (Ecstasy) Abuse Research Report. National Institute on Drug Abuse. Sept., 2017, https://www.drugabuse.gov/publications/research-reports/mdma-ecstasy-abuse/what-are-mdmas-effects-on-brain#:~:text=MDMA%20causes%20greater%20release%20of%20serotonin%20and%20norepinephrine%20than%20of%20dopamine.&text=Serotonin%20is%20a%20neurotransmitter%20that,mood%2Delevating%20effects%20people%20experience.
6. Curran, H.V. (2000). “Is MDMA (‘Ecstasy’) Neurotoxic in Humans? An Overview of Evidence and of Methodological Problems in Research.” Neuropsychobiology, 42:34-41.
7. “Selective serotonin reuptake inhibitors (SSRIs).” Mayo Clinic. 17 Sept., 2019, https://www.mayoclinic.org/diseases-conditions/depression/in-depth/ssris/art-20044825.
8. Feduccia, A.A., Jerome, L., Mithoefer, M.C., Holland, J. (2020). “Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy.” Psychopharmacology, 238:581-588 (2021).