A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis

TY - JOUR

T1 - A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD

T2 - A systematic review and meta-analysis

AU - Illingworth, Benjamin Jg

AU - Lewis, Declan J

AU - Lambarth, Andrew T

AU - Stocking, Kate

AU - Duffy, James Mn

AU - Jelen, Luke A

AU - Rucker, James J

PY - 2020/12/20

Y1 - 2020/12/20

N2 - RATIONALE: Novel, evidence-based treatments are required for treatment-resistant post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine (MDMA) has beneficially augmented psychotherapy in several small clinical trials.OBJECTIVE: To review the use of MDMA-assisted psychotherapy in treatment-resistant PTSD.METHODS: Systematic searches of four databases were conducted from inception to February 2020. A meta-analysis was performed on trials which were double-blinded, randomised, and compared MDMA-assisted psychotherapy to psychotherapy and placebo. The primary outcomes were the differences in Clinician Administered PTSD Scale (CAPS-IV) score and Beck's Depression Inventory (BDI). Secondary outcome measures included neurocognitive and physical adverse effects, at the time, and within 7 days of intervention.RESULTS: Four randomised controlled trials (RCTs) met inclusion criteria. When compared to active placebo, intervention groups taking 75 mg (MD -46.90; 95% (confidence intervals) CI -58.78, -35.02), 125 mg (MD -20.98; 95% CI -34.35, -7.61) but not 100 mg (MD -12.90; 95% CI -36.09, 10.29) of MDMA with psychotherapy, had significant decreases in CAPS-IV scores, as did the inactive placebo arm (MD -33.20; 95% CI -40.53, -25.87). A significant decrease in BDI when compared to active placebo (MD -10.80; 95% CI -20.39, -1.21) was only observed at 75 mg. Compared to placebo, participants reported significantly more episodes of low mood, nausea and jaw-clenching during sessions and lack of appetite after 7 days.CONCLUSION: These results demonstrate potential therapeutic benefit with minimal physical and neurocognitive risk for the use of MDMA-assisted psychotherapy in TR-PTSD, despite little effect on Beck's Depression Inventory. Better powered RCTs are required to investigate further.INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS: CRD42019109132 available online at www.crd.york.ac.uk/prospero.

AB - RATIONALE: Novel, evidence-based treatments are required for treatment-resistant post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine (MDMA) has beneficially augmented psychotherapy in several small clinical trials.OBJECTIVE: To review the use of MDMA-assisted psychotherapy in treatment-resistant PTSD.METHODS: Systematic searches of four databases were conducted from inception to February 2020. A meta-analysis was performed on trials which were double-blinded, randomised, and compared MDMA-assisted psychotherapy to psychotherapy and placebo. The primary outcomes were the differences in Clinician Administered PTSD Scale (CAPS-IV) score and Beck's Depression Inventory (BDI). Secondary outcome measures included neurocognitive and physical adverse effects, at the time, and within 7 days of intervention.RESULTS: Four randomised controlled trials (RCTs) met inclusion criteria. When compared to active placebo, intervention groups taking 75 mg (MD -46.90; 95% (confidence intervals) CI -58.78, -35.02), 125 mg (MD -20.98; 95% CI -34.35, -7.61) but not 100 mg (MD -12.90; 95% CI -36.09, 10.29) of MDMA with psychotherapy, had significant decreases in CAPS-IV scores, as did the inactive placebo arm (MD -33.20; 95% CI -40.53, -25.87). A significant decrease in BDI when compared to active placebo (MD -10.80; 95% CI -20.39, -1.21) was only observed at 75 mg. Compared to placebo, participants reported significantly more episodes of low mood, nausea and jaw-clenching during sessions and lack of appetite after 7 days.CONCLUSION: These results demonstrate potential therapeutic benefit with minimal physical and neurocognitive risk for the use of MDMA-assisted psychotherapy in TR-PTSD, despite little effect on Beck's Depression Inventory. Better powered RCTs are required to investigate further.INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS: CRD42019109132 available online at www.crd.york.ac.uk/prospero.

UR - http://www.scopus.com/inward/record.url?scp=85097882256&partnerID=8YFLogxK

U2 - 10.1177/0269881120965915

DO - 10.1177/0269881120965915

M3 - Review article

C2 - 33345689

SN - 0269-8811

SP - 269881120965915

JO - Journal of psychopharmacology (Oxford, England)

JF - Journal of psychopharmacology (Oxford, England)

ER -