Hope for new mental health treatment options

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MDMA and psilocybin may show promise for mental health treatment when administered in closely clinically supervised settings, independent panel finds

MDMA and psilocybin may show potential as therapeutic agents for the treatment of key mental health disorders, according to an independent review commissioned by the TGA.

The panel included pharmacist and pharmacology professor Dr Andrew Somogyi from the University of Adelaide, alongside pharmacologist Dr Mark Connor from Macquarie University and psychiatrist Professor Steve Kisely.of Metro South Health in Queensland.

They reviewed 14 randomised controlled trials—eight on MDMA and six on psilocybin—with inactive or active controls in the treatment of ICD-10 mental, behavioural or developmental disorders.

Diagnoses of interest included post-traumatic stress disorder (PTSD), treatment-resistant depression (TRD), obsessive-compulsive disorder, social anxiety in adults with autism, and anxiety or depression in life-threatening disease.

In all eight MDMA studies, both the intervention group and controls received supplementary intense psychotherapy. Half of the studies used inactive placebo as the control while the remainder used low doses of MDMA.

There were statistically significant differences for MDMA doses of greater than 100 mg in comparison with inactive or active controls, between four and 12 weeks following administration.

The panel found a “strong effect size” on MDMA symptom scores compared to active controls in post-traumatic stress disorder (Standardised Mean Difference=-0.86, 95%CI=-1.23 to -0.50; k=4).

MDMA also resulted in statistically significant improvements in social anxiety in adults with autism when compared to placebo.

Effect sizes were large in all comparisons but with wide confidence intervals.

Among the six psilocybin studies, two used low-dose psilocybin as the control and another two used the vasodilator niacin to induce a mild physiological reaction (e.g. flushing) without any psychological effects.

One study reported statistically significant differences between psilocybin and placebo (niacin) in treatment-resistant depression.

Another reported statistically significant differences between high and low dose psilocybin for subjects with anxiety or depression in life-threatening disease.

Psilocybin was superior to remaining on a wait list in a third study and equally effective as registered antidepressant escitalopram in a fourth study.

In a fifth study there were no statistically significant differences between psilocybin and controls at the two-week follow-up, although both groups showed longer-term improvements following cross-over.

In the final study there was no significant effect of dose on obsessive-compulsive symptoms, which the reviewers suggested was possibly because of low numbers and unexpectedly high response to the very low dose placebo.

Both MDMA and psilocybin were well tolerated in all the studies. The main adverse effects for MDMA were anxiety, restlessness, fatigue, jaw-clenching, headache and transient increases in blood pressure; and for psilocybin, they were anxiety, headache and transient increases in blood pressure.

Effect sizes ranged from small to strong and 95% confidence intervals were wide. Evidence was strongest for MDMA, especially in doses of over 100 mg. By contrast, randomised findings for psilocybin were largely limited to short follow-up data prior to cross-over.

However trial quality, including blinding and follow-up, was variable and only a small proportion of potential participants were included in the randomised phase.

“Overall, study quality was not optimal, despite studies being described as double–blinded,” said the panel.

“Although we were only able to combine results from nine studies for either beneficial or adverse effects, we did demonstrate statistically significant differences of the two psychedelic agents between both inactive and active treatments for either continuous scores or dichotomous responses.

“It is important to note that this was in highly supportive and structured environments including intense psychotherapy sessions in many cases.

We conclude that MDMA and psilocybin may show promise in highly selected populations but only where these medicines are administered in closely clinically supervised settings and with intensive professional support.”

Waiting on a decision

Advocacy group Mind Medicine Australia (MMA) welcomed the results, following its bid this year to the TGA to reschedule these medicines from Schedule 9 of the Poisons Standard to Schedule 8—which the TGA initially knocked back in its interim decision.

“It should be emphasised that MMA’s application for rescheduling of these medicines was restricted to treatments occurring only in medically controlled environments by trained professionals and prescribed by a psychiatrist or specialist addiction physician,” said the group, in acknowledgement of the findings.

“It is not envisaged that patients will ever be allowed to take these substances away from the clinical environment.”

Peter Hunt AM, Chair of the MMA, added: “We are very hopeful that these medicinal therapies will now be rescheduled as controlled medicines under the Poisons Standard.

“This will enable psychiatrists, who are already getting approvals from the TGA to treat seriously ill and suicidal patients under its Special Access Scheme on a case-by-case basis, to apply for individual permits from State and Territory Governments around Australia.

“What we need now is a nationally standardised approach for providing medical approvals to those who are suffering desperately.”

Now that the independent review has been published, it is up to the TGA to make a final decision on applications to downschedule MDMA and psilocybin to Schedule 8.

In March this year, Health Minister Greg Hunt launched a $15 million competitive grant round to kickstart Australian clinical trials exploring the use of psilocybin, MDMA and ketamine to treat mental illnesses resistant to first-line treatments.

While the early results of trials in Australia and internationally are extremely encouraging, more research is “desperately needed” before the approaches can be used by psychiatrists outside of controlled clinical trials, said Minister Hunt.

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