Psilocybin and Depression

IF YOU WANT TO EASE SYMPTOMS FOR TREATMENT-RESISTANT DEPRESSION, you may wish to consider a 25-milligram dose of synthetic psilocybin. In combination with psychotherapy, this treatment effectively eases treatment (at least for the short term).

“I didn’t want my picture taken because I was going to cry. I didn’t know why I was going to cry, but I knew that if anybody spoke to me or looked at me too closely, the tears would fly out of my eyes, and the sobs would fly out of my throat, and I’d cry for a week. I could feel the tears brimming and sloshing in me like water in a glass that is unsteady and too full.”
― Sylvia Plath

Have you had treatment for depression without symptom improvement? You may have treatment-resistant depression.

While many individuals respond to counseling (psychotherapy) or medicines such as an antidepressant, standard treatments are insufficient for some. Sometimes these interventions are not associated with symptom improvement; for others, the problems get better but recur.

The symptoms of treatment-resistant depression range from mild to severe. Many interventions are sometimes required to discover something efficacious.

Treatment-resistant depression — Management

What is treatment-resistant depression? The term refers to major depressive episodes that don’t respond satisfactorily despite two trials of anti-depressant therapy. However, there is no universally accepted definition.

Black and white image of a young woman sitting on the floor, leaning forward to clutch her knees. — Photo by Victoria Volkova on Unsplash

The term “difficult to treat” depression is a descriptor for treatment-resistant depression. “Pseudoresistance” is a descriptor of treatment failures due to an inadequate dose or duration of medicines or non-adherence to treatment.

The Mayo Clinic (USA)-endorsed treatment-resistant depression management strategies include:

Give your current medications more time. Antidepressants typically take four to eight weeks (or more) to achieve maximal effectiveness (and for side effects to improve).
Optimizing the medicine dose. Selected individuals may improve with a higher dose of a medicine than is usually prescribed. Of course, a professional medical practitioner should supervise any changes.
Switching antidepressants.
Adding another antidepressant type. Targeted neurotransmitters linked to mood include dopamine, serotonin, and norepinephrine.
Consider adding a medication typically used for another condition. Adding some drugs to an antidepressant is known as augmentation. This approach may include anti-anxiety medicines, thyroid hormones, mood stabilizers, antipsychotics, and others.
Consider pharmacogenetic testing. This testing approach seeks to identify certain genes that indicate how well your body can metabolize a medication. While the tests are not guaranteed to show if a particular medicine will work for you, the tests can provide treatment clues, especially for those who have had poor results with a particular medicine or struggle with side effects. Your insurance plan may not cover the tests.

Psychological counseling

Psychological counseling (psychotherapy) by a psychiatrist, psychologist, or another mental health professional can be very effective. For many, psychotherapy combined with medication works best. The former can help identify underlying concerns that may add to your depression.

While working with your therapist, you can also learn specific behaviors and strategies to overcome your depression. The Mayo Clinic (USA) offers that psychotherapy can help you with the following:

Find better ways to cope with life’s challenges.
Deal with previous emotional trauma
Manage relationships in a healthier fashion
Learn how to reduce stress effects in your life
Address substance use

Psilocybin and treatment-resistant depression

Sometimes, despite medicines and psychotherapy, depression symptoms don’t improve. The minority who don’t improve (or improve only to see symptoms recur) may have treatment-resistant depression.

A man stands on a rock, looking at the ocean in the distance. The scene is a hazy blue. — Photo by Yoal Desurmont on Unsplash

A randomized, double-blind clinical trial is the largest hallucinogen study for treatment-resistant depression. Let’s get right to the findings:

Subjects who received 25 milligrams of psilocybin had a much greater reduction in depression for at least three weeks compared with the control groups (those receiving ten versus one milligram of the drug).

Those receiving the 25-milligram dose had a three-week remission rate of 29 percent, with 37 percent having at least a halving of their depression scores. Lead investigator Dr. Guy Goodwin, speaking at a press briefing, puts the response rate in perspective:

The bad news? At the three-month mark, only one in five on the 25-milligram dose of psilocybin reported significant improvement. Again, Dr. Goodwin:

“It’s important to understand that response rates in these patients are usually somewhere between 10 and 20 percent, and we are seeing remission rates at three weeks of 30 percent.”

Study details

Researchers conducted this multicenter trial at 22 sites in 10 countries. The study included 233 individuals with treatment-resistant depression. The study’s primary endpoint was the change from baseline to three weeks in Montgomery-Asberg Depression Rating Scale (MADRS) depression survey scores. The MADRS scale ranges from 0 to 60, with higher scores indicating more severe depression.

The investigators randomly assigned subjects to receive 25 milligrams, 10 milligrams, or one milligram of psilocybin. Participants taking medicines stopped at least two weeks before the baseline visit and had an average MADRS score of 32 or 33 in each group.

Each participant met with a study therapist approximately three times to build a relationship and to prepare for the psychedelic experience. On the day of psilocybin, each subject listened to a tailored music playlist while wearing eyeshades and reclining in a comfortable chair.

Each psychotherapy intervention lasted six to eight hours, with two therapists present throughout the session. The following day, the subjects returned for a therapist-led “integration” session designed to help participants explore insights from their session.