Psilocybin Therapy Shows Promise in Bipolar Disorder

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COMPASS Pathways recently shared that early data from an investigator-initiated trial (IIT) appears to signal that the company’s COMP360 psilocybin therapy might be an effective treatment for Bipolar II Disorder (BD-II). In fact, 12 out of 14 participants in the trial met the criteria for response and remission three months after their psilocybin treatment.

The early results of this Phase 2 open label trial, led by Dr. Scott Aaronson and sponsored by Sheppard Pratt Health System, were presented at the recent Annual Meeting of the American College of Neuropsychopharmacology (ACNP). This trial, financed by COMPASS Pathways, is one of a dozen completed or ongoing IITs that have explored COMP360 psilocybin therapy as a potential treatment for a range of psychiatric and neurological indications.

Other COMPASS-affiliated IITs look at a number of indications that include body dysmorphic disorder, anorexia nervosa and chronic cluster headaches. COMPASS has shared that these investigator-initiated, “signal-generating” trials may be used to inform future drug development efforts.

A predominant focus of COMPASS’ efforts, and clinical psilocybin research more broadly, has been on their apparent antidepressant effects. Accordingly, psilocybin’s potential efficacy as treatments for indications such as Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD) is one of the most intensely explored areas of the field, with COMPASS’ lead program targeting the latter.

In fact, over 35% of all clinically-focused trials on psychedelics that we monitor at Psychedelic Alpha have a primary focus on a depressive disorder. However, only a very small portion of these trials investigate psychedelics as potential treatments for bipolar depression (also known as bipolar disorder, formerly known as “manic depression”).

To understand why this may be the case, we should first look at what differentiates bipolar depression from other more commonly investigated depressive disorders.

As aforementioned; to date, the vast majority of drug development efforts have been focused on unipolar depression, which includes Major Depressive Disorder (MDD) and the treatment-resistant population who have not responded to two or more treatment options for their unipolar depression (see Psychedelic Alpha’s Bulletin on the COMPASS Phase 3 Trial for more).

However, there is another class of disorders that often share MDD’s classic presentation of depressive symptoms, but are differentiated based on the often cyclical presence of manic or hypomanic episodes (McIntyre et al., 2020).

Manic and hypomanic episodes are diagnosed based on different sets of criteria. However, both types of episodes are characterized by a “distinct period of abnormally and persistently elevated, expansive, or irritable mood and persistently increased goal-directed activity or energy” (American Psychiatric Association, 2013).

Hypomania has often been described as the “less severe” of the two episodes. Accordingly, unlike manic episodes, hypomanic episodes are considered to be “not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization” (ibid.).

Nonetheless, the episode still leads to uncharacteristic and observable changes in functioning for the individual. Individuals who exhibit psychotic features during these periods are classified as experiencing manic episodes (ibid.).

It is important to note that not all bipolar disorders are the same. In fact, the DSM-5 Diagnostic Criteria distinguishes between a number of different subtypes, two of which are Bipolar I Disorder (BD-I) and Bipolar II Disorder (BD-II). These disorders are delineated based on symptom presentation as outlined in different diagnostic manuals.

An individual diagnosed with BD-I will have had at least one manic episode that may or may not have occurred before or after a hypomanic or a major depressive episode. Conversely, an individual who had experienced a hypomanic episode along with a major depressive episode, without any manic episodes, would satisfy the diagnostic criteria for BD-II.