Psychedelic-Assisted Therapy for Depression

In the treatment of depression, psilocybin and ketamine have been most investigated for their potential in treating treatment-resistant depression.

Psilocybin-Assisted Therapy for Depression

As we learned in Molecular Foundations, psilocybin has been shown in a number of clinical trials to be effective in treating depression. In a study of 59 participants, psilocybin was shown to be superior to escitalopram for treating depression, with 57% achieving remission with psilocybin and only 28% with escitalopram; many other secondary outcomes also favoured psilocybin (Carhart-Harris et al., 2021). Furthermore, initial findings from two long-term studies demonstrated that treatment results were sustained for at least 6 months post-treatment (Carhart et al., 2018; Griffiths et al., 2016).

Activity

Please read the abstracts of three studies below which focus on psilocybin-assisted therapy for depression.

Did You Know?

The anti-depressant effects of psychedelic-assisted therapy appear to be immediately following treatment, in comparison with the several weeks it takes for antidepressant medication or psychotherapy to be effective (Johansen et al., 2022).

Ketamine-Assisted Therapy for Depression

Ketamine has over 50 years of data recorded supporting its safety and efficacy as an anaesthetic agent and to treat depression in both clinical and research outpatient settings (Kohtala, 2021). However, the scientific literature combining ketamine and psychotherapy as a treatment for depression is scarce.

One study observed that ketamine-assisted therapy significantly improved scores to anxiety, well-being, PTSD, major depressive disorder, and substance use disorder in patients with severe symptoms before treatment (Dore et al., 2019). Importantly, ketamine did not produce any physical dependence (Dore et al., 2019).

Activity

Please read the abstracts of three studies below which focus on ketamine-assisted therapy for depression.

Proposed Neurological Mechanisms of Action

How classic psychedelics, like psilocybin and LSD, work in depression remains largely unknown. It is thought that effects may alter connectivity in brain regions comprising the default mode network by reducing connectivity within this network, whereas increased connectivity is associated with major depressive disorder.

Another potential mechanism may relate to the finding of enhanced responsiveness to emotional faces on the day following a psilocybin Medicine Session. This could possibly indicate an effect on apathy symptoms associated with depression.

Other studies have noted increases in neuroplasticity, while others have indicated anti-inflammatory effects, whereas inflammation may also be implicated in depression (Johansen et al., 2022).

Transdiagnostic Considerations for Psychedelic-Assisted Therapy for Depression

There are several transdiagnostic considerations for psychedelic-assisted therapy for depression.

Please ensure that you read through all items before proceeding by selecting each title.

Zeifman et al. (2020) observed that experiential avoidance was much lower at the 2-week and 4-week intervals following psychedelic use which was associated with lower depression and suicidality scores.

Psychological flexibility has been observed to be negatively correlated with depression scores when clients have been evaluated after their Medicine Session (Davis et al., 2020; Close et al., 2020).

Mystical type experiences during Medicine Sessions have been linked to an overall improvement in client wellbeing (Griffiths et al., 2018; Griffiths et al., 2011) in addition to a reduction of depression symptoms (Griffiths et al., 2016; Ross et al., 2016).

Mystical type experiences often include four aspects:

  • Mysticism, in other words, a sense of unity and sacredness

  • Positive mood

  • Transcendence of time and space

  • Difficulty describing the experience (Johansen et al., 2022)

While anxiety is not considered a symptom of depression, many clients present with comorbid anxiety and depression, and the DSM-5 included a qualifier “with anxious distress” to major depressive disorder, acknowledging the effect of anxiety on treatment choices and response.

50-60% of adults with a lifetime history of major depressive disorder also have a history of anxiety disorder, often co-occurring.

Studies have demonstrated clients with co-occurring anxiety:

  • Take longer to respond to treatment

  • Have worsening symptom severity

  • Increased rates of suicidal behaviour

  • Higher rates of mental health utilization

  • Increased rates of re-occurrence (Banov et al., 2019)

Approaches and treatments that target transdiagnostic factors shared between depression and anxiety such as some psychedelic-assisted therapies may therefore be of value when considering treatment options.

Systematic reviews have focused on

  • Establishing treatment efficacy (Muttoni et al., 2019)

  • Understanding the neurological mechanisms of change (Romeo et al., 2021)

  • Broader studies (dos Santos & Hallak, 2020; Kadriu et al., 2021)

Therefore, more research is needed to better collate findings on the psychological processes of classic psychedelics in the treatment of depression and identify literature gaps (Johansen et al., 2022).

Question

In the Fundamentals of Psychedelic-Assisted Therapy course, we learned about the 10 characteristics of the therapeutic stance in order to build a successful therapeutic relationship with the client. Can you recall all 10 characteristics?

The therapeutic stance is intended to assist clients to deepen their inner experience while also reducing experiential avoidance and enhancing psychological flexibility, two key transdiagnostic considerations. The 10 characteristics of the therapeutic stance include:

    • Inner-directed therapy

    • Unconditional positive regard
    • Love
    • Empathetic abiding presence and listening
    • Being grounded, self-regulated, and aligned
    • Orientation towards phenomenology
    • Relationship-centered care
    • Appreciation for human suffering
    • Self-awareness and ethical integrity
    • Top-down versus bottom-up processing

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