Abstract
Background: Evidence suggests that classical psychedelics can promote enduring changes in personality, attitudes and optimism, as well as improvements in mental health outcomes.Aim: To investigate the effects of a composite intervention, involving psilocybin, on pessimism biases in patients with treatment-resistant depression (TRD).Methods: Patients with TRD (n = 15) and matched, untreated non-depressed controls (n = 15) performed the Prediction Of Future Life Events (POFLE) task. The POFLE task requires participants to predict the likelihood of certain life events occurring within a 30-day period, after which the actual rate of event occurrence is reported; this gives an index of potential pessimism versus optimism bias. Psilocybin was administered in two oral dosing sessions (10 and 25 mg) one week apart. Main outcome measures were collected at baseline and one week after the second dosing session.Results: Patients showed a significant pessimism bias at baseline [t(14) = -3.260, p = 0.006; 95% CI (-0.16, -0.03), g = 1.1] which was related to the severity of their depressive symptoms (rs = -0.55, p = 0.017). One week after psilocybin treatment, this bias was significantly decreased [t(14) = -2.714, p = 0.017; 95% CI (-0.21, -0.02), g = 0.7] and depressive symptoms were greatly improved [t(14) = 7.900, p < 0.001; 95% CI (16.17, 28.23), g = 1.9]; moreover, the magnitude of change in both variables was significantly correlated (r = -0.57, p = 0.014). Importantly, post treatment, patients became significantly more accurate at predicting the occurrence of future life events [t(14) = 1.857, p = 0.042; 95% CI (-0.01, 0.12), g = 0.6] whereas no such change was observed in the control subjects.Conclusion: These findings suggest that psilocybin with psychological support might correct pessimism biases in TRD, enabling a more positive and accurate outlook.
Highlights
Major depressive disorder (MDD) is one of the foremost contributors to the overall global burden of disease (Marcus et al, 2012)
The Prediction Of Future Life Events (POFLE) task requires participants to predict the likelihood of certain life events occurring within a 30day period, after which the actual rate of event occurrence is reported; this gives an index of potential pessimism versus optimism bias
These findings suggest that psilocybin with psychological support might correct pessimism biases in treatmentresistant depression (TRD), enabling a more positive and accurate outlook
Summary
Major depressive disorder (MDD) is one of the foremost contributors to the overall global burden of disease (Marcus et al, 2012). The cognitivebias model of depression states that patients have an unrealistic negative perspective of themselves and the world more generally (Beck, 1967, 1976; Beck and Rush, 1979). A key cognitive feature in MDD is that patients expect the future to be bleak and anticipate unfavorable outcomes when facing life events of unknown emotional impact. More recent findings have since supported the cognitive-bias model of depression over the depressive realism hypothesis, demonstrating, for example, that MDD patients exhibit pessimistic biases when anticipating future life events (Strunk et al, 2006; Strunk and Adler, 2009). Evidence suggests that classical psychedelics can promote enduring changes in personality, attitudes and optimism, as well as improvements in mental health outcomes
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