Depression

A single intravenous dose of ketamine produced significant antidepressant effects within 110 minutes that persisted for one week.

randomized, placebo-controlled, double-blind crossover study Sample size: 18

MBCT significantly reduced relapse/recurrence in patients with three or more previous episodes, but not in those with only two episodes.

randomized controlled trial Sample size: 145

High-dose psilocybin produced large and sustained decreases in depressed mood and anxiety, with about 80% of participants showing clinically significant improvement at 6-month follow-up.

randomized controlled trial Sample size: 51

Single-dose psilocybin (0.3 mg/kg) plus psychotherapy produced rapid, robust, and enduring reductions in anxiety and depression in patients with cancer-related psychological distress.

double-blind, placebo-controlled, crossover trial Sample size: 29

Argues that ketamine rapidly induces synaptogenesis and reverses synaptic deficits caused by chronic stress, supporting a synaptogenic hypothesis of depression and treatment response.

review

Psilocybin was well tolerated and associated with marked reductions in depressive symptoms at one week and three months after treatment in patients with treatment-resistant depression.

open-label feasibility trial Sample size: 12

MBCT reduced relapse from 78% to 36% in patients with three or more previous episodes, but was associated with a higher relapse rate in those with only two episodes.

randomized controlled trial Sample size: 73

Psilocybin did not show a significant difference in antidepressant effects compared to escitalopram at week 6.

randomized controlled trial

Describes the development of MBCT, a psychological intervention incorporating mindfulness training to reduce relapse in recurrent major depression.

theoretical or philosophical paper

Psilocybin with therapy produced large, statistically significant reductions in depression severity compared with a waiting list control, with 71% of participants showing a clinically significant response at week 1 and 54% in remission at week 4.

randomized controlled trial Sample size: 24

Ketamine produced greater improvement in depression severity than midazolam 24 hours after a single infusion, with a 7.95-point lower MADRS score and a 64% response rate versus 28%.

randomized controlled trial Sample size: 73

Argues that Mindfulness-Based Cognitive Therapy offers a new approach to preventing relapse in recurrent depression by combining cognitive therapy with mindfulness practices.

review

A single 25 mg dose of psilocybin, but not 10 mg, significantly reduced depression scores at three weeks compared to a 1 mg control dose in treatment-resistant depression.

phase 2 double-blind randomized controlled trial Sample size: 233

Two doses of psilocybin produced large, rapid reductions in depressive symptoms that persisted for six months in patients with treatment-resistant depression.

open-label trial Sample size: 20

A single intravenous dose of ketamine produced robust and rapid antidepressant effects in patients with treatment-resistant bipolar depression.

randomized, placebo-controlled, double-blind, crossover, add-on study Sample size: 18

Current esketamine exposure was not associated with a statistically distinguishable difference in recorded nonfatal, medically attended suicide attempt or intentional self-harm (HR 1.017, 95% CI 0.670-1.544, p=0.938).

retrospective cohort study Sample size: 23140

Ketamine reduced MADRS scores by 7.3 points more than midazolam at day 14 (95% CI, -12.0 to -2.5; P = .003; Cohen d = 0.7).

randomized controlled trial Sample size: 68

Both single and repeated infusions of ketamine significantly improve suicidality and depressive symptoms in patients with a major depressive episode.

systematic review and meta-analysis

Argues that there is a high unmet need in TRD and that payers want additional data on psilocybin for comparative effectiveness, patient selection, and cost-effectiveness, plus building a mental health professional network for safe administration and follow-up care.

commentary

Sound-based meditation led to lower anxiety (HADS-A difference -2.55), depression (HADS-D difference -2.39), salivary cortisol (-2.54 nmol/L), and systolic blood pressure (-7.62 mmHg) compared to music control.

randomized controlled trial Sample size: 100

Psilocybin-assisted therapy produces rapid depression symptom reduction in major depressive disorder, treatment-resistant depression, and cancer-related distress; MDMA-assisted therapy showed robust PTSD symptom reduction in two phase three trials.

review

Argues that repeated subanesthetic ketamine infusions may rapidly improve depressive and anxiety symptoms in TRBPD with acceptable short-term safety, but relapse after induction and variable predictors underscore the need for individualized maintenance planning.

commentary

Depressive symptoms and rumination improved over six months across all treatment groups, with the combination of esketamine and metacognitive training showing the largest reductions.

observational cohort

Argues that a physiologically based pharmacokinetic/pharmacodynamic model can simulate psilocybin and psilocin exposure and receptor occupancy, offering a tool to optimize dosing for treatment-resistant depression.

theoretical or computational modeling paper

Proposes that Buddhist psychology, with its focus on ignorance and attachment as causes of suffering, offers a complementary approach to Western psychology for addressing youth mental health issues.

theoretical or philosophical paper