Major Depressive Disorder
Conditions
Brief summary
Background: Major Depressive Disorder is one of the most prevalent mental illnesses, leading to substantial personal distress and economical consequences. Pharmacological Treatment is limited and relapse is frequent. Lysergic acid diethylamide (LSD) was extensively investigated in humans in the 1950s and 1960s and was shown to attenuate depressive symptoms. Clinical research with LSD ended in the 1970s due to regulatory restrictions but its use for personal and recreational purposes continued. In recent years, there has been a renewed interest in the use of hallucinogens in psychiatric research and practices, reconsidering LSD's antidepressant potential. Larger, well-designed and placebo-controlled studies are warranted. This study will evaluate the potential benefits of LSD-assisted psychotherapy in patients suffering from Major Depressive Disorder. Objective: To test the efficacy of LSD in patients with Major Depressive Disorder. Design: Randomised, double-blind, active-placebo-controlled trial using either two moderate to high doses of LSD (100 µg and 100 µg or 100 µg and 200 µg) as intervention and two low doses of LSD (25 µg and 25 µg) as active-placebo control. Participants: 60 patients aged \> 25 years with Major Depressive Disorder (according to DSM-V). Main outcome measures: Change in depressive symptomatology (IDS, BDI), anxiety (STAI), and general psychopathology (SCL-90) compared with active-placebo-assisted psychotherapy.
Interventions
DRUGLSD
LSD administration per os
Sponsors
Department of Psychiatry Basel (UPK Basel; Prof. Dr. med. Stefan Borgwardt)
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Major Depressive Disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V) * \> 25 years * Sufficient understanding of the German language
Exclusion criteria
* \< 25 years * Concomitant diagnosis of past or present psychotic disorder * Concomitant diagnosis of past or present bipolar disorder * First degree relative with a psychotic disorder * Unable or unwilling to discontinue antidepressant medication * Pregnancy or breastfeeding * Known hypersensitivity to LSD * Somatic disorders including central nervous system (CNS) involvement * Known or suspected non-compliance, drug or alcohol abuse * Metal implants * Weight \< 42 kg * Suicide risk or very likely to require psychiatric hospitalisation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in depressive symptoms assessed by questionnaire compared with active placebo | Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD | Inventory of Depressive Symptomatology (IDS-C, clinician-rated). Scores are obtained by summing responses to the items, with a total score ranging from 0 to 84 and higher scores indicating more and/or stronger depressive symptoms. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in state and trait anxiety assessed by questionnaire compared with active placebo | Baseline; 2 weeks post-intervention | State-Trait Anxiety Inventory (STAI). State and trait anxiety are being assessed separately. Each type of anxiety is being represented by 20 different items. Scores range from 20 to 80, with higher scores indicating greater anxiety. |
| Changes in general psychopathology assessed by questionnaire compared with active placebo | Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD | Symptom Check List (SCL-90, 90-item version). Consists of 9 subscales investigating psychopathological symptoms (somatization, obsessive-compulsivity, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism), offering five answers (i.e. not at all, a little, fairly, a lot, extremely). SCL-90 total score = 360; subscale total score = 40. Higher scores indicate greater psychological impairment. |
| Changes in existential anxiety assessed by questionnaire compared with active placebo | Baseline; 2 weeks after first treatment; 2 weeks after second treatment | Existential Concerns Questionnaire (EAQ). Item scores are assessed in a yes/no format. |
| Changes in mindfulness assessed by questionnaire compared with active placebo | Baseline; 2 weeks after first treatment; 2 weeks after second treatment | Five Facet Mindfulness Questionnaire (FFMQ). Item scores are assessed on a scale from 1 (never) to 5 (very often or always). Higher scores indicate higher greater levels of mindfulness. |
| Changes in humility assessed by questionnaire compared with active placebo | Baseline; 6 weeks post-treatment | Elliot Humility Scale (EHS). Item scores are assessed on a scale from 1 (strongly disagree) to 5 (strongly agree). Higher scores indicate higher greater levels of humility. |
| Changes in humility assessed by questionnaire | Baseline; 6 weeks post-treatment compared with active placebo | Jankowski Humility Scale (JHS). Item scores are assessed on a scale from 1 (not at all) to 5 (absolutely). Higher scores indicate higher greater levels of humility. |
| Changes in the personality trait absorption assessed by questionnaire compared with active placebo | Baseline | Tellegen Absorption Scale (TAS). Item scores are assessed on a scale from 0 (not at all) to 4 (absolutely). Higher scores indicate higher greater levels of trait absorption. |
| Acute subjective effects assessed via questionnaire compared with active placebo | At weeks 3 and 7 | The Visual Analog Scale (VAS). Items assess acute subjective drug effects (e.g. intensity, liking) Item scores are assessed on a visual scale ranging from 1% to 100%. Higher scores indicate greater subjective effects. |
| Characteristics of altered states of consciousness assessed by questionnaire | At weeks 3 and 7 | States of Consciousness Questionnaire (SCQ). Items retrospectively assess subjective drug effects. Item scores are assessed on a scale ranging from 0 to 5. Higher scores indicate greater subjective effects associated with a different state of consciousness. |
| Characteristics of altered states of consciousness assessed by questionnaire compared with active placebo | At weeks 3 and 7 | 5-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). Items retrospectively assess subjective drug effects. Item scores are assessed on a visual scale ranging from 1% to 100%. Higher scores indicate greater subjective effects associated with a different state of consciousness. |
| Changes in mystical-type experiences assessed by questionnaire | Baseline; 6 weeks post-treatment compared with active placebo | Mysticism Scale (MS). Item scores are assessed on a scale ranging from +4 (extremely accurate) to -4 (extremely inappropriate). Higher scores indicate greater levels of mystical experiences. |
| Acquisition of physical conditions / complaints assessed by questionnaire | Baseline; at weeks 2, 3, 5, 7, 9, 13 | List of complaints (LC). Assesses acute complaints (e.g. pain, coughing, nausea) in a yes/no frmat. A higher number of yes answers indicates more complaints. Total yes score ranges from 0 to 65. |
| Change in depressive symptoms assessed by questionnaire compared with active placebo | Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD | Beck Depression Inventory (BDI). Scores are obtained by summing responses to the items, with a total score ranging from 0 to 63 and higher scores indicating more and/or stronger depressive symptoms. |
| Subjective evaluation of mood assessed by questionnaire | Baseline; at weeks 2, 3, 5, 7, 9, 13 | Adjective Mood Rating Scale (clinician version (AMRS-C), patient version (AMRS-P). Scale consists of 60 adjectives describing different moods (e.g. nervous, concentrated, drowsy), offering four response possibilities (i.e. not at all, a little, fairly, strongly). Items are analyzed separately. |
| Assessment of personality by questionnaire | Baseline | NEO-Five-Factor-Inventory (NEO-FFI). The NEO-FFI assesses five personality traits (i.e. neuroticism, extraversion, openness, agreeableness and conscientiousness) on a scale from 1 (strongly disagree) to 5 (strongly agree). Higher scores indicate higher manifestation of a particulare personality trait. |
| Assessment of religiosity by questionnaire | Baseline | Religiosity Scale (Z-Scale). This 7-item scale assesses the degree of religiosity on ascending scales ranging from not at all to very often. Higher scores indicate higher levels of religiosity. |
| Persisting effects of treatment assessed by questionnaire | 12 weeks post-treatment | Persisting Effects Questionnaire (PEQ). Scores are assessed on a scale from 0 (not at all) to 5 (extremely). Higher scores (under consideration of reverse-scored items) indicate stronger persisting treatment effects. |
| Changes in brain-derived neurotrophic factor (BDNF) | One day and 12 weeks post-treatment | Changes in brain-derived neurotrophic factor as measured by blood concentrations compared with active placebo |
| Changes in hypothalamic-pituitary-adrenal (HPA) axis function | 2 weeks post-treatment | Changes in hypothalamic-pituitary-adrenal (HPA) axis function as measured with salivary cortisol awakening responses compared with active placebo |
| Changes in immunoregulation and Inflammation compared with active placebo | One day and 12 weeks post-treatment | Measured via blood levels of macrophage migration inhibitory factor and interleukin-1 beta |
| Brain activation during fearful face processing and working memory processing compared with placebo | One week pre-treatment and one day post-treatment | Functional Magnetic Resonance Imaging (fMRI) |
| Brain Perfusion in treatment condition compared with active placebo | One week pre-treatment and one day post-treatment | Diffusion Tensor Imaging (DTI) |
| Brain Perfusion compared with active placebo | One week pre-treatment and one day post-treatment | Arterial Spin Labeling (ASL) |
| Changes in sleep patterns | From one week pre-treatment to two weeks post-treatment | Actigraphy |
| Perception of therapeutic alliance assessed by questionnaire | 1 week pre-treatment | Helping Alliance Questionnaire (therapist version (HAQ-T), patient version (HAQ-P). Item scores are assessed on a scale ranging from 1 (very accurate) to 6 (very inaccurate). Lower scores indicate increased subjective helping alliance. |
Countries
Switzerland
Outcome results
None listed