Appendix D | 14.4

Data and Tables

Appendix D - Audio Recording

14.4.1 Common Comparators

Condition	Netherlands (NL)	Germany (DE)	Czech Republic (CZ)	United Kingdom (UK)
Treatment‑Resistant Depression (TRD)	Pharmacotherapy Augmentation: Adding lithium, atypical antipsychotics Electroconvulsive Therapy (ECT) Repetitive Transcranial Magnetic Stimulation (rTMS) Psychotherapy: Cognitive Behavioral Therapy (CBT) Esketamine Nasal Spray (limited use)	Pharmacotherapy Augmentation ECT rTMS Psychotherapy: CBT, psychodynamic therapy Esketamine Nasal Spray (Spravato)	Pharmacotherapy Augmentation ECT Psychotherapy: CBT Limited Access to Esketamine	Pharmacotherapy Augmentation ECT rTMS (approved by NICE) Psychotherapy: CBT Esketamine Nasal Spray (Spravato)
Post‑Traumatic Stress Disorder (PTSD)	Eye Movement Desensitization and Reprocessing (EMDR) Trauma‑Focused CBT Pharmacotherapy: SSRIs (paroxetine, sertraline)	EMDR Trauma‑Focused CBT Pharmacotherapy: SSRIs, venlafaxine Trauma‑Focused Psychotherapy	Pharmacotherapy: SSRIs Limited Use of EMDR Trauma‑Focused CBT EMDR Pharmacotherapy: SSRIs Prazosin (off‑label for nightmares)	Pharmacotherapy: SSRIs Prazosin (off‑label for nightmares)
Major Depressive Disorder (MDD)	Antidepressants: SSRIs, SNRIs Psychotherapy: CBT Combined Treatment Lifestyle Interventions	Antidepressants: SSRIs, SNRIs, TCAs Psychotherapy: CBT, psychodynamic therapy Combined Treatment	Antidepressants: SSRIs, SNRIs Psychotherapy: CBT Combined Treatment	Antidepressants: SSRIs, SNRIs Psychotherapy: CBT, interpersonal therapy Combined Treatment
Anxiety Disorders (SAD, GAD)	Antidepressants: SSRIs, SNRIs Psychotherapy: CBT Benzodiazepines (short‑term use) Pregabalin (for GAD)	Antidepressants: SSRIs, SNRIs Psychotherapy: CBT, psychodynamic therapy Benzodiazepines (short‑term use) Pregabalin	Antidepressants: SSRIs, SNRIs Psychotherapy: CBT Benzodiazepines (short‑term use) Buspirone	Antidepressants: SSRIs, SNRIs Psychotherapy: CBT Benzodiazepines (short‑term use) Pregabalin (for GAD) Buspirone

Notes

TRD (Treatment-Resistant Depression):
- Netherlands (NL): Emphasis on pharmacotherapy augmentation, ECT, rTMS, and psychotherapy. Esketamine nasal spray is available but with limited use.
- Germany (DE): Similar to NL, with the addition of psychodynamic therapy. Esketamine nasal spray (Spravato) is approved and utilised.
- Czech Republic (CZ): Standard augmentation strategies and ECT are common. Access to newer treatments like esketamine may be limited.
- United Kingdom (UK): Follows NICE guidelines, utilising pharmacotherapy augmentation, ECT, rTMS, and esketamine nasal spray.
PTSD (Post-Traumatic Stress Disorder):
- NL & DE: EMDR is widely accepted and practised, along with trauma‑focused CBT and pharmacotherapy.
- CZ: Trauma‑focused psychotherapy is standard, with SSRIs commonly prescribed. EMDR use is growing but not as widespread.
- UK: Trauma‑focused CBT and EMDR are recommended by NICE. Pharmacotherapy is considered when psychotherapy is not effective or feasible.
MDD (Major Depressive Disorder):
- All Countries: Standard treatment involves antidepressants (primarily SSRIs and SNRIs) and psychotherapy (mainly CBT). Combined treatment approaches are common.
Anxiety Disorders (SAD, GAD):
- All Countries: First‑line treatments are SSRIs and SNRIs, along with CBT. Benzodiazepines are used cautiously for short‑term relief. Pregabalin is specifically noted for GAD in NL, DE, and UK.
Additional Considerations:
- Psychotherapy Approaches:
  - CBT is the most commonly used psychotherapy across all countries.
  - Psychodynamic Therapy is more prevalent in DE.
  - Interpersonal Therapy is recognised in the UK for MDD.
- Pharmacotherapy Details:
  - SSRIs (Selective Serotonin Reuptake Inhibitors): Commonly prescribed include sertraline, paroxetine, and fluoxetine.
  - SNRIs (Serotonin‑Norepinephrine Reuptake Inhibitors): Venlafaxine and duloxetine are frequently used.
  - Benzodiazepines: Used with caution due to dependency risks; primarily for acute anxiety symptoms.
  - Pregabalin: Approved for GAD in several countries; usage may vary.
- Innovative Treatments:
  - Esketamine Nasal Spray (Spravato): Approved for TRD in DE and UK; availability and acceptance are increasing in NL.
  - rTMS: Approved and used in NL, DE, and UK for TRD; availability may be limited in CZ.

14.4.2 Primary and Secondary Endpoints

Condition	Commonly Used Measures	Primary/Secondary	Outcomes in Psychedelic Studies
MDD/TRD	MADRS (Montgomery Asberg Depression Rating Scale)	Primary	Significant reductions in MADRS scores in psilocybin trials (e.g., Goodwin et al., 2022).
MDD/TRD	QIDS-SR-16 (Quick Inventory of Depressive Symptomatology-Self Report)	Primary/Secondary	Improved remission rates in psilocybin vs. escitalopram studies (Carhart-Harris et al., 2021).
MDD/TRD	HAM-D (Hamilton Depression Rating Scale)	Secondary	HAM-D reductions observed alongside MADRS improvements, though less commonly reported.
PTSD	CAPS-5 (Clinician-Administered PTSD Scale)	Primary	MDMA-assisted therapy showed significant CAPS-5 score reductions (Mitchell et al., 2023).
PTSD	PCL-5 (PTSD Checklist for DSM-5)	Secondary	PCL-5 improvements align with MDMA-related symptom relief, though secondary outcome.
Addiction	TLFB (Timeline Followback) for substance use	Primary	Reductions in substance use observed in psilocybin studies for alcohol use disorder (Bogenschutz et al., 2022).
Addiction	ASI (Addiction Severity Index)	Secondary	ASI scores improved but with variability across addiction types.
Suicidality	C-SSRS (Columbia-Suicide Severity Rating Scale)	Primary	Reductions in C-SSRS severity after psychedelic treatment, particularly psilocybin.
Suicidality	Beck Scale for Suicide Ideation (BSS)	Secondary	BSS scores dropped significantly post-therapy in early psilocybin trials.
Anxiety Disorders	STAI (State-Trait Anxiety Inventory)	Primary	Marked STAI reductions in trials for anxiety associated with life-threatening illness.
Anxiety Disorders	HAM-A (Hamilton Anxiety Rating Scale)	Secondary	HAM-A improvements demonstrated in LSD and psilocybin trials for SAD (Gründer et al., 2024).