Trial PaperAnxiety DisordersChronic PainDepressive DisordersPTSDMajor Depressive Disorder (MDD)MicrodosingImmunology & InflammationKetamine

Ketamine-assisted psychotherapy treatment of chronic pain and comorbid depression: a pilot study of two approaches

This observational pilot of ten people with chronic pain and comorbid major depressive disorder compared a high‑dose intramuscular "psychedelic" KAPT protocol with a low‑dose sublingual "psycholytic" protocol and found reductions in depression, pain, anxiety and PTSD symptoms overall, with larger and more consistent decreases in the psychedelic group though differences were not statistically significant given the small sample. The authors conclude KAPT may be beneficial for chronic pain/MDD comorbidity and recommend larger controlled trials to determine optimal dosing and administration.

Authors

  • Batievsky, D.
  • Weiner, M.
  • Kaplan, S. B.

Published

Frontiers in Pain Research
individual Study

Abstract

Chronic pain and depression diagnoses are skyrocketing. There is an urgent need for more effective treatments. Ketamine was recently established to alleviate pain and depression, but many gaps remain in the scientific literature. This paper reports the findings of an observational preliminary study that explored the efficacy of ketamine-assisted psychotherapy (KAPT) for chronic pain/major depressive disorder (MDD) comorbidity. Researchers evaluated two KAPT approaches to determine optimal route of administration/dose. Ten individuals diagnosed with a chronic pain disorder and MDD receiving KAPT were recruited: five individuals pursuing the psychedelic approach (high doses administered intramuscularly 24 h before therapy) and five individuals pursuing the psycholytic approach (low doses administered sublingually via oral lozenges during therapy). To evaluate differences between altered states of consciousness each approach induces, participants completed the Mystical Experience Questionnaire (MEQ30) after their first (T-1), third (T-2) and sixth/final (T-3) treatment sessions. Primary outcomes were change in Beck Depression Inventory (BDI) scores and Brief Pain Inventory (BPI) Short Form scores from baseline (T0) to (T-1)–(T-3). Secondary outcomes were changes in Generalized Anxiety Disorder (GAD-7) Scale scores and Post-Traumatic Stress Disorder Checklist (PCL-5) scores at each timepoint. Statistically significant differences between each approach were not observed, but the small sample’s limited statistical power makes changes seen worth noting. All participants’ symptoms declined throughout treatment. Psychedelic treatment participants saw a larger, more consistent decrease. Researchers conclude that KAPT may be effective for treating chronic pain/MDD comorbidity, anxiety and Post-Traumatic Stress Disorder (PTSD). Findings imply that the psychedelic approach may be more effective. This pilot study serves as a basis for more extensive research that will inform how clinicians administer treatment to optimize outcomes.

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Research Summary of 'Ketamine-assisted psychotherapy treatment of chronic pain and comorbid depression: a pilot study of two approaches'

Introduction

Araya and colleagues frame the study within rising rates of both major depressive disorder (MDD) and chronic pain in the US, and the limited effectiveness of standard pharmacological and psychotherapeutic approaches for many patients. They note ketamine's multiple putative mechanisms—NMDA antagonism leading to enhanced glutamatergic/AMPA signalling and synaptogenesis, anti-inflammatory effects, modulation of cortical dynamics and dopamine availability, and distinct subjective psychological effects including altered states and trauma processing—and argue these mechanisms may be relevant to both depression and centrally sensitised pain. The authors highlight several gaps in the literature: uncertainty about optimal route of administration (beyond IV data), uncertainty about whether higher doses that produce altered states are necessary for therapeutic benefit, limited study of ketamine paired with psychotherapy, and scarce data on ketamine for co-occurring chronic pain and depression. This pilot study therefore set out to examine two clinical KAPT (ketamine-assisted psychotherapy) approaches in patients with comorbid MDD and a chronic pain disorder. Specifically, the investigators compared a ‘‘psychedelic’’ model (higher intramuscular doses given 24 hours before therapy) with a ‘‘psycholytic’’ model (lower oral/sublingual doses administered during therapy), asking whether route and dose (and the altered states they produce) differentially affect depressive, pain, anxiety, and PTSD symptoms. The authors present this as an initial, observational contribution intended to guide larger, controlled studies.

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References (10)

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