A Multicriteria Decision Analysis Comparing Pharmacotherapy for Chronic Neuropathic Pain, Including Cannabinoids and Cannabis-Based Medical Products

Abstract

Background: Pharmacological management of chronic neuropathic pain (CNP) still represents a major clinical challenge. Collective harnessing of both the scientific evidence base and clinical experience (of clinicians and patients) can play a key role in informing treatment pathways and contribute to the debate on specific treatments (e.g., cannabinoids). A group of expert clinicians (pain specialists and psychiatrists), scientists, and patient representatives convened to assess the relative benefit-safety balance of 12 pharmacological treatments, including orally administered cannabinoids/cannabis-based medicinal products, for the treatment of CNP in adults. Methods: A decision conference provided the process of creating a multicriteria decision analysis (MCDA) model, in which the group collectively scored the drugs on 17 effect criteria relevant to benefits and safety and then weighted the criteria for their clinical relevance. Findings: Cannabis-based medicinal products consisting of tetrahydrocannabinol/cannabidiol (THC/CBD), in a 1:1 ratio, achieved the highest overall score, 79 (out of 100), followed by CBD dominant at 75, then THC dominant at 72. Duloxetine and the gabapentinoids scored in the 60s, amitriptyline, tramadol, and ibuprofen in the 50s, methadone and oxycodone in the 40s, and morphine and fentanyl in the 30s. Sensitivity analyses showed that even if the pain reduction and quality-of-life scores for THC/CBD and THC are halved, their benefit-safety balances remain better than those of the noncannabinoid drugs. Interpretation: The benefit-safety profiles for cannabinoids were higher than for other commonly used medications for CNP largely because they contribute more to quality of life and have a more favorable side effect profile. The results also reflect the shortcomings of alternative pharmacological treatments with respect to safety and mitigation of neuropathic pain symptoms. Further high-quality clinical trials and systematic comprehensive capture of clinical experience with cannabinoids is warranted. These results demonstrate once again the complexity and multimodal mechanisms underlying the clinical experience and impact of chronic pain.

Keywords: CBMP; MCDA; analgesics; cannabis-based medical products; multicriteria decision analysis; neuropathic pain.

FIG. 1.

The Effects Tree for assessing the relative benefit–safety of neuropathic pain pharmacotherapy.

FIG. 2.

Scores agreed by participants for pain relief.

FIG. 3.

The overall weighted preference values for the neuropathic pain pharmacotherapies. More blue means more benefit, more red indicates more safety.

FIG. 4.

Contributions to the totals by each of the 17 effects. The top blue (pain relief) and yellow (quality of life) sections of each bar show the magnitude of benefits; the rest show safety.

FIG. 5.

Benefit preference values versus the safety preference values shown in Table 3.

FIG. 6.

Sensitivity analysis for pain relief.

FIG. 7.

The results of sensitivity analyses on the input preference scores for THC/CBD and THC. Halving the Pain Control scores gives the left plot. An additional halving of the quality-of-life scores is shown in the right plot. CBD, cannabidiol; THC, tetrahydrocannabinol.

FIG. 8.

THC/CBD is better for quality of life, but duloxetine is better for pain relief. This pattern is similar for gabapentinoids and amitriptyline as comparators with THC/CBD.