Journal Article Annotations
2024, 4th Quarter

Chronic Pain

Annotations by Alissa Hutto, MD
January, 2025

Non-opioid psychiatric medications for chronic pain: systematic review and meta-analysis.

PUBLICATION #1 — Chronic Pain

Non-opioid psychiatric medications for chronic pain: systematic review and meta-analysis.

Shahana Ayub, Anil Krishna Bachu, Lakshit Jain, Shanli Parnia, Siddhi Bhivandkar, Rizwan Ahmed, Jasleen Kaur, Surya Karlapati, Sakshi Prasad, Hansini Kochhar, Oghenetega Esther Ayisire, Saloni Mitra, Bikona Ghosh, Sushma Srinivas, Sahar Ashraf, Bhavani Nagendra Papudesi, Palash Kumar Malo, Shoib Sheikh, Michael Hsu, Domenico De Berardis, Saeed Ahmed.

Abstract: Front Pain Res (Lausanne). 2024 Oct 10:5:1398442. doi: 10.3389/fpain.2024.1398442. eCollection 2024.

Background
The escalating number of deaths related to opioid usage has intensified the pursuit of non-opioid alternatives for managing chronic pain. It’s often observed that psychiatric comorbidities coexist in patients suffering from chronic pain. There are a variety of psychotropic medications that have demonstrated effectiveness in treating both psychiatric symptoms and pain. This systematic review and meta-analysis aim to assess the effectiveness of various psychiatric drugs in managing specific types of chronic pain, including fibromyalgia, neuropathic pain, and chronic low back pain.

Methods
A comprehensive search of five major databases was conducted through February 2023 to identify randomized controlled trials (RCTs) that met our inclusion criteria, focusing on outpatients Over 18 years of age with chronic pain. The study assessed the effectiveness of duloxetine, mirogabalin, pregabalin, gabapentin, and tricyclic antidepressants (TCAs), including serotonin-norepinephrine reuptake inhibitors (SNRIs), across various chronic pain conditions such as fibromyalgia, neuropathic pain, and chronic low back pain. The primary outcome measures included pain reduction, improvement in function, and quality of life. Of the 29 RCTs in the systematic review, 20 studies qualified for the meta-analysis. The analysis was stratified by pain type and treatment duration (short-term ≤14 weeks vs. long-term >14 weeks), using Hedge’s g standardized mean differences and a random-effects model, along with sensitivity and subgroup analyses.

Results
The overall short-term intervention effect across all studies was significant (SMD −1.45, 95% CI −2.15 to −0.75, p < 0.001), with considerable heterogeneity (I² = 99%). For fibromyalgia, both duloxetine and mirogabalin demonstrated substantial efficacy with SMDs of −2.42 (95% CI −3.67 to −1.18, p < 0.0001) and −2.10 (95% CI −3.28 to −0.92, p = 0.0005), respectively. Conversely, treatments for neuropathic pain and chronic low back pain, including those with amitriptyline and desipramine, did not show significant benefits. The effectiveness of gabapentin could not be conclusively determined due to limited representation in the data. Additionally, no consistent long-term benefits were observed for any of the medications.

Conclusions
While the results of this study underscore the importance of exploring non-opioid alternatives for chronic pain management, particularly in light of the opioid crisis, it is crucial to interpret the findings carefully. Our analysis suggests that certain psychiatric medications, such Duloxetine and mirogabalin demonstrated significant short-term efficacy in fibromyalgia patients. However, their effectiveness in treating neuropathic pain and chronic low back pain was not statistically significant. Additionally, the effectiveness of gabapentin and other medications, such as pregabalin for neuropathic pain, could not be conclusively determined due to limited data and high study heterogeneity. No consistent long-term benefits were observed for any of the drugs studied, raising questions about their sustained efficacy in chronic pain management. These findings highlight the need for further research to understand better the role of psychiatric medications in managing specific chronic pain conditions without prematurely concluding that they are ineffective or unsuitable for these purposes.

Annotation

The finding:
The study focused on non-opioid psychiatric drugs, and they aimed to update the current knowledge base about using psychiatric medications for pain treatment with the ultimate goal of contributing to guidelines for psychiatrists seeking to use these medications for chronic pain. Through analysis of 20 randomized controlled trials (RCTs), the summary measure of difference in pain scores for psychiatric medication versus placebo was statistically significant, but there was a lot of heterogeneity between trials. This overall significant difference remained in sensitivity analyses, but in subgroup analysis, the only significant effects were from duloxetine and mirogabalin being used in the short term for treatment of fibromyalgia.

Strength and weaknesses:
The study used a comprehensive search of five major databases (PubMed, Scopus, EMBASE, Web of Science, and Cochrane Library) to identify relevant randomized controlled trials as well as a “snowballing method” to find additional studies. They also focused on specific chronic pain conditions, including fibromyalgia, neuropathic pain, and chronic low back pain, which allowed for targeted analysis. The study conducted sensitivity analyses by excluding studies with active placebos, small sample sizes, and high risk of bias, which increases the robustness of the findings. Overall, it felt like a good update on the literature in recent years. There are some caveats however. They note a considerable amount of heterogeneity among the included trials but the high heterogeneity was not resolved in any of the sensitivity analyses. The effectiveness of the medications could not be conclusively determined due to limited data and high study heterogeneity. Additionally, they focused only on psychoactive non-opioid pharmacotherapies, excluding other non-psychoactive treatments such as NSAIDs, lidocaine patches, or capsaicin, and in our real patient population it is highly likely that people with chronic pain will also be on other medications. Adherence rates were not always clearly reported in the reviewed studies, which could have influenced the results. Despite comparing their results with other recent reviews and acknowledging the effects of duloxetine and mirogabalin compared with placebo for fibromyalgia, they were not able to give any specific guidelines.

Relevance:
For consultation-liaison psychiatrists, this review provides a good update on recent literature about some psychiatric medications being used in certain pain conditions, but it is not a practice-changing paper. The findings about duloxetine and mirogabalin may help in discussion with patients who have fibromyalgia, both to suggest a trial may be helpful and possibly to temper long-term expectations. As the authors pointed out, more research is needed to develop actionable guidelines for psychiatric medication use for chronic pain conditions.