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Randomized Controlled Trial
. 2022 Oct;66(4):404-410.
doi: 10.1002/mus.27637. Epub 2022 Jun 24.

A secondary analysis of PAIN-CONTRoLS: Pain's impact on sleep, fatigue, and activities of daily living

Salman F Bhai  1   2 , Alexandra Brown  3 , Byron Gajewski  3 , Kim S Kimminau  4 , Lemuel R Waitman  5 , Mamatha Pasnoor  6 , Richard J Barohn  7 ; PAIN-CONTRoLS Study Team
Affiliations
Randomized Controlled Trial

A secondary analysis of PAIN-CONTRoLS: Pain's impact on sleep, fatigue, and activities of daily living

Salman F Bhai et al. Muscle Nerve. 2022 Oct.

Abstract

Introduction/aims: Peripheral neuropathies commonly affect quality of life of patients due to pain, sleep disturbances, and fatigue, although trials have not adequately explored these domains of care. The aim of this study was to assess the impact of nortriptyline, duloxetine, pregabalin, and mexiletine on pain, sleep, and fatigue in patients diagnosed with cryptogenic sensory polyneuropathy (CSPN).

Methods: We implemented a Bayesian adaptive design to perform a 12-wk multisite, randomized, prospective, open-label comparative effectiveness study in 402 CSPN patients. Participants received either nortriptyline (n = 134), duloxetine (n = 126), pregabalin (n = 73), or mexiletine (n = 69). At prespecified analysis timepoints, secondary outcomes, Patient Reported Outcomes Measurement Information System (PROMIS) surveys including Short Form (SF)-12, pain interference, fatigue, and sleep disturbance, were collected.

Results: Mexiletine had the highest quit rate (58%) due to gastrointestinal side effects, while nortriptyline (38%) and duloxetine (38%) had the lowest quit rates. If tolerated for the full 12 wk of the study, mexiletine had the highest probability (>90%) of positive outcomes for improvements in pain interference and fatigue. There was no significant difference among the medications for sleep disturbance or SF-12 scores. Adverse events and lack of efficacy were the two most common reasons for cessation of therapy.

Discussion: Physicians caring for patients with CSPN should consider mexiletine to address pain and fatigue, although nortriptyline and duloxetine are better medications to trial first since they are better tolerated. Future research should compare other commonly used medications for CSPN to determine evidence-based treatment strategies.

Keywords: fatigue; pain; randomized control trial; sensory neuropathy; sleep.

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Conflict of interest statement

Disclosure of Conflicts of Interest

None of the authors has any conflict of interest to disclose.

Figures

Figure 1:
Figure 1:
Median Quit Rates Across Time
Figure 2:
Figure 2:
Likert Pain Scale Hierarchical Linear Model and PROMIS Pain Interference Hierarchical Linear Model
Figure 3:
Figure 3:
PROMIS Fatigue Interference Hierarchical Linear Model and PROMIS Sleep Interference Hierarchical Linear Model
Figure 4:
Figure 4:
SF-12 Physical Component Scale (PCS) Hierarchical Linear Model and SF-12 Mental Component Scale (MCS) Hierarchical Linear Model
See this image and copyright information in PMC

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