Carbamazepine for Chronic Muscle Pain: A Retrospective Assessment of Indications, Side Effects, and Treatment Response

Abstract

Myopathies fall under the umbrella of rare diseases, however, muscle pain is a relevant, under-recognized symptom with limited treatment options. Carbamazepine is an oral sodium channel blocker approved for the treatment of seizures and neuropathic pain. In 54 individuals receiving carbamazepine for muscle pain, we retrospectively assessed the subjective treatment response, side effects, and reasons for carbamazepine discontinuation. The underlying diagnoses leading to muscle pain were diverse, ranging from metabolic (n = 5) and other hereditary (n = 9) to acquired (n = 2) myopathies and myotonia syndromes (n = 22). Under carbamazepine (daily dose 254 ± 138 mg), patients reported a significant reduction of pain, quantified by an 11-point numeric rating scale (−1.9 ± 1.8, p < 0.001). Compared to age- and sex-matched controls, our sensory assessment revealed a significant dysfunction of Aδ-nerve fibers in patients with chronic muscle pain. Neuropathic pain components identified by the painDETECT questionnaire or quantitative sensory testing did not seem to influence the reported treatment response. Side effects (n = 18) such as fatigue, elevated liver enzymes, and diarrhea, as well as lack of pain improvement (n = 6), led to carbamazepine discontinuation in 44.4% (24/54). Mediated by dysfunctional Aδ-nerve fibers, muscle pain is common in a variety of myopathies. Carbamazepine may reduce pain levels, but comes with therapy-limiting side effects.

Keywords: carbamazepine; myalgia; myopathy; neuropathic pain; quantitative sensory testing.

Figure 1

(a,b). Study collective. (a) Screening process and selection of our study cohort. Out of 1683 patients and 3168 visits, 54 patients fulfilled our inclusion criteria, which were adult myopathy patients (>18 years) that were symptomatically treated with carbamazepine due to chronic muscle pain. Patients with carbamazepine treatment due to other indications were not included. (b) Overview of all included muscle diseases. The most frequent diagnoses were myopathies of unknown origin and cramp-fasciculation syndrome, including benign forms and neuromyotonia. We also included very rare diseases such as nemaline myopathy and central core myopathy.

Figure 2

Sensory profiles. Z-score sensory profile of all patients (n = 24) compared with a sex-, age -, and location-matched control group (n = 24). The profile shows loss of function for non-painful thermal stimuli (CDT, WDT, TSL) corresponding to small fiber dysfunction. The presence of mechanical hyperalgesia to pinprick (MPT) and dynamic mechanic allodynia (DMA) points towards possible secondary central sensitization of the nociceptive system. The vibrotactile hypoesthesia (VDT) is consistent with large fiber involvement in this patient group. The increased number of paradoxical heat sensations (PHS) might be attributed to peripherally or centrally disturbed thermal discrimination. Stars denote the level of significance with * p < 0.05; ** p < 0.01 (one-way ANOVA).

Figure 3

(a–c). NRS evaluation. (a) Response to therapy with carbamazepine. Patients were asked to score their pain levels before and under carbamazepine treatment. The NRS level was significantly lower under treatment. (b) NRS reduction did not correlate with QST results. The y-axis depicts the change in NRS before and under treatment. There was no significant difference in pain reduction between patients with normal and abnormal QST results. (c) NRS reduction correlated with painDETECT-scores. The y-axis depicts the change in NRS before and after treatment. Pain reduction was significantly greater in patients with a normal painDETECT questionnaire (p < 0.05) than in patients, whose questionnaire showed unclear results or results indicative of neuropathic pain. Stars denote the level of significance with * p < 0.05; *** p < 0.001.