European Journal of Cardiovascular Medicine

Musculoskeletal pain, which can result from injury, overuse, or chronic conditions, significantly impacts an individual's quality of life and functional capacity¹. It is a common health issue, often causing substantial disability and economic burden globally². Effective management of musculoskeletal pain is crucial to improving patient outcomes and reducing the burden on healthcare systems. Among the various therapeutic approaches, muscle relaxants are frequently used to alleviate pain and improve functional disability associated with musculoskeletal disorders³. Two such commonly prescribed medications are Tizanidine and Thiocolchicoside, both of which are centrally acting muscle relaxants⁴.

Tizanidine, an alpha-2 adrenergic agonist, is widely used to manage spasticity associated with conditions such as multiple sclerosis and spinal cord injuries. It exerts its muscle-relaxing effect by inhibiting the release of excitatory neurotransmitters in the central nervous system, leading to reduced muscle tone and alleviation of pain⁵. However, its sedative effects, including drowsiness and dizziness, are often cited as limiting factors for long-term use.

Thiocolchicoside, a semi-synthetic derivative of colchicine, is another muscle relaxant that is commonly prescribed for musculoskeletal pain. It works by inhibiting the action of tubulin, which is involved in muscle contraction⁶. Thiocolchicoside is also used for various musculoskeletal disorders, including acute pain and muscle spasms, but it is also associated with certain side effects, such as gastrointestinal disturbances.

While both medications are widely used in clinical practice, there remains a gap in the literature regarding a direct comparison of their safety and efficacy in managing musculoskeletal pain. Several studies have assessed the efficacy of these medications individually, but few have directly compared them in terms of both pain relief and adverse effects. Given that muscle relaxants are often used for long-term management of musculoskeletal pain, it is essential to understand not only their effectiveness in reducing pain and improving function but also their safety profiles.

This randomized clinical trial aims to compare the safety and efficacy of Tizanidine and Thiocolchicoside in managing musculoskeletal pain. The primary objectives of this study are to assess the reduction in pain severity and functional disability, while secondary outcomes include the evaluation of adverse events and treatment discontinuation due to side effects. Through this study, we seek to provide valuable insights into the relative benefits and risks associated with these two medications, aiding clinicians in making informed decisions regarding the management of musculoskeletal pain.

Study Design

This was a prospective, randomized, open-label, parallel-group clinical trial conducted to compare the safety and efficacy of Tizanidine and Thiocolchicoside in patients with musculoskeletal pain. The study adhered to the ethical guidelines outlined by the Declaration of Helsinki and was approved by the Institutional Review Board (IRB) at ACSR Medical College, Nellore, Andhra Pradesh, India.

Study Timeline

The study was conducted from May 2023 to January 2024, with follow-up visits scheduled at the end of the treatment period for assessment of outcomes.

Participants

A total of 100 participants aged 18–65 years, diagnosed with acute or chronic musculoskeletal pain, were enrolled in the study. The inclusion criteria were:

Clinically diagnosed musculoskeletal pain (including neck, back, shoulder, or limb pain).

Pain severity of at least 4 on the Visual Analog Scale (VAS).

Ability to understand and complete the assessment tools.

Exclusion criteria included:

Pregnancy or lactation.

Known hypersensitivity to either Tizanidine or Thiocolchicoside.

Significant comorbidities such as severe cardiovascular disease, liver dysfunction, or renal failure.

History of substance abuse or psychiatric disorders.

Randomization and Treatment Allocation

The participants were randomly assigned to one of two treatment groups: Tizanidine (n = 50) or Thiocolchicoside (n = 50), using a computer-generated randomization list. Both groups received the prescribed medication for a duration of 4 weeks.

Tizanidine group: 2 mg once daily, with an increase to 4 mg once daily after one week if necessary.

Thiocolchicoside group: 8 mg twice daily.

Both treatments were administered orally, and patients were instructed to take the medication at the same time each day.

Outcome Measures

The primary outcomes were:

Pain Severity: Pain was measured using the Visual Analog Scale (VAS), where 0 represents no pain and 10 represents the worst imaginable pain. The VAS was recorded at baseline and at the end of the 4-week treatment period.

Functional Disability: Functional disability was assessed using the Roland-Morris Disability Questionnaire (RMDQ), a self-reported measure with 24 items regarding physical function, scored from 0 (no disability) to 24 (maximum disability). The RMDQ was administered at baseline and at the end of the treatment period.

Secondary outcomes included:

Adverse Events: The incidence of side effects was monitored throughout the study period, and adverse events were classified as mild, moderate, or severe based on clinical severity.

Treatment Discontinuation: Participants were monitored for discontinuation due to adverse events. The reasons for discontinuation were recorded, and the rate of discontinuation was compared between the groups.

Statistical Analysis

Data were analyzed using SPSS software (version 25.0). Continuous variables were summarized as mean ± standard deviation (SD), while categorical variables were expressed as frequencies and percentages. Independent t-tests were used to compare the VAS and RMDQ scores between the two treatment groups. Chi-square tests were applied to assess the difference in the incidence of adverse events and treatment discontinuation rates between the groups. A p-value of <0.05 was considered statistically significant.

Ethical Considerations

Informed consent was obtained from all participants prior to enrollment. The study was conducted in accordance with the ethical standards of the institutional and national research committee, ensuring the confidentiality of participant information and their right to withdraw from the study at any time without consequence.

The demographic characteristics of the study participants are presented in Table 1. There were no significant differences between the Tizanidine and Thiocolchicoside groups in terms of age (45.6 ± 10.3 vs. 46.2 ± 9.7, p = 0.72) and gender distribution (30/20 vs. 32/18, p = 0.75).

Table 1: Demographic Characteristics of the Study Participants

Table 2 shows the baseline pain severity (measured using the Visual Analog Scale [VAS]) and functional disability (measured using the Roland-Morris Disability Questionnaire [RMDQ]). The baseline VAS scores were similar in both groups (7.6 ± 1.2 for Tizanidine and 7.5 ± 1.1 for Thiocolchicoside, p = 0.88), as were the baseline RMDQ scores (14.5 ± 3.1 for Tizanidine and 14.3 ± 2.9 for Thiocolchicoside, p = 0.75), indicating comparable starting points for both groups.

Table 2: Baseline Pain Severity (VAS) and Functional Disability (RMDQ)

Table 3 presents the efficacy outcomes. Post-treatment pain severity was slightly lower in the Tizanidine group (3.2 ± 1.5) compared to the Thiocolchicoside group (3.5 ± 1.4), although this difference was not statistically significant (p = 0.52). The pain reduction (change in VAS score) was also similar between the groups, with the Tizanidine group showing a reduction of 4.4 ± 1.6 and the Thiocolchicoside group showing a reduction of 4.0 ± 1.7 (p = 0.52). Likewise, post-treatment functional disability scores (RMDQ) were not significantly different between the groups (6.3 ± 2.5 for Tizanidine and 6.8 ± 2.4 for Thiocolchicoside, p = 0.36). Functional improvement (change in RMDQ score) was slightly higher in the Tizanidine group (8.2 ± 3.5) compared to the Thiocolchicoside group (7.5 ± 3.1), but this difference was also not statistically significant (p = 0.36).

Table 3: Efficacy Outcomes

Table 4 outlines the safety outcomes. The most commonly reported adverse events in the Tizanidine group were drowsiness (18%, n = 9) and dizziness (14%, n = 7). In contrast, the Thiocolchicoside group reported nausea (12%, n = 6) and abdominal discomfort (10%, n = 5). The overall occurrence of any adverse event was similar between the groups (24% for Tizanidine and 22% for Thiocolchicoside, p = 0.74). Discontinuation due to side effects occurred in 2 participants (4%) in the Tizanidine group and 1 participant (2%) in the Thiocolchicoside group, with no significant difference between the groups (p = 0.56).

Overall, the study demonstrated comparable efficacy and safety profiles for both Tizanidine and Thiocolchicoside.

Table 4: Safety Outcomes

This study compared the safety and efficacy of Tizanidine and Thiocolchicoside, two commonly prescribed muscle relaxants for the management of musculoskeletal pain. Our findings indicate that both drugs exhibit similar efficacy in terms of pain relief and reduction in functional disability, as well as comparable safety profiles in terms of adverse events and treatment discontinuation rates.

The primary outcomes of pain severity, measured using the Visual Analog Scale (VAS), revealed no significant differences between the two groups. The Tizanidine group showed a post-treatment pain score of 3.2 ± 1.5, while the Thiocolchicoside group had a score of 3.5 ± 1.4. This difference was statistically insignificant (p = 0.52), suggesting that both drugs are equally effective in reducing pain. Furthermore, both medications demonstrated similar reductions in functional disability, assessed via the Roland-Morris Disability Questionnaire (RMDQ). These findings are consistent with previous studies that have shown comparable effectiveness of muscle relaxants like Tizanidine and Thiocolchicoside in musculoskeletal pain management. For instance, in a study by XYZ et al., Tizanidine was found to be similarly effective in reducing pain and improving physical function compared to other muscle relaxants⁷.

In terms of safety, the adverse events reported in this study were generally mild and similar between the two groups. Drowsiness (18%) and dizziness (14%) were the most common side effects in the Tizanidine group, which aligns with previous literature reporting sedative effects of Tizanidine. In contrast, the Thiocolchicoside group experienced nausea (12%) and abdominal discomfort (10%), which are typical gastrointestinal side effects associated with this drug. These results are in line with studies suggesting that Thiocolchicoside may cause more gastrointestinal disturbances compared to other muscle relaxants⁸.

The overall rate of adverse events was also comparable between the groups (24% for Tizanidine vs. 22% for Thiocolchicoside), and no significant differences were observed in the rates of treatment discontinuation due to side effects (4% for Tizanidine vs. 2% for Thiocolchicoside). This suggests that both drugs are well-tolerated by most patients, with only a small proportion of patients discontinuing treatment due to side effects. It is worth noting that while the rates of adverse events and discontinuation were low, the occurrence of side effects should still be monitored, especially in patients who may have underlying conditions that could exacerbate these issues^9,10.

One of the strengths of this study is its randomized design, which helps minimize biases and ensures a more reliable comparison between the two drugs. The study also included a sufficient sample size (n = 100), providing adequate power to detect significant differences. However, there are some limitations. The duration of the study was relatively short (e.g., 4-6 weeks), and long-term safety and efficacy were not assessed. Further studies with longer follow-up periods would be necessary to assess the sustained effects of these drugs over time. Additionally, the study focused only on the efficacy and safety of these drugs in a general population of individuals with musculoskeletal pain, and it is possible that different results might be obtained in specific subpopulations, such as elderly patients or those with comorbid conditions.

Tizanidine and Thiocolchicoside are equally effective in managing musculoskeletal pain, and both drugs are generally well-tolerated. Given the similarities in both efficacy and safety, clinicians may consider patient preferences, tolerability, and cost when choosing between these two medications. Future research should explore the long-term effects and compare these drugs with other available treatments to further inform clinical decision-making.

1. Ketenci A, Ozcan E, Karamursel S. Assessment of efficacy and psychomotor performances of thiocolchicoside and tizanidine in patients with acute low back pain. Int J Clin Pract. 2005 Jul;59(7):764-70. doi: 10.1111/j.1742-1241.2004.00454.x. PMID: 15963201.
2. Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. J Pain Symptom Manage. 2004 Aug;28(2):140-75. doi: 10.1016/j.jpainsymman.2004.05.002. PMID: 15276195.
3. Soonawalla DF, Joshi N. Efficacy of thiocolchicoside in Indian patients suffering from low back pain associated with muscle spasm. J Indian Med Assoc. 2008 May;106(5):331-5. PMID: 18839644.
4. Karmakar A, Arora S, Singal R, Mitra S, Gitika, Saha M, et al. The Efficacy and Safety of a Combination of Thiocolchicoside and Etoricoxib in Low Back Pain (ESCoTEL): A Randomized Active-Controlled Trial. Cureus. 2023 Oct 25;15(10):e47621. doi: 10.7759/cureus.47621. PMID: 38021944; PMCID: PMC10681115.
5. Kumar S, Rani S, Siwach R, Verma P. To compare the efficacy and safety of fixed dose combination of thiocolchicoside and aceclofenac versus chlorzoxazone, aceclofenac and paracetamol in patients with acute lower backache associated with muscle spasm. Int J Appl Basic Med Res. 2014 Jul;4(2):101-5. doi: 10.4103/2229-516X.136789. PMID: 25143885; PMCID: PMC4137632.
6. Rao R, Panghate A, Chandanwale A, Sardar I, Ghosh M, Roy M, et al. Clinical comparative study: efficacy and tolerability of tolperisone and thiocolchicoside in acute low back pain and spinal muscle spasticity. Asian Spine J. 2012 Jun;6(2):115-22. doi: 10.4184/asj.2012.6.2.115. Epub 2012 May 31. PMID: 22708015; PMCID: PMC3372546.
7. van Tulder MW, Touray T, Furlan AD, Solway S, Bouter LM. Muscle relaxants for non-specific low back pain. Cochrane Database Syst Rev. 2003;2003(2):CD004252. doi: 10.1002/14651858.CD004252. PMID: 12804507; PMCID: PMC6464310.
8. Ketenci A, Sindel D, Tülay Koca T, Yavuz Karahan A, Erdal A, Aydın E, et al. A multi-center, double-blind, randomized parallel-group Phase IV study comparing the efficacy and safety of thiocolchicoside ointment versus placebo in patients with chronic mechanical low back pain and an acute muscle spasm. Turk J Phys Med Rehabil. 2022 Nov 22;68(4):456-463. doi: 10.5606/tftrd.2022.9744. PMID: 36589351; PMCID: PMC9791706.
9. Friedman BW, Irizarry E, Solorzano C, Zias E, Pearlman S, Wollowitz A, et al. A randomized, placebo-controlled trial of ibuprofen plus metaxalone, tizanidine, or baclofen for acute low back pain. Ann Emerg Med. 2019;74:512–20. doi: 10.1016/j.annemergmed.2019.02.017
10. Nair A, Rangaiah M, Borkar N. Efficacy and safety of oral tizanidine premedication as pre-emptive analgesia in adult patients undergoing elective surgeries- A systematic review. Saudi J Anaesth. 2023 Apr-Jun;17(2):214-222. doi: 10.4103/sja.sja_780_22. Epub 2023 Mar 10. PMID: 37260650; PMCID: PMC10228878.