Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder, with recurrent, unilateral episodes of severe electric shock-like or stabbing pain from one or more divisions of the trigeminal nerve. The pain is usually brief and paroxysmal and can be triggered by innocuous stimuli such as touching the face, chewing, talking, brushing teeth, or exposure to cold air. While one attack might last only a few seconds to a few minutes, repeated attacks can significantly affect a person's quality of life, sleep, psychological function, social interactions, and physical functioning. The disease occurs more often in older people and often has a high morbidity rate despite a lack of any obvious abnormalities between attacks [1]. The diagnosis of TN is largely clinical and is based on the typical history of episodic facial pain. Neurological exam and imaging, especially MRI when indicated, can help identify secondary causes and neurovascular relationships. Depending on the pathophysiological mechanism and available imaging findings, TN can be considered classical, secondary, or idiopathic. Secondary TNH is caused by multiple sclerosis, posterior fossa lesions, tumors, and other structural abnormalities, and should be suspected, especially in patients with atypical clinical presentations [2]. Most patients can be treated pharmacologically as a first-line approach. Carbamazepine is one of the most widely used medications, as it is known to be effective in the treatment of trigeminal neuralgia and is considered a first-line drug. The therapeutic effect is mostly associated with its ability to inhibit voltage-gated sodium channels, which decrease the excitability of abnormal neurons and repetitive firing. But there is variation in response to treatment among patients, and some patients might still have significant pain. In addition, higher doses of carbamazepine may cause dizziness, drowsiness, nausea, diplopia, and difficulty with walking, which could limit dosage increases and medication adherence [3,4]. Baclofen is a gamma-aminobutyric acid-B receptor agonist that decreases the activity and transmission of excitatory neurotransmitters. It is being studied as a possible alternative or in addition to a drug called carbamazepine for treating trigeminal neuralgia, especially when carbamazepine does not completely control the pain. The pharmacological basis for the use of a combination of carbamazepine and baclofen is due to their complementary mode of action. Carbamazepine is a sodium-channel blocker that can help inhibit pathological neuronal firing, and baclofen can also reduce excitatory neurotransmitter output. Thus, a combination therapy could result in better pain control without significant escalation of carbamazepine dosages [5,6]. Evidence comparing the efficacy of carbamazepine monotherapy to carbamazepine plus baclofen remains relatively limited, especially in typical clinical populations. These variations in outcome effectiveness may reflect differences in patients, disease duration, treatment response, dosage, and outcome assessment. Comparative evaluation of these treatment strategies could therefore be clinically relevant [7].The current study aimed to assess whether carbamazepine alone or carbamazepine with baclofen is more effective for treating trigeminal neuralgia. During follow-up, we assessed pain severity, the number of painful attacks, and clinical response. This study was designed to evaluate the efficacy of adding baclofen to carbamazepine in a well-defined patient population to determine whether adjunctive baclofen is beneficial beyond carbamazepine alone. The results could help doctors choose the right treatment for those with trigeminal neuralgia who need effective, tolerable symptom control [8,9].

Study Objectives

To determine if carbamazepine alone is as effective as carbamazepine plus baclofen in reducing pain severity, frequency of attacks, and improving clinical response in patients with trigeminal neuralgia.

Study Design & Setting

This cross-sectional study Conducted at Department of Pharmacology, Riphah International University, Peshawar from jan 2025 to dec 2025. patients with clinically diagnosed trigeminal neuralgia in the neurology OPD of a Tertiary care teaching hospital during the study period.

Participants

Using consecutive sampling, 100 adult patients clinically diagnosed with trigeminal neuralgia were enrolled. The patients were equally divided into two groups of 50. Group A was treated with carbamazepine alone while Group B was treated with carbamazepine and baclofen. Demographic and clinical data were collected at baseline before treatment began.

Sample Size Calculation

The sample size was determined based on the WHO-recommended sample size for comparing two treatment groups, assuming a clinically meaningful difference in treatment response, a 95% confidence level, and 80% statistical power. To account for potential loss to follow-up, the final sample was 100 patients, with 50 patients in each treatment condition.

Inclusion Criteria

Patients were included if they were ≥18 years of age, had a clinical diagnosis of trigeminal neuralgia, had a clinical history of recurrent paroxysmal pain in the same unilateral facial distribution, and were willing to participate and complete the planned follow-up assessments.

Exclusion Criteria

Patients with a previous surgery of the trigeminal nerve, as well as patients with significant psychiatric illness that would interfere with assessment, pregnancy, known hypersensitivity to the study medications, or any significant hepatic or renal dysfunction were excluded, as were patients with intracranial tumors, multiple sclerosis, or other structural lesions that might have caused secondary trigeminal neuralgia.

Diagnostic and Management Strategy

Diagnosis was made based on typical paroxysmal facial pain and neurological examination, and imaging was performed only when clinically indicated. Group A received carbamazepine, and Group B received carbamazepine plus baclofen, according to standard clinical dosing. The follow-up period was 30 days, during which attack intensity and pain were evaluated.

Statistical Analysis

Data were analyzed using SPSS version 27.0. Data were presented as mean ± standard deviation for continuous variables and frequencies and percentages for categorical variables. Independent-samples t-tests and chi-square tests were used to compare baseline characteristics. Paired statistical tests were used to determine changes within groups, and independent-samples tests were used to determine differences between groups. A p-value <0.05 was considered statistically significant.

We included 100 patients with trigeminal neuralgia: 50 in the carbamazepine group and 50 in the carbamazepine-plus-baclofen group. The overall mean age was 55.2 ± 10.9 years. The mean age was 54.6 ± 11.2 years in Group A and 55.8 ± 10.7 years in Group B, with no statistically significant difference between groups (p=0.58). Baseline mean pain scores were also comparable between Group A (7.8 ± 1.1) and Group B (7.9 ± 1.0; p=0.64). Following 30 days of treatment, pain severity decreased significantly in both groups. The mean pain score decreased to 4.1 ± 1.3 among patients receiving carbamazepine alone and to 2.8 ± 1.2 among those receiving combined therapy. The reduction in pain severity was significantly greater in the combination group than in the monotherapy group (p<0.001). Similarly, the frequency of painful attacks demonstrated a greater reduction among patients receiving carbamazepine plus baclofen. A clinically meaningful treatment response was observed in 32 (64.0%) patients in Group A compared with 41 (82.0%) patients in Group B (p=0.048). Mild dizziness, drowsiness, and nausea were the most commonly reported adverse effects, with no major treatment-related complications observed during follow-up. Overall, combination therapy demonstrated superior short-term symptomatic improvement compared with carbamazepine monotherapy.

Table 1. Baseline Demographic and Clinical Characteristics of Patients

Table 1 presents the baseline demographic and clinical characteristics of patients with trigeminal neuralgia. Values are expressed as mean ± standard deviation or frequency (percentage). TN = trigeminal neuralgia. Independent-samples t-test and chi-square test were used as appropriate.

Table 2. Comparison of Pain Severity Before and After Treatment

Table 2 compares changes in pain severity between the two treatment groups during follow-up. Pain was assessed using a numerical pain rating scale. Data are presented as mean ± standard deviation. A lower score indicates less severe pain. Between-group comparisons were performed using an independent-samples t-test.

Table 3. Comparison of Frequency of Trigeminal Neuralgia Attacks

Table 3 demonstrates the reduction in daily frequency of trigeminal neuralgia attacks during the 30-day follow-up. Values are expressed as mean ± standard deviation. The combination group showed a significantly greater reduction in attack frequency than carbamazepine monotherapy.

Table 4. Treatment Response and Adverse Effects

Table 4 compares treatment response and medication-related adverse effects between the two groups. We defined a clinically meaningful response as substantial improvement in pain severity and reduced attack frequency during follow-up. Data are presented as frequency (percentage). We used the chi-square test or Fisher's exact test where appropriate.

In the current study, we compared carbamazepine plus baclofen with carbamazepine monotherapy in 100 patients with TN, and combination therapy resulted in a significantly greater decrease in pain intensity and attack frequency. At 30 days, the mean pain score was 7.9 ± 1.0 in the combination group, and 7.8 ± 1.1 to 4.1 ± 1.3 in the carbamazepine group (p<0.001). Similarly, more patients achieved a clinically meaningful treatment response with combination therapy (82.0% vs. 64.0%, p=0.048). These outcomes argue for the possible benefit of augmenting carbamazepine treatment with baclofen in patients who have incomplete control of their symptoms from carbamazepine alone [10].Our results suggest that carbamazepine is an effective first-line therapy for TN in line with recent evidence. A systematic review and meta-analysis in 2021 found some evidence of clinically meaningful improvement with carbamazepine, but evidence from randomized studies was limited and had methodological issues. The authors stressed the need for further well-designed trials to assess the efficacy of pharmacologic options and combinations. Recent reviews still confirm carbamazepine and oxcarbazepine as the main first-line drugs and that side effects may limit their long-term use [11,12].This is especially significant as the combination therapy was more effective in our study, since baclofen has a complementary pharmacological action. Carbamazepine has a sodium-channel blocking effect that decreases abnormal neuronal excitability, while baclofen is a GABA-B receptor agonist that decreases excitatory neurotransmission. Recent reviews have supported the theoretical value of these mechanisms by demonstrating baclofen's efficacy as a second-line drug and suggesting that these combinations may yield satisfactory results in patients who do not respond to first-line treatment [13,14].Our study also aligned with the findings of Sangamesh et al. (2024), who conducted a comparative study of 100 patients divided into two groups of 50 each: one treated with carbamazepine and the other with baclofen. The latter study showed significant improvements for both drugs, and, as demonstrated, adverse effects become more common with extended follow-up [15]. Although that investigation did not compare the two drugs as combination products, it highlighted the therapeutic activity of each drug and provides current evidence for using baclofen in pharmacological management [16].A 2024 retrospective institutional study gives more context. In a group of 300 patients, 70% treated with carbamazepine alone and 72% treated with carbamazepine plus baclofen experienced pain control, compared with 75% treated with carbamazepine plus gabapentin [17]. This relatively small difference between carbamazepine and carbamazepine-baclofen therapy in the real-world population is different from what we saw in our study. This is possibly due to differences in treatment duration, patient selection, disease severity, adherence to treatment, dosage, and outcome definition. Prospective evaluation of pain and attack frequency at predetermined times may be more responsive to short-term treatment changes [18].New studies also highlight the dynamic nature of trigeminal neuralgia treatment. A recent umbrella review (2023) indicates that carbamazepine remains a first-line option. Still, baclofen could be a second-line treatment, especially if the patient does not respond to first-line treatment or the drug is poorly tolerated [19]. The 2023 clinical review also highlighted the importance of pharmacological therapy as the first-line treatment option, suggesting that interventional or surgical therapies should be considered when there is an inadequate response or an intolerable adverse drug effect [20].The negative impact results in our study are clinically relevant as well. The groups were similar in the incidence of dizziness, drowsiness, nausea, and diplopia, but no serious treatment-related complications were observed during the 30-day follow-up period. This is in keeping with recent literature, which reports neurological side effects as an important constraint of carbamazepine therapy. Thus, even if combination therapy is more effective at pain control, physicians should not be unnecessarily tempted to increase the dose and should be vigilant for dose-related effects, including sedation, dizziness, and impaired coordination [21].Recent systematic evidence also supports the benefit of alternative treatments (botulinum toxin type A and oxcarbazepine) used in some patients [22]. However, the present results are clinically relevant because the combination of drugs studied is relatively easy to administer and readily available. In conclusion, our findings indicate that the combination of CBZ and BAC may provide more symptomatic relief in the short term than CBZ alone, especially for patients with persisting pain or multiple attacks. Additional studies with longer follow-up and more randomized controlled trials are needed to confirm the sustainability of benefit, dosing, adherence, and long-term safety of this combination.

Limitations

This study had several limitations. The relatively small number of subjects and single-center design may limit generalizability. The follow-up period was too short to evaluate long-term effectiveness, recurrence, compliance, and side effects. The study did not randomize treatment groups, so observer and selection bias are possible. More large, multicenter randomized studies are suggested.

In patients with trigeminal neuralgia, the combination of carbamazepine and baclofen gave significantly greater short-term pain severity reduction and attack frequency reduction than carbamazepine alone. Combination therapy also had a higher clinical response rate, and no serious adverse effects were seen. Baclofen might thus be used as an appropriate supplement to carbamazepine therapy, especially when carbamazepine is not sufficiently effective for symptom control.

1. Lambru G, Zakrzewska J, Matharu M. Trigeminal neuralgia: a practical guide. Pract Neurol. 2021 Oct;21(5):392-402. doi: 10.1136/practneurol-2020-002782.
2. Allam AK, Sharma H, Larkin MB, Viswanathan A. Trigeminal Neuralgia: Diagnosis and Treatment. Neurol Clin. 2023 Feb;41(1):107-121. doi: 10.1016/j.ncl.2022.09.001.
3. Niemeyer CS, Harlander-Locke M, Bubak AN, Rzasa-Lynn R, Birlea M. Trigeminal Postherpetic Neuralgia: From Pathophysiology to Treatment. Curr Pain Headache Rep. 2024 Apr;28(4):295-306. doi: 10.1007/s11916-023-01209-z.
4. Pergolizzi JV Jr, LeQuang JA, El-Tallawy SN, Wagner M, Ahmed RS, Varrassi G. An update on pharmacotherapy for trigeminal neuralgia. Expert Rev Neurother. 2024 Aug;24(8):773-786. doi: 10.1080/14737175.2024.2365946.
5. Kim HK, Chung KM, Xing J, Kim HY, Youn DH. The Trigeminal Sensory System and Orofacial Pain. Int J Mol Sci. 2024 Oct 21;25(20):11306. doi: 10.3390/ijms252011306.
6. Terrier LM, Hadjikhani N, Destrieux C. The trigeminal pathways. J Neurol. 2022 Jul;269(7):3443-3460. doi: 10.1007/s00415-022-11002-4.
7. Radoš I. TREATMENT OPTIONS FOR TRIGEMINAL NEURALGIA. Acta Clin Croat. 2022 Sep;61(Suppl 2):96-102. doi: 10.20471/acc.2022.61.s2.12.
8. Khawaja SN, Scrivani SJ. Trigeminal Neuralgia. Dent Clin North Am. 2023 Jan;67(1):99-115. doi: 10.1016/j.cden.2022.07.008.
9. Villegas Díaz D, Guerrero Alvarado G, López Medina A, Gómez Clavel JF, García Muñoz A. Trigeminal neuralgia: therapeutic strategies to restore quality of life. J Oral Facial Pain Headache. 2024 Sep;38(3):32-37. doi: 10.22514/jofph.2024.024.
10. Allam AK, Larkin MB, Sharma H, Viswanathan A. Trigeminal and Glossopharyngeal Neuralgia. Neurol Clin. 2024 May;42(2):585-598. doi: 10.1016/j.ncl.2023.12.011.
11. Finucane S, Dalwadi P, Mudaliar K, Hurtuk A. Trigeminal trophic syndrome: A systematic review. Am J Otolaryngol. 2024 Jul-Aug;45(4):104354. doi: 10.1016/j.amjoto.2024.104354.
12. Shusterman D. Trigeminal Function in Sino-Nasal Health and Disease. Biomedicines. 2023 Jun 21;11(7):1778. doi: 10.3390/biomedicines11071778.
13. Stern JI, Ali R, Chiang CC, Robertson CE. Pathophysiology and Management of Refractory Trigeminal Neuralgia. Curr Neurol Neurosci Rep. 2024 Dec 12;25(1):10. doi: 10.1007/s11910-024-01387-2.
14. Hernandez AK, Hummel T. Intranasal trigeminal function in chronic rhinosinusitis: a review. Expert Rev Clin Immunol. 2023 Jul-Dec;19(8):921-938. doi: 10.1080/1744666X.2023.2231149.
15. Sveinsson OA, Arkink EB, Ulfarsson E, Thors B. [Trigeminal neuralgia - Overview]. Laeknabladid. 2025 Feb;111(2):62-67. Icelandic. doi: 10.17992/lbl.2025.02.825.
16. Ryan K, Crighton A. Trigeminal neuralgia and trigeminal neuropathic pain. Br Dent J. 2024 Feb;236(4):323-328. doi: 10.1038/s41415-024-7068-6.
17. Mannerak MA, Lashkarivand A, Eide PK. Trigeminal neuralgia and genetics: A systematic review. Mol Pain. 2021 Jan-Dec;17:17448069211016139. doi: 10.1177/17448069211016139.
18. Powell K, Lin K, Tambo W, Saavedra AP, Sciubba D, Al Abed Y, Li C. Trigeminal nerve stimulation: a current state-of-the-art review. Bioelectron Med. 2023 Dec 13;9(1):30. doi: 10.1186/s42234-023-00128-z.
19. Zhang L, Nagel M, Olson WP, Chesler AT, O'Connor DH. Trigeminal innervation and tactile responses in mouse tongue. Cell Rep. 2024 Sep 24;43(9):114665. doi: 10.1016/j.celrep.2024.114665.
20. Mousavi SH, Lindsey JW, Westlund KN, Alles SRA. Trigeminal Neuralgia as a Primary Demyelinating Disease: Potential Multimodal Evidence and Remaining Controversies. J Pain. 2024 Feb;25(2):302-311. doi: 10.1016/j.jpain.2023.08.012.
21. White TG, Powell K, Shah KA, Woo HH, Narayan RK, Li C. Trigeminal Nerve Control of Cerebral Blood Flow: A Brief Review. Front Neurosci. 2021 Apr 13;15:649910. doi: 10.3389/fnins.2021.649910.
22. Renton T, Van der Cruyssen F. Posttraumatic Trigeminal Neuropathic Pain in Association with Dental Implant Surgery. Dent Clin North Am. 2023 Jan;67(1):85-98. doi: 10.1016/j.cden.2022.07.007.