For TN patients who are intolerant of, or have contraindications to first line therapies, baclofen, lamotrigine or gabapentin are frequently viable alternatives [
17,
20••,
28]. Moreover, patients who do not respond to first-line carbamazepine monotherapy have demonstrated potential benefits from combination therapy [
20••,
32]. Nevertheless, there is a lack of randomized controlled trials directly comparing the efficacy of monotherapy against combination therapy in treating TN [
28]. Each of these second line therapies come with certain pitfalls. Baclofen, a GABA
B receptor agonist, reduces the number of painful episodes and prolongs remission [
20••]. The adverse effects of baclofen within a therapeutic window of up to 80 mg/day encompass drowsiness, muscle weakness, fatigue, and cognitive deficits. Additionally, the narrow therapeutic range of baclofen necessitates vigilant monitoring during dose initiation, with tapering recommended [
20••,
33]. The effectiveness of baclofen is constrained by these adverse effects, often hindering the administration of an adequate oral dose required for meaningful pain alleviation [
29]. Lamotrigine is an anticonvulsant that inhibits glutamate release by blocking voltage-gated sodium channels [
20••,
24]. Within a therapeutic dosage range of up to 600 mg/day, its adverse effects may include sleepiness, dizziness, headache, vertigo, and ataxia [
20••,
28,
34]. However, evidence supporting its efficacy is generally low [
10,
34]. Gabapentin, an anticonvulsant designed to mimic the neurotransmitter GABA, lacks clear evidence regarding its effectiveness as monotherapy [
20••]. A recent comprehensive examination involving a systematic review and meta-analysis, which scrutinized 18 randomized controlled trials, confirmed the efficacy and enhanced tolerability of this treatment in contrast to carbamazepine. However, the overall quality of the studies included in the analysis was deemed insufficient [
35]. Due to the scarcity of evidence, it is understandable that some experts recommend early surgical referrals for patients unresponsive to first-line therapy, as they are less likely to respond to alternative medications for trigeminal neuralgia [
28,
29].