Pharmacological,153 See Table 6
Carbamazepine is highly efficacious in CTN and is usually the first drug tested. The number needed to treat (NNT) for any pain relief for carbamazepine in CTN is 1.9, and for significant effectiveness is 2.6.[154,155] Its success in CTN has been extrapolated by some clinicians to serve as a diagnostic test. However, a number of patients may be initially resistant, and others become refractory to carbamazepine therapy. On the other hand, recent studies established that, over a 2-year follow-up, patients with TN do not generally become refractory to medication. Oxcarbazepine, a carbamazepine derivative, is also efficacious in CTN[40,157] with less side effects, other than hyponatremia, but patients may also develop resistance. Barbemazepine (CBZ) and OXC are the most commonly used drugs in the management of TN, but both can cause serious cognitive impairment. Their most common significant side effects include tiredness 31.3%, sleepiness 18.2%, memory problems 22.7%, disturbed sleep 14.1%, difficulty concentrating and unsteadiness 11.6%. These are largely more common in CBZ. Interestingly, females reported significantly more side effects than males, and this effect remained when controlling for body mass index, concomitant drugs, body weight, percentage body fat, increased vigilance, and desire to report side effects. The potential toxic dose for females is approximately 1200 mg of OXC and 800 mg of CBZ and 1800 mg of OXC and 1200 mg of CBZ for males. Pharmacokinetic and pharmacodynamic differences are thus likely to be the reason for these sex differences. Therefore, females may need to be prescribed lower doses in view of their tendency to reach toxic levels at lower dosages. When transferring patients between OXC and CBZ, an OXC dose of +30% relative to CBZ is usually required Table 6.
Baclofen, with a low side effect profile, may be titrated to relatively high doses (80 mg/day) with a NNT of 1.4. However, a strong synergistic effect with both carbamazepine and phenytoin is reported, making baclofen suitable for combined therapy, which is its more common use. Gabapentin has not been rigorously tested in CTN but may be useful in selected CTN cases.[160,161] Pregabalin (150–600 mg/day) significantly improved pain in patients with CTN after 8 weeks in 60%–70% of treated cases.[69,162] Lamotrigine is effective as add-on therapy but needs slow titration. It is unclear whether topiramate is effective for CTN.[164,165] Phenytoin was the first drug for CTN and is prescribed at 150–200 mg twice daily but has a relatively low success rate (25%). Side effects such as drowsiness and dizziness occur in 10% of patients even at low doses. Long-term use can induce osteomalacia.
Based on the current evidence, we initiate therapy with carbamazepine and transfer patients at the earliest opportunity to the controlled release formulation that has less side effects. If carbamazepine causes troublesome side effects, we reduce the dose and add baclofen, gabapentin, pregabalin, or lamotrigine. Alternatively, oxcarbazepine as monotherapy or with add-on therapy may be tried. In refractory cases, drug combinations as above should be tried. It is important to appreciate that breakthrough pain may occur in successfully treated patients and require temporary dose adjustment; in extreme cases, inpatient care with intravenous phenytoin may be needed. The issue is that no matter which protocol is used, patients' QoL can be severely affected by significant motor, cognitive, sensory, and biological side effects.
Headache. 2021;61(6):817-837. © 2021 Blackwell Publishing