Approximately 23% of all MS patients suffer from non-trigeminal, nonparoxysmal central pain (CP). This pain is generally considered difficult to treat effectively; tricyclic antidepressants, anti epileptic drugs or analgesics are most commonly used. In this study, the pain relieving effects of amitriptyline and carbamazepine were investigated.
The design was a randomised double-blind, three-phase, crossover, placebo-controlled trial. Twenty-three patients with definitive MS entered the study (mean age 55 year, range 40-79 years), all had been thoroughly investigated in a project on CP in MS, and no one showed signs of depression. The treatment phases lasted four weeks, and were separated by a one-week washout. The final doses were 75 mg for amitriptyline and 600 mg for carbamazepine (adjusted from 800 mg, because of side-effects). The effect of treatment was assessed by two daily ratings of pain using a 10- step verbal rating scale (VRS), and at the end of each treatment period using a 5-step global rating scale. For the assessment of depression the Comprehensive Psychopathological Rating Scale (CPRS) was used.
Originally 23 patients were included in the study, but due to side-effects 7 patients discontinued during the amitriptyline phase, and 12 during the carbamazepine phase. With carbamazepine this occurred at low doses (100-200 mg).
The results show that amitriptyline significantly reduced non-paroxysmal CP in MS, compared to placebo (VRS 4.2 vs. 5.3; p<0.05) and according to the global rating; nine of 14 patients were responders (64%). The effect could already be seen during the second week of treatment. The plasma concentrations of amitriptyline and its active metabolite nortriptyline were higher in the responders (329 nmol/l) that in the non-responders (252 nmol/l, n.s). CPRS scores for depression were normal, and were not altered by the medication.
Two of nine patients treated with carbamazepine reported some pain relief, but the effect did not reach significance when compared with placebo. No correlation was found between effect and plasma concentration.
It is concluded that amitriptyline, but not carbamazepine, has a weak effect on non-paroxysmal CP in MS, and that MS patients appear to be particularly sensitive to the side-effects of the two drugs.