Usefulness of a Double-Blind Placebo-Controlled Response Test to Demonstrate Rapid Onset Analgesia with Phenytoin 10% Cream in Polyneuropathy

Figures & data

Table 1 Patient Characteristics

	All Patients (N = 12)	Responders (N = 6)	Non-Responders (N = 6)
Age in years, mean (SD)	64.2 (11.0)	63.3 (14.0)	65.0 (8.1)
Men/women, N	6/6	2/4	4/2
Duration of pain in years, mean (SD)	6.1 (7.0)	10.3 (7.9)	1.9 (1.7)
Current analgesic co-medication, N (%)	7 (58)	4 (67)	3 (50)
Pre-test NRS mean (SD)	6.1 (1.4)	6.2 (1.5)	6.0 (1.4)
Use of neuropathic pain medication, N	6	3	3
Diagnosis	N	N	N
Chronic idiopathic axonal polyneuropathy	5	4	1
Chemotherapy induced polyneuropathy	4	2	2
Diabetic polyneuropathy	3	0	3
Anatomical Areas of Pain
Both feet	6	3	3
Both feet and lower legs	3	2	1
Both feet, lower legs and hands	1	0	1
Fingertips	2	1	1
Pain Characteristics	N (%)	N (%)	N (%)
Burning	10 (83)	5 (83)	5 (83)
Painful cold	7 (58)	4 (67)	3 (50)
Electric shocks	5 (42)	2 (33)	3 (50)
Tingling	12 (100)	6 (100)	6 (100)
Pins and needles	6 (50)	3 (50)	3 (50)
Numbness	10 (83)	5 (83)	5 (83)
Itching	1 (8)	1 (17)	6 (100)
Hypesthesia to touch	7 (58)	4 (67)	3 (50)
Hypesthesia to pinprick	7 (58)	2 (33)	5 (83)
Allodynia	8 (67)	4 (67)	4 (67)

Abbreviations: N: number of patients, SD: standard deviation.

Table 2 Analgesic Effect of Phenytoin versus Placebo on NRS Score After 30 Minutes

Population	Phenytoin		Placebo		Mean Difference
	Post Application NRS Score				Mean NRS Difference
	Mean	95% CI	Mean	95% CI	Mean	95% CI	P-value
All patients (N = 12)	4.3	3.5 to 5.1	5.2	4.4 to 6.0	0.9	0.4 to 1.4	0.003
Responders* (N = 6)	3.0	2.5 to 3.5	4.3	3.8 to 4.8	1.3	1.1 to 1.8	< 0.001
Non-responders (N = 6)	5.7	5.2 to 6.2	6.2	5.7 to 6.7	0.5	−0.2 to 1.2	0.2
	% Pain Reduction from Baseline				Mean % Difference
	Mean	95% CI	Mean	95% CI	Mean	95% CI	P-value
All patients (N = 12)	29	13 to 45	12	−2 to 26	17	6 to 28	0.006
Responders* (N = 6)	51	40 to 62	28	15 to 42	22	13 to 32	0.001
Non-responders (N = 6)	8;	−5 to 20	−4	−20 to 11	12	−12 to 36	0.3

Note: *Responder is defined as ≥2 points pain reduction on the NRS as well as ≥1 point difference between the phenytoin 10% cream and the placebo cream applied area in favour of phenytoin 10% cream.

Abbreviations: NRS, 11-point numerical rating scale, CI, confidence interval; N, number of patients.

Table 3 Minimal Pain Reduction of 30% and 50%

Population	Phenytoin	Placebo
	MPR50 N (%)	MPR50 N (%)
All patients (N = 12)	4 (33)	1 (8)
Responders (N = 6)	4 (67)	1 (17)
	MPR30 N (%)	MPR30 N (%)
All patients (N = 12)	6 (50)	3 (25)
Responders (N = 6)	6 (100)	3 (50)

Abbreviations: MPR30, minimal pain reduction of ≥30%; MPR50, minimal pain reduction of ≥50%; N, number of patients.

Figure 1 Individual results of DOBRET.

Abbreviation: NRS, 11-point numerical rating scale in which 0 is no pain and 10 worst pain ever.