Imipramine and pregabalin combination for painful polyneuropathy

a randomized controlled trial

Jakob V Holbech, Flemming W Bach, Nanna B Finnerup, Kim Brøsen, Troels S Jensen, Søren H Sindrup

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Monotherapy with first-line drugs for neuropathic pain often fails to provide sufficient pain relief or has unacceptable side effects because of the need for high doses. The aim of this trial was to test whether the combination of imipramine and pregabalin in moderate doses would relieve pain more effectively than monotherapy with either of the drugs. This was a randomized, double-blind, placebo-controlled, crossover, multicenter trial consisting of four 5-week treatment periods in patients with painful polyneuropathy. Treatment arms were imipramine 75 mg/d vs pregabalin 300 mg/d vs combination therapy vs placebo. Patients with polyneuropathy and symptoms for more than 6 months, age 20 to 85 years, pain intensity ≥4 on a 0- to 10-point numeric rating scale (NRS) and pain at least 4 days a week were included in the trial. A total of 262 patients were screened for participation, 73 patients were randomized, and 69 patients were included in the data analysis. The effect on average pain in comparison with placebo was: combination (-1.67 NRS points, P < 0.001), imipramine (-1.08 NRS points, P < 0.001), and pregabalin (-0.48 NRS points, P = 0.03). The combination therapy had significantly lower pain scores than both monotherapies: combination vs imipramine (P = 0.009), combination vs pregabalin (P < 0.001). During combination therapy, the dropout rate was higher and the patients reported a higher rate and severity of side effects. Combination of moderate doses of the tricyclic antidepressant imipramine and pregabalin could be considered as an alternative to high-dosage monotherapy. However, the trial also emphasized that balance between efficacy and safety is an issue.

OriginalsprogEngelsk
TidsskriftPain
Vol/bind156
Udgave nummer5
Sider (fra-til)958-66
ISSN0304-3959
DOI
StatusUdgivet - 2015

Fingeraftryk

Imipramine
Randomized Controlled Trials
Placebos
Patient Participation
Pharmaceutical Preparations
Cross-Over Studies
Multicenter Studies
Safety

Citer dette

Holbech, Jakob V ; Bach, Flemming W ; Finnerup, Nanna B ; Brøsen, Kim ; Jensen, Troels S ; Sindrup, Søren H. / Imipramine and pregabalin combination for painful polyneuropathy : a randomized controlled trial. I: Pain. 2015 ; Bind 156, Nr. 5. s. 958-66.
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abstract = "Monotherapy with first-line drugs for neuropathic pain often fails to provide sufficient pain relief or has unacceptable side effects because of the need for high doses. The aim of this trial was to test whether the combination of imipramine and pregabalin in moderate doses would relieve pain more effectively than monotherapy with either of the drugs. This was a randomized, double-blind, placebo-controlled, crossover, multicenter trial consisting of four 5-week treatment periods in patients with painful polyneuropathy. Treatment arms were imipramine 75 mg/d vs pregabalin 300 mg/d vs combination therapy vs placebo. Patients with polyneuropathy and symptoms for more than 6 months, age 20 to 85 years, pain intensity ≥4 on a 0- to 10-point numeric rating scale (NRS) and pain at least 4 days a week were included in the trial. A total of 262 patients were screened for participation, 73 patients were randomized, and 69 patients were included in the data analysis. The effect on average pain in comparison with placebo was: combination (-1.67 NRS points, P < 0.001), imipramine (-1.08 NRS points, P < 0.001), and pregabalin (-0.48 NRS points, P = 0.03). The combination therapy had significantly lower pain scores than both monotherapies: combination vs imipramine (P = 0.009), combination vs pregabalin (P < 0.001). During combination therapy, the dropout rate was higher and the patients reported a higher rate and severity of side effects. Combination of moderate doses of the tricyclic antidepressant imipramine and pregabalin could be considered as an alternative to high-dosage monotherapy. However, the trial also emphasized that balance between efficacy and safety is an issue.",
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Imipramine and pregabalin combination for painful polyneuropathy : a randomized controlled trial. / Holbech, Jakob V; Bach, Flemming W; Finnerup, Nanna B; Brøsen, Kim; Jensen, Troels S; Sindrup, Søren H.

I: Pain, Bind 156, Nr. 5, 2015, s. 958-66.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Imipramine and pregabalin combination for painful polyneuropathy

T2 - a randomized controlled trial

AU - Holbech, Jakob V

AU - Bach, Flemming W

AU - Finnerup, Nanna B

AU - Brøsen, Kim

AU - Jensen, Troels S

AU - Sindrup, Søren H

PY - 2015

Y1 - 2015

N2 - Monotherapy with first-line drugs for neuropathic pain often fails to provide sufficient pain relief or has unacceptable side effects because of the need for high doses. The aim of this trial was to test whether the combination of imipramine and pregabalin in moderate doses would relieve pain more effectively than monotherapy with either of the drugs. This was a randomized, double-blind, placebo-controlled, crossover, multicenter trial consisting of four 5-week treatment periods in patients with painful polyneuropathy. Treatment arms were imipramine 75 mg/d vs pregabalin 300 mg/d vs combination therapy vs placebo. Patients with polyneuropathy and symptoms for more than 6 months, age 20 to 85 years, pain intensity ≥4 on a 0- to 10-point numeric rating scale (NRS) and pain at least 4 days a week were included in the trial. A total of 262 patients were screened for participation, 73 patients were randomized, and 69 patients were included in the data analysis. The effect on average pain in comparison with placebo was: combination (-1.67 NRS points, P < 0.001), imipramine (-1.08 NRS points, P < 0.001), and pregabalin (-0.48 NRS points, P = 0.03). The combination therapy had significantly lower pain scores than both monotherapies: combination vs imipramine (P = 0.009), combination vs pregabalin (P < 0.001). During combination therapy, the dropout rate was higher and the patients reported a higher rate and severity of side effects. Combination of moderate doses of the tricyclic antidepressant imipramine and pregabalin could be considered as an alternative to high-dosage monotherapy. However, the trial also emphasized that balance between efficacy and safety is an issue.

AB - Monotherapy with first-line drugs for neuropathic pain often fails to provide sufficient pain relief or has unacceptable side effects because of the need for high doses. The aim of this trial was to test whether the combination of imipramine and pregabalin in moderate doses would relieve pain more effectively than monotherapy with either of the drugs. This was a randomized, double-blind, placebo-controlled, crossover, multicenter trial consisting of four 5-week treatment periods in patients with painful polyneuropathy. Treatment arms were imipramine 75 mg/d vs pregabalin 300 mg/d vs combination therapy vs placebo. Patients with polyneuropathy and symptoms for more than 6 months, age 20 to 85 years, pain intensity ≥4 on a 0- to 10-point numeric rating scale (NRS) and pain at least 4 days a week were included in the trial. A total of 262 patients were screened for participation, 73 patients were randomized, and 69 patients were included in the data analysis. The effect on average pain in comparison with placebo was: combination (-1.67 NRS points, P < 0.001), imipramine (-1.08 NRS points, P < 0.001), and pregabalin (-0.48 NRS points, P = 0.03). The combination therapy had significantly lower pain scores than both monotherapies: combination vs imipramine (P = 0.009), combination vs pregabalin (P < 0.001). During combination therapy, the dropout rate was higher and the patients reported a higher rate and severity of side effects. Combination of moderate doses of the tricyclic antidepressant imipramine and pregabalin could be considered as an alternative to high-dosage monotherapy. However, the trial also emphasized that balance between efficacy and safety is an issue.

U2 - 10.1097/j.pain.0000000000000143

DO - 10.1097/j.pain.0000000000000143

M3 - Journal article

VL - 156

SP - 958

EP - 966

JO - Pain

JF - Pain

SN - 0304-3959

IS - 5

ER -