title: Imipramine and pregabalin combination for painful polyneuropathy: a randomized controlled trial.
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.
authors.affiliation: Department of Neurology, Odense University Hospital, Odense, Denmark Department of Neurology, Aalborg University Hospital, Aalborg, Denmark Department of Neurology and Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark Department of Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Jakob V
authors.initials: JV
authors.lastname: Holbech
authors.forename: Flemming W
authors.initials: FW
authors.lastname: Bach
authors.forename: Nanna B
authors.initials: NB
authors.lastname: Finnerup
authors.forename: Kim
authors.initials: K
authors.lastname: Brøsen
authors.forename: Troels S
authors.initials: TS
authors.lastname: Jensen
authors.forename: Søren H
authors.initials: SH
authors.lastname: Sindrup
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007099:Imipramine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D000069583:Pregabalin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000700:Analgesics; D000069583:Pregabalin; D007099:Imipramine