title: Pain phenotype as a predictor for drug response in painful polyneuropathy-a retrospective analysis of data from controlled clinical trials.
abstract: The drugs available for treatment of neuropathic pain have somewhat disappointing efficacy with many patients left with limited or no effect. Individualized treatment based on phenotype according to presumed underlying pain mechanism(s) has been proposed to improve outcomes. We report a retrospective analysis of phenotype-specific effects of several neuropathic pain drugs, which were studied in a series of crossover, placebo-controlled, clinical trials. The data originate from 7 trials with similar design and outcome recordings, which all had a thorough baseline registration of symptoms, signs, and quantitative sensory testing. The latter was used to phenotype patients into subgroups reflecting presumed pain mechanisms. There were a total of 361 patient records distributed over treatments with 4 antidepressants and 4 anticonvulsants. Five of the drugs reduced total pain significantly compared with placebo. Only a few phenotype-specific differences in total pain reduction were found within the investigated drugs. Thus, imipramine reduced total pain 1.84 (CI: 0.02-3.67) and pregabalin 0.81 (CI: -0.67 to 2.29) in patients with than without gain of sensory function. Pregabalin showed a better effect in patients with preserved large fiber function with a mean difference in total pain reduction 1.31 (CI: 0.15-2.47). No phenotype-specific effects were found for venlafaxine, escitalopram, oxcarbazepine, valproic acid, levetiracetam, or St. John's wort. Thus, this post hoc analysis of 8 drugs with mainly nonselective actions on neuropathic pain mechanisms found limited usefulness of sensory phenotyping in pain as the basis for individualized treatment.
authors.affiliation: Department of Neurology, Odense University Hospital, Odense, Denmark Department of Neurology, Aalborg University Hospital, Aalborg, Denmark Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark Department of Neurology, Aarhus University Hospital, Aarhus, 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: Troels S
authors.initials: TS
authors.lastname: Jensen
authors.forename: Søren H
authors.initials: SH
authors.lastname: Sindrup
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy*; D010641:Phenotype; D011115:Polyneuropathies / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000700:Analgesics; D000927:Anticonvulsants; D000928:Antidepressive Agents