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Cited by 231Cancer Treatment and PharmacologyPain Mechanisms and TreatmentsChemotherapy-related skin toxicity

Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy

Hammack, Julie E., Michalak, John C., Loprinzi, Charles L., Sloan, Jeff A., Novotny, Paul J., Soori, Gamini S., Tirona, Maria Tria, Rowland, Kendrith M., Stella, Philip J., Johnson, Joanne A.·2002·Pain
DOI 10.1016/s0304-3959(02)00047-7
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Abstract

Tricyclic antidepressants have been reported to relieve the paresthesiae associated with peripheral neuropathies of many etiologies. We designed a randomized, double-blind, placebo-controlled, crossover trial to establish the efficacy of nortriptyline in the treatment of cis-diamminedichloroplatinum (CDDP)-induced paresthesiae. The study included 51 evaluable patients with CDDP-induced peripheral neuropathy and painful paresthesiae. The study consisted of two 4 week phases, separated by a 1 week 'wash-out' period, in which patients received escalating dosages of either placebo or nortriptyline. The target maximum dose of nortriptyline was 100 mg/day. Each patient filled out pre-randomization and then weekly questionnaires assessing paresthesiae severity, hours of sleep, quality of life, and adverse effects over the 9 week study. No significant differences in paresthesia were observed in the first treatment period between nortriptyline and placebo (means of 49 and 55 respectively on a 0-100 point scale, P=0.78). Although some evidence of a modest effect in favor of nortriptyline was observed during the second treatment period (about one patient in five got a 10-point reduction in pain from drug above placebo effect), this occurred in the presence of a strong carryover effect. Linear models analysis and Bayes methods confirmed that the effect of nortriptyline on paresthesia was modest at best. Hours of sleep increased in the nortriptyline phase (P=0.02). There was no significan…

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  • In patients with skin complaints, total sleep time improved for those treated with nortriptyline (100mg), compared to placebo, but daytime sleepiness was reported as a problem in the treatment group.

    “In a study of patients with skin complaints (Hammack et al., 2002), total sleep time improved for those treated with nortriptyline (100mg), compared to placebo. However, daytime sleepiness was reported as a problem in the treatment group.”

    From Antidepressants and their effect on sleep (2005) · cites this paper as Hammack et al., 2002

  • One study of nortriptyline suggested longer sleep latency.

    “although one study of nortriptyline suggested longer sleep latency (Hammack et al., 2002)”

    From Antidepressants and their effect on sleep (2005) · cites this paper as Hammack et al., 2002

  • Amitriptyline, trimipramine, nortriptyline, dothiepin and doxepin have all been associated with sedation.

    “Amitriptyline (Hindmarch et al., 2000), trimipramine (Sonntag et al., 1996), nortriptyline (Hammack et al., 2002), dothiepin (Blacker et al., 1988) and doxepin (Hajak et al., 2001) have all been associated with sedation, while imipramine (Volkers et al., 2002) and desipramine (Shipley et al., 1985) are less likely to be linked with sedation, but have been associated with insomnia; the evidence is”

    From Antidepressants and their effect on sleep (2005) · cites this paper as Hammack et al., 2002

  • Amitriptyline, nortriptyline and particularly dothiepin have frequently been linked with poorer reports of daytime drowsiness.

    “At the same time, amitriptyline (Rosenzweig et al., 1998), nortriptyline (Hammack et al., 2002) and (particularly) dothiepin (Wilson et al., 2002) have frequently been linked with poorer reports of daytime drowsiness.”

    From Antidepressants and their effect on sleep (2005) · cites this paper as Hammack et al., 2002

Cites

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Research works printed but not linked: 33

  1. Abt, 1981, Problems of repeated significance testing., Controlled Clinical Trials, 1, 377, 10.1016/0197-2456(81)90042-8 · DOI
  2. Bobbio, 1994, Completeness of reporting trial results: effect on physicians willingness to prescribe., Lancet, 343, 1209, 10.1016/S0140-6736(94)92407-4 · DOI
  3. Cavaletti, 1992, Cisplatin-induced peripheral neurotoxicity is dependent on total-dose intensity and single-dose intensity., Cancer, 69, 203, 10.1002/1097-0142(19920101)69:1<203::AID-CNCR2820690133>3.0.CO;2-1 · DOI
  4. Chapman, 1985, Pain measurement: an overview., Pain, 22, 1, 10.1016/0304-3959(85)90145-9 · DOI
  5. Edelbroek, 1986, Analgesic and antidepressive effects of low-dose amitriptyline in relation to its metabolism in patients with chronic pain., Clin Pharmacol Ther, 39, 156, 10.1038/clpt.1986.27 · DOI
  6. Gelfand, 1990, Sampling based approaches to calculating marginal densities., J Am Stat Assoc, 85, 398, 10.1080/01621459.1990.10476213 · DOI · Paper page
  7. Gomez-Perez, 1985, Nortriptyline and fluphenazine in the symptomatic treatment of diabetic neuropathy. A double blind crossover study., Pain, 23, 395, 10.1016/0304-3959(85)90010-7 · DOI
  8. Gregg, 1992, Cisplatin neurotoxicity: the relationship between dosage, time and platinum concentration in neurologic tissues and morphologic evidence of toxicity., J Clin Oncol, 10, 795, 10.1200/JCO.1992.10.5.795 · DOI
  9. Guyatt, 1993, Measuring health-related quality of life., Ann Int Med, 118, 622, 10.7326/0003-4819-118-8-199304150-00009 · DOI
  10. Hills, 1979, The two-period crossover clinical trial., Br J Clin Pharmacol, 8, 7, 10.1111/j.1365-2125.1979.tb05903.x · DOI
  11. Hovestadt, 1992, The course of neuropathy after cessation of cisplatin treatment, combined with ORG 2766 or placebo., J Neurol, 239, 143, 10.1007/BF00833914 · DOI
  12. Kvinesdal, 1984, Imipramine treatment of painful diabetic neuropathy., J Am Med Assoc, 251, 1727, 10.1001/jama.1984.03340370059031 · DOI
  13. Langohr, 1982, An open and double-blind cross-over study on the efficacy of clomipramine (Anafranil) in patients with painful mono- and polyneuropathies., Eur Neurol, 21, 309, 10.1159/000115497 · DOI
  14. LoMonoco, 1992, Cisplatin neuropathy: clinical course and neurophysiological findings., J Neurol, 239, 199, 10.1007/BF00839140 · DOI
  15. Max, 1987, Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood., Neurology, 37, 589, 10.1212/WNL.37.4.589 · DOI
  16. Max, 1991, Efficacy of desipramine in painful diabetic neuropathy., Pain, 45, 3, 10.1016/0304-3959(91)90157-S · DOI
  17. Max, 1992, Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy., N Engl J Med, 326, 1250, 10.1056/NEJM199205073261904 · DOI
  18. McQuay, 1996, A systematic review of antidepressants in neuropathic pain., Pain, 68, 217, 10.1016/S0304-3959(96)03140-5 · DOI
  19. Mendel, 1986, A trial of amitriptyline and fluphenazine in the treatment of painful diabetic neuropathy., J Am Med Assoc, 255, 637, 10.1001/jama.1986.03370050079025 · DOI
  20. OBrien, 1984, Procedures for comparing samples with multiple endpoints., Biometrics, 40, 1079, 10.2307/2531158 · DOI
  21. Onghena, 1992, Antidepressant-induced analgesia in chronic non-malignant pain: a meta-analysis of 39 placebo-controlled studies., Pain, 49, 205, 10.1016/0304-3959(92)90144-Z · DOI
  22. Panerai, 1990, A randomized, within-patient, cross-over, placebo-controlled trial on the efficacy and tolerability oft the tricyclic antidepressants chlorimipramine and nortriptyline in central pain., Acta Neurol Scand, 82, 34, 10.1111/j.1600-0404.1990.tb01584.x · DOI
  23. Pocock, 1975, Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial., Biometrics, 31, 1103, 10.2307/2529712 · DOI · Paper page
  24. Selby, 1984, The development of a method for assessing the quality of life of cancer patients., Br J Cancer, 50, 13, 10.1038/bjc.1984.134 · DOI
  25. Sindrup, 1999, Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action., Pain, 83, 389, 10.1016/S0304-3959(99)00154-2 · DOI
  26. Sindrup, 1990, Concentration-response relationship in imipramine treatment of diabetic neuropathy symptoms., Clin Pharmacol Ther, 47, 509, 10.1038/clpt.1990.65 · DOI
  27. Sindrup, 1990, Clomipramine vs desipramine vs placebo in the treatment of diabetic neuropathy symptoms. A double blind crossover study., Br J Clin Pharmacol, 30, 683, 10.1111/j.1365-2125.1990.tb03836.x · DOI
  28. Sindrup, 1990, The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms., Pain, 42, 135, 10.1016/0304-3959(90)91157-E · DOI
  29. Sloan, 1998, Incorporating quality of life measurement in oncology clinical trials., Proc Am Stat Assoc, 158, 282
  30. Spitzer, 1981, Measuring the quality of life of cancer patients., J Chron Dis, 34, 585, 10.1016/0021-9681(81)90058-8 · DOI
  31. Thompson, 1984, Cisplatin neuropathy: clinical, electrophysiologic, morphologic, and toxicologic studies., Cancer, 54, 1269, 10.1002/1097-0142(19841001)54:7<1269::AID-CNCR2820540707>3.0.CO;2-9 · DOI
  32. Woolf, 1999, Neuropathic pain: aetiology, symptoms, mechanisms, and management., Lancet, 353, 959, 10.1016/S0140-6736(99)01307-0 · DOI
  33. Young, 1985, Pain relief in diabetic neuropathy: the effectiveness of imipramine and related drugs., Diabetic Med, 2, 363, 10.1111/j.1464-5491.1985.tb00652.x · DOI

Cited by

Sorted by citations

Authors
Hammack, J. E., Michalak, J. C., Loprinzi, C. L., Sloan, J. A., Novotny, P. J., Soori, G. S., Tirona, M. T., Rowland, K. M., Stella, P. J., & Johnson, J. A.
Affiliations
  • Mayo Clinic (US)
  • National Institutes of Health (US)
Corresponding author
Loprinzi, Charles L.
ORCID
Venue
Pain
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2002-07
Volume
98
Issue
1
Pages
195-203
ISSN
0304-3959 (ISSN-L)
DOI
10.1016/s0304-3959(02)00047-7
OpenAlex
W2035062443
Cited by
231
References
2
Citations by year
2026: 5 · 2025: 5 · 2024: 9 · 2023: 9 · 2022: 8 · 2021: 15 · 2020: 16 · 2019: 12 · 2018: 10 · 2017: 13 · 2016: 11 · 2015: 16 · 2014: 18 · 2013: 11 · 2012: 3
FWCI
1.86
Type
journal article
Language
en
Open access
closed
Locations
  • Pain (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (U10CA035113, U10CA035103, U10CA035448, U10CA063848, U10CA035415, U10CA037404, U10CA025224, U10CA052352, U10CA035195, U10CA063849, U10CA035269, U10CA035101, U10CA060276)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Dermatology › Chemotherapy-related skin toxicity
Keywords
nortriptyline, cisplatin-induced peripheral neuropathy, chemotherapy-induced peripheral neuropathy, paresthesia, tricyclic antidepressants, neuropathic pain, residual effects, crossover trial, quality of life, sleep, adverse effects
MeSH terms
Antidepressive Agents, Tricyclic, Cisplatin, Dose-Response Relationship, Drug, Double-Blind Method, Humans, Nortriptyline, Palliative Care, Paresthesia, Peripheral Nervous System Diseases, Quality of Life, Severity of Illness Index, Sleep, Treatment Failure, Cross-Over Studies

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