Skip to main content

Advertisement

Log in

Amitriptyline

A Review of its Pharmacological Properties and Therapeutic Use in Chronic Pain States

  • Drug Evaluation
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Summary

Synopsis

Amitriptyline is a tricyclic antidepressant agent which also has analgesic properties. Whether its analgesic effects are linked to its mood-altering activity or attributable to a discrete pharmacological action (or a combination of both) is unknown.

Clinical trials demonstrate that oral amitriptyline achieves at least a good or moderate response in up to two-thirds of patients with post-herpetic neuralgia and three-quarters of patients with painful diabetic neuropathy, neurogenic pain syndromes that are often unresponsive to narcotic analgesics. Amitriptyline has also demonstrated efficacy in heterogeneous groups of patients with chronic non-malignant pain. Other possible areas of use for amitriptyline are in patients with fibromyalgia or as an adjuvant for uncontrolled cancer pain, although evidence for the latter application is limited.

Adverse events resulting from the antimuscarinic activity of amitriptyline (primarily dry mouth and sedation) are commonly reported, even at the low dosages used for the control of pain. Low starting doses and careful dosage titration may help to minimise these effects. Orthostatic hypotension and tachycardia, sometimes associated with tricyclic antidepressant agents, may also pose a problem in the elderly.

In summary, amitriptyline has a valuable place in the treatment of chronic pain conditions that affect the elderly provided that the drug is used judiciously to minimise adverse effects. Importantly, amitriptyline remains the best studied of the antidepressant agents in post- herpetic neuralgia and diabetic neuropathy and is an important and effective treatment option in these syndromes.

Pharmacological Properties

Two theories have been proposed to explain the analgesic activity of tricyclic antidepressant agents: firstly, that any analgesic activity is secondary to their antidepressant effects; and secondly, that they have an independent analgesic effect. Clinical data suggest that analgesia may be produced independently of the antidepressant effects of these agents; however, the precise mechanism by which this is achieved is unknown.

The analgesic effects of amitriptyline have been documented in several animal models after either single or multiple doses, but the relevance of these models to chronic pain states in humans is unknown. Amitriptyline produced dose-dependent analgesia to each of 3 different noxious stimuli in 2 studies.

Amitriptyline is rapidly absorbed after oral administration, but has a low oral bioavailability because of a large first-pass effect. The pharmacokinetics of amitriptyline (like those of other tricyclic antidepressants) are characterised by large interpatient variability. The drug is widely distributed throughout the body and is highly protein bound. Amitriptyline is extensively metabolised in the liver; the major metabolite, nortriptyline, is pharmacologically active. The terminal elimination half-life of amitriptyline ranges from 12.9 to 36.1 hours. No clear effect of older age on the pharmacokinetics of amitriptyline has been defined, although clearance may be decreased. There is no clear relationship between amitriptyline plasma concentrations and analgesic effect, although concentrations of amitriptyline plus nortriptyline needed to produce a significant analgesic effect appear to be lower than those required for an antidepressant effect.

Therapeutic Use

In patients with post-herpetic neuralgia of at least 3 months’ duration, oral amitriptyline achieved a 21 to 46% reduction in pain intensity from baseline as assessed by a visual analogue scale after 3 to 6 weeks’ treatment. 47 to 67% of patients reported a good or excellent response to therapy. When subjective assessment parameters were used, amitriptyline achieved significantly better pain relief than placebo or comparator agents (lorazepam, zimeldine and maprotiline).

Up to 74% of patients with painful diabetic neuropathy reported at least good or moderate pain relief after 6 to 8 weeks’ treatment with amitriptyline. Amitriptyline achieved a significantly greater reduction in pain intensity (29 to 51%) than placebo (15%) but had a similar effect to topical capsaicin (42%) or desipramine (28%). Limited clinical data in central post-stroke pain suggest that amitriptyline may be useful in these patients.

36% of patients with fibromyalgia showed clinical improvement after 6 months’ treatment with amitriptyline compared with 19% of placebo recipients. According to 2 patient surveys, amitriptyline was as effective as other agents and treatment modalities commonly used in this patient group. Results obtained with amitriptyline in patients with rheumatoid arthritis are conflicting.

Even in a heterogeneous group of patients, namely those presenting at a pain clinic with chronic nonmalignant pain, amitriptyline demonstrated small but significant analgesic effects compared with placebo in 2 of 3 studies. These results are supported by a meta-analysis which demonstrated an overall mean analgesic effect size of 0.73 for amitriptyline.

Antidepressant agents, including amitriptyline, are widely recommended and used as adjuvant agents in patients with cancer pain. However, few clinical trials have prospectively investigated the efficacy of amitriptyline in this patient group.

Tolerability

The adverse events most commonly reported with amitriptyline, even at the relatively low dosages used in pain syndromes, result from its antimuscarinic activity. 27 to 80% of patients with pain syndromes in clinical trials reported dry mouth and 17 to 62% reported tiredness/drowsiness. Since tolerance to these effects often develops, low starting doses and careful dosage titration may help to minimise toxicity. Up to 18% of patients withdrew from amitriptyline therapy as a result of adverse events.

Orthostatic hypotension and tachycardia can pose a problem in elderly patients receiving tricyclic agents at dosages in the antidepressant range; there is evidence that these effects may occur, albeit infrequently, at the lower dosages used in the treatment of pain. As with other tricyclic antidepressant agents, raised glucose levels can occur with amitriptyline.

Dosage and Administration

For the treatment of chronic pain states, amitriptyline should be started at a dosage of 10 to 25 mg/day and increased by 10 to 25 mg/week to the maximum suggested or tolerated dosage. To minimise the risk of adverse events in the elderly, amitriptyline should be started at a low dosage (10 mg/day) and titrated gradually in 10mg increments. The suggested maximum dosage for the treatment of neurogenic pain is 75 mg/day.

Amitriptyline, like other tricyclic antidepressant agents, should be administered with caution in patients with urinary retention, prostatic hypertrophy, glaucoma, constipation, impaired liver function or cardiovascular disease. It should be avoided in those with heart block or arrhythmias or immediately after myocardial infarction and in patients with severe liver disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Zagami AS. Chronic tension-type headache: rational drug treatment options. CNS Drugs 1995 Aug; 4(2): 90–8

    Article  Google Scholar 

  2. Richelson E. Antimuscarinic and other receptor-blocking properties of antidepressants. Mayo Clin Proc 1983 Jan; 58: 40–6

    PubMed  CAS  Google Scholar 

  3. Dray A, Urban L, Dickenson A. Pharmacology of chronic pain. Trends Pharmacol Sci 1994 Jun; 15: 190–7

    Article  PubMed  CAS  Google Scholar 

  4. Onghena P, Van Houdenhove B. Antidepressant-induced analgesia in chronic non-malignant pain: a meta-analysis of 39 placebo-controlled studies. Pain 1992; 49: 205–19

    Article  PubMed  CAS  Google Scholar 

  5. Feinmann C. Pain relief by antidepressants: possible modes of action. Pain 1985; 23: 1–8

    Article  PubMed  CAS  Google Scholar 

  6. Max MB, Culnane M, Schafer SC, et al. Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology 1987 Apr; 37: 589–96

    Article  PubMed  CAS  Google Scholar 

  7. Zitman FG, Linssen ACG, Edelbroek PM, et al. Low dose amitriptyline in chronic pain: the gain is modest. Pain 1990 Jul; 42: 35–42

    Article  PubMed  CAS  Google Scholar 

  8. Watson CP, Evans RJ, Reed K, et al. Amitriptyline versus placebo in postherpetic neuralgia. Neurology 1982 Jun; 32: 671–3

    Article  PubMed  CAS  Google Scholar 

  9. Max MB, Schafer SC, Culnane M, et al. Amitriptyline, but not lorazepam, relieves postherpetic neuralgia. Neurology 1988 Sep; 38: 1427–32

    Article  PubMed  CAS  Google Scholar 

  10. Max MB, Lynch SA, Muir J, et al. Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. N Engl J Med 1992 May 7; 326: 1250–6

    Article  PubMed  CAS  Google Scholar 

  11. Frank RG, Kashani JH, Parker JC, et al. Antidepressant analgesia in rheumatoid arthritis [see comments]. J Rheumatol 1988 Nov; 15: 1632–8

    PubMed  CAS  Google Scholar 

  12. Magni G, Conlon P, Arsie D. Tricyclic antidepressants in the treatment of cancer pain: a review. Pharmacopsychiatry 1987; 20: 160–4

    Article  PubMed  CAS  Google Scholar 

  13. Bowsher D. Pain syndromes and their treatment. Curr Opin Neurol Neurosurg 1993 Apr; 6: 257–63

    PubMed  CAS  Google Scholar 

  14. Watson CP, Evans RJ. A comparative trial of amitriptyline and zimelidine in post-herpetic neuralgia. Pain 1985 Dec; 23: 387–94

    Article  PubMed  CAS  Google Scholar 

  15. Bowsher D. Central pain. Pain Reviews 1995; 2: 175–86

    Google Scholar 

  16. Watanabe Y, Saito H, Abe K. Tricyclic antidepressants block NMDA receptor-mediated synaptic responses and induction of long-term potentiation in rat hippocampal slices. Neuropharmacology 1993 May; 32: 479–86

    Article  PubMed  CAS  Google Scholar 

  17. Ardid D, Guilbaud G. Antinociceptive effects of acute and’ chronic’ injections of tricyclic antidepressant drugs in a new model of mononeuropathy in rats. Pain 1992; 49: 279–87

    Article  PubMed  CAS  Google Scholar 

  18. Seltzer Z, Tal M, Sharav Y. Autotomy behavior in rats following peripheral deafferentation is suppressed by daily injections of amitriptyline, diazepam and saline. Pain 1989 May; 37: 245–50

    Article  PubMed  CAS  Google Scholar 

  19. Abad F, Feria M, Boada J. Chronic amitriptyline decreases autotomy following dorsal rhizotomy in rats. Neurosci Lett 1989 Apr 24; 99: 187–90

    Article  PubMed  CAS  Google Scholar 

  20. Casas J, Gibert-Rahola J, Chover AJ, et al. Test-dependent relationship of the antidepressant and analgesic effects of amitriptyline. Methods Find Exp Clin Pharmacol 1995; 17(9): 583–8

    PubMed  CAS  Google Scholar 

  21. Acton J, McKenna JE, Melzack R. Amitriptyline produces analgesia in the formalin pain test. Exp Neurol 1992 Jul; 117: 94–6

    Article  PubMed  CAS  Google Scholar 

  22. Tura B, Tura SM. The analgesic effect of tricyclic antidepressants. Brain Res 1990 Jun 4; 518: 19–22

    Article  PubMed  CAS  Google Scholar 

  23. Dirksen R, Van diejen D, Van luijtelaar ELJM, et al. Site- and test-dependent antinociceptive efficacy of amitriptyline in rats. Pharmacol Biochem Behav 1994 Jan; 47: 21–6

    Article  PubMed  CAS  Google Scholar 

  24. de Felipe MC, de Ceballos ML, Fuentes JA. Hypoalgesia induced by antidepressants in mice: a case for opioids and serotonin. Eur J Pharmacol 1986 Jun 17; 125: 193–9

    Article  PubMed  Google Scholar 

  25. Ventafridda V, Bianchi M, Ripamonti C, et al. Studies on the effects of antidepressant drugs on the antinociceptive action of morphine and on plasma morphine in rat and man. Pain 1990; 43: 155–62

    Article  PubMed  CAS  Google Scholar 

  26. Sacerdote P, Brini A, Mantegazza P, et al. A role for serotonin and beta-endorphin in the analgesia induced by some tricyclic antidepressant drugs. Pharmacol Biochem Behav 1987; 26: 153–8

    Article  PubMed  CAS  Google Scholar 

  27. Courteix C, Bardin M, Chantelauze C, et al. Study of the sensitivity of the diabetes-induced pain model in rats to a range of analgesics. Pain 1994 May; 57: 153–60

    Article  PubMed  CAS  Google Scholar 

  28. Butler SH, Weil-Fugazza J, Godefroy F, et al. Reduction of arthritis and pain behaviour following chronic administration of amitriptyline or imipramine in rats with adjuvant-induced arthritis. Pain 1985 Oct; 23: 159–75

    Article  PubMed  CAS  Google Scholar 

  29. Opitz K, Borchert U. On the management of pain using antidepressive agents [in German]. Klin Wochenschr 1967 Sep 1; 45: 887–8

    Article  PubMed  CAS  Google Scholar 

  30. Schulz P, Dick P, Blaschke TF, et al. Discrepancies between pharmacokinetic studies of amitriptyline. Clin Pharmacokinet 1985; 10: 257–68

    Article  PubMed  CAS  Google Scholar 

  31. Furlanut M, Benetello P. The pharmacokinetics of tricyclic antidepressant drugs in the elderly. Pharmacol Res 1990; 22(1): 15–25

    Article  PubMed  CAS  Google Scholar 

  32. Brøsen K, Gram LF. Clinical significance of the sparteine/debrisoquine oxidation polymorphism. Eur J Clin Pharmacol 1989; 36: 537–47

    Article  PubMed  Google Scholar 

  33. Jerling M, Bertilsson L, Sjöqvist F. The use of therapeutic drug monitoring data to document kinetic drug interactions: an example with amitriptyline and nortriptyline. Ther Drug Monit 1994 Feb; 16: 1–12

    Article  PubMed  CAS  Google Scholar 

  34. von Moltke LL, Greenblatt DJ, Shader RI. Clinical pharmacokinetics of antidepressants in the elderly: therapeutic implications. Clin Pharmacokinet 1993; 24(2): 141–60

    Article  Google Scholar 

  35. Rascol O, Tran M-A, Bonnevialle P, et al. Lack of correlation between plasma levels of amitriptyline (and nortriptyline) and clinical improvement of chronic pain of peripheral neurologic origin. Clin Neuropharmacol 1987 Dec; 10: 560–4

    Article  PubMed  CAS  Google Scholar 

  36. Edelbroek PM, Linssen AC, Zitman FG, et al. Analgesic and antidepressive effects of low-dose amitriptyline in relation to its metabolism in patients with chronic pain. Clin Pharmacol Ther 1986 Feb; 39: 156–62

    Article  PubMed  CAS  Google Scholar 

  37. Pilowsky I, Hallett EC, Bassett DL, et al. A controlled study of amitriptyline in the treatment of chronic pain. Pain 1982 Oct; 14: 169–79

    Article  PubMed  CAS  Google Scholar 

  38. Watson CPN, Chipman M, Reed K, et al. Amitriptyline versus maprotiline in postherpetic neuralgia: a randomized, double-blind, crossover trial. Pain 1992 Jan; 48: 29–36

    Article  PubMed  CAS  Google Scholar 

  39. Zitman FG, Linssen ACG, Edelbroek PM, et al. Does addition of low-dose flupentixol enhance the analgetic effects of low-dose amitriptyline in somatoform pain disorder. Pain 1991 Oct; 47: 25–30

    Article  PubMed  CAS  Google Scholar 

  40. Spilker B. Guide to clinical trials. New York: Raven Press, 1991

    Google Scholar 

  41. Bowsher D. Neurogenic pain syndromes and their management. Br Med Bull 1991 Jul; 47: 644–66

    PubMed  CAS  Google Scholar 

  42. Watson PN, Evans RJ. Postherpetic neuralgia: a review. Arch Neurol 1986 Aug; 43: 836–40

    Article  PubMed  CAS  Google Scholar 

  43. Bowsher D. Post-herpetic neuralgia in older patients. Incidence and optimal treatment. Drugs Aging 1994 Dec; 5: 411–8

    Article  PubMed  CAS  Google Scholar 

  44. Woodforde JM, Dwyer B, McEwen BW, et al. Treatment of post-herpetic neuralgia. Med J Aust 1965 Nov 20; 2: 869–72

    PubMed  CAS  Google Scholar 

  45. Lee JJ, Gauci CAG. Postherpetic neuralgia: current concepts and management. Br J Hosp Med 1994 Dec 14–1995 Jan 17; 52: 565–7, 570

    PubMed  CAS  Google Scholar 

  46. Watson CPN, Watt VR, Chipman M, et al. The prognosis with postherpetic neuralgia. Pain 1991; 46: 195–9

    Article  PubMed  CAS  Google Scholar 

  47. de Moragas JM, Kierland RR. The outcome of patients with herpes zoster. Arch Dermatol 1957; 75: 193–6

    Article  Google Scholar 

  48. Bhala BB, Ramamoorthy C, Bowsher D, et al. Shingles and postherpetic neuralgia. Clin J Pain 1988; 4: 169–74

    Article  Google Scholar 

  49. Bowsher D. Acute herpes zoster and postherpetic neuralgia: effects of acyclovir and outcome of treatment with amitriptyline [see comments]. Br J Gen Pract 1992 Jun; 42: 244–6

    PubMed  CAS  Google Scholar 

  50. Bowsher D. The effects of acyclovir therapy for herpes zoster on treatment outcome in postherpetic neuralgia. Eur J Pain 1994; 15(1): 9–12

    Google Scholar 

  51. Bowsher D. Pathophysiology of PHN: towards a rational treatment [abstract no. 28]. In: Proceedings of the 2nd International Conference on the Varicella-Zoster Virus: 1994 Jul 7–8: Paris, France

  52. Herne K, Cirelli R, Lee P, et al. Antiviral therapy of acute herpes zoster in older patients. Drugs Aging 1996 Feb; 8(2): 97–112

    Article  PubMed  CAS  Google Scholar 

  53. Weis O, Sriwatanakul K, Weintraub M. Treatment of post-herpetic neuralgia and acute herpetic pain with amitriptyline and perphenazine. S Afr Med J 1982 Aug 21; 62: 274–5

    PubMed  CAS  Google Scholar 

  54. Taub A. Relief of postherpetic neuralgia with psychotropic drugs. J Neurosurg 1973 Aug; 39: 235–9

    Article  PubMed  CAS  Google Scholar 

  55. Bianchetti L. Drug therapy of so-called postherpetic neuralgia, the only valid alternative. Clinical experience in 43 treated cases [in Italian]. Minerva Med 1986 Jan 14; 77: 47–50

    PubMed  CAS  Google Scholar 

  56. Milligan NS, Nash TP. Treatment of post-herpetic neuralgia. A review of 77 consecutive cases. Pain 1985 Dec; 23: 381–6

    Article  PubMed  CAS  Google Scholar 

  57. Clarke IM. Amitriptyline and perphenazine (Triptafen DA) in chronic pain. Anaesthesia 1981 Feb; 36: 210–2

    Article  PubMed  CAS  Google Scholar 

  58. Raftery H. The management of post herpetic pain using sodium valproate and amitriptyline. J Ir Med Assoc J 1979 Sep 28; 72: 399–401

    CAS  Google Scholar 

  59. Hampf G, Bowsher D, Nurmikko T. Distigmine and amitriptyline in the treatment of chronic pain. Anesth Prog 1989 Mar–Apr; 36: 58–62

    PubMed  CAS  Google Scholar 

  60. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977–86

    Article  Google Scholar 

  61. Bertherat J, Netter JM, Timsit J, et al. Diabetic thoracoabdominal neuropathy. Clinical and electrophysiological study with evaluation of the autonomic nervous system [in French]. Presse Med 1993 Feb 13; 22: 201–4

    PubMed  CAS  Google Scholar 

  62. Mitas JA 2d, Mosley Jr CA, Drager AM. Diabetic neuropathic pain: control by amitriptyline and fluphenazine in renal insufficiency. South Med J 1983 Apr; 76: 462–3,467

    Article  PubMed  Google Scholar 

  63. Battla H, Silverblatt CW. Clinical trial of amitriptyline and fluphenazine in diabetic peripheral neuropathy. South Med J 1981 Apr; 74: 417–8

    Article  PubMed  CAS  Google Scholar 

  64. Davis JL, Lewis SB, Gerich JE, et al. Peripheral diabetic neuropathy treated with amitriptyline and fluphenazine. JAMA 1977 Nov 21; 238: 2291–2

    Article  PubMed  CAS  Google Scholar 

  65. Hoogwerf BJ. Amitriptyline treatment of painful diabetic neuropathy: an inadvertent single-patient clinical trial [letter]. Diabetes Care 1985 Sep–Oct; 8: 526–7

    PubMed  CAS  Google Scholar 

  66. Young RJ, Clarke BF. Pain relief in diabetic neuropathy: the effectiveness of imipramine and related drugs. Diabet Med 1985 Sep; 2: 363–6

    Article  PubMed  CAS  Google Scholar 

  67. Biesbroeck R, Bril V, Hollander P, et al. A double-blind comparison of topical capsaicin and oral amitriptyline in painful diabetic neuropathy. Adv Ther 1995 Mar–Apr; 12: 111–20

    PubMed  CAS  Google Scholar 

  68. Leijon G, Boivie J. Central post-stroke pain — a controlled trial of amitriptyline and carbamazepine. Pain 1989 Jan; 36: 27–36

    Article  PubMed  CAS  Google Scholar 

  69. Koppel BS. Amitriptyline in the treatment of thalamic pain. South Med J 1986 Jun; 79: 759–61

    Article  PubMed  CAS  Google Scholar 

  70. Kluger NJ, Clifford JS, Cavanagh RJ, et al. A case of a chemically dependent patient with a thalamic pain syndrome treated with amitriptyline. J Addict Dis 1991; 10: 97–102

    Article  PubMed  CAS  Google Scholar 

  71. Gonzales GR, Herskovitz S, Rosenblum M, et al. Central pain from cerebral abscess: thalamic syndrome in AIDS patients with toxoplasmosis. Neurology 1992; 42: 1107–9

    Article  PubMed  CAS  Google Scholar 

  72. Stauffer JD. Antidepressants and chronic pain. J Fam Pract 1987; 25(2): 167–70

    PubMed  CAS  Google Scholar 

  73. Clauw DJ. Fibromyalgia: more than just a musculoskeletal disease. Am Fam Physician 1995 Sep 1; 52: 843–51

    PubMed  CAS  Google Scholar 

  74. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 Criteria for the classification of fibromyalgia: report of the multicenter criteria committee. Arthritis Rheum 1990 Feb; 33(2): 160–72

    Article  PubMed  CAS  Google Scholar 

  75. Simms RW, Felson DT, Goldenberg DL. Development of preliminary criteria for response to treatment in fibromyalgia syndrome. J Rheumatol 1991 Oct; 18: 1558–63

    PubMed  CAS  Google Scholar 

  76. Carette S, Bell MJ, Reynolds WJ, et al. Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia: a randomized, double-blind clinical trial. Arthritis Rheum 1994 Jan; 37: 32–40

    Article  PubMed  CAS  Google Scholar 

  77. Carette S, McCain GA, Bell DA, et al. Evaluation of amitriptyline in primary fibrositis. A double-blind, placebo-controlled study. Arthritis Rheum 1986 May; 29: 655–9

    Article  PubMed  CAS  Google Scholar 

  78. Goldenberg DL, Felson DT, Dinerman H. A randomized, controlled trial of amitriptyline and naproxen in the treatment of patients with fibromyalgia. Arthritis Rheum 1986 Nov; 29: 1371–7

    Article  PubMed  CAS  Google Scholar 

  79. Jaeschke R, Adachi J, Guyatt G, et al. Clinical usefulness of amitriptyline in fibromyalgia: the results of 23 N-of-1 randomized controlled trials. J Rheumatol 1991 Mar; 18: 447–51

    PubMed  CAS  Google Scholar 

  80. Scudds RA, McCain GA, Rollman GB, et al. Improvements in pain responsiveness in patients with fibrositis after successful treatment with amitriptyline. J Rheumatol 1989 Nov; 16 Suppl. 19: 98–103

    Google Scholar 

  81. Goldenberg DL. Treatment of fibromyalgia syndrome. Rheum Dis Clin North Am 1989 Feb; 15: 61–71

    PubMed  CAS  Google Scholar 

  82. Isomeri R, Mikkelsson M, Latikka R Effects of amitriptyline and cardiovascular fitness training on the pain of fibromyalgia patients [abstract]. Scand J Rheumatol 1992; 21 Suppl. 94: 47

    Google Scholar 

  83. Goldenberg DL, Mayskiy M, Mossey C, et al. The independent and combined efficacy of fluoxetine and amitriptyline in the treatment of fibromyalgia [abstract no. 460]]. Arthritis Rheum 1995 Sep; 38(9) Suppl.: S229

    Google Scholar 

  84. Grace EM, Bellamy N, Kassam Y, et al. Controlled, double-blind randomized trial of amitriptyline in relieving articular pain and tenderness in patients with rheumatoid arthritis. Curr Med Res Opin 1985; 9(6): 426–9

    Article  PubMed  CAS  Google Scholar 

  85. McQuay HJ, Carroll D, Glynn CJ. Low dose amitriptyline in the treatment of chronic pain. Anaesthesia 1992 Aug; 47: 646–52

    Article  PubMed  CAS  Google Scholar 

  86. McQuay HJ, Carroll D, Glynn CJ. Dose-response for analgesic effect of amitriptyline in chronic pain. Anaesthesia 1993 Apr; 48: 281–5

    Article  PubMed  CAS  Google Scholar 

  87. Merskey H, Hester RA. The treatment of chronic pain with psychotropic drugs. Postgrad Med J 1972 Oct; 48: 594–8

    Article  PubMed  CAS  Google Scholar 

  88. Duthie AM. The use of phenothiazines and tricyclic antidepressants in the treatment of intractable pain. S Afr Med J 1977 Feb 19; 51: 246–7

    PubMed  CAS  Google Scholar 

  89. Pilowsky I, Barrow CG. A controlled study of psychotherapy and amitriptyline used individually and in combination in the treatment of chronic intractable, ‘psychogenic’ pain [see comments]. Pain 1990 Jan; 40: 3–19

    Article  PubMed  CAS  Google Scholar 

  90. Pilowsky I, Spence N, Rounsefell B, et al. Out-patient cognitive-behavioural therapy with amitriptyline for chronic non-malignant pain: a comparative study with 6-month follow-up. Pain 1995 Jan; 60: 49–54

    Article  PubMed  CAS  Google Scholar 

  91. Egbunike IG, Chaffee BJ. Antidepressants in the management of chronic pain syndromes. Pharmacotherapy 1990; 10: 262–70

    PubMed  CAS  Google Scholar 

  92. Jacox A, Carr DB, Payne R. New clinical-practice guidelines for the management of pain in patients with cancer. N Engl J Med 1994 Mar 3; 330(9): 651–5

    Article  PubMed  CAS  Google Scholar 

  93. Gastmeier K, Hass M, Schott H, et al. Pain therapy for urologic cancer patients at the Potsdam district hospital — initial results [in German]. Z Urol Nephrol 1990 Oct; 83: 547–54

    PubMed  CAS  Google Scholar 

  94. Kocher R. The use of psychotropic drugs in the treatment of cancer pain. Recent Results Cancer Res 1984; 89: 118–26

    Article  PubMed  CAS  Google Scholar 

  95. Magni G, Arsie D, de Leo D. Antidepressants in the treatment of cancer pain: a survey in Italy. Pain 1987; 29: 347–53

    Article  PubMed  CAS  Google Scholar 

  96. Breivik H, Rennemo F. Clinical evaluation of combined treatment with methadone and psychotropic drugs in cancer patients. Acta Anaesthesiol Scand 1982; 74 Suppl.: 135–40

    Article  CAS  Google Scholar 

  97. World Health Organization. Cancer pain relief. Geneva: WHO, 1986

    Google Scholar 

  98. Chaturvedi SK. Pain relief in active patients with cancer [letter]. BMJ 1989 Feb 18; 298: 461

    Google Scholar 

  99. Noyes Jr R. Treatment of cancer pain. Psychosom Med 1981 Feb; 43(1): 57–70

    PubMed  Google Scholar 

  100. Richlin DM, Jamron LM, Novick NL. Cancer pain control with a combination of methadone, amitriptyline, and non-narcotic analgesic therapy: a case series analysis. J Pain Symptom Manage 1987 Spring; 2: 89–94

    Article  PubMed  CAS  Google Scholar 

  101. Ventafridda V, Bonezzi C, Caraceni A, et al. Antidepressants for cancer pain and other painful syndromes with deafferentation component: comparison of amitriptyline and trazodone. Ital J Neurol Sci 1987 Dec; 8: 579–87

    Article  PubMed  CAS  Google Scholar 

  102. Bagheri H, Picault P, Schmitt L, et al. Pharmacokinetic study of yohimbine and its pharmacodynamic effects on salivary secretion in patients treated with tricyclic antidepressants. Br J Clin Pharmacol 1994 Jan; 37: 93–6

    Article  PubMed  CAS  Google Scholar 

  103. Glassman AH. Cardiovascular effects of tricyclic antidepressants. Annu Rev Med 1984; 35: 503–11

    Article  PubMed  CAS  Google Scholar 

  104. Mamdani FS. Pharmacologic management of herpes zoster and postherpetic neuralgia. Can Fam Phys 1994 Feb; 40: 321–32

    CAS  Google Scholar 

  105. Clark Jr CM, Lee DA. Prevention and treatment of the complications of diabetes mellitus. N Engl J Med 1995 May 4; 332: 1210–7

    Article  PubMed  Google Scholar 

  106. Rains C, Bryson HM. Topical capsaicin: a review of its pharmacological properties and therapeutic potential in post-herpetic neuralgia, diabetic neuropathy and osteoarthritis. Drugs Aging 1995 Oct; 7(4): 317–28

    Article  PubMed  CAS  Google Scholar 

  107. Masi AT. An intuitive person-centred perspective on fibromyalgia and its management. Baillieres Clin Rheumatol 1994; 8(4): 957–93

    Article  PubMed  CAS  Google Scholar 

  108. Wilke WS. Treatment of “resistant” fibromyalgia. Rheum Dis Clin North Am 1995 Feb; 21(1): 247–60

    PubMed  CAS  Google Scholar 

  109. Burckhardt CS, Bjelle A. Education programmes for fibromyalgia patients: description and evaluation. Baillieres Clin Rheumatol 1994 Nov; 8(4): 935–55

    Article  PubMed  CAS  Google Scholar 

  110. Warfield CA, Stein JM. The pain clinic: the use of systemic analgesics. Hosp Pract Off Ed 1982; 17(7): 88A–B, 88dm 88H passim

    Google Scholar 

  111. Baines M. Pain relief in active patients with cancer: analgesic drugs are the foundation of management. BMJ 1989 Jan 7; 298: 36–8

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Various sections of the manuscript reviewed by: S. Carette, Department of Medicine, Centre Hospitalier de l’Université Laval, Sainte Foy, Québec, Canada; B.M. Fusco, Department of Clinical Medicine, University ‘La Sapienza’ of Rome, Rome, Italy; K. Ghose, Department of Pharmacology, University of Otago, Dunedin, New Zealand; J.J. Lee, Pain Relief Clinic, Worcester Royal Infirmary, Ronkswood Branch, Worcester, England; F.H. McDowell, Winifred Masterton Burke Rehabilitation Hospital, White Plains, New York, USA; G. Olive, Service de Pharmacologie Clinique, Service de Biochimie, Hôpital Saint-Vincent de Paul, Paris, France; P. Onghena, Department of Educational Sciences, Katholieke Universiteit Leuven, Leuven, Belguim; I. Pilowsky, Department of Psychiatry, University of Adelaide, Adelaide, Australia; C.P.N. Watson, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bryson, H.M., Wilde, M.I. Amitriptyline. Drugs & Aging 8, 459–476 (1996). https://doi.org/10.2165/00002512-199608060-00008

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-199608060-00008

Keywords

Navigation