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Meta-analysis of 38 placebo-controlled studies examining the antidepressant-induced analgesic effect

Published online by Cambridge University Press:  18 September 2015

P. Onghena*
Affiliation:
licentiaat klinische en mathematische psycholie, aspirant N.F.W.O.
B. van Houdenhove
Affiliation:
neuropsychiater, buitengewoon docent Faculteit Geneeskunde K.U. Leuven
*
Faculteit Psychologie en Pedagogische Wetenschappen, Centrum voor Mathematische Psychologie en Psychologische Methodologie, Tiensestraat 102, B-3000 Leuven

Summary

For all controlled studies that bear upon the analgesic-effect of antidepressants, a meta-analysis was conducted to get an estimation of the effect size and to get a sight on the possible modes of action. For this purpose both content and methodological variables were coded for each study. The mean size of the analgesic effect is 0.63. This means that the average patient getting an antidepressant has less pain than 74% of the patients getting a placebo. However because of selective drop-out and the use of psychometri-cally inadequate pain scales, this may be an over-estimation. Real analgesic qualities of antidepressive agents seem to offer the most plausible explanation for the effect, but the importance of serotonin reuptake blocking is not confirmed. A main objection, however, is that in all studies the depression variable was insufficiently controlled at inclusion. Because both the estimation of the effect size as the explanation of the effect are confounded with methodological doubts, it is concluded that further studies need to be done to overcome these difficulties.

Type
Research Article
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 1990

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References

Literatuur

1.Paoli, MF, Darcourt, G, Cossa, P. Note préliminaire sur l'action de l'imipramine dans les états douloureux. Rev Neurol 1960; 102:38–9.Google Scholar
2.France, RD, Houpt, JL, Ellinwood, EH. Therapeutic effects of antidepressants in chronic pain. Gen Hosp Psychiat 1984; 6: 55–63.CrossRefGoogle ScholarPubMed
3.Feinmann, C. Pain relief by antidepressants: Possible modes of action. Pain 1985; 23: 18.CrossRefGoogle ScholarPubMed
4.Gershon, S. Chronic pain: Hypothesized mechanism and rationale for treatment. Neuropsychobiol 1986; 15(Suppl 1):22–7.CrossRefGoogle ScholarPubMed
5.Van Houdenhove, B, Knapen, P. De relatie tussen chronische pijn en depressie (II): Therapeutische aspecten. Tijdschr Psychiat 1986; 28: 145–65.Google Scholar
6.Blumer, D, Heilbronn, M. Second-year follow-up study on systematic treatment of chronic pain with antidepressants. Henry Ford Hosp med J 1981;29:67–8.Google ScholarPubMed
7.Lascelles, RG. Atypical facial pain and depression. Br J Psychiat 1966; 112:651–9.CrossRefGoogle ScholarPubMed
8.Turkington, RW. Depression masquerading as diabetic neuropathy. JAMA 1980; 243: 1147–50.CrossRefGoogle ScholarPubMed
9.Aronoff, MG, Evans, WO. Doxepin as an adjunct in the treatment of chronic pain. J clin Psychiat 1982; 43:42–7.Google ScholarPubMed
10.Hanks, GW. Psychotropic drugs. Postgrad med J 1984; 60: 881–5.CrossRefGoogle ScholarPubMed
11.Walsh, TT. Antidepressants in chronic pain. Clinical Neuropharmacol 1983;6:271–95.CrossRefGoogle ScholarPubMed
12.Kocher, R. Use of psychotropic drugs for the treatment of chronic severe pain. In: Bonica, JJ, Albe-Fessard, D, eds. Advances in pain research and therapy: Vol 1. New York: Raven Press, 1976, 579–82.Google Scholar
13.Kocher, R. Die Behandlung chronischer Schmerzen mit Psychopharmaka. Schweiz med Wochensch 1978; 108:686–91.Google Scholar
14.Kocher, R. Psychopharmaka bei chronischen Schmerzen. Schweiz Rundschau Med Prax, 1982; 71: 1790–94.Google Scholar
15.Meyers, C. L'association mélitrancène-flupentixol: Bistouri chimique ou outil d'estompage de la douleur chronique. Med Hyg 1985; 43:630–4.Google Scholar
16.Meyers, C, Noël, G, Piraux, A, Jacquy, J. Une approche du traitement du trijumeau fantôme. Acta neural belg 1972; 72:355–65.Google Scholar
17.Eberhard, G, von Knorring, L, Nilsson, HL, Lundquist, U, Björling, G, Linder, H, Svärd, KO, Tysk, L. A Double blind randomized study of clomipramine versus maprotiline in patients with idiopathic pain syndromes. Neuropsychobiol 1988; 19:2534.CrossRefGoogle ScholarPubMed
18.Johansson, F, von Knorring, L. A double-mind controlled study of a serotonin uptake inhibitor (zimelidine) versus placebo in chronic pain patients. Pain 1979; 7: 6978.CrossRefGoogle Scholar
19.Johansson, F, von Knorring, L, Sedvall, G, Terenius, L. Changes in endorphins and 5-hydroxyindole-acetic acid in cerebrospinal fluid as a result of treatment with a serotonin reuptake inhibitor (zimelidine) in chronic pain patients. Psychiat Res 1980; 2:167–72.CrossRefGoogle ScholarPubMed
20.Loldrup, D, Langemark, M, Hansen, HJ, Olesen, J, Bech, P. Clomipramine and mianserin in chronic idiopathic pain syndrome: A placebo controlled study. Psychopharmacol 1989; 99: 17.CrossRefGoogle ScholarPubMed
21.Messing, RB, Lytle, LD. Serotonin-containing neurons: Their possible role in pain and analgesia. Pain 1977; 4:121.CrossRefGoogle ScholarPubMed
22.Evans, W, Gensler, F, Blackwell, B, Galbrecht, C. The effects of antidepressant drugs on pain relief and mood in the chronically ill. Psychosomatics 1973; 14: 214–9.CrossRefGoogle ScholarPubMed
23.Jenkins, DG, Ebbutt, AF, Evans, CD. Tofranil in the treatment of low back pain. J int med Res 1976; 4(Suppl 2): 2840.Google ScholarPubMed
24.Wheatly, D. Antidepressants in elderly arthritics. Practitioner 1986; 230:477–81.Google Scholar
25.Smith, ML, Glass, GV. Meta-analysis of psychotherapy outcome studies. Am Psychol 1977; 32: 752–60.CrossRefGoogle ScholarPubMed
26.Rosenthal, R. Combining results of independent studies. Psychol Bull 1978; 85: 185–93.CrossRefGoogle Scholar
27.Smith, ML, Glass, GV, Miller, TI. The benefits of psychotherapy. Baltimore: Johns Hopkins University Press, 1980.Google Scholar
28.Melzack, R. The McGill Pain Questionnaire: Major properties and scoring methods. Pain 1975; 1: 277–99.CrossRefGoogle ScholarPubMed
29.Huskisson, EC. Visual Analogue Scales. In: Melzack, R ed. Pain measurement and assessment. New York: Raven Press, 1983, 33–7.Google Scholar
30.Cohen, J. Statistical power analysis for the behavioral sciences, 2nd ed. Hillsdale: Lawrence Erlbaum Associates, 1988.Google Scholar
31.US Department of Helath & Human Services. Medline Database, rev ed. Torrance: Ebsco Electronic Information, 1989.Google Scholar
32.Glass, GV, McGaw, B, Smith, ML. Meta-analysis in social research. Beverly Hills: Sage, 1981.Google Scholar
33.Kielholz, P, Pöldinger, W, Adams, C. Masked depression: A didactic concept for the diagnosis and treatment of somatised depressions. Köln-Lövenich: Deutscher Arzte-Verlag, 1982.Google Scholar
34.Richelson, E. Closing lecture. Pharmacol Toxicol Supplement (Denmark) 1990; 66: 144–8.CrossRefGoogle Scholar
35.Alcoff, J, Jones, E, Rust, P. Newman, R. Controlled trial of imipramine for chronic low back pain. J Fam Prac 1982; 14:841–6.Google ScholarPubMed
36.Carette, S, McCain, GA, Bell, DA, Fam, AG. Evaluation of amitripty-line in primary fibrositis: a double-blind, placebo-controlled study. Arthr Rheumat 1986;29:655–9.CrossRefGoogle Scholar
37.Couch, SR, Hassanein, RS. Amitriptyline in migraine profylaxis. Arch Neurol 1979; 36: 695–99.CrossRefGoogle Scholar
38.Davidoff, G, Guarracini, M, Roth, E, Sliwa, J, Yarkony, G. Trazodone hydrochloride in the treatment of dysesthetic pain in traumatic myelopathy: A randomized, double-blind, placebo-controlled study. Pain 1987; 29: 151–61.CrossRefGoogle ScholarPubMed
39.Diamond, S. Psychogenic headaches with mixed anxiety and depression. Ill med J, 1975; 03: 268–9.Google Scholar
40.Diamond, S, Baltes, BJ. Chronic tension headache treated with amitriptyline: A double-blind study. Headache 1971; 2: 110–6.CrossRefGoogle Scholar
41.Evans, W, Gensler, F, Blackwell, B, Galbrecht, C. The effects of antidepressant drugs on pain relief and mood in the chronically ill. Psychosomatics 1973; 14: 214–9.CrossRefGoogle ScholarPubMed
42.Feinmann, C. Psychogenic facial pain: Presentation and treatment. J psychosom Res 1983; 27:403–10.CrossRefGoogle ScholarPubMed
43.Fogelholm, R, Murros, K. Maprotiline in chronic tension headache: A double-blind cross-over study. Headache 1985; 25:273–5.CrossRefGoogle ScholarPubMed
44.Frank, RG, Kashani, JH, Parker, JC, Beck, NC, Brownlee-Duffeck, M, Elliott, TR, Haut, AE, Atwood, C, Smith, E, Kay, DR. Antidepressant analgesia in rheumatoid arthritis. J Rheum 1988; 15: 1632–8.Google ScholarPubMed
45.Ganvir, P, Beaumont, G, Seldrup, J. A comparative trial of clomipramine and placebo as adjunctive therapy in arthralgia. J int med Res 1980; 8(Suppl 3): 60–6.Google ScholarPubMed
46.Goldenberg, DL, Felson, DT, Dinerman, H. A randomized, controlled trial of amitriptyline and naproxen in the treatment of patients with fibromyalgia. Arthr Rheumat 1986; 29: 1371–7.CrossRefGoogle ScholarPubMed
47.Gomersall, JD, Stuart, A. Amitriptyline in migraine prophylaxis: Changes in pattern of attacks during a controlled clinical trial. J Neurol Neurosurg Psychiat 1973; 36:684–90.CrossRefGoogle ScholarPubMed
48.Gomez-Perez, FJ, Rull, JA, Dies, H, Rodriguez-Rivera, JG, Gonzalez-Barranco, J, Lozano-Castaneda, D. Nortriptyline and fluphenazine in the symptomatic treatment of diabetic neuropathy: A double-blind cross-over study. Pain 1985; 23: 395400.CrossRefGoogle ScholarPubMed
49.Gourlay, GK, Cherry, DA, Cousins, MJ, Love, BL, Graham, JR, McLachlan, MD. A controlled study of a serotonin reuptake blocker, zimelidine, in the treatment of chronic pain. Pain 1986; 25: 3552.CrossRefGoogle ScholarPubMed
50.Gringas, M. A clinical trial of tofranil in rheumatic pain in general practice. J int med Res 1976; 4(Suppl 2): 41–9.Google Scholar
51.Hameroff, SR, Cork, RC, Scherer, K, Crago, BR, Neuman, C, Womble, JR, Davis, TP. Doxepin effects on chronic pain, depression and plasma opioids. J clin Psychiat 1982; 43:22–7.Google ScholarPubMed
52.Hameroff, SR, Weiss, JL, Lerman, JC, Cork, RC, Watts, KS, Crago, BR, Neuman, CP, Womble, JR, Davis, TP. Doxepin's effects on chronic pain and depression: A controlled study. J clin Psychiat 1984; 45:4752.Google ScholarPubMed
53.Jenkins, DG, Ebbutt, AF, Evans, CD. Tofranil in the treatment of low back pain. J int med Res 1976; 4(Suppl 2): 2840.Google ScholarPubMed
54.Johansson, F, von Knorring, L. A double-blind controlled study of a serotonin uptake inhibitor (zimelidine) veeersus placebo in chronic pain patients. Pain 1979; 7:6978.CrossRefGoogle ScholarPubMed
55.Lance, JW, Curran, DA. Treatment of chronic tension headache. Lancet 1964; I: 1236–9.CrossRefGoogle Scholar
56.Lascelles, RG. Atypical facial pain and depression. Br J Psychiat 1966; 112:651–9.CrossRefGoogle ScholarPubMed
57.Loldrup, D, Hansen, HJ, Langemark, M, Olesen, J, Bech, P. Discomfort or disability in patients with chronic pain syndrome. Psychother Psychosom 1987;48:60–2.Google Scholar
58.Loldrup, D, Langemark, M, Hansen, HJ, Olesen, J, Bech, P. Clomipramine and mianserin in chronic idiopathic pain syndrome: A placebo controlled study. Psychopharmacol 1989; 99:17.CrossRefGoogle ScholarPubMed
59.MacNeill, AL, Carson Dick, W. Imipramine and rheumatoid factor. J int med Res 1976; 4(Suppl 2): 2327.Google ScholarPubMed
60.Macfarlane, JG, Jalali, S, Grace, EM. Trimipramine in rheumatoid arthritis: A double-blind trial in relieving pain and joint tenderness. Currmed Res Opin 1986; 10: 8993.CrossRefGoogle ScholarPubMed
61.Martucci, N, Agnoli, A, Manna, V, Bocola, V. Headache and noradrenergic involvement: Study with alpha-2 stimulants and blockers. Clin Neuropharmacol 1984; 7(Suppl 1): 656-–7.CrossRefGoogle Scholar
62.Martucci, N, Manna, V, Porto, C, Agnoli, A. Migraine and the noradrenergic control of vasomotricity: A study with alpha-2 stimulant and alpha-2 blocker drugs. Headache 1985; 25:95100.CrossRefGoogle ScholarPubMed
63.Max, MB, Schafer, SC, Culnane, M, Gracely, RH, Smoller, B, Dubner, R. Amitriptyline but not lorazepam relieves postherpetic neuralgia. Pain 1988; 31 (Suppl 4): 348.Google Scholar
64.Max, MB, Schafer, SC, Culnane, M, Smoller, B, Dubner, R, Gracely, RH. Amitriptyline, but not lorazepam, relieves postherpetic neuralgia. Neurol 1988; 38: 1427–32.CrossRefGoogle Scholar
65.McDonald Scott, WA. The relief of pain with an antidepressant in arthritis. Practitioner 1969; 202: 802–7.Google Scholar
66.Monro, P, Swade, C, Coppen, A. Double blind comparative study of mianserin versus placebo in the prophylaxis of migraine. Clin Neuropharmacol 1984;7(Suppl 1): 645–55.CrossRefGoogle Scholar
67.Monro, P, Swade, C, Coppen, A. Mianserin in the prophylaxis of migraine: A double-blind study. Acta psychiat scand 1985; 72(Suppl 320): 98103.CrossRefGoogle Scholar
68.Morland, TJ, Storli, OV, Mogstad, TE. Doxepin in the prophylactic treatment of mixed ‘vascular’ and tension headache. Headache 1979; 19:382–3.CrossRefGoogle ScholarPubMed
69.Okasha, A, Ghaleb, HA, Sadek, A. A double blind trial for the clinical management of psychogenic headache. Br J Psychiat 1973; 122: 181–3.CrossRefGoogle ScholarPubMed
70.Panerai, AE, Tiengo, M, Movilia, PG, Bianchi, M, Monza, GC. A controlled trial on the effectiveness of antidepressants in central pain. Pain 1987; 31 (Suppl 4): 348.CrossRefGoogle Scholar
71.Pheasant, H, Bursk, A, Goldfarb, J, Azen, SP, Weiss, JN, Borelli, L. Amitriptyline and chronic low-back pain: A randomized double-blind crossover study. Spine 1983; 8: 552–7.CrossRefGoogle ScholarPubMed
72.Pilowsky, I, Hallet, EC, Basset, DL, Thomas, PG, Penhall, RK. A controlled study of amitriptyline in the treatment of chronic pain. Pain 1982; 14:169–79.CrossRefGoogle ScholarPubMed
73.Sharav, Y, Singer, E, Schmidt, E, Dionne, RA, Dubner, R. The analgesic effect of amitriptyline on chronic facial pain. Pain 1987; 31: 199209.CrossRefGoogle ScholarPubMed
74.Watson, CP, Evans, RJ, Reed, K, Merskey, H, Goldscmith, L, Warsh, J. Amitriptyline versus placebo in post-herpetic neuralgia. Neurol 1982;32:671–3.CrossRefGoogle Scholar
75.Wheatly, D. Antidepressants in elderly arthritics. Practitioner 1986; 230:477–81.Google Scholar
76.Watson, CPN. Therapeutic window for amitriptyline analgesia. Can med Assoc J 1984; 130: 105–6.Google ScholarPubMed