Skip to main content
SpringerLink
Log in

Benefits and Risks of Pharmacotherapy for Dysthymia

A Systematic Appraisal of the Evidence

  • Original Research Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Background: Dysthymia is a prevalent form of subthreshold depressive disorder, associated with considerable disability and high co-morbidity. This paper systematically appraises the evidence for the efficacy and acceptability of the pharmacological treatment for this condition.

Methods: Randomised, controlled trials evaluating the efficacy of drug therapies for dysthymia were included. A comprehensive search of the literature was performed, aiming to avoid publication bias. Pooled relative risks (RR) and 95% CIs were calculated with the Random Effect Model method. The number needed to treat (NNT) and number needed to harm (NNH) were estimated for statistically significant results.

Results: Twenty-five trials were included for the main comparisons. Regarding placebo-controlled trials (n = 16), similar results were obtained in terms of efficacy for different groups of drugs, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and other drugs (sulpiride, amineptine, and ritanserin). The pooled RR for treatment response was 0.68 (95% CI 0.57–0.81) for TCA and the NNT was 4.3 (95% CI 3.2–6.5); 0.68 (95% CI 0.56–0.82) for SSRIs (NNT 5.1; 95% CI 3.9–7.7); 0.59 (95% CI 0.48–0.71) for MAOIs (NNT 2.9; 95% CI 2.2–4.3). Other drugs (amisulpride, amineptine and ritanserin) showed similar results. The equivalent efficacy between antidepressants as found in trials where active medications were compared confirmed the efficacy findings from placebo trials. In general, patients treated with a TCA were more likely to report adverse events, compared with placebo and SSRIs.

Conclusions: Pharmacotherapy for dysthymia appears to be an effective short-term treatment for dysthymic disorder. Newer antidepressants are equally effective and have better acceptability than TCAs, although their higher cost must be balanced against this assumed advantage.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1
Table II
Fig. 2

Similar content being viewed by others

References

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-III). 3rd ed. Washington, DC: American Psychiatric Association, 1980

  2. Weissman MM, Leaf PJ, Bruce ML, et al. The epidemiology of dysthymia in five communities: rates, risks, comorbidity and treatment. Am J Psychiatry 1988; 145(7): 815–9

    PubMed  CAS  Google Scholar 

  3. Akiskal HS. Dysthymic disorder: psychopathology of proposed chronic depressive subtypes. Am J Psychiatry 1983; 140: 11–20

    PubMed  CAS  Google Scholar 

  4. Thase ME, Fava M, Halbreich U, et al. A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia. Arch Gen Psychiatry 1996; 53: 777–84

    Article  PubMed  CAS  Google Scholar 

  5. WPA Dysthymia Working Group. Dysthymia in clinical practice. Br J Psychiatry 1995; 166: 174–83

    Google Scholar 

  6. Kocsis JH. Chronic depression: the efficacy of pharmacotherapy. In: Akiskal HS, Cassano GB, editors. Dysthymia and the spectrum of chronic depression. New York: The Guilford Press, 1997

    Google Scholar 

  7. Lima MS, Moncrieff J. A comparison of drugs versus placebo for the treatment of dysthymia: a systematic review. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 3. Oxford: Update Software, 1998

    Google Scholar 

  8. Lima MS, Hotopf M, Wessely S. The efficacy of drug treatments for dysthymia. Psychol Med 1999; 29(6): 1273–89

    Article  PubMed  Google Scholar 

  9. Schulz KF, Chalmers I, Hayes RJ, et al. Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995; 273: 408–12

    Article  PubMed  CAS  Google Scholar 

  10. Altman DG. Confidence intervals for the number needed to treat. BMJ 1998; 317: 1309–12

    Article  PubMed  CAS  Google Scholar 

  11. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-III-R). 3rd ed., revised. Washington, DC: American Psychiatric Association, 1987

  12. Stewart JW, McGrath PJ, Liebowitz MR, et al. Treatment outcome validation of DSM-III depressive subtypes: clinical usefulness in outpatients with mild to moderate depression. Arch Gen Psychiatry 1985; 42: 1148–53

    Article  PubMed  CAS  Google Scholar 

  13. Reyntjens A, Gelders YG, Hoppenbrouwers MLJA, et al. Thymosthenic effects of ritanserin (R 55667), a centrally acting serotonin-S2 receptor blocker. Drug Dev Res 1986; 8: 205–11

    Article  CAS  Google Scholar 

  14. Kocsis JH, Frances AJ, Voss C, et al. Imipramine treatment for chronic depression. Arch Gen Psychiatry 1988; 45: 253–7

    Article  PubMed  CAS  Google Scholar 

  15. Stewart JW, McGrath PJ, Quitkin FM, et al. Relevance of DSM-III depressive subtype and chronicity of antidepressant efficacy in atypical depression: differential response to phenelzine, imipramine, and placebo. Arch Gen Psychiatry 1989; 46: 1080–7

    Article  PubMed  CAS  Google Scholar 

  16. Botte L, Evrard JL, Gilles C, et al. Controlled comparison of RO 11-1163 (moclobemide) and placebo in the treatment of depression. Acta Psychiatr Belg 1992; 92: 355–69

    PubMed  CAS  Google Scholar 

  17. Bella R, Biondi R, Raffaele R, et al. Effect of acetyl-L-carnitine on geriatric patients suffering from dysthymic disorders. Int J Clin Pharmacol Res 1990; 10: 355–60

    PubMed  CAS  Google Scholar 

  18. Costa e Silva J. Traitement des dysthymies par de faibles doses d’amisulpride. Etude comparative amisulpride 50 mg/j versus placebo. Annales De Psychiatrie 1990; 5(3): 242–9

    Google Scholar 

  19. Bersani G, Pozzi F, Marini S, et al. 5-HT2 receptor antagonism in dysthymic disorder: a double-blind placebo-controlled study with ritanserin. Acta Psychiatr Scand 1991; 83: 244–8

    Article  PubMed  CAS  Google Scholar 

  20. Bakish D, Lapierre YD, Weinstein R, et al. Ritanserin, imipramine and placebo in the treatment of dysthymic disorder. J Clin Psychopharmacol 1993; 13(6): 409–14

    Article  PubMed  CAS  Google Scholar 

  21. Hellerstein DJ, Yanowitch P, Rosenthal J, et al. A randomized double-blind study of fluoxetine versus placebo in the treatment of dysthymia. Am J Psychiatry 1993; 150: 1169–75

    PubMed  CAS  Google Scholar 

  22. Boyer P, Lecrubier Y. Atypical antipsychotic drugs in dysthymia: placebo controlled studies of amisulpride versus imipramine, versus amineptine. Eur Psychiatry 1996; 11Suppl. 3: 135S–40S

    Article  Google Scholar 

  23. Ravindran AV, Guelfi JD, Lane RM, et al. Treatment of dysthymia with sertraline: a double-blind, placebo-controlled trial in dysthymic patients without major depression. J Clin Psychiatry 2000; 61(11): 821–7

    Article  PubMed  CAS  Google Scholar 

  24. Reyntjens A, Gelders YG, Hoppenbrouwers MLJA, et al. Thymosthenic effects of ritanserin (R 55667), a centrally acting serotonin-S2 receptor blocker. Drug Dev Res 1986; 8: 205–11

    Article  CAS  Google Scholar 

  25. Vanelle JM. Controlled efficacy study of fluoxetine in dysthymia. Br J Psychiatry 1997; 170: 345–50

    Article  PubMed  CAS  Google Scholar 

  26. Versiani M, Amrein R, Stabl M. Moclobemide and imipramine in chronic depression (dysthymia): an international double-blind, placebo-controlled trial. International Collaborative Study Group. Int Clin Psychopharmacol 1997; 12: 183–93

    Article  PubMed  CAS  Google Scholar 

  27. Williams Jr JW, Barrett J, Oxman T, et al. Treatment of dysthymia and minor depression in primary care: a randomized controlled trial in older adults. JAMA 2000; 284(12): 1519–26

    Article  PubMed  CAS  Google Scholar 

  28. Kocsis JH, Sutton BM, Frances AJ. Long-term follow-up of chronic depression treated with imipramine. J Clin Psychiatry 1991; 52: 56–9

    PubMed  CAS  Google Scholar 

  29. Kocsis JH, Friedman RA, Markowitz JC, et al. Maintenance therapy for chronic depression: a controlled clinical trial of desipramine. Arch Gen Psychiatry 1996; 53: 769–74

    Article  PubMed  CAS  Google Scholar 

  30. Harrison W, Rabkin J, Stewart JW, et al. Phenelzine for chronic depression: a study of continuation treatment. J Clin Psychiatry 1986; 47: 346–9

    PubMed  CAS  Google Scholar 

  31. Otero FJ, Hernandez-Herrero C, Martinez-Arevalo M-J, et al. Fluoxetine/bentazepam combination in the treatment of dysthymic disorders. Curr Ther Res 1994; 55 (5): 519–31

    Article  Google Scholar 

  32. Hellerstein DJ, Yanowitch P, Rosenthal J, et al. Long-term treatment of double depression: a preliminary study with serotonergic antidepressants. Prog Neuropsychopharmacol Biol Psychiatry 1994; 18: 139–47

    Article  PubMed  CAS  Google Scholar 

  33. Geisler A, Mygind S, Knudsen R, et al. Ritanserin and flupenthixol in dysthymic disorder. Nord J Psychiatry 1992; 46: 237–43

    Article  Google Scholar 

  34. Guelfi JD, Pichot P, Dreyfus JF. Efficacy of tianeptine in anxious-depressed patients: results of a controlled multicenter trial versus amitriptiline. Neuropsychobiology 1989; 22: 41–8

    Article  PubMed  CAS  Google Scholar 

  35. Leon CA, Vigoya J, Conde S, et al. Comparacion del efecto de la amisulprida y la viloxacina en el tratamiento de la distimia (Therapeutic efficacy of amisulpride and viloxazine in the treatment of dysthymia: a comparison). Acta Psiquiatr Psicol Am Lat 1994; 40(1): 41–9

    PubMed  CAS  Google Scholar 

  36. Rosenthal J, Hemlock C, Hellerstein DJ, et al. A preliminary study of serotonergic antidepressants in treatment of dsythymia. Prog Neuropsychopharmacol Biol Psychiatry 1992; 16: 933–41

    Article  PubMed  CAS  Google Scholar 

  37. Salzmann E, Robin JL. Multicentric double-blind study comparing efficacy and safety of minaprine and imipramine in dysthymic disorders. Neuropsychobiology 1995; 31: 68–75

    Article  PubMed  CAS  Google Scholar 

  38. Smeraldi E, Haefele E, Crespi G, et al. Amisulpride versus fluoxetine in dysthymia: preliminary results of a double-blind comparative study. Eur Psychiatry 1996; 11Suppl. 3: 141S–3S

    Article  Google Scholar 

  39. Vallejo J, Gastro C, Catalan R, et al. Double-blind study of imipramine versus phenelzine in melancholias and dysthymic disorders. Br J Psychiatry 1987; 151: 639–42

    Article  PubMed  CAS  Google Scholar 

  40. Furukawa TA, Streiner DL, Young LT. Antidepressant and benzodiazepine for major depression. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2002

    Google Scholar 

  41. Bacaltchuk J, Hay P. Antidepressants versus placebo for people with bulimia nervosa. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2002

    Google Scholar 

  42. Kapczinski F, Schmitt R, Lima MS. The use of antidepressants for generalized anxiety disorder. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2002

    Google Scholar 

  43. Mulrow CD, Williams Jr JW, Trivedi M, et al. Treatment of depression: newer pharmacotherapies: evidence report/technology assesment no. 7. Prepared by the San Antonio Evidence-based Practice Center based at The University of Texas Health Science Center at San Antonio under Contract 290-97-0012

  44. Barbui C, Hotopf M, Freemantle N, et al. Treatment discontinuation with selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants (TCAs). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 4. Oxford: Update Software, 2002

    Google Scholar 

Download references

Acknowledgements

We would like to thank Dr J. Kocsis, Dr M. Versiani, Dr A. Ravindran, Dr D. Hellerstein and Dr A. Reyntjens, authors of clinical trials in dysthymia who provided additional information for this review. Dr De Lima has a grant for research from CNPq, Ministry of Education, Brazil.

The authors have no conflicts of interest directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Departamento de Saúde Mental, Faculdade de Medicina, Universidade Federal de Pelotas and Universidade Católica de Pelotas, UFPel. Av. Duque de Caxias 250, Pelotas, Rio Grande do Sul, Brazil

    Maurício S. De Lima

  2. Institute of Psychiatry, London, United Kingdom

    Maurício S. De Lima

  3. Guy’s King’s and St Thomas’ School of Medicine, King’s College, London, United Kingdom

    Matthew Hotopf

Authors
  1. Maurício S. De Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew Hotopf
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Lima, M.S., Hotopf, M. Benefits and Risks of Pharmacotherapy for Dysthymia. Drug-Safety 26, 55–64 (2003). https://doi.org/10.2165/00002018-200326010-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-200326010-00006

Keywords

Search

Navigation