CNS Drugs

, Volume 19, Issue 4, pp 313–324

Social Functioning

Should it Become an Endpoint in Trials of Antidepressants?
Review Article

Abstract

DSM-IV has recommended use of the Social and Occupational Functioning Scale (SOFAS) as a clinician-rated global assessment scale for measuring social functioning; this scale is analogous to the Clinical Global Impression (CGI) scale traditionally used as a secondary outcome measure in patients with depressive symptoms. However, we believe that health-related quality of life is the most appropriate indicator of social functioning when considering this dimension as an endpoint in clinical trials of antidepressants. As health-related quality of life is a purely subjective measure, patient-rated questionnaires have been found to be most important in this context. In this respect, the Sheehan Disability Scale has been recommended as the most relevant global self-reported assessment of social functioning in trials of antidepressants.

A review of questionnaires found that the three most frequently used scales selectively directed at obtaining information about social functioning in trials of antidepressants are the Social Adjustment Scale — Self Report (SAS-SR), the Social Adaptation Self-Evaluation Scale (SASS) and the Short-Form Health Survey (SF-36). However, the number of placebo-controlled trials of antidepressants that have used these scales is still too limited to allow comparisons in terms of responsiveness.

Health-related quality of life includes dimensions other than social functioning, e.g. physical health and mental health (including both cognitive and affective problems). The SF-36 includes subscales relating to physical and mental health, which, like the social functioning subscales, are measured in terms of degrees of well being. Another quality-of-life questionnaire, the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), covers social, mental and physical problems, in this case measured in terms of degrees of satisfaction. Recently, the Q-LES-Q has been reduced from a comprehensive scale including 60–92 items to a brief version including 15 items. An additional item measures overall life satisfaction. As most of the items in the brief Q-LES-Q include social functioning, the scale can be considered as an alternative to SF-36 or the Sheehan Disability Scale when the focus is on satisfaction with treatment. However, there are insufficient numbers of trials of antidepressants using these questionnaires to allow comparisons.

The examples of trials of antidepressants with the SF-36 subscales discussed in this review have mostly involved SSRIs. These trials have demonstrated that although antidepressants improve social functioning compared with placebo over a 6-week treatment period, the endpoint scores are still significantly below the national norms at this point. Only after 12 weeks of therapy are the endpoint scores of the social functioning scales within the limits of the national norms. In relapse prevention trials or in maintenance trials to prevent recurrence of depression, comparisons of social functioning scores with national norms can be important supplementary indicators of the need for treatment.

In conclusion, social functioning as part of the health-related concept of the patient-reported quality-of-life measure should constitute an endpoint in trials of antidepressants to help clarify the goals of treatment in patients with major depression. In medium- and long-term trials, SF-36 subscales should be used as a supplement to symptom-orientated scales. In trials of shorter (6–8 weeks) duration, use of other scales such as the SAS-SR, the Q-LES-Q or the Sheehan Disability Scale should be considered. These scales should be considered as supplementary to each other rather than alternatives; it may be necessary to use more than one of these scales in a trial.

References

  1. 1.
    Bech P. Pharmacological treatment of depressive disorders: a review. In: Maj M, Sartorius N, editors. Depressive disorders (WPA series evidence and experience in psychiatry). 2nd ed. Chichester: John Wiley & Sons, 2002: 89–128Google Scholar
  2. 2.
    Kuhn R. Über die Behandlung depressiver Zustände mit einem Iminodibenzylderivat (G22355). Schweiz Med Wochenschr 1957; 87: 1135–40PubMedGoogle Scholar
  3. 3.
    O’Sullivan RL, Fava M, Augustin C, et al. Sensitivity of the six-item Hamilton Depression Rating Scale. Acta Psychiatr Scand 1997; 95: 379–84PubMedCrossRefGoogle Scholar
  4. 4.
    Bagby RM, Ryder AG, Schuller DR, et al. The Hamilton Depression Rating Scale: Has the gold standard become a lead weight? Am J Psychiatry 2004; 161: 2163–79PubMedCrossRefGoogle Scholar
  5. 5.
    Bech P, Gram LF, Dein E, et al. Quantitative rating of depressive states. Acta Psychiatr Scand 1975; 51: 161–70PubMedCrossRefGoogle Scholar
  6. 6.
    Bech P, Allerup P, Gram LF, et al. The Hamilton Depression Scale: evaluation of objectivity using logistic models. Acta Psychiatr Scand 1981; 63: 290–9PubMedCrossRefGoogle Scholar
  7. 7.
    Angst J. Depression and anxiety: a review of studies in the community and in primary health care. In: Sartorius N, Goldberg D, de Girolamo G, et al., editors. Psychological disorders in general medical settings. Toronto: Hogrefe and Huber, 1990: 60–8Google Scholar
  8. 8.
    Hordern A. Tranquility denial: stress and its impact today. Melbourne: Rigby, 1976Google Scholar
  9. 9.
    Bech P. The Bech-Rafaelsen Melancholia Scale (MES) in clinical trials of therapies in depressive disorders: a 20-year review of its use as outcome measure. Acta Psychiatr Scand 2002; 106: 252–64PubMedCrossRefGoogle Scholar
  10. 10.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. (DSM-IV). Washington, DC: American Psychiatric Association, 1994Google Scholar
  11. 11.
    Bech P, Allerup P, Reisby N, et al. Assessment of symptom change from improvement curves on the Hamilton Depression scale in trials with antidepressants. Psychopharmacology (Berl) 1984; 84: 276–81CrossRefGoogle Scholar
  12. 12.
    Storosum JG, van Zwieten BJ, van den Brink W, et al. Suicide risk in placebo-controlled studies of major depression. Am J Psychiatry 2001; 158: 1271–5PubMedCrossRefGoogle Scholar
  13. 13.
    Khan A, Khan SR, Leventhal RM, et al. Symptom reduction and suicide in patients treated with placebo in antidepressant clinical trials: a replication analysis of the Food and Drug Administration database. Int J Neuropsychiatry 2001; 4: 113–8Google Scholar
  14. 14.
    Goldman HH, Skodol AE, Lave TR. Revising axis V for DSM-IV: a review of measures of social functioning. Am J Psychiatry 1992; 149: 1148–56PubMedGoogle Scholar
  15. 15.
    Guy W. Early Clinical Drug Evaluation (ECDEU) assessment manual for psychopharmacology. Publication No. 76-338. Rockville (MD): National Institute of Mental Health, 1976Google Scholar
  16. 16.
    Sheehan DV. The anxiety disease. New York: Scribners, 1983Google Scholar
  17. 17.
    Sheehan DV. The Sheehan disability scale. In: Rush AJ, Pincus HA, First MB, et al., editors. Handbook of psychiatric measures. Washington, DC: American Psychiatric Association, 2000: 113–5Google Scholar
  18. 18.
    Hirschfeld RM, Montgomery SA, Keller MB, et al. Social functioning in depression: a review. J Clin Psychiatry 2000; 61: 268–75PubMedCrossRefGoogle Scholar
  19. 19.
    Bech P. Quality of life in the psychiatric patient. London: Mosby-Wolfe, 1998Google Scholar
  20. 20.
    Weissman MM. Social functioning and the treatment of depression. J Clin Psychiatry 2000; 61 Suppl. 1: 33–8Google Scholar
  21. 21.
    Weissman MM, Olfson M, Gameroff MJ, et al. A comparison of three scales for assessing social functioning in primary care. Am J Psychiatry 2001; 158: 460–6PubMedCrossRefGoogle Scholar
  22. 22.
    Weissman MM, Bothwell S. Assessment of social adjustment by patient self-report. Arch Gen Psychiatry 1976; 33: 1111–5PubMedCrossRefGoogle Scholar
  23. 23.
    Bosc M. Assessment of social functioning in depression. Compr Psychiatry 2000; 41: 63–9PubMedCrossRefGoogle Scholar
  24. 24.
    Ware JE, Sherbourne C. The MOS 36-Item Short-Form Health Survey (SF-36): conceptual framework and item selection. Med Care 1992; 30: 473–83PubMedCrossRefGoogle Scholar
  25. 25.
    Lecrubier Y, Bourin M, Moon CA, et al. Efficacy of venlafaxine in depressive illness in general practice. Acta Psychiatr Scand 1997; 95: 485–93PubMedCrossRefGoogle Scholar
  26. 26.
    Coulehan JL, Schulberg HC, Block MR, et al. Treating depressed primary care patients improves their physical, mental, and social functioning. Arch Intern Med 1997; 157: 1113–20PubMedCrossRefGoogle Scholar
  27. 27.
    Souetre E, Martin P, Lozet H, et al. Quality of life in depressed patients: comparison of fluoxetine and major tricyclic antidepressants. Int Clin Psychopharmacol 1996; 11: 45–52PubMedCrossRefGoogle Scholar
  28. 28.
    Gleason OC, Yates WR, Isbell MD, et al. An open-label trial of citalopram for major depression in patients with hepatitis C. J Clin Psychiatry 2002; 63: 194–8PubMedCrossRefGoogle Scholar
  29. 29.
    Simon GE, VonKorff M, Heiligenstein JH, et al. Initial antidepressant choice in primary care: effectiveness and cost of fluoxetine vs tricyclic antidepressants. JAMA 1996; 275: 1897–902PubMedCrossRefGoogle Scholar
  30. 30.
    Russell JM, Koran LM, Rush J, et al. Effect of concurrent anxiety on response to sertraline and imipramine in patients with chronic depression. Depress Anxiety 2001; 13: 18–27PubMedCrossRefGoogle Scholar
  31. 31.
    Venditti LN, Arcelus A, Birnbaum H, et al. The impact of antidepressant use on social functioning: reboxetine versus fluoxetine. Int Clin Psychopharmacol 2000; 15: 279–89PubMedCrossRefGoogle Scholar
  32. 32.
    Bech P, Lunde M, Undén M. Social Adaptation Self-evaluation Scale (SASS): psychometric analysis as outcome measure in the treatment of patients with major depression in the remission phase. Int J Psychiatry Clin Pract 2002; 6: 141–6CrossRefGoogle Scholar
  33. 33.
    Dubini A, Bosc M, Polin V. Do noradrenaline and serotonin differentially affect social motivation and behaviour? Eur Neuropsychopharmacol 1997 Apr; 7Suppl. 1: S49–55PubMedCrossRefGoogle Scholar
  34. 34.
    Massana J, Moller HJ, Burrows GD, et al. Reboxetine: a double-blind comparison with fluoxetine in major depressive disorder. Int Clin Psychopharmacol 1999 Mar; 14: 73–8PubMedCrossRefGoogle Scholar
  35. 35.
    Tse WS, Bond AJ. Difference in serotonergic and noradrenergic regulation of human social behaviours. Psychopharmacology (Berl) 2002; 159: 216–21CrossRefGoogle Scholar
  36. 36.
    Gandek B, Ware JE. Translating functional health and well-being: international quality of life assessment (IQOLA) project studies of the SF-36 health survey. J Clin Epidemiol 1998, 51 (11, Special Issue)Google Scholar
  37. 37.
    van der Heijden PG, van Buuren S, Fekkes M, et al. Unidimensionality and reliability under Mokken scaling of the Dutch language version of the SF-36. Qual Life Res 2003; 12: 189–98PubMedCrossRefGoogle Scholar
  38. 38.
    Speer DC. Mental health outcome evaluation. San Diego (CA): Academic Press, 1998Google Scholar
  39. 39.
    Heiligenstein JH, Ware Jr JE, Beusterien KM, et al. Acute effects of fluoxetine versus placebo on functional health and well-being in late-life depression. Int Psychogeriatr 1995; 7 Suppl.: 125–37PubMedCrossRefGoogle Scholar
  40. 40.
    McHorney CA, Kosinski M, Ware JE. Comparison of the costs and quality of norms for the SF-36 health survey collected by mail versus telephone interview: results from a national survey. Med Care 1994; 32: 551–67PubMedCrossRefGoogle Scholar
  41. 41.
    Ware JE, Kosinski M, Bayliss MS. Comparison of methods for the scoring and statistical analysis of SF-36 health profile and summary measures: summary of results from the Medical Outcomes Study. Med Care 1995; 33(4 Suppl.): AS264–79PubMedGoogle Scholar
  42. 42.
    Kroenke K, West SL, Swindle R, et al. Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. JAMA 2001; 286: 2947–55PubMedCrossRefGoogle Scholar
  43. 43.
    Beusterien KM, Steinwald B, Ware JE. Usefulness of the SF-36 Health Survey in measuring health outcomes in the depressed elderly. J Geriatr Psychiatry Neurol 1996; 9: 13–21PubMedGoogle Scholar
  44. 44.
    Hirschfeld RM, Dunner DL, Keitner G, et al. Does psychosocial functioning improve independent of depressive symptoms? A comparison of nefazodone, psychotherapy, and their combination. Biol Psychiatry 2002; 51: 123–33PubMedCrossRefGoogle Scholar
  45. 45.
    Kocsis JH, Schatzberg A, Rush AJ, et al. Psychosocial outcomes following long-term, double-blind treatment of chronic depression with sertraline vs placebo. Arch Gen Psychiatry 2002; 59: 723–8PubMedCrossRefGoogle Scholar
  46. 46.
    Rosenberg R. Outcome measures of antidepressive therapy. Acta Psychiatr Scand Suppl 2000; 402: 41–4PubMedCrossRefGoogle Scholar
  47. 47.
    Hopper CL, Bakish D. An examination of the sensitivity of the six-item Hamilton Rating Scale for Depression in a sample of patients suffering from major depressive disorder. J Psychiatry Neurosci 2000; 25: 178–184Google Scholar
  48. 48.
    Demyttenaere K, de Fruyt J. Getting what you ask for: on the selectivity of depression rating scales. Psychother Psychosom 2003; 72: 61–70PubMedCrossRefGoogle Scholar
  49. 49.
    Bech P, Cialdella P, Haugh M, et al. A meta-analysis of randomised controlled trials of fluoxetine versus placebo and tricyclic antidepressants in the short-term treatment of major depression. Br J Psychiatry 2000; 176: 421–8PubMedCrossRefGoogle Scholar
  50. 50.
    Bech P. Meta-analysis of placebo-controlled trials with mirtazapine using the core items of the Hamilton Depression Scale as evidence of a pure antidepressive effect in the short-term treatment of major depression. Int J Neuropsychopharmacol 2001; 4: 337–45PubMedCrossRefGoogle Scholar
  51. 51.
    Bech P, Tanghoj P, Andersen HF, et al. Citalopram dose-response revisited using an alternative psychometric approach to evaluate clinical effects of four fixed citalopram doses compared to placebo in patients with major depression. Psychopharmacology (Berl) 2002; 163: 20–5CrossRefGoogle Scholar
  52. 52.
    Beck AT, Ward CH, Mendelson M. An inventory for measuring depression. Arch Gen Psychiatry 1961; 4: 561–71PubMedCrossRefGoogle Scholar
  53. 53.
    Zung WWK. A self-rating depression scale. Arch Gen Psychiatry 1965; 12: 63–70PubMedCrossRefGoogle Scholar
  54. 54.
    Naughton MJ, Wiklund I. A critical review of dimension-specific measures of health-related quality of life in cross-cultural research. Qual Life Res 1993; 2: 397–432PubMedCrossRefGoogle Scholar
  55. 55.
    Bech P. Clinical effects of selective serotonin reuptake inhibitors. In: Dahl SG, Gram LF, editors. Clinical pharmacology in psychiatry. Berlin: Springer, 1989: 81-93Google Scholar
  56. 56.
    Mezzich JE, Berganza CE, von Cranach M, et al. Essentials of the World Psychiatric Association’s International Guidelines for Diagnostic Assessment (IGDA). Br J Psychiatry 2003; 182Suppl. 145: 37–63Google Scholar
  57. 57.
    Stassen HH, Angst J, Delini-Stula A. Delayed onset of action of antidepressant drugs? Survey of results of Zurich meta-analysis. Pharmacopsychiatry 1996; 29: 87–96PubMedCrossRefGoogle Scholar
  58. 58.
    Thunedborg K, Black C, Bech P. Beyond the Hamilton depression scores in long-term treatment of manic-melancholic patients: prediction of recurrence of depression by quality of life measurements. Psychother Psychosom 1995; 64: 131–40PubMedCrossRefGoogle Scholar
  59. 59.
    Lydiard RB, Stahl SM, Hertzman M, et al. A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression. J Clin Psychiatry 1997; 58: 484–91PubMedCrossRefGoogle Scholar
  60. 60.
    Miller IW, Keitner GI, Schatzberg AF, et al. Psychosocial functioning before and after treatment with sertraline or imipramine. J Clin Psychiatry 1998; 59: 608–19PubMedCrossRefGoogle Scholar
  61. 61.
    Endicott J, Nee J, Harrison W, et al. Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure. Psychopharmacol Bull 1993; 29: 321–6PubMedGoogle Scholar
  62. 62.
    Endicott J. Quality of life enjoyment and satisfaction questionnaire (Q-LES-Q). In: Rush AJ, Pincus HA, First MB, et al., editors. Handbook of psychiatric measures. Washington, DC: American Psychiatric Association, 2000: 143–4Google Scholar
  63. 63.
    Burke WJ, Gergel I, Bose A. Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry 2002; 63: 331–6PubMedCrossRefGoogle Scholar
  64. 64.
    Bech P, Tanghøj P, Cialdella P, et al. Escitalopram dose-response revisited: an alternative psychometric approach to evaluate clinical effects of escitalopram compared to citalopram and placebo in patients with major depression. Int J Neuropsychopharmacol 2004; 7(3): 283–90PubMedCrossRefGoogle Scholar
  65. 65.
    Finkel SI, Richter EM, Clary CM. Comparative efficacy and safety of sertraline versus nortriptyline in major depression in patients 70 and older. Int Psychogeriatr 1999; 11: 85–99PubMedCrossRefGoogle Scholar
  66. 66.
    Guidelines on psychotropic drugs for the EC: antidepressant medicinal products. Eur Neuropsychopharmacol 1994; 4: 61–77CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  1. 1.Psychiatric Research Unit, WHO Collaborating Centre for Mental HealthFrederiksborg General HospitalHillerødDenmark

Personalised recommendations