, Volume 119, Issue 4, pp 440–448 | Cite as

Onset and time course of antidepressant action: psychopharmacological implications of a controlled trial of electroconvulsive therapy

  • R. H. Segman
  • M. Gorfine
  • B. Lerer
  • B. Shapira
Original Investigation


Onset and time course of antidepressant effect were examined in 47 patients with major depressive disorder who had been randomly assigned to twice weekly bilateral, brief pulse electroconvulsive therapy plus one simulated treatment per week (ECT×2) or to a three times weekly schedule of administration (ECT×3). Rapid improvement was observed in the ECT×3 group in whom the number of real ECTs to 30% reduction on the Hamilton Depression Scale (HAM-D) was 3.2±1.90, administered over 7.3±4.43 days and to 60% reduction, 5.9±3.09 real ECTs over 13.7±7.21 days. Among the responders in both groups combined, 24.3±29.58% of the overall improvement in HAM-D was contributed by the first real ECT, 60.9±28.13% by the first four real ECTs and 91.6±25.82% by the first eight. Although 85.3% of the responders had reached 60% HAM-D improvement after eight ECTs, a clinically significant minority (14.7%) responded later in the course (ECT 9–12). However, response was predictable on the basis of symptomatic improvement (30% on the HAM-D) by the sixth real ECT. Thirty-three out of 34 responders would have been correctly identified by this criterion and only 2 out of 13 non-responders mis-identified (P<0.000001). Once achieved, the antidepressant effect was stable, without continuation pharmacotherapy, until 1 week after the last treatment and on lithium carbonate (Li) or Li plus clomipramine for a further 3 weeks. These findings confirm the clinical impression that ECT is a rapidly effective treatment for major depression with a shorter latency than generally reported for antidepressant drugs. Elucidation of its neurobiological mechanisms could contribute to the development of pharmacological agents with a similar profile.

Key words

Electroconvulsive therapy Antidepressants Onset of action Time course 


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  1. Abrams R (1988) Electroconvulsive therapy, 2nd edn. Oxford University Press, New YorkGoogle Scholar
  2. American Psychiatric Association (1990) The practice of ECT: recommendations for practice, training and privileging. Task force report on ECT. American Psychiatric Press, Washington DCGoogle Scholar
  3. Brandon S, Cowley P, McDonald C, Neville P, Palmer R, Wellstood-Eason S (1984) Electroconvulsive therapy: results in depressive illness from the Leicestershire trial. BMJ 228:22–25Google Scholar
  4. Fabre LF (1985) Treatment of depression in outpatients: a controlled comparison of the onset of action of amoxapine and maprotiline. J Clin Psychiatry 46:521–524Google Scholar
  5. Gachoud JP, Mikkelsen H, Ammar S, Widlocher D, Jouvent R (1992) Theoretical considerations and perspectives on the onset of action of moclobemide. Psychopharmacology 106 [Suppl]:96–97Google Scholar
  6. Gangadhar BN, Kapur BL, Kalyasundaram S (1982) Comparison of ECT with imipramine in endogenous depression a double blind study. Br J Psychiatry 141:367–371Google Scholar
  7. Gregory S, Shawcross CR, Gill D (1985) The Nottingham ECT Study: a double-blind comparison of bilateral, unilateral and simulated ECT in depressive illness. Br J Psychiatry 146:520–524Google Scholar
  8. Guy W (1976) ECDEU assessment manual for psychopharmacology. NIMH, Rockville, Md., pp 217–222Google Scholar
  9. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62Google Scholar
  10. Israel Ministry of Health (1990) Guidelines for the use of electroconvulsive therapy. JerusalemGoogle Scholar
  11. Katz MM, Koslow SH, MAAS JW, Frazer A, Bowden CL, Casper R, Croughan J, Kocsis J, Redmond E (1987) The timing, specificity and clinical prediction of tricyclic drug effects in depression. Psychol Med 17:297–309Google Scholar
  12. Khan A, Cohen S, Dager S, Avery DH, Dunner DL (1989) Onset of response in relation to outcome in depressed outpatients with placebo and imipramine. J Affect Dis 17:33–38Google Scholar
  13. Kindler S, Shapira B, Hadjez J, Abramowitz M, Brom D, Lerer B (1991) Factors influencing response to bilateral ECT in major depression. Convuls Ther 7:245–254Google Scholar
  14. Kukopulos A, Reginaldi D, Tondo L, Bernabei A, Calieri B (1977) Spontaneous length of depression and response to ECT. Psychol Med 7:626–629Google Scholar
  15. Lerer B (1987) Neurochemical and other neurobiological consequences of ECT: Implications for the pathogenesis and treatment of affective disorders. In: Meltzer H (ed) Psychopharmacology: the third generation of progress. Raven Press, New YorkGoogle Scholar
  16. Lerer B, Shapira B, Calev A, Tubi N, Drexler H, Kindler S, Lidsky D, Scwartz JE (1995) Antidepressant and cognitive adverse effects of twice versus three times weekly ECT. Am J Psychiatry (in press)Google Scholar
  17. Lichtenberg P, Lerer B (1989) Implications of clinical spectrum for mechanisms of action: ECT and tricyclic antidepressants reconsidered. Convuls Ther 5:216–226Google Scholar
  18. McAllister DA, Perri MG, Jordan RC, Rauscher FP, Sattin A (1987) Effects of ECT given two versus three times weekly. Psychiatry Res 21:63–69Google Scholar
  19. Mendels J, Johnston R, Mattes J, Riesenberg R (1993) Efficacy and safety of b.i.d. doses of venlafaxine in a dose response study. Psychopharmacol Bull 29:169–174Google Scholar
  20. Nagayama H, Kagano K, Ikezaki A, Tashiro T (1991) Prediction of efficacy of antidepressant by 1-week test therapy in depression. J Affect Dis 23:213–216Google Scholar
  21. Pettinati HM (1994) Speed of ECT? Convuls Ther 10[1]:69–73Google Scholar
  22. Post RM, Uhde TW, Rubinow DR, Huggins T (1987) Differential time course of antidepressant effects after sleep deprivation, ECT, and carbamazepine: clinical and theoretical implications. Psychiatry Res 22:11–19Google Scholar
  23. Prudic J, Sackeim HA, Devanand DP (1990) Medication resistance and clinical response to electroconvulsive therapy. Psychiatry Res 31:287–296Google Scholar
  24. Quitkin FM, Rabkin JD, Markowitz JM, Stewart JW, McGrath PJ, Harrison W (1987) Use of pattern analysis to identify true drug response. A replication. Arch Gen Psychiatry 44:259–264Google Scholar
  25. Quitkin FM, Stewart JW, McGrath PJ, Nunes E, Ocepek-Welikson K, Tricamo E, Rabkin JG, Klein DF (1993) Further evidence that a placebo response to antidepressants can be identified. Am J Psychiatry 150:566–570Google Scholar
  26. Rich CL, Spiker DG, Jewell SW, Neil JF, Black NA (1984) The efficiency of ECT: I. Response in depressive episodes. Psychiatry Res 11:167–176Google Scholar
  27. Rifkin A (1988) ECT versus tricyclic antidepressants in depression: a review of the evidence. J Clin Psychiatry 49:3–7Google Scholar
  28. Rodger CR, Scott AI, Whalley LJ (1994) Is there a delay in the onset of the antidepressant effect of electroconvulsive therapy? Br J Psychiatry 164:106–109Google Scholar
  29. Roemer RA, Dubin WR, Jaffe R, Lipshutz L, Sharon D (1990) An efficacy study of single-versus double-seizure induction with ECT in major depression. J Clin Psychiatry 51:473–478Google Scholar
  30. Sackeim HA, Decina P, Prohovnik I (1987) Seizure threshold in electroconvulsive therapy. Arch Gen Psychiatry 44:355–360Google Scholar
  31. Sackeim HA, Prudic J, Devanand DP, Decina P, Kerr B Malitz S (1990) The impact of medication resistance and continuation pharmacotherapy on relapse following response to electroconvulsive therapy in major depression. J Clin Psychopharmacol 10:96–104Google Scholar
  32. Shapira B, Lerer B, Gilboa D (1987) Facilitation of electroconvulsive therapy by caffeine pretreatment. Am J Psychiatry 144:1199–1202Google Scholar
  33. Spitzer RL, Endicott J, Robins E (1989) Research diagnostic criteria for a selected group of functional disorders. New York Psychiatric Institute, New YorkGoogle Scholar
  34. Stassen HH, Delini-Stula A, Angst J (1993) Time course of improvement under antidepressant treatment: a survival-analytical approach. Eur Neuropsychopharmacol 3:127–135Google Scholar
  35. Stromgren LS (1975) Therapeutic results in brief-interval unilateral ECT. Acta Psychiatr Scand 52:246–255Google Scholar
  36. Stromgren LS, Christensen AL, Fromholt P (1976) The effects of brief — interval unilateral ECT on memory. Acta Psychiatr Scand 54:336–346Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • R. H. Segman
    • 1
  • M. Gorfine
    • 1
    • 4
  • B. Lerer
    • 1
    • 2
  • B. Shapira
    • 2
    • 3
  1. 1.Department of PsychiatryHadassah-Hebrew University Medical CenterJerusalemIsrael
  2. 2.Depression Treatment UnitHerzog HospitalJerusalemIsrael
  3. 3.Department of PsychiatryHebrew University-Hadassah Medical SchoolJerusalemIsrael
  4. 4.Laboratory of Applied Statistics, Department of StatisticsHebrew UniversityJerusalemIsrael

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