logo
logo
Psychopharmacology  |  Psychopathology  |  Speech Characteristics  |  Electroencephalography  |  Psychiatric Genetics  |  Inflammation  |  Home
unisig

Improvement under Amitriptyline and Oxaprotiline versus Placebo

Efficacy Criteria

The sample of this study consisted of moderately depressed male (n=154) and female (n=275) patients, diagnosed according to DSM-III criteria as suffering from major depression, and 17-73 years old. Of these, 120 were treated with oxaprotiline, 120 with amitriptyline and 189 with placebo. Efficacy criteria were the Hamilton Depression (HAMD), the Hamilton Anxiety (HAMA), and the Zung Self-rating scales. Eight ratings with exact calendar dates over a period of 40 days were available for analysis. Accordingly, our investigation into the time course of improvement was based on these calendar dates which varied by typically ±2 days around the pre-specified "design days" of the study protocol, thus enabling a considerably improved time resolution over the full study period.

Differences Between Treatment Modalities

Our results showed that the sensitivity in discriminating between treatment groups was substantially enhanced through the inclusion of drop-outs and consideration of the effect of time to withdrawal as co-variable. Premature withdrawal from the trial due to inefficacy occurred earliest under placebo (50% within the first 8 days), whereas less than 40% dropped out within the first 12 days under active treatments. The most interesting and unexpected finding of the analysis was that the time course of improvement among responders was independent of treatment modality, and thus identical in all three groups. Specifically, the efficacy of any of the given treatments was reflected only by the total number of responders and non-responders. Once triggered, the time course of recovery from illness became identical to that of spontaneous remissions as observed under placebo. This finding strongly suggests that antidepressants may not change the pattern ('Gestalt') of the natural course of recovery from depression, but rather, they seem to trigger recovery in a subgroup of patients who otherwise would remain non-responders.

References

Angst J, Stassen HH, Woggon B: Effect of neuroleptics on positive and negative symptoms and the deficit state. Psychopharmacology 1989; 99: 41-46
Angst J, Delini-Stula A, Stabl M, Stassen HH: Is a cutoff score a suitable measure of treatment outcome in short-term trials in depression? A methodological meta-analysis. Human Psychopharmacology 1993; 8: 311-317
Stassen HH, Delini-Stula A, Angst J: Time course of improvement under antidepressant treatment: a survival-analytical approach. Eur Neuropsychopharmacol 1993; 3: 127-135
Stassen HH, Angst J, Delini-Stula A: Severity at baseline and onset of improvement in depression. Meta-analysis of Imipramine and Moclobemide vs Placebo. Eur Psychiatry 1994; 9: 129-136
Stassen HH, Angst J: Methods of estimating onset of improvement. Eur Neuropsychopharma­cology 1994; 4,3: 284-285
Kuny S, Stassen HH: Cognitive performance in patients recovering from depression. Psychopathology 1995; 28: 190-207
Stassen HH, Angst J, Delini-Stula A: Delayed onset of action of antidepressant drugs? Survey of results of Zurich meta-analyses. Pharmacopsychiatry 1996; 29: 87-96
Stassen HH, Angst J, Delini-Stula A: Delayed onset of action of antidepressant drugs? Survey of results of Zurich meta-analyses. Eur Psychiatry 1997; 12: 166-176
Angst J, Stassen HH: Methodische Probleme der Prüfung von Antidepressiva. In: Stieglitz RD, Fähndrich E, Möller HJ (eds): Syndromale Diagnostik psychischer Störungen. Hogrefe, Göttingen 1998: 5-12
Stassen HH, Angst J, Delini-Stula A: Onset of improvement under fluoxetine and moclobemide. Eur Psychiatry 1998; 13,3: 128-133
Stassen HH, Kuny S,. Hell D: The speech analysis approach to determining onset of improvement under antidepressants. Eur Neuropsychopharmacology 1998; 8,4: 303-310
Stassen HH, Angst J, Delini-Stula A: Fluoxetine versus moclobemide: cross-comparison between the time course of improvement. Pharmacopsychiatry 1999; 32: 56-60
Montgomery SA, Bech P, Blier P, Moller HJ, Nierenberg AA, Pinder RM, Quitkin FM, Reimitz PE, Rosenbaum JF, Rush AJ, Stassen HH, Thase ME: Selecting methodologies for the evaluation of differences in time to response between antidepressants. J Clin Psychiatry 2002; 63(8): 694-699
Stassen HH, Dahmen N, Hell D, Nürnberg P, Sander T, Toliat MR, Szegedi A: Genetic predisposition of antidepressant drug response. Am J Med Genetics 2003; 122: 123-124
Stassen HH, Angst J: Wirkung und Wirkungseintritt in der Antidepressiva-Behandlung. Medizinspektrum 2004; 15: 15-17
Stassen HH, Angst J, Scharfetter C, Szegedi A: Therapie mit Antidepressiva: Erfolg von genetischen Faktoren abhängig? Leading Opinions, Neurologie & Psychiatrie 2005; 6: 25-27
Lavergne F, Berlin I, Gamma A, Stassen H, Angst J: Onset of improvement and response to mirtazapine in depression: a multicenter naturalistic study of 4771 patients. Neuropsychiatric Disease and Treatment 2005; 1(1): 59-68
Stassen HH, Scharfetter C: Vulnerability, resilience and response to psychotropic drugs: shared genetic factors? Am J Med Genetics 2006; 141: 707-708
Stassen HH, Angst J, Hell D, Scharfetter C, Szegedi A: Is there a common resilience mechanism underlying antidepressant drug response? Evidence from 2848 patients. J Clin Psychiatry 2007; 68(8): 1195-1205
Szegedi A, Jansen WT, Van Willigenburg AP, Van der Meulen E, Stassen HH, Thase ME: Early improvement as a predictor of treatment outcome in patients with major depressive disorder: Why the first 2 weeks really matter —evidence from 6562 patients. J Clin Psychiatry 2009; 70(3): 344-353
Lötscher K, Anghelescu IG, Braun S, Bridler R, Stassen HH: Polypharmacy in psychiatry: clinical practice versus empirical evidence. Eur Neuropsychopharmacol. 2010; 20 (Suppl. 3): 378-379
Kemp DE, Ganocy SJ, Brecher M, Carlson BX, Edwards S, Eudicone JM, Evoniuk G, Jansen W, Leon AC, Minkwitz M, Pikalov A, Stassen HH, Szegedi A, Tohen M, Van Willigenburg AP, Calabrese JR: Clinical value of early partial symptomatic improvement in the prediction of response and remission during short-term treatment trials in 3369 subjects with bipolar I or II depression. J Affect Disord. 2011; 130(1-2): 171-179
Stassen HH, Anghelescu IG, Angst J, Böker H, Lötscher K, Rujescu D, Szegedi A, Scharfetter C: Predicting Response to Psychopharmacological Treatment. Survey of Recent Results. Pharmacopsychiatry 2011; 44: 263-272

 

Onset of improvement
Table 11: Cumulative rates of improvers as a function of time under oxaprotiline (n=120; 77 improvers [64%]), amitriptyline (n=120; 102 improvers [85%]) and placebo (n=189; 120 improvers [64%]). Improvement is defined as a 20% sustained baseline score reduction. It is worth noting that the time characteristics of improvement are virtually identical under all three treatment modalities.
[ Comments and suggestions to Webmaster ] k454910@bli.uzh.ch
[ Home ]
Impressum  |  Acknowledgements