Research report
Combining psychotherapy and antidepressants in the treatment of depression

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Abstract

Objective: To compare the efficacy of antidepressants with that of antidepressants plus psychotherapy (“combined therapy”) in the treatment of depression. Method: 6 month randomised clinical trial of antidepressants (N=84) and combined therapy (N=83) in ambulatory patients with Major Depression and a 17-item HDRS baseline score of at least 14 points. The antidepressant protocol provides for three successive steps in case of intolerance or inefficacy: fluoxetine, amitriptyline and moclobemide. The combined therapy condition consists, in addition to pharmacotherapy, of 16 sessions of Short Psychodynamic Supportive Psychotherapy. Efficacy is assessed using the 17-item HDRS, the CGI of Severity and of Improvement, the depression subscale of the SCL-90, and the Quality of Life Depression Scale. The data analysis is conducted on three samples: the intention-to-treat sample, the per protocol sample and the observed cases sample. Results: After randomisation, 32% of the patients refused the proposed pharmacotherapy while 13% refused the proposed combined therapy. In 24 weeks, 40% of the patients who started with the pharmacotherapy stopped medication; 22% of those receiving the combined therapy did so. The difference in success rates is statistically significant, favouring combined therapy, in 23%, 31% and 62% of the patients after 8, 16 and 24 weeks of treatment, respectively. At week 24, the mean success rate is 40.7% in the pharmacotherapy group and 59.2% in the combined therapy group. Conclusion: Patients found combined treatment significantly more acceptable, they were significantly less likely to drop out of combined therapy and, ultimately, significantly more likely to recover. Combined therapy is preferable to pharmacotherapy in the treatment of ambulatory patients with major depression.

Introduction

Many clinicians are convinced that combined therapy, i.e., psychotherapy plus antidepressants, is the treatment of choice for ambulatory patients suffering from depression. They believe that, in these patients, combined therapy is more efficacious than one of its components, psychotherapy or antidepressants alone. These views, however, are not supported by empirical evidence. A Medline search of literature revealed four reviews of studies comparing combined therapy with antidepressants and/or with psychotherapy Conte et al., 1986, Robinson et al., 1990, Wexler and Cicchetti, 1992, Manning et al., 1992. There is, of course, considerable overlap between these four reviews which actually cover thirteen separate articles. The general conclusion is: “On most measures in most studies, the effect of combined therapy equals either psychotherapy or pharmacotherapy alone, whereas in some studies, the combination shows some superiority” (Manning and Frances, 1991). The thoroughness of a fifth review means that it deserves special attention (U.S. Department of Health and Human Services, 1993). It reports on mean short-term intent-to-treat response rates. The rate is 51.2% in patients treated with tricyclic antidepressants (102 studies) and 47.4% in patients treated with selective serotonin reuptake inhibitors (39 studies). The excess response rate over placebo is 21.3% for TCAs (46 studies) and 20.1% for SSRIs (23 studies). The response rate is 46.6% for cognitive therapy (22 studies), 55.3% for behaviour therapy (13 studies), 34.8% for brief dynamic therapy (8 studies) and 52.3% for interpersonal therapy (1 study). It is 34.6% in patients treated with a combination of behaviour therapy and antidepressants (2 studies), and 53.7% in patients treated with a combination of cognitive therapy with antidepressants (5 studies). These results indicate that both antidepressants and psychotherapy are efficacious treatments in ambulatory depressed patients, but the combination does not seem to offer any advantage. A “mega-analysis”, or meta-analysis of original data, of 595 patients with major depressive disorder enrolled in 6 standardized treatment protocols found new evidence in support of the widespread clinical impression that combined therapy is superior to psychotherapy alone for treatment of more severe, recurrent depressions, but not for the treatment of less severely depressed patients (Thase et al., 1997). In short, the strong convictions of clinicians and the hard data of researchers are difficult to reconcile on this topic. This article reports on the results of a randomised clinical trial comparing the efficacy of combined therapy with that of antidepressants alone in a six-month treatment programme for ambulatory patients with DSM-III-R-defined Major Depression, presenting a 17-item Hamilton Depression Rating Scale (HDRS) (Hamilton, 1967) baseline score of at least 14 points.

Section snippets

Study group

The study sample consists of all consecutive patients newly registered during a period of two years at an outpatient clinic of the Psychiatrisch Ziekenhuis Amsterdam in the inner city of Amsterdam. There are 4 inclusion criteria and 9 exclusion criteria. The inclusion criteria are: age between 18 and 60 years, DSM-III-R-defined Major Depression (with or without dysthymia), a 17-item HDRS baseline score of at least 14 points and written informed consent. The exclusion criteria were: presentation

Results

A total of 167 patients are randomised (pharmacotherapy N=84; combined therapy N=83) using block randomisation. Four blocks are formed, defined by sex and age. Of the randomised patients, 38 patients refuse the proposed treatment: 27 in the pharmacotherapy and 11 in the combined therapy group. This difference for the refusals between the two conditions is significant (chi-square=9.572, df=2, P=0.008).

The group which actually starts the treatment therefore consists of 129 patients: 57 in the

Discussion

Until now, very few studies have been undertaken of brief psychodynamic psychotherapy, either alone or in combination with medication. This study addresses the pragmatic question of differential clinical utility of two fully operational treatment programmes, both representative of actual clinical practice. It must be made clear that the results do not constitute evidence that SPSP, which is applied here in combination with pharmacotherapy, is in itself an effective form of psychotherapy. The

Conclusion

Patients found combined treatment significantly more acceptable, they were significantly less likely to drop out of combined therapy and, ultimately, significantly more likely to recover. In this study, the excess remission rate of combined therapy (psychotherapy plus antidepressants) over pharmacotherapy is approximately 20% after 24 weeks of treatment. This equals the excess success rate of pharmacotherapy over placebo in short time studies. Combined therapy seems preferable to

Acknowledgements

This study has been supported by an unrestricted educational grant from Eli Lilly Nederland. It has been carried out by the Mentrum Depression Research Group.

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