- Email: [email protected]
Does early response predict outcome in psychotherapy and combined therapy for major depression?
Journal of Affective Disorders 105 (2008) 261 – 265 www.elsevier.com/locate/jad
Brief report
Does early response predict outcome in psychotherapy and combined therapy for major depression? ☆ Henricus L. Van a,⁎, Robert A. Schoevers a , Simone Kool a , Mariëlle Hendriksen a , Jaap Peen a , Jack Dekker a,b a
Depression Research Group of Mentrum Health Care Amsterdam, The Netherlands b Clinical Psychology, Free University Amsterdam, The Netherlands
Received 8 February 2007; received in revised form 18 April 2007; accepted 19 April 2007 Available online 22 May 2007
Abstract Background: To examine the predictive value of early response for final outcome of psychotherapy and combined therapy in major depression. Methods: Mild- to moderately depressed patients were treated with either Short-Term Psychodynamic Supportive Psychotherapy (SPSP) (N = 63) only, or combined with an antidepressant (N = 127). Early response was defined as a reduction of more than 25% on the HAM-D-17 after 2 months. Outcome was determined in terms of complete nonresponse and remission rates. Associations between early response and outcome were examined using logistic regression analysis. Results: In SPSP, early nonresponse was clearly related to final nonresponse (OR = 3.57). Nevertheless, remission was not predicted by early response, and 26% of the early nonresponders ultimately achieved remission. In combined therapy, both final nonresponse (OR 7.13) and remission (OR 3.66) were associated with early nonresponse. Limitations: In this study, SPSP was the only psychotherapy examined. The design did not provide feedback to the therapist of the independently measured depression score after two months. Conclusion: Although a number of early nonresponsive patients will achieve remission, this study points out that these patients are at risk factor for ultimate treatment failure. This could be an indication for clinicians to adapt their treatment strategy. © 2007 Elsevier B.V. All rights reserved. Keywords: Early response; Outcome; Psychotherapy; Combined therapy; Major depression
☆
Conflicts of interest: All authors declare that they do not have any actual or potential conflict of interest with other people or organizations within three years of beginning the work submitted that could inappropriately influence our work. Contributors: Henricus L. Van contributed to the design the study, did the literature searches, included and treated patients in the trials, contributed to the statistical analysis and wrote both the previous concepts and final draft of the manuscript. Robert A. Schoevers and Jack Dekker contributed to the design of the study, contributed to the statistical analysis and the interpretation of data and other actual final draft of the paper. Jaap Peen undertook the statistical analysis and contributed to the final draft of the paper. Simone Kool and Marielle Hendriksen contributed to the design of the study, included and treated patients in the trials and contributed to the final draft of the paper. Role of funding source: The original trials were supported by unrestricted educational grants from Eli Lilly Nederland and Wyeth Nederland. Eli Lilly Nederland and Wyeth Nederland had no further role in study design; in collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper or publication. None of the authors do have any actual or potential conflict of interest including any financial, personal or other relationships with other organizations within three years of beginning the work submitted that could inappropriately influence, or be perceived to influence, to their work. ⁎ Corresponding author. Mentrum Mental Health Hospital, PO Box 75848, 1070 AVAmsterdam, The Netherlands. Tel.: +31 20 5904440; fax: +31 20 4898150. E-mail address: [email protected] (H.L. Van). 0165-0327/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2007.04.016
262
H.L. Van et al. / Journal of Affective Disorders 105 (2008) 261–265
Although major depressive disorders can be treated effectively, a substantial number of patients do not fully respond. In order to identify patients who will respond the association between pre-treatment patient characteristics and outcome has frequently been investigated. This has yielded a number of potential predictors, but results appear to be conflicting (Nierenberg, 2003). Instead of investigating pre-treatment characteristics, an alternative approach would be to make use of patterns of early response as predictors of treatment outcome. This would enable clinicians to shorten the duration of an unsuccessful treatment, and proceed to the next step in the treatment protocol. There is general agreement that response by week 4 is related to outcome of treatment with antidepressants, and that in case of complete early nonresponse a switch in antidepressant medication is indicated (Quitkin et al., 1996). However, only a few studies have addressed the predictive value of early response in psychotherapy for depression (Renaud et al., 1998) and the results remain open for debate. Finally, although the usefulness of combining pharmacotherapy and psychotherapy has been demonstrated (Keller et al., 2000) we are not aware of studies addressing the predictive value of early response in combined therapy. The aim of this study was to investigate the relationship between early response and outcome in depressed patients, treated with either Short-Term Psychodynamic Supportive Psychotherapy (SPSP) only, or combined with an antidepressant. In contrast with the assessment of early (non) response in antidepressants, there is no agreed-upon definition in psychotherapy for early response (Haas et al., 2002). We decided to measure response at week 8, assuming, on theoretical grounds, that by then early non-specific or placebo effects may have passed and an initial specific effect of the psychotherapy have emerged. Currently, complete treatment failure is defined as less than 25% decrease on an accepted depression rating scale (Hirschfeld et al., 2002). In order to identify all patients with an apparent initial effect, we therefore adopted the 25% decrease in depression symptoms as the cut off score to determine whether there is an early response.
dam. The original trials successively compared pharmacotherapy with combined therapy (De Jonghe et al., 2001), and psychotherapy with combined therapy (de Jonghe et al., 2004). Of the third study, comparing an antidepressant with either 8 or 16 sessions of psychotherapy (Dekker et al., 2005) only the data of the latter were included. The patients were adults with DSM-IV defined major depressive disorder and HAM-D-17 score of 14–25. The treatment modalities lasted for a period of six months. Depression scores were rated independently with the HAM-D-17 after 2 months and after 6 months of treatment. The psychotherapy consisted of sixteen sessions of Short-Term Psychodynamic Supportive Psychotherapy (SPSP). SPSP focuses on the affective, behavioral and cognitive aspects of relationships that may be discussed from both an interpersonal and an intrapersonal perspective (de Jonghe, 2005; Van et al., 2006). The therapists were trained psychiatrists or psychotherapists. They met regularly to discuss audiotaped sessions and to ensure adherence to the psychotherapy manual. In two trials patients started with fluoxetine, in one trial with venlafaxine. In cases of intolerance or obvious complete nonresponse, the antidepressant was replaced by nortriptyline. To control for a potential influence of medication switch on outcome, an additional analysis was performed excluding these patients. The sample and procedures have been described in greater detail in previous publications. To control for a possible dosage-effect, only patients who fully completed treatments were included. This concerns 63 out of 97 patients in psychotherapy and 127 out of 171 in combined therapy. Completers and non completers did not differ with respect to baseline characteristics. The HAM-D-17 reduction after 8 weeks of treatment was divided into two categories: early response (N 25% reduction) or early nonresponse (b 25% reduction). As outcome variables we defined complete nonresponse (b25% reduction), remission (HAM-D-17b 7) and partial response (N25% reduction but no remission achieved). Differences between categories at the end of treatment were analyzed using Chi2 test. Next, a logistic regression analysis was performed, adjusting for initial severity of depression as a covariate.
2. Methods
3. Results
The data were drawn from three RCTs conducted in two outpatient facilities of the Mentrum Mental Health Care, a large psychiatric teaching hospital in Amster-
In the whole sample, 67% of the patients were female. The average age was 35.4 (SD = 10.45). The mean HAMD-17 at baseline was 18.7 (SD 3.0). Overall, 33% of the
1. Introduction
H.L. Van et al. / Journal of Affective Disorders 105 (2008) 261–265
263
Fig. 1. Complete nonresponse, partial response and remission (%) at the end of treatment in early nonresponders and early responders.
patients in SPSP and 45% in combined therapy achieved remission. Although this difference was suggestive, it was not statistically significant (Chi2 2.56; p = 0.11). Treatment outcome was compared between early responders and early nonresponders (Fig. 1). In the psychotherapy condition, 31 out of 63 patients were identified as early nonresponders. Of these, 14 patients (45%) remained in this category until the end of treatment, 9 (25%) showed a partial response and 8 (26%) achieved remission. Among the 32 psychotherapy patients with an early response, 12 (38%) achieved remission, 14 (44%) had a partial response and 6 (19%) reverted to complete nonresponse. With respect to final complete nonresponse, the difference between early nonresponders and responders was statistically significant with respect to complete nonresponse (Chi2 = 5.069, df = 1, p b 0.01). This was not the case for the differences in remission rates (Chi2 = 0.994, df = 1, p = 0.319). In the combined therapy condition, 50 out of 127 patients were identified as early nonresponders. Of these, 21 patients (42%) remained nonresponsive until the end of treatment, 26 showed a partial response and 13 patients (26%) ultimately achieved full remission. Of the 77 combined therapy patients with an early response, 46 (60%) achieved remission, 22 a partial response
whereas 9 (12%) reverted to complete nonresponse. With respect to final complete nonresponse the difference between early nonresponders and responders was statistically significant, both with respect to complete nonresponse (Chi2 = 16.019, df = 1, p b 0.001) and remission (Chi2 = 12.435, df = 1, p b 0.001). Subsequently, in a logistic regression analysis controlling for initial depression severity, odds ratios were computed (Table 1). In psychotherapy final nonresponse was significantly related to nonresponse at week 8. However, remission was not related to early response.
Table 1 Odds ratios (95% confidence interval) for HAM-D-17 scores at week 8 with outcome at week 24 SPSP
OR (C.I.)
P
Week 8
Week 24
Nonresponse Response
Nonresponse Remission
3.57 (1.14–11.22) 1.72 (0.59–5.06)
b0.05 ns
Combined therapy Nonresponse Nonresponse Response Remission
7.13 (2.59–16.63) 3.66 (1.68–7.99)
b0.00 b0.00
264
H.L. Van et al. / Journal of Affective Disorders 105 (2008) 261–265
In combined therapy, final nonresponse was related to early nonresponse and the achievement of remission to early response. In combined therapy, 30 patients switched antidepressant medication. Excluding these patients from the analysis did not change the findings. 4. Discussion The results presented in this study showed an equivocal relationship between early response and outcome in psychotherapy for major depression. Nonresponse after 8 weeks of treatment was clearly predictive of final nonresponse. However, when addressing remission as an outcome measure, early response was not related to outcome. This suggests that in some patients, psychotherapy may require more time than 8 weeks before favorable effects become noticeable. A potential theoretical explanation of this delayed effectiveness may be the time needed to establish a beneficial psychotherapeutic relationship. In combined therapy, both complete nonresponse and remission at the end of treatment were related to the depression scores after 8 weeks. In particular, early nonresponse carried a large risk of final nonresponse (OR 7.13). Still, it should be noted that even among these early nonresponders, a quarter achieved remission at the end of therapy. Few studies specifically analyzed the predictive value of early response in psychotherapy. The available studies measured response after one of the first sessions (Renaud et al., 1998) or included patients with a variety of diagnoses who were treated with varying types and duration of psychotherapy (Percevic et al., 2006). A strength of this study is that it concerns all patients with the same diagnosis treated with one form of standardized psychotherapy. This enabled us to determine the time–response relationship under relatively homogeneous conditions. There are also a number of limitations. The study concerns a post hoc analysis of data that were not originally collected to explore the predictive value of early response. SPSP was the only psychotherapy examined. It is not certain whether the results can be generalized to other short-term psychotherapies for depression. Pre-treatment patient's characteristics that might influence speed of change, such as level of social impairment were not taken into account. Finally, the design did not enable feedback to the therapist about the independently determined depression score. Especially in cases of poor progress this may increase attendance for patients and improve outcome (Whipple et al.,
2003). On the other hand, for a lot of clinicians it may be difficult to arrange a systematic and independently measured feedback. In this sense the presented design reflects common practice. Overall, it can be concluded that early nonresponse carries an important risk for final non-response. At the same time a substantial number of early nonresponsive patients do remit following prolonged psychotherapy or combined therapy. Clearly it would be of help if clinicians could identify these patients and subsequently allocate the optimal treatment. Future research should therefore ideally combine data on early response with other potential predictors such as pre-treatment patient's characteristics. At present, we believe that in depressed patients treated with psychotherapy only, the addition of an antidepressant should be considered in cases of early nonresponse in order to increase their chance of final remission. In line with the recent findings of the STAR⁎D project (Rush et al., 2006) a switch of antidepressants appears to be a logical step for non responsive patients in combined therapy. Nevertheless, the effectiveness of this step in case of a prolonged psychotherapeutic treatment has not yet been demonstrated and needs further research. References Dekker, J., Molenaar, P.J., Kool, S., van Aalst, G., Peen, J., de Jonghe, F., 2005. Dose-effect relations in time-limited combined psychopharmacological treatment for depression. Psych. Med. 35, 47–58. De Jonghe, F., 2005. Short-term Psychodynamic Supportive Psychotherapy. Benecke N.I., Amsterdam. (in Dutch). De Jonghe, F., Kool, S., van Aalst, G., Dekker, J., Dekker, J., 2001. Combining psychotherapy and antidepressants in the treatment of depression. J. Affect. Disord. 64, 217–229. De Jonghe, F., Hendriksen, M., van Aalst, G., Kool, S., Peen, J., Van, H.L., Eijnden, E., Dekker, J., 2004. Psychotherapy and combined therapy (pharmacotherapy plus psychotherapy) in the treatment of depression. Br. J. Psychiatry 185, 37–45. Haas, E., Hill, R., Lambert, M.J., Morrel, B., 2002. Do early responders to psychotherapy maintain treatment gains? J. Clin. Psychol. 58, 1157–1172. Hirschfeld, R.M.A., Montgomery, S.A., Aguglia, E., Aguglia, M., Delgado, P., Delgado, M., Hawley, C., Kasper, S., Kasper, M., Massana, J., Mendlewicz, J., Möller, H., Nemeroff, C.B., Nemeroff, J., Such, P., Torta, R., Versiani, M., 2002. Partial response and nonresponse to antidepressant therapy: current approaches and treatment options. J. Clin. Psychiatry 63, 826–837. Keller, M.B., McCullough, J.P., Klein, D.N., Arnow, B., Dunner, D.L., Gelenberg, A.J., Markowitz, J.C., Nemeroff, C.B., Russell, J.M., Thase, M.E., Trivedi, M.H., Zajecka, J., 2000. A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N. Engl. J. Med. 342, 1462–1470. Nierenberg, A.A., 2003. Predictors of response to antidepressants: general principles and clinical implications. Psychiatr. Clin. North Am. 26, 345–352.
H.L. Van et al. / Journal of Affective Disorders 105 (2008) 261–265 Percevic, R., Lambert, J., Kordy, H., 2006. What is the predictive value of responses to psychotherapy for its future course? Empirical explorations and consequences for outcome monitoring. Psychother. Res. 16, 364–374. Quitkin, F.M., McGrath, P.J., Stewart, J.W., Ocepek-Welikson, K., Taylor, B.P., Nunes, E., Delivannides, D., Agosti, V., Donovan, S., Petkovan, E., Klein, D.F., 1996. Chronological milestones to guide drug change. When should clinicians switch antidepressants. Arch. Gen. Psychiatry 53, 782–792. Renaud, J., Brent, S.A., Baugher, M., Birmaher, B., Kolko, D., Bridge, J., 1998. Rapid response to psychosocial treatment for adolescent depression: a two year follow-up. J. Am. Acad. Child Adolesc. Psych. 37, 1184–1190. Rush, J., Trivedi, M.H., Wisniewski, S.R., Nierenberg, A.A., Stewart, J.W., Warden, D.W., Niederehe, G., Thase, M.Th., Lavori, W., Lebowitz, B.D., McGrath, P.J., Rosenbaum, J.F., Sackeim, H.A.,
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Kupfer, D.J., Luther, J., Fava, M., 2006. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR⁎D report. Am. J. Psychiatry 163, 1905–1917. Van, H.L., Kool, S., Hendriksen, M., van Aalst, G., Schoevers, R., 2006. Short-term psychodynamic supportive psychotherapy. CME Course Brochure of the 159th Annual Meeting of the American Psychiatric Association, Toronto, Canada, Course 38. Whipple, J.L., Lambert, M.J., Vermeersch, D.A., Smart, D.W., Smart, S.L., Hawkins, E.J., 2003. Improving the effects of psychotherapy: the use of early identification of treatment failure and problemsolving strategies in routine practice. J. Couns. Psychol. 50, 59–68.
Brief report
Does early response predict outcome in psychotherapy and combined therapy for major depression? ☆ Henricus L. Van a,⁎, Robert A. Schoevers a , Simone Kool a , Mariëlle Hendriksen a , Jaap Peen a , Jack Dekker a,b a
Depression Research Group of Mentrum Health Care Amsterdam, The Netherlands b Clinical Psychology, Free University Amsterdam, The Netherlands
Received 8 February 2007; received in revised form 18 April 2007; accepted 19 April 2007 Available online 22 May 2007
Abstract Background: To examine the predictive value of early response for final outcome of psychotherapy and combined therapy in major depression. Methods: Mild- to moderately depressed patients were treated with either Short-Term Psychodynamic Supportive Psychotherapy (SPSP) (N = 63) only, or combined with an antidepressant (N = 127). Early response was defined as a reduction of more than 25% on the HAM-D-17 after 2 months. Outcome was determined in terms of complete nonresponse and remission rates. Associations between early response and outcome were examined using logistic regression analysis. Results: In SPSP, early nonresponse was clearly related to final nonresponse (OR = 3.57). Nevertheless, remission was not predicted by early response, and 26% of the early nonresponders ultimately achieved remission. In combined therapy, both final nonresponse (OR 7.13) and remission (OR 3.66) were associated with early nonresponse. Limitations: In this study, SPSP was the only psychotherapy examined. The design did not provide feedback to the therapist of the independently measured depression score after two months. Conclusion: Although a number of early nonresponsive patients will achieve remission, this study points out that these patients are at risk factor for ultimate treatment failure. This could be an indication for clinicians to adapt their treatment strategy. © 2007 Elsevier B.V. All rights reserved. Keywords: Early response; Outcome; Psychotherapy; Combined therapy; Major depression
☆
Conflicts of interest: All authors declare that they do not have any actual or potential conflict of interest with other people or organizations within three years of beginning the work submitted that could inappropriately influence our work. Contributors: Henricus L. Van contributed to the design the study, did the literature searches, included and treated patients in the trials, contributed to the statistical analysis and wrote both the previous concepts and final draft of the manuscript. Robert A. Schoevers and Jack Dekker contributed to the design of the study, contributed to the statistical analysis and the interpretation of data and other actual final draft of the paper. Jaap Peen undertook the statistical analysis and contributed to the final draft of the paper. Simone Kool and Marielle Hendriksen contributed to the design of the study, included and treated patients in the trials and contributed to the final draft of the paper. Role of funding source: The original trials were supported by unrestricted educational grants from Eli Lilly Nederland and Wyeth Nederland. Eli Lilly Nederland and Wyeth Nederland had no further role in study design; in collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper or publication. None of the authors do have any actual or potential conflict of interest including any financial, personal or other relationships with other organizations within three years of beginning the work submitted that could inappropriately influence, or be perceived to influence, to their work. ⁎ Corresponding author. Mentrum Mental Health Hospital, PO Box 75848, 1070 AVAmsterdam, The Netherlands. Tel.: +31 20 5904440; fax: +31 20 4898150. E-mail address: [email protected] (H.L. Van). 0165-0327/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2007.04.016
262
H.L. Van et al. / Journal of Affective Disorders 105 (2008) 261–265
Although major depressive disorders can be treated effectively, a substantial number of patients do not fully respond. In order to identify patients who will respond the association between pre-treatment patient characteristics and outcome has frequently been investigated. This has yielded a number of potential predictors, but results appear to be conflicting (Nierenberg, 2003). Instead of investigating pre-treatment characteristics, an alternative approach would be to make use of patterns of early response as predictors of treatment outcome. This would enable clinicians to shorten the duration of an unsuccessful treatment, and proceed to the next step in the treatment protocol. There is general agreement that response by week 4 is related to outcome of treatment with antidepressants, and that in case of complete early nonresponse a switch in antidepressant medication is indicated (Quitkin et al., 1996). However, only a few studies have addressed the predictive value of early response in psychotherapy for depression (Renaud et al., 1998) and the results remain open for debate. Finally, although the usefulness of combining pharmacotherapy and psychotherapy has been demonstrated (Keller et al., 2000) we are not aware of studies addressing the predictive value of early response in combined therapy. The aim of this study was to investigate the relationship between early response and outcome in depressed patients, treated with either Short-Term Psychodynamic Supportive Psychotherapy (SPSP) only, or combined with an antidepressant. In contrast with the assessment of early (non) response in antidepressants, there is no agreed-upon definition in psychotherapy for early response (Haas et al., 2002). We decided to measure response at week 8, assuming, on theoretical grounds, that by then early non-specific or placebo effects may have passed and an initial specific effect of the psychotherapy have emerged. Currently, complete treatment failure is defined as less than 25% decrease on an accepted depression rating scale (Hirschfeld et al., 2002). In order to identify all patients with an apparent initial effect, we therefore adopted the 25% decrease in depression symptoms as the cut off score to determine whether there is an early response.
dam. The original trials successively compared pharmacotherapy with combined therapy (De Jonghe et al., 2001), and psychotherapy with combined therapy (de Jonghe et al., 2004). Of the third study, comparing an antidepressant with either 8 or 16 sessions of psychotherapy (Dekker et al., 2005) only the data of the latter were included. The patients were adults with DSM-IV defined major depressive disorder and HAM-D-17 score of 14–25. The treatment modalities lasted for a period of six months. Depression scores were rated independently with the HAM-D-17 after 2 months and after 6 months of treatment. The psychotherapy consisted of sixteen sessions of Short-Term Psychodynamic Supportive Psychotherapy (SPSP). SPSP focuses on the affective, behavioral and cognitive aspects of relationships that may be discussed from both an interpersonal and an intrapersonal perspective (de Jonghe, 2005; Van et al., 2006). The therapists were trained psychiatrists or psychotherapists. They met regularly to discuss audiotaped sessions and to ensure adherence to the psychotherapy manual. In two trials patients started with fluoxetine, in one trial with venlafaxine. In cases of intolerance or obvious complete nonresponse, the antidepressant was replaced by nortriptyline. To control for a potential influence of medication switch on outcome, an additional analysis was performed excluding these patients. The sample and procedures have been described in greater detail in previous publications. To control for a possible dosage-effect, only patients who fully completed treatments were included. This concerns 63 out of 97 patients in psychotherapy and 127 out of 171 in combined therapy. Completers and non completers did not differ with respect to baseline characteristics. The HAM-D-17 reduction after 8 weeks of treatment was divided into two categories: early response (N 25% reduction) or early nonresponse (b 25% reduction). As outcome variables we defined complete nonresponse (b25% reduction), remission (HAM-D-17b 7) and partial response (N25% reduction but no remission achieved). Differences between categories at the end of treatment were analyzed using Chi2 test. Next, a logistic regression analysis was performed, adjusting for initial severity of depression as a covariate.
2. Methods
3. Results
The data were drawn from three RCTs conducted in two outpatient facilities of the Mentrum Mental Health Care, a large psychiatric teaching hospital in Amster-
In the whole sample, 67% of the patients were female. The average age was 35.4 (SD = 10.45). The mean HAMD-17 at baseline was 18.7 (SD 3.0). Overall, 33% of the
1. Introduction
H.L. Van et al. / Journal of Affective Disorders 105 (2008) 261–265
263
Fig. 1. Complete nonresponse, partial response and remission (%) at the end of treatment in early nonresponders and early responders.
patients in SPSP and 45% in combined therapy achieved remission. Although this difference was suggestive, it was not statistically significant (Chi2 2.56; p = 0.11). Treatment outcome was compared between early responders and early nonresponders (Fig. 1). In the psychotherapy condition, 31 out of 63 patients were identified as early nonresponders. Of these, 14 patients (45%) remained in this category until the end of treatment, 9 (25%) showed a partial response and 8 (26%) achieved remission. Among the 32 psychotherapy patients with an early response, 12 (38%) achieved remission, 14 (44%) had a partial response and 6 (19%) reverted to complete nonresponse. With respect to final complete nonresponse, the difference between early nonresponders and responders was statistically significant with respect to complete nonresponse (Chi2 = 5.069, df = 1, p b 0.01). This was not the case for the differences in remission rates (Chi2 = 0.994, df = 1, p = 0.319). In the combined therapy condition, 50 out of 127 patients were identified as early nonresponders. Of these, 21 patients (42%) remained nonresponsive until the end of treatment, 26 showed a partial response and 13 patients (26%) ultimately achieved full remission. Of the 77 combined therapy patients with an early response, 46 (60%) achieved remission, 22 a partial response
whereas 9 (12%) reverted to complete nonresponse. With respect to final complete nonresponse the difference between early nonresponders and responders was statistically significant, both with respect to complete nonresponse (Chi2 = 16.019, df = 1, p b 0.001) and remission (Chi2 = 12.435, df = 1, p b 0.001). Subsequently, in a logistic regression analysis controlling for initial depression severity, odds ratios were computed (Table 1). In psychotherapy final nonresponse was significantly related to nonresponse at week 8. However, remission was not related to early response.
Table 1 Odds ratios (95% confidence interval) for HAM-D-17 scores at week 8 with outcome at week 24 SPSP
OR (C.I.)
P
Week 8
Week 24
Nonresponse Response
Nonresponse Remission
3.57 (1.14–11.22) 1.72 (0.59–5.06)
b0.05 ns
Combined therapy Nonresponse Nonresponse Response Remission
7.13 (2.59–16.63) 3.66 (1.68–7.99)
b0.00 b0.00
264
H.L. Van et al. / Journal of Affective Disorders 105 (2008) 261–265
In combined therapy, final nonresponse was related to early nonresponse and the achievement of remission to early response. In combined therapy, 30 patients switched antidepressant medication. Excluding these patients from the analysis did not change the findings. 4. Discussion The results presented in this study showed an equivocal relationship between early response and outcome in psychotherapy for major depression. Nonresponse after 8 weeks of treatment was clearly predictive of final nonresponse. However, when addressing remission as an outcome measure, early response was not related to outcome. This suggests that in some patients, psychotherapy may require more time than 8 weeks before favorable effects become noticeable. A potential theoretical explanation of this delayed effectiveness may be the time needed to establish a beneficial psychotherapeutic relationship. In combined therapy, both complete nonresponse and remission at the end of treatment were related to the depression scores after 8 weeks. In particular, early nonresponse carried a large risk of final nonresponse (OR 7.13). Still, it should be noted that even among these early nonresponders, a quarter achieved remission at the end of therapy. Few studies specifically analyzed the predictive value of early response in psychotherapy. The available studies measured response after one of the first sessions (Renaud et al., 1998) or included patients with a variety of diagnoses who were treated with varying types and duration of psychotherapy (Percevic et al., 2006). A strength of this study is that it concerns all patients with the same diagnosis treated with one form of standardized psychotherapy. This enabled us to determine the time–response relationship under relatively homogeneous conditions. There are also a number of limitations. The study concerns a post hoc analysis of data that were not originally collected to explore the predictive value of early response. SPSP was the only psychotherapy examined. It is not certain whether the results can be generalized to other short-term psychotherapies for depression. Pre-treatment patient's characteristics that might influence speed of change, such as level of social impairment were not taken into account. Finally, the design did not enable feedback to the therapist about the independently determined depression score. Especially in cases of poor progress this may increase attendance for patients and improve outcome (Whipple et al.,
2003). On the other hand, for a lot of clinicians it may be difficult to arrange a systematic and independently measured feedback. In this sense the presented design reflects common practice. Overall, it can be concluded that early nonresponse carries an important risk for final non-response. At the same time a substantial number of early nonresponsive patients do remit following prolonged psychotherapy or combined therapy. Clearly it would be of help if clinicians could identify these patients and subsequently allocate the optimal treatment. Future research should therefore ideally combine data on early response with other potential predictors such as pre-treatment patient's characteristics. At present, we believe that in depressed patients treated with psychotherapy only, the addition of an antidepressant should be considered in cases of early nonresponse in order to increase their chance of final remission. In line with the recent findings of the STAR⁎D project (Rush et al., 2006) a switch of antidepressants appears to be a logical step for non responsive patients in combined therapy. Nevertheless, the effectiveness of this step in case of a prolonged psychotherapeutic treatment has not yet been demonstrated and needs further research. References Dekker, J., Molenaar, P.J., Kool, S., van Aalst, G., Peen, J., de Jonghe, F., 2005. Dose-effect relations in time-limited combined psychopharmacological treatment for depression. Psych. Med. 35, 47–58. De Jonghe, F., 2005. Short-term Psychodynamic Supportive Psychotherapy. Benecke N.I., Amsterdam. (in Dutch). De Jonghe, F., Kool, S., van Aalst, G., Dekker, J., Dekker, J., 2001. Combining psychotherapy and antidepressants in the treatment of depression. J. Affect. Disord. 64, 217–229. De Jonghe, F., Hendriksen, M., van Aalst, G., Kool, S., Peen, J., Van, H.L., Eijnden, E., Dekker, J., 2004. Psychotherapy and combined therapy (pharmacotherapy plus psychotherapy) in the treatment of depression. Br. J. Psychiatry 185, 37–45. Haas, E., Hill, R., Lambert, M.J., Morrel, B., 2002. Do early responders to psychotherapy maintain treatment gains? J. Clin. Psychol. 58, 1157–1172. Hirschfeld, R.M.A., Montgomery, S.A., Aguglia, E., Aguglia, M., Delgado, P., Delgado, M., Hawley, C., Kasper, S., Kasper, M., Massana, J., Mendlewicz, J., Möller, H., Nemeroff, C.B., Nemeroff, J., Such, P., Torta, R., Versiani, M., 2002. Partial response and nonresponse to antidepressant therapy: current approaches and treatment options. J. Clin. Psychiatry 63, 826–837. Keller, M.B., McCullough, J.P., Klein, D.N., Arnow, B., Dunner, D.L., Gelenberg, A.J., Markowitz, J.C., Nemeroff, C.B., Russell, J.M., Thase, M.E., Trivedi, M.H., Zajecka, J., 2000. A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N. Engl. J. Med. 342, 1462–1470. Nierenberg, A.A., 2003. Predictors of response to antidepressants: general principles and clinical implications. Psychiatr. Clin. North Am. 26, 345–352.
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