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 Treatment options for major depression have been a central issue of psychiatric investigation. Medications and psychotherapy have been extensively studied and used in clinical practice. The efficacy of antidepressant drugs is supported by many placebo-controlled trials and represents the current standard of treatment (1,2). Brief psychotherapies are commonly used as antidepressant therapy and have been studied by several authors (3–9). IPT ranks among models of psychotherapy that have been effective in treating depressive disorders (10–18). Accordingly, IPT has been recommended in the practice guidelines for depression and has been more widely used in clinical practice (1). Recently, combined therapy (using antidepressant drugs and brief psychotherapy) has been increasingly evaluated and has proven more efficacious than monotherapy in the treatment of depression, particularly in selected clinical populations (that is, chronic or severe depression). Authors reported response rates of 50% to 85% with combined therapy, compared with 35% to 55% with either only drugs or only psychotherapy (19–25). Few systematic investigations have been conducted on combined treatment of patients with depression and comorbid personality disorders. A recent study found that combined therapy is more effective than pharmacotherapy alone in patients with depression and personality disorders (26). Further, Cyranowski and others treated patients suffering from depression with IPT and found that subjects meeting criteria for a personality disorder more frequently needed adjunctive SSRI treatment to achieve remission of depressive episodes (16). Although this comorbidity is very common (53% to 85% in BPD samples) (27–31) and exerts significant effects on severity of depression and social impairment (27,32,33), there are currently no studies that focus on combined treatment of major depression that affects patients with BPD. The use of psychotherapy in treating these patients is central to the investigation of this topic. In our opinion, IPT is a good option as it is both recommended to treat major depression and listed in treatment guidelines among new, promising psychotherapies for BPD (34,35). Aim of the StudyWe designed this study to compare the efficacy of combined therapy (that is, a serotonergic antidepressant plus IPT) with monotherapy (that is, an antidepressant) in patients with depression and comorbid BPD. MethodsThe study participants were selected from patients attending the Service for Personality Disorder of the Unit of Psychiatry, Department of Neuroscience, University of Turin. We included consecutive outpatients who received a DSM-IV-TR (36) diagnosis of BPD and then met criteria for a major depressive episode (that is, mild to moderate). Diagnoses were made by an expert clinician and were confirmed using the structured clinical interview for DSM-IV Axis I and II disorders (37,38). We excluded individuals with a lifetime diagnosis of delirium, dementia, amnestic or other cognitive disorders, schizophrenia or other psychotic disorders, and patients whose major depressive episode was an expression of bipolar disorder. Exclusion criteria also considered a current diagnosis of substance abuse disorder and whether an individual was treated with psychotropic drugs or psychotherapy during the 2 months prior to the study. Female patients of childbearing age were excluded if they were not using an adequate method of birth control (according to the judgment of the clinician). Written informed consent was obtained from all patients prior to their participation. We followed the Declaration of Helsinki guidelines. Patients were randomly assigned to 1 of 2 treatment groups: pharmacotherapy alone or combined therapy. Patients underwent their respective treatments for 24 weeks. Pharmacotherapy Of the initial 39 participants, 19 patients received fluoxetine 20 mg to 40 mg daily plus clinical management. Initially, fluoxetine was prescribed at a fixed dosage of 20 mg daily with the opportunity to increase the dosage to 40 mg daily beginning in Week 2, depending on clinical judgment. Each patient was given 4 appointments, the first 2 fortnightly and the last 4 monthly. A psychiatrist provided pharmacotherapy and clinical management. Combined Therapy The other 20 patients received fluoxetine plus IPT. IPT consisted of weekly sessions lasting 1 hour and was conducted referring to the Interpersonal Psychotherapy of Depression Manual (39). Patients in the combined therapy group were treated by a psychotherapist who was not the psychiatrist prescribing the medication and who had 5 years of experience practising IPT. The psychotherapy and the pharmacotherapy started at the same time. All patients were repeatedly assessed (that is, at baseline, Week 12, and Week 24) with the following measures:
The assessments were performed by an investigator who was blind to the treatment methods. Remission was defined by a decreased HDRS score (≥ 40%), with a final score of ≤ 8, and a score of 1 (that is, very much improved) or 2 (that is, much improved) on the Improvement item of the CGI. We performed statistical analyses using the software program SPSS version 12.0. Only those patients who completed the study were included in the analysis. We used t tests and chi-square tests to compare demographic and clinical characteristics (that is, age, sex, the Severity item of the CGI, and HDRS and HARS scores) at baseline. We used Pearson’s chi-square test to compare the number of respondents between subgroups of patients treated with combined therapy or pharmacotherapy alone. We used the univariate GLM to calculate the effects of 2 factors (that is, the duration and the type of treatment) on each assessment scale score. P values were considered significant when P < 0.05 .ResultsInitially, there were 39 patients enrolled in the study. At intake, there were no significant differences between the 2 treatment groups with regard to age, sex, the Severity item of the CGI, and HDRS and HARS scores. Owing to noncompliance, 7 patients discontinued treatment during the first 3 weeks. Of these individuals, 4 were in the medication-only group, and 3 were in the combined therapy group. We performed statistical analyses on the 32 patients (that is, 16 patients in each group) who completed the 24 weeks of treatment. The sample had a mean age of 26.4, SD 3.7, years. The ratio of men to women was 3 to 5. At the endpoint, 75% (n =12) of combined-treatment patients and 62.5% (n =10) of medication-only patients achieved remission. Statistical comparison with Pearson’s test did not show a significant difference (c2 = 0.562, P = 0.446). Results of the univariate GLM performed on the Severity item of the CGI, HDRS, and HARS results are presented in Table 1. On each scale, we found that the time factor had a significant effect (P = 0.0005). The treatment factor showed a significant effect (P = 0.005) only on the HDRS, which indicates a higher score change in the subgroup receiving combined therapy.
We applied the GLM to the 5 factors of the SAT-P. The results are presented in Table 2. There was a significant change in all the factors related to the length of treatments (P < 0.001). We found that the interaction of the time factor and the treatment factor had a significant effect on the psychological functioning factor (P = 0.017): the efficacy of combined therapy was greater in function over the course of treatment. The treatment factor (P = 0.020) and the interaction of the time and treatment factors
Results of the univariate GLM applied to the 8 domains of the IIP-64 are described in Table 3. Findings differ depending on which domain is considered. Neither time nor treatment factors had a significant effect on any of the following 4 domains: domineering or controlling, nonassertive, overly accommodating, and self-sacrificing. Both the time (P < 0.005) and the treatment factor (P < 0.05) had a significant effect on the intrusive or needy, vindictive or self-centred, and cold or distant domains. These results indicate that combined therapy has more of an impact on these areas than drug therapy. The time factor (P = 0.0005) and the interaction between the time factor and the treatment factor (P = 0.021) both had a significant effect on the socially inhibited factor, which shows that combined therapy had better results and that the difference between treatments increased with the length of therapy.
DiscussionOur study compared combined therapy (that is, fluoxetine plus IPT) with pharmacotherapy alone (that is, fluoxetine) in the treatment of patients with a major depressive episode and preexisting BPD. We chose fluoxetine because it is a widely used antidepressant and it is recommended by APA treatment guidelines for BPD (35,49). Our patients were treated with IPT because this approach has been proposed and studied for the treatment of major depressive disorder (5,39) and is now considered one of the effective psychotherapies for BPD (35,50). The 2 treatment modes do not differ significantly in rates of remission, improvement of global psychopathology, and reduction of anxious symptoms. Significant differences favouring combined therapy have been found in depressive symptoms and in factors related to subjective quality of life and dysfunctional patterns of interpersonal relationships. Rates of remission do not differ significantly between the combined-treatment group and the pharmacotherapy group (75%, compared with 62.5%). This finding is concordant with a recent metaanalysis conducted by de Mello and others who considered studies of combined therapy using IPT, compared with pharmacotherapy alone, in depressive disorders (18). Nevertheless, this review did not consider the presence of personality disorders in patients with depression. Significant differences between treatments in our patients concern symptoms of depression and measures of social and relational functioning. A comparison with the literature data is not easy. Many authors have found that concomitant personality disorders have negative effects on the treatment outcome of patients with major depression, both on depressive symptoms and on social functioning (51–54). A study by Kool and others compared combined treatment and pharmacotherapy of depression, examining the effect of personality disorders on differences in clinical response (26). In patients with concomitant personality disorders, combined therapy was superior to pharmacotherapy in measures of global psychopathology, depressive symptoms, and quality of life. These differences were not found in patients without Axis II comorbidity. We must emphasize at least 2 differences between our study and Kool and others’ study: Kool and others provided short psychodynamic supportive psychotherapy, although BPD was only one of the Axis II diagnoses in their sample and only the fourth most frequent. Regarding subjective quality of life as measured by the SAT-P, our results show that IPT combined with fluoxetine is significantly superior to the antidepressant alone in changing the psychological functioning and the social functioning factors. The first factor deals with self-esteem, psychological autonomy, and problem-solving ability. The second factor refers to the quality of social relations. These results are consistent with recent literature that indicates an improvement in quality of life and social skills both in patients with depression (17,22,55,56) and in patients with BPD treated with combined therapy (34,57–59). Nevertheless, studies concerning quality of life in patients receiving combined therapy for a codiagnosis of major depression and BPD are not available. Our findings on the data collected with IIP-64 are heterogeneous if single domains are considered. The vindictive or self-centred, cold or distant, socially inhibited, and intrusive or needy domains show higher changes over time with combined therapy than with drug therapy. As these domains appear to be related to symptoms of BPD such as fear of abandonment and unstable relationships, we can suggest that the association of IPT with an antidepressant is effective not only at increasing improvement of depressive symptoms but also in modifying dysfunctional relationship patterns that reflect the abnormalities of borderline personality. Conversely, the domineering or controlling and nonassertive domains do not change significantly with either treatment. The case is the same for the overly accommodating and self-sacrificing domains, but it is important to note that scores of these 2 domains are included, according to the manual of the IIP-64, in a norm-based range beginning at baseline (50). It is not clear why some domains of the IIP-64 change significantly after treatment of a depressive episode while others do not. Perhaps the domineering or controlling and nonassertive domains are expressions of BPD features, such as identity disturbance, that are highly persistent and cannot be affected by a 6-month treatment period. We can propose an overall explanation of the differences between combined treatment and pharmacotherapy alone in patients with BPD and major depression. We suggest that these patients are affected by depressive symptoms as a consequence of maladaptive personality traits that influence mood reaction to interpersonal difficulties. Combining IPT with antidepressant treatment may produce additional effects on these traits and contribute to improvements in depression and relational functioning. In conclusion, our findings confirm that combined therapy is more effective than pharmacotherapy alone, both on symptoms and on social and relational functioning of patients with BPD and major depressive disorder. If these data were replicated, the combination of a serotonergic antidepressant and IPT could be proposed as a preferred treatment for the large proportion of patients with BPD who suffer from depression. More extensive studies, including a larger sample and a comparison between combined therapy and IPT alone, are needed to confirm these clinical suggestions. Our study is limited by the lack of follow-up assessments to evaluate whether clinical results are maintained over time and whether improved quality of life and relational functioning achieved with combined therapy can influence the prevention of recurrence of depressive episodes. We are currently collecting follow-up data that will be analyzed and presented in a forthcoming paper. Funding and SupportThis study received no funding and no support. References1. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder. Washington (DC): American Psychiatric Press; 2000. 2. National Institute for Clinical Excellence. Depression: management in primary and secondary care. Clinical Guidelines 23. London (UK): NICE; 2004. 3. Robinson LA, Berman JS, Neimeyer RA. Psychotherapy for the treatment of depression: a comprehensive review of controlled outcome research. Psychol Bull 1990;108:30–49. 4. Svartberg M, Stiles TC. Comparative effects of short-term psycodinamic psychotherapy: a meta-analysis. J Consult Clin Psychol 1991;59:704–14. 5. Depression Guideline Panel. Treatment of major depression. Clinical practice, number 5. Depression in Primary Care: volume 2. US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research. Rockville (MD): AHCPR Publication nr 93–0551; 1993. 6. Jarrett RB, Rush AJ. Short-term psychotherapy of depressive disorders: current status and future directions. Psychiatry 1994;57:115–32. 7. Hardy GE, Barkham M, Shapiro DA, Stiles WB, Rees A, Reynolds S. Impact of cluster C personality disorders on outcomes of contrasting brief psychotherapies for depression. J Consult Clin Psychol 1995;63:997–1004. 8. DeRubeis RJ, Hollon SD, Amsterdam JD, Shelton RC, Young PR, Salomon RM, and others. Cognitive therapy vs medications in the treatment of moderate to severe depression. Arch Gen Psychiatry 2005;62:409–16. 9. McPherson S, Cairns P, Carlyle J, Shapiro DA, Richardson P, Taylor D. The effectiveness of psychological treatments for treatment resistant depression: a systematic review. Acta Psychiatr Scand 2005;111:331–40. 10. Frank E, Kupfer DJ, Wagner EF, McEachran AB, Cornes C. Efficacy of interpersonal psychotherapy as a maintenance treatment of recurrent depression. Arch Gen Psychiatry 1991;48:1053–9. 11. Elkin I, Gibbons RD, Shea MT, Sotsky SM, Watkins JT, Pilkonis PA. Initial severity and differential treatment outcome in the national institute of mental health treatment of the depression collaborative research program. J Consult Clin Psychol 1995;6:841–7. 12. Weissman MM. Interpersonal psychotherapy: current status. Keio J Med 1997;46:105–10. 13. Grote NK, Frank E. Difficult to treat depression: the role of contexts and comorbidities. Biol Psychiatry 2003;53:660–70. 14. Markowitz JC. Developments in interpersonal psychotherapy. Can J Psychiatry 1999;44:556–61. 15. Markowitz JC. Interpersonal psychotherapy for chronic depression. J Clin Psychol 2003;59:847–58. 16. Cyranowsky JM, Frank E, Winter E, Rucci P, Novick D, Pilkonis P, and others. Personality pathology and outcome in recurrently depressed women over two years of maintenance interpersonal psychotherapy. Psychol Med 2004;34:659–69. 17. Swartz HA, Frank E, Shear MK, Thase M, Fleming MAD, Scott J. A pilot study of brief interpersonal psychotherapy for depression among women. Psychiatr Serv 2004;55:448–50. 18. de Mello FM, Mari JJ, Bacaltchuk J, Verdeli H, Neugebauer R. A systematic review of research findings on the efficacy of interpersonal therapy for depressive disorders. Eur Arch Psychiatry Clin Neurosci 2005;225:75–82. 19. Thase ME, Greenhouse JB, Frank E, Reynolds CF, Pilkonis PA, Hurley K, and others. Treatment of major depression with psychotherapy or psychotherapy-pharmacotherapy combinations. Arch Gen Psychiatry 1997;54:1009–15. 20. Thase ME. When are psychotherapy and pharmacotherapy combinations the treatment of choice for major depressive disorder? Psychiatr Q 1999;70:333–46. 21. Keller MB, McCullough JP, Klein DN, Arnow B, Dunner DL, Gelenberg AJ, and others. A comparison of nefazodone, the cognitive-behavioral analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med 2000;342:1462–70. 22. de Jonghe F, Kool S, van Aalst G, Dekker J, Peen J. Combining psychotherapy and antidepressants in the treatment of depression. J Affect Disord 2001;64:217–29. 23. Dunner DL. Acute and maintenance treatment of chronic depression. J Clin Psychiatry 2001;62:10–6. 24. Nemeroff CB, Heim CM, Thase ME, Klein DN, Rush AJ, Schatzberg AF, and others. Differential responses to psychotherapy vs pharmacotherapy in patients with chronic forms of major depression and childhood trauma. Proc Natl Acad Sci USA 2003;100:14293–6. 25. Hollon SD, Jarrett RB, Nierenberg AA, Thase ME, Trivedi M, Rush AJ. Psychotherapy and medication in the treatment of adult and geriatric depression: which monotherapy or combined treatment? J Clin Psychiatry 2005;66:455–68. 26. Kool S, Dekker J, Duijsens IJ, de Jonghe F, Puite B. Efficacy of combined therapy and pharmacotherapy for depressed patients with or without personality disorders. Harv Rev Psychiatry 2003; 11:133–41. 27. Comtois KA, Cowley DS, Dunner DL, Roy-Byrne PP. Relationship between borderline personality disorder and Axis I in severity of depression and anxiety. J Clin Psychiatry 1999;60:752–758. 28. Zimmerman M, Mattia JI. Axis I diagnostic comorbidity and borderline personality disorder. Compr Psychiatry 1999;40:245–52. 29. Johnson DM, Shea MT, Yen S, Battle CL, Zlotnick C, Sanislow CA, and others. Gender difference in borderline personality disorder: findings from the collaborative longitudinal personality disorders study. Compr Psychiatry 2003;44:284–92. 30. Zanarini MC, Frankenburg FR, Hennen J, Reich DB, Silk KR. Axis I comorbidity in patients with borderline personality disorder: 6-years follow up and prediction of time to remission. Am J Psychiatry 2004;161:2108–14. 31. Zittel Conklin C, Westen D. Borderline personality disorder in clinical practice. Am J Psychiatry 2005;162:867–75. 32. Rothschild L, Zimmerman M. Borderline personality disorder and age of onset in major depression. J Personal Disord 2002;16:189–99. 33. Bellino S, Patria L, Paradiso E, Di Lorenzo R, Zanon C, Zizza M, and others. Major depression in patients with borderline personality disorder: a clinical investigation. Can J Psychiatry 2005;50:234–8. 34. Stone MH. Clinical guidelines for psychotherapy for patients with borderline personality disorders. Psychiatr Clin North Am 2000;23:193–210. 35. Oldham JM. Guideline watch. Practice guideline for the treatment of patients with borderline personality disorder. Arlington (VA): American Psychiatric Association; 2005 p 4–6. 36. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed Text revision. Washington (DC): American Psychiatric Press; 2000. 37. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical interview for DSM-IV axis I disorders (SCID-I). Washington (DC): American Psychiatric Press; 1997. 38. First MB, Gibbon M, Spitzer RL, Williams JBW, Benjamin LS. Structured clinical interview for DSM-IV Axis II disorders (SCID-II). Washington (DC): American Psychiatric Press; 1997. 39. Klerman GL, Weissman MM, Rounsaville BJ, Chevron ES. Interpersonal psychotherapy of depression. New York (NY): Basic Books; 1984. 40. Guy W. ECDEU assessment manual for psychopharmacology. US department of health, education, and welfare publication (ADM) 76–338. Rockville (MD): National Institute of Mental Health; 1976. p 218–22. 41. Hamilton M. A rating scale for depression. J Neurol, Neurosurg Psychiatry 1960;23:56–62. 42. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychology 1959;32:50–5. 43. Majani G, Callegari S. SAT-P satisfaction profile. Soddisfazione soggettiva e qualitB della vita. Trento (IT): Erickson; 1998. 44. Horowitz LM, Alden LE, Wiggins JS, Pincus AL. Inventory of interpersonal problems. San Antonia (TX): Harcourt Assessment; 2000. 45. Borkovec TD, Newman MG, Pincus AL, Lytle R. A component analysis of cognitive-behavioral therapy for generalized anxiety disorder and the role of interpersonal problems. J Consult Clin Psychol 2002;70:288–98. 46. Vittengl JR, Clark LA, Jarrett RB. Interpersonal problems, personality pathology and social adjustment after cognitive therapy for depression. Psychol Assess 2003;15:29–40. 47. Leichsenring F, Biskup J, Kreische R, Staats H. The Gottingen study of psychoanalytic therapy: first results. Int J Psychoanal 2005;86:433–55. 48. Loffler-Statska H, Ponocny-Seliger E, Fischer-Kern M, Leithner K. Utilization of psychotherapy in patients with personality disorder: the impact of gender, character traits, affect regulation and quality of object-relations. Psychol Psychother 2005;78:531–48. 49. American Psychiatric Association. Practice guidelines for the treatment of patients with borderline personality disorder. Am J Psychiatry 2001;158:1–52. 50. Markowitz JC. Interpersonal therapy. In: Oldham JM, Skodol AE, Bender D, editors. The textbook of personality disorders. Washington (DC): American Psychiatric Press; 2005. 51. Frank E, Kupfer DJ, Jacob M, Jarret D. Personality features and response to acute treatment in recurrent depression. J Pers Disorders 1987;1:14–26. 52. Shea MT, Pilkonis PA, Beckham E, Collins JF, Elkin I, Sotsky SM, and others. Personality disorders and treatment outcome in the NIMH treatment of depression collaborative research program. Am J Psychiatry 1990;147:711–8. 53. Ezquiaga E, Garcia-Lopez A, de Dios C, Leiva A, Bravo M, Montejo J. Clinical and psychosocial factors associated with the outcome of unipolar major depression: a one year prospective study. J Affect Disord 2004;79:63–70. 54. Gunderson JG, Morey LC, Stout RL, Skodol AE, Shea MT, McGlashan TH, and others. Major depressive disorder and borderline personality disorder revisited: longitudinal interactions. J Clin Psychiatry 2004;65:1049–56. 55. Weissman MM, Klerman GL, Prusoff BA, Sholomskas D, Padian N. Depressed outpatients. Results one year after treatment with drugs and /or interpersonal psychotherapy. Arch Gen Psychiatry 1981;38:51–5. 56. Hirschfeld RM, Dunner DL, Keitner G, Klein DN, Koran LM, Kornstein SG, and others. Does psychosocial functioning improve independent of depressive symptoms? A comparison of nefazodone, psychotherapy, and their combination. Biol Psychiatry 2002;51:123–33. 57. Livesley WJ. A practical approach to the treatment of patients with borderline personality disorder. Psychiatr Clin North Am 2000;23:211–32. 58. Gunderson JG. Borderline personality disorder: a clinical guide. Washington (DC): American Psychiatric Publishing, 2001. 59. Karterud S, Pedersen G, Bjordal E, Brabrand J, Friis S, Haaseth O. Day treatment of patients with personality disorders: experiences from a Norwegian treatment research network. J Personal Disord 2003;17:243–62. Author(s)Manuscript received October 2005, revised, and accepted March 2006. 1. Assistant Professor, Unit of Psychiatry, Department of Neuroscience, University of Turin, Torino, Italy. 2. Clinical Psychologist, Unit of Psychiatry, Department of Neuroscience, University of Turin, Torino, Italy. 3. Psychiatry Resident, Unit of Psychiatry, Department of Neuroscience, University of Turin, Torino, Italy. 4. Professor, Unit of Psychiatry, Department of Neuroscience, University of Turin, Torino, Italy. Address for correspondence: Dr S Bellino, Unit of Psychiatry, Department of Neuroscience, University of Turin, Via Cherasco 11, 10126 Torino, Italy e-mail: silvio.bellino@unito.it
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