What is the best sequential treatment strategy in the treatment of depression? Adding pharmacotherapy to psychotherapy or vice versa?

BACKGROUND: Insufficient response to monotreatment for depression is a common phenomenon in clinical practice. Even so, evidence indicating how to proceed in such cases is sparse. METHODS: This study looks at the second phase of a sequential treatment algorithm, in which 103 outpatients with moderately severe depression were initially randomized to either short-term supportive psychodynamic therapy (PDT) or antidepressants. Patients who reported less than 30% symptom improvement after 8 weeks were offered combined treatment. Outcome measures were the Hamilton Depression Rating Scale (HAM-D), the Clinical Global Impression of Severity and Improvement, the SCL-90 depression subscale and the EuroQOL questionnaire. RESULTS: Despite being nonresponsive, about 40% of patients preferred to continue with monotherapy. At treatment termination, patients initially randomized to PDT had improved more than those initially receiving antidepressants, as indicated by the HAM-D and the EuroQOL, independently of whether the addition was accepted or not. CONCLUSIONS: Starting with psychotherapy may be preferable in mildly and moderately depressed outpatients. For patients who receive either PDT or antidepressants, combined therapy after early nonresponse seems to be helpful. Nevertheless, this sequential strategy is not always preferred by patients.

Speed of action: the relative efficacy of short psychodynamic supportive psychotherapy and pharmacotherapy in the first 8 weeks of a treatment algorithm for depression.

OBJECTIVE: To examine the efficacy and speed of action of short-term psychodynamic supportive psychotherapy (SPSP) in comparison to pharmacotherapy (PhT) in the acute treatment of depression. METHOD: This study reported on the first 8 weeks of a treatment algorithm for depression. 70 patients with a depressive episode according to DSM-IV were randomized to PhT, 71 patients were randomized to SPSP. The acceptability of the psychotherapy was greater than pharmacotherapy. RESULTS: At the end of the first 8 weeks of treatment, attrition rates were similar in both conditions. PhT-patients were better off at 4 weeks according to two of the four measures The superiority of PhT was clearer on the self-report than on the independent measure. CONCLUSIONS: There are signs that the benefits of PhT over SPSP--where detected--are short-lived and cover mostly the first month of treatment. The progression of these patients through the rest of their treatments, and afterwards, will be reported in further contributions.

[Treatment of depressive disorder and comorbid personality pathology: combined therapy versus pharmacotherapy]. / Behandeling van de depressieve stoornis en comorbide persoonlijkheidspathologie: gecombineerde therapie versus farmacotherapie.

BACKGROUND: Comorbidity of depressive and personality disorder occurs frequently, in literature percentages of around 50 to nearly 80 percent are found. Also in the Mentrum depression study on which this article is grounded, high percentages of around 66% were found. There is no equivocal treatment method of choice in literature, and opinions differ as to whether personality pathology has an adverse influence on the efficacy of the treatment for depression. AIM: To compare the results of pharmacotherapy and combined therapy in the treatment of depressive disorders in patients with and without comorbid personality disorder. METHOD: A 6 month randomised clinical trial of antidepressants and combined therapy in ambulatory patients with major depressive disorder and a baseline score of at least 14 points on the 17-item Hamilton Rating Scale for Depression. Pharmacotherapy follows three subsequent steps in case of intolerance/inefficacy: fluoxetine, amitriptyline and moclobemide. In addition combination therapy includes 16 short-term sessions of psychodynamic supportive psychotherapy. Possible personality pathology is assessed by means of the 'Vragenlijst Kenmerken Persoonlijkheid' (a self report version of the International Personality Disorder Examination). Analyses of (co) variance and chi-squared tests were applied to assess the differences in both treatment conditions in the group with and without personality pathology. RESULTS: Combined therapy was significantly more effective than pharmacotherapy for depressed patients with personality disorders. For depressed patients without personality disorders, combined therapy was not more effective than pharmacotherapy alone. CONCLUSION: The combination of psychotherapy and pharmacotherapy seems to be the treatment of choice for depressed patients with comorbid personality pathology.

Dose-effect relations in time-limited combined psycho-pharmacological treatment for depression.

BACKGROUND: A limited number of psychotherapy sessions in combination with medication is preferable to pharmacotherapy only in the treatment of ambulatory patients with major depression. Whether there is a relation between the number of sessions and the efficacy of the treatment is uncertain. METHOD: Randomized clinical trial comparing two treatment conditions in outpatients with major depression. All patients studied had a baseline score of at least 14 points on the 17-item Hamilton Depression Rating Scale. The two conditions consist of 8-session or 16-session Short Psychodynamic Supportive Psychotherapy, both in combination with pharmacotherapy. Efficacy was 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. RESULTS: The rate of change would seem to indicate that eight sessions are preferable for both moderately and severely depressed patients, although the results converged again at the end. Furthermore, in terms of satisfaction with the number of sessions and drop-out percentages during treatment, no differences were found between the conditions. CONCLUSION: In the light of the outcome analysis (faster remission after fewer sessions), a short version of the psychotherapy treatment in a combined course of treatment seems to be justified.

Tibolone and 5alpha-dihydrotestosterone alone or in combination with an antiandrogen in a rat breast tumour model.

Tibolone was combined with the antiandrogen flutamide to determine whether the inhibition of tumour growth in the prophylactic 7,12-dimethylbenz(a)anthracene (DMBA) rat model could be attributed to androgenic properties of one of its metabolites. The mean tumour load after tibolone (0.25 or 1.0 mg/kg twice daily orally for 10 weeks) was 125 and 255 versus 718 mm2 for placebo. The mean number of tumours were 1.2 and 2.0 versus 5.8, respectively. Combined with flutamide (10 mg/kg twice daily orally) both doses of tibolone did not result in an increase compared to placebo, but in significantly lower tumour loads (160 and 64 versus 718 mm2, respectively) and smaller numbers of tumours (0.8 and 1.0 versus 5.8, respectively). The differences between tibolone monotherapy and the combination groups with flutamide were not statistically significant indicating that flutamide did not reverse tibolone's inhibition of tumour growth. The positive control, 5alpha-dihydrotestosterone (DHT), entirely suppressed tumour development and flutamide abolished the inhibitory effect of DHT. Thus, unlike DHT, tibolone does not exert its beneficial effect in DMBA-induced tumours via the androgen receptor, but acts via different mechanisms.

Combining psychotherapy and antidepressants in the treatment of depression.

OBJECTIVE: To compare the efficacy of antidepressants with that of antidepressants plus psychotherapy ("combined therapy") in the treatment of depression. METHODS: 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.