Department of Psychiatry, University of Amsterdam, and Depression Research Group, Mentrum Institute for Mental Health, Amsterdam
Depression Research Group, Mentrum Institute for Mental Health, Amsterdam
Department of Clinical Psychology, Free University of Amsterdam, and Depression Research Group, Mentrum Institute for Mental Health, Amsterdam, The Netherlands
Correspondence: Dr J. Dekker, Mentrum GGZ Amsterdam, dep. Onderzoek en Ontwikkeling, PO Box 75848, 1070 AV Amsterdam, The Netherlands. Tel: +31 20 6352833; fax: +31 20 6352840; e-mail: jack.dekker{at}mentrum.nl
Declaration of interest Supported by an unrestricted educational grant from Wyeth Nederland.
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ABSTRACT |
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Aims To investigate whether combined therapy has advantages over psychotherapy alone.
Method A 6-month randomised clinical trial compared Short Psychodynamic Supportive Psychotherapy (n=106) with combined therapy (n=85) in ambulatory patients with mild or moderate major depressive disorder diagnosed using DSMIV criteria. Antidepressants were prescribed according to a protocol providing four successive steps in case of intolerance or inefficacy: venlafaxine, selective serotonin reuptake inhibitor, nortriptyline and nortriptyline plus lithium. Efficacy was assessed using the 17-item Hamilton Rating Scale for Depression, the Clinical Global Impression of Severity and of Improvement, and the depression sub-scale of the Symptom Checklist.
Results The advantages of combining antidepressants with psychotherapy were equivocal. Neither the treating clinicians nor the independent observers were able to ascertain them, but the patients experienced them clearly.
Conclusions The advantages of combining antidepressants with psychotherapy are equivocal.
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INTRODUCTION |
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METHOD |
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The flow of the patients through the first stages of the trial is shown in Fig. 1.
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The application of these criteria, other than the HRSD baseline scores, to 4035 newly registered out-patients selected 372 patients. Of these, 69 patients (18%) were excluded because of an HRSD baseline score lower than 12 points, and 70 (19%) because of a score higher than 24 points, leaving 233 patients who were asked to consent to randomisation. This means that, apart from other criteria, nearly a quarter of the patients presenting with a major depressive episode and an HRSD baseline score of at least 12 points were excluded because of the severity of their illness. The inclusion and exclusion criteria are the usual ones in clinical pharmacotherapy research. In regard to psychotherapy, no selection criterion was applied. Factors such as ego strength, introspection, psychological-mindedness or verbal abilities were not taken into account. After a complete description of the study to the patients, written informed consent was obtained. After randomisation, 17 patients refused the allocated intervention (see results).
Study design
This 6-month trial had a randomised, parallel group design. It was preceded
by a 2-week period in which the diagnosis was assessed by means of a
semi-structured interview (Huyser et
al, 1996), the inclusion and exclusion criteria were checked,
and the baseline assessments were made. This period was used, if necessary, as
a drug wash-out period (without placebo). A 6-month follow-up after the end of
the trial is intended.
All patients were treated by experienced psychodynamic psychotherapists or by residents who were supervised once a week. The psychotherapy provided was Short Psychodynamic Supportive Psychotherapy (SPSP), a draft of which is available in Dutch from the authors upon written request. It is based on the principles enunciated by, among others, Werman (1984), Strupp & Binder (1984), Rockland (1989) and de Jonghe et al (1994). It consists of up to 16 sessions delivered within a 6-month period. Termination of the therapy in fewer sessions, if there is agreement between patient and therapist, is allowed. All psychotherapy sessions in the trial were audiotaped. The therapists met weekly for an hour-long discussion of their tapes; F.deJ., a fully trained psychoanalyst who formulated the guidelines for SPSP, participated in most of these meetings, listening to several tapes for each of the psychotherapists, and was especially attentive to the adherence to the manual.
In the combined therapy condition the psychotherapy started within 2 weeks of the start of pharmacotherapy. All patients receiving combined therapy were given, in addition to SPSP, antidepressant medication prescribed according to the protocol set out in the Appendix. The intended medication period was 6 months. The protocol provides for four consecutive steps to allow for intolerance or inefficacy. The first step is the prescription of the serotoninnoradrenaline reuptake inhibitor venlafaxine. Depending on the patients response, this therapy continues at the same or an increased dosage, or the patient is switched to step 2, in which a selective serotonin reuptake inhibitor (SSRI) is substituted (for details, see Appendix). In the event of SSRI intolerance or inefficacy, the medication is changed to the tricyclic antidepressant nortriptyline in step 3, and if this too is inefficacious, lithium is added to step 4. The sequence in this protocol is arbitrary, but not unfounded. Venlafaxine is an efficacious and safe antidepressant with a relatively mild side-effect profile. In lower dosage it acts as an SSRI, at higher dosage it also acts as a noradrenaline reuptake inhibitor (Harvey et al, 2000). Nortriptyline is less safe and presents burdensome side-effects, but its efficacy is undisputed. Lithium addition is the best-studied addition procedure (for augmenting tricyclic antidepressant therapy). The psychiatrist makes eight follow-up appointments of 15 min each with the patient, the first four at 2-week intervals, the last four at monthly intervals. If considered necessary by the psychiatrist, e.g. when medication change is required, additional appointments are permitted. The task of the psychiatrist is to provide pharmacotherapy and clinical management. The latter consists of psycho-education, discussing the effects and side-effects of medication, motivating the patient to comply with the medication regimen, and providing practical and emotional support.
Outcome measures
Efficacy was defined by intra- and inter-group differences at several
assessment points. The principal outcome measure was the difference between
the assessments at baseline and those at week 24. The primary instrument was
the 17-item Hamilton Rating Scale for Depression (HRSD;
Hamilton, 1967), rated by
three independent observers, using a semi-structured interview
(de Jonghe, 1994;
Kupka et al, 1996).
The reliability of these raters assessments was established before the
study began and during the study they discussed their audiotaped assessments
monthly with one of the authors (F.deJ.). Although the patients and the
treating physicians were not masked to randomisation, the raters were not
informed about the treatment condition and were instructed to restrict
themselves to discussion of the HRSD items only. The magnitude of the
differences is expressed in effect sizes. Efficacy is also expressed in
success rates. Success (remission) is defined as an HRSD final score of 7
points or less.
The second instrument used was the Clinical Global Impression (CGI; Guy, 1976), both of severity (CGIS) and of improvement (CGII). Assessments were made by the treating clinicians. The third instrument was a self-rating scale: the Depression sub-scale of the Symptom Checklist 90 (SCLD; Arrindell & Ettema, 1986). Success according to these instruments was defined as a final score of 12 on the CGIS or CGII, and as an improvement of at least 1 standard deviation on the SCLD. In short, efficacy assessments were based on data drawn from three sources: the treating clinicians, the patients and independent observers. The assessments were made at weeks 4, 8, 12 and 24.
At each assessment 17 somatic complaints, whether or not related to therapy, were systematically inquired about and rated on a five-point scale (1, absent; 5, extreme). These complaints were nausea, headache, diarrhoea, constipation, dizziness, dry mouth, skin anomalies, eye problems, excessive sweating, drowsiness, shaking or trembling, loss of libido, fever, weight gain, weight loss, loss of appetite and other complaints. Scores 1 and 2 were subsequently converted to 0 (absent) and scores 3, 4 and 5 to 1 (present), before calculating a mean score for each treatment group.
Statistical analysis
Analysis of covariance (ANCOVA), including the initial measures as
covariants, and multivariate analyses of variance (MANOVA) were used to test
intra-group and inter-group differences. In addition, one-group prepost
effect sizes and comparative effect sizes (Cohens d;
Cohen, 1988) were calculated as
the standard difference between two means, using the pooled standard deviation
as denominator (Rosnow & Rosenthal,
1996). Pearson chi-squared calculations (two-sided, level of
significance P<0.05) were used to compare refusal rates, base
rates, withdrawal rates, success rates and somatic complaints; analysis of
variance was used to compare mean age, total number of somatic complaints and
psychotherapy sessions. Finally, using the HRSD remission rates and the
SCLD success rates, KaplanMeier survival estimates were
calculated, and the curves obtained were compared using the log-rank test to
take into account both the rate of remission and the time needed to achieve
remission.
Our main results were calculated in a per protocol sample, which consists of all patients who started with the treatment they were allotted to. Secondary results were calculated in an intention-to-treat sample, which consisted of all randomised patients. In both of these samples the last observation carried forward method was applied. Secondary results were also calculated in an observed-cases sample, which consisted of all patients who completed the treatment, and in this sample only the observed data were used.
Patients were considered to have withdrawn from pharmacotherapy if they stopped taking medication for any reason, or experienced no benefit after the four treatment steps in the protocol. Patients were considered to have withdrawn from psychotherapy if they stopped attending the sessions without the agreement of their therapist, but not if therapy was terminated before session 16 or before week 24 by mutual agreement. Patients randomised to the combined therapy condition could withdraw from both aspects of treatment.
At the start of the study, we expected a recovery rate difference of about 15%, with a success rate about 65% in the combined condition and 50% in the psychotherapy condition. Based on 0.75 power to detect a significant difference (P=0.05, one-sided), the intention was to involve about 200 participants in the study (100 in each condition).
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RESULTS |
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The characteristics of the 191 patients in the per protocol sample are
given in Table 1. Their mean
age was 35.5 years (s.d.=10.7). There was no significant difference between
the two treatment conditions, except that psychiatric treatment during the
current episode was more frequent in the psychotherapy group
(2=3.90, d.f.=1; P=0.048). The psychotherapy
withdrawal rates are shown in Table
2. Three-quarters of the patients in the psychotherapy condition
and 84% in the combined therapy condition terminated their psychotherapy with
the agreement of their therapist; this difference is not statistically
significant. These patients had a mean of 13 psychotherapy sessions in both
treatment conditions.
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Pharmacotherapy withdrawal rates are shown in Table 3. The rate was less than 10% after 8 weeks, but climbed to 35% at week 24.
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Table 4 presents the efficacy results, expressed in mean HRSD, CGI and SCL scores. Intra-group differences between baseline and week-24 assessments are statistically significant in both treatment conditions for both the per protocol and observed-cases samples. Inter-group differences at week 24 are statistically significant (ANCOVA) in the per protocol sample according to the CGII (P<0.05) and the SCLD (P<0.001). In the observed-cases sample, statistically significant inter-group differences at week 24 are shown by the HRSD (P<0.046) and the SCLD (P<0.001). In the intention-to-treat sample no difference between the two treatment groups was found at any point by any assessment method (according to the Bonferroni-adjusted P value).
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As we calculated P separately for each time point and outcome in this table, a Bonferroni correction seems prudent. With 15 assessments in each sample and a mean intercorrelation of about 0.4 between the assessments, a probability of about 0.01 is more accurate, in which case only the difference in SCLD scores in this table is relevant. This is also the case with the MANOVA analyses: only the SCLD score shows significant inter-group differences (F=4.32, d.f.=1; P=0.008). Table 5 presents the efficacy results in the per protocol sample, expressed in effect sizes.
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Table 6 presents the efficacy results, expressed in success rates. In the per protocol sample, the success rates at week 24 vary between 32% and 69% in the psychotherapy condition, and between 42% and 79% in the combined therapy condition. If CGI success is defined as a score of 1 or 2 on either the severity or the improvement scale, the success rates at week 24 rise to 73% for psychotherapy and to 81% for combined therapy. Statistically significant excess success rates at week 24 are shown by the SCLD in both samples (with P values close to the Bonferroni-adjusted value of 0.01), and in neither sample by the other scales.
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An overview of the main results is presented in Table 7. In the intention-to-treat sample no difference between the two treatment groups was found at any moment by any assessment method (according to the Bonferroni-adjusted P value). The KaplanMeier survival curves for the two treatment groups (of the per protocol sample) in terms of HRSD remission and SCLD success are shown in Figs 2 and 3.
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In analysis of the KaplanMeier survival estimates based on the HRSD, the mean time needed to achieve remission was 138 days in the psychotherapy group and 129 days in the combined therapy group. There is no significant difference between the two treatment groups in the distribution of time to remission (log rank=2.39, d.f.=1, P=0.122). In the estimates based on the SCLD the mean time needed to achieve success was 120 days in the psychotherapy group and 104 days in the combined therapy group. From week 4 on, the differences between the two treatment groups are significant (log rank=5.30, d.f.=1, P= 0.021). In both treatment groups, somatic complaints decreased between the baseline and end-point assessments. No statistically significant inter-group difference between the mean scores of somatic complaints was found at any assessment point. As far as individual items are concerned, 6 of the 17 complaints were significantly more frequent in one of the two treatment conditions: dry mouth and excessive sweating in combined therapy, and headache, nausea, trembling or shaking and other complaints in psychotherapy.
Follow-up data on this study sample are still being gathered.
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DISCUSSION |
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Study design
Our study addresses the pragmatic question of the differential clinical
utility of two fully realised treatment packages, both representative of
actual clinical practice. To preserve external validity, limits were set to
scientific rigour; there was no psychotherapy plus placebo condition, nor an
antidepressant plus sham psychotherapy condition. The treating clinician
emphasised to patients the importance of compliance, but there was no pill
count nor plasma level confirmation. Our study did not address questions about
therapeutic factors.
The randomisation in our study appears successful. However, there is one statistically significant difference between the treatment conditions, and it is one that possibly disadvantaged the psychotherapy arm: more patients in the psychotherapy condition (26%) than in the combined therapy condition (14%) had undergone a psychiatric treatment during the present episode, apparently to no avail, before entering the trial.
Acceptability
More patients (99%) agreed to receive psychotherapy than agreed to combined
therapy (84%). The fact that many depressed patients refused pharmacotherapy
comes as no surprise; it is a daily problem in clinical practice.
Feasibility
The feasibility of a 6-month course of psychotherapy is fair. That the mean
number of actual sessions was less than 16 was foreseen, and is explicable;
patients and therapists go on holiday, and sometimes they get influenza. More
importantly, it is not unusual for patient and therapist to agree that a
course of fewer than 16 sessions is enough. To nobodys surprise, 25% of
the patients in the psychotherapy condition broke off their therapy.
Interestingly, only 16% did so in the combined therapy group. The difference
is not statistically significant, but at least we can say that adding
pharmacotherapy to psychotherapy is not detrimental to the feasibility of the
latter.
The feasibility of 2 months of anti-depressant therapy, in our study combined with psychotherapy, is fair: after 8 weeks less than 10% of the patients had abandoned treatment. Long-term feasibility is poor; nevertheless, after 20 weeks less than 30% of patients had withdrawn from the study. This result is above expectation; in antidepressant research a drop-out rate up to 30% after 46 weeks of treatment is generally considered acceptable. Adding psychotherapy to pharmacotherapy seems to improve the feasibility of the latter treatment. On the other hand, after 24 weeks of treatment only 65% of the patients were still taking antidepressants. Again, this accords with general research findings: poor compliance is a major problem in any long-term medical treatment.
Efficacy
Statistically significant and clinically relevant improvements between the
baseline assessment and week 24 are shown on all instrument ratings in both
treatment groups. The magnitude of the improvement is illustrated by the one
group (prepost) effect sizes (see
Table 5). The effect sizes vary
but they are all large (defined as 0.8 or more by
Cohen, 1988). In this context,
the results of Lipsey & Wilson
(1993) are interesting: these
authors reported that the mean one-group (prepost) effect size of
psychological interventions is 0.76 (45 meta-analyses). Another indicator of
intra-group improvement is the success rates at week 24 (see
Table 6). In both conditions
they vary from moderate to large. These results corroborate the widely held
view that combined therapy is an efficacious treatment of depression, and
support the more controversial view that psychotherapy too (in this case SPSP)
is an effective treatment of depression.
Statistically significant inter-group differences appear as early as week 4. However, the relevance of these data is limited. In 4 weeks SPSP has not yet had a fair chance to show its efficacy. Nobody expects psychotherapy to provide rapid results. The main results (HRSD scores at week 24 in the per protocol sample) do not demonstrate statistically significant differences between the treatment groups (Table 7). This result is corroborated by the facts that the comparative HRSD effect size is small and that the survival analysis does not indicate any superiority of combined therapy over pharmacotherapy. In contradistinction to this, the SCLD scores do show, in both the per protocol sample and the completers sample, statistically significant and clinically relevant inter-group differences, all of which favour combined therapy over psychotherapy. The comparative SCLD effect size is 0.49, a value considered medium by Cohen (1988), and the survival analysis confirms the superiority of combined therapy. Thus, only the SCLD consistently provides evidence supporting the view that combined therapy is more efficacious than psychotherapy alone. In a previous study (de Jonghe et al, 2001), in which we investigated the advantages of combined therapy over pharmacotherapy alone, we similarly found that it was the SCLD, rather than the HRSD and the CGI, assessments that consistently demonstrated significant differences.
Different instruments combined with different definitions of success unsurprisingly result in different success rates. In addition, the emotional involvement of the observers differ: the HRSD scores determined by therapy-independent, assumedly more neutral raters, the CGI scores by probably more optimistic clinicians who were evaluating the treatment they provided, and the SCLD scores by patients evaluating their own depression. The one-group prepost effect sizes computed at week 24 in the total study group show that the clinicianCGI combination is considerably more optimistic than the patientSCLD or the observerHRSD combinations. The latter two seem to agree quite well. The optimism of the clinicianCGI combination is also reflected in the fact that, if CGI success is defined as a score of 1 or 2 on either the severity or the improvement scale, the success rates at week 24 are 73% in the psychotherapy group and 81% in the combined therapy group. However, when it comes to possible differences in efficacy between the treatment conditions, the comparative effect sizes at week 24 show that it is the patients who detect a clinically meaningful difference, not the clinicians or the independent raters. The last finding is the more noteworthy, considering that Hamilton (1967) intended the HRSD to be an instrument suitable for the assessment of pharmacotherapy, and hence deliberately selected items he believed sensitive to antidepressant therapy.
Side-effects
Combining antidepressant therapy with psychotherapy does not increase the
overall frequency of somatic complaints. Unsurprisingly, dry mouth and
excessive sweating were more frequent in the combined therapy group, but the
more frequent occurrence of headache, nausea, trembling or shaking and
other complaints in the psychotherapy group seems to be either a
spurious or a mysterious finding.
Other relevant research
The paucity of studies investigating the relative value of psychotherapy
and combined therapy in the treatment of depression is striking. We found only
seven studies, five of which were published more than 10 years ago, addressing
this issue in ambulatory psychiatric patients with major depressive disorder
and assessing individual psychotherapy proper. Results are not only scarce,
they are also conflicting. Three studies report the efficacy of combined
therapy to be superior to that of psychotherapy, whereas four do not find a
significant difference. In some respects our results seem to concur with those
of Keller et al
(2000), Blackburn et
al (1981) and Weissman
et al (1979), who
report a superior efficacy of combined therapy over psychotherapy. However,
our main results seem to concur with those of Thase et al
(1997), Hollon et al
(1993), Beck et al
(1985) and Murphy et
al (1981), who report an
equal efficacy of both forms of treatment. The main differences in design
between the eight studies make comparisons precarious. The patients in our
study sample were certainly less severely depressed than those studied by
Keller et al (2000),
all of whom had chronic depression compared with 85% of our patients.
Depression in our sample was probably less than in the more
severe subgroup and greater than in the less severe
subgroup studied by Thase et al
(1997), who found a
significant difference in efficacy in their former subgroup. Another
consideration is that the length of our study (24 weeks) was greater than that
of the seven other studies. In addition, it may be mentioned that we studied
both a per protocol and an observed-cases sample, that in our study the HRSD
scores were assessed by an independent observer, not by the treating
clinician, that we asked the opinion of the patient, and that we worked with
experienced psychotherapists or intensively supervised residents.
Concluding remarks
In summary, we investigated the possible advantages of combining
antidepressants with psychotherapy in ambulatory patients with mild to
moderate major depressive disorder. We found that psychotherapy is more
acceptable than combined therapy. The 6-month feasibility of psychotherapy was
fair, that of combined therapy was poor. None the less, both therapies were
efficacious in reducing the symptoms of depression. The advantages of
combining antidepressants with SPSP appeared equivocal. Neither the treating
clinicians nor the independent observers were able to ascertain them, but the
patients experienced them clearly.
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APPENDIX |
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Step 2
In case of venlafaxine intolerance or inefficacy, change the medication to
a selective serotonin reuptake inhibitor (SSRI). Preference is given to
fluoxetine or, as a second option, fluvoxamine. However, the choice can be
influenced by the patients preference or treatment history. The chosen
SSRI is prescribed according to a specific guideline, different but comparable
with that described in step 1 (further details available from the authors upon
request).
Step 3
In case of SSRI intolerance or inefficacy, the medication is switched to
nortriptyline, a tricyclic antidepressant, at a dosage of 50 mg per day. What
happens afterwards depends on the duration of the treatment and the reaction
of the patient (Table A2).
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Step 4
In case of nortriptyline inefficacy, lithium is added. Plasma
concentrations are maintained in the range 0.81.2 mmol/l.
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Clinical Implications and Limitations |
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LIMITATIONS
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REFERENCES |
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Arrindell, W. A. & Ettema, J. M. M. (1986) SCL90. Handleiding bif een Multidimensionele Psychopathologie-indicator. Lisse: Swet & Zeitlinger.
Beck, A. T., Hollon, S. D., Young, J. E., et al (1985) Treatment of depression with cognitive therapy and amitriptyline. Archives of General Psychiatry, 42, 142 -148.[Abstract]
Blackburn, I. M., Bishop, S., Glen, A. I. M., et al (1981) The efficacy of cognitive therapy in depression: a treatment trial using cognitive therapy and pharmacotherapy, each alone and in combination. British Journal of Psychiatry, 139, 181 -189.[Abstract]
Cohen, J. (1988) Statistical Power Analysis for the Behavioural Sciences (2nd edn). Hillsdale, NJ: Lawrence Erlbaum.
de Jonghe, F. (1994) Leidraad voor het scoren van de Hamilton Depression Rating Scale. Amsterdam: Benecke Consultants.
de Jonghe, F., Rijnierse, P. & Janssen, R. (1994) Psychoanalytic supportive psychotherapy. Journal of the American Psychoanalytic Association, 42, 421 -446.[Medline]
de Jonghe, F., Kool, S., Aalst, G., et al (2001) Combining psychotherapy and antidepressants in the treatment of depression. Journal of Affective Disorders, 64, 217 -229.[CrossRef][Medline]
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology. Revised DHEW Pub. (ADM). Rockville, MD: National Institute for Mental Health.
Hamilton, M. (1967) Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology, 6, 278 -296.
Harvey, A. T., Rudolph, R. L. & Preskorn, S. H.
(2000) Evidence of the dual mechanisms of action of
venlafaxine. Archives of General Psychiatry,
57, 503
-509.
Hollon, S. D., Shelton, R. C. & Davis, D. D. (1993) Cognitive therapy of depression: conceptual issues and clinical efficacy. Journal of Consulting and Clinical Psychology, 61, 270 -275.[CrossRef][Medline]
Huyser, J., Jonghe, F. de, Jonkers, F., et al (1996) The Manual for the Diagnosis of Major Depression (MDMD): description and reliability. International Journal of Methods in Psychiatric Research, 6, 1 -4.[CrossRef]
Keller, M. B., McCullough, J. P., Klein, D. N., et al
(2000) A comparison of nefazodone, the cognitive
behavioral-analysis system of psychotherapy and their combination for the
treatment of chronic depression. New England Journal of
Medicine, 342, 1462
-1470.
Kool, S., Dekker, J., Duijsens, I. J., et al (2003) Changes in personality pathology after pharmacotherapy and combined therapy for depressed patients. Journal of Personality Disorders, 17, 60 -72.[CrossRef][Medline]
Kupka, R. W., de Jonghe, F., Koeter, M., et al (1996) Betrouwbaarheid van een semi-gestructureerd interview voor de Hamilton-depressieschaal. Tijdschrift voor Psychiatrie, 38, 759 -765.
Lipsey, M. W. & Wilson, D. B. (1993) The efficacy of psychological, education, and behavioral treatment: confirmation from meta-analysis. American Psychologist, 48, 1181 -1209.[CrossRef][Medline]
Murphy, G. E., Simons, A. D., Wetzel, R. D., et al (1981) Cognitive therapy and pharmacotherapy, singly and together in the treatment of depression. Archives of General Psychiatry, 41, 33 -41.
Rockland, L. H. (1989) Supportive Therapy. A Psychodynamic Approach. New York: Basic Books.
Rosnow, R. L. & Rosenthal, R. (1996) Computing contrasts, effect sizes, and counternulls on other peoples published data: general procedures for research consumers. Psychological Methods, 1, 331-340.[CrossRef]
Strupp, H. H. & Binder, J. L. (1984) Psychotherapy in a New Key. A Guide to Time-limited Dynamic Psychotherapy. New York: Basic Books.
Thase, M. E., Greenhouse, J. B., Frank, E., et al (1997) Treatment of major depression with psychotherapy or psychotherapypharmacotherapy combinations. Archives of General Psychiatry, 54, 1009 -1015.[Abstract]
Weissman, M. M., Prushoff, B. A., Dimascio, A., et al (1979) The efficacy of drugs and psychotherapy in the treatment of acute depressive episodes. American Journal of Psychiatry, 136, 555 -558.[Medline]
Werman, D. S. (1984) The Practice of Supportive Psychotherapy. New York: Brunner/Mazel.
Received for publication July 17, 2003. Revision received November 14, 2003. Accepted for publication January 24, 2004.
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