References
For children and adults, the references include abstracts
Background and rationale for the sequenced treatment alternatives to relieve
depression (STAR*D) study.
Fava M - Psychiatr Clin North Am - 01-JUN-2003; 26(2): 457-94, x
The range of treatment options available for patients with MDD has been outlined previously [12] . The
Agency for Health Care Policy and Research review and meta-analysis [6] [12] and many others [1] [2] [22]
reveal that about 50% of all nonpsychotic MDD outpatients initially exposed to either a time-limited
psychotherapy targeted for depression or a single antidepressant medication respond to treatment,
which means that the other half continue to be symptomatic and functionally impaired after this initial
treatment level.
Furthermore, of depressions that respond, only about 50% to 65% attain remission [23] (ie, they no
longer present residual symptoms of depression). In shorter randomized controlled trials of
medications lasting 6 to 8 weeks, symptomatic remissions occur in about 20% to 30% of all those
initially randomized to treatment; 20% to 30% respond (ie, have a 50% reduction in total symptoms)
but without remission (ie, their Hamilton Rating Scale for Depression [17-item] [HAM-D17] [24] [25] score
is >7); 10% to 15% partially respond (ie, they have a ≥25% and <50% reduction in baseline symptom
severity); and 20% to 35% are nonresponders (ie, they have <25% reduction in total symptoms) [2] .
These numbers also seem to apply to time-limited depression-targeted psychotherapy [26] [27] .
It is unknown how to treat depressed patients for whom two or more treatment attempts have
been unsuccessful
A second major group of depressed persons with a substantial public health impact are those who
have not responded to multiple trials of medications and psychotherapy. These individuals may
account for 10% to 30% of the total population with MDD. Because of the chronicity and severity of
their illness, they may use 40% to 50% of treatment resources over prolonged time periods. These
individuals are also more likely to commit suicide and are more likely to suffer greater morbidity or
even mortality from their GMCs [28] [29] . These individuals also typically require high medication costs
(because they are often treated with polypharmacy), and in some instances multiple psychiatric
admissions. One of the aims of STAR*D is to focus on the treatment of these types of participants.
Cognitive therapy for depression.
Rupke SJ - Am Fam Physician - 1-JAN-2006; 73(1): 83-6Effectiveness
of Cognitive
Therapy
UNIPOLAR MAJOR DEPRESSION
Numerous studies and meta-analyses[8] [9] [10] [11] [12] [13] [14] [15] [16] demonstrate convincingly that cognitive
therapy or CBT effectively treats patients with unipolar major depression. Several studies [9] [10] [11] have
shown that cognitive therapy is superior to no treatment or to placebo. Two comprehensive metaanalyses[11] [13] showed that cognitive therapy is as effective as interpersonal or brief psychodynamic
therapy in managing depression. They also showed that cognitive therapy is as effective and possibly
more effective than pharmacotherapy in managing mild to moderate unipolar depression.[11] [13]
The National Institute of Mental Health Treatment of Depression Collaborative Research Program
compared the effectiveness of two forms of psychotherapy (i.e., interpersonal therapy and CBT) with
imipramine (Tofranil) or placebo in the treatment of 250 patients with major depressive disorder.[14]
The study[14] found no significant differences between the therapies; however, the two psychotherapies
were slightly less effective than imipramine but more effective than placebo. A meta-analysis[12] of four
studies, which included 169 patients with major depression, showed similar results for tricyclic
antidepressants and CBT. The evidence suggests that cognitive therapy is a valid alternative to
antidepressants for patients with mild to moderate depression and possibly for patients with more
severe depression. Figure 1 is an algorithm for determining if CBT is appropriate.
Figure 1. Algorithm for determining if CBT is appropriate for treating a patient with depression. (CBT = cognitive behavior
therapy; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th ed.)
COMBINATION THERAPY
Early studies[15] [16] on the effectiveness of combination cognitive and antidepressant therapy had
conflicting results. Later evidence suggests that this combination may be more effective than either
therapy alone for some patients. A meta-analysis[17] that included six studies and 595 patients showed
that patients with severe depression benefited from the combination of psychotherapy and
pharmacotherapy. However, only two trials studied CBT, and patients with less severe depression
gained little from the combination.[17] A more recent study[18] of 681 patients
with chronic major depression compared nefazodone (Serzone), CBT, and combination therapy.
Patients benefited significantly more from combined CBT and antidepressant therapy than from either
treatment alone (85 percent in the combined treatment group versus 55 percent for nefazodone alone
and 52 percent for CBT alone; P < .001, number needed to treat [NNT] = 3).[18]
MANAGING RELAPSE
In addition to effectively managing acute episodes of unipolar major depression, cognitive therapy also
can prevent relapse. One study[4] showed that cognitive therapy significantly reduced the risk of
relapse compared with discontinuation of medication. Cognitive therapy was similar to maintenance
medication in preventing relapse.[4] A meta-analysis[11] that included eight studies showed that 29.5
percent of patients treated with cognitive therapy relapsed, compared with 60 percent of those treated
with antidepressants. However, the studies were small (241 patients total), used tricyclic
antidepressants, and did not specify the duration of therapy. Although these studies may not be
conclusive for patients previously treated with antidepressants, cognitive therapy does seem to
decrease the risk of relapse.
MANAGING RESIDUAL SYMPTOMS
Several studies[19] [20] [21] have evaluated the effectiveness of cognitive therapy or CBT in patients who
have residual depressive symptoms following adequate antidepressant therapy—a group with high
rates of relapse and persistent symptoms. Two small studies[20] [21] of 40 patients with unipolar major
depression and residual symptoms following antidepressant therapy showed that patients treated with
CBT initially had fewer residual symptoms and fewer depressive episodes after six years compared
with those treated with clinical therapy.
A more recent, larger study[19] randomized 158 patients who did not respond to adequate
antidepressant therapy to receive cognitive therapy with clinical management or clinical management
alone. All patients continued pharmacotherapy, which is a common practice. Remission rates of
major depression increased, and relapse rates significantly decreased in patients treated with
cognitive therapy compared with those who were not (29 versus 47 percent, NNT = 6). [19] Cognitive
therapy seems to add to the effect of pharmacotherapy in patients with residual depression.
COGNITIVE THERAPY IN ADOLESCENTS
Although most studies have evaluated adult populations, few have evaluated the effect of CBT in
adolescents. A meta-analysis[22] of six studies with 191 patients showed that CBT was significantly
more effective than placebo or inactive interventions in managing adolescent depressive disorder (36
versus 62 percent, NNT = 4). Although these findings were demonstrated only in mild to moderate
depression, the results warrant further study.
American Journal of Psychiatry 163:210-216, February 2006
doi: 10.1176/appi.ajp.163.2.210
© 2006 American Psychiatric Association
Treatment-Resistant Bipolar Depression: A STEP-BD Equipoise Randomized
Effectiveness Trial of Antidepressant Augmentation With Lamotrigine, Inositol, or
Risperidone
Andrew A. Nierenberg, M.D., Michael J. Ostacher, M.D
All patients were in a current major depressive episode that was nonresponsive to a
combination of adequate doses of established mood stabilizers plus at least one
antidepressant. Patients were randomly assigned to open-label adjunctive
treatment with lamotrigine, inositol, or risperidone for up to 16 weeks. The primary
outcome measure was the rate of recovery, defined as no more than two symptoms
meeting DSM-IV threshold criteria for a mood episode and no significant symptoms
present for 8 weeks. RESULTS: No significant between-group differences were seen
when any pair of treatments were compared on the primary outcome measure.
However, the recovery rate with lamotrigine was 23.8%, whereas the recovery rates
with inositol and risperidone were 17.4% and 4.6%, respectively. Patients receiving
lamotrigine had lower depression ratings and Clinical Global Impression severity
scores as well as greater Global Assessment of Functioning scores compared with
those receiving inositol and risperidone. CONCLUSIONS: No differences were found
in primary pairwise comparison analyses of open-label augmentation with
lamotrigine, inositol, or risperidone. Post hoc secondary analyses suggest that
lamotrigine may be superior to inositol and risperidone in improving treatmentresistant bipolar depression.
American Journal of Psychiatry 163:232-239, February 2006
doi: 10.1176/appi.ajp.163.2.232
© 2006
OBJECTIVE: The authors examined the comparative risks of switches in mood
polarity into hypomania or mania during acute and continuation trials of adjunctive
antidepressant treatment of bipolar depression. METHOD: One hundred fifty-nine
patients with bipolar I disorder or bipolar II disorder participated in a total of 228
acute (10-week) randomized trials of bupropion, sertraline, or venlafaxine as an
adjunct to a mood stabilizer. Patients in 87 of these trials entered continuation
treatment for up to 1 year. Antidepressant response and the occurrence of
subthreshold brief hypomania (emergence of brief hypomania [at least 1 but <7
days] or recurrent brief hypomania) and threshold switches (emergence of fullduration hypomania [ 7 days] or mania) were blindly assessed by using clinicianrated daily reports of mood-associated dysfunction on the National Institute of
Mental Health Life Chart Method. RESULTS: Threshold switches into full-duration
hypomania and mania occurred in 11.4% and 7.9%, respectively, of the acute
treatment trials and in 21.8% and 14.9%, respectively, of the continuation trials.
The rate of threshold switches was higher in the 169 trials in patients with bipolar I
disorder (30.8%) than the 59 trials in patients with bipolar II disorder (18.6%). The
ratio of threshold switches to subthreshold brief hypomanias was higher in both the
acute (ratio=3.60) and continuation trials (ratio=3.75) of venlafaxine than in the
acute and continuation trials of bupropion (ratios=0.85 and 1.17, respectively) and
sertraline (ratios=1.67 and 1.66, respectively). In only 37 (16.2%) of the original 228
acute antidepressant trials, or in only 23.3% of the patients, was there a sustained
antidepressant response in the continuation phase in the absence of a threshold
switch. CONCLUSIONS: Adjunctive treatment with antidepressants in bipolar
depression was associated with substantial risks of threshold switches to fullduration hypomania or mania in both acute and long-term continuation treatment.
Of the three antidepressants included in the study, venlafaxine was associated with
the highest relative risk of such switching and bupropion with the lowest risk.
Bupropion-SR, Sertraline, or Venlafaxine-XR after
Failure of SSRIs for Depression
A. John Rush, M.D., Madhukar H. Trivedi, M.D., Stephen R. Wisniewski,
Ph.D., Jonathan W. Stewart, M.D., Andrew A. Nierenberg, M.D., Michael
E. Thase, M.D., Louise Ritz, M.B.A., Melanie M. Biggs, Ph.D., Diane
Warden, Ph.D., M.B.A., James F. Luther, M.A., Kathy Shores-Wilson,
Ph.D., George Niederehe, Ph.D., Maurizio Fava, M.D., for the STAR*D
Study Team
ABSTRACT
Background After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor
(SSRI), it is not known whether switching to one antidepressant is more effective than switching to
another.
Methods We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder
who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the
following drugs for up to 14 weeks: sustained-release bupropion (239 patients) at a maximal daily dose
of 400 mg, sertraline (238 patients) at a maximal daily dose of 200 mg, or extended-release
venlafaxine (250 patients) at a maximal daily dose of 375 mg. The study was conducted in 18 primary
and 23 psychiatric care settings. The primary outcome was symptom remission, defined by a total
score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of the
study. Scores on the Quick Inventory of Depressive Symptomatology — Self Report (QIDS-SR-16),
obtained at treatment visits, determined secondary outcomes, including remission (a score of 5 or less
at exit) and response (a reduction of 50 percent or more on baseline scores).
Results Remission rates as assessed by the HRSD-17 and the QIDS-SR-16, respectively, were 21.3
percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for
sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response
rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent
for extended-release venlafaxine. These treatments did not differ significantly with respect to
outcomes, tolerability, or adverse events.
Conclusions After unsuccessful treatment with an SSRI, approximately one in four patients had a
remission of symptoms after switching to another antidepressant. Any one of the medications in the
study provided a reasonable second-step choice for patients with depression
Volume 354:1243-1252
March 23, 2006
Number 12
Next
Medication Augmentation after the Failure of SSRIs
for Depression
Madhukar H. Trivedi, M.D., Maurizio Fava, M.D., Stephen R. Wisniewski,
Ph.D., Michael E. Thase, M.D., Frederick Quitkin, M.D., Diane Warden,
Ph.D., M.B.A., Louise Ritz, M.B.A., Andrew A. Nierenberg, M.D., Barry D.
Lebowitz, Ph.D., Melanie M. Biggs, Ph.D., James F. Luther, M.A., Kathy
Shores-Wilson, Ph.D., A. John Rush, M.D., for
the STAR*D Study Team
ABSTRACT
Background Although clinicians frequently add a second medication to an initial, ineffective
antidepressant drug, no randomized controlled trial has compared the efficacy of this approach.
Methods We randomly assigned 565 adult outpatients who had nonpsychotic major depressive
disorder without remission despite a mean of 11.9 weeks of citalopram therapy (mean final dose, 55
mg per day) to receive sustained-release bupropion (at a dose of up to 400 mg per day) as
augmentation and 286 to receive buspirone (at a dose of up to 60 mg per day) as augmentation. The
primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item
Hamilton Rating Scale for Depression (HRSD-17) at the end of this study; scores were obtained over
the telephone by raters blinded to treatment assignment. The 16-item Quick Inventory of Depressive
Symptomatology — Self-Report (QIDS-SR-16) was used to determine the secondary outcomes of
remission (defined as a score of less than 6 at the end of this study) and response (a reduction in
baseline scores of 50 percent or more).
Results The sustained-release bupropion group and the buspirone group had similar rates of HRSD17 remission (29.7 percent and 30.1 percent, respectively), QIDS-SR-16 remission (39.0 percent and
32.9 percent), and QIDS-SR-16 response (31.8 percent and 26.9 percent). Sustained-release
bupropion, however, was associated with a greater reduction (from baseline to the end of this study) in
QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1 percent, P<0.04), a lower QIDS-SR-16
score at the end of this study (8.0 vs. 9.1, P<0.02), and a lower dropout rate due to intolerance (12.5
percent vs. 20.6 percent, P<0.009).
Conclusions Augmentation of citalopram with either sustained-release bupropion or buspirone appears
to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have
certain advantages, including a greater reduction in the number and severity of symptoms and fewer
side effects and adverse events.
Am J Psychiatry. 2005 Jul;162(7):1351-60.
Related Articles, Links
A randomized, double-blind, placebo-controlled trial of
quetiapine in the treatment of bipolar I or II depression.
Calabrese JR, Keck PE Jr, Macfadden W, Minkwitz M, Ketter TA, Weisler
RH, Cutler AJ, McCoy R, Wilson E, Mullen J.
University Hospitals of Cleveland and Case University School of Medicine,
11400 Euclid Ave., Suite 200, Cleveland, OH 44106, USA.
joseph.calabrese@uhhs.com
OBJECTIVE: There is a major unmet need for effective options in the
treatment of bipolar depression. METHOD: Five hundred forty-two
outpatients with bipolar I (N=360) or II (N=182) disorder experiencing a
major depressive episode (DSM-IV) were randomly assigned to 8 weeks of
quetiapine (600 or 300 mg/day) or placebo. The primary efficacy measure
was mean change from baseline to week 8 in the Montgomery-Asberg
Depression Rating Scale total score. Additional efficacy assessments included
the Hamilton Depression Rating Scale, Clinical Global Impression of severity
and improvement, Hamilton Anxiety Rating Scale, Pittsburgh Sleep Quality
Index, and Quality of Life Enjoyment and Satisfaction Questionnaire.
RESULTS: Quetiapine at either dose demonstrated statistically significant
improvement in Montgomery-Asberg Depression Rating Scale total scores
compared with placebo from week 1 onward. The proportions of patients
meeting response criteria (> or =50% Montgomery-Asberg Depression Rating
Scale score improvement) at the final assessment in the groups taking 600
and 300 mg/day of quetiapine were 58.2% and 57.6%, respectively, versus
36.1% for placebo. The proportions of patients meeting remission criteria
(Montgomery-Asberg Depression Rating Scale < or =12) were 52.9% in the
groups taking 600 and 300 mg/day of quetiapine versus 28.4% for placebo.
Quetiapine at 600 and 300 mg/day significantly improved 9 of 10 and 8 of 10
Montgomery-Asberg Depression Rating Scale items, respectively, compared
to placebo, including the core symptoms of depression. Treatment-emergent
mania rates were low and similar for the quetiapine and placebo groups
(3.2% and 3.9%, respectively). CONCLUSIONS: Quetiapine monotherapy is
efficacious and well tolerated for the treatment of bipolar depression.
Symptom clusters as predictors of late response to antidepressant
treatment.
Trivedi MH - J Clin Psychiatry - 01-AUG-2005; 66(8): 1064-70
From NIH/NLM MEDLINE
NLM Citation ID:
16086624 (PubMed)
Full Source Title:
Journal of Clinical Psychiatry
Publication Type:
Clinical Trial; Journal Article; Multicenter Study
Language:
English
Author Affiliation:
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas 75390-9119,
USA. madhukar.trivedi@utsouthwestern.edu
Authors:
Trivedi MH; Morris DW; Grannemann BD; Mahadi S
Abstract:
OBJECTIVE: While there is some indication from studies in the acute phase of antidepressant
treatment that there are differences in the timing of improvement in symptoms, relatively little work has
explored the patterns of change for specific symptom clusters and the predictability of these changes
to signal eventual response during the acute phase of treatment. This article investigates the use of
clusters of symptoms on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) to define the
pattern of late response versus nonresponse to antidepressant medication. METHOD: Using principal
component analysis, the HAM-D-17 was divided into 4 symptom clusters (mood, sleep/psychic
anxiety, appetite, and somatic anxiety/weight). Data for 996 patients with major depressive disorder
(DSM-III-R criteria), who participated in a 12-week acute phase study with nefazodone, were
subjected to a post hoc analysis of changes in symptom cluster scores. Patients were divided into 3
groups: early responders (< 4 weeks), late responders (4-12 weeks), and nonresponders (> 12
weeks) as defined by < 50% reduction in HAM-D-17 scores from baseline. The late-responder and
nonresponder groups were subjected to the principal component analysis. Data were collected from
October 1992 to November 1994. RESULTS: There were significant differences in the pattern of
symptom change on the mood cluster (weeks 3-4) (p < .0001), the sleep/psychic anxiety cluster
(weeks 3-4) (p < .003), and the somatic anxiety/weight cluster (weeks 3-4) (p < .01) for the late
responders compared to the nonresponders. Using change scores, a discriminant function analysis
correctly assigned 127 of the 182 late responders and 85 of the 133 nonresponders, or 70% of the late
responders and 64% of the nonresponders, to their final response groups. CONCLUSION: Monitoring
changes in symptom clusters from the HAM-D-17 during this crucial early stage (first 4 weeks) can be
used to distinguish late responders (after week 4) from nonresponders. Successful identification of
nonresponders based on symptom cluster change in the first 4 weeks would facilitate a shortening of
an ineffective treatment trial and allow for necessary changes in treatment strategy, helping physicians
more closely follow treatment guidelines
Remission rates with 3 consecutive antidepressant trials: effectiveness
for depressed outpatients.
Quitkin FM - J Clin Psychiatry - 01-JUN-2005; 66(6): 670-6
From NIH/NLM MEDLINE
NLM Citation ID:
15960558 (PubMed)
Full Source Title:
Journal of Clinical Psychiatry
Publication Type:
Clinical Trial; Journal Article; Randomized Controlled Trial
Language:
English
Author Affiliation:
Department of Therapeutics, Columbia University College of Physicians and Surgeons, New York
State Psychiatric Institute, New York, USA.
Authors:
Quitkin FM; McGrath PJ; Stewart JW; Deliyannides D; Taylor BP; Davies CA; Klein DF
Abstract:
OBJECTIVE: This effectiveness study assessed remission rates in patients who had the opportunity to
receive up to 3 antidepressant trials if unresponsive. METHOD: One hundred seventy-one
consecutive outpatients entered 1 of 3 studies for the treatment of major depressive disorder (DSMIV criteria) from January 1999 through December 2001. This group primarily received fluoxetine as a
first treatment in trials lasting 6 to 12 weeks (a small number received gepirone). If unimproved,
patients received a second or third trial (primarily clinician's choice). A standard criterion to determine
remission-a score of 7 or less on the 17-item Hamilton Rating Scale for Depression-was used. In order
to contrast remission rates with first-generation antidepressants, patients' outcomes in a previously
published study that compared placebo, phenelzine, and imipramine were also examined (N = 420).
RESULTS: In an intent-to-treat analysis, 66% (113/171) of patients who were treated with secondgeneration antidepressants and 65% (275/420) of patients who were treated with first-generation
antidepressants eventually achieved remission. CONCLUSIONS: Remission rates in the effectiveness
study are approximately 20% higher than the rates usually cited, a result of our choice to examine
outcome following 3 treatment trials. This choice is dictated by good clinical practice. The usual
procedure when comparing treatment modalities is to assess outcome after a single anti-depressant
trial. The cumulative high remission rates suggest antidepressants are effective and should
encourage more patients to seek treatment and physicians to develop techniques to improve patient
adherence.
Chronic depression: medication (nefazodone) or psychotherapy (CBASP)
is effective when the other is not.
Schatzberg AF - Arch Gen Psychiatry - 01-MAY-2005; 62(5): 513-20
From NIH/NLM MEDLINE
NLM Citation ID:
15867104 (PubMed)
Full Source Title:
Archives of General Psychiatry
Publication Type:
Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial
Language:
English
Author Affiliation:
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford,
CA 94305-5717, USA. afschatz@stanford.edu
Authors:
Schatzberg AF; Rush AJ; Arnow BA; Banks PL; Blalock JA; Borian FE; Howland R; Klein DN; Kocsis
JH; Kornstein SG; Manber R; Markowitz JC; Miller I; Ninan PT; Rothbaum BO; Thase ME; Trivedi MH;
Keller MB
Abstract:
CONTEXT: Although various strategies are available to manage nonresponders to an initial treatment
for depression, no controlled trials address the utility of switching from an antidepressant medication
to psychotherapy or vice versa. OBJECTIVE: To compare the responses of chronically depressed
nonresponders to 12 weeks of treatment with either nefazodone or cognitive behavioral analysis
system of psychotherapy (CBASP) who were crossed over to the alternate treatment (nefazodone, n =
79; CBASP, n = 61). DESIGN: Crossover trial. SETTING: Twelve academic outpatient psychiatric
centers. PATIENTS: There were 140 outpatients with chronic major depressive disorder; 92 (65.7%)
were female, 126 (90.0%) were white, and the mean age was 43.1 years. Thirty participants dropped
out of the study prematurely, 22 in the nefazodone group and 8 in the CBASP group.
INTERVENTIONS: Treatment lasted 12 weeks. The dosage of nefazodone was 100 to 600 mg/d;
CBASP was provided twice weekly during weeks 1 through 4 and weekly thereafter. MAIN OUTCOME
MEASURES: The 24-item Hamilton Rating Scale for Depression, administered by raters blinded to
treatment, the Clinician Global Impressions-Severity scale, and the 30-item Inventory for Depressive
Symptomatology-Self-Report. RESULTS: Analysis of the intent-to-treat sample revealed that both the
switch from nefazodone to CBASP and the switch from from CBASP to nefazodone resulted in
clinically and statistically significant improvements in symptoms. Neither the rates of response nor the
rates of remission were significantly different when the groups of completers were compared.
However, the switch to CBASP following nefazodone therapy was associated with significantly less
attrition due to adverse events, which may explain the higher intent-to-treat response rate among
those crossed over to CBASP (57% vs 42%). CONCLUSIONS: Among chronically depressed
individuals, CBASP appears to be efficacious for nonresponders to nefazodone, and nefazodone
appears to be effective for CBASP nonresponders. A switch from an antidepressant medication to
psychotherapy or vice versa appears to be useful for nonresponders to the initial treatment.
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