STAR*D Depression Study Finds Cognitive Therapy Beneficial, Rarely Chosen

Marlene Busko

May 17, 2007

May 17, 2007 — Following failed initial therapy for depression with the selective serotonin reuptake inhibitor (SSRI) citalopram, cognitive therapy was selected by fewer patients but was as effective as second-step therapy with other medications, according to results from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

Two articles based on these findings are published in the May issue of the American Journal of Psychiatry.

Michael E. Thase, MD, from the University of Pittsburgh, in Pennsylvania, and the lead author of an article comparing the effectiveness of second-step treatments in STAR*D, told Medscape that this study highlighted 2 main outcomes. Among patients who accepted switching from citalopram to other medications or to cognitive therapy, outcomes were equally effective, and cognitive therapy had the advantage of lower adverse-effect burden. Among patients who accepted augmentation treatment with medication or cognitive therapy, medication produced more rapid effectiveness and was almost as well tolerated as cognitive therapy.

Stephen R. Wisniewski, PhD, also at the University of Pittsburgh, and the lead author of the article about patient preference in second-step treatments in STAR*D, commented to Medscape that patients who chose to switch had experienced adverse events or lack of improvement in symptom severity with the initial therapy. Patients who chose to augment their initial therapy had responded to therapy, but their depression had not remitted completely. Socioeconomic factors (such as education) rather than factors such as response or adverse effects with initial treatment played a role in patients' willingness to choose cognitive therapy as their second-step treatment.

STAR*D Rationale

Dr. Thase and colleagues write that less than 50% of patients with major depressive disorder experience remission during an initial course of antidepressant therapy. STAR*D was designed to find the best subsequent treatment for patients who did not adequately benefit from first-step treatment. Dr. Thase explained to Medscape that "depression-focused psychotherapies, of which cognitive therapy is the most widely studied, are effective alternatives to medication, and we wanted to compare the relative merits of psychotherapy instead of a different medication."

STAR*D, which is designed with 4 treatment levels (for patients who do not become symptom-free at earlier levels), enrolled 4041 adult outpatients with major depressive disorders.

The first treatment step, level 1, consisted of 12 to 14 weeks of citalopram. With input from their physicians, the approximately two thirds of patients who did not achieve remission with level-1 therapy could agree to be randomized to level-2 augmentation or switch strategies, with or without cognitive therapy.

The level-2 treatments and the number of patients randomized to them were:

  • Three augmentation strategies: adding the norepinephrine-dopamine reuptake inhibitor bupropion (n = 56), buspirone (n = 61), or cognitive therapy (n = 65) to ongoing citalopram.

  • Four switch strategies: discontinuing citalopram and starting therapy with the SSRI sertraline (n = 27), bupropion (n = 28), or the serotonin-norepinephrine reuptake inhibitor venlafaxine (n = 31), or cognitive therapy (n = 36).

Remission rates among STAR*D level-2 participants who switched to other medications ranged from 18% to 25%, and remission rates for those who augmented medications were 30%, according to 2 previously published reports.

Effectiveness of Second-Step Strategies

Thase et al found that cognitive therapy, both alone (switch) and in combination with citalopram (augmentation), was generally as effective as the various second-step pharmacologic strategies studied in STAR*D.

Percentage of Patients who Remitted,* Cognitive Therapy vs Medication
Type of Level-2 Treatment
Cognitive Therapy
*Met remission criteria on Hamilton Rating Scale of Depression.

The authors note, however, that remission occurred a median of 20 days faster with medication augmentation than with cognitive-therapy augmentation, which could be important when speedy response is imperative.

Dr. Thase commented to Medscape that the clinical implications are that psychotherapies can be considered as part of a "menu" of treatment options for patients who do not improve with initial medication, since switching to psychotherapy seemed to be as effective as switching to medication and had the advantage of having fewer adverse effects. Medication augmentation provided a faster response and was reasonably well tolerated. He added, "It would be important in future studies to see whether there are ways in which we can facilitate the delivery of cognitive therapy to improve convenience and cost."

The group writes that "less than one third of patients remitted with any of the level-2 treatments in STAR*D, which indicates that there is room for improvement in the treatment of depression." They add that since only one fourth of patients treated with cognitive therapy completed the full 16-session protocol, future research should examine alternative delivery methods and ways to improve therapy mastery in fewer sessions.

Patient Preference

Dr. Wisniewski commented that they found that the "switchers" were people who had no change in symptom severity or had adverse effects and the "augmenters" were people who responded but did not achieve remission with initial therapy. Of the 1439 participants who entered second-step treatment, only 1% were willing to accept all treatment strategies. In addition, the 29% overall acceptance of cognitive therapy was lower than what the group had anticipated, based on their earlier research findings. Dr. Wisniewski suggested that this study's design, which excluded people who wanted cognitive therapy right away, might have played a role in these low cognitive-therapy acceptance rates.

Willingness to Accept Different Level-2 Treatment Strategies in STAR*D
Acceptable Treatment
STAR*D Level-2 Participants (%)
All 7 treatment options
Cognitive therapy only
Cognitive therapy as part of a switch and/or augmentation strategy

Participants who were more likely to accept cognitive therapy had more education or a family history of depression or bipolar disorder or had spent a greater amount of time taking level-1 treatment.

"If 1 Way Doesn't Work, Try Another Way" to Treat Depression

Myrna M. Weissman, PhD, from the New York State Psychiatric Institute, in New York, who wrote an accompanying editorial, commented: "We can't take a message away from these studies that people don't want cognitive therapy: they weren't offered it [as an initial therapy]." She added that it also may have been less convenient for people to obtain cognitive therapy, and some patients might have been reluctant to break existing relationships with their medication-treating physicians.

"I think that the big take-home message is that there are many different ways of treating depression," she said, adding, "If 1 doesn't work, try another and don't give up." She added that most depressed patients may need trials of different medications and/or psychotherapy to achieve remission, and clinicians need to give each treatment enough time to work, monitor the patient, and pay attention to the patient's preferences.

The STAR*D study was funded by the National Institute of Mental Health. Medications were provided at no cost by Bristol-Myers Squibb, Forest Pharmaceuticals, GlaxoSmithKline, King Pharmaceuticals, Organon, Pfizer, and Wyeth Pharmaceuticals.

Dr. Thase has served in an advisory or consulting capacity to or received speaker's honoraria from AstraZeneca, Bristol-Myers Squibb, Cephalon, Cyberonics, Eli Lily, GlaxoSmithKline, Janssen Pharmaceutica, MedAvante, Neuronetics, Novartis, Organon, Sanofi-Aventis, Sepracor, Shire US, and Wyeth Pharmaceuticals and has equity holdings in MedAvante.

Dr. Wisniewski has provided consultation to Bristol-Myers Squibb, Cyberonics, and ImaRx Therapeutics and has received research support from the National Institute of Mental Health.

The financial disclosures of the other authors are listed in the articles.

Am J Psychiatry . 2007;164:739-752 , 753-760 , and 693-696.


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