Combination Therapy Best for Chronic Depression

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For patients with a single episode of mild to moderate major depression, treatment with medication seems to be about as effective as treatment with psychotherapy. In patients with severe episodes, medication is usually recommended. But in patients with chronic depression, the best treatment hasn’t been established, partly because up to one-third of these patients don’t respond well to either treatment.

Now a new study shows that combining medication and psychotherapy for patients with chronic major depression may produce significantly better results than using either of the treatments alone. Furthermore, the study reports a much higher response rate than is usually seen in non-chronic depression.

In a study of more than 500 patients who’d been continuously depressed for at least two years, those who received both treatments for 12 weeks had an overall response rate of 85 percent compared to just over 50 percent for each of the single-treatment groups. Response was defined as either “remission” — achieving a normal score on a commonly used depression measure — or “satisfactory” — reducing one’s score by at least half.

“This is the first time that combination therapy has been proven to be so much more effective than either medication or psychotherapy alone,” stated lead investigator Dr. Martin B. Keller from Brown University in Providence, Rhode Island. “For some of the study patients who underwent combination therapy, it was the first time in more than 20 years that they could sustain pleasure and function fully at work and with family and friends”.

The patients were randomly assigned to receive one of three regimens: the antidepressant nefazodone (Serzone), a form of cognitive-behavior therapy specially designed for patients with chronic depression, or both treatments. Those taking the drug were started at 100 mg twice a day, with the dose increased gradually to between 300 and 620 mg daily. Patients receiving psychotherapy began with two sessions a week, switching to one session a week after four weeks.

The researchers explain that in the specific psychotherapy used, called the “cognitive behavioral-analysis system of psychotherapy,” or CBASP, “patients learn how their cognitive and behavioral patterns produce and perpetuate their interpersonal problems and learn how to remedy maladaptive patterns of interpersonal behavior”. This approach has met with success in some smaller studies, and is based on the well-established system of cognitive therapy.

The researchers, located at 12 centers around the United States, also looked at response rates for all the patients who actually started the study, regardless of whether they completed it. This is important because people who drop out may do so because the treatment isn’t working or because they can’t tolerate its side effects. About one-quarter of each treatment group dropped out. Among those taking nefazodone alone, 14 percent dropped out because of side effects, compared to seven percent of those getting combination therapy. Only about one percent of each group said they quit because their treatment wasn’t effective.

Among these larger groups, combination therapy still produced significantly greater improvements. Just under half of each of the single-treatment groups responded to treatment compared to almost three-quarters of those getting both treatments.

“These findings on the dual treatment approach for the treatment of chronic depression are incredibly exciting,” stated Dr. Madhukar Trivedi of the University of Texas Southwestern Medical Center in Dallas. “The large difference in response rates after only three months of treatment is truly astonishing.”

Despite their enthusiasm, however, the researchers do point out that their findings can’t be generalized to all patients with chronic depression. Writing in the May 18th issue of The New England Journal of Medicine, they note that their study has limitations. The most important of these, writes Dr. Jan Scott of Gartnavel Hospital in Glasgow, Scotland, is the narrow range of patients allowed into the study. In an editorial in the same issue, Dr. Scott points out that because the study excluded patients who had a history of other psychiatric conditions, these results may be of limited help to physicians.

The conditions that were excluded include schizophrenia, psychosis, bipolar disorder, obsessive-compulsive disorder, panic and anxiety disorders, post-traumatic stress syndrome, certain kinds of personality disorders and substance abuse. All of these conditions frequently occur along with depression. But for a study’s results to be clear, patients with more than just depression are usually excluded.

“Concentrating on short-term outcomes creates a snapshot of depression and its treatment that is not easy to reconcile with the realities of clinical practice,” notes Dr. Scott, citing another reason that more research will be needed. For example, long-term follow-up might reveal that the single-treatment groups eventually “catch up” to the combination group. If so, researchers would need to figure out who would benefit most from the early effectiveness of dual treatment.

Overall, however, both Scott and the original researchers agree that these findings are very promising. Both groups call for more research to verify and expand these results to make them as useful as possible for practicing physicians.

Editorial Commentary: Chronic depression is generally considered more difficult to treat than shorter duration depressions. While though an 85 percent response rate is considered excellent for even mild or moderate depressions. Therefore, there is great interest in seeing if this response is sustained, and if so, what about the study explains its high rate of success –the type of psychotherapy, the drug, or the way the study was conducted.