Intensive-Treatment Gains Lost by Five-Year Follow-Up

A two-year, intensive, community-based intervention targeting people with first-episode schizophrenia improved clinical outcome when compared with standard treatment, but the effects were not sustainable at follow-up five years after the start of the intervention.

Statistically significant differences were seen on positive and negative symptom scales at one- and two-year follow-up between patients receiving the intensive intervention and those receiving standard care. But those differences disappeared when the patients were reassessed at five years, according to a report in the July Archives of General Psychiatry.

Substance abuse also was decreased significantly in the intervention group at two years, but that difference also was not sustained at five years.

Improvements were sustained at five years on measures of use of supportive housing and hospitalization days. Study author Mette Bertelsen, M.Sc., told Psychiatric News that the capacity to live independently, a proxy for social functioning, is critical, so improvements on those two measures demonstrate the longer-term efficacy of intensive intervention during the first psychotic episode.

She stressed, however, that the failure of patients with psychotic symptoms to sustain improvement indicates that “[t]wo years of this intensive treatment is too short a period, at least for most of the patients,” she told Psychiatric News.

Bertelsen is a member of the Department of Psychiatry at Bispebjerg Hospital and Copenhagen University Faculty of Health Science in Denmark.

In the study, 547 first-episode patients were randomized to either assertive community-based intervention or to standard treatment beginning in January 1998. After two years, all patients were transitioned into standard treatment.

Patients were assessed at baseline, at two-year follow-up, and at five years after randomization (three years after transitioning to standard treatment). Information on the following topics was collected: main diagnosis and substance abuse; symptoms according to the Scale for Assessment of Psychotic Symptoms and Scale for Assessment of Negative Symptoms; sociodemographic factors; global assessment of functioning and symptoms; duration of untreated psychosis; and suicidal behavior, measured by self-reporting of suicide attempts and suicidal ideation.

There was considerable attrition from the study; 369 patients were followed at two years, and 301 patients followed at five years. (To account for the attrition, investigators used “intention to treat” analysis—a statistical method that assumes the outcome data missing at follow-up are randomly distributed, and so analyzes individual outcomes according to the group to which subjects were randomized.)

The intensive early-intervention program consisted of three core elements: family treatment, social skills training, and assertive community treatment (ACT) ACT is the team-treatment approach developed in the 1960s by Leonard Stein, M.D., and Mary Ann Test, Ph.D., designed to provide comprehensive, community-based psychiatric treatment, rehabilitation, and support for serious mental illness.

Standard treatment consisted of offering the patient treatment at a community mental health center. Each patient was in contact with a physician, a community mental health nurse, and, in some cases, a social worker. Home visits were possible, but office visits were the general rule.

The success at two years in diminishing psychotic symptoms underscores a trend in schizophrenia research focusing on rapid and aggressive treatment of the first episode of psychosis. But the failure to sustain improvements over time would appear—on the surface—to run counter to findings about the efficacy of early intervention, particularly findings by psychiatrist Thomas McGlashan, M.D.

McGlashan's Treatment and Intervention in Psychosis Study (TIPS) in Norway has shown that early intervention that significantly diminishes the duration of psychosis has beneficial effects for patients over the long-term course of schizophrenia. Most recently, for instance, he and colleagues showed that reducing the duration of untreated acute psychosis in first-episode patients prevents the worsening of negative symptoms—such as cognitive deficits and lack of volition—at two-year follow-up (Psychiatric News, July 4).

But both McGlashan and Bertelsen emphasized that there are crucial differences in study design between TIPS and the Bertelsen study.

“TIPS compares the outcome of first-episode psychosis where the same treatment package is applied to two separate populations of first-episode patients, one population that is detected and treated earlier in the course of their first psychosis than the other,” McGlashan told Psychiatric News. “It tests the effect of timing of the same treatment. [The Bertelsen study] compares the outcome where different treatment packages are applied to two separate populations of first-episode patients with no difference in the timing of the treatments. It tests the effect of different treatments applied at the same time in the course of the disorder, not the effect of the same treatment applied at different times in the course of the disorder.”

Bertelsen echoed those remarks. “Our study was not as such designed specifically to shortening the duration of psychosis, and the effort to do so was not carried out systematically as in the TIPS project,” she said.

She added that there was no significant difference between duration of psychosis at baseline between the two groups (46 weeks as a median for the intervention group versus 53 weeks for the standard group).

“Bearing in mind the TIPS project, naturally it would be even more beneficial if educational campaigns in the community were being established in order to get people in treatment as soon as possible,” Bertelsen continued. She added that 46 and 53 weeks of untreated psychosis is “a very long time, especially when the TIPS project has proven that it is possible to bring it down to approximately eight weeks.”

She added, “I think it is important to stress that psychosis is a serious illness, and it matters to start treating quickly and intensively in the early phases. The nature of psychosis and schizophrenia calls for patience—and two years is simply not enough.” ▪