Great(er) Expectations

Although the successful treatment of schizophrenia is most often measured by symptom reduction and relapse prevention, the quality of everyday life and the ability to function independently are equally important to patients and families. To date, antipsychotic medications have not yet been shown to directly impact quality of life, particularly social and vocational functioning, to the degree hoped. Clinicians are challenged to prescribe medications that not only reduce symptoms but somehow also enable patients to become better functioning members of society. Presumably, as positive and negative symptoms of schizophrenia subside, subjective quality of life and objective measures of psychosocial functioning might be expected to improve. In this issue, two interesting and somewhat complementary articles focus on quality of life and competitive work performance of patients with schizophrenia. Both examine the promises and the limits of our current means of improving psychosocial functioning in these patients.

In the first article, Marvin Swartz and colleagues expand on findings of NIMH’s Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, presenting results derived from Quality of Life Scale (1) ratings. The analysis concentrated on those patients who continued their assigned medications for at least 12 months (a third of the overall sample). The authors chose a 12-month time frame to allow adequate time for improvement while still having a reasonably large remaining group to analyze. Subsequent analyses showed similar results for the 6- and 18-month cohorts.

Contrary to predictions, researchers found no evidence to favor any of the second-generation antipsychotic medications with regard to improving Quality of Life Scale scores. As expected, patients’ baseline quality of life ratings showed impairment, especially in the vocational domain. After 12 months, only modest improvements were associated with any of the randomly assigned medications, with no differences found among any of the individual medications. The patients with lower baseline Quality of Life Scale scores reported the greatest gains (although remaining significantly impaired), whereas those with the highest baseline scores showed little to no improvement. The authors postulated a ceiling effect for the latter group. Unfortunately, those with lower Quality of Life Scale scores at baseline comprised less than a quarter of the subgroup that stayed on their assigned medication regimen at least 12 months. Thus, those who might have gained the most were least likely to continue long enough to reap these benefits.

The “buzz” about the CATIE results has been the rather disappointing continuation rates for all the studied antipsychotics (2 – 4) . Swartz et al. examined the characteristics of those patients who remained on their medication regimen for at least 12 months. They discovered an essential truth about schizophrenia: those who do better in a trial are usually better at the start. At baseline they scored lower on symptom rating scales, had more favorable attitudes toward medication, were less depressed, abused fewer illicit substances, and had higher initial psychosocial functioning scores. But another implication of this study is that when a wide range of patients with schizophrenia are enrolled in a clinical trial, different strategies may be required depending on how initial presentations and prognostic assessments vary. For patients with poorer prognostic profiles at baseline, for whom expectations of functional improvements might be lower at the start, immediate initiation of strategies to increase adherence and to aggressively treat substance abuse when indicated may be necessary (5, 6) .

The Swartz et al. study confirms that improving quality of life does not come prepackaged in a medication bottle. As these authors state, “More intensive psychosocial rehabilitative services, including cognitive rehabilitation, may be needed to affect more substantial gains in functioning….For patients unable to work, with limited access to vocational and rehabilitative services, even optimal medication may not be reasonably expected to improve…community functioning.”

This statement provides a perfect segue to the second paper, in which Susan McGurk and colleagues examine the effect of cognitive training on supported employment services at two community health centers in Brooklyn, N.Y., over 2–3 years. Both sites serve predominately disadvantaged, minority patients with low educational achievement. In this study a small number of patients with schizophrenia were randomly assigned to receive supported employment alone or supported employment with cognitive training with the goal of increasing competitive work. Competitive work, the gold standard of vocational functioning, means competing in the marketplace for real work and real wages. Rates of competitive employment for patients with schizophrenia range from 10%–20% (7, 8) . The cognitive training administered by trained cognitive specialists, the “Thinking Skills for Work Program,” consisted of an extensive analysis of the cognitive work difficulties, computer-based training, planning sessions, and ongoing on-the-job assistance. Both study sites were also rated on the fidelity of their adherence to the supported employment model utilizing a standardized scale (9) . The average follow-up period for patients was 2 years. The good news was that those in the combined program (supported employment with cognitive training) were more likely to work, held more jobs, worked for a longer time, and made more money. An additional benefit to those randomly assigned to the combined strategy was an improvement in depressive and autistic preoccupations as measured by the Positive and Negative Syndrome Scale (PANSS) at 3 months. In other words, those who worked more were less depressed and less internally isolated. The not-so-good news was that despite these noteworthy efforts, the mean number of weeks worked over the 2-year follow-up was only 27 weeks, roughly 6 months. Working for a quarter of the evaluation period (significantly better than the 5 weeks worked by those in the supported employment alone group) is laudable but still falls far short of independent self-sufficiency. One further note: although both study sites embraced the concepts of supported employment and cognitive training, one site scored lower on “fidelity” to the supported employment model. In turn, patients at that site performed worse than those at the more adherent site.

So what do these two studies together tell us about the psychosocial functioning of patients with schizophrenia? The Swartz et al. study coupled with the results of other CATIE publications demonstrate that medication adherence is challenging and that no one medication seems to be a clear winner when balancing all factors. But medication adherence is the stable platform that reduces exacerbations and rehospitalization (10) . And this stability is necessary before any sustained psychosocial treatment can be applied. Supported employment with cognitive training appears to be one good next step for stable patients. The McGurk et al. study shows that adding cognitive training significantly improved time at work and reduced depressive preoccupations and isolating thinking. However, as with medication treatment, functional gains were limited and clearly dependent on adherence to the treatment. Both of these studies highlight expectations and desires to increase independent living for our patients. Such “greater expectation” requires more holistic approaches to treating patients with schizophrenia, employing both pharmacological and psychosocial interventions in the service of increasing each patient’s quality of life and prognosis. These interventions deserve large-scale, comprehensive, and integrated research programs to determine the most effective treatment combinations.