Environmental supports targeted at global functional outcome improved global community functioning in individuals with schizophrenia. Environmental supports targeted at medication adherence alone improved adherence to antipsychotic medications in schizophrenia as assessed by unannounced, in-home pill counts. Data support that individually tailored environmental supports improve targeted behaviors.
This is the first randomized trial to demonstrate that the systematic application of individually tailored environmental supports in CAT and Pharm-CAT improve adherence to oral antipsychotic medication in individuals with schizophrenia. Adherence was significantly higher in CAT and Pharm-CAT as compared with TAU during treatment and 6 months after home visits were withdrawn. The average level of medication adherence in CAT and Pharm-CAT across a 15-month period remained close to 80%. CAT/Pharm-CAT treatment and perhaps the continued use of these previously provided supports after the withdrawal of home visits can sustain an important behavior change that has major public health implications.11
It is important to note that supports improved adherence to medication whether or not they were embedded in the context of a CAT program that targeted multiple additional areas of functional outcome. Maintenance of medication adherence gains in CAT and Pharm-CAT may result from the formation of habit behavior with the repeated use of environmental cues.
Adherence data obtained from unannounced, in-home pill counts suggested more robust treatment effects than data obtained from pharmacy records. Differences may reflect that filling a prescription only ensures that medication is available to be taken. Larger samples may be needed when using pharmacy refill data to examine the efficacy of interventions. This study provides important support for the feasibility of conducting in-home pill counts and their sensitivity to change with targeted behavioral interventions.
While there were not significant differences in positive symptoms across treatment groups, rates of relapse utilizing a composite measure as suggested by Schooler et al35
were significantly lower with CAT and Pharm-CAT treatment compared with TAU. This finding corresponds to published data indicating that poor adherence is a significant predictor of relapse.11
Moreover, medication adherence has been characterized as a foundation upon which the rehabilitation and recovery process is built.41
CAT improved functional outcome as compared with TAU and to Pharm-CAT. This finding replicates what was found in our previous trials. The number needed to treat to improve functional outcome compared with TAU was 1.4 during treatment. This is important in that CAT is a fairly labor intensive treatment. A low NNT indicates that the intensity of treatment may be justified by clinically important outcomes. Surprisingly, statistically significant improvement in functioning was noted for Pharm-CAT over TAU. While Full-CAT treatment made a far more robust and longer standing impact upon functional outcome, it is possible that better medication adherence in the Pharm-CAT group may have been a platform which allowed minimal functional improvement to occur even in the absence of a comprehensive rehabilitation program. However, results clearly indicate that the Full-CAT program has significant benefits for functional outcomes over a program targeting only medication adherence. It is important to determine whether limiting the goals of treatment to improving medication adherence and preventing relapse is enough. More individuals in the Pharm-CAT group began to drop during the last part of treatment. It may be that to keep individuals involved in intensive treatment, functional goals important to the individual need to be targeted. Medication in Full-CAT treatment can be seen as a means to help the individual achieve a broader range of goals. Moreover, when an individual is resistant to working on medication adherence, working on other issues can keep them engaged in treatment so that adherence can be approached again at a later point. Such individuals are likely to drop out of a treatment targeting adherence only. Because home visits can be labor intensive, it may make more sense to get more out of each visit by targeting the broad range of adaptive behaviors. This approach is likely to produce the best results with little additional financial burden.
Functional gains in CAT were sustained throughout the first 3 months after the withdrawal of home visits but the CAT group was no longer significantly better than TAU or Pharm-CAT by the 6-month follow-up. Environmental supports for complex functional behaviors may need more individual tailoring, adjustment, and reinforcement in a changing environmental context than a relatively circumscribed behavior such as adherence. It is a common practice to examine whether behavioral improvements with psychosocial treatments are maintained when the treatment is withdrawn. This is not a standard applied to medication treatments, and is likely most applicable to psychosocial treatments that focus on systematic teaching of skills which are anticipated to be sustained after treatment is withdrawn. For a treatment such as CAT which is expected to bypass cognitive problems rather than restore cognitive functioning, it is unclear whether treatment should be withdrawn. It may make more sense after an initial treatment period to decrease the frequency of visits in an attempt to maintain gains while controlling the costs of treatment, or to train family members or other caregivers to establish and alter environmental supports. Future research on sustaining treatment gains and comparing the costs and benefits of CAT with skills training programs would be important to pursue.
Contrary to the results of previous studies, mean levels of psychosis did not significantly improve in the CAT and Pharm-CAT groups in comparison to those in TAU. These findings may suggest that in effect, taking medication as prescribed prevented relapse but did not result in a statistically significant reduction in symptoms. There are several possible interpretations of this finding.
Symptoms of psychosis were mild on average at baseline. Further improvement may have been difficult to demonstrate with this starting point. It could also be true that lack of accurate information on adherence available to treating psychiatrists may make it difficult for them to optimize medication regimens to produce the best outcomes in terms of symptomatology. In a recent study, we found that among partially adherent outpatients with schizophrenia, adherence as measured with Medication Event Monitoring (MEMS; caps that record day and time opened) was not correlated with either symptoms or symptom improvement over a 12-week period.42
These findings raise interesting questions. What is the right amount of medication for an individual patient? How can the right dose be determined in the context of limited or no information about the patient's adherence? How adherent is adherent and over what time period? Future studies that feed adherence data back to providers in an effort to optimize dose may be needed.
It is important to note that symptom scores did not worsen in CAT even though patients were more involved in social and role functioning. Increased social and role demands may increase stress. Stress in turn can worsen symptoms. Better functional status in the context of stable psychotic symptoms translates to a positive outcome for CAT patients.
Pharm-CAT is a new treatment that improves adherence to medication and reduces rates of relapse. Pharm-CAT and CAT add to the growing number of interventions targeting this problem for individuals with schizophrenia. Clinical experience suggests that Pharm-CAT is likely to be best suited for individuals who are willing to take medication but who may miss doses due to distraction, memory problems, poor planning and problem solving, chaotic environments, and negative symptoms. For individuals with more ambivalence toward medication, CAT treatment may be able to help them to connect medication adherence to improvements in functional outcomes. For individuals refusing medications altogether, interventions such as cognitive behavior therapy,43
or compliance therapy45
may be important precursors to Pharm-CAT. Willingness to take medication may be a necessary but not sufficient condition to improve actual adherence to medication. Combining treatments focusing on changing attitudes and insight with the use of environmental supports to change behavior may lead to improved adherence outcomes for a broader range of individuals.
These results must be examined within the context of the study's methodological limitations. A significant number of inpatient recruits did not make it to the point of randomization into treatment for this outpatient treatment study. Results can only apply to those individuals treated as outpatients or inpatients who have successfully negotiated the transition from inpatient to outpatient status. Participants in the study had been ill on average for more than a decade. The extent to which these techniques would be helpful to individuals with a more recent onset of schizophrenia should be examined in future research. In future studies including a baseline period of assessment for medication adherence prior to randomization would be important. In-home pill counts could not be conducted by blinded observers given the nature of environmental supports. However, pharmacy records were not subject to observer bias. It is also likely that more adherent individuals agreed to participate in the study; a common problem in adherence research. Moreover, assessments of medication adherence involve error that may overestimate or underestimate actual adherence. Methodological problems with pill counts and pharmacy records are outlined elsewhere.29
The fact that medication adherence improved, while psychotic symptoms did not suggests that our notions about adequate adherence and optimal dosing may have been formed in the ambiguous environment of partial adherence or negotiation and may need to be altered to maximize the outcomes of our patients.
Despite these methodological limitations, the study provides strong support for the benefits of CAT and Pharm-CAT with respect to improving medication adherence and for the benefits of CAT for improving functional outcomes.