Sample
Consecutive patients referred to a specialized psychiatric team for psychosis were asked to participate in the study. The catchment area of the team was the northeast half of Sør-Trøndelag County in the middle of Norway during the first 2 years of the study and the entire county for the rest of the inclusion period. The whole county has a population of about 270.000 inhabitants. The recent-onset patients were selected for the study if they were diagnosed with DSM-IV [10] schizophrenia, schizoaffective or schizophreniform disorders by psychologists or psychiatrists trained to administer the Structured Clinical Interview for the DSM-IV [11] reliably. Clinically stable patients aged between 18 and 35 years who were prescribed antipsychotic medication and expected to reside in the county for at least 1 year after inclusion were asked to participate in the study. Patients with major substance use disorders or mental retardation were excluded. Recent-onset was defined as the emergence of distinct initial psychotic symptoms for the first time within the past 2 years. Very brief and transient experiences of psychotic symptoms prior to the past 2 years were not classified as distinct psychotic symptoms. Efforts were made to get referrals of all patients with a recent onset psychotic disorder in the catchment area. Invitations for study referral were sent to the psychiatric inpatient units, outpatient clinics, and general practitioners in the catchment area. Written informed consent was obtained after the procedures were fully explained to the patients and baseline assessments completed before inclusion from all included patients. The study was approved by The Regional Committee for Research Ethics, Middle Norway.
Interventions
All the 50 included patients received standard treatment which was regular case management with antipsychotic drugs, supportive housing and day care, crisis inpatient treatment at 1 of 2 psychiatric hospitals, rehabilitation that promoted independent living and work activity, brief psychoeducation, and supportive psychotherapy. In addition, the patients randomized to integrated treatment received structured family psychoeducation, cognitive – behavioural family communication and problem solving skills training, intensive crisis management provided at home, and individual cognitive-behavioural strategies for residual symptoms and disability [12, 13]. More details of the intervention and the results on new episodes, rehospitalisation, function and adherence to antipsychotic medication are reported elsewhere [8, 9]. The two interventions seemed to be equal in effects on adherence to medication. The dose of antipsychotic medication was kept to the lowest effective level. Although combination therapy and switch of antipsychotics occurred, monotherapy was preferred and plasma assays were used on clinical indications to optimise dose and to verify adherence. The physicians had no restrictions when they selected antipsychotics. Some of the patients having problems adhering to oral medication were offered depot injections.
Assessments
Registration of antipsychotic medication adherence was based on patient interviews. Information on adherence was also gathered from therapists, carers, plasma assays, and patient records. The information on adherence gathered from plasma assays was not assessed on a regular basis. If a patient later revealed that she or he had given incorrect information about adherence at an earlier visit, the records for adherence were corrected. Medication adherence was recorded at inclusion and bimonthly for the 2 years, and information gathered at later visits and information from informal carers, therapists and patient records was used to compensate for missing values. Adherence was graded on a 4 point scale according to Tarrier [14]: 0: Up to 1 week without medication, 1: Up to 1 month without medication or 4 times more than 1 week without medication, 2: Up to 5 months without medication, 3: five months or more without medication. Patients with 1 month or more or 4 single weeks or more without medication were rated as non-adherent with medication. Patients receiving depot injections of antipsychotics at any time were recorded as depot users. Because use of depot antipsychotics was nearly always associated with non-adherence with oral antipsychotics, adherence with oral antipsychotics was also compared with non-adherent patients and the depot users combined. Target Psychotic Symptoms measured each individual's unique hallucinations, delusions and thought disorders on a 0–7 scale [15]. Suggesting symptom exacebarations, extra measure times were executed. Brief Psychiatric Rating Scale, BPRS, was assessed bi-monthly [16]. The Positive and Negative Symptom factors derived for first episode schizophrenia were used to measure these dimensions [17].
Global Assessment of Functioning; GAF [10], assessed overall functioning at 0, 12 and 24 months.
Continuous records were kept of medication and psychosocial treatment adherence, hospital admissions and suicidal behaviour.
Ratings were made by independent raters who were blind to treatment conditions and trained to obtain a 0.8 kappa coefficient of inter-rater reliability on all rating scales.
Operationalised variables
Psychotic recurrences and exacerbations: An episode of relapse was defined as a two-point increase and a score of six or seven on the Target Symptoms Ratings Scale (0–7) AND a score of six or seven on one of the key psychotic symptom items on the BPRS (1–7). In addition this was confirmed by an independent person (researcher, family member, clinician, case manager, etc) as a significant worsening [18]. Persistent psychotic symptoms were defined as scoring more than four on BPRS hallucinations or unusual thought content for more than six consecutive months during the study period. Symptoms at baseline were assessed by the Brief Psychiatric Rating Scale (BPRS), Target Symptoms Rating Scale and Global Assessment of Function (GAF). Substance abuse was not systematically assessed after the patients were included in the study. Records were kept of medication and psychosocial treatment adherence, hospital admissions and suicidal behaviour. All included patients were included in the outcome analyses.
Statistics
Categorical factors were compared using Chi Square tests. Ordinal variables were compared using the Mann-Whitney test. To predict outcome, i.e. persistent psychosis, relapse and admittances to hospital, separate logistic regression analyses were performed with adherence to antipsychotic medication or use of depot antipsychotics as the explanation variable. All data analyses were performed with the Statistical Package for Social Sciences Version 14.0. An alfa level of 0.05 was selected.