Treatment of patients with first-episode psychosis: two-year outcome data from the Danish National Schizophrenia Project

Abstract

First episode psychosis interventions have been in focus in the last two decades in an attempt to improve the course and outcome of schizophrenic disorders. The Danish National Schizophrenia Project began in 1997 its intake of patients, aged 16-35, with a first psychotic episode of a schizophrenic spectrum disorder, diagnosed by ICD-10 (F20-29). The study was carried out as a prospective, longitudinal, multicentre investigation, encompassing 16 centres, spread all over the country. The sample consists of 562 patients consecutively diagnosed during two years. Patients were treated with "supportive psychodynamic psychotherapy as a supplement to treatment as usual", "integrated, assertive, psychosocial and educational treatment programme", or "treatment as usual". Data on symptoms and social function and sociodemographic data were obtained at inclusion, and at year 1 and 2. The three sub-cohorts did not differ at baseline. After one year, the total sample of patients improved significantly concerning symptoms and social function. The significance of the improvement remained after two years. After one year, patients in the two intervention groups improved more concerning symptoms and social function than patients in the treatment-as-usual group. Improvement in the intervention groups continued into the second year. Patients receiving integrated assertive treatment faired better than those being treated with the less intensive method of supportive psychodynamic psychotherapy, and the latter group improved more than the treatment-as-usual group.

A leading hypothesis, originally proposed in the 1950s and later turned into object of research, assumes that a critical period exists in the first years of first-episode psychosis, in which crucial biological and psychosocial changes are laid down in the mind of the patient, forming the predictors of long-term outcome. During the last 15 years, an effort has been made internationally to collect evidence-based support for that assumption, and to evaluate the long-term results of interventions in that critical period (1-9).

Several simultaneous factors led, in the latter part of the 1990s, to the establishment of a Danish clinical contribution to the field of early secondary prevention for schizophrenia and related disorders. Denmark had a few years earlier contributed to a Nordic study of early psychotherapeutic approaches to schizophrenia (1), but the small Danish sample called for another investigation with largescale ambitions.

Moreover, in the beginning of 1990s, figures were published in Denmark concerning criminality, suicide and homelessness in people with schizophrenia. Governmental money was granted to investigate and counteract these problems as well as minimize the individual damages that hindered young psychotics to enter the working market and led them to acquire a social pension at a young age. Programmes of early, rapid and sustained interventions after the first signs of psychosis were requested.

Since the 1930s, the Danish Mental Health Service has had a tradition for equal access to and economically free treatment for all inhabitants regardless of their location of living, income, race or religion. In this welfare system, private psychiatric hospitals or clinics for severe psychiatric conditions do not exist. Mental health treatment is organized according to sectorized psychiatry, in which district psychiatric offices (with staff ranging from 6 to 20 persons), located outside the hospital, work in close connection with the hospital units. General practitioners and private practicing specialists only care for a small percentage of the patients treated for schizophrenia and related disorders. Pathways to treatment of psychotic patients and the quality of their care can be considered equal in the country.

METHODS

The Danish National Schizophrenia Project is a prospective, comparative, longitudinal study with a minimum intervention period of two years and the assessment of participants at baseline and at 1, 2 and 5 years after inclusion (10). Participants were allocated to three different treatments: a) "supportive psychodynamic psychotherapy" (N=119), in which they were offered scheduled, manualized, supportive individual psychotherapy (one 45-min session per week, for a period of 1-3 years) and/or group psychotherapy (one 60-min session per week for a period of 1-3 years), in addition to treatment as usual; b) "integrated treatment" (N=139), in which they were offered an integrated treatment package (a scheduled, 2-year programme consisting of assertive community treatment, psychoeducational multifamily treatment, social skills training, and antipsychotic medication) (11); c) treatment as usual (N=304), in which they were offered many different therapies (psychological methods, medication, medical advice and treatment by the inpatient and day-hospital service), administered according to patients' needs, and the available resources of the clinic at the time of treatment, not delivered in any prescheduled manner.

Participants were consecutively referred patients aged 16-35 years, with a first-episode psychosis of the schizophrenic spectrum (ICD-10, F20-29). Written informed consent was obtained from all patients, although not necessarily in the initial phase of the treatment. Patients were excluded if they had a diagnosis of mental retardation or other organic brain damage, severe alcohol or drug abuse, or were not sufficiently proficient Danish speakers.

Patients with first-episode psychosis, admitted to either the inpatient unit or the community mental health centre, were systematically assessed within two weeks, and included if they fulfilled the above criteria. The assessments were conducted by trained, independent research teams, connected to each centre.

The test battery was applied shortly after inclusion, and at year 1 and 2. The battery included the following variables: a) demographic and socioeconomic data; b) diagnosis according to ICD-10 research criteria determined by clinical observation and judgement, and further confirmed by the Operational Criteria Checklist for Psychotic Illness (OPCRIT) (12); c) clinical status determined by the OPCRIT, the Global Assessment of Functioning (GAF) in DSM-IV (13), the Strauss-Carpenter Outcome Scale (14,15), and the Positive and Negative Syndrome Scale (PANSS) (16).

Supportive psychodynamic psychotherapy and the integrated treatment were conducted according to manuals. Regular supervision was provided for both kinds of interventions to enhance adherence to the manuals. The manualized psychodynamic psychotherapy for group treatment and for individual treatment aimed at a realistic cognition of psychosocial events (encompassing attitudes towards illness and medication, the creation of realistic social goals and affectively meaningful interactions in daily-life interpersonal relationships) and was focussed on the understanding of emotions from the past as well as in the present. The manuals described the initial, the middle and the terminating phase of the dynamic treatment.

The psychoeducational family treatment was manualized according to McFarlane et al (17). The focus of each session was problem solving and the development of skills to cope with aspects of the illness. The social skills training was manualized, based on selected modules from Liberman (18) and Bellack (19).

Logistic regression with generalized estimating equations was used for dichotomous variables and linear mixed models were used for continuous variables. These methods were used to compare the three sub-cohorts at baseline, at year 1 and 2, and for differences between baseline and year 1 and 2. In the calculation of changes from baseline to year 1 and 2, the analyses were adjusted for the baseline values. All tests were two-sided and the level of significance was 0.05. The Bonferroni correction was used in the interpretation of the results.

RESULTS

A total number of 562 patients (361 males and 201 females; age range 16.2-35.9 years, mean 24.1 years), mainly of Nordic origin (92%), met the inclusion criteria and gave informed consent.

The three cohorts were similar at baseline concerning age, diagnosis, PANSS positive score, GAF symptom score, GAF function score, GAF total score, and admission/nonadmission to hospital during the last year before inclusion to the study.

At year 1 and 2, data were obtained from respectively 450 patients (80%) and 362 patients (64.4%). The remaining patients in the three groups did not differ from the group from which data were not obtained concerning age, sex, diagnosis, GAF and PANSS total scores. There were no sociodemographic differences at year 1 and 2 between the three investigated groups. In the F20 group of patients with schizophrenia, 80% participated in the rating at year 1 and 68% at year 2.

At year 1, a significant improvement was found for GAF symptom score, GAF function score, GAF total score, PANSS positive score (p<0.0001), and PANSS negative score (p<0.04) when the three sub-cohorts were sampled together. More than half of the patients (54%) had more contact with friends at year 1 compared to baseline, 18% had more work and 58% had fewer symptoms. For year 2, the same comparison showed that 57% had more contact with friends, 27% had more work and 65% had fewer symptoms.

Similarly, from baseline to year 2 significant changes appeared in the GAF and PANSS variables (p<0.0001) when the three treatment groups were sampled together. In general, changes from baseline to year 1 were bigger than the changes from year 1 to 2. However, the latter changes were significant for scores of GAF symptoms, GAF total and PANSS negative (p<0.009) (Table 1).

Table 1.

Clinical and social outcome for first episode psychotic patients in three different treatment modalities: changes from baseline to year 2

	SPP	IT	TaU	p
GAF symptoms	4.60 (-0.93; 10.13)	6.06 (-0.63; 12.75)	0	0.1072
GAF function	4.04 (-0.60; 8.68)	7.20 (2.46; 11.94)	0	0.0086
GAF total	3.63 (-1.13; 8.39)	6.42 (1.22; 11.62)	0	0.0400
PANSS positive symptoms	-1.27 (-2.79; 0.25)	-1.96 (-3.59; -0.32)	0	0.0406
PANSS negative symptoms	1.73 (-0.46; 3.91)	-3.05 (-5.57; -0.54)	0	0.0035

Results from generalized linear mixed model (odds ratio) or linear mixed model (parameter estimate) with 95% confidence interval, adjusted for baseline value.

SPP - supportive psychodynamic psychotherapy; IT - integrated treatment; TaU - treatment as usual; GAF v Global Assessment of Functioning;

PANSS - Positive and Negative Syndrome Scale

A comparison of the improvements in the three groups at year 1 revealed a clear tendency in favour of the two intervention groups compared with the treatment-as-usual group. When drug and alcohol misuse were taken into consideration as confounding factors, we found that both interventions produced significant improvements in GAF function score (p<0.02) and PANSS negative score (p<0.02); the significance remained with the Bonferroni correction.

After two years, the two intervention groups had a greater improvement than the treatment-as-usual group concerning the scores of GAF function, GAF total and PANSS positive. The integrated treatment showed the greatest improvement and this improvement reached the level of statistical significance compared to treatment as usual for scores of GAF and PANSS, except from GAF symptoms (Table 1). After the Bonferroni correction, PANSS negative and GAF function remained significant.

DISCUSSION

The strengths of our study were: a) the number of consecutively referred patients; b) the inclusion of different types of treatment centres (small/big, urban/rural, university/ non-university) in all three groups being compared; c) the percentage of the Danish population covered by the study (about 45%); d) the comparison of two different treatment modalities with standard treatment of a supposedly good quality; e) the treatment conducted mainly by average trained therapists and not by master clinicians.

The Danish National Schizophrenia Project was thus carried out in a naturalistic and realistic manner, and it mimicked the natural conditions of the National Health System at that moment of its development (1998-2000). This supports the generalization of the results as well as the possibility of recommending in the future the use of both clinical measures and treatment methods in the dayto- day practice of psychiatry. It is furthermore in accordance with the current evidence according to which pragmatically defined integrated treatment programmes and effectiveness studies are more useful in the planning of schizophrenia prevention than narrowly defined regulatory models and efficacy studies (20).

An additional positive element is the creation of a tenable and durable network of centres that collaborate with the same treatment methods, the same measurement scales, and on the ground of the same treatment values. The collaboration needs a sort of idealistic tenor, and it has to take place in spite of the possibility of no funding. The reward for each centre is the qualification of interviewers being trained in the use of psychometric scales, and therapists being trained in the chosen methods of treatment.

Our study found that integrated treatment and supportive psychodynamic psychotherapy may improve outcome after one year of treatment for people with first-episode psychosis compared to treatment as usual. After two years this tendency clearly continued, significantly for the integrated treatment on some variables of PANSS and GAF.

Previous studies have found a positive outcome of different kinds of integrated treatment programmes compared to standard treatment (21). These programmes contain different curative elements, and some also include the possibility of offering psychodynamic psychotherapy to selected patients. It is, however, not immediately possible to detect and distil the specific curative factors of the integrated programmes. Possible curative factors in the integrated treatment of our study could be: a) the multifamily therapy and the rapid, consistent, integrated long-term involvement of the treatment team with a low case load (10 patients per staff person), spending more hours with the patient per week than the one-hour/week individual psychotherapy added to the treatment as usual; b) the specific targeting of the patient's return to the working market, school or other educational programme; c) the specific targeting of reverting the patient's status from inpatient to outpatient; and d) the cognitive approach and the social skills training.

Previous studies comparing psychodynamic psychotherapy to standard treatment have shown diverse results, some in favour of the psychodynamic treatment (22), others against (23). Positive outcome has mainly been associated with very experienced therapists or master clinicians, who rapidly could create and maintain a therapeutic alliance. However, none of the previous studies concerned firstepisode psychosis, and it is by no means given that we can extend the knowledge from these elder studies of psychotherapy of schizophrenia to our sample.

Possible curative factors in the supportive psychodynamic psychotherapy of our study could be: a) the establishment of a tenable working alliance; b) the use of the interactions in the therapeutic space to understand emotion and cognition in the daily communication and psychosocial processes; c) making the patient aware of both the helpful and the destructive aspects of his/her coping style and defence mechanisms; d) helping the patient integrating feelings and narratives (turning sense impressions into thoughts, and thoughts into thinking); e) focussing on the non-psychotic aspects of the human being and addressing the psychotic parts from that perspective; f) re-orienting the mind in its process of overcoming and defending against the painful losses it has experienced. Future integrated programmes may consider integrating also these psychodynamic aspects in the treatment.

One limitation of the study is the lack of individual randomization of all patients. Another limitation to the interpretation of the results is the lack of data for 32% of the patients after two years. This was not expected, but was mainly due to one major centre. A third limitation is the relatively few variables we can use in the project to compare all three treatment modalities. However, separate projects exist which will use more variables to compare integrated treatment and supportive psychodynamic psychotherapy separately with treatment-as-usual groups.