Primary prevention of psychosis through interventions in the symptomatic prodromal phase, a pragmatic Norwegian Ultra High Risk study

Joa et al. BMC Psychiatry Primary prevention of psychosis through interventions in the symptomatic prodromal phase, a pragmatic Norwegian Ultra High Risk study Inge Joa 0 1 Jens Gisselgrd 1 Kolbjrn Brnnick 0 1 Thomas McGlashan 2 Jan Olav Johannessen 0 1 0 Network for medical sciences, University of Stavanger , 4036 Stavanger , Norway 1 Psychiatric Division, Stavanger University Hospital, TIPS- Centre for Clinical Research in Psychosis , Armauer Hansensvei 20, N-4011 Stavanger , Norway 2 Department of Psychiatry, Yale University , New Haven, CT , USA Background: Evidence has been accumulating that it may be possible to achieve prevention in psychotic disorders. The aim of the Prevention Of Psychosis (POP) study is to reduce the annual incidence of psychotic disorders in a catchment area population through detection and intervention in the prodromal phase of disorder. Prodromal patients will be recruited through information campaigns modelled on the Scandinavian early Treatment and Intervention in Psychosis (TIPS) study and assessed by low-threshold detection teams. Methods/Design: The study will use a parallel control design comparing the incidence of first episode psychotic disorders between two Norwegian catchment areas with prodromal detection and treatment (Stavanger and Fonna) with two catchment areas without a prodromal intervention program (Bergen and stfold). The primary aim of the current study is to test the effect of a Prodromal Detection and Treatment program at the health care systems level. The study will investigate: 1) If the combination of information campaigns and detection teams modelled will help in identifying individuals (age 13-65, fulfilling study inclusion criteria) at high risk of developing psychosis early, and 2) If a graded, multi-modal treatment program will reduce rates of conversion compared to the rates seen in follow-along assessments. Discussion: Positive results could potentially revolutionize therapy by treating risk earlier rather than disorder later and could open a new era of early detection and intervention in psychosis. Negative results will suggest that the potential for psychosis is determined early in life and that research should focus more on genetically linked neurodevelopmental processes. If we can identify people about to become psychotic with high accuracy, we can track them to understand more about how psychosis unfolds. Appropriate intervention at this stage could also prevent or delay the onset of psychosis and/or subsequent deterioration, i.e., social and instrumental disability, suicide, aggressive behavior, affective- and cognitive deficits. Psychosis; Schizophrenia; Prodromal; Ultra-high risk; Early detection - Background Mental illness is the largest cause of disability in developed countries, and psychotic disorders (schizophrenia/ bipolar disorder) are ranked among the leading causes of total burden of disease and cost of lifetime disability worldwide. In spite of high research activity the mechanisms behind these disorders are still primarily unknown and the effects of available treatments are also limited and mostly palliative. Most patients experience a relative long period with non-psychotic symptoms before their first psychotic episode characterized by unspecific- and more specific symptom constellations (prodrome/Ultra High Risk (UHR) state). At the onset of psychosis, many have already experienced a loss of cognitive- and psychosocial functioning. We now know that individuals at high risk for psychotic disorders can be identified before this point of time. The present study builds on experiences from the Scandinavian Early Treatment and Intervention in Psychosis (TIPS) study [1,2], where the use of information campaigns and detection teams were instrumental in reducing the duration of untreated psychotic symptoms in the first episode. This reduction was followed by a more benign course of the disorder over ten years of treatment [3]. We here hypothesize that a similar program (Prodromal Detection and Treatment program - PDT) - aimed at identifying and treating help seeking individuals at high risk for developing psychotic disorders will a) significantly increase the number of high risk individuals that get in contact with the relevant services and b) that these individuals will be detected at a very early stage of illness development. After contact the high risk individuals will be allocated to a structured follow-along by a designated case manager or to a graded, multi-modal and primarily psychosocial treatment intervention. Patients will be offered active antipsychotic medication only at imminent risk of conversion to psychosis. We also hypothesize that the multi-modal treatment intervention will significantly reduce the number of persons converting to psychosis, and thus influence the incidence of new cases of firstepisode psychosis. The study is designed as a regional multi-center study, involving central research- and clinical psychiatric organizations across the Health Vest region in Southern Norway, with significant international cooperation, and will involve all service levels from general practitioners to specialized psychiatric services. Two Norwegian treatment centers covering a population of 440 000 will collaborate in recruiting prodromal patients to the study: Stavanger and Fonna hospitals. The project organization has additional involvement from the research departments at Bergen University Hospitals and Sykehuset stfold Hospital for establishing a first-episode psychosis incidence registration as another part of this research initiative. All study enrolled patients will be asked for blood samples and to be a part of the Norwegian NASATS program Severe Mental Illness, aiming to identify new genetic variants associated with severe mental disorders [4]. Rationale Schizophrenia and other psychotic disorders are serious, costly, and disabling. They typically emerge in late adolescence and early adulthood, a critical phase of neurological, psychological and social development. Even if the number of new cases per year is low (varying between 15 in the TIPS study [1] to 30 per 100 000 per year [5], their early onsets combined with a high risk of chronic symptoms makes these into disorders with a high prevalence (1%). Many patients display significant impairments already at start of first treatment, and it is known that course and outcome are poorer in patients that come late into treatment. Results from the TIPS study show for the first time that treatment can be initiated significantly earlier in psychotic disorders. This is in turn associated with less severe psychotic symptoms, suicidality and functional disabilities already at first treatment [1,6]. Followup after two- and five years in treatment demonstrate long-term advantages in the form of less severe negative symptoms, cognitive deficits, depressive symptoms and global dysfunction [7,8] and for the level of recovery rates up t (...truncated)