early diagnosis and intervention in psychosis: perspective from turkey
Transkript
early diagnosis and intervention in psychosis: perspective from turkey
Clinical Neuropsychiatry (2008) 5, 6, 290-294 EARLY DIAGNOSIS AND INTERVENTION IN PSYCHOSIS: PERSPECTIVE FROM TURKEY Meram Can Saka, M. KazÚm YazÚcÚ Abstract Schizophrenia is still one of the costliest problems of mankind on both personal and societal levels. Since schizophrenia has been defined there had been hopes to arrest the disorder in early phases. In last 20 years there had been a growing interest in early diagnosis and intervention area, a corresponding rise in reported studies and some encouraging results. There are some issues demanding serious attention like non-applicability of studies to general population, exclusion of negative and depressive symptoms from contemporary high risk definitions and treating groups with a significant proportion not expected to have clinical disorder. After current psychiatric services and early diagnosis and intervention efforts in Turkey are described the authors conclude that contributions to the field from Turkey with limited resources but high levels of accessibility and attainability of medical treatment, young population, high rates of intra-national migration between very different life circumstances, ethnic groups, different family and social relation patterns can be of use worldwide. Key Words: Schizophrenia Early Intervention Declaration of Interest: None Meram Can Saka1, MD, M. KazÚm Yazici2*, MD 1 Ankara University, School of Medicine, Psychiatry Department 2. Hacettepe University, Faculty of Medicine, Department of Psychiatry Corresponding Author M. KazÚm YazÚcÚ, Hacettepe University Faculty of Medicine, Department of Psychiatry, Ankara 06100, Turkey Email: kyazici@hacettepe.edu.tr The arrival of second generation antipsychotics with fewer extrapyramidal side effects, followed recently by others with less metabolic side effects led psychiatrists to a relative optimism and a renewed interest in remission in management of schizophrenia (van Os et al. 2006) but still the results of pharmacological or psychosocial treatments are not satisfactory and an important portion of patients are not active in social, occupational life reporting low levels of satisfaction (Perkins et al. 2006). Thus schizophrenia is still one of the costliest health problems on both personal and societal levels, causing immense amount of suffering to the patient and the family and high financial loads to the nation (Murray et al. 1996). The prevalence of schizophrenia may be lower in developing compared to developed countries (Saha et al. 2005) the costs though can be estimated to be alike. In the quest for etiology despite a multitude of new findings and better results from molecular and genetic studies we still dont have an established model that produces some solid intervention targets else than D2 receptors, leaving a dim hope for a more effective treatment in short or medium term. The hope to arrest schizophrenia in early phases is not new. Bleuler called the prodrome phase latent schizophrenia and thought that the underlying disease process may come to a halt at any stage of its early development (Bleuler 1911). Others followed his lead for early diagnosis (Cameron 1938, Sullivan 1927) but no significant intervention studies had been reported until last decades. It has been proposed that untreated psychosis may be toxic, leading to irreversible damage affecting long term outcome (Sheitman and Lieberman 1998) backed up with the association of some outcome parameters with duration of untreated psychosis (Marshall et al. 2005, Melle et al. 2004, Perkins et al. 2005). Last 20 years witnessed a multitude of early diagnosis and intervention studies throughout the world (McGorry et al. 2005) mostly from developed countries. McGorry relates the presence of around 200 early intervention centers worldwide (McGorry et al. 2007) and results have been accumulating. In enriched samples of treatment seeking subjects with subsyndromal psychosis symptoms, reported conversion rates to schizophrenia and other psychotic clinical disorders are around 30-40 percent and of those that will progress to clinical disorders, up to 80 percent can be predicted (Cannon et al. 2008, Häfner and Maurer 2005). Intervention studies using antipsychotics and/ or psychosocial interventions to prevent conversion to schizophrenia or other psychotic disorders report SUBMITTED JULY 2008, ACCEPTED NOVEMBER 2008 290 © 2008 Giovanni Fioriti Editore s.r.l. Early Diagnosis and Intervention in Psychosis: Perspective from Turkey significant results, like reducing the conversion risk around 20% which corresponds to a more than half of the total risk (McGlashan et al. 2006, McGorry et al. 2002, Morrison et al. 2004). Though encouraging, there are some points to consider to interpret those results. The predictive values of prodromal criteria are mediated by the structure of the early detection services in which they are embedded and applied. The patient samples investigated in mentioned studies (Häfner et al. 1999, McGlashan et al. 2006, McGorry et al. 2002) are highly enriched patient samples, filtered at two or more assessment steps to be directed to the speciality clinics (van Os and Verdoux 2003). This is a serious shortcoming for applicability of these results to general population for achievement of public health targets. Cannon et al., in the biggest study to date, stated that The results are not expected to be useful in general population screening (Cannon et al. 2008). Depressive and negative symptoms seem to be the first symptoms in the prodromal period (Häfner et al. 1999). Their importance is highlighted by the well established association with younger age and poor prognosis (Gillberg et al. 1993, Remschmidt 2002). Negative symptoms are not included in contemporary high risk definitions (Simon et al. 2007), maybe leaving out the most poor prognosis future patients from prevention efforts. Cornblatt and colleagues have recently proposed a high risk definition with negative symptoms (Cornblatt et al. 2003) but leading those subjects with high withdrawal to seek treatment may prove out to be quite problematic. Even the most systematic programs today are exceptions in general health services (Yung et al. 2007). Prevention programs must be implemented to all health system to have a substantial effect on schizophrenia prevalence but a significant proportion of even schizophrenia patients are not getting required medical attention not only in countries like Turkey with insufficient funds for health services but also in developed countries like USA. In intervention studies %30-50 of groups converts to psychosis leaving a 50-70 percent without a clinical diagnosis, which may well be the case for the rest of their lives. Treating subjects with the chance to never become clinically disturbed raises a number of ethical challenges, in particular the imperative to do no harm. Unnecessary additional stress for the patient and the family, stigma and unwanted consequences are possible effects of both psychosocial and medical treatments. Medication side effects like EPS and metabolic changes and possible effects on developing adolescent brain should be assessed meticulously for the risk-benefit ratio. In the only intervention study using antipsychotics as the sole intervention (McGlashan et al. 2006), high dropout rate due to weight gain and sedation is alerting. Focusing early diagnosis and intervention (EDI) efforts to subjects with considerable positive symptoms, if not highly disabling negative and depressive ones (Häfner and Maurer 2005), means we are trying to reduce risk of progression and severity rather than the disorder itself. The perfect prevention should take place before any symptoms and relieve those at risk or all the population by an innocuous intervention. To reach such prevention measures, risk factors for the disorder and Clinical Neuropsychiatry (2008) 5, 6 their timing (prenatal, adolescence etc) must be defined clearly. Population attributable risks of 10.5% for winter spring birth, 36.5% for urban effect, 14% for cannabis use and 5-10% for birth complications are quite impressing (McGrath 2003, Moore et al. 2007, Mortensen et al. 1999) but as those risk factors are proxies for real risk modifying factors and the real factors responsible like infectious agents, psychosocial effects etc. are to be clarified, they are not suitable for intervention targets yet. Efforts for perfect prevention may be delayed until we know a lot more about real risk factors but McGrath reminds us about the miasma theory that led to the improved sanitation long before the discovery of microorganisms and the consumption of limes on long sea voyages to prevent scurvy before understanding of ascorbic acid (McGrath 2003). The long delay between a possible prenatal risk factor and the onset of psychotic disorder and the complex nature of schizophrenia including gene-environment interaction and multiple etiopathogenic processes under the psychosis title may limit our hope for such a shortcut to be discovered but we think this should be a target kept alive. Progress from risk factors study can always be expected. Results from cannabis studies alerted the United Kingdom authorities and their stance on cannabis changed. First episode psychosis and first few years may bear an important opportunity to effect long term compliance and outcome. Specialized services with intensive and sometimes assertive care may be more efficient and economical on the long run (McGorry et al. 2007). This field is still demanding, in both research and services. Epidemiology is offering us new risk factor gradients and large scale epidemiological studies with multiple approaches addressing neurobiology, genetics with the power of animal models and molecular strategies may have the highest yield. Field studies of subjects with sub-clinical positive and negative symptoms, including those who do not demand treatment can be expected to be most informative. Representative sample sizes which will lead to population attributable risk estimates should be targeted. Follow up of such samples concentrating on environmental factors, functional changes and geneenvironment interactions are surely needed. It should be remembered that the revelation of risk factors for cardiovascular disorders were possible not only after progress in related basic sciences but after field studies including thousands and thousands of subjects. Though not affecting such a big percentage of the population, psychosis is associated with very high personal and societal burdens and the priority it deserves should be addressed in funding and design of EDI studies. Turkish psychiatry has been aware of the now strongly established cannabis psychosis association for quite a while. Mazhar Osman Uzman, one of the founders of modern psychiatry in Turkey, defined a schizophrenic reaction elicited by cannabis use and drew attention to the association more than 50 years ago (Songar 1971). In Turkey cannabis use is neither prevalent in the community nor in schizophrenics. Alptekin et al. (2005) screened general population for psychotic symptoms and reported a rate of 3.6%, which 291 Meram Can Saka, M. KazÚm YazÚcÚ is lower than most of the similar studies and cannabis use was reported in only 3 of 1268 subjects. Fortunately right now it is not an important risk factor for Turkey however in the light of rising substance problems and high international and intra-national migration, it is a factor to keep in mind as it may become more important in the near future. It is obvious that we need consensus prodrome criteria with high predictive values convenient for public health practice, more robust data about antipsychotics efficacy for preventing or delaying conversion to psychosis and especially associated disability, long term extrapyramidal, metabolic and developmental side effects. Still clinician facing functional deterioration and increasing positive or negative symptoms must intervene. In Turkey early psychotic symptoms are traditionally approached with antidepressants, supportive and family oriented psychotherapy, in compliance with the current data and guidelines. But when the psychotic break seems imminent antipsychotics are considered. At this point the risk benefit ratio must be assessed for each patient individually, taking into account all the listed disadvantages; which seems to be the case in Turkish psychiatry too. Almost all the population of Turkey is covered by Health Insurance System, with different agencies for different professions (civil servants, workers, tradesmen) and other government funds for people with low income - no profession and atypical antipsychotics became available in Turkey almost immediately after they are introduced in USA and EU. Thus prodromal patients from every walk of life have been treated with atypical antipsychotics since they are available. Contrary to the availability of medications, there are almost no specialized rehabilitation services or community treatments in psychiatry with the exception of a few short lived examples, built on some personal efforts. The number of psychiatrists, psychiatric beds and supporting personnel (psychologist, social worker etc.) are way below the preferred levels. Indeed a big majority of the psychiatric services in Turkey are provided by the government with eight big mental health hospitals located throughout the country supplying most of the psychiatric beds. Government hospitals in most cities have psychiatrists but few have inpatient facilities. Thus accessing outpatient treatments may be difficult for a part of the community, especially to those who live in the rural areas but inpatient facilities are inadequate for everyone alike. In addition to the limited accessibility of psychiatric services, primary health services also provide limited care for people with mental illness (KÚlÚc et al. 1994). Low rate of mental health referrals in general health care (YÚldÚz M et al. 2003) also contributes to low service utilization in Turkey. In YÚldÚz et als (2003) study, designed to assess general practitioners attitudes and behavior towards psychotic disorders, practitioners in primary care settings report encountering patients with psychosis rarely. To us, the reasons behind this may be either the dysfunctional referring system causing psychosis patients to apply to specialty clinics and psychiatrists first or they are not recognized by general practitioners. Likewise in the community survey conducted by SaXduyu et al. (2001) 292 on a wide sample in Turkey, the majority of participants identified schizophrenia as a mental illness (76.5%), the most commonly endorsed causes being stressful life events (54.3%) and weak mental constitution (52%). Three quarters of the sample chose medical treatment as the first thing to do and 90% of those assessed psychiatry as the proper address and only %3.5 thought traditional or local treatments beneficial. Those results also stress that there are a lot to do for the utilization of primary care for mental disorders. Yet the possibility of practitioners failure to recognize psychosis is important for mental disorders that are not prominent and especially for prodrome. In YÚldÚz et als above mentioned study (2003), almost a half of GPs sought structured and advanced education about psychosis, supporting this possibility. Governmental and other professional authorities had organized some educational activities for practitioners aiming to raise recognition and treatment rates of depression and, PTSD after big earthquakes, but none for schizophrenia. Ucok et al. (2006) report a small scale study on education against stigma related to schizophrenia, where practitioners developed a more favorable view on availability and their capability of participating to the treatment of schizophrenia. Thus, primary health care remains at the central stage for mental health promotion activities in Turkey (Uçok et al. 2006). There are no specialized centers or government funds for EDI studies in Turkey yet. A serious drawback to EDI studies is the scarceness of epidemiological data on schizophrenia and psychosis. Previously mentioned study of Alptekin et al. (2005) gave an opinion on psychotic symptoms. A large scale study to assess incidence and prevalence as well as treatment and service use has been started recently with first results expected in 2010 (Binbay et al., personal communication, June 1, 2008). Some groups are working on early psychosis (Atbasoglu et al. 2005) and highly cited DUP studies have been reported (Uçok et al. 2004). The first completed high risk study in Turkey, to our knowledge, is Aydin and Ucoks study in that the changes in the brains of high risk subjects were investigated by using magnetic resonance spectroscopy (Aydin et al. 2008). To our knowledge, there are no reported EDI studies. Schizophrenia Proneness Instrument Adult Version (SPI-A) (Schultze-Lutter et al. 2006) has recently been adapted to Turkish, supervised by one of the authors (MKY) and is about to be submitted by the group who are conducting a psychosis prediction project in adolescents with high genetic loading for schizophrenia with structural and metabolic brain imaging and electrophysiological testing. Another big scale follow-up of normal young adults with assessment of sub-clinical psychosis, academic and social functioning is also going on with results expected soon by the group of the other author (MCS). The same group have adapted the Chapman Magical Ideation scale and adopting other Wisconsin schizotypy scales to Turkish (Atbasoglu et al. 2003). As seen EDI studies are in infancy in Turkey. After accumulation of some epidemiological data, experience with research in this group and with hopefully more positive results from the world, we can hope to create public opinion, governmental support and funds for EDI Clinical Neuropsychiatry (2008) 5, 6 Early Diagnosis and Intervention in Psychosis: Perspective from Turkey studies. Extensive early diagnosis and intervention systems may be seen as an overambitious target for Turkey for now, considering very limited resources for rehabilitation and almost no community treatments like halfway houses or assertive community treatments for schizophrenia. EDI is expected to be cost effective in both personal and financial burdens of the disorder, if disabling and chronic nature of the disorder can be overcome. 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