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IntroductionOff-label use of antipsychotics has increased in many countries. In adult populations antipsychotics off-label prescriptions varied from 40 to 75% of all AP users.ObjectivesTo examine the off-label prescribing practices and experiences of antipsychotic medication in Finland.MethodsAn electronic questionnaire on physicians’ prescription practices of antipsychotics, especially for off-label use, was sent in 2019 for physicians (n=1195) in different health care facilities including primary health care, occupational health care, in- and outpatient mental health services and services for substance abuse. The sample was selected by systematic and convenience sampling covering five university hospital areas in Finland.ResultsIn total, 216 physicians (18% of the target sample) participated in the study, and 94% had prescribed antipsychotics for off-label use. The most common off-label indications were insomnia and anxiety. The most common antipsychotic used was quetiapine. Off-label antipsychotics was not prescribed as a first-choice medication: 99% of the physicians reported that the patients with off-label use have previously had other medications for the corresponding symptoms. In all, 88% of clinicians monitored the patients’ clinical condition, whereas metabolic values were followed more rarely. About 68% of physicians reported more benefit than harm from the antipsychotics off-labeluse.ConclusionsAntipsychotics are often prescribed for off-label use, most commonly for insomnia and anxiety. Most of the physicians see more benefits than harms for the patient in off-label use. There is a need to analyse the long-term benefits and harms of off-label use of antipsychotics and create more detailed treatment algorithms and clinical recommendations for such use.DisclosureNo significant relationships.

Few studies have compared time trends for the incidence of psychosis. To date, the results have been inconsistent, showing a decline, an increase or no significant change. As far as we know, no studies explored changes in prevalence of early risk factors. The aim of this study was to investigate differences in early risk factors and cumulative incidences of psychosis by type of psychosis in two comparable birth cohorts. The Northern Finland Birth cohorts (NFBCs) 1966 (N = 12 058) and 1986 (N = 9432) are prospective general population-based cohorts with the children followed since mother's mid-pregnancy. The data for psychoses, i.e. schizophrenia (narrow, spectrum), bipolar disorder with psychotic features, major depressive episode with psychotic features, brief psychosis and other psychoses (ICD 8-10) were collected from nationwide registers including both inpatients and outpatients. The data on early risk factors including sex and place of birth of the offspring, parental age and psychosis, maternal education at birth were prospectively collected from the population registers. The follow-up reached until the age of 27 years. An increase in the cumulative incidence of all psychoses was seen (1.01% in NFBC 1966 v. 1.90% in NFBC 1986; p < 0.001), which was due to an increase in diagnosed affective and other psychoses. Earlier onset of cases and relatively more psychoses in women were observed in the NFBC 1986. Changes in prevalence of potential early risk factors were identified, but only parental psychosis was a significant predictor in both cohorts (hazard ratios ≥3.0; 95% CI 1.86-4.88). The difference in psychosis incidence was not dependent on changes in prevalence of studied early risk factors. Surprisingly, increase in the cumulative incidence of psychosis and also changes in the types of psychoses were found between two birth cohorts 20 years apart. The observed differences could be due to real changes in incidence or they can be attributable to changes in diagnostic practices, or to early psychosis detection and treatment.

Summary Aim We compared the course and outcome of schizophrenia in two groups: (i) hospitalised patients (HP) (n = 5980) who were identified based on their first hospital admission for schizophrenia and (ii) outpatient‐treated patients (OTP) who received disability pension because of schizophrenia but who had no hospital admissions for schizophrenia or other psychotic disorder before having been granted a disability pension for schizophrenia (n = 1220). Outcomes were compared using data on mortality, psychiatric hospital utilisation, relapse rate and occupational functioning. Methods A nationwide register‐based 5‐year follow‐up study of all first‐onset schizophrenia cases between 1998 and 2003 in Finland. The data were linked with the register information of hospital admissions, disability pensions and National Causes of Death Registers. Results When outcome of treatment was evaluated using mortality rate, relapses, hospital treatment and involuntary admissions as outcome measures, results indicated that OTP group had got along better with their illnesses than HP group. The mortality rates, number of psychiatric treatment days and relapse rate during the 5‐year follow up were significantly lower in OTP group. Within the OTP group, there was a notable subgroup of never HP (n = 737, 60.4%), who did not require any psychiatric hospitalisation during the 5‐year follow up. Conclusions Patients first identified as outpatients had better outcomes than patients first identified following a hospitalisation. Future studies are required to establish whether outpatient treatment is associated with more favourable prognosis, even after fully adjusting for severity of initial symptoms. The higher suicide mortality of hospital‐treated patients suggests that hospital treatment of first‐onset patients does not protect from suicide.

As a prerequisite to the use of the Finnish National Hospital Discharge Register in psychiatric epidemiological research, we studied the diagnostic reliability of the register in terms of the psychiatric morbidity experienced by a national birth cohort. We investigated all entries to the register for a sample based upon the Northern Finland 1966 birth cohort at the age of 16 years (n = 11017). Until the end of 1993 (age 27 years), a total of 563 subjects had a register diagnosis indicating a psychiatric illness, 37 of them being schizophrenia. When operational criteria (DSM-III-R) were applied to clinical information in the available original hospital records for cases of psychosis, personality disorder and substance abuse (n = 249), 71 fulfilled criteria for schizophrenia, including all of the 37 cases in the register and an additional 34 (48% false-negatives), most frequently diagnosed in the register as schizophreniform or other psychosis. Despite the official use of DSM-III-R nomenclature, it appears that the clinical concept of schizophrenia in Finland, manifest within the register, remains very restrictive. The application of operational criteria is a necessary prerequisite for scientific research on schizophrenia.

Background. Mental disorders often begin during the formative years of education. They may disrupt education and lead to social underachievement. Methods. We examined the impact of mental disorders treated in hospital (ages 16–29) on educational attainment up to 31 years in the Northern Finland 1966 Birth Cohort (N = 10581). People discharged due to mental illness were grouped by DSM-III-R diagnoses (of schizophrenia, other psychoses and non-psychotic disorders) and were compared with those having no such hospital treatment. Associations between diagnoses and educational outcome (completion of basic level, upper secondary or tertiary education) were analysed stratified by age at onset (early onset < 22 years v. later), and adjusted for confounding by perinatal risk, early motor development, maternal education, family structure, parental social class, and school achievement using prospective data from earlier assessments and logistic regression analysis. Results. Twelve per cent of the comparison group completed basic level education, 62% upper secondary, and 26% tertiary education. People with early onset disorder tended to stagnate in the basic level. Early onset schizophrenia and all non-psychotic cases had 3- to 6-fold adjusted odds for this outcome. Many with early onset schizophrenia completed secondary education, but none completed the tertiary level. Hospitalization for non-psychotic disorder increased the risk of underachievement in tertiary education for those with early onset. Conclusions. Mental disorder treated in hospital truncates education. Failure to complete higher education may contribute to the ‘social exclusion’ of the mentally ill through reduced opportunities in later occupational life and failure to accumulate social capital.

Subtle motor, emotional, cognitive and behavioral abnormalities are often present in apparently healthy children and adolescents who later develop schizophrenia. This suggests that some aspects of causation are established long before psychosis is manifest. We aim to develop a descriptive model of the factors contributing to the development of schizophrenia. Our main focus is on genetic factors, pregnancy and delivery complications, early development and scholastic performance. This is done by reviewing the Northern Finland 1966 Birth Cohort, its scientific activities (publications and work in progress) and selected literature.

Background. Early separation of a child from the mother has been considered a risk factor for later depression. We investigated the association between very early separation and depression in adulthood in a unique dataset. Method. The index cohort consisted of 3020 subjects born in 1945–1965 in Finland, isolated from their family due to tuberculosis in the family and placed in special nurseries, immediately after birth, for an average time of 7 months. Those subjects alive at 1 January, 1971 were identified. For every index subject two reference subjects were chosen, the matching criteria being sex, year of birth and place of birth. Data on depression were obtained from the Finnish Hospital Discharge Register by the end of year 1998. Results. In males, 4·2% of the index subjects and 2·6% (Adjusted Rate Ratio RR 1·7, 95% CI 1·3–2·3) of the reference subjects had been treated in hospital due to a depressive episode. In females the respective figures were 3·9% for index subjects and 3·6% (RR 1·1, 95% CI 0·8–1·5) for reference subjects. Conclusions. The index subjects had an elevated risk for hospital treated depression in adulthood. One explanation may be that the very early temporal separation from the mother at birth may have unfavourable effects on later psychological development. On the other hand, separation from the parents at birth was not found to be strongly associated with severe adulthood depression.

We have studied the possible interaction of erythromycin and itraconazole, both inhibitors of cytochrome P450 3A4 isoenzyme (CYP3A4), with intravenous lignocaine in nine healthy volunteers using a randomized cross-over study design. The subjects were given oral placebo, erythromycin (500 mg three times a day) or itraconazole (200 mg once a day) for 4 days. Intravenous lignocaine 1.5 mg x kg(-1) was given with an infusion for 60 min on the fourth day of pretreatment with placebo, erythromycin or itraconazole. Timed plasma samples were collected until 11 h. The concentrations of lignocaine and its metabolite monoethylglycinexylidide (MEGX) were measured by gas chromatography. The area under the lignocaine concentration-time curve was similar during all three phases but erythromycin significantly increased the elimination half-life of lignocaine from 2.5 to 2.9 (0.7) h compared with placebo. Following itraconazole administration, t1/2 was 2.6 h. The values for plasma clearance and volume of distribution at steady state were similar during all the phases. Compared with placebo and itraconazole, erythromycin significantly increased MEGX peak concentrations by approximately 40% and AUC(0-11 h) by 45-60%. The plasma decay of lignocaine administered intravenously is virtually unaffected by the concomitant administration of erythromycin and itraconazole. However, erythromycin increases the concentrations of MEGX, which indicates that erythromycin either increases the relative amount of lignocaine metabolized via N-de-ethylation or decreases the further metabolism of MEGX. Further studies are necessary to elucidate the clinical significance of the erythromycin-induced elevated concentrations of MEGX during prolonged intravenous infusions of lignocaine.

Aims: Higher rates of psychiatric morbidity among non-participants may lead to biased estimates of prevalence and incidence in epidemiological studies of psychiatric disorders. We had a unique opportunity to explore psychiatric morbidity and non-participation in a large epidemiological survey including questionnaires and a clinical examination. Methods: Members of the Northern Finland 1966 Birth Cohort were included in the study. In phase I, a postal questionnaire was mailed to all those with a known address in 1997 (N=11,540). In phase II, all subjects living in northern Finland or the Helsinki area (N=8463) were invited to a clinical examination. In phase , clinical examination participants were given a questionnaire with psychological subscales to be filled in at home and returned by mail. The data on hospital-treated psychiatric disorders were obtained from the Finnish Hospital Discharge Register. Educational level was obtained from Statistics Finland. Results: The participation rates were 76%, 71% and 61% in phases I, II and IH3 respectively. Subjects with any psychiatric disorder participated less actively than those without any psychiatric disorder in all phases, in both genders and at all educational levels. Participation was not found to vary across specific disorders. Gender or education did not explain the association of psychiatric disorders with participation. Conclusions: Owing to non-participation, the true prevalence of psychiatric disorders may be higher than the prevalence estimated from epidemiological field surveys.

This study examined the association between infant developmental milestones and educational level at 31 years of age in the Northern Finland 1966 Birth Cohort (n=12 058). Developmental data (age at standing, walking, speaking, and measures of bowel and bladder control) were gathered from children's welfare centres. Information on type of schooling at 14 years of age was reported by children and parents. School achievement at 16 years of age and educational level at 31 years were obtained from national registers. Those who reached infant developmental milestones sooner in their first year of life had significantly better (p<0.05) mean scores in teacher ratings at 16 years, and at 31 years they were more likely to have achieved a better educational level than slower developers. The adjusted odds ratios for individuals who developed more slowly to remain at a basic educational level (7 to 16y) ranged significantly from 1.1 to 1.3. The possibility of advancing from secondary to tertiary level was 1.4 times greater in faster developers than in slow developers. In conclusion, those who develop faster during their first year of life tend to attain higher levels of education in adolescence and adulthood.