Signe Olrik Wallenstein Jensen

The heterogeneity of the depressive syndrome: when numbers get serious.

The current criteria for major depression (1) have been criticized for the heterogeneity of the clinical syndrome they define. This has led to suggestions of alternative classifications, most recently by G. Parker in this journal (2). According to the critics, the polymorphic syndrome is partly to blame for the fact that the treatment of depression still has not moved beyond the trial and error approach and that the genetics and neurobiology underlying the depressive disorder still remain largely unknown and without practical significance (3). Two of the most interesting studies on major depression, conducted within recent years, reflect this problem:

Increasing mortality gap for patients diagnosed with schizophrenia over the last three decades — A Danish nationwide study from 1980 to 2010

OBJECTIVE The objective of this study is to describe secular trends in the average age of death in patients with schizophrenia and to compare these with the general population. METHODS This is a longitudinal linkage study from 1 January 1980 to 31 December 2010 using the Danish Psychiatric Research Register and the Danish Cause of Death Register. Data were analyzed using descriptive statistics and survival analysis. RESULTS The average age of death in the schizophrenia population (62.2 years; 95% CI, 61.9-62.5) was lower compared to the general population (73.4 years; 95% CI, 73.4-73.4), P<0.001. In the general population we found, for men, an average increase in the age of death of 0.28 years (95% CI, 0.27-0.28) per calendar year, and for women an increase in age of death of 0.31 years (95% CI, 0.31-0.32) per calendar year (both P<0.001). In contrast, age of death decreased in the schizophrenia population: the change in average age of death for males was 0.04 years (95% CI, -0.09 to 0.00) per calendar year (P<0.05), and the comparable estimate for females was -0.05 years (95% CI, -0.09 to 0.01) per calendar year (P<0.05). A similar pattern existed after acts of self-harm as cause of death were excluded from the analyses. Patients diagnosed with schizophrenia had an increased mortality rate compared with the general population (hazard ratio, 2.05; 95% CI, 2.01-2.09). CONCLUSIONS On average, patients with schizophrenia die younger than the general population, independent of intentional self-harm as cause of death.

Second‐generation antipsychotic effect on cognition in patients with schizophrenia—a meta‐analysis of randomized clinical trials

To investigate the effect of second‐generation antipsychotics on cognitive function in patients diagnosed with schizophrenia or schizoaffective disorder.

Changes in the diagnosed incidence of early onset schizophrenia over four decades

Objective: To explore changes in the diagnosed incidence of early onset schizophrenia (EOS) from 1971 to 2010.

Risk factors for conversion from unipolar psychotic depression to bipolar disorder

Patients with unipolar psychotic depression (PD) are at high risk of developing bipolar disorder (BD). This conversion has important implications for the choice of treatment. This study, therefore, aimed to identify risk factors associated with diagnostic conversion from PD to BD.

Comparative Effectiveness of Risperidone Long-Acting Injectable vs First-Generation Antipsychotic Long-Acting Injectables in Schizophrenia: Results From a Nationwide, Retrospective Inception Cohort Study

OBJECTIVE To compare in a generalizable sample/setting objective outcomes in patients receiving first-generation antipsychotic long-acting injectables (FGA-LAIs) or risperidone-LAI (RIS-LAI). METHODS Nationwide, retrospective inception cohort study of adults with International Classification of Diseases-10 schizophrenia using Danish registers from 1995 to 2009 comparing outcomes between clinicians/patients choice treatment with FGA-LAIs or RIS-LAI. Primary outcome was time to psychiatric hospitalization using Cox-regression adjusting for relevant covariates. Secondary outcomes included time to all-cause discontinuation and psychiatric hospitalization in patients without LAI possession gap >28 days, and number of bed-days after psychiatric hospitalization. RESULTS Among 4532 patients followed for 2700 patient-years, 2078 received RIS-LAI and 2454 received FGA-LAIs (zuclopenthixol decanoate = 52.2%, perphenazine decanoate = 37.2%, haloperidol decanoate = 5.0%, flupenthixol decanoate = 4.4%, fluphenazine decanoate = 1.3%). RIS-LAI was similar to FGA-LAIs regarding time to hospitalization (RIS-LAI = 246.2±323.7 days vs FGA-LAIs = 276.6±383.3 days; HR = 0.95, 95% confidence interval (CI) = 0.87-1.03, P = 0.199) and time to all-cause discontinuation (RIS-LAI = 245.8±324.0 days vs FGA-LAIs = 287.0±390.9 days; HR = 0.93, 95% CI = 0.86-1.02, P = 0.116). Similarly, in patients without LAI discontinuation, RIS-LAI and FGA-LAIs did not differ regarding time to hospitalization (RIS-LAI = 175.0±268.1 days vs FGA-LAIs = 210.7±325.3 days; HR = 0.95, 95% CI = 0.86-1.04, P = 0.254). Finally, duration of hospitalization was also similar (incidence rate ratio = 0.97, 95% CI = 0.78-1.19, P = 0.744). Results were unchanged when analyzing only patients treated after introduction of RIS-LAI. CONCLUSIONS In this nationwide cohort study, RIS-LAI was not superior to FGA-LAIs regarding time to psychiatric hospitalization, all-cause discontinuation, and duration of hospitalization. Given the cost of hospitalization and second-generation antipsychotic (SGA)-LAIs, these findings require consideration when making treatment choices, but also need to be balanced with the individual relevance of adverse effects/patient centered outcomes. In future, head-to-head trials and additional nationwide database studies including other SGA-LAIs is needed.

Cognitive Profile of Children and Adolescents with Anorexia Nervosa

Objective Few studies of cognitive functioning in children and adolescents with anorexia nervosa (AN) have been conducted. The aim of this study was to examine the neurocognitive and intelligence profile of this clinical group. Method The study was a matched case–control (N = 188), multi-centre study including children and adolescents with AN (N = 94) and healthy control participants (N = 94). Results The results suggest that Full Scale Intelligence Quotient (Wechsler Intelligence Scale for Children-III/Wechsler Adult Intelligence Scale-III) in this patient group is close to the normal population mean of 100. Individuals with AN exhibited significantly worse performance in nonverbal intelligence functions (i.e. Wechsler Intelligence Scale for Children-III/Wechsler Adult Intelligence Scale-III, Perceptual Organization Index) and in verbal memory (Test of Memory and Learning—Second Edition, Memory for Stories) and motor speed (Cambridge Neuropsychological Test Automated Battery, Simple and Choice Reaction Time) compared with healthy control participants. No significant difference in set-shifting ability (Cambridge Neuropsychological Test Automated Battery, Intra-Extra Dimensional Set Shift and Trail Making Test B) was found. Conclusions Inefficiency in nonverbal intelligence functions and in specific cognitive functions was found in this study of children and adolescents with AN.

Schizophrenia, antipsychotics and risk of hip fracture: A population-based analysis

In a nationwide study using linkage of Danish hospital registers we examined predictors of hip fracture (ICD-10: S72) in 15,431 patients with schizophrenia (ICD-10: F20 or ICD-8: 295) and 3,807,597 population controls. Shorter education, disability pension, lifetime alcohol abuse, somatic co-morbidity, antipsychotics (IRR=1.19; 95% CI 1.15-1.24), antidepressant (IRR=1.18; 95% CI 1.16-1.20), anticholinergics (IRR=1.29; 95% CI 1.22-1.36), benzodiazepines (IRR=1.06; 95% CI 1.04-1.08) and corticosteroids (IRR=1.44; 95% CI 1.36-1.53) were significant predictors. In 556 persons with schizophrenia and hip fracture (matched to 1:3 to schizophrenia controls without hip fracture), antipsychotic polypharmacy predicted hip fracture. Analyses among antipsychotic monotherapy patients showed no differential effect of individual antipsychotics. A dose-response relationship of hip fracture and lifetime antipsychotics consumption was found (IRR=1.13 95% CI 1.07-1.19) and both prolactin-increasing and non-prolactin-increasing antipsychotics contributed to the effect. In conclusion, several factors, including complex psychopharmacological treatment, contribute in the prediction of hip fracture in large populations. Preventive strategies should focus attention to severely ill patients with high likelihood of a receiving complex psychopharmacologic treatment and high doses of antipsychotics.

Neuroleptic malignant syndrome-an 11-year longitudinal case-control study.

Objective: To describe patients with neuroleptic malignant syndrome (NMS), to establish occurrence of NMS, to investigate risk factors of NMS, and to investigate mortality associated with NMS. Method: We conducted a longitudinal register linkage case-control study of NMS. Result: In health care registers covering the period from 1996 to 2007, we identified, among 224 372 patients with organic, psychotic, affective, or neurotic diagnosis, 83 patients with NMS, equivalent to an occurrence of 0.04%. Treatment with second-generation antipsychotics (SGAs) in the 3 months preceding admission increased the NMS risk (OR 4.66; 95% CI 1.96 to 11.10) and also first-generation antipsychotics (FGAs) of high potency (OR 23.41; 95% CI 5.29 to 103.61) and mid potency (OR 4.81; 95% CI 1.96 to 11.79), and depot antipsychotics (OR 4.53; 95% CI 1.60 to 12.80). Benzodiazepines (BDZs) also increased the risk of NMS (OR 3.43; 95% CI 1.68 to 12.80). NMS was associated with an increased mortality (HR 1.88; 95% CI 1.19 to 2.98) in patients, compared with sex-, age-, and diagnosis-matched control subjects, but no significant difference in mortality between patients and control subjects was observed after the initial 30 days (P = 0.27). Conclusions: The occurrence of NMS is low, and the prediction of NMS is difficult. Previous treatment with FGAs, SGAs, and BDZs was identified as a risk factor for developing NMS. NMS increased mortality within 30 days after NMS.

Increasing number of incident ADHD cases in psychiatric treatment

During the last decade, the awareness has grown that ADHD (Attention Deficit Hyperactivity Disorder) is a disorder not only in children and adolescents but also in adults. Psychiatrists are becoming more aware of adults with ADHD symptoms, particularly in parents of children with an ADHD diagnosis. Apparently, some of the symptoms persist and lead to psychosocial difficulties and disabilities in adulthood. Studies indicate that at least 2% of the adult population suffer from ADHD compared with 5–7.7% of the children, however, with a wide range (1). The increasing professional interest in ADHD is illustrated by a rise in the number of publications on ADHD; for example, a PubMed search (20 February 2012) using the search word ADHD identified 714 titles published in 2001 and 1924 published 10 years later, in 2011. When searching for attention deficit hyperactivity , 699 and 1731 titles were identified, respectively. Increases of 169% and 148% were identified for the two search words, respectively, over the 10-year period. ADHD is a DSM-IV diagnosis. In the ICD-10, introduced in 1992 and used in Denmark since 1994, this diagnosis is grouped under F.90 (clinical diagnosis). Symptoms may vary with age and from person to person. The criteria for an ADHD diagnosis in adulthood are expected to be more precisely defined in the coming ICD-11. Adults respond positively to medical and psychosocial interventions. In both children and adults, there is a huge variability in the treatment statistics; for example, Zoëga et al. (2) investigated the use of defined daily dose (DDD) of psychopharmacological compounds registered for treatment for ADHD per population. Within the five Nordic countries, Denmark, Finland, Iceland, Norway and Sweden, a factor 5 was identified, ranging from the highest number of DDD used per population unit in Iceland to the lowest in Sweden, with a factor 7 between Finland and Iceland in young adolescents. When a new diagnosis suddenly increases in numbers, a certain pattern is seen. First, very few cases are diagnosed over a longer period of time; second, the number of registered cases increases radically, subsequently flattens, then decreases and finally reaches a somewhat lower level than the peak, with this lower level illustrating the incidence of the disorder in the population as discussed already years ago (3). Several factors influence this pattern: i) a new disease might have been identified; ii) a defined diagnosis has been created to explain a well-known syndrome (e.g. PTSD); iii) a new treatment method has been established to meet a well-known disease or symptom constellation; iv) increased attention in the healthcare system, in the population and in the media; v) intensified activity in the pharmaceutical industry to increase attention to a disease ⁄ syndrome and possibilities of medication; vi) lobbying from patient organizations and ⁄ or relative organizations; vii) lobbying from professional groups; viii) increasing political interest and other possible factors too. To illustrate the increasing number of ADHD, we made a search in the Danish Central Psychiatric Research Register (3) in which all contacts to the public secondary health service in Denmark are registered, including in-patients and out-patients. The latter included also community-based service. The secondary psychiatric health care in Denmark is all public reporting to the Danish Central Psychiatric Research Register (4) except for privately practising psychiatrists who are relatively few in numbers, approximately 150 (Denmark has 5.5 million inhabitants). There are no private psychiatric hospitals in Denmark. Incidence rates defined as first time with the ADHD diagnosis in the register were calculated for each of the years in the period 1994–2010 as the number of cases in each age stratum divided by the total population size in the corresponding age stratum. Incidence rates were age-standardized to account for possible different age distributions within the study period. We applied a standard population based on the (average) age composition in the study period. The following ICD-10 diagnostic codes were included when given as main diagnosis to inpatient, outpatient and emergency room visitors: disturbance of activity and attention (F90.0); hyperkinetic conduct disorder (F90.1); other hyperkinetic disorders (F90.8); and hyperkinetic disorder, unspecified (F90.9). New cases of ADHD in children and adolescents in psychiatric treatment were relatively stable from 1994 (when ICD-10 was introduced in Denmark) until around 2000 when the curve started going up. The first cases in adults are registered in the early years of the century, with the rates later rising steeply following the same pattern as seen in children and adolescents. The yearly increase in incidence rates for the two groups was further described by fitting exponential curves. The curves were fitted by nonlinear least squares: for the group <20 years of age: exp()396.13 + 0.1967 year); for the group ‡20 years of age: exp()777.75 + 0.3862 year). The important information