Rationale and design for cognitive behavioral therapy for anxiety disorders in children with autism spectrum disorder: a study protocol of a randomized controlled trial.

BACKGROUND: Autism spectrum disorder (ASD) is found in approximately 1% of the population and includes core symptoms that affect general and social development. Beside these core symptoms, it is suggested that up to 60% of children with ASD suffer from comorbid anxiety disorders which may further affect educational, social and general development as well as quality of life. The main goal of this study is to examine the effectiveness of a manualized cognitive behavioral therapy (CBT) anxiety program adapted for children with ASD. METHODS: This study is a randomized controlled trial (RCT). Fifty children with ASD and anxiety, aged 7 to 13 years, will be randomly assigned to group CBT or a wait-list control (WL) condition. The design will follow a two (CBT and WL) by two (pre-post assessment) mixed between-within design. The control group will receive intervention after the waitlist period of 13 weeks. Primary outcomes are diagnostic status and severity of the anxiety disorders, measured with The Anxiety Disorder Interview Schedule for DSM-IV, Parent and Child Versions. Secondary outcomes are parent and child ratings on questionnaires on the child's level of anxiety and impact on everyday life. Additional outcomes entail information gathered from parents, child and teachers on the child's behavior and negative self-statements, together with social and adaptive skills. Follow-up data will be collected 3 months after intervention. DISCUSSION: This study aims to evaluate the effectiveness of a manualized CBT program in Danish children with ASD and anxiety within a mental health clinic setting. The hypothesis is that training anxiety reduction skills will decrease anxiety in children, as well as ensure better psychosocial development for the child in general. TRIAL REGISTRATION: https://ClinicalTrials.gov ( NCT02908321 ). Registered 19th of September 2016.

Prenatal exposure to antipsychotic medication and use of primary health care system in childhood: a population-based cohort study in Denmark.

BACKGROUND: Antipsychotic (AP) medication is increasingly used for many health conditions. Prenatal exposure to AP medication has been associated with several adverse outcomes, but the findings remain inconsistent. PURPOSE: We aimed to investigate prenatal exposure to AP medication and the use of primary health care system in childhood. SUBJECTS AND METHODS: All live-born singletons in Denmark during 1997-2012 were identified in the nationwide Danish National Patient Register and followed until December 31, 2013 (n = 963,010). Information on prenatal exposure to AP medication was obtained from the Danish Register of Medicinal Product Statistics. Contacts to the general practitioner (GP) were used as a proxy for the overall health of the children. Negative binomial regression was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between prenatal exposure to AP medication and number and type of GP contacts, excluding routine well-child visits and vaccinations. The models were adjusted for sex and birth date of the child, maternal age, parity, cohabitation status, income, education, smoking status, diagnosis of substance abuse, severe psychiatric disorder, depression and epilepsy as well as the use of antiepileptic drugs, antidepressants, benzodiazepines and insulin. RESULTS: The prenatally AP-exposed children had 7% more GP contacts than unexposed children, IRR: 1.07 (95% CI: 1.03, 1.11). The association was slightly stronger among children of mothers with no diagnosis of severe psychiatric disorder (IRR: 1.08, 95% CI: 1.04-1.13) than among children of mothers with severe psychiatric disorder (IRR: 1.03, 95% CI: 0.96-1.11), but the difference was not statistically significant. We found no difference between prenatally AP-exposed children and their unexposed siblings, IRR: 1.00 (95% CI: 0.97-1.04) for total contacts. CONCLUSION: Children of women using AP medication in pregnancy had more GP contacts in childhood than children of mothers not using AP medication. However, this might be explained by confounding from maternal behavior and mental illness.

Off-label prescribing of psychotropic drugs in a Danish child and adolescent psychiatric outpatient clinic.

This study aimed to describe the level of off-label treatment with psychotropic drugs at a child and adolescent psychiatric outpatient clinic in Denmark. We performed a cross-sectional study assessing records on patients treated with medicine at two outpatient clinics at the child and adolescent psychiatric ward, on 1 day in 2014. Prescriptions of drugs from ATC group N05-N06 were classified according to label status. Six hundred and fifteen drug prescriptions distributed on nine different drugs were prescribed to 503 children eligible for this study. Overall results showed that 170 of the 615 prescriptions were off-label, which corresponds to 27.6 %. Attention deficit hyperkinetic disorder (ADHD) drugs were prescribed 450 times (73.2 %) of which 11 prescriptions were off-label (2.4 %). Other psychotropic drugs comprised 165 (26.8 %) prescriptions and of these 159 (96.4 %) were off-label. With 106 prescriptions, melatonin was the most prescribed of these drugs; all prescriptions were off-label. The main reasons for classifying prescriptions as off-label were age and indication of treatment. This cross-sectional study reveals that medical treatment of children with other psychotropic drugs than ADHD drugs is usually off-label. ADHD drugs were, as the only drug group, primarily prescribed on-label. Although off-label prescription may be rational and even evidence based, the responsibility in case of, e.g. adverse drug reactions is a challenge, and clinical trials in children should be incited.

Apgar-score in children prenatally exposed to antiepileptic drugs: a population-based cohort study.

OBJECTIVES: It is unknown if prenatal exposure to antiepileptic drugs (AEDs) increases the risk of low Apgar score in offspring. SETTING: Population-based study using health registers in Denmark. PARTICIPANTS: We identified all 677 021 singletons born in Denmark from 1997 to 2008 and linked the Apgar score from the Medical Birth Register with information on the women's prescriptions for AEDs during pregnancy from the Danish Register of Medicinal Product Statistics. We used the Danish National Hospital Registry to identify mothers diagnosed with epilepsy before birth of the child. Results were adjusted for smoking and maternal age. RESULTS: Among 2906 children exposed to AEDs, 55 (1.9%) were born with an Apgar score ≤7 as compared with 8797 (1.3%) children among 674 115 pregnancies unexposed to AEDs (adjusted relative risk (aRR)=1.41 (95% CI 1.07 to 1.85). When analyses were restricted to the 2215 children born of mothers with epilepsy, the aRR of having a low Apgar score associated with AED exposure was 1.34 (95% CI 0.90 to 2.01) When assessing individual AEDs, we found increased, unadjusted RR for exposure to carbamazepine (RR=1.86 (95% CI 1.01 to 3.42)), valproic acid (RR=1.85 (95% CI 1.04 to 3.30)) and topiramate (RR=2.97 (95% CI 1.26 to 7.01)) when compared to unexposed children. CONCLUSIONS: Prenatal exposure to AEDs was associated with increased risk of being born with a low Apgar score, but the absolute risk of a low Apgar score was <2%. Risk associated with individual AEDs indicate that the increased risk is not a class effect, but that there may be particularly high risks of a low Apgar score associated with certain AEDs.

Risk of Fetal Death after Treatment with Antipsychotic Medications during Pregnancy.

BACKGROUND: Antipsychotic medications are increasingly used during pregnancy. Nevertheless, fetal risks are still not fully studied. It is currently unclear whether the antipsychotic treatment might induce a higher risk of fetal death. We aimed to determine if use of antipsychotic medication during pregnancy is associated with an increased risk of spontaneous abortion or stillbirth. METHODS: In a historical cohort study, we identified all clinically recognized pregnancies registered in the nationwide Danish registries from 1997 to 2008 (N = 1,005,319). Exposure was defined as any prescription of antipsychotic medications redeemed by the pregnant women during the exposure window, and recorded in the Danish National Prescription Register. Outcome was defined as any spontaneous abortion or stillbirth recorded in the Danish National Hospital Register and the Danish Medical Birth Register respectively. RESULTS: Women exposed to antipsychotic medications during pregnancy had a 34% higher risk of spontaneous abortion (adjusted relative risk = 1.34; 95% confidence interval = 1.22; 1.46) compared to unexposed women, but a similar risk compared to women exposed prior to (but not during) pregnancy (adjusted relative risk = 1.04; 95% confidence interval = 0.93; 1.17). The risk of spontaneous abortion was not increased in exposed pregnancies when compared to unexposed pregnancies in the same women (adjusted hazard ratio = 1.11; 95% CI = 0.94; 1.31). A twofold higher risk of stillbirth was found in women exposed to antipsychotic medications compared with unexposed women (relative risk = 2.27; 95% confidence interval = 1.45; 3.55) and compared with women exposed only prior to pregnancy (relative risk = 2.06; 95% confidence interval = 1.01; 4.19). CONCLUSIONS: The increased risk of spontaneous abortion found in women treated with antipsychotic medications during pregnancy is most likely due to confounding factors. The risk of stillbirth was twofold higher in pregnancies exposed to antipsychotic medication during pregnancy. Treatment with antipsychotic medications during pregnancy requires careful consideration.

Adverse pregnancy outcomes after exposure to methylphenidate or atomoxetine during pregnancy.

OBJECTIVE: To determine if prenatal exposure to methylphenidate (MPH) or atomoxetine (ATX) increases the risk of adverse pregnancy outcomes in women with attention deficit/hyperactivity disorder (ADHD). MATERIALS AND METHODS: This was a population-based cohort study of all pregnancies in Denmark from 1997 to 2008. Information on use of ADHD medication, ADHD diagnosis, and pregnancy outcomes was obtained from nationwide registers. RESULTS: We identified 989,932 pregnancies, in which 186 (0.02%) women used MPH/ATX and 275 (0.03%) women had been diagnosed with ADHD but who did not take MPH/ATX. Our reference pregnancies had no exposure to MPH/ATX and no ADHD diagnosis. Exposure to MPH/ATX was associated with an increased risk of spontaneous abortion (SA; ie, death of an embryo or fetus in the first 22 weeks of gestation) (adjusted relative risk [aRR] 1.55, 95% confidence interval [CI] 1.03-2.36). The risk of SA was also increased in pregnancies where the mother had ADHD but did not use MPH/ATX (aRR 1.56, 95% CI 1.11-2.20). The aRR of Apgar scores <10 was increased among exposed women (aRR 2.06, 95% CI 1.11-3.82) but not among unexposed women with ADHD (aRR 0.99, 95% CI 0.48-2.05). CONCLUSION: MPH/ATX was associated with a higher risk of SA, but our study indicated that it may at least partly be explained by confounding by indication. Treatment with MPH/ATX was however associated with low Apgar scores <10, an association not found among women with ADHD who did not use MPH/ATX.

Birth outcomes after prenatal exposure to antiepileptic drugs--a population-based study.

OBJECTIVE: We studied the potential impact of antiepileptic drugs (AEDs) on fetal growth and gestational age at birth. METHODS: In the Danish Medical Birth Registry, we identified all pregnancies with birth outcomes from 1997 to 2008 and linked with data from the Danish National Prescription Register. We used binomial regression to study preterm birth (<37 weeks), low birth weight (<2,500 g), and small for gestational age (SGA), adjusted for potential confounding factors including maternal age, smoking, substance abuse, cohabitation, income, education, and parity. RESULTS: We identified 679,762 singletons, and 2,928 (0.4%) of these had been exposed to AEDs. Exposure to AEDs was associated with a risk of preterm birth (adjusted risk ratio (aRR) 1.32; 95% confidence interval [CI] 1.16-1.50) when compared to unexposed children. However, when stratifying on maternal epilepsy, there was no association between AED exposure and preterm birth in offspring of women with epilepsy (aRR 1.00; 95% CI 0.82-1.21), whereas there was a risk associated with AED exposure in offspring of women without epilepsy (aRR 1.56; 95% CI 1.27-1.92). AED exposure was associated with a risk of being born with low birth weight (aRR 1.40; 95% CI 1.22-1.60) both for children born of women with epilepsy (aRR 1.32; 95% CI 1.06-1.63) and children born of women without epilepsy (aRR 1.61; 95% CI 1.28-2.02). The risk of being born SGA associated with AED exposure (aRR 1.21; 95% CI 1.10-1.34) was found both in offspring of women with epilepsy (aRR 1.19; 95% CI 1.02-1.37) and without epilepsy (aRR 1.21; 95% CI 1.01-1.45). SIGNIFICANCE: Prenatal AED exposure was associated with low birth weight and risk of being born SGA, but only with preterm birth among women without epilepsy.

Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study.

OBJECTIVE: To determine whether use of antiepileptic drugs during pregnancy may increase the risk of spontaneous abortion or stillbirth. DESIGN: Population based cohort study. SETTING: Register based study in Denmark, 1997-2008. PARTICIPANTS: 983,305 pregnancies identified in the Danish medical birth register and the Danish national hospital discharge register from 1 February 1997 to 31 December 2008 were linked to the Danish Register of Medicinal Product Statistics to obtain information on use of antiepileptic drugs. MAIN OUTCOME MEASURES: Risk ratio of spontaneous abortion and stillbirth after use of antiepileptic drugs during pregnancy, estimated by using binomial regression adjusting for potential confounders of maternal age, cohabitation, income, education, history of severe mental disorder, and history of drug misuse. RESULTS: Antiepileptic drugs were used in a total of 4700 (0.5%) pregnancies. 16 out of 100 pregnant women using antiepileptics and 13 out of 100 pregnant women not using antiepileptics experienced a spontaneous abortion. After adjusting for potential confounders pregnant women using antiepileptics had a 13% higher risk of spontaneous abortions than pregnant women not using antiepileptics (adjusted risk ratio 1.13, 95% confidence interval 1.04 to 1.24). However, the risk of spontaneous abortion was not increased in women with an epilepsy diagnosis (0.98, 0.87 to 1.09), only in women without a diagnosis of epilepsy (1.30, 1.14 to 1.49). In an analysis including women with at least two pregnancies with discordant antiepileptic drug use (for example, use in the first pregnancy but not in the second), the adjusted hazard ratio for spontaneous abortion was 0.83 (0.69 to 1.00) for exposed pregnancies compared with unexposed pregnancies. Stillbirth was identified in 18 women who used antiepileptic drugs (unadjusted risk ratio 1.29, 0.80 to 2.10). CONCLUSION: Among women with epilepsy and when analysing the risk in antiepileptic drug discordant pregnancies in the same woman, we found no overall association between the use of antiepileptic drugs during pregnancy and spontaneous abortions. Therefore unmeasured confounding may explain the slight increased risk for spontaneous abortion with any antiepileptic drug use (among women both with and without epilepsy). We found no association between antiepileptic drug use during pregnancy and stillbirth, but the statistical precision was low.

Antidepressant exposure in pregnancy and risk of autism spectrum disorders.

BACKGROUND: Both the use of antidepressant medication during pregnancy and the prevalence of autism spectrum disorder have increased during recent years. A causal link has recently been suggested, but the association may be confounded by the underlying indication for antidepressant use. We investigated the association between maternal use of antidepressant medication in pregnancy and autism, controlling for potential confounding factors. METHODS: We identified all children born alive in Denmark 1996-2006 (n=668,468) and their parents in the Danish Civil Registration System. We obtained information on the mother's prescriptions filled during pregnancy from the Danish National Prescription Registry, and on diagnoses of autism spectrum disorders in the children and diagnoses of psychiatric disorders in the parents from the Danish Psychiatric Central Register. In a cohort analysis, we estimated hazard ratios of autism spectrum disorders in children exposed to antidepressant medication during pregnancy compared with children who were not exposed, using Cox proportional hazards regression analysis. Furthermore, we estimated the risk for autism spectrum disorder in a sibling design. RESULTS: Children exposed prenatally to antidepressants had an adjusted hazard ratio of 1.5 (95% confidence interval [CI] 1.2-1.9) for autism spectrum disorder compared with unexposed children. Restricting the analysis to children of women with a diagnosis of affective disorder, the adjusted hazard ratio was 1.2 (95% CI 0.7-2.1), and the risk was further reduced when exposed children were compared with their unexposed siblings (adjusted hazard ratio 1.1; 95% CI 0.5-2.3). CONCLUSION: After controlling for important confounding factors, there was no significant association between prenatal exposure to antidepressant medication and autism spectrum disorders in the offspring.

Prenatal antidepressant exposure and risk of spontaneous abortion - a population-based study.

PURPOSE: To estimate the risk of spontaneous abortion after use of antidepressant medication during pregnancy. METHODS: From the Danish Medical Birth Registry and the Danish National Hospital Registry, we identified all pregnancies leading to in- or outpatient contacts in Denmark from February 1997 to December 2008. The Danish Registry of Medicinal Product Statistics provided information on the women's prescriptions for antidepressants during pregnancy. We obtained information on women who were diagnosed with depression from the Danish Psychiatric Central Registry. Adjusted relative risks (aRR) of spontaneous abortion were estimated according to exposure to antidepressants or maternal depression using binomial regression. RESULTS: Of the 1,005,319 pregnancies (547,300 women) identified, 114,721 (11.4%) ended in a spontaneous abortion. We identified 22,061 pregnancies exposed to antidepressants and 1,843 with a diagnosis of depression with no antidepressant use, of which 2,637 (12.0%) and 205 (11.1%) ended in a spontaneous abortion, respectively. Antidepressant exposure was associated with an aRR of 1.14 (95% confidence interval (CI) 1.10-1.18) for spontaneous abortion compared with no exposure to antidepressants. Among women with a diagnosis of depression, the aRR for spontaneous abortion after any antidepressant exposure was 1.00 (95% CI 0.80-1.24). No individual selective serotonin reuptake inhibitor (SSRI) was associated with spontaneous abortions. In unadjusted analyses, we found that mirtazapine, venlafaxine, and duloxetine were associated with spontaneous abortions among women with depression but we had no information on potential differences in disease severity and only few pregnancies were exposed in the population. CONCLUSION: We identified a slightly increased risk of spontaneous abortion associated with the use of antidepressants during pregnancy. However, among women with a diagnosis of depression, antidepressants in general or individual SSRI in particular were not associated with spontaneous abortions. Further studies are warranted on the newer non-SSRI antidepressants, as we had insufficient data to adjust for important confounding factors.

Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism.

IMPORTANCE: Valproate is used for the treatment of epilepsy and other neuropsychological disorders and may be the only treatment option for women of childbearing potential. However, prenatal exposure to valproate may increase the risk of autism. OBJECTIVE: To determine whether prenatal exposure to valproate is associated with an increased risk of autism in offspring. DESIGN, SETTING, AND PARTICIPANTS: Population-based study of all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). We analyzed the risks associated with all autism spectrum disorders as well as childhood autism. Data were analyzed by Cox regression adjusting for potential confounders (maternal age at conception, paternal age at conception, parental psychiatric history, gestational age, birth weight, sex, congenital malformations, and parity). Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first. MAIN OUTCOMES AND MEASURES: Absolute risk (cumulative incidence) and the hazard ratio (HR) of autism spectrum disorder and childhood autism in children after exposure to valproate in pregnancy. RESULTS: Of 655,615 children born from 1996 through 2006, 5437 were identified with autism spectrum disorder, including 2067 with childhood autism. The mean age of the children at end of follow-up was 8.84 years (range, 4-14; median, 8.85). The estimated absolute risk after 14 years of follow-up was 1.53% (95% CI, 1.47%-1.58%) for autism spectrum disorder and 0.48% (95% CI, 0.46%-0.51%) for childhood autism. Overall, the 508 children exposed to valproate had an absolute risk of 4.42% (95% CI, 2.59%-7.46%) for autism spectrum disorder (adjusted HR, 2.9 [95% CI, 1.7-4.9]) and an absolute risk of 2.50% (95% CI, 1.30%-4.81%) for childhood autism (adjusted HR, 5.2 [95% CI, 2.7-10.0]). When restricting the cohort to the 6584 children born to women with epilepsy, the absolute risk of autism spectrum disorder among 432 children exposed to valproate was 4.15% (95% CI, 2.20%-7.81%) (adjusted HR, 1.7 [95% CI, 0.9-3.2]), and the absolute risk of childhood autism was 2.95% (95% CI, 1.42%-6.11%) (adjusted HR, 2.9 [95% CI, 1.4-6.0]) vs 2.44% (95% CI, 1.88%-3.16%) for autism spectrum disorder and 1.02% (95% CI, 0.70%-1.49%) for childhood autism among 6152 children not exposed to valproate. CONCLUSIONS AND RELEVANCE: Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy. For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control.

Risk of substance use disorders following prenatal or postnatal exposure to bereavement.

INTRODUCTION: Substance use disorder (SUD) is associated with major socioeconomic consequences but its etiology is only partly known. The disease predisposition may be established early in life and prenatal stress may play a role. We aimed to examine whether prenatal maternal bereavement, as the indicator of prenatal stress, was associated with an increased risk of SUD in offspring. METHODS: This population-based cohort study included all children born in Denmark (N=1686416) and Sweden (N=2563659) from 1973 to 1997. The exposure was maternal bereavement by the death of a close relative 1 year before or during pregnancy. Children were followed from 10 years of age until their death, migration, onset of substance abuse, or December 31st, 2007. The main outcome is hospitalization due to substance use disorder (SUD). RESULTS: A total of 100363 children (2.45%) were born to mothers who had experienced bereavement 1 year before or during pregnancy. Overall, these exposed children had a similar risk of hospitalization due to SUD (IRR=1.02, 95% CI: 0.98-1.07), compared to unexposed children. Children born to mothers who lost a spouse during pregnancy had a two-fold risk (IRR=2.19, 95% CI: 1.74-2.76) and similar elevated risks were observed in children whose mothers lost a spouse during the first 10 years after child birth. CONCLUSIONS: Our data do not support a programming role of prenatal stress following maternal bereavement on SUD later in life. The increased risk in relation to spousal bereavement may mostly be explained by postpartum changes in familial environment.

Is OPTAx useful for monitoring the effect of stimulants on hyperactivity and inattention? A brief report.

PURPOSE: The purpose of this study was to investigate whether OPTAx, an objective measurement of hyperactivity, impulsivity and inattention can be used to measure the positive clinical effect of stimulants found in children with hyperkinetic disorder (HKD) or attention deficit disorder without hyperactivity. METHOD: A total of 22 boys and one girl, with ages ranging between 7-12 years, diagnosed with HKD or attention deficit disorder without hyperactivity and receiving treatment with stimulants were tested with OPTAx, with and without stimulants. The main parameters investigated were: displacement, area, accuracy, variability, errors of commission and errors of omission. RESULTS: OPTAx showed a significant improvement on all parameters during stimulant treatment compared with no treatment. The improvement measured by OPTAx was supported by clinical assessment, which found that 95% of the children improved much or very much on the Clinical Global Assessment Scale during stimulant treatment. CONCLUSIONS: The objective parameters of the OPTAx reflected the clinical improvement found in children with HKD or attention deficit disorder without hyperactivity during stimulant treatment. This suggests a greater role for objective measurements such as OPTAx in daily clinical practise.

Parent and child acceptability and staff evaluation of K-SADS-PL: a pilot study.

BACKGROUND: Standardised diagnostic interviews are used increasingly in child and adolescent psychiatry; yet little is known about the attitudes towards such interviews among parents, children and staff members. In this study, we have aimed to assess (1) the K-SADS-PL's acceptability to parents and children (2) the usefulness of the interview as perceived by the staff. METHODS: Following the implementation of a semi-structured diagnostic interview in the standard assessment, parents, children, and staff were asked to fill in, anonymously, a brief questionnaire enquiring about their impression of the interview. RESULTS: Parental satisfaction with the parent interview was very high. Parental satisfaction with the child interview was high as well, although a small group of children were reported to be more sad/hyperactive or difficult immediately after the interview. However, these were found among the younger children only, and mainly children with conduct problems. Most children found that the interview was a good or fairly good way to talk about how they felt, but more than half the children found the interview boring to some extent, and a few felt worse after the interview than they did before. The staff found the interview to be useful in most cases, primarily for diagnostic purposes. CONCLUSIONS: Semi-structured diagnostic interviews are well accepted by parents and children, and have good face validity among staff members. To young children with many conduct difficulties the interview may seem overwhelming, and future work should focus on ways of making diagnostic interviews more engaging for children.

[Evidence for psychopharmacological treatment of depression in children and adolescents?]. / Hvilken evidens er der for medikamentel behandling af depression hos børn og unge?

Depression in children and adolescents is relatively prevalent and may have serious consequences. Treatment of depressive disorders may be psychotherapeutic or psychopharmacological. A systematic literature search was performed and the evidence for a psychopharmacological treatment of depressive disorders in children and adolescents was described. Emphasis is put on treatment with selective serotonin reuptake inhibitors as these are the best-documented agents in the treatment of depression in children and adolescents.

[What evidence is there for treating depression in children and adolescents with cognitive therapy?]. / Hvilken evidens er der for behandling af depression hos børn og unge med kognitiv terapi?

Depression in children and adolescents is relatively prevalent and may have serious consequences. Treatment of depressive disorders may be psychotherapeutic or psychopharmacological. A systematic literature search was performed, and the evidence for treatment of depressive disorders in children and adolescents with cognitive behavioural therapy is described.

ICD-10 classification in Danish child and adolescent psychiatry--have diagnoses changed after the introduction of ICD-10?

The aim was to test this in a nationwide register study of diagnoses used in child and adolescents psychiatry in Denmark. A larger number of different diagnoses were expected to be applied after the introduction of the 10th version of the International Classification of Diseases (ICD-10). Reflecting the time trend, we particularly expected an increase in the number of neuropsychiatric diagnoses. From the Danish Psychiatric Central Register data were drawn on clinical discharge diagnoses. All patients aged 0-15 years examined at psychiatric hospitals from 1995-2002 were included; 22,469 children and adolescents with a first contact were registered. The most frequent discharge diagnoses were pervasive development disorders (PDD; 11.9%), adjustment disorders (10.6%), conduct disorder (9.5%), emotional and anxiety disorders (7.6%), hyperkinetic disorders (7.3%), and specific developmental disorders (7.3%). We found a significant increase in the number of neuropsychiatric and affective diagnoses and a significant decrease in the number of adjustment, conduct and anxiety diagnoses during the study period. Of the 22,469 diagnoses, 45% were only partly specified according to ICD-10. Thirty-four per cent had diagnoses unspecified on the four-character level (Fxx.9) and 11% had Z-diagnoses. A larger number of different diagnoses and an increase in the use of neuropsychiatric diagnoses were seen after the introduction of ICD-10. Many diagnoses were only partly specified; consequently, a more detailed specification of the ICD-10 is still required.

Internalizing disorders in child psychiatric patients across time: diagnoses and causes for referral.

With regard to internalizing disorders we wanted to describe: 1) a possible change in diagnoses over time; 2) a possible corresponding change in causes for referral; 3) correspondence of hospital diagnosis with causes for referral. For 70 randomly selected records/year (n=560), referral papers were examined and compared with register-data on all 8-13-year-old children examined in the study period (1995-2002). The hospital-based frequency increased for depressive disorders and obsessive-compulsive disorder (OCD) and decreased for anxiety disorders. A corresponding increase occurred for depressive and OCD symptoms as cause for referral. Agreement between referral causes and subsequent clinical diagnoses was modest. In most cases (68%) referred for internalizing symptoms, a clinical diagnosis within the internalizing spectrum was given. The increase in the diagnoses of depressive disorder and OCD seems partly due to an increase in patients referred for these disorders. Referrers identify internalizing disorders reliably but child psychiatric examination leads to more precise diagnoses.

[Depression in children and adolescents]. / Depression hos børn og unge.

This article reviews the recent literature on depression in children and adolescents. We describe the current knowledge about clinical presentation, epidemiology, prognosis and risk factors with a focus on the differences from depression in adults.

The Children's Depression Inventory and classification of major depressive disorder: validity and reliability of the Danish version.

The study examines the validity and reliability of the Danish version of the Children's Depression Inventory (CDI) in a child psychiatric population. Participants were 149 child psychiatric patients aged 8-13 and their parents. After diagnostic interview with the Kiddie-Schedule for Affective Disorders and Schizophrenia, the children completed the CDI. A subgroup of 44 children repeated the CDI after 2 weeks. The psychometric properties of the Danish CDI were similar to those reported for the English version. CDI is moderately correlated with other measures for depressive disorder, but the instrument is not sufficiently reliable or valid to be used as a single diagnostic or screening measure in a child psychiatric population.