Introduction Mirtazapine is a tetracyclic piperazino-azepine antidepressant with a unique mechanism of action through modulating serotonergic and noradrenergic neurotransmission. Being the second-choice medication in childhood depression, it is also used alone or as an add-on to treat insomnia, eating or other internalizing disorders. Despite its therapeutic benefits, no systematic therapeutic drug monitoring (TDM) examination of mirtazapine in children and adolescent exists.

Pharmacotherapeutic interventions are available for most psychiatric disorders in children. Evidence for these interventions varies, depending on the targeted disorders. For attention-deficit/hyperactivity disorder, a sound database on efficacy and safety of medication exists. For other common disorders or psychopathological phenomena like disruptive behavior, anxiety disorders, depressive disorders, or autism, data on efficacy and safety are much scarcer. This selective review aims to provide an overview about current psychopharmacological interventions in child and adolescent psychiatry. The literature indicates either a lower efficacy than other interventions or less beneficial effects compared to possible adverse events in these cases. Most guidelines recommend psychopharmacotherapy in children to be embedded in a psychosocial or therapeutic intervention plan. Decision for medication depends on the severity of symptoms, chronicity, and, most important, impairment of the child in academic performance, family relationships, and everyday life. The high rates of off-label use in the age group of children are often due to a lack of market authorization studies less indicative of low efficacy. As adverse events need to be monitored closely, pharmacotherapy should mainly be restricted to experienced mental health care providers.

OBJECTIVEResearch in adults has identified an association between bipolar disorder and suicidal behavior. This relationship, however, has been insufficiently investigated in adolescents to date.METHODS1,117 adolescents from 13 German schools (mean age = 14.83, SD = .63; 52.7% females) completed an extended German version of the Center for Epidemiological Studies Depression Scale (CES-D), which assesses depressive and manic symptoms during the last week, as well as the Self-Harm Behavior Questionnaire (SHBQ) for the assessment of lifetime suicidal behavior.RESULTSIn the present sample 39.4% of the girls and 23.1% of the boys reported lifetime suicidal thoughts and 7.1% of the girls as well as 3.9% of the boys a lifetime history of suicide attempts. 18.7% of the adolescent sample revealed elevated symptoms of depression and 9% elevated levels of mania symptoms. Elevated sum scores of depression and mania were associated with a higher number of suicidal ideations and suicide attempts. A block-wise regression analysis revealed that sum scores of depression and mania predicted suicidal ideations best. Concerning suicide attempts, the best predictors were age as well as depression and mania sum scores.CONCLUSIONSSuicidal behavior was reported more often when adolescents demonstrate symptoms of mania as well as symptoms of depression than when they demonstrate only depressive symptoms. The presence of bipolar symptoms in adolescents should alert clinicians to the heightened possibility of suicidal behavior.

Background: The goal of this pilot study was to examine the feasibility and clinical outcomes of a brief (6-session) group therapy programme in adolescent outpatients with depression. The programme had previously been assessed in in-patients, with positive results. Methods: A total of 15 outpatients aged 13 to 18 years took part in the programme between October 2010 and May 2011, in 3 separate groups of 4–6 participants each. The outcomes measured were feasibility of the programme, as assessed by attendance rate, user feedback, fidelity of implementation, and response to treatment, as assessed by preand post-intervention measurement of depressive symptoms, quality of life, and suicidal ideation. Results: The programme demonstrated good feasibility, with a mean attendance rate of 5.33 out of 6 sessions, a mean rating by participants on overall satisfaction with the programme of 7.21 out of 10 (SD = 1.89), and a 93% concurrence between the contents of the sessions and the contents of the treatment manual. Compared to baseline scores, depressive symptoms at follow-up test were significantly reduced, as assessed by the Children’s Depression Rating Scale Revised (F(1, 12) = 11.76, p < .01) and the Beck Depression Inventory Revision (F(1, 32) = 11.19, p < .01); quality of life improved, as assessed by the Inventory of Quality of Life (F(1, 31) = 5.27, p < .05); and suicidal ideation was reduced. No significant changes were seen on the measures of the Parent Rating Scale for Depression and the Clinical Global Impression scale. Conclusions: Based on the results of this pilot study, it is feasible to further assess this brief outpatient treatment programme in a randomized controlled trial without further modifications.

Fluoxetine is an antidepressant, a selective serotonin reuptake inhibitor (SSRI) used primarily in the treatment of major depression, panic disorder and obsessive compulsive disorder. Chiral separation of racemic fluoxetine is necessary due to its enantioselective metabolism. In order to develop a suitable method for chiral separation of fluoxetine, cyclodextrin (CD) modified capillary electrophoresis (CE) was employed. A large number of native and derivatized, neutral and ionized CD derivatives were screened to find the optimal chiral selector. As a result of this process, heptakis(2,3,6-tri-O-methyl)-β-CD (TRIMEB) was selected for enantiomeric discrimination. A factorial analysis study was performed by orthogonal experimental design in which several factors are varied at the same time to optimize the separation method. The optimized method (50 mM phosphate buffer, pH = 5.0, 10 mM TRIMEB, 15 °C, + 20 kV, 50 mbar/1 s, detection at 230 nm) was successful for baseline separation of fluoxetine enantiomers within 5 min. Our method was validated according to ICH guidelines and proved to be sensitive, linear, accurate and precise for the chiral separation of fluoxetine.

Introduction: Information about therapeutic serum levels of fluoxetine (FLX) and its major metabolite norfluoxetine (NORFLX) in children and adolescents is scarce.Methods: Therapeutic drug monitoring (TDM) of FLX was routinely performed in 71 subjects treated for a major depressive disorder (MDD) (10-60 mg/d FLX, median: 20 mg/d). Correlations between serum concentration and dosage, age, gender, smoking habits and adverse events were analysed.Results: Serum concentrations of the active moiety (FLX + NORFLX) ranged from 21 to 613 ng/mL mean concentration of 213 +/- 118 ng/mL, median: 185 ng/mL). High inter-individual variability in serum concentrations of the active moiety of FLX at each dosage level was observed and no relationship between serum concentration and clinical outcome was found. Apart from smoking, none of the factors tested had a significant effect on the serum concentration.Discussion: It was shown that serum concentrations of the active moiety of FLX in children and adolescents seem to be similar to those in adults, with a high level of inter-individual variation. The proportion of patients who showed benefits from treatment with a dose of 20 mg/d FLX was high.

Measurements to ensure high quality psychotherapy have been arranged for a long time to justify social costs caused by psychotherapy. To determine the effectiveness of psychosocial interventions, criteria of effectiveness as well as adequate methods to measure achievements during therapy need to be specified. Mostly, standardised self-ratings and ratings by others are used, which can be applied economically within the data assessment process. However individual goals which may be reached by patients as a result of interventions are insufficiently assessed by these methods. The Goal Attainment Scale (GAS) is an instrument to evaluate specific, individual goals during a psychosocial intervention. By using the standardised values and the GAS data simultaneously a comparison of individuals and various treatments can be done. This clearly indicates an advantage to solely qualitative assessments. Various therapy studies concerned with the effectiveness of psychotherapy showed GAS in combination with standardised data assessments as an effective and economic way for scientific quality control and evaluation research.

Objective: The "Forensic Operationalized Therapy/Risk Evaluation System" (FOTRES) was developed to assess risk, risk management and monitoring of treatment progress and quality in forensic services. Little is known about the psychometric properties of the instrument, in particular interrater reliability. Material and methods: 15 patients in forensic psychiatry have been rated by three independent raters based solely on the files of the penitentiary. Results: Intraclass correlation (ICC) for the main area structural risk was low (ICC = 0.23); for the area likelihood of successful treatment, the ICC was higher (ICC = 0.53). In both areas, there were subscales with good and with remarkably low agreement. Adjusting for mean differences changed the ICCs only slightly. Conclusions: Interrater reliability of the FOTRES areas that have been analysed is not consistently satisfactory. Clinical relevance: The instrument offers the possibility of categorizing the information needed in forensic psychiatry and is of clinical value, but the suggested scores should be taken with care.

Objective: Depressive symptomatology has been observed in some school shooters. Does the treatment with antidepressants, especially with selective serotonin reuptake inhibitors (SSRI), lead to activation known from the pharmacological treatment of juvenile depression? Method: Systematic literature review with additional selective references regarding the neurobiology of the serotonergic system of suicidal patients. Results:To date no studies have been published about a link between antidepressant medication and school shootings. The phenomenon of behavioural toxicity in children and adolescents has been well described. Neurobiological findings show alterations in the serotonergic system of suicidal patients, depending on whether they are employing more or less aggressive/impulsive methods of suicide. Discussion: By virtue of a paucity of data (due to school shootings being rare events) there is hardly any evidence supporting a causal relationship between medication and school shootings. Clinically relevant points: Risk patients receiving antidepressant medication should be screened for aggressive phantasy. Based on the recent literature aggressive tendencies are no contraindication for antidepressant medication but they should lead to careful monitoring of these patients.

Attention deficit hyperactivity disorder (ADHD) will be symptomatic in at least a third of the patients during adolescence and young adulthood. During childhood and early adolescence, patients often show certain clumsiness aside the typical motor hyperactivity. Therefore children, adolescents and adults with AND should be encouraged to get exercise which can meliorate motor abilities. If athletic activities shape to competitive sport, medication with psychostimulants might be problematic because they are listed as forbidden substances by the World Anti-Doping Agency. An expert certificate might lead to an exemption for the training; during competition psychostimulants invariably are forbidden. This brief review elucidates the relevance of exercise as a useful module in the AND therapy. Secondly, it points out the procedures and modalities how AND patients treated with psychostimulants are able to participate in contests.

Purpose of the Study: The availability of licensed medication for children and adolescents depends on the frequency of clinical trials within this age group. In Germany legislation the framework for clinical trials was changed essentially in 2004 by the 12th amendment on the German Drug Code (AMG). This paper studies the changes in applications to the IRBs for clinical trials in adults and minors before and after implementation of the 12th amendment.Methods: In total four IRB were included in the study. All IRB were located in one German state, all were located at universities or medical schools. Two of the universities have a clinical research unit (CRU) funded by the German Ministry of Research, one of these CRUs has additionally a unit specialised on conducting trials with minors (PadNET). All data were assessed by the applications to the IRB between 2002 and 2006 and analysed by the number of applications, inclusion criteria (with minors or without) and the funding status (investigator initiated trials=IIT or funded by industry).Results: The total number of applications was stable over the observation period (2002: 1192; 2006: 1231). The number of applications according German Drug Code showed no essential changes (2002: 484; 2006: 504). The number of applications for trials which included minors was low and remained on this low level (2002: 41; 2006: 28). Immediately before and after implementation of the amendment the number of applications increased or, respectively, decreased. IIT with minors constituted a higher proportion of all clinical trials with minors, but in total the number of IIT with minors was low.Discussion: The 12th amendment to the German Drug Code had only slight effects on the number of clinical trials in general and especially on the number of clinical trials with minors. Overall, clinical trial with minors make only a small proportion of all applications for clinical trials to the IRB in Germany. The EU regulation on medical products for children may cause an increasing number of clinical trials with minors in the future.

The prevalence of autism spectrum disorders as reported by epidemiological studies has been rising in the last years. In the USA and other countries the overall estimate of prevalence of typical autism was three per 10 000 in the 70ies and above 30 per 10 000 in the 90ies of the last century. The objective of this paper was to review results of surveys on the prevalence of autism and to discuss if methodological factors are responsible for its increase. We found that change in diagnostic criteria, better case identification, increasing awareness among parents, teachers and professionals and higher treatment rates accounts for the majority of this increase. However it remains a rest that might warrant further explanation. In conclusion a real increase in autism cannot be ruled out. Possible explanations are the increasing rate of preterm births and prenatal environmental factors, A survey on autism in Germany could contribute to define the public health burden and future care needs in this country.

Aims:Children of mentally ill parents are at high risk to develop psychiatric disorders. Psychiatric disorders often limit parenting skills and there are obstacles to accept professional help for the children. The study aimed to explore the prevalence of mentally ill parents in inpatient treatment, emotional and behavioural problems of their children, access to support for their children and obstacles for receiving support.Method:Inpatients of psychiatric hospitals of a county were examined by questionnaires (amongst other scales the Strengths and Difficulties Questionnaire (SDQ).Results:104 patients with children were detected, 81 patients with 165 children were enrolled. Most of the patients had more than one child and most of them had more than 3 prior inpatient treatments. Results in the SDQ indicated an up to fife fold increased number of children with emotional/behavioural problems compared to non-psychiatric samples. Even it 40% of the patients were dissatisfied with the care of their children during treatment, they seek seldom professional help. 51% have strong resentments against the youth welfare custodies. 55% quote that they cancelled or missed former inpatient treatments because of the inadequate nurturance of their children.Conclusion:Identification of children with need for professional support can be improved by using standardized questionnaires. Study results imply that psychiatrist should focus on parenthood of their patients and specialised offers of support are needed.

Objective:This study aimed to examine the lifetime-prevalence of suicidal ideation, suicide attempts and depressive symptoms in a community sample of non-referred German adolescents.Method:The Self Harm Behavior Questionnaire (SHBQ) and the German version of the Center for Epidemiological studies- Depression scale (CES-D) were used to assess suicidal ideation, suicide threats, suicide attempts, and depression scores in a German school sample (n=665; age range:14-17; mean age: 14.81; SD: 0.66).Results:Lifetime suicidal ideation was reported by 239 (35.94 %) students, of whom 102 had planned an attempt and 41 had already started preparations. 104 (15.64 %) students reported, that they had at least once in their lifetime threatened others to commit suicide. Actually conducted suicide attempts were reported by 43 (6.47 %) students, of whom only five reported, that they had received medical treatment after their attempt. Depression scores were elevated in adolescents reporting suicidal ideation (mean CES-D score: 21.92; p< .0001) and suicide attempts (mean CES-D score: 22.86; p< .0001).Conclusion:In accordance with international prevalence rates, suicidal ideation is a common phenomenon among adolescents. A small proportion of a school sample, with elevated levels of depressive symptomatology, reports suicide attempts. This fact highlights the need for awareness and prevention programmes within the school context.

Selective mutism is rare with a prevalence below 1% in the general population, but a higher prevalence in populations at risk (children with speech retardation, migration). Evidence for treatment strategies is hardly available. This case report provides information on the treatment of selective mutism in an 8-year-old girl with preexisting thalassaemia major. As medications she received penicillin prophylaxis (500000 IE/d) and deferasirox (Exjade: 20-25 mg/kg/d), an iron chelator. The preexisting somatic disease and treatment complicated the treatment, as there are no data about pharmacological combination therapy. Psychotherapy in day treatment, supported by the use of the SSRI fluoxetine (10 mg), led to a decrease in the selective mutism score from 33 to 12 points, GAF improved by 21 points.[GRAPHICS].Mean levels of fluoxetine plus norfluoxetine were 287.8 ng/ml without significant level fluctuations.