ABSTRACT
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 eff ect 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.
Subject(s)
Depressive Disorder, Major/drug therapy , Drug Monitoring/statistics & numerical data , Fluoxetine/pharmacokinetics , Fluoxetine/therapeutic use , Selective Serotonin Reuptake Inhibitors/pharmacokinetics , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adolescent , Age Factors , Child , Cohort Studies , Depressive Disorder, Major/blood , Depressive Disorder, Major/psychology , Dose-Response Relationship, Drug , Drug Monitoring/methods , Feasibility Studies , Female , Fluoxetine/adverse effects , Fluoxetine/analogs & derivatives , Fluoxetine/blood , Humans , Male , Selective Serotonin Reuptake Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/blood , Sex Characteristics , Smoking/psychology , Young AdultABSTRACT
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; 20-25mg/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. Mean levels of fluoxetine plus norfluoxetine were 287.8 ng/ml without significant level fluctuations.
Subject(s)
Bone Marrow Transplantation/psychology , Child, Hospitalized/psychology , Mutism/psychology , beta-Thalassemia/psychology , Bone Marrow Transplantation/adverse effects , Child , Cognitive Behavioral Therapy , Combined Modality Therapy , Female , Fluoxetine/therapeutic use , Humans , Mutism/drug therapy , Mutism/therapy , Selective Serotonin Reuptake Inhibitors/therapeutic use , Treatment Outcome , beta-Thalassemia/drug therapy , beta-Thalassemia/therapyABSTRACT
Tourette's syndrome (TS) is characterised by motor and vocal tics. The clinical manifestation during childhood and the frequent remission during early adulthood point to a dysregulation in the maturation of neuronal pathways. As a neurobiological correlate, the cortico-striato-thalamo-cortical circuit is the main focus of research. Two main features of a movement, the speed and direction of a movement, are controlled by the basal ganglia. Both features are dysregulated in TS.â Besides the motor symptoms, patients with TS suffer from comorbidities such as attention deficit hyperactivity syndrome, depression and obsessive compulsive disorders. Tics are modified in frequency and intensity by actions that require a high level of concentration such as reading or by distress, e.g., teasing by peers. The results of structural and functional imaging data support the hypothesis of altered signal transmission in the basal ganglia and a dysfunction in the limbic system. They also point to a complex interaction between cortical motor areas, the anterior cingulum, prefrontal regions and the basal ganglia.
Subject(s)
Tourette Syndrome/epidemiology , Tourette Syndrome/psychology , Tourette Syndrome/therapy , Animals , Comorbidity , Diagnosis, Differential , History, 19th Century , Humans , Magnetic Resonance Imaging , Nervous System/physiopathology , Neurobiology , Tics/therapy , Tourette Syndrome/diagnosis , Tourette Syndrome/historyABSTRACT
Attention-deficit/hyperactivity disorder (ADHD), the most common neurobehavioural disorder and amyotrophic lateral sclerosis (ALS), the most common adult motoneuron disease, may be two distinct entities on first sight. This paper aims to highlight parallels concerning clinical features and neurobiology. The presence of increased physical and psychological activity and largely non-progressive frontal dysfunction associated with impaired executive control and decreased attention are characteristic clinical features of both, ADHD and ALS. At the neurobiological level, there is evidence for hyperactivity in the glutamatergic system and a - potentially related - dopaminergic hypoactivity in ADHD and ALS. The clinical features of ALS resembling ADHD are particularly characteristic for the premorbid stage of the patient. Therefore, we hypothesize that clinical features of ADHD may be a risk factor for the development of ALS. This hypothesis is currently of unknown pathogenetic, but of potential future therapeutic relevance. Our hypothesis of a link between ADHD and ALS could also be considered as an example how research on neurodevelopmental diseases might influence the understanding and possibly the prevention and treatment of neurodegenerative diseases.
Subject(s)
Amyotrophic Lateral Sclerosis/physiopathology , Attention Deficit Disorder with Hyperactivity/physiopathology , Models, Neurological , Neurobiology , Neurodegenerative Diseases/physiopathology , Humans , Risk FactorsABSTRACT
Methylphenidate (MPH) is the most common used drug in child and adolescent psychiatry. Despite of this fact, however, little is known about its exact pharmacological mechanisms. Here we investigated the toxic effects of MPH in vitro in human embryonic kidney (HEK-293) cells stably expressing the human dopamine transporter (HEK-hDAT cells) and in cultured rat embryonic (E14.5) mesencephalic cultures. MPH alone (up to 1 mM) affected neither the growth of HEK-hDAT cells nor the survival of dopaminergic (DA) neurons in primary cultures after treatment up to 72 h. No differences in neuronal arborisation or in the density of synapses were detected. 1-methyl-4-phenylpyridinium (MPP(+)) showed no toxic effect in HEK-293 cells, but had significant toxic effects in HEK-hDAT cells and DA neurons. MPH (1 microM - 1 mM) dose-dependently reduced this cytotoxicity in HEK-hDAT cells and primary mesencephalic DA neurons. The presented results show that application of MPH alone does not have any toxic effect on DA cells in vitro. The neurotoxic effects of MPP(+) could be significantly reduced by co-application of MPH, an effect that is most likely explained by MPH blocking the DAT.
