Current developments in the psychopharmacological treatment of childhood and adolescent bipolar disorder

Bipolar disorder (BD) of childhood and adolescence is not rare but difficult to diagnose because of its atypical presentation compared with that of adults. Similar to treatment for adults with BD, pharmacotherapy is considered as the first-line treatment for pediatric BD and usually involve the use of mood stabilizing agents such as lithium, carbamazepine, and valproate and antipsychotic agents, such as risperidone, olanzapine, and quetiapine. Sufficient data was not obtained about pharmacotherapy of BD and most of the studies to date do not have standard assessment protocols and placebo control groups. In this article we aimed to review all controlled, open, and special designed studies and to inform about their findings. According to results from published studies: 1- There are few well-designed clinical trials and systematic treatment with prospective follow-up is essential for methodology, 2- lithium and divalproex sodium appear to have comparable efficacy at the end of the trials, 3- some controlled data were obtained for safety and efficacy of quetiapine, 4- stimulants should be used cautiously but are not contraindicated

Pediatric Bipolar Disorders: From the Perspective of Turkey

Introduction: In Turkey, there is much controversy and skepticism about the existence of mania in children and adolescents, and a paucity of rigorous data. Despite ongoing controversy, the view that pediatric Bipolar Disorder(BD) is rare or non-existent has been increasingly challenged not only by case reports but also by systematic research. Methods: Diagnostic and Statistical Manual for Mental Disorders (DSM) criteria are usually employed in these research studies and case reports and it was strongly suggested that pediatric BD may not be rare but that it may be difficult to diagnose. Results: In concordance with the current literature, euphoric mood and episodic course is rare in Turkish children and adolescents and the affective phenomenology is often mixed and dysphoric, with affective storms and temper outbursts. Comorbidity (especially with ADHD) is a big issue in accurate diagnosis and treatment. Conclusion: There are promising treatment studies, but we need more studies in both prepubertal children and adolescents about phenomenology, etiology, and treatment of this important condition

Adjunctive olanzapine treatment in bipolar adolescents responding insufficiently to mood stabilizers - Four case reports

This report was aimed to evaluate the efficacy of olanzapine treatment as an adjunct therapy to mood stabilizers in the treatment of four adolescents responding insufficiently to mood stabilizers. All patients were diagnosed with bipolar I disorder according to DSM IV criteria. YMRS (Young mania rating scale) and CGI (Clinical global impression, improvement and therapeutic effectiveness scales) were used to evaluate overall response of the episode to the drugs. All patients with no adequate response to mood stabilizers did respond to adjunctive olanzapine treatment (10-30 mg/per day). It has been suggested that antipsychotics may be useful as an adjunct to mood stabilisers in bipolar disorder. However, further research is warranted regarding the use of atypical antipsychotics in children and adolescents

Neutrophil-lymphocyte and platelet-lymphocyte ratios among adolescents with bipolar disorder: A preliminary study

We aimed to evaluate the neutrophil lymphocyte and platelet lymphocyte ratios among euthymic adolescents with bipolar disorder (BD) type I. Thirty-six adolescents with BD and 30 healthy controls were included in the study. The diagnosis was made by experienced physicians using the Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version and the affective module of Washington University in St. Louis Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia-Present State and Lifetime. Blood samples were taken during euthymia, which was defined as Young Mania Rating Scale and Hamilton Depression Rating Scale scores below 7. There was no significant difference in neutrophil lymphocyte ratio and platelet lymphocyte ratio between the patient and control group. Considering the literature, we may speculate that in the early stages, euthymia is associated with a lower inflammatory response, and prolongation of BD causes increased inflammatory processes predominant even in euthymia. In pediatric BD, further studies that assess neutrophil lymphocyte ratio and platelet lymphocyte ratio during different mood episodes and that identify neutrophil lymphocyte ratio and platelet lymphocyte ratio changes during the course of the disease will clarify the role of inflammation in the etiology of pediatric BD

Risperidone versus haloperidol in children and adolescents with AD - A randomized, controlled, double-blind trial

The aim of the study was to compare safety, efficacy and tolerability of risperidone with haloperidol in the treatment of Autistic Disorder (AD). Method This study was designed as a double-blind, prospective, for a 12-week period. A total of 30 subjects, between the ages of 8 and 18 with AD based on DSM IV criteria, were included in the study. Behavioral Rating Scales were performed by the investigators and the parents. Safety assessment included vital signs, electrocardiogram, electroencephalogram, adverse events, laboratory tests, extrapyramidal symptoms and the side effects. Both treatments were applied in a once daily dosage regimen of 0.01-0.08 mg/kg/day. Results The reduction from baseline in Ritvo-Freeman Real Life Rating Scale (RF-RLRS), sensory motor (subscale I) and language (subscale V) scores were significant in risperidone group (P < 0.05). Compared to haloperidol, risperidone led to a significantly greater reduction in the Aberrant Behavior Checklist (ABC) and Turgay DSM-IV Pervasive Developmental Disorder (PDD) scale scores (P < 0.05 and P < 0.01). There was a greater increase of prolactin in the risperidone group, while alanine amino transferase (ALT) had further increased in the haloperidol group. Sensory motor behaviors (subscale I) and language at the end of the 12th week, RF-RLRS sensory motor and language subscale scores decreased in the risperidone group further than the other group (P < 0.05). Conclusions Risperidone was found to be more effective than haloperidol in the treatment of behavioral symptoms, impulsivity, language skills, and impaired social relations in children with AD. These results demonstrated that both drugs were safe and well tolerated in the treatment of AD

Comparison of long-term efficacy and safety of risperidone and haloperidol in children and adolescents with autistic disorder - An open label maintenance study

Background The aim of the study was to investigate safety, efficacy and tolerability of risperidone in comparison with haloperidol in the long-term treatment of autistic disorder. Methods This was an open-label continuation study of the randomized, double-blind, controlled trial of risperidone and haloperidol study for 12 week in autistic children and adolescents. A total of 28 subjects between 8 and 18 ages with autistic disorder were enrolled to the open label phase of the study. Behavioral rating scales (Clinical Global Impression Scale [CGI-I], Ritvo-Freeman Real Life Rating Scale [RF-RLRS]), Aberrant Behavior Checklist [ABC], Turgay DSM-IV Pervasive Developmental Disorder Rating Scale [TPDDRS]) and safety assessment scales (Extrapyramidal Symptoms Rating Scale [ESRS], UKU-Side Effect Rating Scale) were performed at 12, 16, 20 and 24 weeks, following the 12 week double-blind phase. Risperidone and haloperidol treatments were applied with a once daily dosage regimen as 0.01-0.08 mg/kg/day. Results Risperidone led to a significant greater reduction on CGI scale. There was significant improvement on RF-RLRS sensory motor and language subscale and ABC scores in risperidone group. Weight gain was observed more frequently in the haloperidol group at week 24. Conclusions These results demonstrate that risperidone is more efficacious and well tolerated than haloperidol in the long-term maintenance treatment of autistic disorder

Decreased Right Hippocampal Volumes and Neuroprogression Markers in Adolescents with Bipolar Disorder

Objectives: The aim of the present study was to assess differences and correlations between the hippocampal volumes (HCVs), serum nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) levels in adolescents with bipolar disorder (BP) compared to healthy controls. Methods: Using structural magnetic resonance imaging, we compared HCVs of 30 patients with euthymic BP who were already enrolled in a naturalistic clinical follow-up. For comparison, we enrolled 23 healthy controls between the ages of 13 and 19. The boundaries of the hippocampus were outlined manually. The BDNF and NGF serum levels were measured with the sandwich ELISA. Results: The groups did not differ in the right or left HCVs or in the NGF or BDNF serum levels. However, negative correlations were found between the right HCVs and the duration of the disorder and medication and positive correlations were found between the duration of the medications and the NGF and BDNF levels in the patient group. Additionally, positive correlations were found between the follow-up period and left normalized HCVs in both the BP and lithium-treated groups. Conclusions: The right HCVs may vary with illness duration and the medication used to treat BP; NGF and BDNF levels may be affected by long-term usage. Further research is needed to determine whether these variables and their structural correlates are associated with clinical or functional differences between adolescents with BP and healthy controls. (C) 2015 S. Karger AG, Base