Mood Stabilizers In Children Research Articles

The Role of Mood Stabilizers in Children and Adolescents with Anorexia Nervosa: A 1-year Follow-Up, Propensity Score-Matched Study.

The existing literature on the use of mood stabilizers (MS) in children and adolescents with anorexia nervosa (AN) is limited, for the most part, to small case studies. This was an observational, naturalistic, propensity score-matched study. Subjects treated and not-treated with MS were compared by being matched via propensity score on age, sex, concurrent atypical antipsychotics, and concurrent antidepressants. General and AN-specific psychopathology was assessed with Symptom Check List-90-R, Beck Depression Inventory-II, Eating Disorders Inventory-3, and Body Uneasiness Test-A. Potential differences in admission-discharge modifications (body mass index (BMI), psychopathology) among the two groups were assessed. Finally, re-hospitalizations after 1-year follow-up were assessed with Kaplan-Meier analyses. The study enrolled 234 hospitalized patients (15.9+/-3.3 years; 26, 11.1% receiving MS). After propensity-score matching, 26 MS patients matched with 26 MS-not-treated subjects were included. MS were used for a mean of 126.1 (+/-87.3) days, and two cases of side effects were documented (alopecia and somnolence with valproate). No significant difference between MS-treated and not-treated patients emerged concerning admission-discharge improvements in BMI and AN-specific or general psychopathology. The cumulative survival from re-hospitalization at 12 months was 64,4% (95%-CI, 31.3-97.5) for MS and 58.7% (95%-CI, 22.2-95.2) for MS-not-treated subjects. No significant difference in survival rate emerged (hazard ratio, 0.04; Log-rank test: p=0.846). This propensity score-matched study expands on the scant existing evidence of the use and side effects of MS in children and adolescents with AN. These results should be assessed in wider longitudinal samples.

Safety of 80 antidepressants, antipsychotics, anti-attention-deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta-review of 78 adverse effects.

Mental disorders frequently begin in childhood or adolescence. Psychotropic medications have various indications for the treatment of mental dis-ordersin this age group and are used not infrequently off-label. However, the adverse effects of these medications require special attention during developmentally sensitive periods of life. For this meta-review, we systematically searched network meta-analyses and meta-analyses of randomized controlled trials (RCTs), individual RCTs, and cohort studies reporting on 78 a priori selected adverse events across 19 categories of 80 psychotropic medications - including antidepressants, antipsychotics, anti-attention-deficit/hyperactivity disorder (ADHD) medications and mood stabilizers - in children and adolescents with mental disorders. We included data from nine network meta-analyses, 39 meta-analyses, 90 individual RCTs, and eight cohort studies, including 337,686 children and adolescents. Data on ≥20% of the 78 adverse events were available for six antidepressants (sertraline, escitalopram, paroxetine, fluoxetine, venlafaxine and vilazodone), eight antipsychotics (risperidone, quetiapine, aripiprazole, lurasidone, paliperidone, ziprasidone, olanzapine and asenapine), three anti-ADHD medications (methylphenidate, atomoxetine and guanfacine), and two mood stabilizers (valproate and lithium). Among these medications with data on ≥20% of the 78 adverse events, a safer profile emerged for escitalopram and fluoxetine among antidepressants, lurasidone for antipsychotics, methylphenidate among anti-ADHD medications, and lithium among mood stabilizers. The available literature raised most concerns about the safety of venlafaxine, olanzapine, atomoxetine, guanfacine and valproate. Nausea/vomiting and discontinuation due to adverse event were most frequently associated with antidepressants; sedation, extrapyramidal side effects, and weight gain with antipsychotics; anorexia and insomnia with anti-ADHD medications; sedation and weight gain with mood stabilizers. The results of this comprehensive and updated quantitative systematic meta-review of top-tier evidence regarding the safety of antidepressants, antipsychotics, anti-ADHD medications and mood stabilizers in children and adolescents can inform clinical practice, research and treatment guidelines.

Anticonvulsants for Psychiatric Disorders in Children and Adolescents: A Systematic Review of Their Efficacy.

Aim: Anticonvulsant medications are frequently used in clinical practice to treat psychiatric disorders in children and adolescents, but the evidence for their efficacy is uncertain. We conducted a systematic review of published randomized controlled trials (RCT) that assessed the psychiatric benefit of anticonvulsants in patients under 18 years of age.Method: The Medline, Scopus, Web of Science, and ClinicalTrials.gov databases were systematically searched for peer-reviewed primary publications of RCTs with a minimum of 10 patients per treatment arm through December 2017.Results: Out of 355 identified non-duplicative publications, 24 met the inclusion criteria. Most RCTs were to treat bipolar disorder (n = 12) or manage recurrent aggression (n = 9). Few (n = 3) had both a multisite design and adequate statistical power. Valproate was the most frequently studied anticonvulsant (n = 15). Out of three placebo-controlled RCTs of valproate in bipolar disorder, none showed efficacy. In four RCTs, valproate was inferior to the antipsychotic risperidone. In several small, single-site RCTs, valproate and sulthiame were better than placebo for the management of recurrent aggression.Conclusions: Currently available RCTs do not support the efficacy of anticonvulsants as mood stabilizers in children. There is some preliminary evidence from small RCTs of the efficacy of some anticonvulsants in the control of aggression and behavioral dyscontrol in conduct disorder, autism, and intellectual disability.

Mood Stabilizers in Children and Adolescents With Autism Spectrum Disorders.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders including autistic disorder, Asperger syndrome, and pervasive developmental disorder not otherwise specified as to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. All these categories are grouped together in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, classification under the category of Autism Spectrum Disorders.Behavioral disorders including irritability, attention-deficit/hyperactivity disorder (ADHD) symptoms, and aggression are additional symptoms found in up to 20% of children and adolescents with ASD and require careful evaluation for appropriate treatment. Attention-deficit/hyperactivity disorder is defined by impaired attention, hyperactivity, and impulsivity, whereas ASD is defined by social dysfunction, communicative impairment, and restricted/repetitive behaviors. They should be distinctly evaluated in children and adolescents with ASD and intellectual disability in contrast to individuals without intellectual disability, because significant differences between these conditions exist. Mood disorders are also common in ASD and should be systematically investigated in this population of children and adolescents. Approximately 50% of children and adolescents with ASD receive medication for comorbid behavioral/ADHD and mood symptoms, mostly stimulants, antiepileptics and antipsychotics. Guidelines for the evaluation and treatment including medications for ADHD-like symptoms have recently been provided and should be carefully considered. Antiepileptic drugs are commonly used in ASDs with epilepsy, because seizures are associated with ASD in 10% to 30% of young patients, and as mood stabilizers. Lithium is another option for children and adolescents with ASD who present with symptoms of a mood disorder, such as elevated moods/euphoria, mania, and paranoia, whether accompanied or not by irritability. Experimental treatments are under investigation and currently include arbaclofen, a γ-aminobutyric acid agent, and N-acetylcisteine, a glutamate agent.

Quetiapine for acute bipolar depression: a systematic review and meta-analysis.

BackgroundPrecise estimated risks and benefits of quetiapine for acute bipolar depression are needed for clinical practice.ObjectiveTo systematically review the efficacy and the tolerability of quetiapine, either as monotherapy or combination therapy, for acute bipolar depression.MethodsWe included all randomized, controlled trials (RCTs) comparing quetiapine with other treatments, including placebo, in patients with acute bipolar depression (bipolar I or II disorder, major depressive episode). Published and unpublished RCTs were identified using the Cochrane Central Register of Controlled Trials, MEDLINE®, Web of Knowledge™, CINAHL®, PsycINFO®, the EU Clinical Trials Register database, and ClinicalTrials.gov. The primary outcome was the change scores of depression rating scales.ResultsEleven RCTs (n=3,488) were included. Two of them were conducted in children and adolescents. The change in depression scores was significantly greater in the quetiapine group compared with the placebo group (mean difference, [MD] =−4.66, 95% confidence interval [CI] −5.59 to −3.73). The significant difference was observed from week 1. Compared with placebo, quetiapine had higher incidence rates of extrapyramidal side effects, sedation, somnolence, dizziness, fatigue, constipation, dry mouth, increased appetite, and weight gain but lower risks of treatment-emergent mania and headache. Quetiapine treatment was associated with significant improvement of clinical global impression, quality of life, sleep quality, anxiety, and functioning.ConclusionQuetiapine monotherapy is effective for acute bipolar depression and the prevention of mania/hypomania switching. Its common adverse effects are extrapyramidal side effects, sedation, somnolence, dizziness, fatigue, constipation, dry mouth, increased appetite, and weight gain. The lower risk of headache in quetiapine-treated patients with acute bipolar depression should be further investigated. The evidence for the use of quetiapine combined with mood stabilizers in children and adolescents with acute bipolar depression is too small to support the clinical practice.

Evidence for Use of Mood Stabilizers and Anticonvulsants in the Treatment of Nonaffective Disorders in Children and Adolescents

Mood stabilizers and anticonvulsants have been frequently used to control behaviors in children and adolescent with nonaffective disorders. The purpose of this study was to review the literature to evaluate the evidence of these agents as treatment options in this subset of patients. We reviewed all the literature between 1949 and 2009 on the use of anticonvulsants and mood stabilizers in controlling severe behavior dysregulation and aggression in child and adolescent who do not meet the criteria for any mood disorder. The review revealed a total of 19 studies. Of the different mood stabilizers/anticonvulsants, both lithium and divalproex showed some promise in treating children and adolescents with nonmood disorders. Larger studies are nevertheless needed to support the ongoing use of these current anticonvulsants and mood stabilizers in children and adolescents with nonmood disorders. Also, further investigation to the potential use in the long term would need to be established, bearing in mind the balance of side effects and treatment benefit.

800,000 “Bipolar Children”

The front cover of the May 26, 2008, Newsweek has a banner headline, "Growing Up Bipolar," with a split-face photograph of a 10-year-old boy named Max. In day care, 18-month-old Max kicked, bit, and spat on his larger peers. Before he was 2 years old, his overwhelmed parents took him to a well-known Boston psychiatrist who quickly diagnosed the toddler as bipolar and placed him on the "mood stabilizer" valproate (Depakote). This is an antiseizure drug that is sufficiently sedating to subdue the mind and behavior of children, at least until the brain compensates, causing the effect to wear off. According to the parents, the doctor told them that the bipolar diagnosis was a "life sentence." It was a life sentence, not to suffer from a mental disorder, but to suffer from lifelong exposure to psychiatric drugs. At the age of 10, Max is already 8 years into his potentially interminable sentence. The first psychiatrist probably put Max on several medications at once because a second psychiatrist wanted to "streamline" the boy's meds. Reducing anyone's medications is a rarity in psychiatry; Max's first psychiatrist must have been overprescribing even by the standards of those of his colleagues who shared his zeal for diagnosing a young child with bipolar disorder. A mere 10 years old, Max has already been on 38 different psychoactive drugs. Newsweek observes, "His parents aren't happy about it, but they have made their peace with it." The magazine concludes, "Max will never truly be OK" because of his "disease." In reality, toxic chemicals will inevitably cause developmental neurotoxicity, suppressing and distorting the growth of Max's brain. Max now leaves suicide notes for his family to find. For several years, the Food and Drug Administration (FDA) has required antidepressant drugs to carry a black box warning concerning the risk of antidepressant-induced suicidality, overstimulation, mania, and a general decline in mental condition (Breggin, 2006). Yet these drugs are frequently used to treat children labeled bipolar. More recently, the FDA issued an "Information for Healthcare Professions" warning about suicidality caused by antiepileptic drugs, many of which are used as mood stabilizers in children, including valproate (Depakote), carbamazapine (Tegretol and Carbatrol), and gabapentin (Neurontin) (FDA, 2008). Tragically, he has become so afraid of psychiatric treatment that after writing his more recent suicide note he sobbed, "Please don't send me to the hospital." From now on, Max, his family, and his doctors will face an increasingly impossible dilemma. If they try to withdraw Max from his multiple psychiatric medications, like most children in similar circumstances he will probably go through severe withdrawal problems with extreme emotional instability and the risk of worsening violence and suicidality. In? fact, we are told that an attempt to take Max off his medications resulted in his displaying hallucinations and delusions, which Newsweek attributes to his worsening condition and his need for drugs. The odds are overwhelming, instead, that he went through a severe withdrawal reaction. But if the doctors keep Max on drugs indefinitely, his brain, mind, and overall condition will further deteriorate (Breggin, 2008). Max is not an illustration of bipolar disorder in children; he is an example of the hazards of exposing small children to multiple psychiatric drugs. It can sometimes be relatively easy and safe to withdraw a child from one or even two psychiatric drugs, especially if the parents are willing to learn improved methods of disciplining their offspring. But when multiple drugs are involved, when the drugs have been taken for a long time, and when the parents are deeply distressed or cannot agree on how to raise their child, withdrawing the child from psychiatric medication can be difficult and hazardous. The Newsweek article makes clear that Max's parents have serious conflicts over how to raise their son, but they have not pursued therapy, marriage counseling, or, apparently, not even parenting classes. …

Clinical Psychopharmacology of Pediatric Mood Stabilizer and Antipsychotic Treatment, Part 2: Methodological Considerations

Article AbstractBecause this piece does not have an abstract, we have provided for your benefit the first 3 sentences of the full text.In last month's ASCP Corner, I discussed some of the challenges and recent developments regarding the available evidence base for the use of antipsychotics and mood stabilizers in children and adolescents. 1 In this month's column, I will focus on some of the pertinent clinical psychopharmacology trials design issues that are relevant to the collection of data in children and adolescents who are in need of antipsychotic or mood stabilizer treatment.While it is clear that studying psychotropic medication effects in children and adolescents is crucial, it is also a difficult task.†‹†‹

Atomoxetine for the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents with Bipolar Disorders

Children and adolescents with bipolar disorder (BD) have a high incidence of comorbid attention-deficit/hyperactivity disorder (ADHD). In this paper, we report a consecutive case series on 7 patients with pediatric BD and ADHD who were treated with atomoxetine-and all but one were also treated in conjunction with mood stabilizers. All patients were outpatients at the Stanford Pediatric Bipolar Disorders Clinic. Information on patients was collected in a retrospective chart review. All but 1 patient demonstrated significant improvement in symptoms of ADHD. No patients had episodes of hypomania or mania during the treatment period. Adverse effects of atomoxetine treatment included sedation, nausea, and decreased appetite. These cases suggest that atomoxetine may be a safe and effective treatment for ADHD in conjunction with mood stabilizers in children with BD.

Two-year prospective follow-up of children with a prepubertal and early adolescent bipolar disorder phenotype.

Longitudinal outcomes of bipolar disorder with onset in the late teenage years or in adulthood have been reported, but little is known about the natural history of childhood-onset mania. This study sought to provide rates and predictors of recovery and relapse in children with a prepubertal and early adolescent bipolar disorder phenotype. Eighty-nine consecutively ascertained outpatient subjects (mean age=10.9 years [SD=2.7]) received comprehensive research assessments, including separate interviews of mothers about their children and of children about themselves, at baseline and at 6, 12, 18, and 24 months after baseline. The study phenotype required DSM-IV mania with elation and/or grandiosity as one criterion to distinguish the study phenotype from a diagnosis of mania based on criteria overlapping with those for attention deficit hyperactivity disorder and to ensure that subjects had at least one of the two cardinal features of mania (i.e., elation and/or grandiosity). Subjects were treated by their own community practitioners. The proportions of subjects who recovered from mania and who relapsed after recovery were 65.2% and 55.2%, respectively. The mean time to recovery was 36.0 weeks (SD=25.0). Relapse occurred after a mean of 28.6 weeks (SD=13.2). Living with an intact biological family significantly predicted rate of recovery, and a low level of maternal warmth significantly predicted rate of relapse. The relatively poor outcomes of these subjects may be related to their phenotypic resemblance to severely ill adults with bipolar disorder who have mixed mania, continuous rapid cycling, psychosis, and treatment-resistant psychopathology. A lower level of effectiveness of mood stabilizers in children cannot be ruled out. Although the significance of maternal warmth as a predictor is consistent with reports in adult mania, the significance of intact family as a predictor may be unique to childhood mania.

Mood Stabilizers in Children and Adolescents

The efficacy of mood stabilizers in children and adolescents has not been studied adequately. This article will review existing studies and highlight some important issues in designing future studies on these agents. Electronic databases including Medline, Psycholnfo, and CRISP were searched for data in children receiving compounds that have mood-stabilizing properties in adults. Some open clinical data and an extremely modest amount of controlled research data suggest lithium, carbamazepine, and valproate may be effective mood stabilizers in children and adolescents. There are no controlled data on other potential mood stabilizers in children. The disorders that may be responsive to mood stabilizers are among the most morbid in child psychiatry. More studies are needed to clarify the efficacy of these compounds in children and adolescents and to provide a rational basis for choosing among them.