Second generation antipsychotics (SGAs) for non-psychotic disorders in children and adolescents: a review of the randomized controlled studies.
ABSTRACT In children and adolescents the Second Generation Antipsychotics (SGAs) represent the class of psychotropic drugs whose use has grown more significantly in recent years: they are primarily used for treatment of patients with disruptive behavior disorders, mood disorders and pervasive developmental disorders or mental retardation. In order to compare the efficacy and tolerability of antipsychotics against placebo or each other, a systematic Medline/PubMed search for randomized, double blind studies on SGA in patients younger than 18 years of age at enrollment, was conducted. Papers on schizophrenia, discussed in another article of this specific issue, were excluded by the efficacy analysis. A set of standard efficacy and safety indices, such as treatment effect sizes (ES), the Numbers Needed to Treat (NNT) and Numbers Needed to Harm (NNH), was used to compare medications. 32 studies analyzing efficacy and/or tolerability of SGAs in children and adolescents with bipolar, autistic or disruptive behavior disorders, and Tourette syndrome were identified. SGAs efficacy on mania, extreme mood variability, irritability, aggression and disruptive behavior appears to be greater than for psychotic symptoms in schizophrenia: average NNT was 2-5, whereas for schizophrenia it varies between 3 for risperidone and 10 for olanzapine, quetiapine, and aripiprazole. As for schizophrenia, different SGAs show a similar efficacy for specific non-psychotic disorders, but they significantly differ in their safety profile. In randomized studies, adverse effects were usually relatively minor, easily predictable and manageable, whereas long-term open-label studies have indicated that some adverse event, such as the metabolic effects, may be severe and potentially life threatening on the long-term. Taken together, these findings suggest that the choice of a specific treatment should be guided primarily by the safety profile of specific antipsychotics, considering specific risk factors (i.e. obesity and BMI, family history of diabetes or cardiovascular disorder, etc) for the single patient.
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ABSTRACT: This study was designed to investigate the metabolic adverse effects (AEs) of second-generation antipsychotics (SGAs) and their relationship with physical activity and non-metabolic AE in children and adolescents. After exclusion of patients with metabolic syndrome, 62 patients (34 children, 28 adolescents) of both genders who were candidates for SGA therapy were selected. Metabolic parameters included fasting blood glucose (FBG), triglyceride (TG), blood pressure (BP), and waist circumference (WC); non-metabolic AEs and physical activity were evaluated at baseline, 1 month, and 3 months after starting the treatment. Mean of post-treatment FBG and TG were significantly higher than the baseline values (P < 0.0001). Compared to the baseline value, significantly more patients developed abnormally high (AbH) FBG at the end point (P = 0.02). There was no significant difference in the frequency of patients with AbH-FBG either at the baseline or at the end point (P > 0.05). The frequency of patients with AbH-TG at the end point was not significantly higher than those with baseline AbH-TG (P = 0.10). Although no patient was obese at baseline, 11 (18%) patients developed abdominal obesity at the end point (P < 0.0001). There was no significant difference in the frequency of non-metabolic AE (P > 0.05). There was no significant correlation between metabolic and non-metabolic AE (P > 0.05). Frequency of inactive patients was significantly more than the baseline value (P-0.008), and abdominal obesity was significantly more prevalent in less active participants (P = 0.03). The present study showed the AE of SGA on FBG and TG, but no effect on BP and WC. We also found that children are more prone to develop abnormally high FBG.Advanced biomedical research. 01/2014; 3:224.
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ABSTRACT: Atypical antipsychotic drugs (AAPDs) are widely used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of AAPD treatment before the brain is fully developed. Indeed, we and others have previously reported that treatment of adolescent rats with olanzapine (OLA; a widely prescribed AAPD) on postnatal days 28-49, under dosing conditions that approximate those employed therapeutically in humans, causes long-term behavioral and neurobiological perturbations. We have begun to study the mechanisms of these effects. Dopamine (DA) and serotonin (5HT) regulate many neurodevelopmental processes. Currently approved AAPDs exert their therapeutic effects principally through their DAergic activities, although in schizophrenia (SZ) and some other diseases for which AAPDs are prescribed, DAergic dysfunction is accompanied by abnormalities of glutamatergic (GLUergic) and γ-aminobutyric acidergic (GABAergic) transmission. Here, we use proton magnetic resonance spectroscopy ((1)H MRS) to investigate the effects of adolescent OLA administration on GABA and GLU levels. We found that the treatment caused long-term reductions in the levels of both GLU and GABA in the nucleus accumbens (NAc) of adult rats treated with OLA during adolescence. The NAc is a key node in the brain's "reward" system, whose function is also disrupted in schizophrenia. Further research into potential, OLA-induced changes in the levels of GLU and GABA in the NAc and other brain areas, and the dynamics and mechanisms of those changes, are an essential step for devising new adjunct therapies for existing AAPDs and for designing new drugs that increase therapeutic effects and reduce long-term abnormalities when administered to pediatric patients. Copyright © 2014 Elsevier B.V. All rights reserved.Schizophrenia Research 12/2014; 161(2-3). · 4.43 Impact Factor
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ABSTRACT: Bipolar disorder is a pernicious illness. Compared with the later-onset form, early onset bipolar disorder is associated with worse psychosocial outcomes, and is characterized by rapid cycling and increased risks of substance abuse and suicide attempts. Controlling mood episodes and preventing relapse in this group of pediatric patients requires careful treatment. Here, we review the effectiveness of aripiprazole for bipolar disorder in children and adolescents, with discussion of this drug's unique pharmacological profile and various clinical study outcomes. Aripiprazole acts as a serotonin 5-HT2A receptor antagonist, as well as a partial agonist of the serotonin 5-HT1A and dopamine D2 receptors. It can be safely used in children and adolescents, as it is highly tolerated and shows lower rates of the side effects typically observed with other antipsychotic drugs, including sedation, weight gain, hyperprolactinemia, and extrapyramidal syndrome. The presently reviewed randomized controlled trials (RCTs) and non-RCTs generally reported aripiprazole to be effective and well-tolerated in children and adolescents with bipolar disorder. However, due to the limited number of RCTs, the present conclusions must be evaluated cautiously. Furthermore, aripiprazole cannot yet be considered a preferred treatment for children and adolescents with bipolar disorder, as there is not yet evidence that aripiprazole shows greater efficacy compared to other second-generation antipsychotics. Additional data are needed from future head-to-head comparison studies.Adolescent Health, Medicine and Therapeutics 01/2014; 5:211-221.