Many patients fail to achieve an adequate response to antidepressant medication. Growing evidence suggests that atypical antipsychotics may augment antidepressant effects, resulting in a greater potential for response. Atypical antipsychotics possess pharmacological actions that are associated with antidepressant properties, including serotonin 5-HT(2) receptor antagonist and 5-HT(1A) and dopamine receptor partial agonist activity. In fact, the term 'atypical antipsychotic' is an unfortunate remnant of the early indication of these drugs in the treatment of schizophrenia. Soon after their introduction, the usefulness of atypical antipsychotics in bipolar disorder was firmly established and their use in the treatment of mood disorders has far outpaced their use in schizophrenia and other psychotic disorders. Aripiprazole has become the first agent to receive US FDA approval for the adjunctive treatment of unipolar depression. Most recently, Symbyax, a fluoxetine/olanzapine combination, received FDA approval for the acute treatment of treatment-resistant depression. This is the first medication to be FDA approved for this indication. In the present article, the usefulness of antipsychotics in the treatment of resistant unipolar depression is reviewed.
"At present, the FDA has approved three medications in this class for that purpose. Two of these medications, aripiprazole and quetiapine , have become among the most prescribed agents for patients with MDD nationally, including in the Veterans Health Administration (DeBattista and Hawkins, 2009; Mohamed et al., 2009). However, data on the long-term effectiveness, safety and total health care costs of this treatment for patients with major depressive disorder are sparse. "
"The mechanism of action underlying the effectiveness of aripiprazole in the treatment of ASDs has not been fully elucidated. A partial agonist effect on dopamine D224–26 and serotonin 5-HT1A27,28 receptors, and an antagonistic effect on serotonin 5-HT2A29 receptors, are proposed pharmacological activities that may be involved. "
[Show abstract][Hide abstract] ABSTRACT: Children with autism have a high rate of irritability and aggressive symptoms. Irritability or self-injurious behavior can result in significant harm to those affected, as well as to marked distress for their families. This paper provides a literature review regarding the efficacy and tolerability of pharmacotherapy for the treatment of irritability in autistic children. Although antipsychotics have not yet been approved for the treatment of autistic children by many countries, they are often used to reduce symptoms of behavioral problems, including irritability, aggression, hyperactivity, and panic. However, among antipsychotics, the Food and Drug Administration has approved only risperidone and aripiprazole to treat irritability in autism. Among atypical antipsychotics, olanzapine and quetiapine are limited in their use for autism spectrum disorders in children because of high incidences of weight gain and sedation. In comparison, aripiprazole and ziprasidone cause less weight gain and sedation. However, potential QTc interval prolongation with ziprasidone has been reported. Contrary to ziprasidone, no changes were evident in the QT interval in any of the trials for aripiprazole. However, head-to-head comparison studies are needed to support that aripiprazole may be a promising drug that can be used to treat irritability in autistic children. On the other hand, risperidone has the greatest amount of evidence supporting it, including randomized controlled trials; thus, its efficacy and tolerability has been established in comparison with other agents. Further studies with risperidone as a control drug are needed.
"5HT1A knockout mice exhibit anxiety behavior , and 5HT1A receptor agonists appear to have anti-anxiety and anti-depressive effects and improve cognitive function . APZ is a partial agonist of serotonin 5HT1A, which is expected to improve anxiety and depression and to reduce antipsychotic-derived EPS [13, 14]. de Quervain et al.  found that genetic variations of 5HT2A receptors affect human episode memory, which indicates that the 5HT2A receptor is closely related with cognitive function . "
[Show abstract][Hide abstract] ABSTRACT: Aripiprazole (APZ) has a unique pharmacological profile, as a partial agonist at the dopamine D2 and serotonin 5HT1A receptors and an antagonist at the serotonin 5HT2A receptor; this drug has few side effects (such as extrapyramidal syndrome, hyperprolactinemia, weight gain, metabolic disorders, and sedation) which are typical problems with other antipsychotic drugs. Due to its high tolerability, it is possible to safely administer it to children and adolescents. Efficacy and tolerability of APZ in children and adolescents have been well demonstrated in many clinical studies, which supported approvals granted by the US Food and Drug Administration (FDA) for schizophrenia, bipolar diseases, and irritability associated with autistic disorder in children and adolescents. APZ is expected to exert sedative, anti-depressive, and anti-anxiety effects, and stabilize emotion. APZ is an antipsychotic drug which could be useful for a wider spectrum of psychiatric disorders in children and adolescents. There is little risk of deterioration (such as disinhibition and acting out) and rapid stabilization is easy to achieve in children and adolescents without definitive diagnoses or with a combination of more than one spectrum of disorders. The effectiveness of APZ in children and adolescents is reviewed and discussed, given its pharmacological profile and the outcomes of various clinical studies. However, randomized or blind studies are still limited, and the majority of reports referenced here are open-label studies and case reports. Conclusions drawn from such studies must be evaluated with caution, and a further accumulation of controlled studies is thus needed.
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