Aripiprazole in children and adolescents: clinical experience
ABSTRACT Despite few supportive data, aripiprazole was being administered to children and adolescents for management of mood instability, aggression, and psychosis. Using a retrospective review (n = 11) and prospective recruitment (n = 6), 17 children and adolescents received aripiprazole 5 to 20 mg/day. Only 4 of 16 bipolar and autistic subjects (25%) demonstrated reduced aggression without adverse events, and the symptoms of 2 of 4 psychotic subjects improved. Coadministration of sedative medications (particularly guanfacine or clonidine) and weight < 58 kg increased the risk of adverse events, such as increased lability and aggression. All three children < 8.6 years old, all four children < 34 kg, and all five children receiving alpha2-agonists developed adverse events prior to clinical efficacy. Age > 11 years, weight > 58 kg, and absence of sedative medications were associated with a 56% (five of nine) success rate. Until larger, prospective studies are completed, caution is advised when considering aripiprazole for smaller children and children receiving sedative medications.
- SourceAvailable from: István Hernádi
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- "Lower dose of GUA was effective in HR rats, while the highest dose of GUA changed the EPM behavior of LRs. GUA reportedly acts as an anxiolytic in humans , however , in our experiments the opposite effect was observed. The agonist, acting on presynaptic autoreceptors, inhibits NE release that may decrease stress and anxiety. "
ABSTRACT: In this study we provide evidence that animals of the same population, although identical in age and sex, have individual reactions to the prefrontal modulation of adrenoceptors. We have examined the dose-dependent action of α(2)-adrenoceptor agents on the anxiety of rats with different response to novelty in the elevated plus maze (EPM) apparatus. Rats were divided into high (HR) and low responder (LR) groups based on their locomotor activity in a novel open field environment. HR rats also showed increased locomotion and low anxiety in the EPM. Prefrontal injection of α(2)-receptor antagonist yohimbine, BRL44408 or imiloxan caused anxiety only in HR rats. The α(2A/D)-receptor agonist guanfacine increased anxiety levels of both groups. However, the effective dose was lower in HR rats. The present results propose different prefrontal adrenoceptor sensitivity of rats showing distinct baseline activity levels.Neuroscience Letters 06/2011; 499(3):219-23. DOI:10.1016/j.neulet.2011.05.231 · 2.06 Impact Factor
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- "The only open label prospective study published to date, reported no adverse events related to discontinuation of aripiprazole.6 However, other long-term retrospective studies reported 17-59% discontinuation rates due to adverse effects.8,9 These previously observed adverse events and subsequent discontinuation of monotherapy with aripiprazole are similar to the adverse events observed in the present study on augmentation with aripiprazole. "
ABSTRACT: Due to co-morbidities and treatment resistant nature of pervasive developmental disorder (PDD), diverse combinations of regimens have been tried. This retrospective study aimed to explore adjunctive use of aripiprazole in children with PDD. Changes in illness severity were measured by Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I) in 14 aripiprazole-treated patients with PDD. Improvement of illness severity was observed after aripiprazole add-on (5.8±0.8 to 4.9±1.0, Z=-2.75, p=0.001). Mean dosage was 7.7 mg/day [standard deviation (SD) 3.3, range 5-15]. A higher mean dosage was observed in group with improvement in symptoms (t=-2.33, df =12, p=0.004). The target symptoms most effectively improved after using aripiprazole were positive psychotic symptoms (mean CGI-I: 2.0±1.4, 3 responders/4 patients, 75% response) followed by aggressive behavior (2.5±1.7, 3/4, 75%), self-injurious behavior (2.0±1.0, 2/3, 67%), stereotypic behavior (2.7±1.2, 2/3, 67%), tic (2.8±1.0, 2/4, 50%), irritability (3.5±2.1, 1/2, 50%), obsessive behavior (2.5±2.1, 1/3, 33%), hyperactivity (3.4±1.6, 3/7, 43%) and mood fluctuation (3, 0/1, no response). Five patients (35%) discontinued aripiprazole due to treatment-emergent adverse effects (akathisia, insomnia, withdrawal). The results of this study suggest that aripiprazole augmentation may be used safely in maladaptive behaviors of some populations of PDD. However, future studies are required to confirm these preliminary findings.Psychiatry investigation 09/2010; 7(3):220-3. DOI:10.4306/pi.2010.7.3.220 · 1.15 Impact Factor
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- "In the United States, aripiprazole is used to treat various childhood and adolescent disorders, including Tourette syndrome, pervasive developmental disorder, conduct disorder, and pediatric bipolar disorder (Findling et al. 2003; Barzman et al. 2004; Stigler et al. 2004; Biederman et al. 2005; Murphy et al. 2005; Stachnik and Nunn-Thompson 2007). This increased usage is occurring even though D2-like partial agonists have seldom been examined using developmental animal models and results from a minority of human clinical studies suggest caution in prescribing aripiprazole to children (Rugino and Janvier 2005). Studies employing adult animal models have established that D2-like partial agonists exhibit low intrinsic activity (i.e., function as antagonists) at normosensitive DA presynaptic receptors. "
ABSTRACT: The purpose of this study was to determine whether aripiprazole, a D2-like partial agonist increasingly prescribed to children, alters DA synthesis via actions at autoreceptors in the dorsal striatum and medial prefrontal cortex (mPFC) of preweanling rats. The ability of dopaminergic agents to alter DOPA accumulation in the striatum and mPFC was measured after NSD-1015 on postnatal day (PD) 20. Dopaminergic tone was manipulated by administering reserpine, gamma-butyrolactone (GBL), or through amphetamine withdrawal. Results showed that the partial agonists aripiprazole and terguride increased striatal DOPA accumulation under normosensitive conditions, but decreased DOPA accumulation in states of low dopaminergic tone. A different pattern of results was observed in the mPFC, because terguride and haloperidol, but not aripiprazole, increased DOPA accumulation under normosensitive conditions. In conclusion, the present data show that aripiprazole affects striatal synthesis modulating autoreceptors in an adult-typical manner during the late preweanling period. Unlike in adult rats, however, the mPFC of preweanling rats appears to contain transitory synthesis modulating autoreceptors that are sensitive to drug manipulation.Journal of Neural Transmission 02/2008; 115(1):97-106. DOI:10.1007/s00702-007-0820-7 · 2.87 Impact Factor