A Promising Preliminary Study of Aripiprazole for Treatment-Resistant Childhood Obsessive-Compulsive Disorder

Ercan, Eyüp Sabri; Ardıç, Ülkü Akyol; Ercan, Elif; Yüce, Deniz; Durak, Sibel

doi:10.1089/cap.2014.0128

Cited by 22 publications

(9 citation statements)

References 22 publications

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“…Our results may prompt consideration of further research into low-dose D 2/3 agonist treatment for OCD, although, here, considerable caution, rigorous risk assessment, and very careful experimental design are advised given prior reports that pramipexole may cause or worsen compulsive behaviors in some people (Kolla et al 2010). Our data are consistent with the potential therapeutic actions of partial D 2/3 agonists; one such drug, aripiprazole, has already been shown to be effective in augmentation in OCD, with some evidence of efficacy at very low doses (Ercan et al 2015; Janardhan Reddy et al 2017; Muscatello et al 2011; Sayyah et al 2012; Veale et al 2014). Additional mechanistic and pragmatic research is warranted to determine which OCD patients are most likely to benefit from dopaminergic treatment.…”

Section: Discussionsupporting

confidence: 86%

Dopaminergic drug treatment remediates exaggerated cingulate prediction error responses in obsessive-compulsive disorder

et al. 2019

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Rationale Patients with obsessive-compulsive disorder (OCD) have been found to show exaggerated error responses and prediction error learning signals in a variety of EEG and fMRI tasks, with data converging on the anterior cingulate cortex as a key locus of dysfunction. Considerable evidence has linked prediction error processing to dopaminergic function. Objective In this study, we investigate potential dopaminergic dysfunction during reward processing in the context of OCD. Methods We studied OCD patients ( n = 18) and controls ( n = 18) whilst they learned probabilistic associations between abstract stimuli and monetary rewards in the fMRI scanner involving administration (on separate visits) of a dopamine receptor agonist, pramipexole 0.5 mg; a dopamine receptor antagonist, amisulpride 400 mg; and placebo. We fitted a Q-learning computational model to fMRI prediction error responses; group differences were examined in anterior cingulate and nucleus accumbens regions of interest. Results There were no significant group, drug, or interaction effects in the number of correct choices; computational modeling suggested a marginally significant difference in learning rates between groups ( p = 0.089, partial ƞ 2 = 0.1). In the imaging results, there was a significant interaction of group by drug ( p = 0.013, partial ƞ 2 = 0.13). OCD patients showed abnormally strong cingulate signaling of prediction errors during omission of an expected reward, with unexpected reduction by both pramipexole and amisulpride ( p = 0.014, partial ƞ 2 = 0.26, 1-β error probability = 0.94). Exaggerated cingulate prediction error signaling to omitted reward in placebo was related to trait subjective difficulty in self-regulating behavior in OCD. Conclusions Our data support cingulate dysfunction during reward processing in OCD, and bidirectional remediation by dopaminergic modulation, suggesting that exaggerated cingulate error signals in OCD may be of dopaminergic origin. The results help to illuminate the mechanisms through which dopamine receptor antagonists achieve therapeutic benefit in OCD. Further research is needed to disentangle the different functions of dopamine receptor agonists and antagonists during bidirectional modulation of cingulate activation. Electronic supplementary material The online version of this article (10.1007/s00213-019-05292-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 86%

Dopaminergic drug treatment remediates exaggerated cingulate prediction error responses in obsessive-compulsive disorder

et al. 2019

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“…Finally, 14 studies that are less methodologically sound are also reported in Table 3: open-label studies with or without randomization (Findling et al 2008b(Findling et al , 2009(Findling et al , 2011Marcus et al 2011a;Ercan et al 2012;Ghanizadeh et al 2014;Ghanizadeh 2016;Lamberti et al 2016;Wang et al 2016;Kim et al 2018;Pan et al 2018) and retrospective studies on files (Olfson et al 2012b;Ercan et al 2015;Akyol Ardic et al 2017) in indications corresponding to FDA approval or off-label indications, such as ADHD, disruptive disorder, emotional regulation disorder, conduct disorder, and resistant obsessive-compulsive disorder. For most of these indications, a significant improvement is reported between the beginning and end of treatment, but the absence of a control group and, in particular, a placebo control group makes it very difficult to conclude that aripiprazole is useful for these nonauthorized indications.…”

Section: Efficacy Datamentioning

confidence: 99%

Aripiprazole in Children and Adolescents

Coustals

Ménard

Cohen

2021

Journal of Child and Adolescent Psychopharmacology

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Objective: To review the use of aripiprazole in children and adolescents. Methods: Medline and Embase databases were systematically searched using the keywords aripiprazole and child or adolescent over the period from 2000 to 2019. The initial screen yielded 163 publications, from which 99 studies were reviewed. Results: Aripiprazole is one of the most widely prescribed atypical antipsychotics. Like others, its use in children and adolescents is becoming commonplace and occurs in off-label indications. Aripiprazole has proven efficacy for several indications in children and adolescents, including schizophrenia, bipolar disorder, Tourette's syndrome, and behavioral impairments associated with autism and intellectual disability. Adverse effects are more important in children and adolescents than adults, particularly weight gain, drowsiness, extrapyramidal effects, and metabolic effects, even though the latter may appear less important than with other atypical antipsychotics. Severe adverse effects often occur in multiple-prescription settings. At present, postprescription monitoring is very poor. Conclusion: Aripiprazole has proven efficacy for several indications in children and adolescents. However, its use requires clinical and paraclinical monitoring to assess the occurrence of adverse events that may challenge the benefit/risk ratio. In addition, off-label prescriptions should be limited, as they appear to account for a significant proportion of aripiprazole use worldwide.

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“…At the end of 12 weeks, there was a significant reduction in the children's Y-BOCS score and improvement in the clinical global impressions–improvement (CGI-I) score. [20] A more recent larger open-label study with 48 children and adolescents who had not responded to at least two SSRIs and CBT also reported similar improvement. [21]…”

Section: Second-generation Antipsychoticsmentioning

confidence: 84%

Antipsychotic augmentation in the treatment of obsessive-compulsive disorder

Thamby

Jaisoorya

2019

Indian J Psychiatry

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Most studies suggest that obsessive-compulsive disorder runs a chronic course. Only 40%–70% of patients respond to first-line treatment with selective serotonin reuptake inhibitors (SSRIs). The most common pharmacological strategy used in clinical practice for partial responders to SSRIs is augmentation with an atypical antipsychotic. This article aims to review the efficacy, tolerability, and comparative efficacy of antipsychotics as augmenting agents in patients who showed inadequate response to SSRIs. In addition to case reports and case series, 15 randomized controls trials, 6 meta-analyses, and 3 expert guidelines have been examined. The findings suggest that one in three SSRI nonresponders improve with antipsychotic augmentation. The presence of comorbid tics and/or schizotypal disorder may predict a better response to antipsychotic augmentation. Among antipsychotics, risperidone, and aripiprazole have the best evidence, with haloperidol being considered second in-line owing to its unfavorable side effect profile. Guidelines recommend that antipsychotics be administered at a low-to-medium dosage for a duration not exceeding 3 months, with mandatory discontinuation if there is no response. Larger studies and head-to-head trials are needed to further explore this treatment strategy.

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A Promising Preliminary Study of Aripiprazole for Treatment-Resistant Childhood Obsessive-Compulsive Disorder

Cited by 22 publications

References 22 publications

Dopaminergic drug treatment remediates exaggerated cingulate prediction error responses in obsessive-compulsive disorder

Dopaminergic drug treatment remediates exaggerated cingulate prediction error responses in obsessive-compulsive disorder

Aripiprazole in Children and Adolescents

Antipsychotic augmentation in the treatment of obsessive-compulsive disorder

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