Antipsychotic and Psychostimulant Drug Combination Therapy in Attention Deficit/Hyperactivity and Disruptive Behavior Disorders: A Systematic Review of Efficacy and Tolerability

  title={Antipsychotic and Psychostimulant Drug Combination Therapy in Attention Deficit/Hyperactivity and Disruptive Behavior Disorders: A Systematic Review of Efficacy and Tolerability},
  author={David Linton and Alasdair M. Barr and William G Honer and Ric M. Procyshyn},
  journal={Current Psychiatry Reports},
This systematic review examines treatment guidelines, efficacy/effectiveness, and tolerability regarding the use of antipsychotics concurrently with psychostimulants in treating aggression and hyperactivity in children and adolescents. Articles examining the concurrent use of antipsychotics and psychostimulants to treat comorbid attention deficit/hyperactivity disorder (ADHD) and disruptive behavior disorders (DBDs) were identified and their results were summarized and critically analyzed… 
Combined stimulant and antipsychotic treatment in adolescents with attention-deficit/hyperactivity disorder: a cross-sectional observational structural MRI study
Meta-analyses suggest normalizing effects of methylphenidate on structural fronto-striatal abnormalities in patients with attention-deficit/hyperactivity disorder (ADHD) are normalizing, and antipsychotic treatment counteracting the normalizing effect of methyl phenidate on brain structure is suggested.
Use and Characteristics of Antipsychotic/Methylphenidate Combination Therapy in Children and Adolescents with a Diagnosis of Attention-Deficit/Hyperactivity Disorder.
It is suggested that a considerable proportion of children and adolescents with ADHD receive MPH in combination with APs and that this is a factor not only during the first years of MPH treatment.
Acute Hyperkinetic Movement Disorders as a Multifactorial Pharmacodynamic Drug Interaction Between Methylphenidate and Risperidone in Children and Adolescents
Health care professionals should be aware that changes to this combination may be associated with a pharmacodynamic drug-drug interaction resulting in acute hyperkinetic movement disorder.
Predictors of concomitant use of antipsychotics and stimulants and its impact on stimulant persistence in pediatric attention deficit hyperactivity disorder.
Concomitant use of atypical antipsychotics was associated with improved LAS treatment persistence in children and adolescents with ADHD and gender, health insurance, region, year of cohort entry, season, physician specialty, coexisting mental health conditions, and general mental health status influenced the concomitantUse of LAS and atypicals antipsychotic agents.
Treatments and compositions for attention deficit hyperactivity disorder: a patent review
This review emphasizes the recent progress in ADHD treatment, which was published in the patent literature from 2005-2015, and focused on novel mechanisms of action and potential treatments for achieving control of ADHD comorbidities, offering theoretical advantages compared with current medication.
Safety and tolerability of antipsychotic agents in neurodevelopmental disorders: a systematic review
Antipsychotic agents used in NDDs were found to mainly cause the following side effects: metabolic disturbances; sedation; prolactin increases and sexual dysfunctions; neurological and behavioral disorders; cardiological and hematological side effects.
Benefits and Limits of Risperidone-Methylphenidate Combination in Child Psychiatry: 3 Cases
Three cases of methylphenidate-risperidone combination show potential benefits to treat comorbid- ADHD with DBD with the psychostimulant-antipsychotic combination and the limits due to the risk of dyskinesia.
Pharmacotherapy of Aggression in Child and Adolescent Psychiatric Disorders.
The available literature points to the importance of identifying the underlying disorder, when possible, and using this information to guide treatment selection, as well as the number of evidence-based medication treatments for aggression.
Psychotropic Treatment Pattern in Medicaid Pediatric Patients With Concomitant ADHD and ODD/CD
“No psychotropic therapy” and stimulants dominate treatment choices in children with ADHD and ODD/CD and Socio-demographic characteristics are associated with combination psychotropic Therapy.
Therapeutic drug levels of second generation antipsychotics in youth: a systematic review.
The only SGA that may require routine therapeutic drug monitoring (TDM) in youth given the current body of research is clozapine; highly variable results were seen in studies of aripiprazole, olanzapine, and risperidone, indicating that more research is needed on plasma levels with these drugs.


Risperidone effects in the presence/absence of psychostimulant medicine in children with ADHD, other disruptive behavior disorders, and subaverage IQ.
Risperidone was a safe and effective treatment, with or without a combined psychostimulant, for both disruptive behavior disorders and comorbid ADHD in children.
Antipsychotic use in children and adolescents: minimizing adverse effects to maximize outcomes.
  • C. Correll
  • Psychology, Medicine
    Journal of the American Academy of Child and Adolescent Psychiatry
  • 2008
The present article aims to succinctly review available data on antipsychotic-related adverse effects in children and adolescents and provide a practical guide for the evaluation and management of antipsychotics-related effects in this vulnerable population.
Risperidone augmentation for treatment-resistant aggression in attention-deficit/hyperactivity disorder: a placebo-controlled pilot study.
Risperidone treatment appears to be well tolerated and modestly effective when used in combination with psychostimulants for treatment-resistant aggression in children with ADHD.
Treatment recommendations for the use of antipsychotics for aggressive youth (TRAAY). Part I: a review.
Double-blind studies should examine the safety and efficacy of atypical antipsychotics compared to each other and to medications from other classes, the efficacy of specific medications for different subtypes of aggression, combining various psychotropic medications, optimal dosages, and long-term safety.
Comparing the efficacy of stimulants for ADHD in children and adolescents using meta-analysis
Amfetamine products may be moderately more efficacious than methylphenidate products, even after controlling for potentially confounding study design features, and this difference in effect size may be due to differences between amfetamine and methyl phenidate in the molecular mechanisms involved in facilitating the dopaminergic neurotransmission.
Methylphenidate combined with aripiprazole in children and adolescents with bipolar disorder and attention-deficit/hyperactivity disorder: a randomized crossover trial.
Although MPH did not worsen manic symptoms, it was not more effective than placebo in improving ADHD symptoms in children and adolescents with JBPD co-morbid with ADHD stabilized with aripiprazole.
Quetiapine addition in methylphenidate treatment-resistant adolescents with comorbid ADHD, conduct/oppositional-defiant disorder, and aggression: a prospective, open-label study.
Quetiapine addition to methyl phenidate was effective in reducing ADHD and aggression in individuals who did not respond sufficiently to OROS methylphenidate alone at a 54-mg/day dose.
Psychopharmacology and Aggression
The results support the common clinical practice of including medications as part of a comprehensive psychoeducational treatment plan for some youth with maladaptive overt aggression within a variety of psychiatric disorders; however, not all referred youth respond to medication for overt aggression-related behavior, supporting the use of additional nonmedication interventions.