Divalproex Treatment for Youth With Explosive Temper and Mood Lability: A Double-Blind, Placebo-Controlled Crossover Design
Abstract
OBJECTIVE: The authors sought to replicate open-label findings showing that specific criteria for explosive temper and mood lability identify disruptive youth who improve while receiving the anticonvulsant divalproex sodium. METHOD: Twenty outpatient children and adolescents (ages 10-18) with a disruptive behavior disorder (oppositional defiant disorder or conduct disorder) met the specific criteria for explosive temper and mood lability. They received 6 weeks of divalproex treatment and 6 weeks of placebo by random assignment. Independent evaluators blind to group assignment assessed response at the end of each phase. RESULTS: At the end of phase 1, eight of 10 subjects had responded to divalproex; zero of 10 had responded to placebo. Of the 15 subjects who completed both phases, 12 has superior response taking divalproex. CONCLUSIONS: This preliminary study replicates open-label findings showing that divalproex is an efficacious treatment for explosive temper and mood lability in disruptive children and adolescents.
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A comparison of behavior therapy combined with either divalproex or stimulants found that divalproex was more efficacious in children with severe aggressive behavior, most of whom also had ADHD.
“However, a comparison of behavior therapy combined with either divalproex or stimulants found that the use of divalproex was more efficacious in children with severe aggressive behavior, most of whom also had ADHD (118).”
From Emotion Dysregulation in Attention Deficit Hyperactivity Disorder (2014) · cites this paper as [118]
Divalproex was found to be superior to placebo in treating explosive temper, mood lability, and CD in adolescents.
“Divalproex was found it to be superior to placebo in treating explosive temper, mood lability [661], and CD [662] in adolescents.”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [661]
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Reeves, G. M., Wehring, H. J., & Riddle, M. A. (2017) · Wiley eBooks · doi:10.1002/9781119092254.ch25 · Cited by 47 · see citing works
Olanzapine treatment in adolescents with severe conduct disorder
Masi, G., Milone, A., Canepa, G., Millepiedi, S., Mucci, M., & Muratori, F. (2005) · European Psychiatry · doi:10.1016/j.eurpsy.2004.11.010 · Cited by 46 · see citing works
“Antiepileptics are often used to manage aggressive and impulsive outbursts in bipolar and nonbipolar aggressive patients, but evidence for their efficacy is still controversial [16,18,25,46].”
BackgroundPharmacotherapy and psychotherapy in cannabis withdrawal and dependence
Benyamina, A., Lecacheux, M., Blecha, L., Reynaud, M., & Lukasiewcz, M. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.8.3.479 · Cited by 45 · see citing works
Balia, C., Carucci, S., Coghill, D., & Zuddas, A. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.01.024 · Cited by 44 · see citing works
A DSM-IV—Referenced Teacher Rating Scale for Use in Clinical Management
Mattison, R. E., Gadow, K. D., Sprafkin, J. N., Nolan, E. E., & Schneider, J. (2003) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000046813.95464.b3 · Cited by 43 · see citing works
Antisocial Personality Disorder
Derefinko, K. J., & Widiger, T. A. (2016) · Springer eBooks · doi:10.1007/978-1-4939-2528-5_13 · Cited by 44 · see citing works
Treatment Options for the Cardinal Symptoms of Disruptive Mood Dysregulation Disorder.
Tourian, L., LeBoeuf, A., Breton, J., Cohen, D., Gignac, M., Labelle, R. J., Guilé, J.-M., & Renaud, J. (2015) · Europe PMC (PubMed Central) · Cited by 43 · see citing works
Nonepileptic Uses of Antiepileptic Drugs in Children and Adolescents
Golden, A. S., Haut, S. R., & Moshé, S. L. (2006) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2005.08.017 · Cited by 41 · see citing works
Sukhodolsky, D. G., Wyk, B. C. V., Eilbott, J. A., McCauley, S. A., Ibrahim, K., Crowley, M. J., & Pelphrey, K. A. (2016) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2015.0164 · Cited by 41 · see citing works
“…for aggressive behavior in children include novel antipsychotic agents such as risperidone (RUPP Autism Network 2002), mood stabilizers such as divalproex (Donovan et al. 2000) and lithium (Malone et al. 2000), and stimulant medications such as methylphenidate (MTA cooperative group 1999).”
Divalproex Sodium Reduces Overall Aggression in Youth at High Risk for Bipolar Disorder
Saxena, K., Howe, M. E., Simeonova, D. I., Steiner, H., & Chang, K. (2006) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2006.16.252 · Cited by 41 · see citing works
“Donovan et al. (2000) reported disruptive behavior disorder (ODD or CD) BIPOLAR DISORDER who met the specific criteria for explosive temper and mood lability 257 .”
Spectrum of effectiveness of valproate in neuropsychiatry
Bowden, C. L. (2006) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.7.1.9 · Cited by 40 · see citing works
Divalproex sodium in the treatment of pediatric psychiatric disorders
Rana, M., Khanzode, L. A., Karnik, N. S., Saxena, K., Chang, K., & Steiner, H. (2005) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.5.2.165 · Cited by 38 · see citing works
Greenhill, L. L., Pliszka, S. R., Dulcan, M. K., Bernet, W., Arnold, V. K., Beitchman, J. H., Benson, R. S., Bukstein, O., Kinlan, J., McClellan, J., et al. (2004) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/foc.2.4.642 · Cited by 36 · see citing works
“A recent report (n=20) suggests that 6 weeks of divalproex treatment for adolescents (ages 10-18) with explosive temper and mood lability has been successful in showing a 70% reduction from baseline in scores on the Modified Overt Aggression Scale and the SCL-90 anger-hostility items (Donovan et al., 2000).”
BackgroundA Comparison of Divalproex and Oxcarbazepine in Aggressive Youth with Bipolar Disorder
MACMILLAN, C. M., KORNDÖRFER, S. R., Rao, S., Fleisher, C., Mezzacappa, E., & Gonzalez–Heydrich, J. (2006) · Journal of Psychiatric Practice · doi:10.1097/00131746-200607000-00003 · Cited by 36 · see citing works
Pharmacological Aspects of the Treatment of Conduct Disorder in Children and Adolescents
Tcheremissine, O. V., & Lieving, L. M. (2006) · CNS Drugs · doi:10.2165/00023210-200620070-00002 · Cited by 35 · see citing works
Use of Dronabinol for Cannabis Dependence: Two Case Reports and Review
LEVIN, F. R., & Kleber, H. D. (2008) · American Journal on Addictions · doi:10.1080/10550490701861177 · Cited by 35 · see citing works
Therapeutic Monitoring of Valproate in Psychiatry
Fleming, J., & Chetty, M. (2006) · Clinical Neuropharmacology · doi:10.1097/01.wnf.0000228209.69524.e8 · Cited by 34 · see citing works
Salpekar, J. A., Conry, J. A., Doss, W., Cushner‐Weinstein, S., Pearl, P. L., Weinstein, S. L., & Gaillard, W. D. (2006) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2006.06.004 · Cited by 34 · see citing works
Psychiatric and Psychosocial Consequences of Pediatric Epilepsy
Salpekar, J. A., & Dunn, D. W. (2007) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2007.08.004 · Cited by 33 · see citing works
Pharmacotherapy and Postdischarge Outcomes of Child Inpatients Admitted for Aggressive Behavior
Blader, J. C. (2006) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000227356.31203.8a · Cited by 33 · see citing works
Davico, C., Canavese, C., Vittorini, R., Gandione, M., & Vitiello, B. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00270 · Cited by 32 · see citing works
Divalproex for the Treatment of Aggression Associated with Adolescent Mania
DelBello, M. P., Adler, C. M., & Strakowski, S. M. (2004) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/1044546041649101 · Cited by 31 · see citing works
“In addition, divalproex has shown a of children and adolescents with disruptive behavior disorders characterized by explosive temper and mood lability (Donovan et al. 1997; Donovan et al. 2000).”
Comorbidity of Conduct Disorder and Bipolar Disorder in Clinically Referred Children and Adolescents
Masi, G., Milone, A., Manfredi, A., Pari, C., Paziente, A., & Millepiedi, S. (2008) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2008.0051 · Cited by 30 · see citing works
“…stabilizers in a significant minority of non-bipolar CD patients is supported by studies suggesting anti-aggressive properties of both lithium (Campbell et al. 1995; Malone et al. 2000) and valproate (Donovan et al. 2000; Steiner et al. 2003; Saxena et al. 2006) in children and adolescents with CD.”
The treatment of severe child aggression (TOSCA) study: Design challenges
Farmer, C., Arnold, L. E., Bukstein, O. G., Findling, R. L., Gadow, K. D., Li, X., Butter, E. M., & Aman, M. G. (2011) · Child and Adolescent Psychiatry and Mental Health · doi:10.1186/1753-2000-5-36 · Cited by 30 · see citing works
“Methodologically rigorous studies of divalproex found it to be superior to placebo in treating explosive temper and mood lability [21] and CD [22] in adolescents.”
Background
- Authors
- Donovan, S. J., Stewart, J. W., Nunes, E. V., Quitkin, F. M., Parides, M., Daniel, W., Susser, E., & Klein, D. F.
- Affiliations
- New York State Psychiatric Institute (US)
- Venue
- American Journal of Psychiatry
- Published
- 2000-05-01
- Volume
- 157
- Issue
- 5
- Pages
- 818-820
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2154371517
- Cited by
- 273
- References
- 6
- Citations by year
- 2025: 7 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 7 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 12 · 2016: 18 · 2015: 7 · 2014: 10 · 2013: 2 · 2012: 9
- FWCI
- 20.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (DA00246)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- divalproex sodium, valproic acid, emotional lability, disruptive behavior disorders, oppositional defiant disorder, conduct disorder, children and adolescents, anticonvulsant therapy, placebo response, replication
- MeSH terms
- Adolescent, Ambulatory Care, Anticonvulsants, Child, Double-Blind Method, Drug Administration Schedule, Female, Humans, Disruptive, Impulse Control, and Conduct Disorders, Male, Placebos, Psychiatric Status Rating Scales, Valproic Acid, Comorbidity, Treatment Outcome, Cross-Over Studies, Attention Deficit and Disruptive Behavior Disorders, Mood Disorders
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