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Choosing a treatment for disruptive, impulse-control, and conduct disorders: limited evidence, no approved drugs to guide treatment.

Chronic disruptive and impulsive behaviors are significant concerns for psychiatric clinicians because of their persistence and potential legal ramifications. To date, few studies have assessed treatment options for pyromania, oppositional defiant disorder (ODD), intermittent explosive disorder (IED), kleptomania, and conduct disorder (CD).

This article reviews the literature on the treatment of these disorders, focusing primarily on randomized, controlled studies. Because of the lack of clinical studies for these disorders, however, case studies and open trials are mentioned for reference. Summaries of supported medication and psychological interventions are provided for each disorder.

Categorizing impulse-control disorders

The DSM-5 created a new chapter on disruptive, impulse control, and conduct disorders that brought together disorders previously classified as disorders usually first diagnosed in infancy, childhood, or adolescence (ODD, CD) and impulse-control disorders not elsewhere classified. These disorders are unified by the presence of difficult, disruptive, aggressive, or antisocial behavior. Disruptive, aggressive, or antisocial behavior usually is a multifaceted behavior, often associated with physical or verbal injury to self, others, or objects or with violating the rights of others. These behaviors can appear in several forms and can be defensive, premeditated, or impulsive.

Despite a high prevalence in the general population (1) and in psychiatric cohorts, (2) disruptive and impulse-control disorders have been relatively understudied. Controlled trials of treatments do not exist for many impulse-control disorders, and there are no FDA-approved medications for any of these disorders.

Oppositional defiant disorder

Irritability, anger, defiance, and temper are specific descriptors of ODD. ODD seems to be a developmental antecedent for some youth with CD, suggesting that these disorders could reflect different stages of a spectrum of disruptive behavior. Transient oppositional behavior is common among children and adolescents, but ODD occurs in 1% to 11% of youth. (3) The disorder is more prevalent among boys before puberty and has an equal sex prevalence in young people after puberty.

Regrettably, most ODD research has included patients with comorbidities, most commonly attention-deficit/hyperactivity disorder (ADHD). Because of this limitation, the drugs and programs discussed below are drawn from meta-analyses and review articles.

Pharmacotherapy. No medications have been FDA-approved for ODD. Studies assessing ODD have employed a variety of methodologies, not all of which are double-blind. The meta-analyses and reviews cited in this section include both randomized and open trials, and should be interpreted as such.

Stimulants are commonly used to treat ODD because of a high comorbidity rate with ADHD, and these drugs have improved ODD symptoms in randomized trials. (4) Methylphenidate and d-amphetamine have shown some efficacy in trials of ODD and CD. (5-7) These medications are most commonly used when ODD is complicated by ADHD symptoms.

Antipsychotics also have been used to treat ODD, with the largest body of research suggesting that risperidone has some efficacy. Risperidone usually is considered a second- or third-line option because it has been associated with adverse effects in children and adolescents and requires caution in younger populations, despite its potential efficacy. (4,8-10)

Alpha-2 agonists--clonidine and guanfacine--have shown some efficacy in treating ODD but have not been studied extensively. Studies of clonidine, however, often have grouped ODD, CD, and ADHD, which limits our understanding of this medication for ODD alone. (4,5,11)

Atomoxetine has been studied for ODD, but its efficacy is limited, with different meta-analyses finding distinct results regarding efficacy. One explanation for these disparate findings is that improvements in oppositional symptoms may be secondary to improvement in ADHD symptoms. (7,12-14)

Psychological treatments. As noted for pharmacotherapy, this section provides general information on empirically studied therapies. A series of meta-analyses have been included for further review, but are not isolated to randomized, controlled studies.

Individual therapy has shown consistent improvements in ODD. Examples include behavior modification therapy and parent-child interaction therapy. These sessions emphasize skills to manage outbursts and erratic emotionality. Emotion regulation and behavior and social skills training have shown significant reductions in target measures. Some of these programs incorporate both patient and parent components. (15-17)

Family / teacher training programs such as "Helping the Noncompliant Child" and the "Triple P" have yielded significant improvements. These programs focus on ways to manage the child's oppositional behavior at home and in the classroom, as well as strategies to limit positive reinforcement for problem behaviors. (17-20)

Group programs have shown some efficacy with ODD. These programs cover a wide number of needs and intents. Examples include the "Incredible Years" program and the Community Parent Education Program. Research has found that these programs show some efficacy as preemptive measures to reduce the rate of ODD among adolescents.

Conclusions. A number of treatment options for ODD have shown some efficacy. However, many of these options have only been studied in patients with comorbid ADHD, which limits current knowledge about ODD as a distinct disorder.

Intermittent explosive disorder

IED is defined by recurrent, significant outbursts of aggression, often leading to assaultive acts against people or property, which are disproportionate to outside stressors and are not better explained by another psychiatric diagnosis. Research suggests IED is common, with 6.3% of a community sample meeting criteria for lifetime IED. (21)

IED symptoms tend to start in adolescence and appear to be chronic. (21,22) People with IED regard their behavior as distressing and problematic. (22) Outbursts generally are short-lived (usually <30 minutes) and frequent (multiple times a month (22)). Legal and occupational difficulties are common. (22)

Pharmacotherapy. Data on drug treatment for IED comes for a small set of double-blind studies (Table, page 32). Although pharmacotherapies have been studied for treating aggression, impulsivity, and violent behavior, only 5 controlled studies are specific to IED.

A double-blind, randomized, placebo-controlled trial of fluoxetine in 100 participants with IED found that fluoxetine produced a sustained reduction in aggression and irritability as early as the second week of treatment. Full or partial remission of impulsive aggressive behaviors occurred in 46% of fluoxetine-treated subjects. These findings have been supported by studies assessing other samples of aggressive patients, but not specifically IED. (23,24) Another treatment study found that oxcarbazepine produced significant improvements in IED symptom severity, specifically on impulsive aggression. (25)

In a randomized, double-blind, placebo-controlled study, 96 participants with Cluster B personality disorders, 116 with IED, and 34 with posttraumatic stress disorder were assigned to divalproex sodium or placebo for 12 weeks. Using an intent-to-treat analysis, divalproex had no significant influence on aggression in patients with IED. (26) Similarly, a study assessing levetiracetam for IED did not show any improvements to measures of impulsive aggression. (27)

Psychological treatments. The only available study on psychological treatments for IED found that patients receiving active cognitive-behavioral therapy (CBT) or group therapy showed significant improvements compared with waitlist controls. These improvements spanned several target symptoms of IED. (28)

Conclusions. Although there is a paucity of treatment studies for IED, fluoxetine may be an effective treatment based on available studies, and oxcarbazepine has shown some preliminary efficacy. CBT also has shown some initial efficacy in reducing symptom severity in IED.

Conduct disorder

The essential feature of CD is a repetitive and persistent pattern of behavior in which the basic rights of others or social norms are violated. (3) These behaviors can entail:

* aggressive conduct that causes or threatens harm to others or to animals

* nonaggressive behavior resulting in property damage

* deceitfulness or theft

* serious violation of rules.

Prevalence among the general population is 2% to 10%. The disorder is more common among boys than girls. (3)

Pharmacotherapy. No medication is FDA-approved to treat CD. Fifteen controlled studies have examined medications in patients with CD (Table, page 32), although a number of these included a high rate of comorbid ADHD.

To date, 7 studies have shown efficacy with lithium for patients with CD. (29-35) A number of trials assessing lithium also included a treatment condition with haloperidol, which showed significant improvement. (29,30,33,34) Both lithium and haloperidol were associated with select deficits on cognitive tests, suggesting that there may be risks associated with these medications.

Preliminary double-blind results have indicated that methylphenidate, risperidone, quetiapine, molindone, thioridazine, and carbamazepine might be effective options for treating CD. (36-43) The evidence for these medications is limited and additional studies are needed to replicate initial findings.

Three studies of divalproex sodium have shown some efficacy in randomized studies comparing high and low dosages of the drug. (40-42) Because these studies did not include a placebo, additional studies are necessary to corroborate these findings.

Psychological treatments. Several forms of behavioral, family-based, and school-based therapies have been found effective in randomized trials. Specifically, behavioral therapy and parental skills training have shown consistent benefits for patients and their families. As with ODD, parental training programs for CD focus on parents' skill acquisition to help manage outbursts and aggressive behavior. These treatments often follow a similar course to those used for other externalizing and disruptive disorders. (44-46)

Conclusions. Based on evidence, psychotherapy and some pharmacotherapies (eg, lithium) could be considered first-line treatment options for CD. Psychotherapy programs have shown efficacy in reducing aggression in high-risk groups. (44) Lithium or antipsychotics could be useful for patients who do not respond sufficiently to psychotherapy. The risk of cognitive deficits with lithium and antipsychotics should be weighed against potential benefits of these medications. (33,34)

Kleptomania

Kleptomania is characterized by repetitive, poorly controlled stealing of items that are not needed for personal use. Kleptomania often begins in late adolescence or early adulthood. (47) The course of the illness generally is chronic, with waxing and waning symptoms. Women are twice as likely as men to suffer from kleptomania. (48) People with kleptomania frequently hoard, discard, or return stolen items. (47)

Most people with kleptomania try unsuccessfully to stop stealing, which often leads to feelings of shame and guilt. (48) Many (64% to 87%) have been arrested because of their stealing behavior (47); a smaller percentage (15% to 23%) have been incarcerated. (48) Suicide attempts are common among these patients. (49)

Pharmacotherapy. There has been only 1 randomized, placebo-controlled study of pharmacotherapy for kleptomania (Table). An 8-week, double-blind, placebo-controlled trial was conducted to evaluate the safety and efficacy of oral naltrexone, 50 to 150 mg/d, in 25 patients with kleptomania. Those taking naltrexone had a significantly greater reduction in total score than those taking placebo on the Yale-Brown Obsessive Compulsive Scale Modified for Kleptomania; in stealing urges; and in stealing behavior. The mean effective dosage of naltrexone was 116.7 ([+ or -] 44.4) mg/d. (50)

Naltrexone was well tolerated, with minimal nausea, and did not cause elevation of liver enzymes.

There is one available open-label study with a double-blind discontinuation phase assessing the efficacy of escitalopram for kleptomania. Continuation of escitalopram during the blinded discontinuation phase did produce lower relapse rates. (51)

Psychological treatments. There are no controlled studies of psychological treatments for kleptomania. Case reports suggest that cognitive and behavioral therapies might be effective:

* A young man who underwent 7 sessions of covert sensitization, combined with exposure and response prevention, over a 4-month period was able to reduce his stealing frequency. (52)

* In another case, a young woman underwent 5 weekly sessions when she was instructed to practice covert sensitization whenever she had an urge to steal. She remained in remission for 14 months with only a single lapse in behavior and with no reported urges to steal. (53)

* In 2 patients, imaginal desensitization in fourteen 15-minutes sessions over 5 days resulted in complete remission of symptoms for a 2-year period. (54)

Conclusions. The single controlled study of naltrexone for kleptomania suggests that naltrexone might be a beneficial treatment for this disorder. No controlled trials of psychosocial interventions have been reported. The current psychological research is based primarily on case reports.

This state of affairs likely is because of (1) the low prevalence of kleptomania and (2) clinical difficulties in treating patients involved in illegal activities. Nevertheless, there is a need for systematic studies of treating this disorder; such studies could involve collaboration across multiple treatment centers because of the disorder's low prevalence.

Pyromania

Pyromania is characterized by (1) deliberate and purposeful fire setting on >1 occasion; (2) tension or affective arousal before the act; (3) fascination with, interest in, curiosity about, or attraction to fire and its situational contexts; and (4) pleasure, gratification, or relief when setting fires or when witnessing or participating in their aftermath. (3)

Although pyromania is thought to be a disorder primarily affecting men, recent research suggests that the sex ratio is equal among adults and may be slightly higher among adolescent females. Mean age of onset usually is late adolescence. Pyromania appears to be chronic if untreated. (55)

Urges to set fires are common and the fire setting is almost always pleasurable. Severe distress follows the fire setting, and persons with pyromania report significant functional impairment. High rates of co-occurring psychiatric disorders (depression, substance use disorders, other impulse-control disorders) are common among persons with pyromania. (55)

Pharmacotherapy. There are no randomized, controlled clinical trials examining pharmacotherapy for treating pyromania. There are no FDA-approved medications for pyromania.

hr case reports, medications that have shown benefit in treating pyromania include topiramate, escitalopram, sertraline, fluoxetine, lithium, and a combination of olanzapine and sodium valproate. An equal number of medications have shown no benefit: fluoxetine, valproic acid, lithium, sertraline, olanzapine, escitalopram, citalopram, and clonazepam. A case report of an 18-year-old man with pyromania described successfully using a combination of topiramate with 3 weeks of daily CBT to achieve significant symptom improvement. (56,57)

Pyromania is a largely unrecognized disorder that causes significant psychological, social, and legal repercussions. Because few persons with pyromania volunteer information regarding fire-setting, it is important that clinicians recognize the disorder and screen patients appropriately. Various treatments have been helpful in case studies, but more research on the etiology and treatment of the disorder is needed. (56,57)

Conclusions based on the literature

In disruptive, impulse-control, and conduct disorders, the systematic study of treatment efficacy and tolerability is in its infancy. With few controlled studies published, it is not possible to make treatment recommendations with confidence. There are no FDA-approved drugs for treating any of these disorders.

Nonetheless, specific psychotherapies and drug therapies offer promising options, but often are based on small studies, often in patient populations with prominent comorbidities, and have not been replicated by independent investigators. For all of these disorders, issues such as which psychotherapy or medication to use and the ideal duration of treatment cannot be sufficiently addressed with the available data.

In conjunction with emerging epidemiological data supporting a relatively high prevalence of disruptive, impulse-control, and conduct disorders, the small amount of data regarding effective treatments highlights the clinical need for additional research.

Bottom Line

Empirically supported treatment options for impulse-control disorders currently are limited, because only select disorders have been studied across multiple trials. New research is needed to confirm possible treatment options and identify effective psychotherapeutic and pharmacological treatment alternatives.

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Related Resources

* Grant JE. Impulse control disorders: a clinician's guide to understanding and treating behavioral addictions. New York, NY: W. W. Norton & Company; 2008.

* Grant JE, Kim SW. Stop me because I can't stop myself: taking control of impulsive behavior. New York, NY: McGrawHill; 2003.

* American Academy of Child and Adolescent Psychiatry. Conduct disorder resource center, http://www.aacap.org/ AACAP/Families_and_Youth/Resource_Centers/Conduct_ Disorder_Resource_Center/Home.aspx.

Drug Brand Names

Atomoxetine * Strattera

Carbamazepine * Tegretol

Citalopram * Celexa

Clonazepam * Klonopin

Clonidine * Catapres

D-amphetamine * Dexedrine

Divalproex sodium * Depakote

Escitalopram * Lexapro

Fluoxetine * Prozac

Guanfacine * Intuniv

Haloperidol * Haldol

Levetiracetam * Keppra

Lithium * Eskalith, Lithobid

Methylphenidate * Ritalin

Molindone * Moban

Naltrexone * ReVia

Olanzapine * Zyprexa

Oxcarbazepine * Trileptal

Quetiapine * Seroquel

Risperidone * Risperdal

Sertraline * Zoloft

Sodium valproate * Depacon

Thioridazine * Mellaril

Topiramate * Topamax

Valproic acid * Depakote

Jon E. Grant, JD, MD, MPH

Professor

Department of Psychiatry & Behavioral Neuroscience

University of Chicago, Pritzker School of Medicine Chicago, Illinois

Eric W. Leppink, BA

Research Specialist

University of Chicago Hospital

Department of Psychiatry & Behavioral Neuroscience

Chicago, Illinois

Disclosures

Dr. Grant receives grant or research support from Brainsway, Forest Pharmaceuticals, and Roche Pharmaceuticals. Mr. Leppink reports no financial relationship with any company whose products are mentioned in this article or with competing products.

Table
Trials (a) of medication for disruptive, impulse-control, and conduct
disorders

Impulse-control        Medication             Design, duration
disorder (b)

Intermittent explosive disorder (IED)
Coccaro et al, 2009    Fluoxetine             Parallel design, 12
(23)                                          weeks

Hollander et al,       Divalproex             Parallel design, 12
2003 (26)                                     weeks

Mattes, 2005 (25)      Oxcarbazepine          Parallel design, 10
                                              weeks

Mattes, 2008 (27)      Levetiracetam          Parallel design, 10
                                              weeks

Conduct disorder
Campbell et al, 1984   Lithium vs             Parallel design, 6
(29)                   haloperidol vs         weeks
                       placebo

Campbell et al, 1995   Lithium vs placebo     Parallel design, 10
(30)                                          weeks

Malone et al, 1998     Lithium vs placebo     Parallel design, 6
(31)                                          weeks

Malone et al, 2000     Lithium vs placebo     Parallel design, 6
(32)                                          weeks

Platt et al, 1981      Lithium vs             Parallel design, 6
(33)                   haloperidol vs         weeks
                       placebo

Platt et al, 1984      Lithium vs             Parallel design, 6
(34)                   haloperidol vs         weeks
                       placebo

Rifkin et al, 1997     Lithium vs placebo     Parallel design, 2
(35)                                          weeks

Cueva et al, 1996      Carbamazepine vs       Parallel design, 6
(36)                   placebo                weeks

Findling et al, 2000   Risperidone vs         Parallel design, 10
(37)                   placebo                weeks

Connor et al, 2008     Quetiapine vs          Parallel design, 7
(38)                   placebo                weeks

Greenhill, 1985 (39)   Molindone vs           Parallel design, 9
                       thioridazine           weeks

Khanzode et al, 2006   High-dose divalproex   Parallel design, 7
(40)                   vs low-dose            weeks

Padhy et al, 2011      High-dose divalproex   Parallel design, 7
(41)                   vs low-dose            weeks

Steiner et al, 2003    High-dose divalproex   Parallel design, 7
(42)                   vs low-dose            weeks

Klein et al, 1997      Methylphenidate vs     Parallel design, 5
(43)                   placebo                weeks

Kleptomania

Grant et al, 2009      Naltrexone             Parallel design, 8
(50)                                          weeks

Koran et al, 2007      Escitalopram           Mixed method
(51)

Impulse-control        Subjects               Mean daily dosage
disorder (b)                                  (+SD)

Intermittent explosive disorder (IED)
Coccaro et al, 2009    100 enrolled, 55       29.8 ([+ or -] 12.6)
(23)                   completers             mg for responders

Hollander et al,       109 subjects, No       1,567 mg
2003 (26)              data on % completers
                       (IED)

Mattes, 2005 (25)      48 enrolled, 24        1500 ([+ or -] 630)
                       completers (45 with    mg
                       at least 4 weeks)

Mattes, 2008 (27)      40 enrolled, 19        2313 ([+ or -]854)
                       completers (34 with    mg
                       adequate trial)

Conduct disorder       82 enrolled, 61
Campbell et al, 1984   completers             Lithium: 500 to
(29)                                          2,000 mg;
                                              Haloperidol: 1.0 to
                                              6.0 mg

Campbell et al, 1995   79 enrolled, 50        600 to 1,800 mg
(30)                   completers

Malone et al, 1998     40 enrolled, 40        1425 ([+ or -] 321)
(31)                   completers             mg

Malone et al, 2000     86 enrolled, 40        1,425 ([+ or -]321)
(32)                   completers             mg

Platt et al, 1981      30 enrolled, 27        1.5 to 6 mg
(33)                   completers

Platt et al, 1984      82 enrolled, 61        Lithium: 1,000 to
(34)                   completers             2,000 mg;
                                              Haloperidol: 1.0 to
                                              6.0 mg

Rifkin et al, 1997     33 enrolled, 26        0.6 to 1.0 mmol/L
(35)                   completers

Cueva et al, 1996      24 enrolled, 22        400 to 800 mg
(36)                   completers

Findling et al, 2000   20 enrolled, 9         0.75 to 1.50 mg
(37)                   completers (4 lost
                       from active group)

Connor et al, 2008     19 enrolled, 8         294 [+ or -] 78 mg
(38)                   completers (1 lost
                       from active group)

Greenhill, 1985 (39)   31 enrolled            Molindone: 27 mg;
                                              Thioridazine: 170 mg

Khanzode et al, 2006   71 enrolled; intent    500 to 1500 mg or
(40)                   to treat analysis      >250

Padhy et al, 2011      70 enrolled, 61        500 to 1500 mg or
(41)                   completers             >250

Steiner et al, 2003    71 enrolled; intent-   500 to 1500 mg or
(42)                   to-treat analysis      >250

Klein et al, 1997      83 enrolled, 74        41.3 mg (no SD
(43)                   completers             provided)

Kleptomania

Grant et al, 2009      25 enrolled, 23        116.7 ([+ or -]
(50)                   completers             44.4) mg

Koran et al, 2007      15 assigned to         20 mg
(51)                   blinded termination

Impulse-control        Outcome
disorder (b)

Intermittent explosive disorder (IED)
Coccaro et al, 2009    Fluoxetine group showed sustained reduction in
(23)                   symptoms

Hollander et al,       Similar improvement in IED and placebo
2003 (26)

Mattes, 2005 (25)      Oxcarbazepine group showed significant
                       reduction in symptoms

Mattes, 2008 (27)      No improvement compared with placebo

Conduct disorder
Campbell et al, 1984   Both active groups showed improvement across
(29)                   measures

Campbell et al, 1995   Lithium showed improvements in aggression
(30)                   symptoms

Malone et al, 1998     Explosive aggression showed greater response vs
(31)                   predatory aggression

Malone et al, 2000     Lithium group had greater reduction of
(32)                   aggression symptoms

Platt et al, 1981      Both active groups showed some cognitive
(33)                   deficits

Platt et al, 1984      Both active groups showed some cognitive
(34)                   deficits

Rifkin et al, 1997     No significant change on aggression measure
(35)

Cueva et al, 1996      No significant differences by group in regard
(36)                   to aggression

Findling et al, 2000   Active group improved across measures
(37)

Connor et al, 2008     Active group improved across measures
(38)

Greenhill, 1985 (39)   Aggressive symptoms improved in both groups

Khanzode et al, 2006   Depression and impulse control improved in
(40)                   high-dosage group

Padhy et al, 2011      High-dosage group showed greater improvement
(41)

Steiner et al, 2003    Moderate improvements on impulse control
(42)

Klein et al, 1997      Active group improved across measures
(43)

Kleptomania

Grant et al, 2009      Naltrexone significantly superior to placebo
(50)

Koran et al, 2007      No improvement compared with placebo for
(51)                   preventing relapse

(a) Double-blind, placebo-controlled

(b) No controlled studies have assessed treatment of pyromania or
oppositional defiant disorder independent of comorbid diagnoses

SD: standard deviation
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Author:Grant, Jon E.; Leppink, Eric W.
Publication:Current Psychiatry
Article Type:Report
Date:Jan 1, 2015
Words:5100
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