Like most medical disorders, intermittent explosive disorder probably is caused by several factors. While scientists do not know the exact causes of the disorder, it is clear that physical and emotional factors play roles in its development. Childhood trauma may also be an important precursor to this disorder.
Biological or physical causes:
Theories about biological or physical causes of intermittent explosive disorder implicate:
- dysfunctional neurotransmitters, or brain chemicals, such as serotonin
- hormones such as testosterone
- regions of the brain linked to emotions and memory, such as the limbic system, or to planning and controlling impulses, such as the frontal lobes
People might either inherit or develop these physical/biological vulnerabilities, which are sometimes associated with mild neurological abnormalities. Predisposing factors in childhood include exposure to drugs or alcohol, head trauma, seizures and brain infections or inflammations.
Emotional or psychological causes:
Studies have shown that people with impulse control disorders such as intermittent explosive disorder are more likely to have a family history of addiction and mood disorders. Childhood trauma is common in people with intermittent explosive disorder.
Research also has shown that people with intermittent explosive disorder often grow up in unstable families marked by severe frustration, physical and emotional abuse, alcoholism, violence and life-threatening situations. They often lack role models to teach them how to control their impulses and emotions.
People might become explosive as a way of compensating for underlying feelings of insecurity and low self-esteem, which are common among people with the disorder. They also might become explosive when confronted with situations that remind them-consciously or unconsciously-of frustrating or dangerous experiences from their childhood. But regardless of the causes, explosive episodes are more likely to occur during periods of stress.
Intermittent explosive disorder can be treated by a variety of clinicians. The disorder is usually treated with pharmacotherapy by a psychiatrist, internist, or nurse practitioner.
Cognitive-behavioral therapy (CBT)
If cognitive-behavioral therapy (CBT) is used in addition to or instead of pharmacotherapy, a psychologist generally provides the psychotherapy. However, psychiatrists, internists, and nurse practitioners can provide all of the treatment if they are trained to administer CBT; treatment by a single clinician is often preferable because it allows for a better understanding of the patient and more consistent care. Patients who are either resistant or refractory to treatment are typically referred to a psychiatrist. The goal of treatment for intermittent explosive disorder is remission, which is defined as resolution of symptoms or improvement to the point that only one or two symptoms of mild intensity persist. For patients who do not achieve remission, a reasonable goal is response, i.e., stabilizing the safety of the patient and others, as well as substantial improvement in the number, intensity, and frequency of symptoms. Response can be quantified (e.g., improvement from baseline ≥ 50 percent) with standardized rating scales such as the clinician administered Overt Aggression Scale-Modified, but this is not standard clinical practice. Patients with intermittent explosive disorder should be advised to avoid intoxication with alcohol and other substances. Epidemiologic studies suggest that substance use disorders significantly increase the risk of violent behavior in schizophrenia, bipolar disorder, and major depressive disorder.
Acute treatment
Clinicians treat intermittent explosive disorder with pharmacotherapy plus cognitive-behavioral therapy (CBT), based upon randomized clinical trials that have demonstrated the limited benefit of each treatment alone. CBT teaches patients to anticipate and better manage aversive environmental stimuli and may thus prevent aggressive impulses. Medications may increase the threshold at which an aggressive impulse triggers an explosive outburst.
Monitoring outcome
Assessment of treatment outcome in patients with intermittent explosive disorder generally ranges from daily to monthly, depending upon the severity of persistent symptoms. Hospitalized patients are monitored daily. Outpatients are commonly seen on a weekly basis until they have responded (i.e., the safety of the patient and others has stabilized and the number, intensity, and frequency of symptoms has improved substantially) for two to four weeks.
At that point the patient can be seen every two to four weeks until they remit. Patients who subsequently deteriorate may need to resume a more frequent schedule of visits.
- Pharmacotherapy: Several medications have demonstrated efficacy for treating impulsive aggressive behavior in patients with intermittent explosive disorder or other psychiatric disorders (e.g., borderline personality disorder).
- First-line: Selective serotonin reuptake inhibitors (SSRIs) are first line pharmacotherapy for intermittent explosive disorder because of their demonstrated efficacy, tolerability, and ease of use. Fluoxetine has been studied most often and is thus preferred. However, other SSRIs are reasonable alternatives. The usual starting dose of fluoxetine is 20 mg taken once daily. For patients who do not respond within two to four weeks, the dose is increased by 10 to 20 mg per day, depending on how well the medication is tolerated. Patients who remain unresponsive to treatment should receive additional increases of 10 to 20 mg per day every two to four weeks as tolerated, to an effective dose. The maximum dose is 60 mg per day. Side effects that occurred significantly more often with fluoxetine included sexual dysfunction, sleep disturbance, nausea, vomiting, and restlessness.
- Resistant patients: Patients with intermittent explosive disorder often do not respond to an SSRI within 6 to 12 weeks of starting the drug. For these resistant patients, tapering and discontinuing the SSRI over one to two weeks at the same time that another medication is started and titrated up is suggested. The SSRI is generally tapered by the same amount for each dose decrease.
The other drugs that are preferred include:
- Phenytoin – The initial dose of phenytoin is 100 mg three times per day or 200 mg in the morning and 100 mg in the evening, depending upon tolerability and problems with adherence. A 12-hour serum trough level should be checked two weeks after the first dose, and one week after any dose change.
- Oxcarbazepine (or carbamazepine) – Oxcarbazepine and carbamazepine have a similar chemical structure, probably have a similar mechanism of action, and are generally regarded as comparable in efficacy for treating impulsive aggressive behavior. Oxcarbazepine is generally preferred because it usually causes fewer side effects and drug-drug interactions. However, carbamazepine may be less expensive and is a reasonable alternative.
The initial dose of oxcarbazepine is 150 or 300 mg per day. The dose is increased every two to four days by 150 to 300 mg per day, taken in two divided doses, to a target dose of 1200 to 2400 mg per day as tolerated.
Carbamazepine is usually started at a dose of 200 mg per day in two divided doses. The dose is increased every five days by 200 mg per day to a target dose of 800 to 1800 mg per day as tolerated.
Although there are no data correlating serum levels with efficacy in reducing impulsive aggression, toxicity may be prevented by maintaining the serum concentration ≤ 10 to 12 mcg/mL; extended release formulations can provide more stable serum levels.
For resistant patients with intermittent explosive disorder who do not respond to phenytoin within 6 to 12 weeks of starting the drug, or do not tolerate the drug, tapering and discontinuing it over one to two weeks at the same time that oxcarbazepine (or carbamazepine) is started and titrated up is suggested. Phenytoin is generally tapered by 50 to 100 mg per day, every two to three days.
The following drugs are suggested in sequence for refractory intermittent explosive disorder; the drugs are listed in order of preference, based upon how often each drug has been studied and how well it worked:
- Lamotrigine – The initial dose of lamotrigine is 25 mg per day for weeks one and two. For weeks three and four, the dose is increased to 50 mg per day, taken in two divided doses (an extended release formulation is available for once a day dosing). The dose can then be titrated up by 25 to 50 mg per day, one week at a time for each increase. This slow titration reduces the risk of life-threatening skin rash. The target dose ranges from 50 to 200 mg per day.
- Topiramate – The initial dose of topiramate is 50 mg per day, taken in two divided doses. The dose is increased by 50 mg per day every week, to a target dose of 200 to 300 mg per day as tolerated.
- Valproate (divalproex) – The initial dose of valproate is 250 mg twice daily, which is increased by 250 mg per day every 3 to 7 days as tolerated, to an effective dose. The maximum dose is 30 mg/kg/day.
- Lithium – The starting dose of lithium is usually 300 mg two or three times daily. The dose should be increased by 300 to 600 mg every one to five days as tolerated. The goal is to reach a therapeutic serum level, which generally occurs with a dose of 900 mg to 1800 mg per day. The target serum level is between 0.8 and 1.2 mEq/L, and levels should usually not exceed 1.2 mEq/L. Patients who cannot tolerate a level of 0.8 mEq/L may respond to a level of 0.6 mEq/L.
For refractory patients with intermittent explosive disorder who do not respond to one third-line drug within 6 to 12 weeks of starting the drug, or do not tolerate the drug, tapering and discontinuing the failed medication over one to two weeks at the same time that another third-line medication is started and titrated up is suggested.
The failed medication is generally tapered by the same amount for each dose decrease. As an example, lamotrigine 200 mg per day is decreased by 50 mg per day, every two to three days.
Cognitive-behavioral therapy
Impulsive aggressive behavior can be reduced with cognitive-behavioral therapy (CBT). CBT teaches patients how to manage aversive stimuli in the day-to-day environment, and may thus prevent aggressive impulses that can trigger explosive outbursts. Efficacious anger management interventions for patients with disorders other than intermittent explosive disorder typically make use of CBT.
Specific techniques used in CBT include:
- Cognitive restructuring (i.e., modifying faulty assumptions and dysfunctional thoughts about frustrating situations and perceived threats; the patient is encouraged to examine the validity of the assumptions and thoughts in light of all the available evidence)
- Relaxation training (e.g., deep breathing as well as progressive muscle relaxation that consists of tensing and relaxing different muscle groups while imagining situations that provoke anger)
- Coping skills training (e.g., role playing potentially provocative situations and rehearsing responses such as walking away)
- Relapse prevention (educating patients that recurrence of impulsive aggressive behavior is common and should be viewed as a lapse or “slip” rather than failure)
CBT works best for highly motivated patients who value a problem-solving approach to their illness. Conversely, CBT is contraindicated for patients who cannot learn the specific techniques that are taught (e.g., patients with moderate to severe cognitive deficits).
CBT can be administered in either a group or individual format. Patients typically receive 8 to 16 sessions of therapy, but some treatment plans may call for 20; each session lasts approximately 60 minutes. The skills taught in therapy are practiced in between sessions.
Nonresponse
CBT should be reconsidered for patients who make little progress after four to eight sessions, depending upon the total number of sessions called for in the initial treatment plan. Motivation should be reassessed and the use of pharmacotherapy discussed if a medication has not been prescribed.
CBT should be terminated for patients who do not engage in treatment (e.g., skip appointments without calling ahead or make no effort to complete homework) despite repeated efforts upon the part of the clinician. Patients who terminate treatment should be allowed to return when they are ready to actively participate.
Maintenance pharmacotherapy
Maintenance pharmacotherapy for intermittent explosive disorder is recommended using the same medication and dose that induced remission. The risk for recurrence of impulsive aggressive outbursts generally persists for months to years. However, there is little high quality evidence to guide decisions about maintenance treatment.
Adverse side effects
Maintenance pharmacotherapy for intermittent explosive disorder may cause side effects (eg, sexual dysfunction due to fluoxetine) that necessitate lowering drug doses within the target dose range.
For patients with intermittent explosive disorder who cannot tolerate maintenance pharmacotherapy with the minimum target dose of the drug that induced remission, switching to another drug is recommended.
The failed medication is tapered and discontinued over one to two weeks by the same amount for each dose decrease. (As an example, fluoxetine 40 mg per day is decreased by 10 mg per day, every one to two days.) At the same time, the new drug is started and titrated up. The choice of the new drug depends upon which medications, if any, were unsuccessful during acute treatment.
Monitoring the patient
Patients who have remitted from intermittent explosive disorder should be interviewed regularly and monitored for recurrence of symptoms as well as medication side effects. Particular attention is given to explosive outbursts, including physical assaults, verbal threats of interpersonal violence, and destruction of property.
Monitoring can be tapered for patients who remit and remain stable, with progressively longer intervals between assessments. As an example, a patient who is seen every two weeks at the time of remission can be seen every two weeks for one or two more visits, then every month for one to three visits, and then every two months for one to three visits. Continuously stable patients can ultimately be seen every three to six months. More frequent visits should be scheduled for patients who develop symptoms or side effects.
Duration and discontinuation
Patients who remit from intermittent explosive disorder receive maintenance pharmacotherapy for at least two years. However, the duration is not established, and some patients require treatment for many years. The duration depends upon clinical factors and is generally longer in patients with:
- Residual symptoms, particularly aggressive impulses and chronic anger
- Ongoing co morbid psychopathology
- Psychosocial impairment or stressors
- A history of suicide attempts or nonsuicidal self-injurious behavior
- A greater number of prior explosive outbursts (e.g., ≥ 30 physical or verbal outbursts)
- Duration of illness for several years (e.g., ≥ 5 years)
- A history of more severe impulsive aggressive behavior (e.g., physical assaults that lead to hospitalization)
If the decision is made to discontinue maintenance pharmacotherapy for intermittent explosive disorder, we suggest slowly tapering the medication over one month to increase the probability of detecting incipient symptoms (e.g., sub threshold incidents in which patients briefly scream) before full-blown explosive outbursts recur.
Based upon clinical experience, we decrease the dose each week by approximately 25 percent of the dose used during maintenance treatment. As an example, fluoxetine 40 mg per day is reduced by 10 mg per day each week until it is discontinued.
If symptoms recur during the taper, the dose should be titrated back up to the full dose used initially to achieve remission. If full-blown explosive outbursts develop despite increasing the dose, and the safety of the patient and others does not stabilize and the number, intensity, and frequency of symptoms do not substantially improve within 6 to 12 weeks of increasing the dose, the recurrence is treated as a new acute episode.
Recurrence — Recurrent symptoms during maintenance pharmacotherapy for intermittent explosive disorder are initially treated by optimizing medication doses. For medications that do not have a suggested therapeutic serum concentration, such as selective serotonin reuptake inhibitors (SSRIs), phenytoin, oxcarbazepine, lamotrigine, or topiramate, the dose should be increased within the target dose range as tolerated. For medications that have a suggested therapeutic serum concentration, such as valproate or lithium, clinicians should ensure serum concentrations are in the therapeutic range, and increase the dose to achieve a higher serum level within the therapeutic range, provided that side effects do not intervene.
If impulsive aggressive behavior recurs during maintenance pharmacotherapy and optimizing the dose does not control symptoms within 6 to 12 weeks, the recurrence is treated as a new acute episode.
For patients with intermittent explosive disorder who decide to stop maintenance pharmacotherapy and successfully taper and discontinue their medication, but subsequently relapse, we suggest restarting the same medication that was discontinued. The relapse is treated as a new acute episode.
