Dr. Ankenman is director of special services at Madison County Hospital in London, OH.

Acknowledgments: The author reports no financial, academic, or other support of this work. 



Are disorders distinct from attention-deficit/hyperactivity disorder (ADHD) prevalent in the overactive patient population? Giddy disinhibition disorder (GDD), a newly described syndrome of impulsive behavior, is distinctive in that the patient shows disinhibited, euphoric reactions to life events. GDD is often coexistent with other behavioral syndromes such as ADHD and obsessive-compulsive disorder, but has several unique symptoms, such as an almost constant giddiness, inability to demonstrate a serious response to consequences, and pain-seeking behavior. GDD is also unique in its response to therapy with naltrexone, which is an oral narcotic antagonist—an opioid receptor blocker. Naltrexone doses for GDD are up to three times higher than the 50 mg/day dose used for treating drug dependency. GDD is most often seen in developmentally disabled (DD) patients. In the author’s outpatient clinic for DD patients, approximately 10% receive naltrexone therapy. Some patients without developmental disability have been diagnosed with GDD?and treated. One such individual’s personal description of his experience illustrates some of the unique features of this disorder.



The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition1 (DSM-IV), does not include many of the behavioral situations seen in psychiatry, particularly in the developmental disabled (DD) population, where functional immaturity often contributes to psychiatric symptomology. Thus, in treating the DD population, physicians are likely to encounter syndromes not identified among the standard population. Since 1991, the Madison County Hospital Special Psychiatric Service in London, Ohio, has diagnosed certain DD individuals as having a disorder not previously defined and has treated them accordingly. The treating physicians have termed that condition “Giddy Disinhibition Disorder” (GDD), due to the increased level of giddy behavior observed in these patients during their social interactions. GDD patients demonstrate extreme tendencies to seek continuous pleasure-producing stimulation. They do not respond well to typical psychotropic medication regimens, but many of them demonstrate improved behavior when treated with the opioid receptor blocker naltrexone. This article describes the clinical features, prevalence, and results of therapy for this proposed disorder.

Due to the prevalence of comorbid conditions in the DD population, patients with GDD were rarely treated with naltrexone monotherapy in the Madison County Hospital clinic. However, there were enough cases of outstanding changes in behavior when naltrexone was added to the medication regime that it seems legitimate to propose GDD as a distinct disorder with a distinct treatment, and to expect that other clinicians will start to recognize it in the future.


Identification and Treatment Of Giddy Disinhibition Disorder

Individuals with GDD are often mistaken for having ADHD. They especially have many of the behaviors in the ADHD hyperactivity/impulsivity criteria, such as fidgeting, inability to stay seated, inability to play quietly, and being “on the go.” However, the GDD patient exhibits several distinct differences:

(1) The patient is continuously giddy, demonstrating excessive, inappropriate enjoyment of repetitive maladaptive acts (eg, the first patient treated would turn over the living room table again and again, laughing each time).
(2) The patient does not alter his/her behavior in response to negative reinforcement. Verbal and even physical confrontation generally brings on more giddy reactivity and laughing.
(3) The patient may not exhibit any defensive reaction against attempts at physical control. If one grabs the patient’s arm in an effort to redirect him/her, the arm may remain nonresponsive and “flabby.”
(4) The patient often seems immune to physical pain and will even seek it at times (eg, several individuals would seek to slam a finger into the hinge side of a closing door or stick a finger into electrical outlets to get shocked).
(5) In addition to the other four symptoms, the patient does not gain significant, lasting benefits from treatment with psychostimulants.

Much of the giddy behavior seen in DD psychiatric patients is attributable to their emotional immaturity. The Madison County Hospital clinic derived the new designation “GDD” for those patients who had such extreme giddy reactivity that it was the dominating problem of their clinical presentation. Standard medication regimens for treating impulsivity were minimally helpful, but, in some cases, the symptoms improved markedly with the administration of the opioid receptor blocker, naltrexone. The use of this medication was attempted because these individuals demonstrated not only indifference to physical pain, but also indifference to the social pressure of authority. This indifference to authority seemed similar to that of some narcotic addicts when they are “high.” It was hypothesized that individuals with GDD might have excessive endorphin activity and might respond to a narcotic-blocking medication.


Use of an Opioid Receptor Blocker

Use of opioid receptor blockers in the DD population has been occasionally mentioned in the literature, particularly for treating self-abusive behavior. Two important understandings were gleaned from these reports.

(A) Some individuals responded instantly, even responding transiently to the short-acting medication naloxone.2 This suggested the existence of an intrinsically high endorphin function that could be counteracted immediately; (B) There was a commonly stated effective dosage of 1–2 mg/kg/day.

Our clinic had seen successful treatment of self-abusive behavior with naltrexone in less than 20% of those administered the drug. A much higher percentage of GDD patients responded to naltrexone, and the response was surprisingly rapid. The first patient treated had decreased “pesky” behavior and “obnoxious” compulsions within 2 days. One child with fetal alcohol syndrome demonstrated increased verbalizations/responses to questions and a decrease in giddiness after 3 weeks of treatment. Individuals who had been in a constant state of disinhibition became more responsive to caregiver direction. However, they could still develop giddy arousal. In general, most individuals were about 50% less giddy. The efficacy of naltrexone was convincingly demonstrated in some patients who were given a low dose in the morning. Their behavior would be controlled until mid-afternoon and then become disinhibited. This responded to the addition of a second dose.

Over 100 patients in the Madison County Hospital clinic have been given a trial of naltrexone for symptoms suggesting GDD. In certain individuals, symptoms of the disorder dominated their entire presenting behavior and persisted for years, suggesting that they had a distinct pathological syndrome. However, in others who responded to naltrexone therapy, GDD symptoms were relatively minor and seemed to resolve over time. There is therefore a question of whether the disrupted physiology involved in GDD represents a true pathology, or an exaggeration of immaturity.  Approximately 50% of responders demonstrated considerable improvement with naltrexone therapy. The others showed modest but sufficient benefit to warrant continued use.

Of the 484 DD patients currently treated by the outpatient service, 46 are presently receiving naltrexone. Most of the recipients are young: 55% are 10–20 years of age and 44% are 20–30 years of age; one patient is over 30 years old. The dosage range is 50–200 mg/day (0.5–3.0 mg/kg/day). Sixty-four percent of current patients receive 1.4–2.4 mg/kg, and the mean is 1.7 mg/kg—a higher average than anticipated. Giving very high doses of naltrexone has rarely produced improved results. Generally, discontinuation trials with the drug have been safe. Those individuals whose behavior worsened when the naltrexone was lowered almost always re-established their previous improvement when the higher dose was reinstated.


Successful Treatment of Giddy Disinhibition Disorder: Case Study

The concept of GDD has remained unreported for a number of years. Although it seems to be a distinct clinical diagnosis with a specific treatment for some individuals, other DD patients presenting with symptoms suggesting GDD did not respond to naltrexone. Furthermore, the patients themselves could not give feedback about the effects of treatment.

In November 1997, a 17-year-old male without developmental disabilities was treated successfully with naltrexone for symptoms that were identified with GDD. The patient was in constant trouble for impulsive acts throughout high school (eg, he once sprayed a fellow students with a spray bottle containing urine). His behavioral problems began in middle school, and seemed to improve when he was treated with methylphenidate. However, at age 14 years, the patient’s symptoms of impulsive, socially disruptive activities returned, and he was given the diagnosis of bipolar disorder. He was then prescribed various stimulants, as well as clonidine, imipramine, valproate, verapamil, and olanzapine, without any success. When first seen by the author, the patient was taking lithium and risperidone. He was briefly treated for obsessive-compulsive disorder, but the behavioral patterns suggesting giddy disinhibition quickly became obvious.

The patient’s inability to respond to adult authority was notable. He also had recently sustained a significant cut to his arm without noticing it. Naltrexone 50 mg QAM was too sedating, but he tolerated 25 mg BID. The patient developed nearly instant control over his inappropriate social reactivity. Once the patient began treatment with naltrexone, both he and his parents rated his social improvement near 100%. His weight was about 75 kg, thus he responded to a much lower dosage of naltrexone (0.66 mg/kg) than used in most DD patients. He remained on lithium and risperidone because there was still a question of his having bipolar disorder.

The patient wrote the following statement about the effect of naltrexone on his behavior:

Before I was on naltrexone, I did not feel out of control even though I was. When I would do something wrong, I would not think it was wrong and I would just laugh about it. When teachers or parents or anyone else would try to correct me, I would just laugh in their faces—not because I wanted to make them mad, but just because I could not help it. I would also laugh in other situations and at other things that were inappropriate. Before I was on any medication at all, I often felt invincible—like I could conquer the world—and would often stay awake for days at a time. When we started fooling around with medicines, it did not do any good. We went through many, many different medications and combinations of medications and they either made me worse and more active, or sedated me to the point where I could hardly function and had many bad side effects. When I went on naltrexone, I noticed improvements immediately. I did not feel the need to laugh at everyone and everything. I have more of a concept of right and wrong and what their consequences are. I do not feel sedated, but I am not out of control for the first time in my life. I feel balanced and I enjoy life very much.

Since 1997, a few other patients without DD have been seen with symptoms suggesting GDD as part of their psychiatric history. These patients identified another symptom—that of disinhibited response to catastrophe. For example, in one patient’s history, it was noted that when a schoolmate cracked his head in a fall on concrete, the sound was so peculiar that he could not help laughing loudly in spite of the serious nature of the injury. As in the DD population, not all individuals who presented with the symptoms have benefited from naltrexone therapy.


Considerations About the Use of Naltrexone

Naltrexone has two Food and Drug Administration-approved indications—the treatment of narcotic addiction and alcohol dependency. Its use in self-abusive behavior is documented in more than a dozen references.3 There have been reports in the literature of benefits using narcotic antagonists in clinical states as diverse as Tourette’s disorder,4 “narrative” hallucinatory experiences,5 and chronic obstructive pulmonary disease.6 Various theories exist concerning the nature of endorphin dysregulation in these conditions. In cases where there is an immediate therapeutic response, it is generally theorized that the “endorphin high” originates from innately elevated endorphin activity rather than being related to a learned behavior. Currently, naltrexone is the only oral narcotic antagonist available, although others are being investigated.7



GDD is presented here as a previously unrecognized symptom cluster seen predominately, but not exclusively, in the DD population. Symptoms of GDD include giddiness, laughing, and pain-seeking behaviors—symptoms which are not included in the DSM-IV criteria for ADHD or the impulse-control disorders. There are extreme cases in which the entire behavioral pattern is dominated by GDD symptoms. A larger percentage of patients demonstrate various GDD symptoms as one of several comorbid states. Both types of patients can demonstrate rapid improvement when treated with an opioid receptor blocker like naltrexone, but some individuals with typical GDD symptoms do not respond to this treatment. Since a number of treated individuals do seem to demonstrate increasing control over their giddy disinhibited behavior over time, there remains the question of whether these symptoms represent a true psychiatric disease state or whether they represent an extreme case of immaturity. Other clinicians will need to determine if GDD is a valid diagnostic entity. Because its symptomology and pharmacologic treatment suggest an endorphin dysfunction, recognition of this syndrome may open the way to definitive research into the role of the endorphin system in psychiatric diseases other than the substance abuse disorders.   PP



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