Open-label use of placebos in the treatment of ADHD: a pilot study.

BACKGROUND: This study examined short-term efficacy, side effects and acceptability of a placebo treatment procedure designed to maintain children with attention deficit hyperactivity disorder (ADHD) on 50% of their usual stimulant dose. METHODS: An open-label prospective crossover trial was conducted in 26 children with ADHD, ages 7-15 years, stable on stimulant therapy, followed at a community-based developmental paediatrics ADHD clinic. Subjects were randomly assigned to one of two orders of experimental conditions: (1) baseline (100%) dose (1 week), then 50% dose (1 week), then 50% dose + placebo (1 week), or (2) baseline (100%), then 50% dose + placebo, then 50% dose. The inert nature of the placebo was fully disclosed to parent and child. Treatment was open-label for child, parents and physician, but single blind for teachers. Main outcome measures included weekly IOWA Conners parent and teacher rating scales, the Pittsburgh side effects rating scale (PSERS) and the Clinical Global Impressions (CGI) scale. RESULTS: Parent IOWA showed ADHD behaviour tended to remain the same when the dose of stimulant medication was reduced with placebo but to deteriorate when the dose was reduced without placebo. There were no significant differences between conditions on the Teacher IOWA. PSERS scores were higher at baseline than on 50% dose. On the CGI, there was a significant difference (P = 0.004) between the 50% dose and the 50% + placebo conditions. Individual subject analysis showed that eight subjects met criteria for responder. CONCLUSIONS: Results indicate that the open-label placebo treatment was acceptable and efficacious in the short term for some children.

A comparison of behavioral and cognitive-behavioral interventions for bulimia nervosa.

This study examined the relative efficacy of cognitive-behavioral and behavioral treatment approaches for bulimia nervosa. Female bulimic Ss were randomly assigned to cognitive-behavioral, behavioral, or attention placebo conditions. At posttreatment, 92% of the cognitive-behavioral group, 100% of the behavioral group, and 69% of the nonspecific self-monitoring group were abstinent from binge eating-purging. At 6-month follow-up, 69% of the cognitive-behavioral group, 38% of the behavioral group, and 15% of the nonspecific self-monitoring group were abstinent from binge eating and purging. The results support the conceptualization of bulimia nervosa as a multifaceted disorder best treated with an approach that directly addresses maladaptive cognitions, problematic behaviors, and the development of more adaptive coping skills.

Varieties of repetitive behavior in autism: comparisons to mental retardation.

Systematic study of abnormal repetitive behaviors in autism has been lacking despite the diagnostic significance of such behavior. The occurrence of specific topographies of repetitive behaviors as well as their severity was assessed in individuals with mental retardation with and without autism. The occurrence of each behavior category, except dyskinesias, was higher in the autism group and autistic subjects exhibited a significantly greater number of topographies of stereotypy and compulsions. Both groups had significant patterns of repetitive behavior co-occurrence. Autistic subjects had significantly greater severity ratings for compulsions, stereotypy, and self-injury. Repetitive behavior severity also predicted severity of autism. Although abnormal repetition is not specific to autism, an elevated pattern of occurrence and severity appears to characterize the disorder.

The changing effector pattern of tardive dyskinesia during the course of neuroleptic withdrawal.

Tardive dyskinesia (TD) is a movement disorder that can be expressed at various body effector points, including the face, neck, arms, fingers, legs, and torso. In this prospective longitudinal study researchers examined whether the effector pattern of TD changed during the course of neuroleptic medication withdrawal in adults with mental retardation. Results indicated that the effector pattern of TD changed over the course of neuroleptic withdrawal. Peak dyskinesia was associated with the involvement of more body areas relative to baseline. Although dyskinesia decreased at follow-up and fewer body areas showed signs of dyskinesia, there were still differences in the effector pattern of dyskinesia relative to baseline at periods of 1 to 2 years following neuroleptic withdrawal. These findings suggest that TD is a dynamic disorder associated with changes in both severity and effector pattern over time.

Sequential analysis of the effects of naltrexone on the environmental mediation of self-injurious behavior.

Accumulated evidence shows that biology and the environment can mediate self-injurious behavior (SIB) in persons with mental retardation. Whether pharmacological treatment alters the environmental mediation of self-injury is unclear. Opioid antagonist effects on sequential dependencies for self-injury were studied in the context of experimental single-subject double-blind placebo-controlled designs. Direct observational data were collected for 4 adult subjects in real time on daily rate of SIB and staff interactions. Clinically significant reductions (i.e., > or = 33%) in SIB rate were observed for 3 of the 4 subjects. For all subjects, the magnitude of the sequential dependency between staff behavior and self-injury was significantly greater during treatment with naltrexone than during treatment with a placebo. Results are discussed in relation to behavioral mechanisms of action regulating medication effects for self-injury.

Diagnosis and fluoxetine treatment of compulsive behavior disorder of adults with mental retardation.

A set of research diagnostic criteria was developed to identify potential obsessive-compulsive disorders among individuals with mental retardation and aberrant behaviors. The behavior disorders of 10 subjects who met criteria for compulsive behavior disorder and 6 subjects who did not (comparison subjects) were treated using the medication fluoxetine. All subjects were evaluated using an A-B open-trial method with 4-month baseline and treatment phases. Seven of the 10 subjects with compulsive behavior disorder responded favorably to fluoxetine treatment; none of the comparison subjects responded favorably to this medication. Further, there appeared to be a relation between manifest motor stereotypies, compulsive behaviors, and response to fluoxetine.

Sudden unexpected death in epilepsy in adults with mental retardation.

The medical records of residents of a facility for persons with mental retardation from January 1, 1978, through December 31, 1997, were analyzed to identify incidence of sudden unexpected death for groups of 180 individuals with and 125 without comorbid epilepsy. Eighty deaths were identified, with 55 occurring in the epilepsy group and 25 in the nonepilepsy group. The rate of sudden unexpected death was 1.3 deaths per 1,000 patient years in the nonepilepsy group and 3.6 deaths per 1,000 patient years in the epilepsy group. The risk factors for sudden unexpected death in the epilepsy group were nonambulatory status and poorly controlled seizure disorder (increased seizure rate and increased number of antiepileptic drugs).

Tourette syndrome associated with mental retardation: a single-subject treatment study with haloperidol.

A Tic Checklist and direct observation tic measurement procedure were developed for the assessment of Tourette syndrome in individuals with mental retardation. Using a single-subject reversal design, we applied this assessment method to the evaluation of haloperidol treatment for a subject with Tourette syndrome and severe mental retardation. Relative to baseline, haloperidol 10 mg/day produced decreases of 66% in simple motor tics, 46% in complex motor tics, 45% in simple vocal tics, and 50% in complex vocal tics. Improvement was also seen in careprovider ratings of tic severity, hyperactivity, and compulsive behaviors.

Preliminary study of altered skin temperature at body sites associated with self-injurious behavior in adults who have developmental disabilities.

In this study, the sensory status of 4 nonverbal adults with mental retardation and severe self-injury was examined using skin temperature measures prior to opiate antagonist treatment. Double-blind, placebo-controlled, experimental ABAB designs were used to evaluate the effects of naltrexone hydrochloride (1.5 mg/kg/day). For each participant, the body site targeted most frequently for self-injury was associated with altered skin temperature and reduced by naltrexone. In all cases, neither infrequent self-injury body sites nor non-self-injury body sites were associated with altered skin temperature. Further controlled studies are warranted to examine the value of assessing pain status and skin temperature in nonverbal patients with mental retardation and related developmental disabilities who present with tissue-damaging SIB.

Variability of stereotypic body-rocking in adults with mental retardation.

The variability of stereotypic body-rocking motions of adults with severe and profound mental retardation not on medication was examined through a kinematic analysis. A matched nonretarded group of adults was also examined in the production of preferred rates of body-rocking. The inter- and intra-individual variability of the body-rocking motions was, on average, higher for the individuals with mental retardation, although a few participants showed as low a variability as the least variable participants in the nonretarded group. These findings provide further evidence that the kinematic variability of stereotypies is not lower than that displayed by others engaged in similar movement activities and support the proposition that low variability of discrete kinematic variables may not be a defining feature of stereotypy.

Blink rate as an index of dopamine function in adults with mental retardation and repetitive behavior disorders.

Direct observation of blink rate was used as a noninvasive, in vivo estimate of dopamine function in adults with mental retardation and repetitive behavior disorders. Blink rate as measured in groups of stereotypy, compulsion, and control subjects was highly stable. Subjects with stereotypies had significantly lower blink rates than did control subjects. Although blink rates for compulsive subjects were not significantly different from those of control subjects, a subgroup of compulsive subjects with comorbid stereotypic behaviors displayed significantly lower blink rates. Significant inverse correlations were found for blink rate and severity of repetitive behavior disorder and for blink rate and ratings of motor slowness. These findings support the hypothesis that stereotyped behavior among adults with mental retardation is mediated by hypodopaminergic function.

Clomipramine treatment for stereotype and related repetitive movement disorders associated with mental retardation.

The efficacy of the serotonin uptake inhibitor clomipramine in the treatment of stereotyped and related repetitive behavior disorders was tested in individuals with severe and profound mental retardation. A double-blind, placebo-controlled crossover trial of clomipramine was associated with significant reductions in the frequency and intensity of stereotyped behavior and teacher ratings of stereotypy, hyperactivity, and irritability as well as increased adaptive engagement and decreased staff intervention for nontargeted behavior problems. Adverse effects occurred in 3 of the 10 subjects. Of the 7 subjects who tolerated the drug, 6 exhibited a clinically significant improvement in one or more repetitive behaviors. Our results provide support for the hypothesis that clomipramine is effective in treating stereotyped and related behaviors associated with mental retardation.

Self-restraint and self-injury: occurrence and motivational significance.

The occurrence of self-restraint was examined in a sample of 99 adults with severe or profound mental retardation who exhibited self-injury. Results showed that 46% of the sample exhibited self-restraint. A significantly higher occurrence of compulsive behaviors was found for subjects who engaged in self-injury and self-restraint when compared to self-injury subjects without self-restraint. To determine the motivational significance of self-restraint, we assessed the response to brief interruption of this behavior. Subjects who engaged in self-restraint responded more negatively to response interruption than did control subjects. These preliminary findings support the hypothesis that self-injury may be related to a compulsive behavior disorder in some individuals who self-restrain.

Dyskinetic movement disorder among adults with mental retardation: phenomenology and co-occurrence with stereotypy.

We screened for the occurrence of dyskinetic and stereotypic movement disorders using item-independent screening protocols to determine whether these forms of movement disorder can be distinguished among adults with mental retardation. Stereotypies and dyskinesias were reliably distinguished in terms of topography. Tardive dyskinesia occurred in 18.2% of a cohort of individuals receiving chronic neuroleptic treatment. Stereotypic movement disorder was associated with increased dyskinesia scores and increased prevalence of tardive dyskinesia. Increased dyskinesia scores were also found for subjects exhibiting stereotypy who had been free of neuroleptic treatment for 3 years. Results indicate that dyskinesia and stereotypy are discriminable movement disorders and provide preliminary support for the hypothesis that they may be related by common mechanisms.

Stereotypy and motor control: differences in the postural stability dynamics of persons with stereotyped and dyskinetic movement disorders.

We examined whether dynamic measures of postural stability differentiated persons with stereotyped movement disorder from persons with dyskinetic movement disorder. Participants from three groups (stereotypy, dyskinesia, control) were given a goal-oriented postural stability task, and performance was measured using a force platform and computerized posturographic techniques. The results showed that both movement disorder groups differed from the control group in the posture task. Further, the stereotypy and dyskinesia groups demonstrated markedly different postural movement profiles. The postural motion of the stereotypy group was characterized by greater amplitude and variability but lower complexity than the dyskinesia group. These results provide support for a motor control model of stereotypy.

Akathisia in adults with mental retardation: development of the Akathisia Ratings of Movement Scale (ARMS).

We developed an akathisia rating scale for use with persons who have mental retardation and screened for the occurrence of akathisia in three samples: 66 adults receiving maintenance neuroleptic treatment, 20 adults not receiving neuroleptics, and 8 adults undergoing neuroleptic dose reduction. The scale had an acceptable level of interrater reliability and validly measured group differences related to neuroleptic treatment status. Using an empirically derived cut-off-score, we estimated the prevalence rate for akathisia to be 5% in neuroleptic-free subjects, 17% in neuroleptic-maintenance subjects, and 25% in neuroleptic-reduction subjects. Akathisia, dyskinesia, and stereotypy manifested as qualitatively different movement topograhies. The occurrence of dyskinesia stereotyped movement disorder was associated significantly with an increased occurrence of akathisia.

Clomipramine treatment for self-injurious behavior of individuals with mental retardation: a double-blind comparison with placebo.

The efficacy of the serotonin (5-HT) uptake inhibitor clomipramine in the treatment of self-injurious behavior (SIB) was tested in individuals with severe and profound mental retardation. Six of the 8 subjects who completed a double-blind, placebo-controlled crossover trial exhibited a clinically significant improvement (50% or greater reduction from placebo) in the frequency of SIB. Clomipramine treatment was also associated with improvement in SIB intensity, frequency of stereotypy and compulsions, teacher ratings of stereotypy and social withdrawal, and frequency of staff intervention required for problem behaviors. Adverse effects (seizure and tachycardia/agitation) occurred in 2 of the 8 subjects. These results represent the first controlled trial of a 5-HT uptake inhibitor in the treatment of SIB in mental retardation.

Dynamics of lip dyskinesia associated with neuroleptic withdrawal.

The lip movements associated with dyskinesia in adults with mental retardation were investigated through a dynamic analysis at medication baseline, at the points of the highest level of withdrawal dyskinesia as indexed by the DISCUS rating scale, and at the lowest level of dyskinesia following complete withdrawal of the medication. Results showed that the changes in the amount of lip oscillations following medication reduction and eventual withdrawal were strongly linked to changes in the structural complexity of the dynamics of lip motions. These findings provide evidence that neuroleptic medication reduces the df of the dynamics of the movement output and that this change is inversely related to the level of tardive dyskinetic motion observed in the clinical setting.

Compulsions in adults with mental retardation: prevalence, phenomenology, and comorbidity with stereotypy and self-injury.

A variety of conceptual similarities between compulsions seen in individuals with obsessive compulsive disorder and stereotypy and self-injury seen in individuals with mental retardation led us to investigate the prevalence, phenomenology, and comorbidity of compulsions in adults with severe or profound mental retardation. We developed simple assessment screening instruments for stereotypy and self-injury and used Gedye's Compulsive Behavior Checklist and found acceptable levels of reliability, stability, and validity for each instrument. Prevalences were as follows: stereotypy: 60.9%; self-injury: 46.6%; and compulsion: 40%. The occurrence of compulsions was significantly positively associated with the occurrence of stereotypy, self-injury, and stereotypy plus self-injury.