Clozapine treatment in a population of adults with mental retardation

BACKGROUND: There is a paucity of data on the use of clozapine in patients with mental retardation and comorbid psychiatric illness. The authors describe their recent clinical experience using clozapine in treatment-refractory patients with mental retardation and severe psychiatric illness. METHOD: A retrospective review was performed on the records of all patients admitted to a university-affiliated, specialized inpatient psychiatry service who were selected for clozapine therapy from March 1994 through December 1997 (N = 33). Patients had DSM-IV diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder, delusional disorder, or psychotic disorder NOS and were considered treatment resistant. All had deficits in functioning well beyond those expected for their degree of cognitive deficits and adaptive delays. RESULTS: Of 33 initial patients, 26 remained on clozapine therapy for a follow-up duration of 5 to 48 months (mean = 24.8 months). Evaluation at follow-up revealed Clinical Global Impressions-Improvement (CGI-I) scores from 1 to 4 with a mean +/- SD improvement of 2.0 +/- 0.8 (much improved). The mean +/- SD rating of the CGI-Efficacy Index was 5 +/- 2.6 (decided improvement and partial remission of symptoms with no interference from side effects). The 6 patients who were not maintained on clozapine therapy over the study period did not significantly differ from the clozapine group in gender, race, age, side effects, or diagnosis. One patient was lost to follow-up. Side effects were mild and transient with constipation being the most common (N = 10). There were no significant cardiovascular side effects and no seizures. No patients discontinued treatment due to agranulocytosis. CONCLUSION: The current investigation lends support to the conclusion that clozapine appears to be safe, efficacious, and well tolerated in individuals with mental retardation and comorbid psychiatric illness.     

Nonambulatory persons with profound mental retardation: Physical, developmental, and behavioral characteristics

Although profound mental retardation is generally associated with various organic etiologies that result in substantial cognitive and behavioral deficits, little is known about specific subgroups of persons with profound mental retardation. This study presents data on the physical, developmental, and behavioral characteristics of a group of 203 nonambulatory persons with profound mental retardation residing within a specialized service setting. The results indicate that nonambulatory persons with profound mental retardation have a high prevalence of physical and medical problems along with high rates of self-injurious, stereotypic, and aggressive behavior. Assessment results from the Stanford-Binet (L-M), Bayley Scales of Infant Development-Mental Scale, and Vineland Adaptive Behavior Scale reveal a high degree of variability in cognitive and adaptive functioning. However, developmental age-equivalent scores of cognitive ability, communication, daily living, socialization, and motor skills for the group fell below the 1-year level. The data illustrate the complexity of needs in providing habilitative services to nonambulatory persons with profound mental retardation.     

Patterns of intellectual, adaptive and behavioral functioning in individuals with mild mental retardation

Many researchers have studied the population of individuals with mild mental retardation (MIMR) as if it is a clear entity. Few researchers have investigated potential subtypes within the MIMR population. The purpose of the present study was to investigate which subtypes can be identified on the basis of intellectual, adaptive and behavioral functioning. Seventy-three individuals with MIMR were assessed on measures of intellectual, adaptive and behavioral functioning. An agglomerative hierarchical cluster-analytic technique was used to define potential subgroups with characteristic behavioral patterns. Four subtypes were identified. The behavioral patterns are described and implications for assessment are discussed.     

The apparent effects of ziprasidone on plasma lipids and glucose.

BACKGROUND: We examined the effects of ziprasidone on body mass index (BMI) and serum levels of glucose, cholesterol, and triglycerides. METHOD: As part of a multicenter study examining different strategies for switching to ziprasidone from other antipsychotics, we evaluated weight and serum glucose, cholesterol, and triglyceride measurements at baseline and following 6 weeks on ziprasidone treatment in 37 patients at our site. RESULTS: Short-term treatment with ziprasidone appeared to lead to significant reduction in serum cholesterol (p < .001) and triglyceride levels (p = .018) independent of changes in BMI. Ziprasidone treatment appeared to have no significant effect on BMI or glucose level, perhaps due to the small number of subjects. CONCLUSION: Ziprasidone appears to independently lead to a lowering of serum lipid levels.     

Handedness distribution in a residential population with severe or profound mental retardation

Handedness within a sample of mentally retarded subjects was assessed using a procedure that includes a large number of items appropriate for lower functioning subjects, with multiple presentations within and between sessions one week apart. Results revealed a dramatic shift from the normal right-handed bias primarily due to the presence of a large mixed-handedness subtype, which proved to be ambiguously handed in that these subjects showed inconsistent hand preference within items. Reasons why this subtype has not been reported previously were discussed, and a model was postulated to explain the resultant handedness distribution in terms of probable central nervous system substrate.     

Assessment and diagnosis of mental illness in persons with mental retardation. Methods and measures

The assessment and diagnosis of psychiatric disorders in individuals with mental retardation has been a neglected area of research. However, current research indicates that these individuals suffer from the same range of psychiatric disorders that is evident in those who are not mentally retarded. A model of assessment and diagnosis of mental illness in this population is presented that incorporates psychiatric as well as behavioral methods. The emphasis is on the comprehensive assessment of an individual's behavior, based on family history, self and informant clinical interviews, rating scales, direct observations, and an experimental analysis of the target behaviors. The model provides the basis for making differential diagnoses in terms of related psychiatric disorders and between psychiatric disorders and behavior problems. Depression and schizophrenia are used as illustrative disorders to describe the application of this model. Given the paucity of literature on the assessment and diagnosis of mental illness in individuals with mental retardation, a number of suggestions are made regarding future research and refinement of the model.     

Weight gain in a controlled study of risperidone in children, adolescents and adults with mental retardation and autism

As part of an ongoing, prospective, ABA design, double-blind crossover study of risperidone versus placebo for the treatment of aggressive, destructive and self-injurious behavior in persons aged 6-65 years with mental retardation (MR) and autism, we measured the weight of 19 subjects at each study visit. We compared mean weight gain during the 16-week acute phase and 24-week open maintenance phase with that during the initial and middle placebo phases statistically, using a linear mixed model procedure. Results of the linear mixed model analysis showed that relative weight gain observed during the acute and maintenance drug phases was significantly greater than that observed during the initial and middle placebo phases respectively (p = .0001 and p = .0001). Over approximately a year, children aged 8-12 (n = 5) gained a mean of 8.2 kg (range = 2.7-17.7 kg); adolescents (n = 6) aged 13-16 gained a mean of 8.4 kg (range 3.6-15.5 kg); adults aged 21-51 (n = 8) gained a mean of 5.4 kg (range 0-9.5 kg). Weight gain observed in this controlled study of risperidone treatment in children, adolescents, and adults with MR and autism was significant. It may be greater in this population than in others reported and in this study was not limited to an acute effect only. Rate of weight gain diminished rapidly on tapering and stopping the drug. Further studies are urgently needed, including those incorporating diet and exercise programming.     

Pharmacologic management of psychiatric and behavioral symptoms in mental retardation

Compared with the general population, individuals with mental retardation demonstrate more susceptibility to psychiatric illness and may display disruptive behaviors. These symptoms significantly can affect an already compromised ability to function and the patient may benefit from pharmacologic intervention. Clinical characteristics of individuals with mental retardation warrant special consideration regarding diagnosis and treatment of their psychiatric and behavioral problems. This article describes the nature of symptoms that are typically the target of pharmacologic intervention, outlines special diagnostic considerations, and examines recent findings and experience with psychotropic medication in mental retardation.     

齐拉西酮治疗老年痴呆精神行为障碍对照研究

目的：探讨齐拉西酮和氟哌啶醇对老年期痴呆患者精神行为症状（BPSD）的疗效和安全性。方法：将60例老年期痴呆伴BPSD患者随机分成两组,分别使用齐拉西酮和氟哌啶醇治疗8周,采用痴呆病理行为评定量表（BEHAVE-AD）,激越行为量表（CMAI）及治疗中出现的症状量表（TESS）评定疗效和不良反应。结果：两组治疗前后BEHAVE-AD和CMAI评分显著下降（P〈0.01）,两组患者之间治疗前后BEHAVE-AD总减分值差异无统计学意义（P〉0.05）,但情感障碍和焦虑两因子减分值差异有统计学意义（P〈0.05）。结论：齐拉西酮和氟哌啶醇治疗老年期痴呆患者BPSD的疗效相当,齐拉西酮的优势在于对情感障碍和焦虑的疗效更加明显,锥体外系不良反应轻。     

Weight survey on adult persons with mental retardation living in the community

Prevalence of underweight and obesity were investigated in 282 mentally retarded persons living on the West Coast of Norway. Data collected in this survey suggest that people with severe mental retardation were more likely to be underweight and people with mild mental retardation were more likely to be obese. Compared to persons of average intellectual levels, persons with mental retardation were found to be over-represented with both underweight and obesity. Food refusal and self-induced vomiting was more present among persons regarded as underweight and reduced control of food intake was related to obesity. Findings suggest that behavioral variables may have explanatory value with respect to both underweight and obesity. Further investigation using functional analysis of behavior is recommended.     

Integrating behavioral and pharmacological interventions in treating clients with psychiatric disorders and mental retardation

While the literature on treatment of dually diagnosed individuals continues to grow, few studies have examined the potential interactions between behavioral interventions and pharmacological interventions in treating persons with a developmental disability and a concurrent psychiatric disorder. The current theoretical paper discusses different manners in which psychotropic medications and behavioral interventions can interact, including the potential for facilitative or inhibitory effects of one treatment modality on the other. Possible permutations of these interactions are discussed. Case examples, including objective measures of psychiatric and behavioral symptoms over time, representing possible illustrations of these permutations, are presented. The authors argue that in many cases the potential effect of one treatment procedure on the efficacy of another may be an important consideration in treating dually diagnosed individuals.     

Empirical classification of behavioral and psychiatric problems in children and adolescents with mental retardation

A quantitative method for typing psychopathology of youngsters with mental retardation was assessed. Parents of 601 students in special educational placements rated them with the ABC. The sample was randomly divided into two subgroups. We used Ward's hierarchical method of cluster analysis and derived eight clusters in Subsample 1 and satisfactory agreement, kappa =.64, for the eight-cluster solution in Subsample 2. Clusters were: Problem Free, Within Normal Limits, Conduct Problem, Shy/Inactive, Hyperactive, Social Withdrawal With Agitation, Undifferentiated Behavior Disturbance, and Autistic-Like Behavior. We also used demographic (age, gender, IQ, physical handicaps) and clinical variables (DSM diagnoses and target behaviors) extracted from school records of 228 participants to appraise validity of the empirically derived clusters. The external data provided modest to strong support for all except one cluster (Social Withdrawal With Agitation).     

Diagnosis and treatment of depression in patients with mental retardation

Depression in mentally retarded individuals is not uncommon and usually is treatable. However, studies of the diagnosis and treatment of psychiatric illnesses in general and depression specifically in this population are relatively rare. Although Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria can be applied to mildly and moderately retarded individuals, the diagnosis of depression in those with intelligence quotients below 35 is challenging. However, the diagnosis of depression in the latter group is possible using modified criteria emphasizing observational data. Criteria include symptoms such as sadness, irritability, decreased social interaction, regression of skills, sleep disturbances, diurnal variation, and aggression. Furthermore, there is a growing body of evidence that antidepressant treatments, especially administration of selective serotonin reuptake inhibitors, are effective in treating depression in mentally retarded patients. This article reviews numerous studies elaborating on the diagnosis, phenomenology, and treatment of depression in mentally retarded individuals.     

Treatment effects of methylphenidate on behavioral adjustment in children with mental retardation and ADHD

OBJECTIVE: The effects of stimulant medication treatment were investigated in children with mental retardation (MR) and attention-deficit/hyperactivity disorder (ADHD). METHOD: Parent and teacher behavioral ratings and reports of side effects were obtained for children (N = 24, mean age = 10.9 years, SD = 2.4) during a placebo-controlled, double-blind, crossover treatment trial with 0.15 mg/kg, 0.30 mg/kg, and 0.60 mg/kg b.i.d. dosages of methylphenidate. RESULTS: The most significant improvements occurred at the 0.60 mg/kg methylphenidate dose for teacher ratings of inattention (p =.024), hyperactivity (p <.001), aggression (p <.001), and asocial behavior (p =.009). No significant improvements, relative to placebo, occurred at the 0.15 mg/kg dosage. Of interest, nearly all significant medication-related behavioral improvements were detected by teachers. However, parents were sensitive raters of side effects, noting more sleeping problems and loss of appetite at the 0.60 mg/kg dose compared with placebo. CONCLUSIONS: These results suggest that symptoms of ADHD can be treated successfully in children with ADHD/MR, and consistent with MTA study results, higher doses were most effective. Furthermore, these improvements were not accompanied by increases in symptoms such as staring, social withdrawal, or anxiety.     

Benzodiazepine behavioral side effects: review and implications for individuals with mental retardation

Behavioral side effects associated with benzodiazepines (such as clonazepam, diazepam, and lorazepam) are an easily overlooked and underrecognized problem with individuals who have mental retardation and can be inadvertently confused with other behavioral or psychiatric conditions. Based upon a literature review, behavioral side effects occurred for 13.0% of 446 individuals with mental retardation who were prescribed benzodiazepines for either behavioral or psychiatric conditions (n = 138, 17.4%), epilepsy (n = 208, 15.4%), or other medical conditions such as myoclonus or cerebral palsy (n = 100, 2.0%). Behavioral side effects for individual benzodiazepines for which data were available ranged from 11.4% to 25.0%. Implications of nonrecognition are discussed, and clinical indicators suggesting review by appropriate medical personnel are provided.     

Multicomponent treatment for blood-injury-injection phobia in a young man with mental retardation

Blood-Injury-Injection Phobia (BIIP) is a subtype of specific phobia, characterized by fear and avoidance of seeing blood, an injury, or receiving an injection. In the current case report, we describe the treatment of BIIP in a young man with mental retardation. The multicomponent treatment consisted of fading (graduated exposure), modeling, noncontingent and differential reinforcement, presession anxiolytic medication, and topical analgesic cream.