Self-injurious behaviour, traumatic life events and alexithymia among treatment-seeking opiate addicts: prevalence, pattern and correlates

Objective

Aim of this study was to determine the prevalence and pattern of self-injurious behaviour (SIB) and identify the predictors of SIB among treatment-seeking opiate addicts.

Methods

Participants were 80 consecutively consenting opiate addicts admitted into community and inpatient treatment programmes of a large South London National Health Service (NHS) Mental Health Trust. Substance dependence was diagnosed with ICD-10. The following instruments were administered: self-injurious behaviour questionnaire, traumatic life events questionnaire, Toronto alexithymia scale and substance abuse assessment questionnaire.

Results

Lifetime SIB prevalence rate was 49% (95% CI = 37–60). There was no difference in lifetime SIB rates of male (50%) and female (46%) patients. The predominate function of SIB among opiate addicts was affect-regulation followed by self-punishment. Using a logistic regression, sexual harassment and difficulty identifying feelings were the only independent significant predictors of SIB, with the influence of age of first traumatic event and gender partialled out.

Conclusion

Given these findings, there is strong evidence to suggest that treatment of opiate addiction should involve routine screening for adult sexual trauma, deficits in emotional regulation and SIB. Where these problems are identified, appropriate psychological intervention should be integral to routine care for affected patients.     

Self-injurious behaviour: a comparison of caffeine and pemoline models in rats

Self-injurious behaviour (SIB) is a debilitating behaviour disorder that can have life-threatening consequences. It is often exhibited in intellectually handicapped and autistic populations, and it has been modeled with pharmacological manipulations in animals. We have characterized the induction of SIB using high doses of caffeine and pemoline in rats. Caffeine only produced very mild SIB in a small proportion of the rats, when administered repeatedly at very high doses (140-185 mg/kg/day). All the caffeine-treated rats showed profound signs of caffeine-toxicity at these doses, and lower doses did not induce any self-injury. On the other hand, pemoline was effective across a range of doses (100-300 mg/kg/day), including doses that did not produce overt signs of toxicity (100-200 mg/kg/day). The topography of the tissue injury sites (tail vs. paws and ventrum) differed between caffeine and pemoline treatments, and across doses of pemoline. The speed of onset, the incidence, and the severity of SIB occurred in a dose-orderly manner across the pemoline doses, and there was substantial individual variability in the induction of SIB when a moderately high dose (200 mg/kg/day) was used. These individual differences in vulnerability to self-injure are reminiscent of the fact that some humans with specific neurobiological disorders express SIB and some individuals with those same disorders do not. Accordingly, the pemoline model of SIB may be useful to investigate the neurobiological basis of factors that contribute to etiology of SIB.     

Cost-effectiveness of memantine in moderate-to-severe Alzheimer's disease patients receiving donepezil*

ABSTRACT

Objective: The efficacy and safety of memantine in patients with moderate-to-severe Alzheimer's disease (AD) receiving stable doses of donepezil were recently demonstrated in a phase III trial. The cost-effectiveness of such therapy is unknown.

Research design and methods: A microsimulation model was developed to depict AD progression over time and associated clinical and economic outcomes. AD progression was measured in terms of decline in cognitive function, as assessed by the Severe Impairment Battery (SIB). At model entry, patients were assumed to have moderate-to-severe AD, to be on stable doses of donepezil, and to begin combination therapy with memantine, or continue to receive donepezil alone; duration of therapy was assumed to be 1 year. Drug efficacy was based on data from a phase III trial. Key assumptions of the model included: (1) efficacy of study drugs would extend to 1 year; (2) measures of cognitive function could be mapped to one another, as well as to global measures of disease severity; and (3) following therapy discontinuation, cognitive function would revert immediately to natural history levels. Cost-effectiveness was assessed in terms of cost (2005 US$) per quality-adjusted life-year (QALY) gained over a lifetime (3% discount rate).

Results: SIB scores were estimated to improve by 3.3 over 1 year from therapy with memantine plus donepezil (vs. donepezil alone). While pharmacotherapy costs were estimated to increase by $1250 during the year of memantine treatment, costs of formal and informal services were estimated to decrease by $1240 over this period and by $1493 (discounted present value) over a lifetime. Findings were sensitive to the assumed SIB score at therapy initiation; cost-effectiveness was better for patients with higher initial SIB scores (i.e., less severe disease).

Conclusion: In patients with moderate-to-severe AD already receiving donepezil, treatment with memantine results in improved clinical outcomes and reduced total costs of care.     

The differential diagnosis of self-injurious behavior in mentally retarded people

Self-injurious behavior (SIB) is sometimes presented as if it were a unitary behavioral entity. It is this assumption that leads to impunity in clinical trials of SIB patients, who are thought to be a homogeneous group. In fact, nothing could be further from the truth. SIB is no more than the occasion for a neuropsychiatric differential diagnosis; first to consider environmental and medical circumstances that may induce SIB; then specific, diagnosable conditions from neurology and psychiatry; then specific syndromes like Lesch-Nyhan and Cornelia de Lange; and then for "idiopathic" cases, the alternative neuro-chemical hypotheses. The goal of differential diagnosis is not only to guide treatment, but also to improve subject homogeneity in clinical trials.     

Paradoxical effects of serotonin and opioids in pemoline-induced self-injurious behavior.

Self-injurious behavior (SIB) is a symptom of various psychiatric disorders with differing etiologies. Although no generally effective pharmacological treatment of SIB is available, subsets of individuals exhibiting SIB have been found to respond to opioid antagonists and selective serotonin reuptake inhibitors (SSRIs). The present study evaluated the efficacy of these two treatments in the pemoline-induced model of self-biting behavior (SBB) in rats. Using a factorial design, adult rats receiving daily pemoline at 100 mg/kg or the peanut oil vehicle were pretreated with either distilled water vehicle (1 cc/kg), naltrexone (1 mg/kg), or paroxetine (1 mg/kg). Each day, animals were rated on the severity of SBB and also periodically behavioral changes were evaluated using various other outcome measures. Paroxetine significantly increased the severity of SBB induced by pemoline, while naltrexone only marginally increased the SBB. These results were not expected and suggest that further studies into the role of serotonin agonists and antagonists are needed in evaluating this model.     

Topiramate attenuates self-injurious behaviour in Prader-Willi Syndrome

Self-injurious behaviour (SIB), most notably skin picking, has been described by various terms in the literature ranging from neurotic/psychogenic excoriations to compulsive/pathological skin picking. Prader-Willi Syndrome (PWS) is a neurogenetic multisystem disorder characterized by infantile hypotonia, mental retardation, short stature, hypogonadism, dysmorphic features, and hyperphagia with a high risk of obesity. Psychiatric manifestations include SIBs in the form of skin picking, nail biting and rectal gouging. Topiramate is a novel anti-epileptic medication without significant liability of weight gain. There are no published reports of topiramate being utilized in PWS or SIB. We report attenuation of SIB with resultant lesion healing in three PWS adults treated with topiramate in an 8-wk open-label trial. Although our findings should be treated with caution, they suggest that double-blind or cross-over studies with topiramate are warranted to establish the possible role of topiramate in attenuating SIB in PWS and other disorders that involve SIB.     

Repeated pemoline produces self-injurious behavior in adult and weanling rats

Self-injurious behavior (SIB) is a serious problem among the mentally handicapped and is often accompanied by other repetitive or stereotyped behaviors. Acute administration of high doses of amphetamine or pemoline to rats produces transient SIB which is accompanied by severe deterioration of the behavioral repertoire. Repeated subcutaneous (SC) administration of pemoline to rats produces a high incidence of SIB without the dramatic behavioral changes produced by high doses of oral pemoline. Repeated pemoline increased locomotions and rears and produced intermittent stereotyped sniffing and licking/biting. However, the animals were still able to eat, drink, sleep and groom. Hotplate tests provided no evidence for analgesia. Because SIB is often associated with human developmental disorders, the effects of repeated SC administration of pemoline to weanling rats was also investigated. SC injections every 12 hours produced a high rate of SIB in weanling rats.     

Lithium and propranolol in aggression and self-injurious behavior in the mentally retarded

The effect of antiaggressive agents on self-injurious behavior (SIB) was retrospectively assessed by studying the charts of mentally retarded individuals with both aggression and SIB who had been treated with either lithium (n = 11) or propranolol (n = 6). The frequency of these two behaviors was examined during the 3 months prior to starting medication and the first 3-month period at either a therapeutic blood level of lithium or at the individual patient's maximum dose of propranolol. The results support an equal reduction in both behaviors with either drug. This suggests that antiaggressive agents may be useful in SIB and raises the possibility that similar biochemical mechanisms may underlie both behaviors.     

Solubility of ( ± )-Ibuprofen and S ( + )-Ibuprofen in the Presence of Cosolvents and Cyclodextrins

Aqueous solubility is an important parameter for the development of liquid formulations and in the determination of bioavailability of oral dosage forms. Ibuprofen (IB), a nonsteroidal anti-inflammatory drug, is a chiral molecule and is currently used clinically as a racemate (racIB). However, the S form of ibuprofen or S(+)-ibuprofen (SIB) is the biologically active isomer and is primarily responsible for the anti-inflammatory activity. Phase solubility studies were carried out to compare the saturation solubilities of racIB and SIB in the presence of common pharmaceutical solvents such as glycerol, sorbitol solution, propylene glycol (PG), and polyethylene glycol (PEG 300) over the range of 20% to 80% v/v in aqueous based systems. The solubilities of the two compounds were also compared in the presence of cyclodextrins such as beta cyclodextrin (CD), hydroxypropyl beta cyclodextrin (HPCD), and beta cyclodextrin sulfobutyl ether sodium salt (CDSB) over the range of 5% to 25% w/v. Solubility determinations were carried at 25°C and 37°C. Cosolvents exponentially increased the solubility of both SIB and racIB, especially in the presence of PG and PEG 300. Glycerol was not very effective in increasing the aqueous solubilities of both compounds, whereas sorbitol solution had a minimal effect on their solubility. PG and PEG 300 increased the solubility of SIB by 400-fold and 1500-fold, respectively, whereas the rise in solubility for racIB was 193-fold and 700-fold, respectively, at 25°C for the highest concentration of the cosolvents used (80% v/v). Of the two compounds studied, higher equilibrium solubilities were observed for SIB as compared with racIB. The derivatized cyclodextrins increased the aqueous solubility of racIB and SIB in a concentration-dependent manner giving A_L type of phase diagrams. The phase solubility diagrams indicated the formation of soluble inclusion complexes between the drugs and HPCD and CDSB, which was of 1:1 stoichiometry. The addition of underivatized CD reduced the solubility of racIB and SIB via the formation of an insoluble complex. The S form formed more stable complexes with HPCD and CDSB as compared with racIB. The solubilization process is discussed in terms of solvent polarity and differential solid-state structure of racIB and SIB. The thermodynamic parameters for the solubilization process are presented.     

Pharmacologic thresholds for self-injurious behavior in a genetic mouse model of Lesch-Nyhan disease

Congenital deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) causes Lesch-Nyhan disease in humans, which is associated with severe and recurrent self-injurious behavior (SIB). The HPRT-deficient knockout mouse model, however, does not display this unusual behavior. The present studies tested whether these mice might be more vulnerable to pharmacologic agents known to cause SIB in normal rodents, including clonidine, Bay K 8644, GBR 12909, methamphetamine, pemoline and caffeine. The results provided three conclusions. First, normal mice did not display SIB using some drugs known to provoke the behavior in rats (GBR 12909, caffeine), indicating important species differences in the expression of the behavior. Second, the C57BL/6J mice did not display SIB using drugs effective for other strains of mice (methamphetamine, pemoline), indicating important strain differences in expression of the behavior. Finally, there was no evidence that the HPRT-deficient mice were more susceptible to SIB when it occurred (clonidine, Bay K 8644).     

Response to rivastigmine or donepezil in Alzheimer's patients with symptoms suggestive of concomitant Lewy body pathology

BACKGROUND: A double-blind randomized trial evaluated the efficacy and tolerability of rivastigmine and donepezil in patients with Alzheimer's disease (AD) over 2 years. Baseline data indicated that some patients had symptoms suggestive of concomitant Lewy body disease. This retrospective analysis investigated whether AD patients with and without symptoms suggesting concomitant Lewy body pathology demonstrated different responses to therapy. METHODS: AD patients were divided by the presence/absence of symptoms suggestive of concomitant Lewy body disease. These were identified by a concomitant diagnosis of dementia with Lewy bodies and/or use of anti-parkinsonian medication at baseline. Baseline characteristics, demographics, changes on efficacy parameters and adverse event (AE) frequencies were calculated for rivastigmine- and donepezil-treated patients. Efficacy parameters were the Severe Impairment Battery (SIB), Mini-Mental State Examination (MMSE), Global Deterioration Scale (GDS), Neuropsychiatric Inventory (NPI) and AD Cooperative Study Activities of Daily Living scale (ADCS-ADL). Main efficacy analyses were based on an intent-to-treat last observation carried forward (ITT-LOCF) population. RESULTS: Both populations reached mean doses of rivastigmine and donepezil that were within therapeutic ranges. Nine hundred and ninety-four AD patients received study drug, of whom 49 (4.9%) had symptoms suggestive of concomitant Lewy body disease (25 rivastigmine, 24 donepezil). In this subpopulation, changes from baseline after 2 years of treatment with rivastigmine were significantly better than those seen with donepezil on the SIB, MMSE and ADCS-ADL (ANCOVA or Wilcoxon analyses, p < 0.05, ITT-LOCF). Statistical significance was not maintained in non-ITT-LOCF analyses, except for EP analyses on the SIB and ADCS-ADL (both p < 0.05). Rivastigmine also provided significantly better functioning than donepezil in patients without Lewy body pathology, as shown by a significant treatment difference at endpoint on the ADCS-ADL (p < 0.05, ITT-LOCF; not maintained in non-ITT-LOCF analyses). NPI changes from baseline did not differ significantly between treatment groups. AD patients with symptoms suggestive of concomitant Lewy body disease receiving rivastigmine or donepezil experienced fewer gastrointestinal side effects, leading to fewer discontinuations due to AEs, compared with patients without Lewy body pathology. CONCLUSION: In this retrospective analysis, AD patients who had symptoms suggestive of concomitant Lewy body disease appeared to show greater treatment responses to rivastigmine than to donepezil, and experienced fewer adverse events under either drug, compared with patients without Lewy body pathology.     

Effect of age on response to rivastigmine or donepezil in patients with Alzheimer's disease

BACKGROUND: Younger Alzheimer's disease (AD) patients appear to differ genetically and neuropathologically from older AD patients, and may experience a more aggressive disease course compared with older patients. A randomised trial investigated the efficacy and tolerability of rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and donepezil, an AChE-selective inhibitor, in patients with AD over a 2-year period. This retrospective analysis investigated whether younger and older patients showed differential tolerability and efficacy responses to cholinesterase inhibitor treatment. METHODS: For the current analysis, patients were divided according to age at baseline: those aged < 75 years and those aged >or= 75 years. Efficacy measures were the Severe Impairment Battery (SIB), Neuropsychiatric Inventory (NPI), Global Deterioration Scale (GDS), Mini-Mental State Examination (MMSE) and the AD Cooperative Study Activities of Daily Living scale (ADCS-ADL). Changes in efficacy parameters and adverse event frequencies were calculated for rivastigmine and donepezil-treated patients in both age groups. Exploratory analyses were also conducted on SIB, ADCS-ADL and NPI in patients who consented to pharmacogenetic testing at baseline. Genotyping of the apolipoprotein E (APOE) epsilon4 allele and the BuChE K-variant was conducted using the TaqMan assay. Main efficacy analyses were based on an intent-to-treat last observation carried forward (ITT-LOCF) population. RESULTS: Of the 994 patients who received the study drug, 362 (36.4%) were younger than 75 years and 632 (63.6%) were aged 75 years or over. Rivastigmine provided significant benefits in younger patients compared with donepezil on the NPI-10, NPI-12, NPI-D, GDS and ADCS-ADL (all p < 0.05, ITT-LOCF). With the exception of the NPI-D in favour of donepezil (p < 0.05, ITT-LOCF), no significant treatment differences were observed in older patients. Younger patients with two wild-type BuChE alleles had a significantly greater response to rivastigmine than donepezil on the ADCS-ADL (p < 0.01, ITT-LOCF) and SIB (p < 0.05, ITT-LOCF). The most common adverse events were nausea and vomiting and these were more frequent in rivastigmine-treated patients. CONCLUSION: In this sub group analysis, patients younger than 75 years of age showed greater treatment responses to rivastigmine than donepezil. Analysis of response by BuChE genotype suggests that this differential effect may be due to the inhibition of BuChE, in addition to AChE, by rivastigmine.     

Rationale for clinical trials of opiate antagonists in treating patients with personality disorders and self-injurious behavior

A subgroup of patients with personality disorders from the DSM-III-R (American Psychiatric Association 1987) "flamboyant" cluster is characterized by repetitive self-injurious behavior (SIB) apparently not motivated by suicidal intent. After describing the clinical and demographic characteristics of these patients, the clinical and preclinical evidence suggesting the involvement of endogenous opiate systems in this behavior is reviewed. Patients with personality disorders and SIB have been found to have elevated levels of plasma beta-endorphin. However, the available evidence is not sufficient to show whether this is a cause of or a consequence of SIB. Behavioral stereotypies resulting in self-injury in animals and SIB in mentally retarded patients have been shown to be abolished by opiate antagonist administration in a significant proportion of both groups. The available evidence suggests that clinical trials of oral opiate antagonist drugs should be undertaken because of the promise such drugs have in the treatment of this sometimes life-threatening disorder.     

Solubility of (+/-)-ibuprofen and S (+)-ibuprofen in the presence of cosolvents and cyclodextrins

Aqueous solubility is an important parameter for the development of liquid formulations and in the determination of bioavailability of oral dosage forms. Ibuprofen (IB), a nonsteroidal anti-inflammatory drug, is a chiral molecule and is currently used clinically as a racemate (racIB). However, the S form of ibuprofen or S(+)-ibuprofen (SIB) is the biologically active isomer and is primarily responsible for the antiinflammatory activity. Phase solubility studies were carried out to compare the saturation solubilities of racIB and SIB in the presence of common pharmaceutical solvents such as glycerol, sorbitol solution, propylene glycol (PG), and polyethylene glycol (PEG 300) over the range of 20% to 80% v/v in aqueous based systems. The solubilities of the two compounds were also compared in the presence of cyclodextrins such as beta cyclodextrin (CD), hydroxypropyl beta cyclodextrin (HPCD), and beta cyclodextrin sulfobutyl ether sodium salt (CDSB) over the range of 5% to 25% w/v. Solubility determinations were carried at 25 degrees C and 37 degrees C. Cosolvents exponentially increased the solubility of both SIB and racIB, especially in the presence of PG and PEG 300. Glycerol was not very effective in increasing the aqueous solubilities of both compounds, whereas sorbitol solution had a minimal effect on their solubility. PG and PEG 300 increased the solubility of SIB by 400-fold and 1500-fold, respectively, whereas the rise in solubility for racIB was 193-fold and 700-fold, respectively, at 25 degrees C for the highest concentration of the cosolvents used (80% v/v). Of the two compounds studied, higher equilibrium solubilities were observed for SIB as compared with racIB. The derivatized cyclodextrins increased the aqueous solubility of racIB and SIB in a concentration-dependent manner giving AL type of phase diagrams. The phase solubility diagrams indicated the formation of soluble inclusion complexes between the drugs and HPCD and CDSB, which was of 1:1 stoichiometry. The addition of underivatized CD reduced the solubility of racIB and SIB via the formation of an insoluble complex. The S form formed more stable complexes with HPCD and CDSB as compared with raclB. The solubilization process is discussed in terms of solvent polarity and differential solid-state structure of raclB and SIB. The thermodynamic parameters for the solubilization process are presented.     

DNA methylation of APBA3 and MCF2 in borderline personality disorder: Potential biomarkers for response to psychotherapy

Borderline personality disorder (BPD) is a severe and complex mental disease associated with high suicidal tendencies and hospitalization rates. Accumulating evidence suggests that epigenetic mechanisms are implicated in the etiology of BPD. A recent epigenome-wide study identified several novel genes which are epigenetically dysregulated in BPD. Those genes include APBA3 and MCF2. Psychotherapy such as Dialectical Behavior Therapy (DBT), an established treatment for BPD, provides an excellent setting to investigate environmental influences on epigenetic mechanisms in order to identify biomarkers for disease status and therapy success. However, the effects of DBT on epigenetic regulation has only been researched in one previous study analyzing BDNF. In the present study, we aimed to investigate the role of DNA methylation of APBA3 and MCF2 as possible biomarkers for treatment outcome in BPD, whilst validating the previous findings of differential DNA methylation in a cohort of 44 BPD patients and 44 well-matched healthy control individuals. Unexpectedly, we did not detect significant DNA methylation differences between patients and control individuals. However, we found a high correlation between the methylation status of APBA3 and MCF2 and therapy outcome: before DBT treatment, both genes were significantly higher methylated in patients responding to therapy compared to patients that did not respond. Our study is the first to report results pointing to possible predictive epigenetic biomarkers of DBT outcome in BPD patients. Following replication in independent cohorts, our finding could facilitate the development of more personalized therapy concepts for BPD patients by including epigenetic information.     

Suicide in alcohol-dependent individuals: epidemiology and management

The association of alcohol dependence with suicidal behaviour is well established although complex. On the basis of epidemiological and clinical evidence, alcohol dependence is known to increase the risk for suicidal ideation, suicide attempts and completed suicide. However, this risk is modulated by a wide variety of factors including sociodemographic, clinical, treatment-related and life situational characteristics as well as current drinking status and the effect of inebriation. Treatment and management of patients with alcohol dependence and concomitant suicidal communication or suicide attempts is crucial, as is the recognition of these patients in emergency and other healthcare service contacts. The treatment strategies cannot be based on evidence derived from randomised clinical trials as such data do not exist. They must rather be based on current knowledge of risk factors for suicidal behaviour, efficacy of treatment for alcohol dependence or relevant co-morbid conditions and problems known to be common in treatment settings. In this article, we review the essential literature on the epidemiological and clinical research in the areas of alcohol dependence and suicidal behaviour. On the basis of current data and clinical experience, we suggest the following principles be followed in the management of alcohol-dependent individuals: (i) suicidal threats or communication by alcohol-dependent individuals in emergency and other contacts should be taken seriously; (ii) other mental disorders should be well evaluated, a consequent treatment plan initiated and follow-up arranged; (iii) appropriate and up-to-date pharmacological treatment should focus on both reducing the amount of drinking and treating symptoms of other mental disorders; (iv) psychotherapeutic efforts should be focused on emerging symptoms of both alcohol use and other mental disorders; and (v) known epidemiological and clinical risk factors, adverse life events in particular, should be recognised and taken into account.     

Self-injurious behavior in the developmentally disabled: assessment techniques.

Self-injurious behavior (SIB) is a major cause of difficulty for the developmentally disabled person. Causes are varied, but medical, neurological, and psychiatric disorders should be considered before nonspecific approaches to treatment are chosen. A careful assessment should include a thorough medical and psychiatric evaluation as well as laboratory and diagnostic studies. Various assessment instruments are available to aid in the evaluation process and, to some extent, in the evaluation of the effectiveness of treatment for SIB.     

Dopamine deficiency in self-injurious behavior

Based on the report that patients with Lesch-Nyhan Syndrome (LNS) have a central deficiency of dopamine similar in magnitude to that seen in Parkinsonism, the age at which dopaminergic neurons are disrupted was proposed to explain the differing symptoms observed in these two disorders. To investigate this hypothesis, brain dopaminergic neurons were lesioned in neonatal and adult rats with 6-hydroxy-dopamine (6-OHDA). Results demonstrated that neonatally lesioned rats had learning deficits and elevated levels of serotonin in the striatum--characteristics observed in LNS. Administration of L-dopa produced self-injurious behavior (SIB) in neonatally lesioned but not adult lesioned rats. Subsequent studies revealed that the SIB induced by L-dopa was dependent upon activation of D1 receptors. The elevated susceptibility of neonatally lesioned rats for SIB was demonstrated further by the enhanced occurrence of SIB when muscimol was administered into the substantia nigra reticulata (SNR). Other studies demonstrated that adenosine agonists could antagonize SIB, suggesting that the reduced adenosine observed in LNS may contribute to this symptom. The basic work being performed should be relevant to LNS and to other developmental disorders exhibiting SIB.     

Reverse migration order of sibutramine enantiomers as a function of cyclodextrin concentration in capillary electrophoresis

The current study demonstrates the reversal of enantiomer migration order (EMO) in capillary electrophoresis (CE) based separations of sibutramines (SIB) as a function of the concentration of two types of cyclodextrin (CD), native β-CD and acetyl-β-CD. At normal working concentrations (<10mM) of either CD, (S)-SIB migrated first. However, at CD concentrations greater than 10mM, (R)-SIB was the first to migrate. This study describes factors involved in determining EMO for sibutramine enantiomers at low and high concentrations of CDs. The reversal of EMO could be explained in terms of the opposing effects of the stability and the limiting complex mobility of the SIB-CD complexes. The enantioseparation of SIB with methyl- and 2-hydroxypropyl-β-CD was possible based on differences in the binding constants of complexes. However, reverse EMO was not observed because of equal mobilities of SIB enantiomers complexed with methyl- and 2-hydroxypropyl-β-CD.     

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.