Mortality and Return to Work of Drug Abusers From Therapeutic Community Treatment 3 Years After Entry

BACKGROUND: The outcome of therapeutic community treatment for drug abuse has been disputed with regard to mortality and rehabilitation to school or work as compared with other treatment modalities. METHOD: All patients (N = 130) admitted to a therapeutic community during 3 consecutive years (1996-1998), who had failed to stop abusing drugs after ambulatory and primary care initiatives, were assessed 1 to 4 years (mean = 36.5 months) after end of treatment. Rates of rehabilitation to school or work, changes in drug use patterns, and mortality were observed. RESULTS: Nine persons died during the observation period (the observation time to death seemed to be shorter in women than in men). The mortality rate per 100 observation years was 2.28. Among the surviving drug abusers, 39% were working or attending school at study endpoint. One fourth currently used drugs, and approximately 14% were enrolled in a methadone maintenance program. Another 13% were in treatment or prison. CONCLUSION: Drug abuse is an activity that increases the mortality rate, but among the surviving persons, a considerable number are rehabilitated, as assessed after a longer observation period. The authors suggest that this outcome could not have been attained with ambulatory general practice-driven services, even with empathic follow-up.     

Drug trajectories among youth undergoing treatment: The influence of psychological problems and delinquency

Previous research has documented associations of addiction with delinquency and psychological problems. However, few studies have evaluated their influence on adolescent's drug use trajectories. The current study aims to examine the influence of these factors on the recovery trajectories of 199 youths aged 15.6 years on average admitted to inpatient and outpatient addiction treatment centers, followed up three and six months later. Results indicate that youth who show higher severity of drug abuse exhibit greater improvement than youth with a lower severity of drug abuse at the onset of treatment. Although psychological problems were associated with baseline drug use, they did not influence drug use trajectory over time. Only delinquency influenced the recovery trajectories of these youth. Results suggest that a high level of delinquency can have a significant effect on the drug recovery process of adolescents and that interventions should attempt to reduce both drug use and delinquency.     

Muscarinic Acetylcholine Receptor Subtypes as Potential Drug Targets for the Treatment of Schizophrenia, Drug Abuse and Parkinson's Disease

The neurotransmitter dopamine plays important roles in modulating cognitive, affective, and motor functions. Dysregulation of dopaminergic neurotransmission is thought to be involved in the pathophysiology of several psychiatric and neurological disorders, including schizophrenia, Parkinson's disease and drug abuse. Dopaminergic systems are regulated by cholinergic, especially muscarinic, input. Not surprisingly, increasing evidence implicates muscarinic acetylcholine receptor-mediated pathways as potential targets for the treatment of these disorders classically viewed as "dopamine based". There are five known muscarinic receptor subtypes (M(1) to M(5)). Due to their overlapping expression patterns and the lack of receptor subtype-specific ligands, the roles of the individual muscarinic receptors have long remained elusive. During the past decade, studies with knock-out mice lacking specific muscarinic receptor subtypes have greatly advanced our knowledge of the physiological roles of the M(1)-M(5) receptors. Recently, new ligands have been developed that can interact with allosteric sites on different muscarinic receptor subtypes, rather than the conventional (orthosteric) acetylcholine binding site. Such agents may lead to the development of novel classes of drugs useful for the treatment of psychosis, drug abuse and Parkinson's disease. The present review highlights recent studies carried out using muscarinic receptor knock-out mice and new subtype-selective allosteric ligands to assess the roles of M(1), M(4), and M(5) receptors in various central processes that are under strong dopaminergic control. The outcome of these studies opens new perspectives for the use of novel muscarinic drugs for several severe disorders of the CNS.     

Drug dreams in outpatients with bipolar disorder and cocaine dependence

Patients with substance abuse or dependence often have dreams about alcohol or drugs during early recovery. However, the literature on drug dreams in rehabilitating patients with drug-related disorders remains limited. No data are available on drug dreams in people with substance-related disorders and other major mental illness. As part of a large study on the use of lamotrigine in patients with bipolar disorder and cocaine dependence, the frequency and nature of drug dreams, triggers for dreams, and response to the dreams during study participation were assessed in 37 outpatients for as long as 36 weeks. Altogether, 74% of participants experienced at least one drug dream during the study. Furthermore, drug dreams rapidly decreased during study participation. The presence of drug dreams at baseline did not predict mood, cocaine craving, or drug use at exit. No clear risk factors for drug dreams were identified. However, drug dreams were related to survival in the study by a negative U-shaped curve relationship in which those participants with the highest and lowest frequency of drug dreams discontinued from the study the earliest. Content of the dreams frequently included drug use or refusing to use the drug. Dreams of drug use tended to occur during the first few weeks of study participation. Most dreams were associated with triggers for drug use. The findings suggest that drug dreams are common in patients with bipolar disorder and cocaine dependence and are similar in nature to those previously reported in people with pure substance abuse.     

Cerebellar Lingula Size and Experiential Risk Factors Associated with High Levels of Alcohol and Drug Use in Young Adults

Previous studies have reported cerebellar abnormalities or static ataxia associated with risk for chronic use of alcohol and drugs. Adverse childhood experience is another strong risk factor for later substance abuse. We therefore sought to ascertain the relationship between morphological phenotypes of the lingula (lobule I) of the anterior cerebellar vermis, and exposure to emotional (EM) versus physical (PM) maltreatment, on the degree of ongoing alcohol or drug use. The study design consisted of a cross-sectional in vivo neuroimaging study, utilizing retrospective assessment of maltreatment history and self-reports of alcohol and substance use. Study participants were 153 subjects (54 M/99F, 21.9 ± 2.2 years) selected for imaging from a database of 1,402 community participants 18–25 years of age, who completed a detailed online screening instrument and met rigorous inclusion/exclusion criteria. Subjects were exposed to only physical abuse or harsh corporal punishment (HCP; PM group, n = 37) and parental verbal abuse and/or witnessing domestic violence (EM group, n = 58) or had no history of maltreatment or axis I disorders (n = 58). The main outcome measures consisted of the gray matter volume of lobule I as measured by manual tracing, number and type of alcoholic beverages consumed during a drinking session, number of sessions per month, and monthly drug use, along with family history of drug and alcohol abuse. Lingula thickness was not attenuated by alcohol use or maltreatment history. However, increased lingula thickness was associated with greater consumption of drugs and hard liquor, particularly in physically maltreated subjects who consumed 2.5- and 2.7-fold more alcohol and used drugs 6.1- and 7.8-fold more frequently than controls or EM subjects, respectively. In conclusion, physical maltreatment was observed to interact with cerebellar morphology resulting in a strong association with alcohol and substance use. Lingula thickness may represent a novel, experientially sensitive, phenotypic risk factor for enhanced alcohol and drug use that perhaps modulates sensitivity to these agents.     

The treatment of chronic insomnia: drug indications, chronic use and abuse liability. Summary of a 2001 New Clinical Drug Evaluation Unit meeting symposium

This paper summarizes a group of presentations and panel discussions on chronic insomnia at the 2001 NCDEU meeting. The presentations and discussions focused on the twin issues of efficacy and concerns of abuse liability with long-term hypnotic therapy. The panel concluded that insomnia may be an epidemiological marker for a variety of difficulties including accidents, increased health care utilization and subsequent development of major depression. Whether or not treatment of insomnia will prevent these long-term problems has not yet been determined. Since the mid-1980s there has been a rapid rise in the off-label use of antidepressants, particularly trazodone, for treating insomnia. Some participants expressed concern at the lack of data for this practice, particularly the absence of dose-response and tolerance information, and noted that the small amount of efficacy data available is not encouraging. Similarly, there are minimal data to support the use of antihistamines as sleep aids; moreover, their side effect profile and interactions with other drugs may be under appreciated. The limited data available on nightly long-term usage of the newer non-benzodiazepine hypnotics, primarily of six-months' duration, suggest an absence of tolerance, but more data for both nightly and non-nightly administration are needed. Insomniacs tend to show therapy-seeking, rather than drug-seeking behavior, and patients without histories of drug abuse are unlikely to self-escalate dosage of currently available hypnotics. There is fairly good agreement on the characteristics of an ideal hypnotic. All currently available agents, while effective and safe, do not achieve this ideal. The next few years are likely to see the appearance of a variety of agents with new and promising mechanisms of action.     

Diagnosis and treatment of co-occurring affective disorders and substance use disorders.

There is growing interest in the co-occurrence of mood and substance use disorders. It is clear that co-occurrence of these disorders is common and has an impact on prognosis and course of both disorders. The diagnostic issues at the interface of substance or alcohol use disorders and affective illnesses are particularly difficult because of the substantial symptom overlap between substance intoxication and withdrawal and symptoms of affective disorders. Over the past few years, advances have been made in the treatment of co-occurring disorders. Further investigation of specifically tailored treatments for patients with co-occurring substance use and other mood disorders is underway. Because many advances have been made in pharmacotherapy of mood disorders in the past 10 years, this progress will impact individuals with co-occurring disorders, because newer agents with less toxicity and fewer adverse effects and interactions with substances of abuse will be evaluated for treating the comorbid condition. Specific considerations in choosing a pharmacologic agent for use in patients with substance use disorders include safety, toxicity, and abuse liability. Although there are few studies specifically targeting pharmacotherapy for co-occurring disorders, those that have been conducted indicate that similar pharmacotherapeutic agents work for mood disorders with or without substance use disorders. In conclusion, although the co-occurrence of substance abuse and mood disorders is an important area in which recent developments provide cause for considerable optimism, much work remains to be done.     

An integration of three approaches to addiction and methadone maintenance treatment: the self-medication hypothesis,the disease model and social criticism

The two models which have most affected theory and practice of addiction medicine have been the disease model and the self-medication hypothesis. The disease model's fundamental concept is that the addicted individual is sick and suffers from a disease. The self-medication hypothesis proposes that drug and alcohol users are attempting to cope with an underlying psychological or social disorder by means of self-medication. These two viewpoints are presented in the light of a number of specific methadone maintenance treatment and drug abuse related issues such as the question whether drug abuse is an illness of the body, the mind or society; whether the disease model really de-stigmatized drug abuse; what the correct methadone dosing policy should be; the place of psychotherapy in methadone maintenance treatment and drug abuse and how polydrug abuse should be treated. These issues are discussed and an integrated approach is suggested stressing the need for social criticism and a renewed social policy towards drug abuse in general and its treatment in particular.     

Pharmacological blocking agents for treating substance abuse

Pharmacological blocking agents are an important treatment approach for the current epidemic of drug abuse. This approach is multidisciplinary, ranging from molecular neuroscience for developing these blocking agents to behavioral therapies for establishing treatment delivery systems. This paper outlines the biological, behavioral, and clinical components of the pharmacological blocking agent approach. Clinical results using two blocking agents, naltrexone for opioid abuse and disulfiram for alcohol abuse, are reviewed as a source of leads in developing potential agents for treating sedative and stimulant abuse. While specific pharmacological antagonists have been developed for benzodiazepines, such agents are not yet available for stimulants. Furthermore, the clinical utility of stimulant antagonists may depend on the development of multisite agents that partially block several neurotransmitter systems rather than target a single-system brain receptor.     

Animal models for assessing drugs of abuse

A major toxic effect that has limited the clinical usefulness of medicinal drugs has been their susceptibility to nonmedical use and abuse by significant segments of the population. Major research efforts have been directed toward the development of safer and more effective therapeutic agents that would not be subject to such misuse, and laboratory animal assessment models have contributed importantly to the evaluation of such compounds. There are now several converging lines of evidence that testify to the reliability and broad generality of observations concerning drug abuse liability in humans based upon such animal laboratory models. The most important point of contact that characterizes the interaction between such animal assessment models and the human drug abuse arena is the demonstrated relationship between the biochemical/pharmacological/toxic properties of drugs on the one hand, and their environmental/behavioral stimulus functions on the other. As a result of these developments in animal model research technology and the consequent advances in knowledge of drug action, an operational basis has been provided for redefining the bewildering range of phenomena and experiential pseudo-phenomena loosely identify with such terms as "addition," "dependence" and "abuse."     

Bipolar disorder with comorbid substance abuse: diagnosis, prognosis, and treatment

Alcohol and drug abuse occur frequently in individuals with bipolar disorder, but clinicians may often feel ill-prepared to identify such multi-diagnosis syndromes, to contextualize drug abuse alongside affective symptoms, and to formulate appropriate treatment strategies. Plausible explanations for high comorbidity rates between bipolar illness and substance use disorders are complex and likely embrace numerous factors that extend beyond simple, older theories about drug use as sheer "self-medication." Evidence from epidemiologic, family-genetic, pharmacologic, psychosocial, and clinical psychopathology studies suggest that a majority of bipolar patients are at risk for developing lifetime drug or alcohol-related problems, which may in turn contribute to more varied and complex clinical presentations, accelerated relapses, worsening of depressive features, poorer lithium response, functional disability, and elevated suicide risk. In this article, the author reviews essential concepts about the phenomenology and treatment outcome of bipolar illness with substance use comorbidities and offers a systematic approach to the diagnosis and management of patients with such dual diagnoses.     

Drug abuse as seen in the University Department of Psychiatry, Kaduna, Nigeria, in 1980-1984

367 new cases of drug abuse and related cases were admitted to the teaching hospital within the study period. These cases comprised approximately 11% of all new admissions during the period. 80% were between 15 and 30 years, and 76% of them were single. People in this age group tend to abuse cannabis and amphetamine more than alcohol, whereas those in the age range 31 years and over, tend to abuse alcohol more, and about 76% of them are married. Cocaine or heroin abuse, did not occur. The use of cannabis was more commonly associated with alcohol than with amphetamine. Abuse of amphetamine in association with alcohol, though present, was not significant. 15 of 367 cases were females (4%), 11 of whom were married.     

Neuropsychological correlates of adolescent substance abuse: four-year outcomes.

Alcohol and other drug use are common in youth, but neurocognitive sequelae are unclear. This study examines the relationship between neuropsychological functioning and protracted substance use in adolescence. One hundred fifteen adolescents, ages 13 to 19 years, were recruited from inpatient substance abuse treatment programs and followed for 4 years. Adolescents were administered a comprehensive battery of neuropsychological tests and evaluated on substance use involvement during treatment, and at 6-month, 1-year, 2-year, and 4-year follow-up time points. Protracted substance abuse over the 4 years of follow-up was associated with significantly poorer subsequent functioning on tests of attention. In addition, alcohol and drug withdrawal accounted for significant variance in visuospatial functioning, above and beyond demographic, educational, and health variables in detoxified late adolescents and young adults. Results suggest that alcohol and drug withdrawal may be a more powerful marker of protracted neuropsychological impairments than other indices of youthful alcohol and drug involvement.     

Drug delivery to tumors of the central nervous system

Contemporary treatment of malignant brain tumors has been hampered by problems with drug delivery to the tumor bed. Inherent boundaries of the central nervous system, such as the blood-brain barrier or the bloodcerebrospinal fluid barrier, and a general lack of response to many chemotherapeutic agents have led to alternative treatment modalities. In general, all these modalities have sought to either disrupt or bypass the physiologic brain barriers and deliver the drug directly to the tumor. This article reviews past, as well as current, methods of drug delivery to tumors of the central nervous system. Special emphasis is placed on biodegradable polymers that can release chemotherapeutic agents against malignant gliomas. A variety of other nonchemotherapeutic drugs, including antiangiogenesis and immunotherapeutic agents, are presented in the context of new polymer technology. Finally, future directions in drug delivery are discussed with an overview on new advances in emerging biotechnology.     

Risperidone treatment of preschool children with thermal burns and acute stress disorder

Pharmacologic treatment of acute stress disorder (ASD) is a novel area of investigation across all age groups. Very few clinical drug trials have been reported in children and adolescents diagnosed with ASD. Most of the available, potentially relevant, data are from studies of adults with posttraumatic stress disorder (PTSD). The atypical antipsychotic agents have been reported to be effective as an adjunctive treatment for adults with PTSD. There have been a limited number of studies published regarding atypical antipsychotic treatment of PTSD in children and adolescents, and there is no current literature available on the use of these agents for children with ASD. This report describes the successful treatment of three preschool-aged children with serious thermal burns as a result of physical abuse or neglect. Each of these children was hospitalized in a tertiary-care children's hospital and was diagnosed with ASD. In all cases, risperidone provided rapid and sustained improvement across all symptom clusters of ASD at moderate dosages. Minimal to no adverse effects were reported. These cases present preliminary evidence for the potential use of risperidone in the treatment of ASD in childhood.     

Impact of substance abuse on the course and outcome of schizophrenia

Numerous pharmacological agents have been shown to have powerful effects on cognitive behavior. Schizophrenia-like reactions have been reported in some instances. There have also been persistent reports of drug abuse among psychiatric patients before and during hospitalization. These phenomena have led to speculation that psychoactive substances are affecting the course and outcome of psychiatric illnesses, and in particular, schizophrenia. This report first reviews the evidence for psychotomimetic effects of various drugs, and then focuses on reports of the effect that substance abuse has on the course of schizophrenia and long-term outcome. The evidence to date indicates that there is a need for a large epidemiological analysis of the interplay between drug abuse and schizophrenia as well as more intensive case studies of afflicted individuals. This discussion concludes with suggestions for improved research methods and two designs for future investigations.     

Diagnosis and treatment of adolescent substance abuse

This paper has demonstrated the persistence of drug abuse as a problem among adolescents and describes cocaine abuse particularly, profiling the typical cocaine abuser. The stagewise progression of drug use has been described. Factors that make youngsters vulnerable to progression to further stages of drug abuse have been suggested. In treatment strategies, the appeal to fear and moral and religious arguments has for the most part necessarily been replaced by an appeal to reason and an educational approach. The coexistence of drug abuse and psychopathology occurs with sufficient frequency to require full medical and psychiatric evaluation in every adolescent who presents with a history of substance misuse. Inpatient and residential treatment, family involvement, and urine monitoring with sufficient aftercare programs seem to be important components of treatment approaches.     

Longitudinal studies of drug abuse in a fifteen-year-old population. 1. Drug career

A representative, stratified sample from a year cohort of ninth-graders, mostly 15 years of age, examined in 1968 with a questionnaire, was followed over a decade in official registers. After 5 and 8 years, subsamples were also interviewed. During the period in question there was a polydrug abuse pattern in the area of Gothenburg, the second city in Sweden with approx. 450,000 inhabitants. The sample comprised 1,047 individuals and the whole year cohort 5,367. The estimated proportions of registered drug abusers in the cohort were 9% men and 8% women. 3% men and 5% women had drug careers for 2 years or less, 1% men and 0.2% women for 10 years or more. Those who became registered had with few exceptions stated drug use in the school questionnaire or had attended special classes or dropped out of school prematurely. After 5 years 60-80% of the registered abuse remained among the men in these groups and 30-40% among the women. According to interviews abuse remained in 70-90% of men who had admitted drug use in the school survey and in 50-60% of the women from the same groups. According to both registers and interviews intravenous abuse of central stimulants had increased among men but decreased among women. After 11 years, 20-60% of the registered abuse remained in men and 5-60% in the women.