Efficacy of indirect dopamine agonists for psychostimulant dependence: a systematic review and meta-analysis of randomized controlled trials

Psychostimulant dependence is characterized by dopamine deficit, which could be reversed with indirect dopamine agonists (IDAs). A systematic review and meta-analysis of randomized, parallel-group, placebo-controlled clinical trials assessing the efficacy of IDAs in psychostimulant-dependent individuals were conducted. The study outcomes were psychostimulant abstinence, assessed by means of urinalysis, and retention in treatment. Risk of bias was determined using a Cochrane Collaboration instrument. Twenty-nine studies fulfilled the inclusion criteria, involving 2,467 participants. Compared with placebo, IDAs increased psychostimulant abstinence (standardized mean difference = 0.20; 95% confidence interval, 0.06-0.35; p = .005) but did not increase retention in treatment. Efficacy was larger in comorbid heroin-dependent individuals and was positively related with treatment length. No study was considered fully free of bias. IDAs appear to be efficacious for reducing psychostimulant use but did not improve retention. Efforts should be undertaken to reduce the risk of bias of clinical trials with psychostimulant-dependent individuals.     

Pharmacological approaches to methamphetamine dependence: a focused review

Methamphetamine dependence is a serious worldwide public health problem with major medical, psychiatric, socioeconomic and legal consequences. Various neuronal mechanisms implicated in methamphetamine dependence have suggested several pharmacological approaches. A literature search from a range of electronic databases (PubMed, EMBASE, PsycInfo, the NIDA research monograph index and the reference list of clinicaltrials.gov) was conducted for the period from January 1985 to October 2009. There were no restrictions on the identification or inclusion of studies in terms of publication status, language and design type. A variety of medications have failed to show efficacy in clinical trials, including a dopamine partial agonist (aripiprazole), GABAergic agents (gabapentin) and serotonergic agents (SSRI, ondansetron, mirtazapine). Three double-blind placebo-controlled trials using modafinil, bupropion and naltrexone have shown positive results in reducing amphetamine or methamphetamine use. Two studies employing agonist replacement medications, one with d-amphetamine and the other with methylphenidate, have also shown promise. Despite the lack of success in most studies to date, increasing efforts are being made to develop medications for the treatment of methamphetamine dependence and several promising agents are targets of further research.     

Measuring nicotine dependence among youth: a review of available approaches and instruments

This paper reviews issues and concepts related to the measurement of nicotine dependence among youth. The primary objectives of this review are to: (1) review the measures of nicotine dependence currently being used; and (2) delineate a future research agenda in an attempt to advance the quality of measurement and instrumentation for this important research endeavor. Existing measures of nicotine dependence, including formal diagnostic interviews, related withdrawal assessments, brief self-report measures, and single-item indicators, are described. While formal diagnostic systems have been considered the 'gold standard' for evaluating dependence clinically, their specific limitations related to use for research purposes are outlined. Each broad class of measure is evaluated in terms of its rationale for use, strengths and limitations, and the extent to which it has successfully been applied to adolescent populations. A research agenda follows in the second section of the paper. In this section, the need for identification and inclusion of a standard set of optimal dependence measures, for enhancement of current measures, and for the onset of a new and comprehensive measures development program is outlined.     

Pharmacotherapies for problematic psychostimulant use: a review of current research

This review summarizes the current status of clinical research on pharmacotherapies for problematic psychostimulant use. The use of psychostimulants, including amphetamine, cocaine and ecstasy, is increasingly a feature of Australian life as is the presentation of patients with psychostimulant disorders. A lack of experience, resources and treatment options have constrained the response of treatment services to such problems. Despite extensive research, particularly in the area of cocaine, no pharmacotherapy has been proven effective in the management of psychostimulant disorders. The harms associated with problematic psychostimulant use warrant further controlled research in innovative approaches integrated with psychosocial interventions. [Shearer J, Gowing LR. Pharmacotherapies for problematic psychostimulant use: a review of current research. Drug Alcohol Rev 2004;23:203 - 211]     

Provider satisfaction with office-based treatment of opioid dependence: a systematic review.

PURPOSE: New federal regulations allow for office-based treatment of opioid dependent patients with opioid agonist medication (e.g., buprenorphine). We sought to evaluate the literature on office-based physicians' acceptance of this practice. METHODS: We searched the MEDLINE database for original research examining office-based providers' acceptance or satisfaction with office-based treatment. Articles included in the analysis met the following criteria: (1) discussed the treatment of patients with substance abuse disorders, (2) focused on the treatment of opioid dependent patients, (3) discussed treatment with opioid agonist therapy, (4) discussed treatment by office-based physicians, (5) presented original research, and (6) provided data examining physician acceptance or satisfaction. RESULTS: Eight studies met the criteria. Their heterogeneity precluded aggregate analysis. Four of 8 studies revealed that providers had a positive perception concerning the efficacy of opioid agonist treatment, 4/8 indicated that providers believed that opioid dependent patients were more complex than others in their practices, and 3/8 studies indicated the need for additional support services. CONCLUSIONS: There are few studies of provider satisfaction with office-based treatment of opioid dependence. This literature reveals overall provider acceptance of this practice but highlights the need for support services. Further research, designed to identify the barriers to provider satisfaction with office-based opioid agonist therapy, is needed to ensure that these barriers do not limit expansion of this practice.     

多巴胺转运体在精神兴奋剂依赖中的作用

精神兴奋剂是一类能够兴奋中枢和外周神经系统并容易产生依赖性的精神活性物质。大量研究表明,单胺类神经递质尤其是多巴胺在精神兴奋剂的行为效应和精神兴奋剂依赖过程中发挥重要作用,而多巴胺转运体控制着神经元内多巴胺的稳态和多巴胺神经通路的传递,因此多巴胺转运体在精神兴奋剂的奖赏和行为刺激效应中具有重要作用。     

The principles of agonist pharmacotherapy for psychostimulant dependence

Issues. Psychostimulant dependence is a chronic, relapsing condition which is highly treatment refractory. No medications to date have been any more successful than placebo in reducing psychostimulant use in dependent patients. Agonist strategies have attracted limited attention. Approach. Successful examples of agonist pharmacotherapy in the treatment of heroin and nicotine dependence are first considered. Agonist pharmacological approaches to the treatment of psychostimulant dependence are then examined, based on the dopamine receptor agonist and indirect dopamine agonist strategies. Finally, the potential extension of the concept of agonist pharmacotherapy to include the novel non-amphetamine-type stimulant, modafinil, is discussed. Conclusions. Agonist approaches appear to be viable with risks outweighed by benefits in carefully selected, monitored and motivated patients. On the other hand, the effectiveness of indirect agonists such as dexamphetamine and methylphenidate are not established. Further research is required to determine optimal treatment models (whether maintenance or withdrawal), effective safe dosages and duration (short or long term). [Shearer J. The principles of agonist pharmacotherapy for psychostimulant dependence. Drug Alcohol Rev 2008;27:301-308]     

Schizophrenia and psychostimulant abuse: a review and re-analysis of clinical evidence

The authors selected articles from those published between 1975 and 1994 that specifically documented psychostimulant abuse in patients determined to be schizophrenic according to recent and relatively uniform diagnostic criteria. These articles indicated that the incidence of psychostimulant abuse in schizophrenics is 2–5 times higher than that of the general public. Additionally, unlike the decline in stimulant use seen in older adults in the general population, high rates of abuse appeared to be maintained in schizophrenics. Although the incidence of abuse in this group was high, comparisons of abuse rates generated by self-report with those obtained by urinalysis indicated that the frequency of abuse is being underestimated by 15–21%. Potential factors contributing to stimulant abuse in schizophrenics, including the disease process, and the influence of chronic neuroleptic medication, were evaluated. Results indicated that the incidence of psychostimulant abuse was neither a common property of psychiatric patients, nor exclusive to schizophrenics, but appeared to be related to chronic treatment with neuroleptic drugs. Symptom severity was generally similar in schizophrenic abusers and non-abusers, which also suggested a degree of independence from the disease process. In a majority of the studies surveyed, abuse of stimulants followed disease onset. It was also found that stimulant abuse was associated with marked increases in hospitalization in this patient group, including those known to be neuroleptic medication compliant. Possible explanations for the initiation and maintenance of psychostimulant abuse in schizophrenics are discussed in relation to clinical and preclinical evidence on drug addiction.     

Antipsychotic drugs in cocaine dependence: A systematic review and meta-analysis

A systematic review and meta-analysis to evaluate the efficacy of antipsychotic drugs in subjects with cocaine dependence is presented. Twelve randomized, double-blind, placebo-controlled clinical trials involving 681 patients were included. Five outcome measures were evaluated: number of dropouts, cocaine use assessed by means of urine benzoylecgonine tests, self-reported cocaine use, craving and Addiction Severity Index. On average, 48% of the enrolled participants were lost to follow-up. In comparison to placebo, antipsychotics did not significantly reduce cocaine use (WMD = 0.01, 95%CI = − 0.12 to 0.13) or improve retention in treatment (RR 0.91, 95%CI = 0.82–1.02). Risperidone reduced slightly dropouts in comparison to placebo (RR = 0.87; 95%CI = 0.79–0.97). To date there is insufficient evidence to justify the use of antipsychotic drugs for cocaine dependence.     

Anticonvulsant drugs in cocaine dependence: A systematic review and meta-analysis

A systematic review and meta-analysis according to the methodology developed by the Cochrane Collaboration and the Quality of Reporting of Meta-Analyses statement based on randomized controlled trials to evaluate the efficacy of anticonvulsants in subjects with cocaine dependence were performed. Fifteen randomized, double-blind, placebo-controlled clinical trials involving 1,236 patients were included. Two outcome measures were evaluated: retention in the anticonvulsant treatment (compared to the placebo treatment) and the subsequent cocaine use, measured by urinalysis results. The efficacy of the seven anticonvulsant drugs analyzed was not homogenous. On average, 50% of the enrolled participants were lost to follow-up. Treatments did not show an improvement in subject retention compared to placebo. Overall, the number of cocaine-positive urine samples was close to statistical significance (95% confidence interval = 0.85–1.06) compared to placebo. Available clinical trials indicate that there is insufficient evidence to justify the use of anticonvulsant drugs in treating cocaine dependence.     

Retention in medication-assisted treatment for opiate dependence: A systematic review

Retention in medication-assisted treatment among opiate-dependent patients is associated with better outcomes. This systematic review (55 articles, 2010–2014) found wide variability in retention rates (i.e., 19%–94% at 3-month, 46%–92% at 4-month, 3%–88% at 6-month, and 37%–91% at 12-month follow-ups in randomized controlled trials), and identified medication and behavioral therapy factors associated with retention. As expected, patients who received naltrexone or buprenorphine had better retention rates than patients who received a placebo or no medication. Consistent with prior research, methadone was associated with better retention than buprenorphine/naloxone. And, heroin-assisted treatment was associated with better retention than methadone among treatment-refractory patients. Only a single study examined retention in medication-assisted treatment for longer than 1 year, and studies of behavioral therapies may have lacked statistical power; thus, studies with longer-term follow-ups and larger samples are needed. Contingency management showed promise to increase retention, but other behavioral therapies to increase retention, such as supervision of medication consumption, or additional counseling, education, or support, failed to find differences between intervention and control conditions. Promising behavioral therapies to increase retention have yet to be identified.     

Genetic approaches to drug dependence.

Pharmacogenetic studies with drugs of abuse are proliferating. Many genetic animal models are now available for studies of the mechanisms of action of a variety of drugs. These models provide unique, genetically defined populations of extremely sensitive and insensitive animals for neuropharmacological analyses. John Crabbe and John Belknap describe how molecular biological methods are being applied to these models in combination with more traditional genetic mapping strategies to identify single genes of importance to drug effects. Pharmacogenetic approaches offer the hope of establishing commonalities of mechanisms among abused drugs.     

Psychosocial interventions for bipolar disorder: a review of literature and introduction of the systematic treatment enhancement program

What is the evidence that psychosocial treatment adds to the efficacy of pharmacotherapy in forestalling episodes of bipolar disorder (BPD)? This article give s the rationale for including psychosocial intervention in the outpatient maintenance of BPD. Attention is placed on the three psychosocial modalities that have achieved empirical support in randomized trials: family psychoeducational treatment, cognitive-behavioral therapy, and interpersonal and social rhythm therapy. These three treatments are being contrasted with a psychosocial control condition in the context of the ongoing, multi-center Systematic Treatment Enhancement Program for Bipolar Disorder (STEP - BD). The objectives, design, and potential contributions of the STEP-BD study are explained. Future directions for the evaluation and dissemination of manual-based psychosocial interventions are discussed.     

Psychosocial interventions for addiction-affected families in Low and Middle Income Countries: A systematic review

AimTo review the literature on psychosocial interventions for addiction affected family members in Low and Middle Income Countries (LMIC).MethodsA systematic review with a detailed search strategy focussing on psychosocial interventions directed towards people affected by addiction without any gender, year or language specifications was conducted. Identified titles and abstracts were screened; where needed full papers retrieved, and then independently reviewed. Data was extracted based on the aims of the study, to describe the modalities, acceptability, feasibility and effectiveness of the interventions.ResultsFour papers met our selection criteria. They were published between 2003 and 2014; the total sample size was 137 participants, and two studies were from Mexico and one each from Vietnam and Malaysia. The predominantly female participants comprised of parents, spouses and siblings. The common components of all the interventions included providing information regarding addiction, teaching coping skills, and providing support. Though preliminary these small studies suggests a positive effect on affected family members (AFM). There was lowering of psychological and physical distress, along with a better understanding of addictive behaviour. The interventions led to better coping; with improvements in self-esteem and assertive behaviour. The interventions, mostly delivered in group settings, were largely acceptable.ConclusionsThe limited evidence does suggest positive benefits to AFMs. The scope of research needs to be extended to other addictions, and family members other than spouse and female relatives. Indigenous and locally adapted interventions are needed to address this issue keeping in mind the limited resources of LMIC. This is a field indeed in its infancy and this under recognised and under-served group needs urgent attention of researchers and policy makers.     

Statistical approaches for evaluating surrogate outcomes in clinical trials: A systematic review

The use of surrogate outcomes that predict treatment effect on an unobserved true outcome may have substantial economic and ethical advantages, through reducing the length and size of clinical trials. There has been extensive investigation of the best means of evaluating putative surrogates. We present a systematic review on the evolution of statistical methods for validating surrogates starting from the defining paper of Prentice (1989). We highlight the fundamental differences in the current statistical evaluation approaches, their advantages and disadvantages, and examine the understanding and perceptions of investigators in this area.     

Traveler's thrombosis: a systematic review

BACKGROUND: Anecdotal evidence suggests a possible link between travel and venous thromboembolism (VTE). We systematically evaluated the evidence from observational studies. METHODS: We searched studies evaluating the risk of venous thrombosis in relation to traveling from MEDLINE and EMBASE up tp March 2004, together with a hand search of reference lists from retrieved literature, and we contacted some of the experts. Observational studies estimating the risks of VTE and isolated calf vein thrombosis were eligible. Methodologic quality was assessed based on prior criteria, and meta-analysis was considered where applicable. RESULTS: A total of 194 English-language publications were initially identified. Sixteen studies were included: 9 case-control, 2 prospective controlled, and 5 other observational studies. They differed drastically in study designs, selection of controls where applicable, mode and duration of travel, and subtypes of VTE under consideration. Ten studies concluded that travel, mostly through air and of prolonged duration, is a risk factor for venous thrombosis and/or pulmonary embolism, and the risk increases for passengers with preexisting venous thrombosis risk factors. Outcomes examined ranged from asymptomatic isolated calf muscle vein thrombosis to severe fatal pulmonary embolism. Conclusions: Current literature is controversial over any association between travel and VTE, and although the quality and power of these studies have been variable, studies of higher quality have shown a strong and significant association between prolonged air travel and VTE. No conclusions could be drawn about other modes of transportation. Since VTE is a disease of multifactorial causation, those with preexisting VTE risk factors are most vulnerable.