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Biomedical subjects

Frances R Levin

Publications and source records attributed to Frances R Levin.

At least 19 recordsLinked to original sources

New Horizons in the Development of Treatments for Substance Use Disorders.

Substance use disorders (SUDs) are a major public health problem in the United States and cause substantial morbidity and mortality. There are meaningful gaps in the available SUD treatment options, and the development of new therapies is urgently needed. While medications with U.S. Food and Drug Administration approval are available for alcohol, nicotine, and opioid use disorders, there are no approved pharmacotherapies for cannabis, cocaine, or methamphetamine use disorders. Behavioral treatments for SUDs have significant limitations in effectiveness and accessibility, and there is a need for the development of both new behavioral treatment options and new models of treatment delivery. The next generation of treatments for SUDs will likely come from a diverse set of interventions, including new drug classes, new technologies, and new methods of delivery.

Humans↗

Treatment of cocaine dependent treatment seekers with adult ADHD: double-blind comparison of methylphenidate and placebo.

The purpose of this double-blind 14-week trial was to compare the efficacy of sustained-release methylphenidate (MPH) to placebo (PBO) in treating adult attention deficit hyperactivity disorder (ADHD) symptoms in current cocaine dependent (CD) treatment seekers. The randomized sample consisted of 106 participants who were predominately male (83%) and 60% Caucasian, 14% Hispanic, 20% African-American and 6% other. All participants met DSM-IV criteria for ADHD and CD. There were no significant demographic differences between the two treatment groups. All participants received weekly individual cognitive behavioral therapy. There was no difference in retention rate based on treatment group (p=.91). The majority of the PBO group and the MPH group reported >30% improvement in their ADHD symptoms (55% versus 47%), with no significant difference between the two groups (p=.44). Using a combined outcome measure (>30% reduction in ADHD symptoms and CGI <3), the response rates were similar for both groups (28% PBO versus 30% MPH; p=.83). Longitudinal analyses of the urine toxicology data using generalized estimating equations, revealed a decrease in the probability of cocaine positive urine samples during the trial for the MPH group compared to the PBO group (p=.001). Further analysis suggested that for the MPH group, ADHD treatment responders, based on a semi structured clinical interview, were more likely to have a reduction in cocaine use compared to the non-ADHD responders. Although sustained-release MPH did not show superiority over PBO in treating ADHD symptoms, this trial provides some evidence that improvement in ADHD symptoms (clinician rated) among those patients receiving MPH, but not placebo, was associated with a reduction in cocaine use.

Adolescent↗

Verbal abilities as predictors of retention among adolescents in a therapeutic community.

The relationship between verbal skills and retention among adolescents in substance abuse treatment is understudied. In order to assess verbal predictors of retention, twenty-eight 16-19 year old adolescents in a therapeutic community for substance abuse were evaluated between 30 and 90 days after admission. These adolescents were then followed prospectively for 1 year. Verbal and non-verbal cognitive screens, audio taped narrative responses, and self-reports of socio-emotional function and psychiatric symptoms were completed. Verbal scores were associated with self-restraint and counselor reports of therapeutic engagement and comprehension. General verbal scores predicted attrition, while therapeutic expressiveness (verbal expressiveness in a therapeutic context) predicted retention. Remediation of verbal communication skills may be an overlooked aspect of the therapeutic process in treating adolescent substance abusers.

Adolescent↗

Treating depression in substance abusers.

The literature on the diagnosis and treatment of depression is reviewed to arrive at recommendations for clinical practice, future research, and models of service delivery. The DSM-IV criteria are found to provide a sound basis for diagnosis, and a review of placebo-controlled trials of antidepressant medications among substance-dependent patients suggests medication is effective in the setting of careful diagnosis, preferably during a currently observed abstinent period. Clinical recommendations offered for the approach to patients with co-occurring depression and substance dependence include the following: 1) Initiate treatment for substance dependence and encourage abstinence; 2) Conduct a careful psychiatric history and apply DSM-IV criteria for primary or substance-induced depression; 3) If depression meets diagnostic criteria and persists despite treatment of substance use disorder, treat the depression. Future research should include trials of psychotherapeutic or behavioral treatments, studies of treatment algorithms and of integrated systems of care, and studies of methods for disseminating diagnostic and treatment methods in an effort to diminish traditional boundaries between the skill sets of mental health and substance abuse clinicians.

Comorbidity↗

Concurrent cannabis use during treatment for comorbid ADHD and cocaine dependence: effects on outcome.

Cannabis is the most widely used illicit substance in the United States with especially high prevalence of use among those with psychiatric disorders. Few studies have examined the relationship between concurrent cannabis use and treatment outcome among patients receiving treatment for comorbid substance abuse and psychiatric disorders. This study investigated the effects of cannabis use on treatment retention and abstinence from cocaine among cocaine dependent patients with Attention Deficit Hyperactivity Disorder (ADHD). Cocaine dependent patients diagnosed with current ADHD (DSM-IV, N = 92) aged 25 to 51 participated in a randomized clinical trial of methylphenidate for treatment of ADHD and cocaine dependence in an outpatient setting. The majority of patients (69%) used cannabis during treatment. Results suggest that moderate/intermittent cannabis users had greater retention rates compared to abstainers and consistent users (p = .02). This study is the first to examine concurrent cannabis use in cocaine dependent patients diagnosed with ADHD.

Adolescent↗

Severity of dependence and motivation for treatment: comparison of marijuana- and cocaine-dependent treatment seekers.

Although marijuana dependence is prevalent, most individuals with marijuana dependence do not seek treatment. There are few data characterizing treatment seeking marijuana-dependent patients compared to patients presenting for treatment of other drugs regarding the severity of illness and motivation for treatment. Forty-two marijuana-dependent individuals were compared to 58 cocaine-dependent individuals seeking treatment. Compared to cocaine-dependent patients, those with marijuana dependence were younger and less likely to be dependent on alcohol or other drugs. Both groups had similar rates of comorbid anxiety and affective disorders. Marijuana-dependent individuals had lower total number of dependence symptoms but had a higher percentage of individuals endorsing withdrawal symptoms. Although marijuana-dependent individuals had less outpatient treatment exposure, the difference between the two groups was not significant and motivation for change, based on the University of Rhode Island Change Assessment, was similar for both groups of treatment seekers. However, the Circumstances, Motivation, Readiness for Treatment Scale suggested that cocaine-dependent individuals were more motivated for treatment. Taken together, these data suggest that treatment seeking marijuana-dependent individuals have substantial withdrawal dependence symptomatology although it is less clear if they are as motivated to seek out treatment as cocaine-dependent treatment seekers.

Adult↗

Assessment of cognitive functioning of methadone-maintenance patients: impact of adult ADHD and current cocaine dependence.

The purpose of this study was to determine if methadone-maintained patients (MMP) with cocaine dependence (CD) and/or adult Attention Deficit Hyperactivity Disorder (ADHD) exhibited compounded cognitive dysfunction associated with their poly-substance use and/or co-morbid psychiatric diagnoses. The sample consisted of 79 MMP (59% male, 51% Caucasian), maintained on methadone doses ranging from 40-130 mg/day, who were placed into one of four diagnostic categories: (1) a control group (no ADHD, no CD) (n = 24), (2) CD alone (n = 18), (3)ADHDalone (n = 18), and (4)ADHD+ CD(n = 19). The California Computerized Assessment Package (CalCAP) was administered to assess cognitive functioning requiring focused and sustained attention in a standardized fashion. There were no group differences on Simple Reaction tasks. Compared to the control group, the ADHD+ CD group was slower and less accurate on 33% of the Choice Reaction (CR) tasks. Specifically, individuals in the ADHD + CD group and the ADHD alone group performed significantly worse on tasks measuring attention and psychomotor responding. These tasks are associated with broader cognitive skills in working memory, language discrimination and flexibility of cognitive sets that may have implications for treatment outcome. Diagnostic services capable of identifying cognitive deficits among MMP with ADHD and/or CD are needed to maximize the likelihood of treatment success and to serve as an indicator for the efficacy of therapeutic approaches.

Adult↗

Evaluation of a combined online and in person training in the use of buprenorphine.

To evaluate buprenorphine training methodology, we surveyed physicians who had completed a combined online and in person buprenorphine curriculum. Of 53/70 (76%) survey respondents, 57% were psychiatrists and 40% generalists. On a scale of 1 (very poor) to 7 (superlative), the overall training rated a mean of 5.8. The online course (5.0) rated lower than in person training components (p < .001) except for material that addressed the logistics of office practice. The in person patient interview received the highest rating (mean 6.3, p < .001). The 67% of physicians who intended to prescribe buprenorphine after the training were more likely than hesitant physicians to agree that the course provided enough information (p < .05) and that telephone access to experienced providers would improve their confidence (p < .05). Physicians hesitant to prescribe cited lack of experience as the main barrier (41%), with 24% concerned about induction difficulty and reimbursement. Overall, physicians preferred in person instruction and may benefit from additional experiential training and support after curriculum participation.

Adult↗

A randomized placebo-controlled trial of gabapentin for cocaine dependence.

BACKGROUND: In laboratory animals, augmentation of GABA neurotransmission results in inhibition of cocaine self-administration and inhibition of reinstatement to cocaine-seeking behaviors. If parallel effects were observed in humans, GABA-ergic medication should be effective both in the abstinence-induction as well as in the relapse-prevention phase of cocaine dependence treatment. Gabapentin is an anticonvulsant medication that increases human brain GABA levels. We evaluated the safety and efficacy of gabapentin combined with relapse-prevention therapy in the treatment of cocaine-dependent individuals. DESIGN: The study involved 129 individuals with cocaine dependence. Of the 99 participants, who were randomized into a double-blind trial 88% were males, 66% were minorities and with an average age of 39 years (range 22-58 years). After 2 weeks of placebo lead-in, participants were randomized to receive either gabapentin 3200 mg (1600 mg bid) or placebo for 12 weeks, followed by 2 weeks of placebo lead-out. Prior to randomization, participants were stratified into four groups based on the principal route of cocaine use (smokers versus intranasal users) and the level of cocaine use during the 2 weeks of lead-in (high level versus low level). Throughout the 16 weeks study, participants received weekly individual relapse-prevention therapy. The outcome measures included: days of cocaine use and a binary indicator of abstinence based on urine toxicology test, self-reported cocaine craving and retention in treatment. RESULTS: Forty-nine percent of randomized patients completed 12 weeks of the trial. Retention did not differ by treatment group but cocaine-smokers dropped out of treatment at a significantly faster rate than intranasal users. For the entire sample, odds of cocaine use over the course of the study did not differ between gabapentin- and placebo-treated individuals. There was a significant difference in the odds of cocaine use between high and low-use groups, with the odds in high-use groups decreasing over time and odds in the low-use groups gradually increasing over the course of the study, such that by the end of the study low and high users were similarly likely to use cocaine. In the low-use group, there was a non-significant trend suggesting that gabapentin-treated subjects had more favorable outcome compared to placebo-treated individuals. There was no treatment effect on abstinence rates, craving or other substance use. Gabapentin at 3200 mg/day was very well tolerated in this group of cocaine-dependent participants. CONCLUSIONS: When combined with weekly individual relapse-prevention therapy, gabapentin 1600 mg bid was no more effective than placebo in the treatment of cocaine dependence. When reviewed in conjunction with other published studies, gabapentin and other GABA enhancing anticonvulsant medications may deserve further study as relapse-preventive agents in cocaine-dependent individuals who achieve abstinence early in treatment.

Adult↗

Response to cocaine, alone and in combination with methylphenidate, in cocaine abusers with ADHD.

Attention deficit hyperactivity disorder (ADHD) is prevalent in adult cocaine abusers. Yet, it remains to be determined how the response to cocaine differs in cocaine abusers with ADHD compared to cocaine abusers without ADHD. Further, since ADHD is commonly treated with stimulants, such as methylphenidate (MPH), it is important to examine whether MPH maintenance alters the response to cocaine in cocaine abusers with ADHD. Thus, the first phase of this study compared the response to cocaine in adult cocaine abusers with ADHD to those without ADHD. The second phase assessed the effects of oral sustained-release methylphenidate (MPH-SR) maintenance (40 and 60 mg) on the response to cocaine only in those with ADHD. Cocaine abusers with ADHD (N=7) and without ADHD (N=7) who were not seeking treatment remained inpatient initially for 1 week, when the effects of cocaine alone were tested (Phase 1). Cocaine abusers with ADHD remained inpatient for an additional 3 weeks, during which the effects of cocaine during oral MPH-SR maintenance were tested (Phase 2). During cocaine fixed dosing sessions, participants received four injections of i.v. cocaine (0, 16 or 48 mg/70 kg), spaced 14 min apart. During cocaine choice sessions, participants had a choice between receiving i.v. cocaine (16 or 48 mg/70 kg) or two tokens, each exchangeable for 2 US dollars. Subjective effects related to ADHD symptoms (e.g. ratings of "Able to Concentrate") were significantly lower in cocaine abusers with ADHD compared to those without ADHD when placebo cocaine was administered. Active cocaine produced similar increases in cardiovascular and positive subjective effects in both groups and there was no difference in cocaine choice between the two groups. These data suggest that the response to cocaine is not different between cocaine abusers with ADHD compared to those without ADHD. When the cocaine abusers with ADHD were maintained on MPH-SR, cardiovascular effects were increased, however, this did not warrant termination of any test session. Maintenance on MPH-SR decreased some of the positive subjective effects of cocaine. Further, maintenance on a high dose of MPH-SR decreased cocaine choice. Thus, oral MPH-SR is safe in combination with repeated cocaine doses and decreases some of the positive and reinforcing effects of cocaine in cocaine abusers with ADHD.

Administration, Oral↗

Treatment of methadone-maintained patients with adult ADHD: double-blind comparison of methylphenidate, bupropion and placebo.

The purpose of this double-blind, three-arm, 12-week trial was to compare the efficacy of sustained-release methylphenidate or sustained-release bupropion to placebo in treating adult attention deficit hyperactivity disorder (ADHD) symptoms. The randomized sample consisted of 98 methadone-maintained patients who were pre-dominantly male (57%) and 40% Caucasian, 40% Hispanic and 20% African American. All participants met DSM-IV criteria for adult ADHD, with 53% meeting DSM-IV criteria for cocaine dependence/abuse. In addition to medication and treatment as usual at a methadone program, individuals received weekly individual cognitive behavioral treatment. Other than current employment status, there were no significant demographic differences across the three treatment groups. Seventy percent completed the 12-week trial. There were no differences in retention rate based on treatment group. A reduction in ADHD symptoms using the adult ADHD rating scale was observed in all three groups, but there were no significant differences in outcome between treatments. The placebo response rate was high, with 46% of the placebo group self-reporting substantial improvement in their ADHD symptoms (>30% reduction in adult ADHD rating scale). Using other ADHD outcome measures, the placebo response and medication response rates were substantially lower. There was no evidence of misuse of medication or worsening of cocaine use among those randomized to methylphenidate. Taken together, sustained-release methylphenidate or sustained-release bupropion did not provide a clear advantage over placebo in reducing ADHD symptoms or additional cocaine use in methadone-maintained patients.

Adult↗

Utility of lead-in period in cocaine dependence pharmacotherapy trials.

We examined whether drug use behaviors during a 2-week lead-in for a pharmacotherapy trial were predictive of retention in treatment and of the level of cocaine use during the subsequent 12 weeks of treatment. Fifty cocaine dependent patients were grouped based on: (1) principal route of cocaine administration: intranasal versus smoking, and (2) level of cocaine use during the 2-week lead-in: high versus low. Results indicate that level of cocaine use during the 2-week lead-in was a significant predictor of cocaine use during the subsequent 12 weeks of treatment. Patients with reported higher level of use during the lead-in period were more likely to continue using cocaine during the treatment. Patients who used smoking as their primary route of cocaine use were more likely to drop out early in the treatment. Findings of this study suggest that route and level of cocaine use during lead-in be used as a covariate in models testing treatment effect.

Adult↗

Adult ADHD and substance abuse: diagnostic and treatment issues.

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral, developmental disorder most often diagnosed during childhood, marked by the core symptoms of inattention, hyperactivity, and impulsivity that results in social, academic, and occupational underachievement. Although the disorder has a prevalence of 3-9% in the general childhood population and 1-5% in the general adult population, it affects between 11 and 35% of "substance-abusing" adults, oftentimes complicating treatment response. The present review discusses diagnostic assessment issues, prevalence, comorbidity, pharmacotherapy, and psychological interventions in substance-abusing adults with ADHD.

Attention Deficit Disorder with Hyperactivity↗

Attention-deficit/hyperactivity disorder and early-onset substance use disorders.

In recent years, there has been an increased recognition of the common comorbidity of attention-deficit/ hyperactivity disorder (ADHD) and substance use disorder (SUD) among adolescents and adults. ADHD can be an important factor in the pathogenesis and maintenance of SUD; moreover, retrospective studies suggest that treating ADHD during childhood may prevent the development of SUD. In addition, treatment of ADHD among adults, and possibly adolescents, with SUD can reduce their risk of relapse. Theoretical mechanisms that may explain the relationship between ADHD and SUD are explored in this paper. Current research and recommended clinical practices related to the diagnosis and treatment of ADHD with SUD in adolescents are discussed as well. More research is needed to definitively assess the effectiveness and safety of medications in this population of youths with ADHD and SUD.

Adolescent↗

Screening and intervention for alcohol and illicit drug abuse:a survey of internal medicine housestaff.

This study attempts to determine how internal medicine housestaff screen and intervene for problematic alcohol and illicit drug use, as well as identify factors correlating with favorable practices. A cross-sectional survey was administered to 93 medical housestaff. Of 64 (69%) respondents, 94% reported routinely screening new patients for alcohol or illicit drug use, while only 52% routinely quantified alcohol consumption and 28% routinely used a screening instrument. Housestaff were unfamiliar with national guidelines and felt unprepared to diagnose substance use disorders, particularly prescription drug abuse. Most routinely counseled patients with alcohol (89%) or illicit-drug problems (91%), although only a third of these patients were referred for formal treatment. More thorough screening practices were associated with greater treatment optimism, while favorable referral practices were associated with greater optimism about 12-step program benefit and difficulty with management. These findings suggest areas to be addressed in residency curricula on substance abuse.

Adult↗

Bipolar disorder and substance abuse.

Substance use disorders are overrepresented in individuals with bipolar and bipolar spectrum disorders. Although awareness of this phenomenon has increased over the past 20 years, few empirically based treatment strategies have been developed for this challenging patient population. This review examines the relationship between bipolar and substance use disorders and treatment options that have been studied in this patient population. First, we examine the high prevalence rates of substance use disorders in individuals diagnosed with bipolar disorder, the common problems associated with establishing a bipolar disorder diagnosis in individuals who abuse substances, the possible explanations for the frequent coexistence of bipolar and substance use disorders, and the negative effect of substance abuse on the course of and treatment outcomes for bipolar disorder. The review then focuses on treatment approaches for this patient population, including integrated group therapy for co-occurring bipolar and substance use disorders and pharmacotherapies that target both disorders. Finally, we present suggestions for medications that might be tested for their efficacy in treating both disorders in specific subgroups of patients with bipolar and substance use disorders.

Bipolar Disorder↗

Treatment of depression in patients with opiate dependence.

Depression is common among opiate-dependent patients and has been associated with worse prognosis. This article reviews the literature on treatment of depressive disorders and symptoms among patients with opiate dependence. Depression bears a complex relationship to opiate dependence and may represent an independent disorder or may be engendered by psychosocial stress or toxic and withdrawal effects of drugs. Primary treatments for opiate dependence (e.g., methadone or buprenorphine maintenance or residential treatment) are associated with substantial improvements in depression. Studies of antidepressant medications have produced mixed results, some positive but more negative. It is not clear what accounts for these differences, and more research is needed to determine how to select opiate-dependent patients most likely to benefit from antidepressants. Fewer studies have examined psychosocial or behavioral interventions, but some of these also show promise. The data suggest a stepped model of care in which depression is evaluated and observed during the outset of treatment for opiate dependence and if it does not improve, specific psychosocial interventions or antidepressant medications tried. Research is needed on such integrated models of care and treatment algorithms to determine their efficacy and cost effectiveness.

Affect↗