Paolo Mannelli

A randomized, double-blind, placebo-controlled trial of augmentation with an extended release formulation of methylphenidate in outpatients with treatment-resistant depression.

We examined the efficacy and tolerability of augmentation with an extended release formulation of methylphenidate (OROS MPH, Concerta) in patients with major depression who were nonresponders or partial responders to antidepressants. Sixty subjects with treatment-resistant depression (TRD) participated in a 4-week, randomized, double-blind, placebo-controlled study of augmentation with methylphenidate (18-54 mg/d). The preexisting antidepressant dose was unchanged. The primary efficacy measure was change in the 21-item Hamilton Depression Rating Scale from randomization to end of treatment. Data were analyzed with intent-to-treat with last observation carried forward approach. There were no statistically significant differences between the methylphenidate (n = 30) and placebo (n = 30) groups in reduction in 21-item Hamilton Depression Rating Scale scores (drug, −6.9; placebo, −4.7) from baseline to end of treatment (F1,47 = 1.24, P = 0.22), although responders were numerically higher in the extended-release methylphenidate group (40.0%) than in the placebo group (23.3%). On the secondary efficacy measures of changes in Clinical Global Impression-Improvement and Severity scores and Beck Depression Inventory-Second Edition, the drug failed to separate from placebo, although the proportion of responders in the drug group were numerically higher than placebo. There were no significant differences in weight, heart rate, and blood pressure changes between the 2 groups. The common adverse events were loss of appetite, nausea, headache, and anxiety. The mean dose of drug was 34.2 mg/d. The study did not demonstrate a statistically significant benefit for augmentation with methylphenidate in TRD. Combination of methylphenidate with antidepressants was well tolerated. Adequately powered, randomized, controlled trials are necessary to fully evaluate the efficacy of extended-release methylphenidate in TRD.

Opiate detoxification of methadone maintenance patients using lefetamine, clonidine and buprenorphine

Thirty-nine methadone maintenance patients were included in a 9-day, double blind, randomized, inpatient detoxification trial. Methadone was tapered to 10 mg/day and then patients were assigned to one of these 3 protocols: clonidine (0.3-0.9 mg/day), lefetamine (60-240 mg/day), buprenorphine (0.15-0.9 mg/day). Buprenorphine treatment was significantly superior to clonidine and to lefetamine (F = 3.96 df = 2, 29 P < 0.05) in controlling objective, subjective and psychological withdrawal symptomatology. Clonidine was more effective than lefetamine in suppressing withdrawal in the first 3 days of treatment (day 3: F = 4.10 df = 2, 30 P < 0.05), and this trend was apparent on the objective and psychological items. In addition to evaluations of the efficacy of the single drugs used, the study showed that tapering methadone to low doses before entering the pharmacologically assisted discontinuation phase was clinically acceptable in detoxification from long-term methadone treatment.

A Double-Blind, Randomized, Placebo-Controlled Trial of Paroxetine Controlled-Release in Irritable Bowel Syndrome

BACKGROUND Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disease that causes significant impairment in quality of life and accounts for

Effects of fluoxetine at antidepressant doses on short-term outcome of detoxified alcoholics

8 billion per year to the healthcare system and loss of productivity in the workplace. OBJECTIVE The authors examined the efficacy and safety of paroxetine controlled-release (paroxetine-CR) in patients with IBS. METHOD Seventy-two patients with IBS participated in a 12-week, double-blind, randomized, placebo-controlled study of paroxetine-CR (12.5 mg-50 mg/day). Efficacy was measured by Composite Pain Scores (primary outcome) and the Clinical Global Impression-Improvement (CGI-I) and Severity (CGI-S) ratings. RESULTS In intent-to-treat analyses, there were no significant differences between paroxetine-CR (N=36) and placebo (N=36) on reduction in Composite Pain Scores, although the proportion of responders on CGI-I was significantly higher in the paroxetine-CR group. The treatment was well tolerated. CONCLUSION The study did not demonstrate a statistically significant benefit for paroxetine-CR over placebo on the primary outcome measure, although there was improvement in secondary outcome measures. Overall, paroxetine-CR seems to have potential benefit in IBS. Studies with adequate samples may clarify the role of paroxetine-CR in IBS.

Changes in tobacco smoking following treatment for cocaine dependence.

&NA; Compulsivity in alcohol‐dependent patients is a frequent cause of early relapse in the post‐detoxification period. The present study is a 2‐month trial on detoxified alcoholics undergoing a double‐blind placebo‐controlled treatment with fluoxetine (20 mg/day). The rating instruments were the Hamilton Depression and Anxiety Scales, a visual analogue scale for alcohol craving and an original scale for evaluating alcohol withdrawal. The abstinence rate for fluoxetine‐treated patients was significantly higher than in the placebo group, whereas no difference between treatments was found on the rating scales. Medical problems, additional psychiatric diagnoses, and family alcoholism were negatively correlated with abstinence. Two subgroups of patients having significantly different characteristics were identified as to the outcome, by means of cluster analysis. They are likely to represent two different stages in the evolution of alcoholism. Our results show that, independently from craving, fluoxetine at antidepressant doses is able to prevent relapses in weaned alcoholics. The anticompulsive therapy can positively influence the short‐term outcome, while other factors are negatively associated with abstinence.

Alcohol and Drug Use Disorders Among Adults in Emergency Department Settings in the United States

Incorporation of smoking cessation into cocaine treatment programs remains a challenge. A major concern is that cocaine abusers may tend to substitute one drug for the other. If this is true, successful treatment of cocaine abuse should lead to an increase in tobacco smoking. We compared tobacco smoking at admission, end of treatment and 9-month follow up for 168 crack cocaine dependent patients entering a 12-week outpatient treatment program for substance abuse. Smoking cessation was not a part of treatment. As expected cocaine patients improved with treatment and showed significant reduction in scores on the Addiction Severity Index (ASI). There were no significant changes in number of cigarettes smoked per day or scores on the Fagerstrom Test for Nicotine dependence (FTND) from baseline to end of treatment or follow-up. Also, there were no differences in the proportions of nonsmokers and smokers who changed their smoking habits over the treatment and follow up period. At follow up subjects who were abstinent as well as those using cocaine showed no changes in tobacco smoking. There is no evidence that reduction in crack cocaine smoking following treatment is accompanied by an increase in tobacco smoking. It appears that concerns over tobacco being substituted for cocaine may be unfounded in this population.

Opioid use affects antioxidant activity and purine metabolism: preliminary results†‡

STUDY OBJECTIVE Improving identification and treatment for substance use disorders is a national priority, but data about various drug use disorders encountered in emergency departments (EDs) are lacking. We examine past-year substance use and substance use disorders (alcohol, 9 drug classes) among adult ED users. Prevalences of substance use and substance use disorders among ED nonusers are calculated for reference purposes. METHODS Using data from the 2007 to 2009 National Surveys on Drug Use and Health, we assessed substance use disorders among noninstitutionalized adults aged 18 years or older who responded to standardized survey questions administered by audio computer-assisted self-interviewing methods. RESULTS Of all adults (N=113,672), 27.8% used the ED in the past year. ED users had higher prevalences than ED nonusers of coexisting alcohol and drug use (15.2% versus 12.1%), drug use (any drug, 16.9% versus 13.0%; marijuana, 12.1% versus 9.7%; opioids, 6.6% versus 4.1%), and alcohol or drug disorders (11.0% versus 8.5%). Among substance users, the ED group on average spent more days using drugs than the non-ED group; ED users manifested higher conditional rates of substance use disorders than ED nonusers (alcohol or drugs, 15.9% versus 11.7%; marijuana, 16.6% versus 13.2%; cocaine, 33.2% versus 22.3%; opioids, 20.6% versus 10.0%; stimulants, 18.6% versus 9.2%; sedatives, 35.0% versus 4.4%; tranquilizers, 12.4% versus 5.2%). Regardless of ED use status, substance-using young adults, men, and less-educated adults showed increased odds of having a substance use disorder. CONCLUSION Drug use is prevalent and combined with high rates of drug use disorders among drug users treated in the ED.

Differences in onset and abuse/dependence episodes between prescription opioids and heroin: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

More must be learned about metabolic and biochemical alterations that contribute to the development and expression of drug dependence. Experimental opioid administration influences mechanisms and indices of oxidative stress, such as antioxidant compounds and purine metabolism. We examined perturbations of neurotransmitter‐related pathways in opioid dependence (OD).

Comparison of Pretreatment Characteristics and Treatment Outcomes for Alcohol-, Cocaine-, and Multisubstance-Dependent Patients

Objectives To examine patterns of onset and abuse/dependence episodes of prescription opioid (PO) and heroin use disorders in a national sample of adults, and to explore differences by gender and substance abuse treatment status. Methods Analyses of data from the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Results Of all respondents, 5% (n = 1815) reported a history of nonmedical PO use (NMPOU) and 0.3% (n = 150) a history of heroin use. Abuse was more prevalent than dependence among NMPOUs (PO abuse, 29%; dependence, 7%) and heroin users (heroin abuse, 63%; dependence, 28%). Heroin users reported a short mean interval from first use to onset of abuse (1.5 years) or dependence (2.0 years), and a lengthy mean duration for the longest episode of abuse (66 months) or dependence (59 months); the corresponding mean estimates for PO abuse and dependence among NMPOUs were 2.6 and 2.9 years, respectively, and 31 and 49 months, respectively. The mean number of years from first use to remission from the most recent episode was 6.9 years for PO abuse and 8.1 years for dependence; the mean number of years from first heroin use to remission from the most recent episode was 8.5 years for heroin abuse and 9.7 years for dependence. Most individuals with PO or heroin use disorders were remitted from the most recent episode. Treated individuals, whether their problem was heroin or POs, tended to have a longer mean duration of an episode than untreated individuals. Conclusion Periodic remissions from opioid or heroin abuse or dependence episodes occur commonly but take a long time. Timely and effective use of treatment services are needed to mitigate the many adverse consequences from opioid/heroin abuse and dependence.

Relationship between serotonin transporter gene polymorphisms and platelet serotonin transporter sites among African-American cocaine-dependent individuals and healthy volunteers

Abstract We investigated whether pretreatment characteristics and measures of outcome differed for alcohol-, cocaine-, and multisubstance-dependent patients receiving outpatient substance abuse treatment. One hundred and forty substance dependent individuals (32 alcohol, 76 cocaine, and 32 multisubstance) enrolled in a 12-week outpatient treatment program were compared across measures of addiction severity, personality, and treatment-readiness at admission. In-treatment, end-of-treatment and 9-month follow-up assessments of treatment outcome were then compared across the three groups. Outcome measures included reduction in problem severity, abstinence, retention, number of sessions attended, dropout, and counselor and patient ratings of treatment benefit. At admission, the multisubstance group had a higher proportion of positive urines, reported more severe drug, alcohol and psychiatric problems, and displayed higher impulsivity and anxiety scores than one or both of the other groups. However, multisubstance patients were more treatment ready in terms of adopting a total abstinence orientation than alcohol or cocaine patients. While a significant reduction in symptoms occurred for the total sample during treatment as well as at follow-up, comparisons of outcomes did not consistently favor any particular group. The three groups had equivalent improvements in eleven of fourteen during-treatment and five of seven follow-up measures. Despite pre-treatment differences, in severity and treatment-readiness, outcomes were more similar than different for alcohol-, cocaine-, and multisubstance-dependent patients. Clinicians should be cautious about forecasting treatment-outcomes for addicted patients based on their primary substances of abuse.