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Alcohol and other xenobiotics may limit the therapeutic effects of medications. We aimed at investigating alcohol-medication interactions (AMI) after the exclusion of confounding effects related to other xenobiotics. We performed a systematic review and meta-analysis of controlled studies comparing the effects induced by alcohol versus placebo on pharmacodynamic and/or pharmacokinetic parameters of approved medications. Certainty in the evidence of AMI was assessed when at least 3 independent studies and at least 200 participants were available. We included 107 articles (3097 participants): for diazepam, cannabis, opioids, and methylphenidate, we found significant AMI and enough data to assign the certainty of evidence. Alcohol consumption significantly increases the peak plasma concentration of diazepam (low certainty; almost 290 participants), cannabis (high certainty; almost 650 participants), opioids (low certainty; 560 participants), and methylphenidate (moderate certainty; 290 participants). For most medications, we found some AMI but not enough data to assign them the certainty grades; for some medications, we found no differences between alcohol and placebo in any outcomes evaluated. Our results add further evidence for interactions between alcohol and certain medications after the exclusion of confounding effects related to other xenobiotics. Physicians should advise patients who use these specific medications to avoid alcohol consumption. Further studies with appropriate control groups, enough female participants to investigate sex differences, and elderly population are needed to expand our knowledge in this field. Short phrases suitable for indexing terms • Among participants taking diazepam, those who consumed alcohol achieved higher peak plasma concentration (low certainty; almost 290 participants) and area under the curve (very low certainty; 270 participants) of this medication compared to those who consumed placebo • Among participants taking cannabis, those who consumed alcohol achieved higher peak plasma concentration (high certainty; almost 650 participants), in a shorter time (very low certainty; more than 300 participants), and have a longer elimination half-life (moderate certainty; almost 250 participants) of Delta (9)-tetrahydrocannabinol (THC) compared to those who consumed placebo • Among participants taking opioids, those who consumed alcohol achieved higher peak plasma concentration (low certainty; 560 participants) and in a shorter time (moderate certainty; 554 participants) of opioids compared to those who received placebo • Among participants taking methylphenidate, those who consumed alcohol achieved higher peak plasma concentration (moderate certainty; 290 participants) and area under the curve of this medication compared to those who consumed placebo

The diagnosis of substance use disorder is currently based on the presence of specifically identified behavioral symptoms. In addition, other psychiatric signs and symptoms accompany addictive behavior, contributing to the full picture of patients’ psychopathologic profile. Historically, such symptoms were confined within the framework of “comorbidity”, as comorbid psychiatric disorders or personality traits. However, an alternative unitary view of the psychopathology of addiction, inclusive of related psychiatric symptoms, has been claimed, with the support of epidemiological, neurobiological, and neuropsychological evidence. In the present article, we highlight the research advancements that strengthen this unified perspective. We then give an account of our group’s definition of a specific SCL-90-based construct of the psychopathology of addiction. Lastly, we discuss the benefits that can be expected to be acquired in the evaluation and treatment of patients with a longitudinal approach including psychological/psychiatric predisposing features, addictive behavior, and psychiatric manifestations.

Background: Pharmacotherapy for Alcohol Dependence (AD) is underutilized. Barriers preventing the use of AD medications include high prices, lack of access to prescribing physicians, and a limited number of available medications. Objective: The study evaluated the use of AD medications in a sample of Italian outpatients who received these medications free of charge, had access to physicians during office hours, and for whom substitution therapy [gamma-hydroxybutyrate (GHB)] was available. We also evaluated the rate of patients who received a combination of non-pharmacological and pharmacological treatments among participants who were still drinking. Methods: SCID for AD and questionnaire were filled by to AD outpatients during a face-to-face interview. Results & Discussion: 345 AD outpatients were interviewed: 58.8% were currently receiving at least one AD medication (GHB: 34.3%, disulfiram: 29.6%, acamprosate: 5.9%; naltrexone: 2.5%; more than one medication: 16.7%). Less than 30% of participants who were still drinking, received a combination of non-pharmacological and pharmacological treatments. Nonetheless, we found higher use of AD medications compared to previous studies conducted in other countries. This higher use of AD medications may be due to access to free medications, prescribing physicians’ style, and a larger number of available medications. Conclusion: Our results confirm the underutilization of AD medications, as less than 60% of AD outpatients received medications, and less than 30% of those who were still drinking, received a combination of non-pharmacological and pharmacological treatments. These findings may be useful in improving our knowledge of the barriers that prevent the use of AD medications in clinical practice.

Background:By applying a Principal Component Analysis (PCA) to the items of the SCL-90 checklist, we previously investigated the psychopathologic structure of individuals with heroin addiction, finding a 5-factor aggregation of psychological/psychiatric symptoms: “Worthlessness and Being trapped,” “

BACKGROUND: Alcohol dependence is a major public health problem characterized by recidivism, and medical and psychosocial complications. The co‐occurrence of major depression in people entering treatment for alcohol dependence is common, and represents a risk factor for morbidity and mortality, which negatively influences treatment outcomes. OBJECTIVES: To assess the benefits and risks of antidepressants for the treatment of people with co‐occurring depression and alcohol dependence. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Specialised Register (via CRSLive), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2017. We also searched for ongoing and unpublished studies via ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/). All searches included non‐English language literature. We handsearched references of topic‐related systematic reviews and the included studies. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials comparing antidepressants alone or in association with other drugs or psychosocial interventions (or both) versus placebo, no treatment, and other pharmacological or psychosocial interventions. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included 33 studies in the review (2242 participants). Antidepressants were compared to placebo (22 studies), psychotherapy (two studies), other medications (four studies), or other antidepressants (five studies). The mean duration of the trials was 9.9 weeks (range 3 to 26 weeks). Eighteen studies took place in the USA, 12 in Europe, two in Turkey, and one in Australia. The antidepressant included in most of the trials was sertraline; other medications were amitriptyline, citalopram, desipramine, doxepin, escitalopram, fluoxetine, fluvoxamine, imipramine, mianserin, mirtazepine, nefazodone, paroxetine, tianeptine, venlafaxine, and viloxazine. Eighteen studies were conducted in an outpatient setting, nine in an inpatient setting, and six in both settings. Psychosocial treatment was provided in 18 studies. There was high heterogeneity in the selection of outcomes and the rating systems used for diagnosis and outcome assessment. Comparing antidepressants to placebo, low‐quality evidence suggested that antidepressants reduced the severity of depression evaluated with interviewer‐rated scales at the end of trial (14 studies, 1074 participants, standardized mean difference (SMD) ‐0.27, 95% confidence interval (CI) ‐0.49 to ‐0.04). However, the difference became non‐significant after the exclusion of studies with a high risk of bias (SMD ‐0.17, 95% CI ‐0.39 to 0.04). In addition, very low‐quality evidence supported the efficacy of antidepressants in increasing the response to the treatment (10 studies, 805 participants, risk ratio (RR) 1.40, 95% Cl 1.08 to 1.82). This result became non‐significant after the exclusion of studies at high risk of bias (RR 1.27, 95% CI 0.96 to 1.68). There was no difference for other relevant outcomes such as the difference between baseline and final score, evaluated using interviewer‐rated scales (5 studies, 447 participants, SMD 0.15, 95% CI ‐0.12 to 0.42). Moderate‐quality evidence found that antidepressants increased the number of participants abstinent from alcohol during the trial (7 studies, 424 participants, RR 1.71, 95% Cl 1.22 to 2.39) and reduced the number of drinks per drinking days (7 studies, 451 participants, mean difference (MD) ‐1.13 drinks per drinking days, 95% Cl ‐1.79 to ‐0.46). After the exclusion of studies with high risk of bias, the number of abstinent remained higher (RR 1.69, 95% CI 1.18 to 2.43) and the number of drinks per drinking days lower (MD ‐1.21 number of drinks per drinking days, 95% CI ‐1.91 to ‐0.51) among participants who received antidepressants compared to those who received placebo. However, other outcomes such as the rate of abstinent days did not differ between antidepressants and placebo (9 studies, 821 participants, MD 1.34, 95% Cl ‐1.66 to 4.34; low‐quality evidence). Low‐quality evidence suggested no differences between antidepressants and placebo in the number of dropouts (17 studies, 1159 participants, RR 0.98, 95% Cl 0.79 to 1.22) and adverse events as withdrawal for medical reasons (10 studies, 947 participants, RR 1.15, 95% Cl 0.65 to 2.04). There were few studies comparing one antidepressant versus another antidepressant or antidepressants versus other interventions, and these had a small sample size and were heterogeneous in terms of the types of interventions that were compared, yielding results that were not informative. AUTHORS' CONCLUSIONS: We found low‐quality evidence supporting the clinical use of antidepressants in the treatment of people with co‐occurring depression and alcohol dependence. Antidepressants had positive effects on certain relevant outcomes related to depression and alcohol use but not on other relevant outcomes. Moreover, most of these positive effects were no longer significant when studies with high risk of bias were excluded. Results were limited by the large number of studies showing high or unclear risk of bias and the low number of studies comparing one antidepressant to another or antidepressants to other medication. In people with co‐occurring depression and alcohol dependence, the risk of developing adverse effects appeared to be minimal, especially for the newer classes of antidepressants (such as selective serotonin reuptake inhibitors). According to these results, in people with co‐occurring depression and alcohol dependence, antidepressants may be useful for the treatment of depression, alcohol dependence, or both, although the clinical relevance may be modest.

Alcohol abuse is one of the most important risk factors for health and is a major cause of death and morbidity. Despite this, only about one-tenth of individuals with alcohol abuse disorders receive therapeutic intervention and specific rehabilitation. Among the various dichotomies that limit an effective approach to the problem of alcohol use disorder treatment, one of the most prominent is integrated treatment versus harm reduction. For years, these two divergent strategies have been considered to be opposite poles of different philosophies of intervention. One is bound to the search for methods that aim to lead the subject to complete abstinence; the other prioritizes a progressive decline in substance use, with maximum reduction in the damage that is correlated with curtailing that use. Reduction of alcohol intake does not require any particular setting, but does require close collaboration between the general practitioner, specialized services for addiction, alcohology services and psychiatry. In patients who reach that target, significant savings in terms of health and social costs can be achieved. Harm reduction is a desirable target, even from an economic point of view. At the present state of neuroscientific knowledge, it is possible to go one step further in the logic that led to the integration of psychosocial and pharmacological approaches, by attempting to remove the shadows of social judgment that, at present, are aiming for a course of treatment that is directed towards absolute abstention.

The aim of this study was to evaluate whether the number of women recruited for studies to establish the efficacy of medications approved for treatment of alcohol dependence (AD) and of alcohol withdrawal syndrome (AWS) is sufficient to reveal possible gender differences in the response to these medications and in suggesting the use of different doses in female patients. Our results show that the rates of women recruited for studies evaluating the efficacy of disulfiram (1%), benzodiazepines (3%), and anticonvulsants (13%) were too low to establish possible gender differences. The rates of women recruited for studies evaluating the efficacy of acamprosate (22%), naltrexone (23%), and nalmefene (30%) were higher and allowed evaluation of data obtained for female patients. Women receive medications for treatment of AD and/or AWS for which efficacy has been demonstrated in studies in which men were more largely represented.

Background Genetic, neurobiological, environmental and psychosocial mechanisms have received considerable attention in exploring the mechanisms that underlie comorbid PTSD and SUD. PTSD and SUD are not necessarily linked by a causal relationship, as the self-medication hypothesis had supposed. They might, in fact, both be caused by a third factor that predisposes these subjects to develop the two disorders (so allowing a unitary perspective). Methods Using a conceptualization of the PTSD spectrum, we studied the PTSD–SUD unitary perspective by testing the correlation between severity of heroin addiction, dose of opioid medication and severity of PTSD spectrum in 82 methadone-treated, heroin-dependent patients. Results Canonical correlation analysis (Wilks Lambda = 0.125 F = 1.41 p = 0.014), univariate and multivariate comparisons between subgroups, identified on the basis of addiction severity, showed a highly positive correlation between the PTSD spectrum and the severity of heroin addiction. In addition, negative correlations were found between PTSD spectrum severity and methadone dose (r = 0.225; p = 0.042). Conclusions This strength and breadth of the correlations encourage us to move towards a unified vision of the two disorders.

Background Cocaine dependence is a public health problem characterised by recidivism and a host of medical and psychosocial complications. Cocaine dependence remains a disorder for which no pharmacological treatment of proven efficacy exists. Objectives To evaluate the efficacy and the acceptability of antipsychotic medications for cocaine dependence. Search methods This review is an update of a previous Cochrane review published in 2007. We searched up to 15 July 2015 in Cochrane Drugs and Alcohol Group Specialised Register (searched in CRSLive); the Cochrane Library (including the Cochrane Central Register of Controlled Trials (CENTRAL); the Database of Abstracts of Reviews of Effects (DARE)); PubMed; EMBASE; CINAHL and Web of Science. All searches included non-English language literature. Selection criteria All randomised controlled trials and controlled clinical trials with focus on the use of any antipsychotic medication for the treatment of cocaine dependence. Data collection and analysis We used standard methodological procedures expected by Cochrane. Main results We included 14 studies (719 participants). The antipsychotic drugs studied were risperidone, olanzapine, quetiapine, lamotrigine, aripiprazol, haloperidol and reserpine. Comparing any antipsychotic drugs versus placebo, we found that antipsychotics reduced dropout: eight studies, 397 participants, risk ratio (RR) 0.75 (95% confidence interval (CI) 0.57 to 0.97), moderate quality of evidence. We found no significant differences for any of the other primary outcomes considered: number of participants using cocaine during the treatment, two studies, 91 participants: RR 1.02 (95% CI 0.65 to 1.62); continuous abstinence, three studies, 139 participants: RR 1.30 (95% CI 0.73 to 2.32); side effects, six studies, 291 participants: RR 1.01 (95% CI 0.93 to 1.10); and craving, four studies, 240 participants: RR 0.13 (-1.08 to 1.35). For all of these comparisons we rated the quality of evidence as low. Comparisons of single drug versus placebo or versus another drug are conducted in few trials with small sample sizes, limiting the reliability of the results. Among these comparisons, only quetiapine seemed to outperform placebo in reducing cocaine use, measured by grams per week: mean difference (MD) -0.54 (95% CI -0.92 to -0.16), by US dollars spent per week: MD -53.80 (95% CI -97.85 to -9.75), and by craving: MD -1.23 (95% CI -2.19 to -0.27), but results came from one study with 60 participants. The major limitations of the studies were the high risk of attrition bias (40% of the included studies) and low quality of reporting, mainly for the risk of selection bias, performance and detection bias, that we rated as being at unclear risk for 75% to 80% of the studies. Furthermore, most of the included studies did not report results on important outcomes such as side effects, or use of cocaine during treatment and craving, which prevented the possibility of including them in statistical synthesis. Authors' conclusions At present, there is no evidence supporting the clinical use of antipsychotic medications in the treatment of cocaine dependence, although results come from only 14 trials, with small sample sizes and moderate to low quality of evidence.

Current "official" nosology (e.g. DSM IV) is largely limited to physical manifestations of addiction that can be objectively observed and are suited to the maintaining of an "atheoretical" perspective. However, addicted subjects display additional psychiatric symptoms that affect their well-being and social functioning and, in accordance with DSM IV, are typically relegated to the domain of psychiatric "comorbidity." We contend that the relationship of these psychiatric symptoms with addiction is very close, as demonstrated by the high frequency of association observed. We further assert that substance use may modify pre-existing psychic structures such as temperament and related subthreshold conditions and lead to addiction as a specific mental disorder, inclusive also of symptoms pertaining to mood/anxiety, or impulse-control dimensions. The present contribution addresses the weaknesses of the current DSM-based nosology of addiction-related mental comorbidity. We highlight the overlap of the biological substrates and the neurophysiology of addictive processes and psychiatric symptoms associated with addiction, and propose the inclusion of specific mood, anxiety, and impulse-control dimensions in the psychopathology of addictive processes. We postulate that addiction reaches beyond the mere result of drug-elicited effects on the brain and cannot be peremptorily equated only with the use of drugs despite the adverse consequences produced. We infer that mood, anxiety and impulse-control dysregulation is at the very core of both the origins and clinical manifestations of addiction and should be incorporated into the nosology of the same, emphasising how addiction is a relapsing chronic condition in which psychiatric manifestations play a crucial role. To conclude, addictionology cannot be severed from its psychopathological connotations, in view of the undeniable presence of symptoms, of their manifest contribution to the way addicted patients feel and behave, and to the role they play in maintaining the continued use of substances.

Objective: The aim of this study was to compare the long-term outcomes of treatment-resistant heroin addicts with and without DSM-IV axis I psychiatric comorbidity (dual diagnosis). Method: 129 heroin addicts who also met criteria for treatment resistance, 66 with one or more DSM-IV axis I psychiatric diagnosis (DD patients), and 63 without DSM-IV axis I psychiatric comorbidity (NDD patients) were monitored prospectively (6 years on average, min. 1, max. 9) along a methadone maintenance treatment program (MMTP). Results: The rates for survival-in-treatment were about 50% for NDD patients and about 70% for DD patients. After 4 years of treatment onwards, such rates tended to become stable. DD patients showed better outcome measures than NDD patients. A significantly higher methadone dose was needed to have DD patients stabilized. Conclusions: Contrary to expectations, treatment-resistant patients with psychiatric comorbidity showed a better long-term outcome than treatment-resistant patients without psychiatric comorbidity.

Cocaine dependence is a disorder for which no pharmacological treatment of proven efficacy exists, advances in the neurobiology could guide future medication developmentTo investigate the efficacy and acceptability of dopamine agonists alone or in combination with any psychosocial intervention for the treatment of cocaine abuse and dependenceWe searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and CINAHL, PsycINFO in June 2011 and researchers for unpublished trialsRandomised and controlled clinical trials comparing dopamine agonists alone or associated with psychosocial intervention with placebo, no treatment, other pharmacological interventionsTwo authors independently assessed trial quality and extracted dataTwenty three studies, 2066 participants, met the inclusion criteria. Comparing any dopamine agonist versus placebo, placebo performed better for severity of dependence, four studies, 232 participants, SMD 0.43 (95% CI 0.15 to 0.71), depression, five studies, 322 participants, SMD 0.42 (95% CI 0.19 to 0.65) and abstinent at follow up RR 0.57 (95% CI 0.35 to 0.93). No statistically significant different for the other outcomes considered. Comparing amantadine versus placebo, results never gain the statistical significance, but there is a trend in favour of amantadine for dropouts and depression. Results on adverse events and depression, were in favour of placebo although the difference do not reach the statistical significance. Comparing bromocriptine and Ldopa/Carbidopa versus placebo, results never reached statistical significance. Comparing amantadine versus antidepressants, antidepressants performed better for abstinence. The other two outcomes considered did not show statistically significant differences although dropouts and adverse events tended to be more common in the antidepressant group.The quality of evidence, assessed according to GRADE method, may be judged as moderate for the efficacy of any dopamine agonist versus placebo and as moderate to high for amantadine versus placebo and versus antidepressants.Current evidence from randomised controlled trials does not support the use of dopamine agonists for treating cocaine dependence. This absence of evidence may leave to clinicians the alternative of balancing the possible benefits against the potential adverse effects of the treatment. Even the potential benefit of combining a dopamine agonist with a more potent psychosocial intervention which was suggested by the previous Cochrane review (Soares 2003), is not supported by the results of this updated review.

Cocaine dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence, none is currently available for cocaine dependence, despite two decades of clinical trials primarily involving antidepressant, anticonvulsivant and dopaminergic medications. Extensive consideration has been given to optimal pharmacological approaches to the treatment of individuals with cocaine dependence, and both dopamine antagonists and agonists have been considered. Anticonvulsants have been candidates for use in the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction.To evaluate the efficacy and safety of anticonvulsants for individuals with cocaine dependence.We searched the Cochrane Drugs and Alcohol Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1966 to June 2014), EMBASE (1988 to June 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to June 2014), Web of Science (1991 to June 2014) and the reference lists of eligible articles.All randomised controlled trials and controlled clinical trials that focus on the use of anticonvulsant medications to treat individuals with cocaine dependence.We used the standard methodological procedures expected by The Cochrane Collaboration.We included a total of 20 studies with 2068 participants. We studied the anticonvulsant drugs carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. Only one study had one arm by which the anticonvulsant was compared with the antidepressant desipramine. Upon comparison of anticonvulsant versus placebo, we found no significant differences for any of the efficacy and safety measures. Dropouts: risk ratio (RR) 0.95, 95% confidence interval (CI) 0.86 to 1.05, 17 studies, 20 arms, 1695 participants, moderate quality of evidence. Use of cocaine: RR 0.92, 95% CI 0.84 to 1.02, nine studies, 11 arms, 867 participants, moderate quality of evidence; side effects: RR 1.39, 95% CI 1.01 to 1.90, eight studies, 775 participants; craving: standardised mean difference (SMD) -0.25, 95% CI -0.59 to 0.09, seven studies, eight arms, 428 participants, low quality of evidence.Although caution is needed when results from a limited number of small clinical trials are assessed, no current evidence supports the clinical use of anticonvulsant medications in the treatment of patients with cocaine dependence. Although the findings of new trials will improve the quality of study results, especially in relation to specific medications, anticonvulsants as a category cannot be considered first-, second- or third-line treatment for cocaine dependence.

Key results: The review authors identified 20 studies with 2068 participants, 77% male, with a mean age of 36 years. The mean duration of the trials was 11.8 weeks (range eight to 24 weeks). All but two of the trials were conducted in the USA, all with outpatients. The anticonvulsant drugs studied were carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. No significant differences were found between placebo and any anticonvulsant in reducing the number of dropouts from treatment, use of cocaine, craving and severity of dependence, depression or anxiety. Side effects were slightly more frequent in the anticonvulsant groups. No current evidence supports the clinical use of anticonvulsant medications for the treatment of cocaine dependence.

Background The relationship between substance use disorders and psychiatric pathology is still an open question. The main aim of the present study was to verify whether the five psychopathological dimensions identified through the SCL-90 tool in a previous study carried out on patients with heroin addiction entering an outpatient opioid agonist treatment (OAT) were also observable in those entering a residential treatment community (TC). Further aims were to look at differences in the psychopathological profiles of patients entering a TC versus an OAT treatment and at the correlation between gender and the observed psychopathology. Methods A confirmatory factor analysis was performed on the results of SCL-90 filled by 1,195 patients with heroin dependence entering TC treatment. It replicates the extraction method previously used on 1,055 OAT patients with heroin addiction by using a principal component factor analysis (PCA). The association between the kind of treatment received (TC or OAT), gender, and the psychopathological dimensions was assessed through logistic regression and general linear model (GLM) analysis. Results The PCA carried out on the SCL-90 results of patients entering a TC yielded a five-factor solution, confirming the same dimensions observed in patients entering an OAT: ‘worthlessness and being trapped’, ‘somatization’, ‘sensitivity-psychoticism’, ‘panic anxiety’, and ‘violence-suicide’. The logistic regression analysis showed a statistically significant association between ‘somatization’ and ‘violence-suicide’ severity score and OAT. GLM analysis showed that psychopathological factorial scores for ‘worthlessness-being trapped’, ‘somatic symptoms’, and ‘panic anxiety’ dimensions were more severe in OAT vs TC male patients and in TC vs OAT female ones. ‘Violence suicide’ followed the same severity pattern for males, but did not differ in TC vs OAT females, while ‘sensitivity-psychoticism’ did not differ in OAT vs TC patients. The five dimensions did not differ in OAT males vs females. Conclusions Our research appears to confirm the existence of a specific aggregation of psychological/psychiatric features within the category of individuals with heroin addiction. It also shows a correlation between the dominant psychopathological subgroup and the assignment to TC versus OAT. Further research is needed to clarify the differences between the five psychopathological subgroups and their determinants.

The aim of this study was to compare the long-term outcomes of treatment-resistant bipolar 1 heroin addicts with peers who were without DSM-IV axis I psychiatric comorbidity (dual diagnosis).104 Heroin-dependent patients (TRHD), who also met criteria for treatment resistance - 41 of them with DSM-IV-R criteria for Bipolar 1 Disorder (BIP1-TRHD) and 63 without DSM-IV-R axis I psychiatric comorbidity (NDD-TRHD) - were monitored prospectively (3 years on average, min. 0.5, max. 8) along a Methadone Maintenance Treatment Programme (MMTP).The rates for survival-in-treatment were 44% for NDD-TRHD patients and 58% for BIP1-TRHD patients (p=0.062). After 3 years of treatment such rates tended to become progressively more stable. BIP1-TRHD patients showed better outcome results than NDD-TRHD patients regarding CGI severity (p0.001) and DSM-IV GAF (p0.001). No differences were found regarding urinalyses for morphine between groups during the observational period. Bipolar 1 patients needed a higher methadone dosage in the stabilization phase, but this difference was not statistically significant.The observational nature of the protocol, the impossibility of evaluating a follow-up in the case of the patients who dropped out, and the multiple interference caused by interindividual variability, the clinical setting and the temporary use of adjunctive medications.Contrary to expectations, treatment-resistant patients with bipolar 1 disorder psychiatric comorbidity showed a better long-term outcome than treatment-resistant patients without psychiatric comorbidity.

Patients on methadone maintenance were forewarned that a law prohibiting take-home dosages was to be enforced within 6 months. At the end of the 6-month period preceding the enforcement of the law the effect of the anticipated suppression of the take-home privilege was studied on a cohort of 211 methadone-maintained patients on take-home dosages. The outcome of the treatment of these patients was compared to that of a control group of 220 patients at the end of a 6-month period prior to the announcement of the new law. The outcome of the study suggests that the restrictive regulation is counterproductive for retaining patients in treatment.

Cocaine dependence is a disorder for which no pharmacological treatment of proven efficacy exists, advances in the neurobiology could guide future medication development.To investigate the efficacy and acceptability of antidepressants alone or in combination with any psychosocial intervention for the treatment of cocaine dependence and problematic cocaine use.We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE and CINAHL in July 2011 and researchers for unpublished trials.Randomised clinical trials comparing antidepressants alone or associated with psychosocial intervention with placebo, no treatment, other pharmacological or psychosocial interventions.Two authors independently assessed trial quality and extracted data.37 studies were included in the review (3551 participants).Antidepressants versus placebo: results for dropouts did not show evidence of difference, 31 studies, 2819 participants, RR 1.03 (Cl 95% 0.93 to 1.14). Looking at Abstinence from cocaine use, even though not statistically significant, the difference shown by the analysis in the three-weeks abstinence rate was in favour of antidepressants (eight studies, 942 participants, RR 1.22 (Cl 95% 0.99 to 1.51)). Considering only studies involving tricyclics, five studies, 367 participants, or only desipramine, four studies, 254 participants, the evidence was in favour of antidepressants. However, selecting only studies with operationally defined diagnostic criteria, statistical significance favouring antidepressants, as well as the trend for significance shown by the full sample, disappeared. Looking at safety issues, the results did not show evidence of differences (number of patients withdrawn for medical reasons, thirteen studies, 1396 participants, RR 1.39 (Cl 95% 0.91 to 2.12)). Subgroup analysis considering length of the trial, associated opioid dependence or associated psychosocial interventions as confounding factors, failed in showing consistent and statistically significant differences in favour of antidepressants.Antidepressants versus other drugs: Comparing antidepressants with dopamine agonists or with anticonvulsants, no evidence of differences was shown on dropouts and on other outcomes (abstinence from cocaine use, adverse events).At the current stage of evidence data do not support the efficacy of antidepressants in the treatment of cocaine abuse/dependence. Partially positive results obtained on secondary outcome measures, such as depression severity, do not seem to be associated with an effect on direct indicators of cocaine abuse/dependence. Antidepressants cannot be considered a mainstay of treatment for unselected cocaine abusers/dependents.

No evidence has been found to support the use of the electrocardiogram (ECG) for preventing cardiac arrhythmias in methadone-treated opioid dependents. A maintenance program with methadone is an effective treatment for people who are dependent on opioids, in terms of increased retention in treatment, reduced use of opioids, reduced human immunodeficiency virus (HIV) transmission and reduced mortality. Nowadays methadone represents the most frequently used medication for this disorder. However, the use of methadone has been associated with a potentially fatal cardiac arrhythmia called torsade de pointes (TdP). Evidence supporting the relationship between methadone and TdP is limited. However, given the risk involved for the life of patients, consensus and recommendations for patients receiving methadone treatment have been developed. Recommended procedures aim to identify patients who present a specific alteration of the ECG, represented by prolongation of the QT interval, which is considered a marker for arrhythmias such as TdP. Patients identified as at risk may then be provided with alternative treatment (reduction of methadone dosage; provision of alternative opioid agonist treatment; treatment of associated risk factors). However, the acceptability of ECG screening has been questioned because the procedures involved may be too demanding and stressful, may interfere with the availability of patients to undergo methadone maintenance and may expose patients to health consequences of untreated opioid addiction, including increased mortality risk. This review looked at the evidence on the efficacy and acceptability of such ECG-based screening procedures. Even though the search was extended to different experimental and non- experimental study designs, the authors did not find any study that fulfilled methodological criteria for the review. Therefore, it is not possible to draw any conclusions about the effectiveness of ECG-based screening strategies for preventing cardiac morbidity/mortality in methadone-treated opioid addicts. Research efforts should focus on strengthening the evidence about the effectiveness of widespread implementation of such strategies and clarifying associated benefits and harms.

Leading Italian studies support the use of γ-hydroxybutyric acid (GHB), not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30–40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of ‘antagonist’ effect by using the ‘psychological threat’ of disulfiram (adversative effect) while taking advantage of the anticraving effect of GHB, despite the limitation of its ‘non-blockade’ effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4%) successfully completed the protocol and were considered to be responders, 18 (34.6%) left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis.

This is the protocol for a review and there is no abstract. The objectives are as follows: This review will assess the efficacy of antidepressants for the treatment of co-occurring depression and alcohol dependence.

While psychiatric comorbidity has been shown to produce a negative impact on the outcome of opioid use disorders, longitudinal studies carried out in the context of methadone maintenance treatment programs (MMTP) to evaluate outcomes strictly linked to methadone efficacy have not demonstrated a similar negative influence. To verify whether results obtained considering psychopathology in terms of formal psychiatric diagnoses were replicated when assessing psychopathology in terms of global psychiatric severity, a retrospective cohort study was designed. 259 patients commencing methadone maintenance treatment were divided into two groups on the basis of SCL-90 severity score and compared for retention in treatment, toxicological urine test results and psychological/psychiatric status throughout a one year period of observation. The results of the study suggest that patients in MMTP with high psychiatric severity are not characterized by a lower retention in treatment or higher substance use than those with low psychiatric severity. Moreover, during treatment high severe psychiatric patient status appears to improve significantly for all psychological/psychiatric dimensions explored by SCL-90. These results are consistent with those obtained in previous studies on the efficacy of MMTP, comprehensive of psychiatric care, irrespective of the severity of psychopathology exhibited by patients at the beginning of treatment.

Individuals suffering from drug addiction may also manifest features of bipolar spectrum disorders. Hyperthymic and cyclothymic temperaments may render individuals vulnerable to later development of substance abuse. Bipolar disorders themselves may be altered or precipitated by substance use, most notably by stimulants (amphetamines), alcohol, and cannabinoids.The clinical usefulness of mood stabilizers, particularly antiepileptics, has been established as safe and effective in substance abusers with and without comorbid mood disorders. Most studies on this issue have been of short duration and focused on the resolution of a currently manifest period of illness. Few studies have been conducted on the usefulness of these drugs on the long-term longitudinal course of these diseases, such as frequently encountered recurrent relapses into states of agitation, impulsivity, and/or dissatisfaction. As opposed to the clinical experience with traditional antidepressants and neuroleptics, antiepileptics do not induce counter-polar states (depressed patients abruptly turning manic or hypomanic; nor patients currently hypomanic or manic turning abruptly depressed). Many clinicians consider antiepileptic mood stabilizers to be the preferred category of medications for the treatment of such patients. Valproate appears to be a potentially fruitful medication to study in these dual diagnosis patients due to preliminary evidence demonstrating its anticraving efficacy.

It is commonly assumed that people who are addicted to certain substances would abuse any substance. This position has never been supported by validly collected and analyzed research data. In this study, the authors examine the use of street methadone by heroin addicts seeking their first agonist opioid treatment in a clinical setting. Fifty-four heroin addicts who resorted to street methadone use were compared by socio-demographic, current clinical, and disease-related variables to 251 peers who do not use street methadone. Heroin addicts who resort to street methadone use are more likely to be females and to have a higher degree of education, are less likely to engage in polyabuse (use of more than three substances), are less severely ill, have been addicted for a shorter period of time, and have been seeking treatment sooner in the course of their disease. Also, they suffer from a wider range of psychopathological distress symptoms. In Italy, resorting to street methadone does not seem to be a surrogate form of heroin addiction, but rather represents means of harm reduction, with treatment seeking occurring shortly after its initiation. This should be accounted for when deciding on take-home policies and issues of potential methadone diversion.

Background Mental symptoms are common in heroin addiction and may arise from issues of addiction and withdrawal, raising doubts about the patients truly having co-morbid psychiatric diagnoses. Methods We studied the mental status of 1090 heroin addicts (831 males and 259 females aged between 16 and 51 years) at the beginning of treatment, and its relationship to relevant demographic and clinical data through the use of standardised instruments. Results A total of 506 (46.42%) heroin addicts showed depressive-anxious symptomatology, 421 (38.62%) had psychomotor excitement and 163 (14.95%) demonstrated a psychotic state. Patients with depressive-anxious symptomatology on the whole had a less severe addictive illness compared to those demonstrating excited and psychotic symptoms. The presence of depressive-anxious features was felt to not necessarily be indicative of the presence of a dual diagnosis. Conclusion The presence of depressive-anxious symptomatology in the clinical presentation in heroin addicts appears to be unrelated to 'dual diagnosis'.

Background: To describe the prevalence and the risk factors of suicidal ideation in a cohort of Italian opioid addicts presenting for treatment. Method: Systematic cross-sectional clinical data on suicidal ideation, socio-demographic variables, psychiatric status, social adjustment, status and history of addiction in 616 patients were gathered. Results: Suicidal thoughts during the past week were reported by 29.1%. Suicidal thoughts were more frequent in patients with bipolar spectrum diagnoses (OR = 1.42) and in patients with depressive and aggressive symptoms (multiple R = 0.47). The odds of having suicidal thoughts were also higher for subjects receiving public welfare benefits (OR = 1.69), unemployed patients (OR = 1.37), those with early onset of heroin dependence (OR = 1.36), living alone (OR = 1.33), and experiencing problems in organizing social contacts and leisure time (OR = 1.28). Conclusion: Current suicidal ideation was a common feature of patients with opioid addiction. Depression and hostility as part of the bipolar spectrum – in the context of early-onset drug dependence, work and social/leisure problems – appear independently associated with suicidal ideation. Given the elevated rates of completed suicide in heroin addiction, these data have implications for preventing suicide in patients with this type of addiction. Prospective data are needed to further address this important clinical and public health agenda.

The purpose of this study was to investigate the effects of methadone treatment and buprenorphine treatment on retention in treatment, urine drug testing results, psychiatric status, social adjustment, and quality of life among patients involved in long-term treatment with the cited medications. Two hundred thirteen patients (106 on buprenorphine treatment and 107 on methadone treatment) were enrolled in this open study at the 3rd month of their treatment and followed up until the 12th month; those who left the program before the end of the 3rd month of their treatment were not included in the study sample. The results of this study show statistically significant improvements in opioid use, psychiatric status, and quality of life between the 3rd and 12th months for both medications. This study suggests the long-term efficacy of methadone treatment and buprenorphine treatment on symptoms of opioid addiction and quality of life.

Alcohol and cocaine abuse result in unsatisfactory treatment outcomes for heroin and illicit opioid addicts engaged in Methadone Maintenance Treatment Programs (MMTPs). This study aims to clarify the impact of MMT, which focuses on cessation of opioid abuse and diminishing psychopathology to acceptable levels (stabilization) on alcohol and cocaine abuse. Of specific interest was whether reduction of polysubstance abuse and associated psychopathological complications diminished illicit opioid abuse and/or increased retention in treatment. Changes in cocaine and alcohol use that occurred in 53 heroin addicts who had been stabilized were monitored. A control group was composed of patients terminated from treatment due to noncompliance with treatment recommendations, poor attendance, or failure to have opioid abuse stabilized, within a year. The association of psychiatric severity with alcohol and cocaine abuse in these methadone maintained patients was assessed. Cessation of illicit opioid abuse and retention in treatment are positively correlated with decrease in alcohol and cocaine abuse and the absence of the psychosocial complications associated with such abuse.

Aims: To identify factors associated with entering any methadone treatment at first admission at an NHS treatment centre in Italy and to investigate determinants of receiving detoxification or maintenance methadone treatments. Methods: Data were analysed from 565 heroin addicts who entered for the first time one of 90 NHS treatment centres in 12 Italian regions between September 1998 and March 2001. Subjects were interviewed at admission by the centre's staff and followed-up for 18 months. Details on treatments provided were recorded using a standardised form. Random effects logistic regression analysis was applied. Results: Factors positively associated with any methadone treatment assignment were: being younger than 25 years and using heroin more than twice a day, having been recently incarcerated, and living with a partner. Independent predictors of admission to methadone maintenance were injecting heroin, having sex without a condom in the previous six months, being HIV positive and having been enrolled at a NHS TC where a psychiatrist was present. Using heroin once a day or more and using cocaine were factors associated with enrolment into detoxification treatment. A significant heterogeneity between centres was observed. Conclusions: Results from this study give an insight into different patient profiles who are enrolled in methadone treatments. The observed heterogeneity between centres indicates the need to develop and implement common guidelines for the access of heroin addicts to substitution treatment. © 2005 Elsevier Ireland Ltd. All rights reserved.

Clinical trials carried out to compare methadone and buprenorphine in the treatment of opioid dependence have generally employed an alcoholic solution of buprenorphine, which has a bioavailability superior to that of the tablets. Since the product available for large scale use is in tablet form, one intended to verify the efficacy of this formulation. In a multicentre randomised controlled double blind study, 72 opioid dependent patients were assigned to treatment with buprenorphine (8 mg/day) or methadone (60 mg/day) for a period of 6 months. The two compounds did not show any significant difference with regard to urinalyses: the average percentage of analyses proving negative was 60.4% for patients assigned to buprenorphine, and 65.5% for those assigned to methadone. With regard to retention, a non-significant trend in favour of methadone was observed. Patients completing the trial improved significantly in terms of psychosocial adjustment and global functioning, as ascertained by the DSM-IV-GAF and symptom checklist-90 (SCL-90) scales, and this was independent of the treatment group. Finally, in the case of buprenorphine, patients who dropped out differed significantly from those who stayed, in terms of a higher level of psychopathological symptoms, and a lower level of psychosocial functioning. The results of the study further support the utility of buprenorphine for the treatment of opioid dependence.

The purpose of this study was to investigate the influence of the severity of concomitant psychiatric symptomatology on some selected measures of methadone maintenance treatment efficacy in a comprehensive methadone maintenance treatment program (MMTP). The cohort studied included 267 patients who entered a maintenance program in the years 1991-92. Two groups of patients differing in the severity of psychiatric symptomatology were obtained on the bases of the referral to the psychiatrist and the ascertainment of a current disorder. These two groups were compared for retention in treatment, urine tests positive for morphine while in treatment and methadone dose during an observation period of 2 years. The outcome of the study suggests that on these outcome parameters, patients on MMTP who are more psychiatrically ill can perform as well as the other patients.

In a double-blind placebo-controlled trial, gamma-hydroxybutyric acid (GHB) (25 mg/kg orally) suppressed most of the withdrawal symptomatology in 14 heroin addicts and 13 methadone-maintained subjects. The GHB effect was prompt (within 15 minutes) and persisted for between 2 and 3 hours. Subsequently, the same patients received GHB in an open study every 2 to 4 hours for the first 2 days and 4 to 6 hours for the following 6 days: most abstinence signs and symptoms remained suppressed and patients reported felling well. Urine analysis failed to detect any presence of opiate metabolites. No withdrawal symptomatology recurred after 8 days of treatment when GHB was suspended, and patients were challenged with an intravenous injection of 0.4 mg naloxone. The results indicate that GHB may be useful in the management of opiate withdrawal.

Negative symptoms, conceptualized as clinical manifestations of schizophrenia, and subsequently described in other psychiatric disorders, include the loss of normal arousal, drive and affective reactivity. In the field of substance abuse, an interesting analogy can be detected between negative symptoms, in their classical meaning, and the amotivational syndrome (AS), which has been described as a form of chronic cannabis intoxication. AS also shows a close resemblance to the reward deficiency syndrome (RDS) of alcoholics and stimulant abusers, and to the post-withdrawal syndrome (PWS) of detoxified heroin addicts. A variety of substances share a common tropism for the dopaminergic system, leading to a state of hypophoria, which seems to represent a common pathway for chronic substance abusers. In the light of these convergences, a common treatment principle for addictive disorders can be enunciated. This consists in resorting to pro-dopaminergic drugs, that are supposed to replace damaged functions and control craving, and in avoiding anti-dopaminergic drugs, that are expected to exacerbate craving and impede the reversal of the reward deficiency.

Cocaine dependence is a disorder for which no pharmacological treatment of proven efficacy exists, advances in the neurobiology could guide future medication development.To evaluate the efficacy and the acceptability of disulfiram for cocaine dependence.We searched: PubMed, EMBASE, CINAHL (up to January 2008), the Cochrane Central Register of Controlled Trials (CENTRAL-The Cochrane Library, 1, 2009), reference lists of trials, main electronic sources of ongoing trials, conference proceedings.Randomised and controlled clinical trials comparing disulfiram alone or associated with psychosocial intervention with no intervention, placebo, or other pharmacological intervention for the treatment of cocaine dependence.Three reviewers independently assessed trial quality and extracted data.Seven studies, 492 participants, met the inclusion criteriaDisulfiram versus placebo: no statistically significant results for dropouts but a trend favouring disulfiram, two studies, 87 participants, RR 0.82 (95% CI 0.66 to 1.03). One more study, 107 participants, favouring disulfiram, was excluded from meta-analysis due high heterogeneity, RR 0.34 (95% CI 0.20 to 0.58). For cocaine use, it was not possible to pool together primary studies, results from single studies showed that, one, out of four comparisons, was in favour of disulfiram (number of weeks abstinence, 20 participants, WMD 4.50 (95% CI 2.93 to 6.07).Disulfiram versus naltrexone: no statistically significant results for dropouts but a trend favouring disulfiram, three studies, 131 participants, RR 0.67 (95% CI 0.45 to 1.01). No significant difference for cocaine use was seen in the only study that considered this outcome.Disulfiram versus no pharmacological treatment: for cocaine use: a statistically significant difference in favour of disulfiram, one study, two comparisons, 90 participants: maximum weeks of consecutive abstinence, WMD 2.10 (95% CI 0.69 to 3.51); number of subjects achieving 3 or more weeks of consecutive abstinence, RR 1.88 (95% CI 1.09 to 3.23).There is low evidence, at the present, supporting the clinical use of disulfiram for the treatment of cocaine dependence. Larger randomised investigations are needed investigating relevant outcomes and reporting data to allow comparisons of results between studies. Results from ongoing studies will be added as soon as their results will be available.

Background A specific psychopathology of addiction has been proposed and described using the self-report symptom inventory (SCL-90), leading to a 5-factor aggregation of psychological/psychiatric symptoms: ‘worthlessness and being trapped’, ‘somatic symptoms’, ‘sensitivity-psychoticism’, ‘panic-anxiety’ and ‘violence-suicide’ in various populations of patients with heroin use disorder (HUD) and other substance use disorders (SUDs). These clusters of symptoms, according to studies that have highlighted the role of possible confounding factors (such as demographic and clinical characteristics, active heroin use, lifetime psychiatric problems and kind of treatment received by the patients), seem to constitute a trait rather than a state of the psychological structure of addiction. These five psychopathological dimensions defined on the basis of SCL-90 categories have also been shown to be correlated with the outcomes of a variety of agonist opioid treatments. The present study aims to test whether the 5-factor psychopathological model of addiction correlates with the outcome (retention rate) of patients with SUDs entering a therapeutic community (TC) treatment. Methods 2016 subjects with alcohol, heroin or cocaine dependence were assigned to one of the five clusters on the basis of the highest SCL-90 factor score shown. Retention in treatment was analysed by means of the survival analysis and Wilcoxon statistics for comparison between the survival curves. The associations between the psychopathological subtypes defined by SCL-90 categories and length of retention in treatment, after taking into account substance of abuse and other sociodemographic and clinical variables, were summarized using Cox regression. Results Patients with cocaine use disorder (CUD) showed poorer outcomes than those with heroin dependence (HUD). Prominent symptoms of “worthlessness-being trapped” lead to a longer retention in treatment than in the case of the other four prominent psychopathological groups. At the multivariate level, age, detoxified status and total number of psychopathological symptoms proved to influence outcome negatively, especially in CUD. Somatic symptoms and violence-suicide symptoms turned out to correlate with dropout from residential treatment. Conclusions The SCL-90 5-factor dimensions can be appropriately used as a prognostic tool for drug-dependent subjects entering a residential treatment.

Alcohol dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Besides psychosocial interventions, different pharmacological interventions have been or currently are under investigation through Cochrane systematic reviews.The primary aim of the review is to assess the benefits/risks of anticonvulsants for the treatment of alcohol dependence.We searched the Cochrane Drugs and Alcohol Group Trials Register (October 2013), PubMed (1966 to October 2013), EMBASE (1974 to October 2013) and CINAHL (1982 to October 2013).Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing anticonvulsants alone or in association with other drugs and/or psychosocial interventions versus placebo, no treatment and other pharmacological or psychosocial interventions.We used standard methodological procedures as expected by The Cochrane Collaboration.A total of 25 studies were included in the review (2641 participants). Most participants were male, with an average age of 44 years. Anticonvulsants were compared with placebo (17 studies), other medications (seven studies) and no medication (two studies). The mean duration of the trials was 17 weeks (range four to 52 weeks). The studies took place in the USA, Europe, South America, India and Thailand. Variation was reported in the characteristics of the studies, including their design and the rating instruments used. For many key outcomes, the risk of bias associated with unclear or unconcealed allocation and lack of blinding affected the quality of the evidence.Anticonvulsants versus placebo: For dropouts (16 studies, 1675 participants, risk ratio (RR) 0.94, 95% confidence interval (Cl) 0.74 to 1.19, moderate-quality evidence) and continuous abstinence (eight studies, 634 participants, RR 1.21, 95% Cl 95% 0.97 to 1.52, moderate-quality evidence), results showed no evidence of differences. Moderate-quality evidence suggested that anticonvulsants reduced drinks/drinking days (11 studies, 1126 participants, mean difference (MD) -1.49, 95% Cl -2.32 to -0.65) and heavy drinking (12 studies, 1129 participants, standardised mean difference (SMD) -0.35, 95% Cl -0.51 to -0.19). Moreover, withdrawal for medical reasons (12 studies, 1410 participants, RR 1.22, 95% Cl 0.58 to 2.56, moderate-quality evidence) showed no evidence of difference, but for specific adverse effects (nine studies, 1164 participants), two of 18 adverse event outcomes favoured placebo. The direction of results was confirmed by subgroup analyses for topiramate and partially for gabapentin and valproate.Anticonvulsants versus naltrexone: No evidence of difference was shown in dropout rates (five studies, 528 participants, RR 0.74, 95% CI 0.52 to 1.06), severe relapse rates (four studies, 427 participants, RR 0.69, 95% Cl 0.44 to 1.07) and continuous abstinence rates (five studies, 528 participants, RR 1.21, 95% Cl 0.99 to 1.49); anticonvulsants were associated with fewer heavy drinking days (three studies, 308 participants, MD -5.21, 95% Cl -8.58 to -1.83), more days to severe relapse (three studies, 244 participants, MD 11.88, 95% Cl 3.29 to 20.46) and lower withdrawal for medical reasons (three studies, 245 participants, RR 0.13, 95% Cl 0.03 to 0.58).At the current stage of research, randomised evidence supporting the clinical use of anticonvulsants to treat alcohol dependence is insufficient. Results are conditioned by heterogeneity and by the low number and quality of studies comparing anticonvulsants with other medications. The uncertainty associated with these results leaves to clinicians the need to balance possible benefits/risks of treatment with anticonvulsants versus other medications as supported by evidence of efficacy.

Methadone represents today the gold standard of efficacy for the pharmacological treatment of opioid dependence. Methadone, like many other medications, has been implicated in the prolongation of the rate-corrected QT (QTc) interval of the electrocardiogram (ECG), which is considered a marker for arrhythmias such as torsade de pointes (TdP). Indications on the association between methadone, even at therapeutic dosages, and TdP or sudden cardiac death have been reported. On these bases, consensus and recommendations involving QTc screening of patients receiving methadone treatment have been developed to identify patients with QTc above the thresholds considered at risk for cardiac arrhythmias, and they provide these individuals with alternative treatment (reduction of methadone dosage; provision of alternative opioid agonist treatment; treatment of associated risk factors).To evaluate the efficacy and acceptability of QTc screening for preventing cardiac-related morbidity and mortality in methadone-treated opioid dependents.We searched MEDLINE, EMBASE, CINAHL (to April 2013), the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library Cochrane Drug and Alcohol Review Group Specialised Register (Issue 3, 2013), main electronic sources of ongoing trials, specific trial databases and reference lists of all relevant papers.Randomised controlled trials (RCTs), controlled clinical trials (CCTs) and non-randomised studies (cohort studies, controlled before and after studies, interrupted time series studies, case control studies) examining the efficacy of QTc screening for the prevention of methadone-related mortality and morbidity in opioid addicts.Two review authors independently screened and extracted data from studies.The search strategy led to the identification of 872 records. Upon full-text assessment, no study was found to meet the quality criteria used for this review.It is not possible to draw any conclusions about the effectiveness of QTc screening strategies for preventing cardiac morbidity/mortality in methadone-treated opioid addicts. Research efforts should focus on strengthening the evidence about the effectiveness of widespread implementation of such strategies and clarifying the associated benefits and harms.