Sodium Oxybate for Alcohol Dependence: A Network Meta-Regression Analysis Considering Population Severity at Baseline and Treatment Duration.

AIMS: The estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients. METHODS: Network meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively. RESULTS: Eight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001. CONCLUSIONS: In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.

Bipolar Spectrum disorders in Parkinson's disease: a systematic evaluation.

OBJECTIVE: Psychiatric disorders are very common in patients affected by Parkinson's disease (PD). However, comorbidity with Bipolar Spectrum disorders is understudied. The aim of this study is to explore the clinical correlates of PD associated with Bipolar Spectrum disorders. METHODS: One hundred PD patients were screened for psychiatric comorbidities, cognitive profile, motor, and non-motor symptoms. The sample was divided into three groups: PD-patients with Bipolar Spectrum disorders (bipolar disorder type I, type II, and spontaneous or induced hypomania; N = 32), PD-patients with others psychiatric comorbidities (N = 39), PD-patients without psychiatric comorbidities (N = 29). Clinical features were compared among the groups using analysis of variance and chi-square test. A logistic regression was performed to evaluate the association between Bipolar Spectrum disorders and early onset of PD (≤50 years) controlling for lifetime antipsychotic use. RESULTS: In comparison with PD patients with and without other psychiatric comorbidity, subjects affected by Bipolar Spectrum disorders were younger, showed more frequently an early onset PD, reported more involuntary movements and a higher rate of impulse control disorders and compulsive behaviors. No differences were observed in indexes of exposure to dopamine agonist treatments. The early onset of PD was predicted by Bipolar Spectrum comorbidity, independently from lifetime antipsychotic use. CONCLUSION: Bipolar Spectrum disorders are common in early onset PD. The presence of bipolar comorbidity could identify a particular subtype of PD, showing higher rates of neurological and psychiatric complications and deserving further investigation.

Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: A meta-regression analysis to develop an enrichment strategy.

BACKGROUND: There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no "spontaneous improvement" prior to treatment initiation (high-severity population) than in a mild-severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD. METHODS: We conducted a systematic literature review on placebo-controlled RCTs for AD.We assigned retained RCTs to high- or mild-severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta-regression analysis. RESULTS: Among the 19 retained RCTs (comprising 1996 placebo-treated patients), 11 trials were high-severity and 8 were mild-severity RCTs. The between-study variability in AR was lower in the high-severity than in the mild-severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high-severity studies (16.8% at 3 months) than the mild-severity studies (36.7% at 3 months). CONCLUSIONS: Pharmacological RCTs for AD should select high-severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.

Can the migration process influence the clinical expression of heroin use disorder in migrants to Italy?

BACKGROUND: For some time now, there has been a strong consensus that the migration process can influence the onset, course, development, outcome, and clinical aspects of psychiatric pathologies. METHODS: In this study, we have analyzed the influence of the migration process on the clinical expression of heroin use disorder (HUD). In a naturalistic case-control study, we compared, both at univariate and multivariate level, 30 migrant HUD (M-HUD) patients with 30 age/gender-matched Italian HUD (IT-HUD) patients. We also analyzed demographic data, drug addiction history, psychopathological symptoms, addictive behavior, and emotional reactivity to life events. RESULTS: Compared with IT-HUD pairs, at HUD Agonist Opioid Treatment, M-HUD patients were characterized by inadequate income and the presence of legal problems. They were more frequently at stage 3 of heroin addiction, with a concomitantly less frequent use of stimulants. Their age at the onset of heroin use was greater than that of subjects in the IT-HUD group. HUD post-traumatic stress disorder spectrum was present and was more severe in all M-HUD patients, but grief reactions and maladaptive behavior were the most discriminant traits. No differences were found in terms of addictive behaviors related to heroin craving or with respect to the severity/typology of psychopathology specific to HUD. CONCLUSIONS: The migratory process does not seem to be correlated with addictive behaviors or with psychopathology specific to HUD. It partly affects HUD history, and specifically correlates with emotional reactivity to loss and traumatic life events, so suggesting that in M-HUD individuals, the link between the migratory syndrome and HUD is very close.

The Development of Temperament Evaluation of Memphis, Pisa, Paris, and San Diego - Auto-questionnaire for Adolescents (A-TEMPS-A) in a Serbian Sample.

BACKGROUND: Previous studies suggest that temperament features of adolescents may be good predictors of the development of future psychopathology in this population. The aim of the study was to adapt the content and validate the psychometric properties of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego - Auto-questionnaire in a sample of Serbian adolescents. SUBJECTS AND METHODS: The sample included 2113 adolescents, 56% girls and 44% boys, average age 16.73±0.47, attending 48 Serbian secondary schools. The base for the development of this scale included Serbian standardised versions as well as the TEMPS-I, Interview version. RESULTS: The final scale is comprised of 36 items, with six factors (depressive, cyclothymic, hyperthymic, irritable, and anxious-cognitive/somatic) explaining 39.9% of the total variance, the internal consistency coefficient α=0.77, and the average test-retest coefficient (rho=0.84). The correlations among the temperaments ranged from weak to moderate, with the highest positive correlations between the depressive, cyclothymic and anxious scales. The highest values were detected on hyperthymic and the lowest on depressive temperament. Significantly higher scores of depressive, cyclothymic and anxious temperaments were detected in girls, whereas boys had higher scores on the hyperthymic scale. CONCLUSIONS: The scale has shown good psychometric properties, which encourages its further use in adolescent population. The results show certain specific features of this population, such as higher scores on all temperament types than the ones in student and adult population and a tendency of socially desirable answers.

Political terrorism and affective polarization in "black" and "red" terrorists in Italy during the years 1968-1988.

Psychiatric evaluations of violent political crime were mostly performed on a case-by-case basis in a forensic environment, which made them unduly dependent on categories of presumed dangerousness and legal responsibility, rather than on a clinical definition of their mental status. In referring to such "clinical" definitions, the disorder we have in mind is not limited to the major, agitated psychotic manias or mixed states. The presence of a dominant temperament, or protracted hypomania, is enough by itself to explain an individual's engagement in a wide range of activities, not necessarily sociopathic or violent. We put forward the hypothesis that formal and transpolitical radical choices, either in favor of an illegal lifestyle or of activities involving a high level of risk, may be linked with certain mental states, especially when considering small clandestine groups showing a high level of internal ideological consensus, and a no-return attitude toward a commitment to radical choices. Available data about the psycho(patho)logical profile of terrorists are still hard to come by. The only available studies are those on identified living terrorists (judging by the trials of those who personally admitted to having been terrorists), and statistical data imply a number of documented cases belonging to the same terrorist organization. In Italy, the period often called the "years of lead [bullets]" displays an interesting viewpoint for the study of terrorist psychology, for two main reasons: first of all, it is a historically defined period (1968-1988), and second, the number of ascertained participants in terrorist activities was quite large.

Towards a psychopathology specific to Substance Use Disorder: Should emotional responses to life events be included?

INTRODUCTION: The severity of emotional responses to life events (PTSD spectrum) as part of Post Traumatic Stress Disorder (PTSD) in Substance Use Disorder (SUD) patients has often been considered from a unitary perspective. Light has also been shed on the possible definition of a specific psychopathology of SUD patients. This psychopathology has been proved to be independent of treatment choice, of being active in using substances, of lifetime psychiatric comorbidity and primary substance of abuse (heroin, alcohol, cocaine). METHODS: To further support this unitary perspective, in this study we have compared the severity and typology of the five psychopathological dimensions found in SUD patients, by dividing 93 HUD patients (77.4% males and 22.6% females), characterized by the lifetime absence of exposure to actual or threatened death, serious injury, or sexual violence, on the basis of the severity of their PTSD spectrum. We used the cut-off that differentiated people developing (High PTSD spectrum; H-PTSD/S) or not developing (Low PTSD spectrum; L-PTSD/S) a PTSD after the earthquake that hit L'Aquila, Italy, in April 2009. RESULTS: Using a canonical correlation analysis, the significant (p<0.001) canonical variate set-one (psychopathology) is saturated negatively by "panic anxiety" and positively by the "worthlessness-being trapped" and "violence-suicide" dimensions. Set-two (PTSD spectrum) is saturated negatively by "emotional, physical and cognitive responses to loss and traumas", and positively by "grief reactions", "re-experiencing numbing", "arousal symptoms" and "personality traits". When comparing the two groups, all five psychopathological dimensions were significantly more severe in H-PTSD/S patients, who were distinguished by higher values of worthlessness-being trapped, sensitivity-psychoticism and violence-suicide symptomatology. No differences were observed regarding the typology of psychopathology. CONCLUSIONS: This study further supports the SUD-PTSD spectrum unitary perspective and argues in favor of the inclusion of the PTSD spectrum in the psychopathology of SUD.

Efficacy and safety of sodium oxybate in alcohol-dependent patients with a very high drinking risk level.

Medication development for alcohol relapse prevention or reduction of consumption is highly challenging due to methodological issues of pharmacotherapy trials. Existing approved medications are only modestly effective with many patients failing to benefit from these therapies. Therefore, there is a pressing need for other effective treatments with a different mechanism of action, especially for patients with very high (VH) drinking risk levels (DRL) because this is the most severely affected population of alcohol use disorder patients. Life expectancy of alcohol-dependent patients with a VH DRL is reduced by 22 years compared with the general population and approximately 90 000 alcohol-dependent subjects with a VH DRL die prematurely each year in the EU (Rehm et al. ). A promising new medication for this population is sodium oxybate, a compound that acts on GABAB receptors and extrasynaptic GABAA receptors resulting in alcohol-mimetic effects. In this article, a European expert group of alcohol researchers and clinicians summarizes data (a) from published trials, (b) from two new-as yet unpublished-large clinical trials (GATE 2 (n = 314) and SMO032 (n = 496), (c) from post hoc subgroup analyses of patients with different WHO-defined DRLs and (d) from multiple meta-analyses. These data provide convergent evidence that sodium oxybate is effective especially in a subgroup of alcohol-dependent patients with VH DRLs. Depending on the study, abstinence rates are increased up to 34 percent compared with placebo with risk ratios up to 6.8 in favor of sodium oxybate treatment. These convergent data are supported by the clinical use of sodium oxybate in Austria and Italy for more than 25 years. Sodium oxybate is the sodium salt of γ-hydroxybutyric acid that is also used as a recreational (street) drug suggestive of abuse potential. However, a pharmacovigilance database of more than 260 000 alcohol-dependent patients treated with sodium oxybate reported very few adverse side effects and only few cases of abuse. We therefore conclude that sodium oxybate is an effective, well-tolerated and safe treatment for withdrawal and relapse prevention treatment, especially in alcohol-dependent patients with VH DRL.

Psychopathology of addiction: Can the SCL90-based five-dimensional structure differentiate Heroin Use Disorder from a non-substance-related addictive disorder such as Gambling Disorder?

BACKGROUND: In the Gambling Disorder (GD), there is no exogenous drug administration that acts as the central core of the traditional meaning of addiction. A specific psychopathology of Substance Use Disorders has been proposed recently. In a sample of Heroin Use Disorder (HUD) patients entering opioid agonist treatment, it became possible to identify a group of 5 mutually exclusive psychiatric dimensions: Worthlessness-Being trapped (W-BT), Somatic Symptoms (SS), Sensitivity-Psychoticism (SP), Panic Anxiety (PA) and Violence-Suicide (VS). The specificity of these dimensions was suggested by the absence of their correlations with treatment choice, active substance use, psychiatric comorbidity and the principal substance of abuse and by the opportunity, through their use, of fully discriminating HUD from Major Depression patients and, partially, from obese non-psychiatric patients. To further support this specificity in the present study, we tested the feasibility of discriminating HUD patients from those affected by a non-substance-related addictive behaviour, such as GD. In this way, we also investigated the psychopathological peculiarities of GD patients. METHODS: We compared the severity and frequency of each of the five aspects found by us, in 972 (83.5% males; mean age 30.12 ± 6.6) HUD and 110 (50% males; average age 30.12 ± 6.6) GD patients at univariate (T test; Chi square) and multivariate (discriminant analysis and logistic regression) level. RESULTS: HUD patients showed higher general psychopathology indexes than GD patients. The severity of all five psychopathological dimensions was significantly greater in HUD patients. Discriminant analysis revealed that SS and VS severity were able to discriminate between HUD (higher severity) and GD patients (lower severity), whereas PA and SP could not. W-BT severity was negatively correlated with SS and VS; GD patients were distinguished by low scores for SS and VS low scores associated with high ones for W-BT. Psychopathological subtypes characterized by SS and VS symptomatology were better represented in HUD patients, whereas PA symptomatology was more frequent in GD individuals. No differences were observed regarding the W-BT and SP dimensions. At multivariate level, the one prominent characteristic of HUD patients was the presence of SS (OR = 5.43) as a prominent qualification for psychopathological status. CONCLUSIONS: Apart from the lower severity of all psychopathological dimensions, only the lower frequency of SS typology seems to be the prominent factor in GD patients. The SCL90-defined structure of opioid addiction seems to be useful even in non-substance-related addictive disorders, as in the case of GD patients, further supporting the possible existence of a psychopathology specific to addiction.

The long-term outcome of patients with heroin use disorder/dual disorder (chronic psychosis) after admission to enhanced methadone maintenance.

BACKGROUND: Over-standard methadone doses are generally needed in the treatment of heroin use disorder (HUD) patients that display concomitant high-severity psychopathological symptomatology. A flexible dosing regimen may lead to higher retention rates in dual disorder (DD), as we demonstrated in bipolar 1 HUD patients, leading to outcomes that are as satisfactory as those of HUD patients without high-severity psychopathological symptomatology. OBJECTIVE: This study aimed to compare the long-term outcomes of treatment-resistant chronic psychosis HUD patients (PSY-HUD) with those of peers without dual disorder (HUD). METHODS: 85 HUD patients who also met the criteria for treatment resistance-25 of them affected by chronic psychosis and 60 without DD-were monitored prospectively for up to 8 years while continuing to receive enhanced methadone maintenance treatment. RESULTS: The rates of endurance in the treatment of PSY-HUD patients were 36%, compared with 34% for HUD patients (p = 0.872). After 3 years of treatment, these rates tended to become progressively more stable. PSY-HUD patients showed better outcome results than HUD patients regarding CGI severity (p < 0.001) and DSM-IV-GAF (p < 0.001). No differences were found regarding good toxicological outcomes or the methadone dosages used to achieve stabilization. The time required to stabilize PSY-HUD patients was shorter (p = 0.034). CONCLUSIONS: An enhanced methadone maintenance treatment seems to be equally effective in patients with PSY-HUD and those with HUD.

Erratum to: Agonist Opioid Treatment as historical comprehensive treatment ('Dole & Nyswander' methodology) is associated with better toxicology outcome than Harm Reduction Treatment.

[This corrects the article DOI: 10.1186/s12991-016-0109-z.].

Risky use and misuse of alcohol and cigarettes in psychiatric inpatients: a screening questionnaire study.

BACKGROUND: Mental disorders are associated with an increased prevalence of substance use disorders (SUDs). Despite this comorbidity being firmly established, alcohol and nicotine risky use and misuse are not routinely and systematically assessed in clinical practice. OBJECTIVE: The aim of this study is to examine the prevalence of risky use of alcohol, alcohol use disorder (AUD), smoking, and nicotine use disorder in people with psychiatric diagnoses and their association with age, gender, and occupational functioning. METHOD: Participants were 210 patients from an inpatient psychiatric ward. Three self-reporting questionnaires were used: the Alcohol Use Disorders Identification Test (AUDIT), the Lübeck Alcoholism Screening Test (LAST), and the Fagerström Test for Nicotine Dependence (FTND). RESULTS: Risky alcohol use or AUD was found in more than one third of patients and was more common in males than in females (p<0.01) and in young people as compared to older adults (p=0.04). Current nicotine consumption concerned over a half participants and was significantly associated with risky alcohol use and AUD (p<0.01). Patients with current SUD had the highest prevalence of both smoking (80%) and alcohol misuse (80%). Low occupational functioning was associated with both alcohol use (p=0.02) and concurrent alcohol and SUDs (p=0.03). CONCLUSIONS: Both alcohol and nicotine risky use and misuse are highly prevalent in people with psychiatric disorders and their concurrent abuse is common. The simultaneous use of different screening questionnaires allows the identification not only of people with frank use disorders, but also those with harmful use, facilitating early detection of people at risk.

Addressing misuse and diversion of opioid substitution medication: guidance based on systematic evidence review and real-world experience.

BACKGROUND: Opioid dependence treatment, comprising opioid substitution treatment (OST) and psychosocial intervention, is accepted to improve outcomes in opioid addiction for both the individual and public health. OST medication such as methadone or buprenorphine may be misused or diverted. This results in failure to recover from addiction, increased crime and the spread of blood-borne viruses. Worldwide, attempts to address misuse and diversion have been proposed and implemented with varying impact. METHODS: A structured, expert-led process recommended the most impact. As an initial step, a broad range of strategies were defined, and a systematic review of published literature identified 37 highly relevant sources of evidence. Experts reviewed this evidence and ranked the list of strategies for effectiveness and ease of implementation, based on their clinical experience. RESULTS/CONCLUSIONS: Three groups of strategies to address misuse or diversion are defined, depending on impact (effectiveness and ease of implementation). Preferred strategies include the promotion of access to treatment and the use of product formulations less likely to be misused. However, additional data and innovative approaches to address this complex problem are needed.

Sexual Dysfunction in Men Receiving Methadone Maintenance Treatment: Clinical History and Psychobiological Correlates.

A variety of studies evidenced a relationship between drug use disorders and sexual dysfunction. In particular, heroin and opioid agonist medications to treat heroin dependence have been found to be associated with erectile dysfunction and reduced libido. Controversial findings also indicate the possibility of factors other than the pharmacological effects of opioid drugs concurring to sexual dysfunction. With the present study, we investigated the link between sexual dysfunction and long-term exposure to opioid receptor stimulation (heroin dependence, methadone maintenance treatment, methadone dosage), the potentially related hormonal changes reflecting hypothalamus-pituitary-gonadal axis function and prolactin (PRL) pituitary release, the role of adverse childhood experiences in the clinical history and the concomitant symptoms of comorbid mental health disorders in contributing to sexual problems. Forty male patients participating in a long-term methadone treatment program were included in the present study and compared with 40 healthy control subjects who never used drugs nor abused alcohol. All patients and controls were submitted to the Arizona Sexual Experiences Scale (ASEX), Child Experiences of Care and Abuse-Questionnaire (CECA-Q) and the Symptom Check List-90 Scale. A blood sample for testosterone and PRL assays was collected. Methadone dosages were recorded among heroin-dependent patients on maintenance treatment. Methadone patients scored significantly higher than controls on the 5-item rating ASEX scale, on CECA-Q and on Symptoms Check List 90 (SCL 90) scale. Testosterone plasma levels were significantly lower and PRL levels significantly higher in methadone patients with respect to the healthy control group. ASEX scores reflecting sexual dysfunction were directly and significantly correlated with CECA-Q neglect scores and SCL 90 psychiatric symptoms total score. The linear regression model, when applied only to addicted patients, showed that methadone dosages were not significantly correlated with sexual dysfunction scores except for 'erectile dysfunction', for which an inverse association was evidenced. Testosterone values showed a significant inverse correlation with ASEX sexual dysfunction scores, CECA-Q neglect scores and psychiatric symptom at SCL 90 among methadone patients. PRL levels were directly and significantly correlated with sexual dysfunction scores, psychiatric symptoms at SCL 90 and CECA-Q neglect scores. Both testosterone and PRL did not correlate with methadone dosages. The present findings appear to support the view of childhood adversities and comorbid psychiatric symptoms contributing to sexual dysfunction and related hormonal changes among methadone patients, challenging the assumption that attributes sexual problems entirely to the direct pharmacological effects of opioid agonist medications.

The Impact of Misuse and Diversion of Opioid Substitution Treatment Medicines: Evidence Review and Expert Consensus.

BACKGROUND/AIMS: Opioid substitution treatment (OST) improves outcomes in opioid dependence. However, controlled drugs used in treatment may be misused or diverted, resulting in negative treatment outcomes. This review defines a framework to assess the impact of misuse and diversion. METHODS: A systematic review of published studies of misuse and diversion of OST medicines was completed; this evidence was paired with expert real-world experience to better understand the impact of misuse and diversion on the individual and on society. RESULTS: Direct impact to the individual includes failure to progress in recovery and negative effects on health (overdose, health risks associated with injecting behaviour). Diversion of OST has impacts on a community that is beyond the intended OST recipient. The direct impact includes risk to others (unsupervised use; unintended exposure of children to diverted medication) and drug-related criminal behavior. The indirect impact includes the economic costs of untreated opioid dependence, crime and loss of productivity. CONCLUSION: While treatment for opioid dependence is essential and must be supported, it is vital to reduce misuse and diversion while ensuring the best possible care. Understanding the impact of OST misuse and diversion is key to defining strategies to address these issues.

The newer Opioid Agonist Treatment with lower substitutive opiate doses is associated with better toxicology outcome than the older Harm Reduction Treatment.

BACKGROUND: Charge-free heroin use disorder treatment in Italy follows two main approaches, i.e., harm reduction treatment (HRT) strategy in community low-threshold facilities for drug addiction and opioid agonist treatment (OAT) in high-threshold facilities for opioid addiction, focusing on pharmacological maintenance according to the Dole and Nyswander strategy. We aimed to compare the impact of HRT and OAT on patient outcome, as assessed through negativity for drugs on about 1-year urinalyses. METHODS: We examined retrospectively the urinalyses of HRT and OAT patients for which at least four randomly sampled urinalyses per month were available for about 1 year, during which patients were undergoing methadone or buprenorphine maintenance; urinalyses focused on heroin, cocaine, cannabinoids, and their metabolites. RESULTS: Included were 189 HRT and 58 OAT patients. The latter were observed for a significantly longer period. There was a higher proportion of heroin- and cocaine-clean urinalyses in OAT patients, with cocaine-clean urinalyses discriminating best between the two groups. OAT patients were older, with longer dependence duration, more severe addiction history, and received lower methadone doses. Buprenorphine maintenance was more often associated with heroin-clean urinalyses. The higher the methadone doses, the lower were the percentage of heroin-clean urinalyses in HRT patients (negative correlation). CONCLUSIONS: The OAT approach was related to higher recovery and polyabuse abstinence rates compared to the HRT approach, despite greater severity of substance use, psychiatric and physical comorbidities. Our results are consistent with the possibility to use lower maintenance opiate doses (after induction and stabilization in methadone treatment according to Dole and Nyswander methodology) in treating heroin addiction. This seemed to be impossible adopting the currently accepted HRT model.

Psychopathology of addiction: May a SCL-90-based five dimensions structure be applied irrespectively of the involved drug?

BACKGROUND: We previously found a five cluster of psychological symptoms in heroin use disorder (HUD) patients: 'worthlessness-being trapped', 'somatic-symptoms', 'sensitivity-psychoticism', 'panic-anxiety', and 'violence-suicide'. We demonstrated that this aggregation is independent of the chosen treatment, of intoxication status and of the presence of psychiatric problems. METHODS: 2314 Subjects, with alcohol, heroin or cocaine dependence were assigned to one of the five clusters. Differences between patients dependent on alcohol, heroin and cocaine in the frequency of the five clusters and in their severity were analysed. The association between the secondary abuse of alcohol and cocaine and the five clusters was also considered in the subsample of HUD patients. RESULTS: We confirmed a positive association of the 'somatic symptoms' dimension with the condition of heroin versus cocaine dependence and of the 'sensitivity-psychoticism' dimension with the condition of alcohol versus heroin dependence. 'Somatic symptoms' and 'panic anxiety' successfully discriminated between patients as being alcohol, heroin or cocaine dependents. Looking at the subsample of heroin dependents, no significant differences were observed. CONCLUSIONS: The available evidence coming from our results, taken as a whole, seems to support the extension of the psychopathological structure previously observed in opioid addicts to the population of alcohol and cocaine dependents.

The impact of psychopathological subtypes on retention rate of patients with substance use disorder entering residential therapeutic community treatment.

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.

Former Heroin-Dependent Alcohol Use Disorder Patients. Prevalence, Addiction History and Clinical Features.

AIMS: To examine the prevalence of former heroin dependence (FHA) in Alcohol Use Disorder (AUD) patients; to compare the clinical characteristics of FHA-AUD patients versus AUD patients without any past use of heroin at alcohol treatment entry; to document the heroin dependence history of FHA-AUD patients, and review treatment strategies for this group. METHODS: Retrospective case review of 448 consecutive AUD patients. RESULTS: The annual entry of FHA-AUD showed stability over the study period of 3 years overall 60/448 (13.3%). FHA-AUD patients showed higher concomitant use of cocaine, benzodiazepines, cannabis and hallucinogens than other heroin addicts. They consumed higher amounts of alcohol at the beginning of their alcohol dependence history, and reached a high maximum level of alcohol consumption, than other AUD patients, and tended to have more physical disorders. The most important signals of FHA-AUD were polyabuse and older age at the time of presentation. FHA-AUD patients tended to have had a severe pattern of heroin dependence associated with inadequate agonist opiate treatment. CONCLUSIONS: The prevalence of FHA-AUD patients is not negligible. This may relate to previous inadequate treatment of heroin addiction contributing to the development of severe AUD. For these patients we propose a reconsideration of 'soft' (low dose) agonist opiate treatment.

Towards a unitary perspective between post-traumatic stress disorder and substance use disorder. Heroin use disorder as case study.

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=0.125F=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.