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Maremmani I.,University of Pisa | Maremmani I.,G Of Lisio Institute Of Behavioral Science | Pani P.P.,Social and Health Services | Rossi A.,Italian Society of General Practitioners | Turchetti G.,Sant'Anna School of Advanced Studies
International Journal of Environmental Research and Public Health | Year: 2015

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 searchfor 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. © 2015 by the authors; licensee MDPI, Basel, Switzerland.


Somaini L.,Addiction Treatment Center | Pacini M.,G Of Lisio Institute Of Behavioral Science | Maremmani I.,G Of Lisio Institute Of Behavioral Science | Maremmani I.,University of Pisa
Heroin Addiction and Related Clinical Problems | Year: 2010

The immune system is an organization of cells and molecules with specialized roles in defending against infection. Communication between the central nervous and the immune system lies at the hart of the neuroimmune axis. There are several data indicating that opioids drugs may influence the immune system. One of the main features of opioid induced alteration of immune function is the development of immunosuppression. However, evidence has been provided to suggest that different opioids drugs may have distinctive effects on the immune system. Methadone is a widely used synthetic 3,3-diphenylpropylamine opioid which primarily acts at the μ opioid receptor. Its most common use is in the therapy for opioid dependence. Besides to their therapeutic efficacy, opioids can produce several well known adverse events, and, as has recently been recognized, can positively interfere with the immune response. Infact, data obtain from animal and human studies have demonstrated that long acting opioids drugs such as methadone is devoid of any intrinsic immunosuppressive activity. This effect may partly depend on the ability of methadone to restore the HPA axis function, that is altered in heroin dependent patient, or by the long-lasting activation of opioid receptors both in the central nervous system and on immune competent cells. HIV and HCV infections are the most frequent infectious disease seen in drugs users. Opioids may facilitate the outbreak of infections through marked immunomodulating effects on the immune respsoses against a virus. The enrolment of heroin patient in MMT programs represents a particularly effective measure for the prevention of HCV and HIV virus transmission and the immunorestoring properties of methadone are particularly relevant in the treatment of concurrent infectious such as HCV frequently associated with heroin addiction. It is evident that the possibility to reach an adequate control of addiction and of concomitant infectious diseases choosing either immunosuppressive drugs or drugs characterized by immunoneutral or immunostimulating effects could represent an important point to be considered in the future in opioid therapy.


Pani P.P.,Social Health Services | Maremmani A.G.I.,University of Pisa | Trogu E.,Psychiatric Unit 2 | Ruiz P.,University of Miami | And 3 more authors.
Heroin Addiction and Related Clinical Problems | Year: 2013

The frequency of the association between substance use and psychiatric disorders is higher than what might be expected as a result of chance alone; the most frequently associated psychiatric symptoms, syndromes and disorders pertain to the domains of mood, anxiety and impulsivity. There are several reasons for taking these psychiatric manifestations into account when evaluating clinical presentations of substance-use disorders. DSM nosology does not seem to grasp the complexity of the interaction between the psychic structures involved, and neurobiological and physiopathological processes activated by encounters with substances of abuse. Based on neurobiological, epidemiological and clinical indications, an integrated, unified perspective explaining the pathophysiology and phenomenology of addiction has been proposed. The lack of substantial changes in the approach to the psychiatric comorbidity of addiction in the DSM V, despite the plausibility of the hypothesis that there may be a close link between addiction and other specific psychiatric conditions, can be explained by the persistent insufficiency of aetiological and pathophysiological evidence which supports that kind of association. The validation of an articulated clinical condition, encompassing part of the grey area of symptomatology that exists between addiction itself and other 'independent' psychopathologies, certainly calls for special attention and specific research programmes.


Pani P.P.,Societa Italiana Tossicodipendenze | Pani P.P.,Social Health Division | Maremmani I.,University of Pisa | Maremmani I.,G Of Lisio Institute Of Behavioral Science | And 4 more authors.
European Addiction Research | Year: 2011

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. Copyright © 2010 S. Karger AG, Basel.


Pani P.P.,Sardinia Regional Dependence Coordination Unit | Maremmani I.,Santa Chiara University Hospital | Maremmani I.,G Of Lisio Institute Of Behavioral Science | Trogu E.,Sardinia Regional Dependence Coordination Unit | And 3 more authors.
Journal of Affective Disorders | Year: 2010

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. © 2009 Elsevier B.V.


Rugani F.,University of Pisa | Bacciardi S.,University of Pisa | Rovai L.,University of Pisa | Pacini M.,G Of Lisio Institute Of Behavioral Science | And 6 more authors.
International Journal of Environmental Research and Public Health | Year: 2012

Background: Ecstasy use is generally chosen by adolescents and young adults for its entactogenic properties (the production of feelings of empathy, love, and emotional closeness to others.) Despite this desired and frequently realized outcome, Ecstasy use has often resulted in the genesis of psychotic symptoms and aggressive behaviors, particularly after chronic and/or intensive use. Methods: To explore the negative consequences of Ecstasy use and to examine the aggressive nature oftentimes seen in many Ecstasy users we employed a case-control study model. We compared, by means of validated psychometric tests, the psychopathological symptoms (BPRS), the aggressiveness (OAS) and the social adjustment (DSM-GAF) of psychotic patients with (n = 23) and without (n = 46) recent user of Ecstasy, during their first psychotic episode and hospitalization. All 23 Ecstasy users were Ecstasy users only. Results: Almost all of the psychotic symptoms were of similar severity in both groups. Blunted affect was milder in users than in non-users, whereas hostility and aggressive behavior was significantly more severe in users than in non-users. Conclusions: psychosis with a high level of aggressiveness and violence constitutes an important 'side-effect' that surely runs counter to the expected entactogenic action of Ecstasy. At a patient psycho-educational level, this study suggests that the use of Ecstasy may be counterproductive with respect to user expectations. © 2012 by the authors; licensee MDPI, Basel, Switzerland.


Maremmani A.G.I.,University of Pisa | Maremmani A.G.I.,G Of Lisio Institute Of Behavioral Science | Dell'Osso L.,University of Pisa | Pacini M.,University of Barcelona | And 7 more authors.
Journal of Addictive Diseases | Year: 2011

Although there are studies describing the prevalence of patients with drug addiction and dual diagnosis, there is a paucity of data regarding the progression from psychiatric disorders to drug addiction or vice versa. A total of 1,090 patients dependent on heroin were interviewed to examine the presence of dual diagnosis and the progression from psychiatric disorders to drug dependence or vice versa. A total of 574 patients met the criteria for a dual diagnosis. A total of 362 patients progressed from substance abuse disorders to psychiatric disorders (SUD-PR) and 144 patients progressed from psychiatric disorders to drug addiction (PSY-PR). SUD-PR patients are more frequently affected by mood disorders. PSY-PR patients were more frequently diagnosed as psychotic or affected by anxiety disorders. The authors' findings suggest that the self-medication theory of dual diagnosis was relevant only for those with existing diagnoses of schizophrenia or anxiety disorders. When treating patients with a dual diagnosis, clinicians should ensure that the same attention is given to the treatment of drug dependence as it is to the treatment of comorbid psychiatric conditions. Copyright © Taylor & Francis Group, LLC.


Dell'Osso L.,University of Pisa | Rugani F.,University of Pisa | Maremmani A.G.I.,University of Pisa | Bertoni S.,University of Pisa | And 3 more authors.
Comprehensive Psychiatry | Year: 2014

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.


Maremmani A.G.I.,University of Pisa | Pani P.P.,Social Health Direction | Rovai L.,University of Pisa | Pacini M.,G Of Lisio Institute Of Behavioral Science | And 2 more authors.
International Journal of Environmental Research and Public Health | Year: 2011

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. © 2011 by the authors.


Maremmani A.G.I.,University of Pisa | Rovai L.,University of Pisa | Pani P.P.,Social Health Services | Maremmani I.,University of Pisa | Maremmani I.,G Of Lisio Institute Of Behavioral Science
Heroin Addiction and Related Clinical Problems | Year: 2012

By recently using an exploratory factor analysis of the 90 items in the SCL-90, we identifed a fve-factor solution for 1055 heroin addicts who answered that questionnaire at treatment entry. On the basis of the highest z-scores obtained on these factors, subjects can be assigned to 5 mutually exclusive groups labelled "worthlessness and being trapped", "somatization", "sensitivity-psychoticism", "panic anxiety", and "violence-suicide". In this study we correlated the distribution within these groups of 455 heroin addicts. The patients belonging to the "worthlessness and being trapped" group had the highest average age and were those who, most frequently, had a white-collar job. Those belonging to the "somatization" group were less frequently at their frst treatment, more frequently reported sleep disturbances and less frequently referred to their use of hallucinogens. The leading distinctive feature of those in the "sensitivity-psychoticism" group was that they were the youngest. Patients belonging to the "panic anxiety" group less frequently reported major problems with their love life, sleep disturbances, and more frequently referred to their use of CNS stimulants. The features of being more excitable and violent brought with them the highest likelihood of belonging to the "violence-suicide" group. These differences were independent of the presence of dual diagnosis. These data support the hypothesis that heroin has as its foundation a specifc psychopathology.

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