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Roux P.,French Institute of Health and Medical Research | Roux P.,Aix - Marseille University | Lions C.,French Institute of Health and Medical Research | Lions C.,Aix - Marseille University | And 15 more authors.
Current Pharmaceutical Design | Year: 2014

Background: Although methadone maintenance treatment (MMT) is recognized as the treatment of reference for opioid dependence, little information is available regarding the dynamic adherence to methadone and its determinants. With data from the Methav-ille trial we investigated the evolution of non-adherence to methadone and the effect of pre-treatment and in-treatment factors on long-term non-adherence to methadone. Methods: We selected 145 patients to study adherence to methadone at 3, 6 and 12 months (M3, M6 and M12, respectively) using a multidimensional questionnaire and a 3-level variable "adherent"/"non adherent"/"highly non-adherent". We then identified the pre-treatment and in-treatment variables associated with long-term non-adherence to methadone at the M12 visit using a univariate logistic regression and two different multivariate models: the first incorporating only the pre-treatment variables, the second adding the in-treatment variables to the pre-treatment ones. Results: At the M12 visit, 35.2% of the participants remained adherent, 55.9% and 9% were non-adherent and highly non-adherent, respectively. The multivariate analysis of long-term non-adherence to methadone showed 4 pre-treatment predictors and 1 in-treatment predictor as follows: being female, not having stable housing, alcohol consumption, cocaine use and perceiving methadone dose as inadequate. Conclusions: Our findings highlight that pre-treatment predictors are important to consider when starting maintenance treatment for opioid dependence, such as cocaine use and problematic alcohol consumption but also low socio-economic levels. In addition, during maintenance treatment, in-treatment predictors such as methadone dose adequacy is a crucial issue to achieve good adherence to MMT. © 2014 Bentham Science Publishers.


Petit A.,Bichat Claude Bernard Hospital | Karila L.,Addiction Research and Treatment Center | Chalmin F.,Bichat Claude Bernard Hospital | Lejoyeux M.,Bichat Claude Bernard Hospital
International Journal of Dermatology | Year: 2014

Excessive indoor tanning, defined by the presence of an impulse towards and repetition of tanning that leads to personal distress, has only recently been recognized as a psychiatric disorder. This finding is based on the observations of many dermatologists who report the presence of addictive relationships with tanning salons among their patients despite being given diagnoses of malignant melanoma. This article synthesizes the existing literature on excessive indoor tanning and addiction to investigate possible associations. This review focuses on the prevalence, clinical features, etiology, and treatment of this disorder. A literature review was conducted, using PubMed, Google Scholar, EMBASE and PsycINFO, to identify articles published in English from 1974 to 2013. Excessive indoor tanning may be related to addiction, obsessive-compulsive disorder, impulse control disorder, seasonal affective disorder, anorexia, body dysmorphic disorder, or depression. Excessive indoor tanning can be included in the spectrum of addictive behavior because it has clinical characteristics in common with those of classic addictive disorders. It is frequently associated with anxiety, eating disorders, and tobacco dependence. Further controlled studies are required, especially in clinical psychopathology and neurobiology, to improve our understanding of excessive indoor tanning. © 2014 The International Society of Dermatology.


Rolland B.,University of Lille Nord de France | Karila L.,Addiction Research and Treatment Center | Geoffroy P.A.,University of Lille Nord de France | Cottencin O.,University of Lille Nord de France
Epilepsy and Behavior | Year: 2011

Cocaine-induced seizures (CIS) and cocaine-induced psychosis (CIP) may be complications of acute cocaine intoxication. CIS could result from a kindling process, involving the glutamate NMDA receptor (NMDAR) phosphorylation state, which is enhanced by activation of the dopamine D1 receptor (D1R). CIP is considered to be more specifically associated with the activity of the dopamine D2 receptor (D2R). The authors describe the case of a 21-year-old woman who presented with recurrent CIP during a period of increased cocaine abuse that ended in two consecutive CIS. This case report may illustrate a possible overlap in the mechanisms underlying CIS and CIP, disclosing some subtle interactions occurring between dopaminergic and glutamatergic receptors during cocaine chronic intoxication. Chronic cocaine exposure usually induces the formation of a NMDAR-D2R complex, which seems to be linked to the usual clinical effects of the drug, but also causes complex formation not to occur in both D2R-based CIP and D1R-based CIS. To explain the case of this patient, we propose a pharmacological hypothesis based on a literature review and implying the lack of formation of this complex, which triggers CIP and CIS. On a more practical level, this case report also encourages practitioners to be aware of the possible co-occurrence of CIP and CIS in cocaine abusers, especially with respect to antipsychotic medications that could be administered in such situations. © 2011 Elsevier Inc.


Karila L.,University Paris - Sud | Karila L.,Addiction Research and Treatment Center | Leroy C.,University Paris - Sud | Leroy C.,French Atomic Energy Commission | And 10 more authors.
Neuropsychopharmacology | Year: 2016

Modafinil is a candidate compound for the treatment of cocaine addiction that binds to the dopamine transporter (DAT) in healthy humans, as observed by positron emission tomography (PET). This mechanism, analogous to that of cocaine, might mediate a putative therapeutic effect of modafinil on cocaine dependence, though the binding of modafinil to DAT has never been assessed in cocaine-dependent patients. We aimed at quantifying the DAT availability during a controlled treatment by modafinil, and its clinical and psychometric correlates in cocaine-dependent patients at the onset of abstinence initiation. Twenty-nine cocaine-dependent male patients were enrolled in a 3-month trial for cocaine abstinence. Modafinil was used in a randomized double-blind placebo-controlled design and was administered as follows: 400 mg/day for 26 days, then 300 mg/day for 30 days, and 200 mg/day for 31 days. Participants were examined twice during a 17-day hospitalization for their DAT availability using PET and [11 C]-PE2I and for assessments of craving, depressive symptoms, working memory, and decision-making. Cocaine abstinence was further assessed during a 10-week outpatient follow-up period. Baseline [11 C]-PE2I-binding potential covaried with risk taking and craving index in striatal and extrastriatal regions. A 65.6% decrease of binding potential was detected in patients receiving modafinil for 2 weeks, whereas placebo induced no significant change. During hospitalization, an equivalent improvement in clinical outcomes was observed in both treatment groups, and during the outpatient follow-up there were more therapeutic failures in the modafinil-treated group. Therefore, these results do not support the usefulness of modafinil to treat cocaine addiction. © 2016 American College of Neuropsychopharmacology.


Reynaud M.,Addiction Research and Treatment Center | Reynaud M.,University Paris - Sud | Karila L.,Addiction Research and Treatment Center | Karila L.,University Paris - Sud
Current Pharmaceutical Design | Year: 2011

Switching from the concept of substance or alcohol dependence to that of addiction has profoundly modified our ways of approaching, treating and organizing the care of this disease. This more complex and subtle approach gives less importance to the substance and its effects and focuses more on the initiation of pathological behavior. It is important to keep in mind that the addictive process associates a substance (more or less addictive), an individual (more or less vulnerable) and an environment (more or less condoning). Today, it is no longer possible to consider that a drug acts on only one receptor or one system. Current understanding of inner regulation mechanisms integrates the interactions between the various stimulated brain pathways. Addiction treatments which should benefit from advances in genetics, neuropsychology and neuroimaging could be increasingly individualized in the years to come. The "addictology" approach has triggered thinking about other therapeutic approaches such as modification of therapeutic objectives toward "risk reductions" or applying this model to behavioral addictions (food, sex, sport, gaming.). This conceptual shift seems to enrich clinical analysis, the therapeutic possibilities and the avenues for research. © 2011 Bentham Science Publishers Ltd.

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