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Digital archive of theses discussed at the University of Pisa


Thesis etd-10162023-220617

Thesis type
Tesi di specializzazione (4 anni)
Thesis title
Emotional dysregulation, craving and hedonic motivation in patients switching from racemic methadone to levomethadone
Course of study
relatore Prof. Perugi, Giulio
  • emotional dysregulation
  • motional drive
  • craving
  • opioid maintenance treatment
  • methadone
  • levomethadone
Graduation session start date
Release date
Background: Methadone is the most utilized drug for replacement therapy in patients with opioid-related addiction. Methadone treatment causes several side effects such as respiratory depression, constipation, sedation, prolonged Qtc, endocrine effects, anhedonia.
Methadone, a chiral opioid, is generally available as the racemic mixture (R/S methadone).
Racemic methadone consists of two enantiomers; the active R-, laevo-,1- or (+) and the inactive S-, dextro-, d or (-) methadone. Enantiomers (R and S) have different pharmacokinetic and pharmacodynamic properties.
Levomethadone is the main therapeutic component of methadone. Levomethadone has approximately 50x the potency of the (S)-(+) enantiomer as well as greater μ-opioid receptor selectivity.
Dextromethadone may contribute significantly to the adverse but not the therapeutic effects of raceme methadone during maintenance treatment to the opioid addiction.
Purpose: the aim of this study was to compare the effectiveness in terms of craving, tolerance, global functioning and emotional dysregulation in patient switching from racemic methadone to levomethadone.
Methods: the clinical effectiveness of l-methadone maintenance treatment (LMMT) have been studied in 40 subjects > with a diagnosis of opioid addiction, previously maintained on methadone treatment (MMT). This is a prospective, observational, non-interventional study involving various italian centers located in Tuscany.
This work provides results of analysis in 43 subjects in MMT at baseline and in 40 subjects who switched to levomethadone, after a two month follow-up. All patients were assessed, at baseline and at follow-up using the VAS Scale, using the Behaviour Rating Inventory of Executive Function Initiate Sub-scale, the ADHD Self Report Scale ASRS, the RIPoSt Questionnaire Reactivity, Intensity, Polarity and Stability Questionnaire, SOWS Subjective Opiate Withdrawal Scale, the WHO Disability Assessment Schedule 2.0 WHODAS, the Bowel Function Index, the Clinical Global Impression Scale CGI.
Results: At baseline we compared subjects in MMT with and without high Emotional dysregulation H-ED (evaluated with RIPoSt Questionnaire Reactivity, Intensity, Polarity and Stability
Questionnaire), with or without Current Substance Use and with or without ASRS>14 (ADHD Self Report Scale). We have found that the group with H-ED have more psychiatric comorbidities, more psycopharmacoterapies, more ADHD features (evaluated with ASRS), lower scores of Behaviour Rating Inventory of Executive Function BRIEF sub-scale, higher scores of WHO Disability Assessment Schedule 2.0 WHODAS; on the comparision between subjects in MMT with and without current substance use we have found that the subjects with current use are younger, have more craving (evaluated with VAS), take more psychopharmacoterapies; the subjects in MMT with ASRS>14 have a lower employment rate, take more psycopharmacoterapies, have more phisical comorbidities, show higher scores of RIPoST, Brief Subscale and Whodas, suffer more from withdrawal symptoms.
At 2 months follow-up subjects switched from racemic methadone to levomethadone suffered less constipation (assessed by Bowel Function Index) and showed decreased scores of BRIEF-A Initiate index, WHODAS 2.0 index, CGI Index.
At the analysis of RIPoSt scale patients with LMMT scored lower score in subscale of Emotional Impulsivity. Finally at 2 months follow-up patients didn’t show different scores in VAS index.
Conclusions: our study suggests that patients with LMMT don’t show significant reduction in craving and substance use. Instead, they show reduced constipation, improved executive functions and global functioning, improved motivational drive and reduced emotional dysregulation (especially impulsivity).