Neuropsychological performance of methadone-maintained opiate users

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 Neuropsychological findings in methadone-substituted opiate users: Systematic review


In the first chapter it was contended that there is a need to clarify the effects of MMT on cognitive function. This chapter presents a systematic review of the published literature that investigates the
relationship between MMT and cognitive function to determine whether factors such as dose,duration, or methadone plasma level are associated with deficits in cognitive function. The information presented in this review highlights some of the methodological difficulties associated with earlier studies that this thesis attempts to address.

Data Sources and search strategy

Studies were identified using searches of MEDLINE (OVID 1950-2013), EMBASE (1980-2013) PsycINFO (1806-2013) and Cochrane CENTRAL. Search terms were a combination of free-text and thesaurus terms (methadone AND cognition), such as “methadone maintenance” and “methadone”, combined with cognition-related terms such as “cognition”, “cognitive function”, “cognitive defect”, “cognitive impairment”, “memory”, “attention”, “executive function”, and “perception”. Different search strings
were used to maximise the relevance of the returned results when searching in different databases (Appendix 1). Peer-reviewed journals and English language limits were used. The distributions of records returned from this search are detailed in (Table 2.1).

Study selection

Further inclusion/exclusion criteria were developed to assess the relevance and quality of studies.Research was selected if it met the following criteria: 1) the study population consisted of individuals with opiate dependence undertaking methadone treatment; 2) cognitive tests were used as study outcome measures; and 3) information about cognitive function related to methadone was clearly presented. The search strategy identified 34 publications from MEDLINE In-Process, 22 from PsycINFO,
21 from EMBASE, and 7 from Cochrane Central. Of the 84 articles, 40 were duplicates and 5 were excluded because of one or more of the following criteria: case study (n=1), the study did not focus on cognitive functions related to methadone (n=3), unavailable electronically (n=1). Thirty-nine publications met the inclusion criteria and were included in this review. Checking the references of all publications did not result in the inclusion of any further studies.

 Data extraction

From the studies included, methodological characteristics (study population, study design, and data analysis), participant characteristics (age, duration, and dosage of MMT) and data regarding cognitive performance associated with MMT were extracted and are summarised into three groups: crosssectional studies (Table 2.2); randomised controlled trials (RCTs) (Table 2.3); and longitudinal studies (Table 2.4). All patients on MMT in the reviewed studies are assumed to be in the maintenance phase unless otherwise reported.

Methodological quality

The methodological quality of the selected studies was assessed using a standardised checklist for observational epidemiological studies developed by Sanderson et al. (224). The checklist is divided into different domains including selection of study participants, description of measurement, control of confounding variables, statistical methods, and conflicts of interest. Criteria for quality assessment are shown in Table 2.5. For each study a total quality score was obtained by summing the positive score on the item of the quality assessment list.

Table of Contents
List of Figures
List of Tables 
List of Abbreviations
Co-authorship forms
Introduction and Overview 
1 Opiates and methadone 
1.1 Introduction 
1.2 Neural systems underlying opiate dependence
1.2.1 Opiates as drugs
1.2.2 Opiate dependence and tolerance
1.2.3 The opiate receptors
1.2.4 Brain reward pathways
1.2.5 Neuroadaptation
1.2.6 Opiate dependence and cognitive function
1.3 Methadone 
1.3.1 Pharmacodynamic of methadone
1.3.2 Side effects
1.3.3 Mixing methadone with other drugs
1.4 Conclusion
2 Neuropsychological findings in methadone-substituted opiate users: Systematic review .
2.1 Introduction 
2.2 Data Sources and search strategy
2.3 Study selection
2.4 Data extraction
2.5 Methodological quality
2.6 Study characteristics
2.6.1 Participants and comparison groups
2.6.2 Measures of cognitive function
2.6.3 Methodologies employed
2.7 Association between cognitive function and MMT
2.7.1 Memory
2.7.2 Attention
2.7.3 Psychomotor speed
2.7.4 Decision making
2.7.5 Emotional interpretation
2.7.6 Verbal functioning
2.8 Other factors associated with cognitive impairments 
2.8.1 Poly or multiple drug use
2.8.2 Methadone dose
2.8.3 Length of MMT
2.8.4 Methadone plasma concentration
2.9 Discussion 
2.10 Conclusion
3 Resting EEG and ERPs findings in methadone-substituted opiate users
3.1 Introduction 
3.2 Electroencephalography (EEG) 
3.2.1 Delta waves
3.2.2 Theta waves
3.2.3 Alpha waves
3.2.4 Beta waves
3.3 Event-related potentials 
3.4 The effect of MMT on EEG/ERP measures: Literature review 
3.5 Literature search strategy 
3.6 Methadone-related effects on resting EEG 
3.7 Methadone-related effects on ERP
3.7.1 Contingent negative variation (CNV)
3.7.2 N75 and P100
3.7.3 N100, N200, P300
3.8 Summary
3.9 Research rationale
3.10 Conclusion
4 Study One: Neuropsychological performance of methadone-maintained opiate users
4.1 Introduction 
4.2 Methods 
4.2.1 Study design
4.2.2 Sample size and power calculations
4.2.3 Participants
4.2.4 Procedures
4.2.5 Materials
4.2.6 Data analysis
4.3 Results
4.3.1 Distribution
4.3.2 Demographics and clinic data
4.3.3 History of substance use
4.3.4 Drug test result
4.3.5 Timing of methadone taking prior to cognitive testing
4.3.6 Neuropsychological performance
4.3.7 Effects related to methadone dose and timing of methadone intake
4.4 Discussion 
4.5 Conclusion
5 Study Two: Changes in resting EEG following methadone treatment in opiate-dependent patients
5.1 Introduction 
5.2 Methods 
5.2.1 Participants
5.2.2 Procedure
5.2.3 Data recording
5.2.4 Data reduction and analysis
5.2.5 Data analysis
5.3 Results
5.3.1 Heart rate (HR)
5.3.2 EEG measures
5.3.3 Methadone dose and time intake related effect
5.4 Discussion 
5.5 Conclusion
6 Study three: Auditory event-related potentials in methadone- substituted opiate users. 
6.1 Introduction 
6.2 Methods 
6.2.1 Participants
6.2.2 Procedure
6.2.3 Stimuli
6.2.4 Data recording
6.2.5 Artefact correction
6.2.6 ERP Scoring
6.2.7 Data analysis
6.3 Results
6.3.1 Heart rate (HR)
6.3.2 Task performance
6.3.3 Event related potentials (ERPs)
6.3.4 Correlation analysis
6.4 Discussion 
6.5 Conclusion
7 General discussion and conclusion
7.1 Summary
7.2 Limitations
7.3 Direction for future research
7.4 Conclusion
Appendix 1: Search strings used when searching in different databases
Appendix 2: Advertisement for opiate users
Appendix 3: Advertisement for healthy volunteers
Appendix 4: Participant information sheet 
Appendix 5: Consent Form 
Appendix 6: The international 10−20 system of electrode placement
Appendix 7: PhD-related research output

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Effects of Methadone Maintenance Treatment on Cognitive Function: Neuropsychological and EEG Studies

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