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A Clinical Research Treatment Outcomes Framework was developed through a published systematic review. NCCRED conducted a comprehensive assessment of the research literature on pharmacotherapy for amphetamine/methamphetamine dependence to inform treatment guidelines and future research directions. A systematic review of 43 randomised controlled trials enrolling 4065 participants and assessing 23 pharmacotherapies for amphetamine/methamphetamine dependence was undertaken, including analysis of clinical research outcomes and measures. Outcomes and measures to assess them varied widely, making it difficult to synthesise the data; pharmacotherapies were most often assessed in defined or biased populations, and study completion rates were low.
To guide further national and international research and clinical practice in the pharmacotherapeutic treatment of methamphetamine dependence, the outcomes and measures to assess them that were used in all reviewed studies were included in the publication in CNS Drugs in April 2020 (https://link.springer.com/article/10.1007%2Fs40263-020-00711-x).
The results of this work can be translated into clinical practice through the application of these measures to determine whether the change or effect is also noted in clinical settings. Future work is needed to develop a consensus around measures used (more broadly) to ensure that research can be further synthesised by meta-analyses.
N.B. “n” refers to the number of studies that used the measure identified
Where possible, links to publications validating the scales discussed below or scales themselves are provided.
Outcome Assessed | Measures Used | Variations on Analysis |
Primary Outcomes | ||
Abstinence | Urine Drug Screen (UDS) (n=41) | Variations in cut-off points and measures: |
Comparing proportion of participants in each group demonstrating abstinence in the final 2 weeks of study – abstinence defined by having all UDS’ test negative and providing at least two UDS per week (n=1) | ||
Comparing proportion of participants in each group demonstrating abstinence in the final 2 weeks of study – abstinence defined by having all UDS’ test negative and providing all UDS in final 2 weeks of study (=3) | ||
Negative UDS during final 2 weeks of treatment and no more than 1 of 3 possible UDS missing per week (n=2) | ||
Weekly proportion of negative UDS (or weekly proportion of positive UDS) (n=5) | ||
Proportion of UDS testing negative during the study (n=5) | ||
Treatment Effectiveness Score (TES): | ||
Joint Probability Index: number of negative (AMPH, MA, ATS) UDS submitted by each participant in each treatment group at time point (end-of-treatment or follow-up visit) divided by the number of participants randomised to that treatment group (n=3) | ||
Longest period of uninterrupted abstinence (n=3) | ||
Percentage of participants with at least: | ||
Drug “free” week: A week in which all non-missing urine samples in the week (3 samples/week) were drug free (AMPH, MA, ATS) (n=1) | ||
Negative “use week” (n=1) | UDS collected 3 times per week: "use week" defined as each 7-day period beginning with first dose of study drug. | |
Self-Report (n=4) | Abstinence for 21 days any time during the study period (n=2) | |
Days per week (e.g. self-reported non-use days) (n=1) | ||
Frequency of use in prior 2 weeks (AMPH, MA, ATS) (n=1) | ||
Drug Diaries | 28-days prospective (n=1) | |
For self-reported MA use substituted for opiates | ||
Hair analysis (n=1) | ||
Changed use / reduction in use (n=7) | Reduction in UDS positive metabolites (n=3) | Decrease in average weekly log10 median urine MA concentrations over treatment period |
Overall change in proportion of positive UDS | Over study period (n=2) | |
New MA use (n=1) | Determined by: MA-positive first sample; following sample with no MA; MA detected in subsequent sample; following sample with MA detected; MA detected in subsequent sample in greater quantities that would be expected on the basis of mean half-life plus 2 Standard Deviations (SD); Participant self-reports new use of MA since prior sample. | |
Treatment efficacy (n=3) | UDS (n=3) | Number of non-use weeks (n=1) |
Craving (n=10) | Visual Analogue Scales (VAS) (n=5) | 10 mm (point) VAS (n=1) |
Penn Craving Scale (n=1) | ||
Withdrawal (n=3) | AWQ (n=1) | |
Amphetamine Cessation Symptoms Assessment (ACSA) (n=1) | ||
Amphetamine Selective Severity Assessment (ASSA) (n=1) | ||
Dependence (n=3) | Leeds Dependence Questionnaire (LDQ) (n=1) | |
Addiction Severity Index (ASI) / ASI-Lite (n=1) | ||
Depression (n=1) | ||
Psychopathology (n=1) | Brief Symptom Inventory (BSI) (n=1) | |
Clinical Impression(n=1) | Clinical Global Impression Scale (CGI) (n=1) | |
Retention in Treatment / Study (n=5) | Average duration of time in care (n=3) | |
Participant Satisfaction (n=3) | Type and number of adverse events (AE’s) (n=3) | |
Feasibility (n=2) | Feasibility to recruit (n=1) | |
Adherence (n=3) | Pharmacy records (n=1) | |
Medication Event Monitoring System (MEMS) caps (n=1) | ||
Study drug metabolites in urine (n=1) |
Outcome Assessed | Measures Used | Variations on Analysis |
Secondary Outcomes | ||
Abstinence | Urine Drug Screen (UDS) (n=10) | Comparing proportion of participants in each group demonstrating abstinence in the final 2 weeks of study – abstinence defined by having all UDS test negative and providing at least two UDS per week (n=2) |
Weekly proportion of negative UDS (or weekly proportion of positive UDS) (n=2) | ||
Proportion of UDS testing negative during the study (n=2) | ||
Treatment Effectiveness Score (TES): | ||
Self-Report | Days since last use (n=1) | |
Abstinence for 21 days any time during the study period (n=1) | ||
Days per week (e.g. self-reported non-use days) (n=4) | ||
Frequency of use in prior 2 weeks (AMPH, MA, ATS) (n=1) | ||
Drug Free Days (n=1) | ||
Time Line Follow Back (TLFB) (n=3) | ||
Opiate Treatment Index (OTI) (n=1) | Drug use subscale | |
Changed use / reduction in use (n=4) | Reduction in UDS positive metabolites (n=2) | Decrease in average weekly log10 median urine MA concentrations over treatment period |
Time to relapse (n=2) | Amongst those who previously achieved abstinence (n=1) | |
Craving (n=25) | Visual Analogue Scales (VAS) (n=16) | 7 mm (point) VAS (n=1) |
Brief Substance Craving Scale (BSCS) (n=6) | ||
Stimulant Craving Questionnaire (STCQ) (n=1) | ||
“Desires for Speed” modification of “Desires for Alcohol” Questionnaire (n=1) | ||
Craving-Questionnaire-Now version (CQ-Now) (n=1) | ||
Withdrawal (n=5) | AWQ (n=3) | |
Amphetamine Cessation Symptoms Assessment (ACSA) (n=1) | ||
Methamphetamine Withdrawal Questionnaire (MAWQ) (n=1) | ||
Dependence (n=14) | Addiction Severity Index (ASI) / ASI-Lite (n=10) | |
Severity of Dependence Scale (SDS) (n=3) | ||
Amphetamine Selective Severity Assessment (ASSA) (n=1) | ||
Depression (n=20) | Beck Depression Inventory (BDI) (n=1) | |
Montgomery-Åsberg Depression Rating Scale (n=2) | ||
Centre for Epidemiologic Studies Depression Scale (CES-D) (n=4) | ||
Hamilton Depression Rating Scale (HAM-D) (n=4) | ||
Beck Depression Inventory II (BDI-II) (n=1) | ||
Depression Anxiety Stress Scale (DASS) (n=1) | Full scale and sub-scores | |
Anxiety (n=3) | Hamilton Rating Scale for Anxiety (HAM-A) (n=1) | |
Beck Anxiety Inventory (n=1) | ||
Anxiety State Index (n=1) | ||
Psychological Distress (n=1) | PHQ-2 (n=1) | |
Psychopathology (n=2) | Brief Symptom Inventory (BSI) (n=1) | |
Positive and Negative Symptoms Scale (PANSS) (n=1) | ||
Clinical Impression (n=9) | Clinical Global Impression Scales: Observer (CGI-O) (n=3) | |
Clinical Global Impression Scales: Self (CGI-S) (n=4) | ||
Retention in Treatment / Study (n=11) | Days admitted as inpatient (n=3) | |
Participant Satisfaction (n=1) | Percentage of participants completing active medication, mean number weeks in treatment (n=1) | |
Adherence (n=13) | Self-report using AIDS Clinical Trials Group Questionnaire (ACTG) (n=1) | |
Pill count (n=7) | ||
Medication Event Monitoring System (MEMS) caps (n=2) | ||
Study drug metabolites in urine (n=2) | ||
Dose logs (n=1) | ||
Risk Behaviour (n=4) | HIV Risk-Taking Behaviour Scale (HRBS) (n=1) | |
HIV Risk Assessment Battery (n=1) | ||
Audio Computer Assisted Interview (ACASI) for self-report (n=2) | Number male partners | |
Attention Deficit Hyperactivity Disorder (ADHD) (n=3) | Adult ADHD Clinical Diagnostic Scale (ACDS) (n=1) | |
Adult ADHD Investigator Symptom Rating Scale (AISRS) (n=1) | ||
Barratt Impulsiveness Scale (n=1) | ||
Neuro-cognition (n=1) | Cambridge Neuropsychological Test Automated Battery (CANTAB) (n=1) | |
Safety (n=7) | Serious Adverse Events (SAE’s) / Adverse Events (AE’s) (n=3) | |
Physiological Indicators (n=4) | Vital statistics (n=3) | |
Quality of Life (n=3) | The Quality of Life Inventory (QoLI) (n=1) | |
Euro-QoL (n=1) | ||
Global Assessment of Functioning (GAF) score (n=1) | ||
Disability (n=1) | Sheehan Disability Scale (n=1) | |
Sleep (n=2) | Athens Insomnia Scale (AIS-5) (n=1) | |
St Mary’s Hospital Sleep Questionnaire (n=1) | ||
Other substance use (n=3) | Cigarettes (n=3) | Weekly number cigarettes in smoker subgroup (n=2) |
Other adverse effects (n=4) | Liver Function Tests (LFTs) (n=1) | |
Abnormal Involuntary Movement Scale (AIMS) (n=1) | ||
Barnes Akathisia Scale (BAS) (n=1) | ||
Simpson Angus Scale (SAS) (n=1) |
National Centre for Clinical
Research on Emerging Drugs
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