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Drug and Alcohol Dependence Nov 2020Stimulant (cocaine and/or methamphetamine) use has increased among people with opioid use disorder. We conducted a systematic review of medications for stimulant use... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stimulant (cocaine and/or methamphetamine) use has increased among people with opioid use disorder. We conducted a systematic review of medications for stimulant use disorders in this population.
METHODS
We searched for randomized controlled trials in multiple databases through April 2019, and dual-screened studies using pre-specified inclusion criteria. Primary outcomes were abstinence defined as stimulant-negative urine screens for ≥3 consecutive weeks; overall use as the proportion of stimulant-negative urine specimens; and retention as the proportion of participants who completed treatment. We rated strength of evidence using established criteria and conducted meta-analyses of comparable interventions and outcomes.
RESULTS
Thirty-four trials of 22 medications focused on cocaine use disorder in patients with opioid use disorder. Most studies enrolled participants stabilized on opioid maintenence therapy, generally methadone. None of the six studies that assessed abstinence found significant differences between groups. We found moderate-strength evidence that antidepressants (desipramine, bupropion, and fluoxetine) worsened retention. There was moderate-strength evidence that disulfiram worsened treatment retention (N = 605, RR 0.86, 95 % CI 0.77 to 0.95). We found low-strength evidence that psychostimulants (mazindol and dexamphetamine) may reduce cocaine use, though the difference was not statistically significant (standard mean difference 0.35 [95 % CI -0.05 to 0.74]). There was only 1 trial for methamphetamine use disorder, which showed insufficient-strength evidence for naltrexone.
CONCLUSIONS
Co-occurring stimulant/opioid use disorder is an important problem for targeting future research. Medication trials for methamphetamine use disorder are lacking in this population. Most of the medications studied for cocaine use were ineffective, although psychostimulants warrant further study.
Topics: Analgesics, Opioid; Antidepressive Agents; Central Nervous System Stimulants; Cocaine; Cocaine-Related Disorders; Female; Humans; Methadone; Naltrexone; Opioid-Related Disorders
PubMed: 32861136
DOI: 10.1016/j.drugalcdep.2020.108193 -
NPJ Schizophrenia Dec 2019The dopamine hypothesis proposes that there is a hypodopaminergic state in the prefrontal cortex and a hyperdopaminergic state in the striatum of patients with...
The dopamine hypothesis proposes that there is a hypodopaminergic state in the prefrontal cortex and a hyperdopaminergic state in the striatum of patients with schizophrenia. Evidence suggests the hyperdopaminergic state in the striatum is due to synaptic dopamine elevation, particularly in the dorsal striatum. However, the molecular mechanisms causing disrupted dopaminergic function in schizophrenia remains unclear. We postulated that the dopamine transporter (DAT), which regulates intra-synaptic dopamine concentrations by transporting dopamine from the synaptic cleft into the pre-synaptic neuron, could be involved in dopaminergic dysfunction in schizophrenia. Therefore, we measured levels of DAT in the cortex and striatum from patients with schizophrenia and controls using postmortem human brain tissue. Levels of desmethylimipramine-insensitive mazindol-sensitive [H]mazindol binding to DAT were measured using in situ radioligand binding and autoradiography in gray matter from Brodmann's area (BA) 10, BA 17, the dorsal striatum, and nucleus accumbens from 15 patients with schizophrenia and 15 controls. Levels of desmethylimipramine-insensitive mazindol-sensitive [H]mazindol binding were significantly higher in BA 10 from patients with schizophrenia (p = 0.004) and significantly lower in the dorsal striatum (dorsal putamen p = 0.005; dorsal caudate p = 0.007) from those with the disorder. There were no differences in levels of desmethylimipramine-insensitive [H]mazindol binding in BA 17 or nucleus accumbens. These data raise the possibility that high levels of DAT in BA 10 could be contributing to lower synaptic cortical dopamine, whereas lower levels of DAT could be contributing to a hyperdopaminergic state in the dorsal striatum.
PubMed: 31792225
DOI: 10.1038/s41537-019-0087-7 -
Journal of Clinical Medicine Mar 2024(1) : The number of severely obese patients worldwide is rapidly increasing. Recently, novel therapeutic approaches, such as bariatric surgery or GLP-1 receptor...
(1) : The number of severely obese patients worldwide is rapidly increasing. Recently, novel therapeutic approaches, such as bariatric surgery or GLP-1 receptor agonists, have emerged, bringing about a paradigm shift in this field. However, these therapies sometimes face challenges, such as peri-surgical complications or supply shortages. Mazindol, which is an appetite suppressant approved decades ago in Japan, remains a valuable option. In this study, we investigated the effectiveness of mazindol in reducing body weight in 147 patients, and we examined the factors influencing said effectiveness. (2) : The patients were divided into four groups based on the treatment cycles they underwent: 1 cycle, 2 cycles, 3-5 cycles, and over 6 cycles. We compared the changes in body weight before and after the treatment among these four groups. Additionally, we sought to identify the factors correlated to the effectiveness of mazindol. (3) : The change in body weight was more pronounced in the group which underwent 3-5 cycles compared to the groups which underwent 1 cycle and 2 cycles; this change was also more pronounced in the group which underwent over 6 cycles compared to those which underwent 1 cycle. Furthermore, we observed a significant correlation between the initial body weight and the extent of body weight change. (4) : Mazindol demonstrated effectiveness in reducing the body weight of patients in a cycle-dependent manner.
PubMed: 38610625
DOI: 10.3390/jcm13071860 -
Forensic Science International Oct 2020The use of psychoactive substances has been associated with increased risk for traffic accidents. Hair testing has become a routine practice in clinical and forensic...
The use of psychoactive substances has been associated with increased risk for traffic accidents. Hair testing has become a routine practice in clinical and forensic toxicological laboratories, with a unique perspective in the investigation of drug consumption. The study aimed to develop and validate a UHPLC-MS/MS method for the determination of multiple drugs in hair, to be used for toxicological examination in driving license granting. Sample preparation was a one-step liquid extraction of milled hair with methanol, which was incubated for 15h at 50°C. The chromatographic separation was performed in a reversed phase column, with a run time of 2.2min. Measured compounds were cocaine, benzoylecgonine, norcocaine, anhydroecgonine methyl ester, cocaethylene, amphetamine, methamphetamine, methylenedioxyamphetamine, methylenedioxymethamphetamine, fenproporex, amfepramone, mazindol, codeine, morphine, 6-monoacetylmorphine, and tetrahydrocannabinol. The assay was linear for all substances (r>0.99), accurate (86.63-105.87 %), and precise, with a cv ranging from 1.9-13.5 % for intra-assay and 3.3-14.3 % for inter-assay. There was no significant carry over effect and the internal standard corrected matrix effect was minimal. The relative uncertainty percentages were below 9% for all the substances at cut-off values. The method was successfully applied to 50 hair samples from injured drivers, with 12% of positivity, including cocaine, MDMA and THC.
Topics: Automobile Driving; Chromatography, High Pressure Liquid; Hair; Humans; Illicit Drugs; Licensure; Limit of Detection; Mass Spectrometry; Psychotropic Drugs; Substance Abuse Detection; Substance-Related Disorders
PubMed: 32771886
DOI: 10.1016/j.forsciint.2020.110428