Music therapy for people with substance use disorders.

BACKGROUND: Substance use disorder (SUD) is the continued use of one or more psychoactive substances, including alcohol, despite negative effects on health, functioning, and social relations. Problematic drug use has increased by 10% globally since 2013, and harmful use of alcohol is associated with 5.3% of all deaths. Direct effects of music therapy (MT) on problematic substance use are not known, but it may be helpful in alleviating associated psychological symptoms and decreasing substance craving. OBJECTIVES: To compare the effect of music therapy (MT) in addition to standard care versus standard care alone, or to standard care plus an active control intervention, on psychological symptoms, substance craving, motivation for treatment, and motivation to stay clean/sober. SEARCH METHODS: We searched the following databases (from inception to 1 February 2021): the Cochrane Drugs and Alcohol Specialised Register; CENTRAL; MEDLINE (PubMed); eight other databases, and two trials registries. We handsearched reference lists of all retrieved studies and relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials comparing MT plus standard care to standard care alone, or MT plus standard care to active intervention plus standard care for people with SUD. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included 21 trials involving 1984 people. We found moderate-certainty evidence of a medium effect favouring MT plus standard care over standard care alone for substance craving (standardised mean difference (SMD) -0.66, 95% confidence interval (CI) -1.23 to -0.10; 3 studies, 254 participants), with significant subgroup differences indicating greater reduction in craving for MT intervention lasting one to three months; and small-to-medium effect favouring MT for motivation for treatment/change (SMD 0.41, 95% CI 0.21 to 0.61; 5 studies, 408 participants). We found no clear evidence of a beneficial effect on depression (SMD -0.33, 95% CI -0.72 to 0.07; 3 studies, 100 participants), or motivation to stay sober/clean (SMD 0.22, 95% CI -0.02 to 0.47; 3 studies, 269 participants), though effect sizes ranged from large favourable effect to no effect, and we are uncertain about the result. There was no evidence of beneficial effect on anxiety (mean difference (MD) -0.17, 95% CI -4.39 to 4.05; 1 study, 60 participants), though we are uncertain about the result. There was no meaningful effect for retention in treatment for participants receiving MT plus standard care as compared to standard care alone (risk ratio (RR) 0.99, 95% 0.93 to 1.05; 6 studies, 199 participants). There was a moderate effect on motivation for treatment/change when comparing MT plus standard care to another active intervention plus standard care (SMD 0.46, 95% CI -0.00 to 0.93; 5 studies, 411 participants), and certainty in the result was moderate. We found no clear evidence of an effect of MT on motivation to stay sober/clean when compared to active intervention, though effect sizes ranged from large favourable effect to no effect, and we are uncertain about the result (MD 0.34, 95% CI -0.11 to 0.78; 3 studies, 258 participants). There was no clear evidence of effect on substance craving (SMD -0.04, 95% CI -0.56 to 0.48; 3 studies, 232 participants), depression (MD -1.49, 95% CI -4.98 to 2.00; 1 study, 110 participants), or substance use (RR 1.05, 95% CI 0.85 to 1.29; 1 study, 140 participants) at one-month follow-up when comparing MT plus standard care to active intervention plus standard care. There were no data on adverse effects. Unclear risk of selection bias applied to most studies due to incomplete description of processes of randomisation and allocation concealment. All studies were at unclear risk of detection bias due to lack of blinding of outcome assessors for subjective outcomes (mostly self-report). We judged that bias arising from such lack of blinding would not differ between groups. Similarly, it is not possible to blind participants and providers to MT. We consider knowledge of receiving this type of therapy as part of the therapeutic effect itself, and thus all studies were at low risk of performance bias for subjective outcomes.  We downgraded all outcomes one level for imprecision due to optimal information size not being met, and two levels for outcomes with very low sample size.  AUTHORS' CONCLUSIONS: Results from this review suggest that MT as 'add on' treatment to standard care can lead to moderate reductions in substance craving and can increase motivation for treatment/change for people with SUDs receiving treatment in detoxification and short-term rehabilitation settings. Greater reduction in craving is associated with MT lasting longer than a single session. We have moderate-to-low confidence in our findings as the included studies were downgraded in certainty due to imprecision, and most included studies were conducted by the same researcher in the same detoxification unit, which considerably impacts the transferability of findings.

An in vitro study on interaction of anisodine and monocrotaline with organic cation transporters of the SLC22 and SLC47 families.

Current study systematically investigated the interaction of two alkaloids, anisodine and monocrotaline, with organic cation transporter OCT1, 2, 3, MATE1 and MATE2-K by using in vitro stably transfected HEK293 cells. Both anisodine and monocrotaline inhibited the OCTs and MATE transporters. The lowest IC50 was 12.9 µmol·L-1 of anisodine on OCT1 and the highest was 1.8 mmol·L-1 of monocrotaline on OCT2. Anisodine was a substrate of OCT2 (Km = 13.3 ± 2.6 µmol·L-1 and Vmax = 286.8 ± 53.6 pmol/mg protein/min). Monocrotaline was determined to be a substrate of both OCT1 (Km = 109.1 ± 17.8 µmol·L-1, Vmax = 576.5 ± 87.5 pmol/mg protein/min) and OCT2 (Km = 64.7 ± 14.8 µmol·L-1, Vmax = 180.7 ± 22.0 pmol/mg protein/min), other than OCT3 and MATE transporters. The results indicated that OCT2 may be important for renal elimination of anisodine and OCT1 was responsible for monocrotaline uptake into liver. However neither MATE1 nor MATE2-K could facilitate transcellular transport of anisodine and monocrotaline. Accumulation of these drugs in the organs with high OCT1 expression (liver) and OCT2 expression (kidney) may be expected.

Mindfulness-based relapse prevention combined with virtual reality cue exposure for methamphetamine use disorder: Study protocol for a randomized controlled trial.

BACKGROUND: Mindfulness-based relapse prevention (MBRP) is a method that combines cognitive behavioral relapse prevention with mindfulness practice. Research suggests that MBRP can effectively reduce withdrawal/craving in people with substance use disorder (SUD). An important part of MBRP is to practice mindfulness meditation to cope with high-risk situations for relapse, such as stimuli and situations associated with drug taking. Virtual reality cue exposure (VRCE) may be a complementary approach to MBRP as it allows for controlled and graded presentations of various high-risk situations with distal and proximal drug cues. The aim of the study is to investigate the effects of MBRP combined with VRCE, in comparison to MBRP alone or treatment as usual, on craving and emotional responses in people with methamphetamine use disorders. METHOD/DESIGN: The study is a parallel randomized controlled study including 180 participants with methamphetamine use disorder. Three parallel groups will receive 8 weeks of MBRP combined with VRCE, MBRP alone, or treatment as usual, respectively. Craving, virtual cue reactivity, anxiety, depression, emotion regulation, mindfulness and drug-related attention bias will be assessed at pre-treatment, post-treatment, and 3 and 6 months of follow-up. DISCUSSION: This innovative study aims at investigating the effects of MBRP combined with VRCE in people with SUD. The combined intervention may have important clinical implications for relapse prevention due to its ease of application and high cost-effectiveness. This study may also stimulate research on the neuronal and psychological mechanisms of MBRP in substance use disorder. TRIAL REGISTRATION NUMBER: ChiCTR-INR-17013041.

The effect of music therapy on cognitive functions in patients with dementia: a systematic review and meta-analysis.

OBJECTIVES: The aim of the present study was to meta-analyze the effect of music therapy (MT) on cognitive functions in patients with dementia. METHOD: A systematic literature search was performed in Medline, PsycINFO, Embase, CINAHL and RILM up to 8 September 2016. We included all randomized controlled trials that compared MT with standard care, or other non-musical types of intervention, evaluating cognitive outcomes in patients with dementia. Outcomes included global cognition, complex attention, executive function, learning and memory, language, and perceptual-motor skills. RESULTS: From 1089 potentially relevant records, 110 studies were assessed for eligibility, and 7 met the inclusion criteria, of which 6 contained appropriate data for meta-analysis (330 participants, mean age range 78.8-86.3). Overall, random-effects meta-analyses suggested no significant effects of MT on all outcomes. Subgroup analysis found evidence of a beneficial effect of active MT on global cognition (SMD = 0.29, 95% CI 0.02 to 0.57, p = 0.04). CONCLUSION: Despite the limited evidence of the present review, it is important to continue supporting MT as a complementary treatment for older adults with dementia. RCTs with larger sample sizes are needed to better elucidate the impact of MT on cognitive functions.

Music therapy for depression.

BACKGROUND: Depression is a highly prevalent mood disorder that is characterised by persistent low mood, diminished interest, and loss of pleasure. Music therapy may be helpful in modulating moods and emotions. An update of the 2008 Cochrane review was needed to improve knowledge on effects of music therapy for depression. OBJECTIVES: 1. To assess effects of music therapy for depression in people of any age compared with treatment as usual (TAU) and psychological, pharmacological, and/or other therapies.2. To compare effects of different forms of music therapy for people of any age with a diagnosis of depression. SEARCH METHODS: We searched the following databases: the Cochrane Common Mental Disorders Controlled Trials Register (CCMD-CTR; from inception to 6 May 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; to 17 June 2016); Thomson Reuters/Web of Science (to 21 June 2016); Ebsco/PsycInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, and PubMed (to 5 July 2016); the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, the National Guideline Clearing House, and OpenGrey (to 6 September 2016); and the Digital Access to Research Theses (DART)-Europe E-theses Portal, Open Access Theses and Dissertations, and ProQuest Dissertations and Theses Database (to 7 September 2016). We checked reference lists of retrieved articles and relevant systematic reviews and contacted trialists and subject experts for additional information when needed. We updated this search in August 2017 and placed potentially relevant studies in the "Awaiting classification" section; we will incorporate these into the next version of this review as appropriate. SELECTION CRITERIA: All randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing music therapy versus treatment as usual (TAU), psychological therapies, pharmacological therapies, other therapies, or different forms of music therapy for reducing depression. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias, and extracted data from all included studies. We calculated standardised mean difference (SMD) for continuous data and odds ratio (OR) for dichotomous data with 95% confidence intervals (CIs). We assessed heterogeneity using the I2 statistic. MAIN RESULTS: We included in this review nine studies involving a total of 421 participants, 411 of whom were included in the meta-analysis examining short-term effects of music therapy for depression. Concerning primary outcomes, we found moderate-quality evidence of large effects favouring music therapy and TAU over TAU alone for both clinician-rated depressive symptoms (SMD -0.98, 95% CI -1.69 to -0.27, 3 RCTs, 1 CCT, n = 219) and patient-reported depressive symptoms (SMD -0.85, 95% CI -1.37 to -0.34, 3 RCTs, 1 CCT, n = 142). Music therapy was not associated with more or fewer adverse events than TAU. Regarding secondary outcomes, music therapy plus TAU was superior to TAU alone for anxiety and functioning. Music therapy and TAU was not more effective than TAU alone for improved quality of life (SMD 0.32, 95% CI -0.17 to 0.80, P = 0.20, n = 67, low-quality evidence). We found no significant discrepancies in the numbers of participants who left the study early (OR 0.49, 95% CI 0.14 to 1.70, P = 0.26, 5 RCTs, 1 CCT, n = 293, moderate-quality evidence). Findings of the present meta-analysis indicate that music therapy added to TAU provides short-term beneficial effects for people with depression if compared to TAU alone. Additionally, we are uncertain about the effects of music therapy versus psychological therapies on clinician-rated depression (SMD -0.78, 95% CI -2.36 to 0.81, 1 RCT, n = 11, very low-quality evidence), patient-reported depressive symptoms (SMD -1.28, 95% CI -3.75 to 1.02, 4 RCTs, n = 131, low-quality evidence), quality of life (SMD -1.31, 95% CI - 0.36 to 2.99, 1 RCT, n = 11, very low-quality evidence), and leaving the study early (OR 0.17, 95% CI 0.02 to 1.49, 4 RCTs, n = 157, moderate-quality evidence). We found no eligible evidence addressing adverse events, functioning, and anxiety. We do not know whether one form of music therapy is better than another for clinician-rated depressive symptoms (SMD -0.52, 95% CI -1.87 to 0.83, 1 RCT, n = 9, very low-quality evidence), patient-reported depressive symptoms (SMD -0.01, 95% CI -1.33 to 1.30, 1 RCT, n = 9, very low-quality evidence), quality of life (SMD -0.24, 95% CI -1.57 to 1.08, 1 RCT, n = 9, very low-quality evidence), or leaving the study early (OR 0.27, 95% CI 0.01 to 8.46, 1 RCT, n = 10). We found no eligible evidence addressing adverse events, functioning, or anxiety. AUTHORS' CONCLUSIONS: Findings of the present meta-analysis indicate that music therapy provides short-term beneficial effects for people with depression. Music therapy added to treatment as usual (TAU) seems to improve depressive symptoms compared with TAU alone. Additionally, music therapy plus TAU is not associated with more or fewer adverse events than TAU alone. Music therapy also shows efficacy in decreasing anxiety levels and improving functioning of depressed individuals.Future trials based on adequate design and larger samples of children and adolescents are needed to consolidate our findings. Researchers should consider investigating mechanisms of music therapy for depression. It is important to clearly describe music therapy, TAU, the comparator condition, and the profession of the person who delivers the intervention, for reproducibility and comparison purposes.

Music therapy for people with schizophrenia and schizophrenia-like disorders.

BACKGROUND: Music therapy is a therapeutic approach that uses musical interaction as a means of communication and expression. Within the area of serious mental disorders, the aim of the therapy is to help people improve their emotional and relational competencies, and address issues they may not be able to using words alone. OBJECTIVES: To review the effects of music therapy, or music therapy added to standard care, compared with placebo therapy, standard care or no treatment for people with serious mental disorders such as schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Study-Based Register (December 2010 and 15 January, 2015) and supplemented this by contacting relevant study authors, handsearching of music therapy journals and manual searches of reference lists. SELECTION CRITERIA: All randomised controlled trials (RCTs) that compared music therapy with standard care, placebo therapy, or no treatment. DATA COLLECTION AND ANALYSIS: Review authors independently selected, quality assessed and data extracted studies. We excluded data where more than 30% of participants in any group were lost to follow-up. We synthesised non-skewed continuous endpoint data from valid scales using a standardised mean difference (SMD). We employed a fixed-effect model for all analyses. If statistical heterogeneity was found, we examined treatment dosage (i.e. number of therapy sessions) and treatment approach as possible sources of heterogeneity. MAIN RESULTS: Ten new studies have been added to this update; 18 studies with a total 1215 participants are now included. These examined effects of music therapy over the short, medium, and long-term, with treatment dosage varying from seven to 240 sessions. Overall, most information is from studies at low or unclear risk of biasA positive effect on global state was found for music therapy compared to standard care (medium term, 2 RCTs, n = 133, RR 0.38 95% confidence interval (CI) 0.24 to 0.59, low-quality evidence, number needed to treat for an additional beneficial outcome NNTB 2, 95% CI 2 to 4). No binary data were available for other outcomes. Medium-term continuous data identified good effects for music therapy on negative symptoms using the Scale for the Assessment of Negative Symptoms (3 RCTs, n = 177, SMD - 0.55 95% CI -0.87 to -0.24, low-quality evidence). General mental state endpoint scores on the Positive and Negative Symptoms Scale were better for music therapy (2 RCTs, n = 159, SMD -0.97 95% CI -1.31 to -0.63, low-quality evidence), as were average endpoint scores on the Brief Psychiatric Rating Scale (1 RCT, n = 70, SMD -1.25 95% CI -1.77 to -0.73, moderate-quality evidence). Medium-term average endpoint scores using the Global Assessment of Functioning showed no effect for music therapy on general functioning (2 RCTs, n = 118, SMD -0.19 CI -0.56 to 0.18, moderate-quality evidence). However, positive effects for music therapy were found for both social functioning (Social Disability Screening Schedule scores; 2 RCTs, n = 160, SMD -0.72 95% CI -1.04 to -0.40), and quality of life (General Well-Being Schedule scores: 1 RCT, n = 72, SMD 1.82 95% CI 1.27 to 2.38, moderate-quality evidence). There were no data available for adverse effects, service use, engagement with services, or cost. AUTHORS' CONCLUSIONS: Moderate- to low-quality evidence suggests that music therapy as an addition to standard care improves the global state, mental state (including negative and general symptoms), social functioning, and quality of life of people with schizophrenia or schizophrenia-like disorders. However, effects were inconsistent across studies and depended on the number of music therapy sessions as well as the quality of the music therapy provided. Further research should especially address the long-term effects of music therapy, dose-response relationships, as well as the relevance of outcome measures in relation to music therapy.

Randomized Trial of Group Music Therapy With Chinese Prisoners: Impact on Anxiety, Depression, and Self-Esteem.

This study investigated the effects of group music therapy on improving anxiety, depression, and self-esteem in Chinese prisoners. Two-hundred male prisoners were randomly assigned to music therapy (n = 100) or standard care (n = 100). The music therapy had 20 sessions of group therapy compared with standard care. Anxiety (State and Trait Anxiety Inventory [STAI]), depression (Beck Depression Inventory [BDI]), and self-esteem (Texas Social Behavior Inventory [TSBI], Rosenberg Self-Esteem Inventory [RSI]) were measured by standardized scales at baseline, mid-program, and post-program. Data were analyzed based on the intention to treat principle. Compared with standard care, anxiety and depression in the music therapy condition decreased significantly at mid-test and post-test; self-esteem improved significantly at mid-test (TSBI) and at post-test (TSBI, RSI). Improvements were greater in younger participants (STAI-Trait, RSI) and/or in those with a lower level of education (STAI-State, STAI-Trait). Group music therapy seems to be effective in improving anxiety, depression, and self-esteem and was shown to be most beneficial for prisoners of younger age or with lower education level.

Pharmacokinetics of acteoside following single dose intragastric and intravenous administrations in dogs.

Acteoside (verbascoside), a phenylethanoid glycoside widely distributed in various plants, has been shown to have potential activity against Alzheimer's disease, attracting great attentions recently. The present study was designed to develop a selective and sensitive LC-MS/MS method for the determination of acteoside in biological samples and carry our a pharmacokinetic (PK) study in beagle dogs. The PK parameters were calculated using non-compartmental models. Following a single-dose oral administration, acteoside was rapidly absorbed and eliminated, with Tmax being between 30 to 45 min and terminal half-life being about 90 min. The areas under the time-concentration curve (AUC) were 47.28 ± 8.74, 87.86 ± 13.33, and 183.14 ± 28.69 mg · min · L(-1) for oral administration of 10, 20, and 40 mg · kg(-1), respectively, demonstrating that the exposure of acteoside proportionally increased with the dose level. The absolute bioavailability of acteoside was around 4%. For all the PK parameters, there were large variations between individual dogs. In conclusion, the pharmacokinetic characteristics observed in the present study can be of great value to help better understand the pharmacological properties of acteoside and to improve the outcome of its clinical use.

Influence of rifampicin on the pharmacokinetics of salvianolic acid B may involve inhibition of organic anion transporting polypeptide (Oatp) mediated influx.

This article studied the possible effect of rifampicin (RIF), an inhibitor of organic anion transporting polypeptide (Oatp), on the pharmacokinetics of salvianolic acid B (SAB) in rats. Rifampicin was administered intravenously 15 min prior to SAB (5 mg/kg) in rats at doses of 0, 5.0, 10.0 and 20.0 mg/kg, respectively. The concentrations of SAB in plasma and bile were determined using a Shimadzu HPLC system coupled to a LC-MS-2010EV mass spectrometer. Compared with the control group, the AUC(0-t) and C(max) values of SAB were increased significantly, while the CL(total) and CL(bile) were decreased significantly. These results suggested that pretreatment with rifampicin prior to SAB administration could decrease significantly the total and bile elimination of SAB and alter its pharmacokinetic profiles. The influence of rifampicin on the pharmacokinetics of SAB may be attributed to the inhibition of Oatp-mediated influx.

Simultaneous determination of six phenolic constituents of Danshen injection in rat plasma by LC-ESI-MS and its application to a pharmacokinetic study.

Salvianolic acid A, salvianolic acid B, danshensu, protocatechuic aldehyde, rosmarinic acid and lithospermic acid are the six major active constituents in Danshen injection. In this study, a rapid, sensitive and specific liquid chromatographic-electrospray ionization-mass spectrometry method for the simultaneous quantitative determination of these compounds in rat plasma was developed. After a single step of liquid-liquid extraction with ethyl acetate, they were eluted by a Hypersil C18 column (5 µm, i.d. 4.6 × 200 mm) within 4 min with a mobile phase consisting of acetonitrile and 0.1% formic acid water solution (35:65, v/v). The assay was linear in the concentration range of 0.05-10 µg mL(-1). Absolute recoveries were above 60%. The precisions and accuracies determined within three consecutive days were within acceptable limits. The method was successfully applied to a pharmacokinetic study in rats after an intravenous administration of Danshen injection.

[Effect of cyclosporine A on the pharmacokinetics of ginkgolide B in rats].

The paper is aimed to investigate the effect of cyclosporine A (CyA) on the pharmacokinetics of ginkgolide B (GB) in rats, and to look for the mechanism of the changes in pharmacokinetic behaviors of GB. GB concentration in plasma, brain homogenate and urine samples of rats was determined by LC-MS. Effects of CyA on plasma levels, brain distributions as well as urinary excretions after intravenous administration of GB were evaluated. CyA co administrated intravenously at 10 mg kg(-1) or 20 mg kg(-1) significantly increased AUC(0-360 min) (P < 0.01) and decreased total CL of GB in rats. While co administrated CYP3A inhibitor itraconazole (ICZ) has no appreciable effect on the pharmacokinetic behavior of GB. CyA increased the brain uptake of GB in a dose-dependent manner. The brain distribution of GB was significantly increased at 5 min by different doses of CyA (P < 0.001), while at 20 and 60 min only high dose of CyA could significantly increase the levels of GB in the brain (P < 0.01 and P < 0.001). Different P-gp inhibitors CyA or verapamil (VER) or digoxin (DGX) decreased the urinary GB excretion, the urinary excretion of GB in 0-8 h were about 34.8% (P < 0.001), 59.4% (P < 0.001) and 79.7% (P < 0.05) of the control, separately. No appreciable effect of ICZ was observed on urinary excretion of GB. Coadministration of P-gp inhibitors CyA could significantly increase the plasma level, accelerate the brain distribution and decrease the urinary excretion of GB.

[Study of pharmacokinetics of aristolochic acid I and II in rats].

OBJECTIVE: To develop an HPLC method for determination of the plasma concentration of aristolochic acid I (AA I ) and aristolochic acid II (AA II) and study their pharmacokinetics in rats. METHOD: The plasma samples were extracted with acetonitrile. The analysis involved a C18 column as stationary phase and methanol, water and acetic acid as mobile phase. The flow rate was 1.0 mL min(-1), the UV detection wavelength was 315 nm. After a single intravenous dose of 5 mg kg(-1) AA in rats, the pharmacokinetic parameters were estimated. RESULT: The calibration curve of AA I was linear over the range from 0.056 mg L(-1) to 56.3 mg L(-1) with a correlation coefficient of 0.9997. The mean recovery rate was 88.7%. The RSD of within-day and between-day were all less than 8%. And the calibration curve of AA II was linear over the range from 0.192 mg L(-1) to 11.52 mg L(-1) with a correlation coefficient of 0. 998 9. The mean recovery was 85.8%. The RSD of within-day was less than 3% and between-day was less than 10%. The main pharmacokinetic parameters were estimated to be as follows: CL = (0.010 +/- 0.003) L min(-1) kg(-1), t(1/2alpha) = (8.2 +/- 1.7) min, t(1/2beta) = (79.6 +/- 28.5) min for AA I; CL = (0.003 +/- 0.001) L min(-1) kg (-1), t(1/2alpha) = (56.7 +/- 38.1) min, t(1/2beta) = (209.3 +/- 37.9) min for AA II. CONCLUSION: The established HPLC method is simple and sensitive to determine the concentration of AA I , AA II and the metabolite of AA I in rat plasma. From the result of animal's test, we can find that AA I was quickly eliminated from plasma, the elimination of AA II and Aristololactam-the metabolite of AA I - were slower than that of AA I.