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Molecular Psychiatry Aug 2023The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin... (Meta-Analysis)
Meta-Analysis
The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use (n = 1869). Two meta-analyses of overlapping studies examining the 5-HT receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers (n = 566), but weak evidence of an effect in those with a family history of depression (n = 75). Another systematic review (n = 342) and a sample of ten subsequent studies (n = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study (n = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.
Topics: Humans; Depression; Serotonin; Receptor, Serotonin, 5-HT1A; Tryptophan; Hydroxyindoleacetic Acid; Antidepressive Agents; Serotonin Plasma Membrane Transport Proteins
PubMed: 35854107
DOI: 10.1038/s41380-022-01661-0 -
The Cochrane Database of Systematic... May 2022Social interaction and social communication are among the central areas of difficulty for autistic people. Music therapy uses music experiences and the relationships... (Review)
Review
BACKGROUND
Social interaction and social communication are among the central areas of difficulty for autistic people. Music therapy uses music experiences and the relationships that develop through them to enable communication and expression, thus attempting to address some of the core problems of autistic people. Music therapy has been applied in autism since the early 1950s, but its availability to autistic individuals varies across countries and settings. The application of music therapy requires specialised academic and clinical training which enables therapists to tailor the intervention to the specific needs of the individual. The present version of this review on music therapy for autistic people is an update of the previous Cochrane review update published in 2014 (following the original Cochrane review published in 2006).
OBJECTIVES
To review the effects of music therapy, or music therapy added to standard care, for autistic people.
SEARCH METHODS
In August 2021, we searched CENTRAL, MEDLINE, Embase, eleven other databases and two trials registers. We also ran citation searches, checked reference lists, and contacted study authors to identify additional studies.
SELECTION CRITERIA
All randomised controlled trials (RCTs), quasi-randomised trials and controlled clinical trials comparing music therapy (or music therapy alongside standard care) to 'placebo' therapy, no treatment, or standard care for people with a diagnosis of autism spectrum disorder were considered for inclusion.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. Four authors independently selected studies and extracted data from all included studies. We synthesised the results of included studies in meta-analyses. Four authors independently assessed risk of bias (RoB) of each included study using the original RoB tool as well as the certainty of evidence using GRADE. MAIN RESULTS: We included 16 new studies in this update which brought the total number of included studies to 26 (1165 participants). These studies examined the short- and medium-term effect of music therapy (intervention duration: three days to eight months) for autistic people in individual or group settings. More than half of the studies were conducted in North America or Asia. Twenty-one studies included children aged from two to 12 years. Five studies included children and adolescents, and/or young adults. Severity levels, language skills, and cognition were widely variable across studies. Measured immediately post-intervention, music therapy compared with 'placebo' therapy or standard care was more likely to positively effect global improvement (risk ratio (RR) 1.22, 95% confidence interval (CI) 1.06 to 1.40; 8 studies, 583 participants; moderate-certainty evidence; number needed to treat for an additional beneficial outcome (NNTB) = 11 for low-risk population, 95% CI 6 to 39; NNTB = 6 for high-risk population, 95% CI 3 to 21) and to slightly increase quality of life (SMD 0.28, 95% CI 0.06 to 0.49; 3 RCTs, 340 participants; moderate-certainty evidence, small to medium effect size). In addition, music therapy probably results in a large reduction in total autism symptom severity (SMD -0.83, 95% CI -1.41 to -0.24; 9 studies, 575 participants; moderate-certainty evidence). No clear evidence of a difference between music therapy and comparison groups at immediately post-intervention was found for social interaction (SMD 0.26, 95% CI -0.05 to 0.57, 12 studies, 603 participants; low-certainty evidence); non-verbal communication (SMD 0.26, 95% CI -0.03 to 0.55; 7 RCTs, 192 participants; low-certainty evidence); and verbal communication (SMD 0.30, 95% CI -0.18 to 0.78; 8 studies, 276 participants; very low-certainty evidence). Two studies investigated adverse events with one (36 participants) reporting no adverse events; the other study found no differences between music therapy and standard care immediately post-intervention (RR 1.52, 95% CI 0.39 to 5.94; 1 study, 290 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: The findings of this updated review provide evidence that music therapy is probably associated with an increased chance of global improvement for autistic people, likely helps them to improve total autism severity and quality of life, and probably does not increase adverse events immediately after the intervention. The certainty of the evidence was rated as 'moderate' for these four outcomes, meaning that we are moderately confident in the effect estimate. No clear evidence of a difference was found for social interaction, non-verbal communication, and verbal communication measured immediately post-intervention. For these outcomes, the certainty of the evidence was rated as 'low' or 'very low', meaning that the true effect may be substantially different from these results. Compared with earlier versions of this review, the new studies included in this update helped to increase the certainty and applicability of this review's findings through larger sample sizes, extended age groups, longer periods of intervention and inclusion of follow-up assessments, and by predominantly using validated scales measuring generalised behaviour (i.e. behaviour outside of the therapy context). This new evidence is important for autistic individuals and their families as well as for policymakers, service providers and clinicians, to help in decisions around the types and amount of intervention that should be provided and in the planning of resources. The applicability of the findings is still limited to the age groups included in the studies, and no direct conclusions can be drawn about music therapy in autistic individuals above the young adult age. More research using rigorous designs, relevant outcome measures, and longer-term follow-up periods is needed to corroborate these findings and to examine whether the effects of music therapy are enduring.
Topics: Adolescent; Autistic Disorder; Bias; Child; Humans; Music Therapy; Odds Ratio; Quality of Life
PubMed: 35532041
DOI: 10.1002/14651858.CD004381.pub4 -
Journal of Clinical Medicine Jul 2019Depression is commonly treated with anti-depressant medication and/or psychological interventions. Patients with depression are common users of complementary therapies,... (Review)
Review
BACKGROUND
Depression is commonly treated with anti-depressant medication and/or psychological interventions. Patients with depression are common users of complementary therapies, such as acupuncture, either as a replacement for, or adjunct to, their conventional treatments. This systematic review and meta-analysis examined the effectiveness of acupuncture in major depressive disorder.
METHODS
A search of English (Medline, PsychINFO, Google Scholar, and CINAL), Chinese (China National Knowledge Infrastructure Database (CNKI) and Wanfang Database), and Korean databases was undertaken from 1980 to November 2018 for clinical trials using manual, electro, or laser acupuncture.
RESULTS
Twenty-nine studies including 2268 participants were eligible and included in the meta-analysis. Twenty-two trials were undertaken in China and seven outside of China. Acupuncture showed clinically significant reductions in the severity of depression compared to usual care (Hedges (g) = 0.41, 95% confidence interval (CI) 0.18 to 0.63), sham acupuncture (g = 0.55, 95% CI 0.31 to 0.79), and as an adjunct to anti-depressant medication (g = 0.84, 95% CI 0.61 to 1.07). A significant correlation between an increase in the number of acupuncture treatments delivered and reduction in the severity of depression ( = 0.015) was found.
LIMITATIONS
The majority of the included trials were at a high risk of bias for performance blinding. The applicability of findings in Chinese populations to other populations is unclear, due to the use of a higher treatment frequency and number of treatments in China. The majority of trials did not report any post-trial follow-up and safety reporting was poor.
CONCLUSIONS
Acupuncture may be a suitable adjunct to usual care and standard anti-depressant medication.
PubMed: 31370200
DOI: 10.3390/jcm8081140 -
PloS One 2019Medical-related professions are at high suicide risk. However, data are contradictory and comparisons were not made between gender, occupation and specialties, epochs of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Medical-related professions are at high suicide risk. However, data are contradictory and comparisons were not made between gender, occupation and specialties, epochs of times. Thus, we conducted a systematic review and meta-analysis on suicide risk among health-care workers.
METHOD
The PubMed, Cochrane Library, Science Direct and Embase databases were searched without language restriction on April 2019, with the following keywords: suicide* AND (« health care worker* » OR physician* OR nurse*). When possible, we stratified results by gender, countries, time, and specialties. Estimates were pooled using random-effect meta-analysis. Differences by study-level characteristics were estimated using stratified meta-analysis and meta-regression. Suicides, suicidal attempts, and suicidal ideation were retrieved from national or local specific registers or case records. In addition, suicide attempts and suicidal ideation were also retrieved from questionnaires (paper or internet).
RESULTS
The overall SMR for suicide in physicians was 1.44 (95CI 1.16, 1.72) with an important heterogeneity (I2 = 93.9%, p<0.001). Female were at higher risk (SMR = 1.9; 95CI 1.49, 2.58; and ES = 0.67; 95CI 0.19, 1.14; p<0.001 compared to male). US physicians were at higher risk (ES = 1.34; 95CI 1.28, 1.55; p <0.001 vs Rest of the world). Suicide decreased over time, especially in Europe (ES = -0.18; 95CI -0.37, -0.01; p = 0.044). Some specialties might be at higher risk such as anesthesiologists, psychiatrists, general practitioners and general surgeons. There were 1.0% (95CI 1.0, 2.0; p<0.001) of suicide attempts and 17% (95CI 12, 21; p<0.001) of suicidal ideation in physicians. Insufficient data precluded meta-analysis on other health-care workers.
CONCLUSION
Physicians are an at-risk profession of suicide, with women particularly at risk. The rate of suicide in physicians decreased over time, especially in Europe. The high prevalence of physicians who committed suicide attempt as well as those with suicidal ideation should benefits for preventive strategies at the workplace. Finally, the lack of data on other health-care workers suggest to implement studies investigating those occupations.
Topics: Health Personnel; Humans; Physicians; Risk Factors; Suicide
PubMed: 31830138
DOI: 10.1371/journal.pone.0226361 -
BJPsych Open Apr 2023There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders. (Review)
Review
BACKGROUND
There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders.
AIMS
To conduct a systematic review and narrative synthesis of low carbohydrate and ketogenic diets (LC/KD) in adults with mood and anxiety disorders.
METHOD
MEDLINE, Embase, PsycINFO and Cochrane databases were systematically searched for articles from inception to 6 September 2022. Studies that included adults with any mood or anxiety disorder treated with a low carbohydrate or ketogenic intervention, reporting effects on mood or anxiety symptoms were eligible for inclusion. PROSPERO registration CRD42019116367.
RESULTS
The search yielded 1377 articles, of which 48 were assessed for full-text eligibility. Twelve heterogeneous studies (stated as ketogenic interventions, albeit with incomplete carbohydrate reporting and measurements of ketosis; diet duration: 2 weeks to 3 years; = 389; age range 19 to 75 years) were included in the final analysis. This included nine case reports, two cohort studies and one observational study. Data quality was variable, with no high-quality evidence identified. Efficacy, adverse effects and discontinuation rates were not systematically reported. There was some evidence for efficacy of ketogenic diets in those with bipolar disorder, schizoaffective disorder and possibly unipolar depression/anxiety. Relapse after discontinuation of the diet was reported in some individuals.
CONCLUSIONS
Although there is no high-quality evidence of LC/KD efficacy in mood or anxiety disorders, several uncontrolled studies suggest possible beneficial effects. Robust studies are now needed to demonstrate efficacy, to identify clinical groups who may benefit and whether a ketogenic diet (beyond low carbohydrate) is required and to characterise adverse effects and the risk of relapse after diet discontinuation.
PubMed: 37066662
DOI: 10.1192/bjo.2023.36 -
The Cochrane Database of Systematic... May 2023Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain antidepressants may be effective in reducing pain with some benefit in improving patients' global impression of change for certain chronic pain conditions. However, there has not been a network meta-analysis (NMA) examining all antidepressants across all chronic pain conditions.
OBJECTIVES
To assess the comparative efficacy and safety of antidepressants for adults with chronic pain (except headache).
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, AMED and PsycINFO databases, and clinical trials registries, for randomised controlled trials (RCTs) of antidepressants for chronic pain conditions in January 2022.
SELECTION CRITERIA
We included RCTs that examined antidepressants for chronic pain against any comparator. If the comparator was placebo, another medication, another antidepressant, or the same antidepressant at different doses, then we required the study to be double-blind. We included RCTs with active comparators that were unable to be double-blinded (e.g. psychotherapy) but rated them as high risk of bias. We excluded RCTs where the follow-up was less than two weeks and those with fewer than 10 participants in each arm. DATA COLLECTION AND ANALYSIS: Two review authors separately screened, data extracted, and judged risk of bias. We synthesised the data using Bayesian NMA and pairwise meta-analyses for each outcome and ranked the antidepressants in terms of their effectiveness using the surface under the cumulative ranking curve (SUCRA). We primarily used Confidence in Meta-Analysis (CINeMA) and Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) to assess the certainty of the evidence. Where it was not possible to use CINeMA and ROB-MEN due to the complexity of the networks, we used GRADE to assess the certainty of the evidence. Our primary outcomes were substantial (50%) pain relief, pain intensity, mood, and adverse events. Our secondary outcomes were moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change (PGIC), serious adverse events, and withdrawal.
MAIN RESULTS
This review and NMA included 176 studies with a total of 28,664 participants. The majority of studies were placebo-controlled (83), and parallel-armed (141). The most common pain conditions examined were fibromyalgia (59 studies); neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of RCTs was 10 weeks. Seven studies provided no useable data and were omitted from the NMA. The majority of studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. In duloxetine studies, standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that of duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Primary efficacy outcomes Duloxetine standard dose (60 mg) showed a small to moderate effect for substantial pain relief (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.69 to 2.17; 16 studies, 4490 participants; moderate-certainty evidence) and continuous pain intensity (standardised mean difference (SMD) -0.31, 95% CI -0.39 to -0.24; 18 studies, 4959 participants; moderate-certainty evidence). For pain intensity, milnacipran standard dose (100 mg) also showed a small effect (SMD -0.22, 95% CI -0.39 to 0.06; 4 studies, 1866 participants; moderate-certainty evidence). Mirtazapine (30 mg) had a moderate effect on mood (SMD -0.5, 95% CI -0.78 to -0.22; 1 study, 406 participants; low-certainty evidence), while duloxetine showed a small effect (SMD -0.16, 95% CI -0.22 to -0.1; 26 studies, 7952 participants; moderate-certainty evidence); however it is important to note that most studies excluded participants with mental health conditions, and so average anxiety and depression scores tended to be in the 'normal' or 'subclinical' ranges at baseline already. Secondary efficacy outcomes Across all secondary efficacy outcomes (moderate pain relief, physical function, sleep, quality of life, and PGIC), duloxetine and milnacipran were the highest-ranked antidepressants with moderate-certainty evidence, although effects were small. For both duloxetine and milnacipran, standard doses were as efficacious as high doses. Safety There was very low-certainty evidence for all safety outcomes (adverse events, serious adverse events, and withdrawal) across all antidepressants. We cannot draw any reliable conclusions from the NMAs for these outcomes.
AUTHORS' CONCLUSIONS
Our review and NMAs show that despite studies investigating 25 different antidepressants, the only antidepressant we are certain about for the treatment of chronic pain is duloxetine. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Evidence for all other antidepressants was low certainty. As RCTs excluded people with low mood, we were unable to establish the effects of antidepressants for people with chronic pain and depression. There is currently no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for the safety of antidepressants for chronic pain at any time point.
Topics: Adult; Humans; Antidepressive Agents; Chronic Pain; Duloxetine Hydrochloride; Milnacipran; Network Meta-Analysis; Pain Management; Randomized Controlled Trials as Topic
PubMed: 37160297
DOI: 10.1002/14651858.CD014682.pub2 -
The Cochrane Database of Systematic... Mar 2023Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children and adolescents... (Review)
Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children and adolescents with ADHD find it difficult to pay attention and they are hyperactive and impulsive. Methylphenidate is the psychostimulant most often prescribed, but the evidence on benefits and harms is uncertain. This is an update of our comprehensive systematic review on benefits and harms published in 2015.
OBJECTIVES
To assess the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, three other databases and two trials registers up to March 2022. In addition, we checked reference lists and requested published and unpublished data from manufacturers of methylphenidate.
SELECTION CRITERIA
We included all randomised clinical trials (RCTs) comparing methylphenidate versus placebo or no intervention in children and adolescents aged 18 years and younger with a diagnosis of ADHD. The search was not limited by publication year or language, but trial inclusion required that 75% or more of participants had a normal intellectual quotient (IQ > 70). We assessed two primary outcomes, ADHD symptoms and serious adverse events, and three secondary outcomes, adverse events considered non-serious, general behaviour, and quality of life.
DATA COLLECTION AND ANALYSIS
Two review authors independently conducted data extraction and risk of bias assessment for each trial. Six review authors including two review authors from the original publication participated in the update in 2022. We used standard Cochrane methodological procedures. Data from parallel-group trials and first-period data from cross-over trials formed the basis of our primary analyses. We undertook separate analyses using end-of-last period data from cross-over trials. We used Trial Sequential Analyses (TSA) to control for type I (5%) and type II (20%) errors, and we assessed and downgraded evidence according to the GRADE approach.
MAIN RESULTS
We included 212 trials (16,302 participants randomised); 55 parallel-group trials (8104 participants randomised), and 156 cross-over trials (8033 participants randomised) as well as one trial with a parallel phase (114 participants randomised) and a cross-over phase (165 participants randomised). The mean age of participants was 9.8 years ranging from 3 to 18 years (two trials from 3 to 21 years). The male-female ratio was 3:1. Most trials were carried out in high-income countries, and 86/212 included trials (41%) were funded or partly funded by the pharmaceutical industry. Methylphenidate treatment duration ranged from 1 to 425 days, with a mean duration of 28.8 days. Trials compared methylphenidate with placebo (200 trials) and with no intervention (12 trials). Only 165/212 trials included usable data on one or more outcomes from 14,271 participants. Of the 212 trials, we assessed 191 at high risk of bias and 21 at low risk of bias. If, however, deblinding of methylphenidate due to typical adverse events is considered, then all 212 trials were at high risk of bias.
PRIMARY OUTCOMES
methylphenidate versus placebo or no intervention may improve teacher-rated ADHD symptoms (standardised mean difference (SMD) -0.74, 95% confidence interval (CI) -0.88 to -0.61; I² = 38%; 21 trials; 1728 participants; very low-certainty evidence). This corresponds to a mean difference (MD) of -10.58 (95% CI -12.58 to -8.72) on the ADHD Rating Scale (ADHD-RS; range 0 to 72 points). The minimal clinically relevant difference is considered to be a change of 6.6 points on the ADHD-RS. Methylphenidate may not affect serious adverse events (risk ratio (RR) 0.80, 95% CI 0.39 to 1.67; I² = 0%; 26 trials, 3673 participants; very low-certainty evidence). The TSA-adjusted intervention effect was RR 0.91 (CI 0.31 to 2.68).
SECONDARY OUTCOMES
methylphenidate may cause more adverse events considered non-serious versus placebo or no intervention (RR 1.23, 95% CI 1.11 to 1.37; I² = 72%; 35 trials 5342 participants; very low-certainty evidence). The TSA-adjusted intervention effect was RR 1.22 (CI 1.08 to 1.43). Methylphenidate may improve teacher-rated general behaviour versus placebo (SMD -0.62, 95% CI -0.91 to -0.33; I² = 68%; 7 trials 792 participants; very low-certainty evidence), but may not affect quality of life (SMD 0.40, 95% CI -0.03 to 0.83; I² = 81%; 4 trials, 608 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
The majority of our conclusions from the 2015 version of this review still apply. Our updated meta-analyses suggest that methylphenidate versus placebo or no-intervention may improve teacher-rated ADHD symptoms and general behaviour in children and adolescents with ADHD. There may be no effects on serious adverse events and quality of life. Methylphenidate may be associated with an increased risk of adverse events considered non-serious, such as sleep problems and decreased appetite. However, the certainty of the evidence for all outcomes is very low and therefore the true magnitude of effects remain unclear. Due to the frequency of non-serious adverse events associated with methylphenidate, the blinding of participants and outcome assessors is particularly challenging. To accommodate this challenge, an active placebo should be sought and utilised. It may be difficult to find such a drug, but identifying a substance that could mimic the easily recognised adverse effects of methylphenidate would avert the unblinding that detrimentally affects current randomised trials. Future systematic reviews should investigate the subgroups of patients with ADHD that may benefit most and least from methylphenidate. This could be done with individual participant data to investigate predictors and modifiers like age, comorbidity, and ADHD subtypes.
Topics: Male; Female; Child; Adolescent; Humans; Methylphenidate; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cross-Over Studies; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 36971690
DOI: 10.1002/14651858.CD009885.pub3 -
Journal of Cannabis Research Jan 2020The therapeutic application of cannabidiol (CBD) is gaining interest due to expanding evidence for its use. (Review)
Review
BACKGROUND
The therapeutic application of cannabidiol (CBD) is gaining interest due to expanding evidence for its use.
OBJECTIVE
To summarize the clinical outcomes, study designs and limitations for the use of CBD and nabiximols (whole plant extract from Cannabis sativa L. that has been purified into 1:1 ratio of CBD and delta-9-tetrahydrocannabinol) in the treatment of psychiatric disorders.
MATERIALS AND METHOD
A systematic review was conducted including case reports, case series, open-label trials, non-randomized and randomized controlled trials (RCTs). The search resulted in 23 relevant studies on CBD and nabiximols in the treatment of a wide range of psychiatric disorders. The quality of evidence was judged by using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence that ranges from Level 1 to Level 5 based on the quality and study design. These levels of evidence help in grading the recommendations, including Grade A (strong), Grade B (moderate), Grade C (weak), and Grade D (weakest).
RESULTS
CBD and CBD-containing compounds such as nabiximols were helpful in alleviating psychotic symptoms and cognitive impairment in patients with a variety of conditions, and several studies provided evidence of effectiveness in the treatment of cannabis withdrawal and moderate to severe cannabis use disorder with Grade B recommendation. There is Grade B recommendation supporting the use of CBD for the treatment of schizophrenia, social anxiety disorder and autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD). Grade C recommendation exists for insomnia, anxiety, bipolar disorder, posttraumatic stress disorder, and Tourette syndrome. These recommendations should be considered in the context of limited number of available studies.
CONCLUSION
CBD and CBD-containing compounds such as nabiximols were helpful in alleviating symptoms of cannabis-related disorders, schizophrenia, social anxiety disorder, and comorbidities of ASD, and ADHD with moderate recommendation. However, there is weaker evidence for insomnia, anxiety, bipolar disorder, posttraumatic stress disorder, and Tourette syndrome. The evidence for the use of CBD and CBD-containing compounds for psychiatric disorders needs to be explored in future studies, especially large-scale and well-designed RCTs.
PubMed: 33526132
DOI: 10.1186/s42238-019-0012-y -
The Cochrane Database of Systematic... Nov 2022Among people with a diagnosis of borderline personality disorder (BPD) who are engaged in clinical care, prescription rates of psychotropic medications are high, despite... (Review)
Review
BACKGROUND
Among people with a diagnosis of borderline personality disorder (BPD) who are engaged in clinical care, prescription rates of psychotropic medications are high, despite the fact that medication use is off-label as a treatment for BPD. Nevertheless, people with BPD often receive several psychotropic drugs at a time for sustained periods.
OBJECTIVES
To assess the effects of pharmacological treatment for people with BPD.
SEARCH METHODS
For this update, we searched CENTRAL, MEDLINE, Embase, 14 other databases and four trials registers up to February 2022. We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals. We did not restrict the search by year of publication, language or type of publication.
SELECTION CRITERIA
Randomised controlled trials comparing pharmacological treatment to placebo, other pharmacologic treatments or a combination of pharmacologic treatments in people of all ages with a formal diagnosis of BPD. The primary outcomes were BPD symptom severity, self-harm, suicide-related outcomes, and psychosocial functioning. Secondary outcomes were individual BPD symptoms, depression, attrition and adverse events.
DATA COLLECTION AND ANALYSIS
At least two review authors independently selected trials, extracted data, assessed risk of bias using Cochrane's risk of bias tool and assessed the certainty of the evidence using the GRADE approach. We performed data analysis using Review Manager 5 and quantified the statistical reliability of the data using Trial Sequential Analysis.
MAIN RESULTS
We included 46 randomised controlled trials (2769 participants) in this review, 45 of which were eligible for quantitative analysis and comprised 2752 participants with BPD in total. This is 18 more trials than the 2010 review on this topic. Participants were predominantly female except for one trial that included men only. The mean age ranged from 16.2 to 39.7 years across the included trials. Twenty-nine different types of medications compared to placebo or other medications were included in the analyses. Seventeen trials were funded or partially funded by the pharmaceutical industry, 10 were funded by universities or research foundations, eight received no funding, and 11 had unclear funding. For all reported effect sizes, negative effect estimates indicate beneficial effects by active medication. Compared with placebo, no difference in effects were observed on any of the primary outcomes at the end of treatment for any medication. Compared with placebo, medication may have little to no effect on BPD symptom severity, although the evidence is of very low certainty (antipsychotics: SMD -0.18, 95% confidence interval (CI) -0.45 to 0.08; 8 trials, 951 participants; antidepressants: SMD -0.27, 95% CI -0.65 to 1.18; 2 trials, 87 participants; mood stabilisers: SMD -0.07, 95% CI -0.43 to 0.57; 4 trials, 265 participants). The evidence is very uncertain about the effect of medication compared with placebo on self-harm, indicating little to no effect (antipsychotics: RR 0.66, 95% CI 0.15 to 2.84; 2 trials, 76 participants; antidepressants: MD 0.45 points on the Overt Aggression Scale-Modified-Self-Injury item (0-5 points), 95% CI -10.55 to 11.45; 1 trial, 20 participants; mood stabilisers: RR 1.08, 95% CI 0.79 to 1.48; 1 trial, 276 participants). The evidence is also very uncertain about the effect of medication compared with placebo on suicide-related outcomes, with little to no effect (antipsychotics: SMD 0.05, 95 % CI -0.18 to 0.29; 7 trials, 854 participants; antidepressants: SMD -0.26, 95% CI -1.62 to 1.09; 2 trials, 45 participants; mood stabilisers: SMD -0.36, 95% CI -1.96 to 1.25; 2 trials, 44 participants). Very low-certainty evidence shows little to no difference between medication and placebo on psychosocial functioning (antipsychotics: SMD -0.16, 95% CI -0.33 to 0.00; 7 trials, 904 participants; antidepressants: SMD -0.25, 95% CI -0.57 to 0.06; 4 trials, 161 participants; mood stabilisers: SMD -0.01, 95% CI -0.28 to 0.26; 2 trials, 214 participants). Low-certainty evidence suggests that antipsychotics may slightly reduce interpersonal problems (SMD -0.21, 95% CI -0.34 to -0.08; 8 trials, 907 participants), and that mood stabilisers may result in a reduction in this outcome (SMD -0.58, 95% CI -1.14 to -0.02; 4 trials, 300 participants). Antidepressants may have little to no effect on interpersonal problems, but the corresponding evidence is very uncertain (SMD -0.07, 95% CI -0.69 to 0.55; 2 trials, 119 participants). The evidence is very uncertain about dropout rates compared with placebo by antipsychotics (RR 1.11, 95% CI 0.89 to 1.38; 13 trials, 1216 participants). Low-certainty evidence suggests there may be no difference in dropout rates between antidepressants (RR 1.07, 95% CI 0.65 to 1.76; 6 trials, 289 participants) and mood stabilisers (RR 0.89, 95% CI 0.69 to 1.15; 9 trials, 530 participants), compared to placebo. Reporting on adverse events was poor and mostly non-standardised. The available evidence on non-serious adverse events was of very low certainty for antipsychotics (RR 1.07, 95% CI 0.90 to 1.29; 5 trials, 814 participants) and mood stabilisers (RR 0.84, 95% CI 0.70 to 1.01; 1 trial, 276 participants). For antidepressants, no data on adverse events were identified.
AUTHORS' CONCLUSIONS
This review included 18 more trials than the 2010 version, so larger meta-analyses with more statistical power were feasible. We found mostly very low-certainty evidence that medication may result in no difference in any primary outcome. The rest of the secondary outcomes were inconclusive. Very limited data were available for serious adverse events. The review supports the continued understanding that no pharmacological therapy seems effective in specifically treating BPD pathology. More research is needed to understand the underlying pathophysiologic mechanisms of BPD better. Also, more trials including comorbidities such as trauma-related disorders, major depression, substance use disorders, or eating disorders are needed. Additionally, more focus should be put on male and adolescent samples.
Topics: Humans; Adolescent; Male; Female; Young Adult; Adult; Borderline Personality Disorder; Reproducibility of Results; Antidepressive Agents; Depressive Disorder, Major; Antipsychotic Agents
PubMed: 36375174
DOI: 10.1002/14651858.CD012956.pub2 -
Patient Preference and Adherence 2022Nonadherence to medications is very common in people with schizophrenia. Numerous methods have been implemented to improve medication adherence. The study aimed to... (Review)
Review
Nonadherence to medications is very common in people with schizophrenia. Numerous methods have been implemented to improve medication adherence. The study aimed to determine what interventions have been used and to assess the effectiveness of these in improving medication adherence in people with schizophrenia. Two electronic databases (PubMed and Science Direct) and a manual search were used to locate RCT studies that examined interventions in medication adherence for schizophrenia, published between 2011 and 2022. The search was conducted using the terms (schizophrenia OR schizophrenic) AND (interventions OR adherence therapy) AND (medication adherence OR medication compliance). Sixteen studies were included, and relevant data were extracted and selected. Sixteen studies used interventions that involve family, health professionals (psychiatrists, psychologists, nurses, and pharmacists), SMS, and smart electronic reminders. Medication adherence was measured using medication refill records from hospital dispensing records or claim databases, electronic devices, plasma blood concentration, and participant self-reporting. Thirteen out of 15 studies showed significant improvements in adherence compared to routine care. The other three studies did not result in improved medication adherence. Interventions with diverse strategies delivered to individuals with schizophrenia showed the potential to reduce medication non-adherence in people with schizophrenia so that they can be utilized as an alternative to support treatment in people with schizophrenia in addition to antipsychotic medication. In future research strategies, it will be necessary to identify the main problems regarding nonadherence in people with schizophrenia individually and also identify the patient's perception of medication, illness, and behavior when taking medication in order to determine the next intervention that will be appropriate based on the patient's needs to improve adherence.
PubMed: 36072918
DOI: 10.2147/PPA.S378951