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Frontiers in Psychiatry 2024Unipolar and bipolar depression present treatment challenges, with patients sometimes showing limited or no response to standard medications. Ketamine and its...
BACKGROUND
Unipolar and bipolar depression present treatment challenges, with patients sometimes showing limited or no response to standard medications. Ketamine and its enantiomer, esketamine, offer promising alternative treatments that can quickly relieve suicidal thoughts. This Overview of Reviews (OoR) analyzed and synthesized systematic reviews (SRs) with meta-analysis on randomized clinical trials (RCTs) involving ketamine in various formulations (intravenous, intramuscular, intranasal, subcutaneous) for patients with unipolar or bipolar depression. We evaluated the efficacy and safety of ketamine and esketamine in treating major depressive episodes across various forms, including unipolar, bipolar, treatment-resistant, and non-resistant depression, in patient populations with and without suicidal ideation, aiming to comprehensively assess their therapeutic potential and safety profile.
METHODS
Following PRIOR guidelines, this OoR's protocol was registered on Implasy (ID:202150049). Searches in PubMed, Scopus, Cochrane Library, and Epistemonikos focused on English-language meta-analyses of RCTs of ketamine or esketamine, as monotherapy or add-on, evaluating outcomes like suicide risk, depressive symptoms, relapse, response rates, and side effects. We included studies involving both suicidal and non-suicidal patients; all routes and formulations of administration (intravenous, intramuscular, intranasal) were considered, as well as all available comparisons with control interventions. We excluded meta-analysis in which the intervention was used as anesthesia for electroconvulsive therapy or with a randomized ascending dose design. The selection, data extraction, and quality assessment of studies were carried out by pairs of reviewers in a blinded manner. Data on efficacy, acceptability, and tolerability were extracted.
RESULTS
Our analysis included 26 SRs and 44 RCTs, with 3,316 subjects. The intervention is effective and well-tolerated, although the quality of the included SRs and original studies is poor, resulting in low certainty of evidence.
LIMITATIONS
This study is limited by poor-quality SRs and original studies, resulting in low certainty of the evidence. Additionally, insufficient available data prevents differentiation between the effects of ketamine and esketamine in unipolar and bipolar depression.
CONCLUSION
While ketamine and esketamine show promising therapeutic potential, the current evidence suffers from low study quality. Enhanced methodological rigor in future research will allow for a more informed application of these interventions within the treatment guidelines for unipolar and bipolar depression.
SYSTEMATIC REVIEW REGISTRATION
[https://inplasy.com/inplasy-2021-5-0049/], identifier (INPLASY202150049).
PubMed: 38362031
DOI: 10.3389/fpsyt.2024.1325399 -
Clinical Pharmacology and Therapeutics Jul 2023The P-glycoprotein efflux pump, encoded by the ABCB1 gene, has been shown to alter concentrations of various antidepressants in the brain. In this study, we conducted a... (Meta-Analysis)
Meta-Analysis Review
The P-glycoprotein efflux pump, encoded by the ABCB1 gene, has been shown to alter concentrations of various antidepressants in the brain. In this study, we conducted a systematic review and meta-analysis to investigate the association between six ABCB1 single-nucleotide polymorphisms (SNPs; rs1045642, rs2032582, rs1128503, rs2032583, rs2235015, and rs2235040) and antidepressant treatment outcomes in individuals with major depressive disorder (MDD), including new data from the Canadian Biomarker and Integration Network for Depression (CAN-BIND-1) cohort. For the CAN-BIND-1 sample, we applied regression models to investigate the association between ABCB1 SNPs and antidepressant treatment response, remission, tolerability, and antidepressant serum levels. For the meta-analysis, we systematically summarized pharmacogenetic evidence of the association between ABCB1 SNPs and antidepressant treatment outcomes. Studies were included in the meta-analysis if they investigated at least one ABCB1 SNP in individuals with MDD treated with at least one antidepressant. We did not find a significant association between ABCB1 SNPs and antidepressant treatment outcomes in the CAN-BIND-1 sample. A total of 39 studies were included in the systematic review. In the meta-analysis, we observed a significant association between rs1128503 and treatment response (T vs. C-allele, odds ratio = 1.30, 95% confidence interval = 1.15-1.48, P value (adjusted) = 0.024, n = 2,526). We did not find associations among the six SNPs and treatment remission nor tolerability. Our findings provide limited evidence for an association between common ABCB1 SNPs and antidepressant outcomes, which do not support the implementation of ABCB1 genotyping to inform antidepressant treatment at this time. Future research, especially on rs1128503, is recommended.
Topics: Humans; Depressive Disorder, Major; Canada; Antidepressive Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biomarkers; Polymorphism, Single Nucleotide; Genotype; ATP Binding Cassette Transporter, Subfamily B
PubMed: 36681895
DOI: 10.1002/cpt.2854 -
Neuroscience and Biobehavioral Reviews Dec 2023This report aimed to compare group differences in social and non-social cognition in autism spectrum disorders (ASD) and schizophrenia, and examine the influence of age... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This report aimed to compare group differences in social and non-social cognition in autism spectrum disorders (ASD) and schizophrenia, and examine the influence of age and other factors on group differences.
METHODS
Literature searches were conducted in Pubmed and Web of Science from January 1980 to August 2022. Original research articles reporting objective measures of cognition were selected.
RESULTS
57 articles involving 1864 patients with schizophrenia and 1716 patients with ASD have been included. Schizophrenia was associated with more severe non-social-cognitive impairment, particularly in fluency (g=0.47;CI[0.17-0.76]) and processing speed domains (g=0.41;CI[0.20-0.62]). Poorer performance in social cognition (Z = 3.68,p = 0.0002) and non-social cognition (Z = 2.48,p = 0.01) in schizophrenia were significantly related to older age. ASD was associated with more severe social cognitive impairment when groups were matched for non-social-cognition (g=-0.18, p = 0.04) or reasoning/problem solving (g=-0,62; CI [-1,06-(-0.08)].
DISCUSSION
While both disorders present with social and non-social cognitive impairments, the pattern and developmental trajectories of these deficits are different. The limitations included heterogeneity of the cognitive measures, and the lack of sufficient information about antipsychotic use.
Topics: Humans; Schizophrenia; Autism Spectrum Disorder; Social Cognition; Social Perception; Cognitive Dysfunction; Cognition
PubMed: 37923237
DOI: 10.1016/j.neubiorev.2023.105441 -
Psychiatry Research May 2024Psychotherapies assisted by psychedelic substances have shown promising results in the treatment of psychiatric disorders. The aim of this systematic review and... (Meta-Analysis)
Meta-Analysis Review
Psychotherapies assisted by psychedelic substances have shown promising results in the treatment of psychiatric disorders. The aim of this systematic review and meta-analysis was to evaluate safety data in human subjects. We carried out a search on MEDLINE, Embase and PsycINFO databases between 2000 and 2022. Standardized mean differences between different dose ranges and between acute and subacute phases were calculated for cardiovascular data after psychedelic administration. Risk differences were calculated for serious adverse events and common side effects. Thirty studies were included in this meta-analysis. There were only nine serious adverse events for over 1000 administrations of psychedelic substances (one during the acute phase and 8 during the post-acute phase). There were no suicide attempts during the acute phase and 3 participants engaged in self-harm during the post-acute phase. There was an increased risk for elevated heart rate, systolic and diastolic blood pressure for all dose range categories, as well as an increased risk of nausea during the acute phase. Other common side effects included headaches, anxiety, and decreased concentration or appetite. This meta-analysis demonstrates that psychedelics are well-tolerated, with a low risk of emerging serious adverse events in a controlled setting with appropriate inclusion criteria.
Topics: Humans; Hallucinogens; Psychotherapy; Anxiety; Anxiety Disorders; Risk Assessment
PubMed: 38579460
DOI: 10.1016/j.psychres.2024.115880 -
BMJ Mental Health Oct 2023This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.
QUESTION
This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.
STUDY SELECTION AND ANALYSIS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and World Federation of Societies of Biological Psychiatry (WFSBP)-grading recommendations, 63 randomised control trials (RCTs) (of which 4219 unique participants have completed the RCTs) and 29 meta-analyses were analysed.
FINDINGS
Provisional recommendations (WFSBP-grade 1) could be made for two molecules in augmentation to antipsychotics: (1) N-acetyl-cysteine (NAC, 1200-3600 mg/day, for >12 consecutive weeks) in improving negative symptoms, general psychopathology (positive and negative syndrome scale for schizophrenia (PANSS) general psychopathology factor (G)-G subscale), with the RCTs with the longer duration showing the most robust findings; (2) polyunsaturated fatty acids (3000 mg/day of eicosapentaenoic acid, for >12 weeks) in improving general psychopathology. Weaker recommendations (ie, WFSBP-grade 2) could be drawn for sarcosine (2 g/day) and minocycline (200-300 mg/day) for improving negative symptoms in chronic schizophrenia (not early schizophrenia), and NAC for improving positive symptoms and cognition. Weak recommendations are not ready for clinical practice. There is provisional evidence that oestrogens and raloxifene are effective in some patients, but further research is needed to determine their benefit/risk ratio.
CONCLUSIONS
The results of this umbrella review should be interpreted with caution as the number of RCTs included in the meta-analyses was generally small and the effect sizes were weak or medium. For NAC, two RCTs with low risk of bias have provided conflicting results and the WFSBP-grade recommendation included also the results of meta-analyses. These drugs could be provisionally prescribed for patients for whom no other treatments have been effective, but they should be discontinued if they prove ineffective.
Topics: Humans; Acetylcysteine; Amino Acids; Anti-Inflammatory Agents; Antipsychotic Agents; Schizophrenia; Meta-Analysis as Topic; Randomized Controlled Trials as Topic
PubMed: 37852631
DOI: 10.1136/bmjment-2023-300771 -
Industrial Psychiatry Journal 2023Cannabis use has been stated as a causal risk factor for the occurrence of schizophrenia and other psychotic disorders. There is a dearth of literature stating the... (Review)
Review
Cannabis use has been stated as a causal risk factor for the occurrence of schizophrenia and other psychotic disorders. There is a dearth of literature stating the association of cannabis with bipolar disorder. This review aimed to find the repercussion of cannabis use on the onset of the first episode of bipolar disorder and the worsening of the symptoms in pre-existing illness. A thorough systematic review of the existing literature was carried out using the PRISMA guidelines. PubMed, Medline, EMBASE, SCOPUS, and Google-scholar databases were searched for studies fitting our study's inclusion and exclusion criteria. A total of 25 studies were included in the systematic review and out of these 25 studies, five prospective studies met the inclusion criteria for the primary outcome meta-analysis. A total sample of 13,624 individuals was included in these five studies. A fixed effect model was used in the meta-analysis of these five studies and it revealed an association between cannabis and bipolar disorder with an effect size of 2.63 (95% CI: 1.95-3.53) (heterogeneity: chi² = 3.01, df = 3 ( = 0.39); I = 0%). Our findings propose that cannabis use may precipitate or worsen bipolar disorder. This highlights the importance of the detrimental effect of cannabis use on bipolar disorder and the need to discourage cannabis use in the youth culture. High-quality prospective studies are required to delineate the effect of cannabis use on bipolar disorder.
PubMed: 38161465
DOI: 10.4103/ipj.ipj_43_23 -
Neuropsychopharmacology : Official... Mar 2024While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated.... (Meta-Analysis)
Meta-Analysis
While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated. Neuromodulation (NM) methods, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) may address SUDs by targeting addiction neurocircuitry. We evaluated the efficacy of NM to improve behavioral outcomes in SUDs. A systematic literature search was performed on MEDLINE, PsychINFO, and PubMed databases and a list of search terms for four key concepts (SUD, rTMS, tDCS, DBS) was applied. Ninety-four studies were identified that examined the effects of rTMS, tDCS, and DBS on substance use outcomes (e.g., craving, consumption, and relapse) amongst individuals with SUDs including alcohol, tobacco, cannabis, stimulants, and opioids. Meta-analyses were performed for alcohol and tobacco studies using rTMS and tDCS. We found that rTMS reduced substance use and craving, as indicated by medium to large effect sizes (Hedge's g > 0.5). Results were most encouraging when multiple stimulation sessions were applied, and the left dorsolateral prefrontal cortex (DLPFC) was targeted. tDCS also produced medium effect sizes for drug use and craving, though they were highly variable and less robust than rTMS; right anodal DLPFC stimulation appeared to be most efficacious. DBS studies were typically small, uncontrolled studies, but showed promise in reducing misuse of multiple substances. NM may be promising for the treatment of SUDs. Future studies should determine underlying neural mechanisms of NM, and further evaluate extended treatment durations, accelerated administration protocols and long-term outcomes with biochemical verification of substance use.
Topics: Humans; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation; Substance-Related Disorders; Behavior, Addictive; Craving; Prefrontal Cortex
PubMed: 38086901
DOI: 10.1038/s41386-023-01776-0 -
The British Journal of Psychiatry : the... Sep 2023The COVID-19 pandemic has transformed healthcare significantly and telepsychiatry is now the primary means of treatment in some countries. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The COVID-19 pandemic has transformed healthcare significantly and telepsychiatry is now the primary means of treatment in some countries.
AIMS
To compare the efficacy of telepsychiatry and face-to-face treatment.
METHOD
A comprehensive meta-analysis comparing telepsychiatry with face-to-face treatment for psychiatric disorders. The primary outcome was the mean change in the standard symptom scale scores used for each psychiatric disorder. Secondary outcomes included all meta-analysable outcomes, such as all-cause discontinuation and safety/tolerability.
RESULTS
We identified 32 studies ( = 3592 participants) across 11 mental illnesses. Disease-specific analyses showed that telepsychiatry was superior to face-to-face treatment regarding symptom improvement for depressive disorders ( = 6 studies, = 561; standardised mean difference s.m.d. = -0.325, 95% CI -0.640 to -0.011, = 0.043), whereas face-to-face treatment was superior to telepsychiatry for eating disorder ( = 1, = 128; s.m.d. = 0.368, 95% CI 0.018-0.717, = 0.039). No significant difference was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined ( = 26, = 2290; = 0.248). Telepsychiatry had significantly fewer all-cause discontinuations than face-to-face treatment for mild cognitive impairment ( = 1, = 61; risk ratio RR = 0.552, 95% CI 0.312-0.975, = 0.040), whereas the opposite was seen for substance misuse ( = 1, = 85; RR = 37.41, 95% CI 2.356-594.1, = 0.010). No significant difference regarding all-cause discontinuation was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined ( = 27, = 3341; = 0.564).
CONCLUSIONS
Telepsychiatry achieved a symptom improvement effect for various psychiatric disorders similar to that of face-to-face treatment. However, some superiorities/inferiorities were seen across a few specific psychiatric disorders, suggesting that its efficacy may vary according to disease type.
Topics: Humans; COVID-19; Pandemics; Psychiatry; Telemedicine; Cognitive Dysfunction; Randomized Controlled Trials as Topic
PubMed: 37655816
DOI: 10.1192/bjp.2023.86 -
European Neuropsychopharmacology : the... Jul 2023Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal... (Meta-Analysis)
Meta-Analysis
Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal formulation) resulting in non-selective MAOI activity at oral doses≥20 mg/day. The present systematic review and meta-analysis appraises the evidence of different formulations/dosages of selegiline across different psychiatric conditions. We inquired PubMed/MEDLINE/Cochrane-Central/WHO-ICTRP/Clarivate-WebOfScience and the Chinese-Electronic-Journal Database from inception to 10/26/2022 for selegiline trials involving psychiatric patients. Random-effects meta-analyses assessed heterogeneity, publication/risk biases, and confidence in the evidence, followed by sensitivity, subgroup, and meta-regression analyses. Co-primary outcomes were: changes in symptom score (standardized mean difference=SMD) and author-defined response (risk ratios=RRs). RRs of adverse events and all-cause discontinuation were secondary and acceptability outcomes, respectively. Systematic-review included 42 studies; meta-analysis, 23. Selegiline outperformed placebo in depressive symptom reduction (SMD=-0.96, 95%C.I.=-1.78, -0.14, k = 10, n = 1,308), depression (RR=1.61, 95%C.I.=1.20, 2.15, k = 9, n = 1,238) and atypical-depression response (RR=2.23, 95%C.I.=1.35, 3.68, k = 3, n = 136). Selegiline failed to outperform the placebo in negative (k = 4) or positive symptoms of schizophrenia (k = 4), attention-deficit-hyperactivity disorder (ADHD) symptoms reduction (k = 2), and smoking abstinence rate (k = 4). Selegiline did not differ from methylphenidate and ADHD scores (k = 2). No significant difference emerged in acceptability, incident diarrhea, headache, dizziness, and nausea RRs, in contrast to xerostomia (RR=1.58, 95%C.I. =1.03, 2.43, k = 6, n = 1,134), insomnia (RR=1.61, 95%C.I.=1.19, 2.17, k = 10, n = 1,768), and application-site reaction for transdermal formulation (RR=1.81, 95%C.I.=1.40, 2.33, k = 6, n = 1,662). Confidence in findings was low/very-low for most outcomes; moderate for depressive symptoms reduction (transdermal). Selegiline proved effective, safe, and well-tolerated for depressive disorders, yet further evidence is warranted about specific psychiatric disorders.
Topics: Humans; Selegiline; Depressive Disorder, Major; Monoamine Oxidase Inhibitors; Attention Deficit Disorder with Hyperactivity; Methylphenidate
PubMed: 37087864
DOI: 10.1016/j.euroneuro.2023.03.012 -
General Hospital Psychiatry 2024Several types of neuromodulation have been investigated for the treatment of fibromyalgia, but they show varied efficacy on pain, functioning, comorbid depression and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Several types of neuromodulation have been investigated for the treatment of fibromyalgia, but they show varied efficacy on pain, functioning, comorbid depression and comorbid anxiety. Whether some types of neuromodulation or some factors are associated with a better response also awaits clarification.
METHODS
We conducted a systematic review and network meta-analysis of randomized controlled trials to evaluate the efficacy of neuromodulation in patients with fibromyalgia. We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and PsycINFO before March 2022. We employed a frequentist random-effects network meta-analysis.
RESULTS
Forty trials involving 1541 participants were included. Compared with sham control interventions, several types of transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS), and high-frequency repetitive transcranial magnetic stimulation (rTMS) were associated with significant reduction of pain, depression, anxiety, and improvement in functioning. Many significantly effective treatment options involve stimulation of the primary motor cortex or dorsolateral prefrontal cortex.
CONCLUSION
We concluded that several types of rTMS, tDCS and tRNS may have the potential to be applied for clinical purposes.
Topics: Humans; Fibromyalgia; Transcranial Direct Current Stimulation; Network Meta-Analysis; Transcranial Magnetic Stimulation; Pain; Treatment Outcome
PubMed: 38382420
DOI: 10.1016/j.genhosppsych.2024.01.007