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Journal of Affective Disorders Oct 2023Antipsychotic medications are increasingly used for difficult-to-treat depression in young people. However, the evidence-base for this is unclear. Our aim was to assess... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic medications are increasingly used for difficult-to-treat depression in young people. However, the evidence-base for this is unclear. Our aim was to assess the evidence for the efficacy of atypical antipsychotics in treating unipolar and bipolar depression in adolescents and young adults.
METHOD
We conducted a comprehensive systematic review and meta-analysis of randomized-control-trial studies (RCTs) of antipsychotic medications for 10- to 25-year-olds with unipolar and bipolar depression. The primary outcome of interest was change in depressive symptoms from baseline to trial endpoint.
RESULTS
No studies were identified that evaluated the use of antipsychotics in the treatment of unipolar depression. However, we identified four studies, of quetiapine, lurasidone and olanzapine/fluoxetine combination, comprising a total of 866 randomized patients, that evaluated treatment of bipolar depression. All studies used the Children's Depression Rating Scale-Revised (CDRS-R). Our meta-analysis revealed the weighted mean difference (WMD) was -4.58 (95 % CI, -6.59 to -2.57) between antipsychotic and placebo-treated groups. Response and remission rates were also significantly in favor of antipsychotic treatment.
LIMITATIONS
There were few studies, several did not address risk-of-bias domains and there was a lack of non-industry sponsored studies.
CONCLUSION
There is an absence of evidence for the use of antipsychotic medications in treatment of youth unipolar depression, and no recommendations can be made. There is some evidence for the efficacy of antipsychotics, specifically lurasidone and olanzapine/fluoxetine combination, in the treatment of young people with bipolar depression. However, this evidence is limited and more studies investigating the use of these medications in young people are needed.
Topics: Child; Adolescent; Young Adult; Humans; Antipsychotic Agents; Bipolar Disorder; Fluoxetine; Olanzapine; Lurasidone Hydrochloride
PubMed: 37467794
DOI: 10.1016/j.jad.2023.07.082 -
Journal of Psychopharmacology (Oxford,... Jul 2023The classical psychedelics, psilocybin, peyote, ayahuasca/-dimethyltryptamine, and lysergic acid diethylamide are considered promising new treatments for psychiatric... (Review)
Review
BACKGROUND
The classical psychedelics, psilocybin, peyote, ayahuasca/-dimethyltryptamine, and lysergic acid diethylamide are considered promising new treatments for psychiatric illnesses, such as depression, anxiety, addiction, and obsessive-compulsive disorders. However, their profound and characteristic subjective effects raise concern for distinctive biases in randomized clinical trials.
METHODS
We performed a systematic literature search to identify all clinical trials on classical psychedelics with patient populations to examine descriptive data and determine the risk of bias. Two independent reviewers searched three databases (PubMed, Embase, and APA PsycNet) and extracted information on study design, study population, use of active or inactive placebo, dropouts, evaluation of blinding of intervention, and reporting of expectancy and therapeutic alliance.
RESULTS
We included 10 papers reporting on 10 unique trials. The trials generally included populations that were predominantly white and highly educated. The trials had small samples and considerable dropout. Blinding was either unsuccessful or not reported regardless of type of placebo. Few trials published protocols, statistical analysis plans (SAPs), and outcomes relating to psychotherapy fidelity. All trials but one were rated as high risk of bias.
CONCLUSION
Successful blinding of intervention is a significant challenge in this field. To better accommodate this, we suggest that future trials use a parallel-group design and utilize an active placebo on a psychedelic-naïve population. Future trials should publish trial protocol and SAPs, use clinician-rated outcomes accessed by a blinded rater, evaluate blinding of intervention, and consider measuring expectancy and therapeutic fidelity.
Topics: Humans; Hallucinogens; Randomized Controlled Trials as Topic; Lysergic Acid Diethylamide; Psilocybin; Anxiety Disorders
PubMed: 37403379
DOI: 10.1177/02698811231180276 -
East Asian Archives of Psychiatry :... Jun 2023Clozapine is a potent antipsychotic medication with a complex receptor profile. It is reserved for treatment-resistant schizophrenia. We systematically reviewed studies...
OBJECTIVE
Clozapine is a potent antipsychotic medication with a complex receptor profile. It is reserved for treatment-resistant schizophrenia. We systematically reviewed studies of non-psychosis symptoms of clozapine withdrawal.
METHODS
CINAHL, Medline, PsycINFO, PubMed, and the Cochrane Database of Systematic Reviews were searched using the keywords 'clozapine,' and 'withdrawal,' or 'supersensitivity,' 'cessation,' 'rebound,' or 'discontinuation'. Studies related to non-psychosis symptoms after clozapine withdrawal were included.
RESULTS
Five original studies and 63 case reports / series were included in analysis. In 195 patients included in the five original studies, approximately 20% experienced non-psychosis symptoms following discontinuation of clozapine. In 89 patients in four of the studies, 27 experienced cholinergic rebound, 13 exhibited extrapyramidal symptoms (including tardive dyskinesia), and three had catatonia. In 63 case reports / series included, 72 patients with non-psychosis symptoms were reported, which were catatonia (n=30), dystonia or dyskinesia (n=17), cholinergic rebound (n=11), serotonin syndrome (n=4), mania (n=3), insomnia (n=3), neuroleptic malignant syndrome (NMS) [n=3, one of them had both catatonia and NMS], and de novo obsessive compulsive symptoms (n=2). Restarting clozapine appeared to be the most effective treatment.
CONCLUSIONS
Non-psychosis symptoms following clozapine withdrawal have important clinical implications. Clinicians should be aware of the possible presentations of symptoms to ensure early recognition and management. Further research is warranted to better characterise the prevalence, risk factors, prognosis, and optimal drug dosing for each withdrawal symptom.
Topics: Humans; Antipsychotic Agents; Catatonia; Cholinergic Agents; Clozapine; Schizophrenia; Substance Withdrawal Syndrome
PubMed: 37400227
DOI: 10.12809/eaap2261 -
Ondansetron-induced QT prolongation among various age groups: a systematic review and meta-analysis.The Egyptian Heart Journal : (EHJ) :... Jul 2023Ondansetron is a selective 5-hydroxytryptamine type 3 serotonin-receptor antagonist with antiemetic properties used inadvertently in the emergency department for...
BACKGROUND
Ondansetron is a selective 5-hydroxytryptamine type 3 serotonin-receptor antagonist with antiemetic properties used inadvertently in the emergency department for controlling nausea. However, ondansetron is linked with a number of adverse effects, including prolongation of the QT interval. Therefore, the purpose of this meta-analysis was to assess the occurrence of QT prolongation in pediatric, adult, and elderly patients receiving oral or intravenously administered ondansetron.
METHODS
A thorough electronic search was conducted on PubMed (Medline) and Cochrane Library from the databases' inception to August 10, 2022. Only those studies were considered in which ondansetron was administered orally or intravenously to participants for the treatment of nausea and vomiting. The prevalence of QT prolongation in multiple predefined age groups was the outcome variable. Analyses were conducted using Review manager 5.4 (Cochrane collaboration, 2020).
RESULTS
A total of 10 studies involving 687 ondansetron group participants were statistically analyzed. The administration of ondansetron was associated with a statistically significant prevalence of QT prolongation in all age groups. An age-wise subgroup analysis was conducted which revealed that the prevalence of QT prolongation among participants younger than 18 years was not statistically significant, whereas it was statistically significant among participants aged 18-50 years and among patients older than 50 years.
CONCLUSIONS
The present meta-analysis provides further evidence that oral or intravenous administration of Ondansetron may lead to QT prolongation, particularly among patients older than 18 years of age.
PubMed: 37395900
DOI: 10.1186/s43044-023-00385-y -
Schizophrenia Bulletin Jan 2024Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. (Meta-Analysis)
Meta-Analysis
Long-Acting Injectable Second-Generation Antipsychotics vs Placebo and Their Oral Formulations in Acute Schizophrenia: A Systematic Review and Meta-Analysis of Randomized-Controlled-Trials.
BACKGROUND AND HYPOTHESIS
Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia.
STUDY DESIGN
We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injectable antipsychotics (SGA-LAIs) olanzapine, risperidone, paliperidone, and aripiprazole with placebo or their oral counterparts in acutely ill patients with schizophrenia. We analyzed 23 efficacy and tolerability outcomes, with the primary outcome being overall symptoms of schizophrenia. The results were obtained through random effects, pairwise meta-analyses, and subgroup tests. The study quality was assessed using the Cochrane-Risk-of-Bias-Tool version-1.
STUDY RESULTS
Sixty-six studies with 16 457 participants were included in the analysis. Eleven studies compared second-generation long-acting injectable antipsychotics (SGA-LAIs) with a placebo, 54 compared second-generation oral antipsychotics (SGA-orals) with a placebo, and one compared an SGA-LAI (aripiprazole) with its oral formulation. All 4 SGA-LAIs reduced overall symptoms more than placebo, with mean standardized differences of -0.66 (95% CI: -0.90; -0.43) for olanzapine, -0.64 (-0.80; -0.48) for aripiprazole, -0.62 (-0.76; -0.48) for risperidone and -0.42 (-0.53; -0.31) for paliperidone. The side-effect profiles of the LAIs corresponded to the patterns known from the oral formulations. In subgroup tests compared to placebo, some side effects were less pronounced under LAIs than under their oral formulations.
CONCLUSIONS
SGA-LAIs effectively treat acute schizophrenia. Some side effects may be less frequent than under oral drugs, but due to the indirect nature of the comparisons, this finding must be confirmed by RCTs comparing LAIs and orals head-to-head.
Topics: Humans; Antipsychotic Agents; Paliperidone Palmitate; Aripiprazole; Olanzapine; Risperidone; Delayed-Action Preparations; Schizophrenia
PubMed: 37350486
DOI: 10.1093/schbul/sbad089 -
Tijdschrift Voor Psychiatrie 2023Metformin is the most investigated pharmacological treatment of antipsychotics-induced weight gain (AIWG). Based on a systematic literature review, the first guideline...
BACKGROUND
Metformin is the most investigated pharmacological treatment of antipsychotics-induced weight gain (AIWG). Based on a systematic literature review, the first guideline for the treatment of AIWG with metformin was recently published.
AIM
To present a step-by-step plan, based on recent literature and clinical experience to monitor, prevent, and treat AIWG.
METHOD
Literature search to give specific advice on the choice of antipsychotic medication, stop, dose reduction or switch of antipsychotic, screening, non-pharmacological and pharmacological interventions to prevent and treat AIWG.
RESULTS
Especially in the first year of antipsychotic treatment timely detection of AIWG through regular monitoring is pivotal. The best way to treat AIWG is to prevent its emergence by choosing an antipsychotic with a favourable metabolic profile. Secondly, by titration of antipsychotic medication to the lowest dose possible. Achieving a healthy lifestyle shows a limited beneficial effect on AIWG. Drug-induced weight loss can be attained by the addition of metformin, topiramate, or aripiprazole. Topiramate and aripiprazole can improve positive and negative residual symptoms of schizophrenia. The evidence on liraglutide is scarce. All augmentation strategies may cause side effects. Besides, in case of nonresponse augmentation therapy should be stopped to prevent unnecessary polypharmacy.
CONCLUSION
In the revision of the Dutch multidisciplinary guideline for schizophrenia, the detection, prevention, and treatment of AIWG deserves more attention.
Topics: Humans; Antipsychotic Agents; Aripiprazole; Topiramate; Weight Gain; Metformin
PubMed: 37323046
DOI: No ID Found -
BMC Neurology Jun 2023Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs. (Meta-Analysis)
Meta-Analysis
The efficacy and safety of metoclopramide in relieving acute migraine attacks compared with other anti-migraine drugs: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs.
METHODS
We searched online databases like PubMed, Cochrane Library, Scopus, and Web of Science till June 2022 for RCTs that compared metoclopramide alone with placebo or active drugs. The main outcomes were the mean change in headache score and complete headache relief. The secondary outcomes were the rescue medications need, side effects, nausea and recurrence rate. We qualitatively reviewed the outcomes. Then, we performed the network meta-analyses (NMAs) when it was possible. which were done by the Frequentist method using the MetaInsight online software.
RESULTS
Sixteen studies were included with a total of 1934 patients: 826 received metoclopramide, 302 received placebo, and 806 received other active drugs. Metoclopramide was effective in reducing headache outcomes even for 24 h. The intravenous route was the most chosen route in the included studies and showed significant positive results regarding headache outcomes; however, the best route whether intramuscular, intravenous, or suppository was not compared in the previous studies. Also, both 10 and 20 mg doses of metoclopramide were effective in improving headache outcomes; however, there was no direct comparison between both doses and the 10 mg dose was the most frequently used dosage. In NMA of headache change after 30 min or 1 h, metoclopramide effect came after granisetron, ketorolac, chlorpromazine, and Dexketoprofen trometamol. Only granisetron's effect was significantly higher than metoclopramide's effect which was only significantly higher than placebo and sumatriptan. In headache-free symptoms, only prochlorperazine was non-significantly higher than metoclopramide which was higher than other medications and showed significantly higher effects only with placebo. In rescue medication, metoclopramide's effect was only non-significantly lower than prochlorperazine and chlorpromazine while its effect was higher than other drugs and showed higher significant effects only than placebo and valproate. In the recurrence rate, studies showed no significant difference between metoclopramide and other drugs. Metoclopramide significantly decreased nausea more than the placebo. Regarding side effects, metoclopramide showed a lower incidence of mild side effects than pethidine and chlorpromazine and showed a higher incidence of mild side effects than placebo, dexamethasone, and ketorolac. The reported extrapyramidal symptoms with metoclopramide were dystonia or akathisia.
CONCLUSION
A dose of 10 mg IV Metoclopramide was effective in relieving migraine attacks with minimal side effects. Compared to other active drugs, it only showed a lower significant effect compared with granisetron regarding headache change while it showed significantly higher effects only with placebo in both rescue medication needs and headache-free symptoms and valproate in only rescue medication need. Also, it significantly decreased headache scores more than placebo and sumatriptan. However, more studies are needed to support our results.
Topics: Humans; Metoclopramide; Sumatriptan; Network Meta-Analysis; Prochlorperazine; Chlorpromazine; Granisetron; Valproic Acid; Ketorolac; Randomized Controlled Trials as Topic; Migraine Disorders; Nausea; Headache
PubMed: 37291500
DOI: 10.1186/s12883-023-03259-7 -
The Cochrane Database of Systematic... Jun 2023Autism spectrum disorder (autism) is a neurodevelopmental condition characterised by impairments in social communication and interaction, plus restricted, repetitive... (Review)
Review
BACKGROUND
Autism spectrum disorder (autism) is a neurodevelopmental condition characterised by impairments in social communication and interaction, plus restricted, repetitive patterns of behaviour and interests. Whilst some people embrace autism as part of their identity, others struggle with their difficulties, and some seek treatment. There are no current interventions that result in complete reduction of autism features. Acetylcholine is a neurotransmitter for the cholinergic system and has a role in attention, novelty seeking, and memory. Low levels of acetylcholine have been investigated as a potential contributor to autism symptomatology. Donepezil, galantamine, and rivastigmine (commonly referred to as acetylcholinesterase inhibitors) all inhibit acetylcholinesterase, and have slightly different modes of action and biological availability, so their effectiveness and side-effect profiles may vary. The effect of various acetylcholinesterase inhibitor on core autism features across the lifespan, and possible adverse effects, have not been thoroughly investigated.
OBJECTIVES
To evaluate the efficacy and harms of acetylcholinesterase inhibitors for people with the core features (social interaction, communication, and restrictive and repetitive behaviours) of autism. To assess the effects of acetylcholinesterase inhibitors on non-core features of autism.
SEARCH METHODS
In November 2022, we searched CENTRAL, MEDLINE, Embase, eight other databases, and two trials registers. We also searched the reference lists of included studies and relevant reviews, and contacted authors of relevant studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs), comparing acetylcholinesterase inhibitors (e.g. galantamine, donepezil, or rivastigmine) of varying doses, delivered orally or via transdermal patch, either as monotherapy or adjunct therapy, with placebo. People of any age, with a clinical diagnosis of autism were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were core features of autism and adverse effects. Secondary outcomes were language, irritability, hyperactivity, and general health and function. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included two RCTs (74 participants). One study was conducted in Iran, the second in the USA, although exact location in the USA is unclear. Galantamine plus risperidone versus placebo plus risperidone One study compared the effects of galantamine plus risperidone to placebo plus risperidone (40 participants, aged 4 years to 12 years). Primary and secondary outcomes of interest were measured postintervention, using subscales of the Aberrant Behavior Checklist (score 0 to 3; higher scores = greater impairment). Very low-certainty evidence showed there was little to no difference between the two groups postintervention for social communication (mean difference (MD) -2.75, 95% confidence interval (CI) -5.88 to 0.38), and restricted and repetitive behaviour (MD -0.55, 95% CI -3.47 to 2.37). Overall autism features were not assessed. Adverse events may be higher in the galantamine plus risperidone group (75%) compared with the placebo plus risperidone group (35%): odds ratio 5.57, 95% CI 1.42 to 21.86, low-certainty evidence. No serious adverse events were reported. Low-certainty evidence showed a small difference in irritability (MD -3.50, 95% CI -6.39 to -0.61), with the galantamine plus risperidone group showing a greater decline on the irritability subscale than the placebo group postintervention. There was no evidence of a difference between the groups in hyperactivity postintervention (MD -5.20, 95% CI -10.51 to 0.11). General health and function were not assessed. Donepezil versus placebo One study compared donepezil to placebo (34 participants aged 8 years to 17 years). Primary outcomes of interest were measured postintervention, using subscales of the Modified Version of The Real Life Rating Scale (scored 0 to 3; higher scores = greater impairment). Very low-certainty evidence showed no evidence of group differences immediately postintervention in overall autism features (MD 0.07, 95% CI -0.19 to 0.33), or in the autism symptom domains of social communication (MD -0.02, 95% CI -0.34 to 0.30), and restricted and repetitive behaviours (MD 0.04, 95% CI -0.27 to 0.35). Significant adverse events leading to study withdrawal in at least one participant was implied in the data analysis section, but not explicitly reported. The evidence is very uncertain about the effect of donepezil, compared to placebo, on the secondary outcomes of interest, including irritability (MD 1.08, 95% CI -0.41 to 2.57), hyperactivity (MD 2.60, 95% CI 0.50 to 4.70), and general health and function (MD 0.03, 95% CI -0.48 to 0.54) postintervention. Across all analyses within this comparison, we judged the evidence to be very low-certainty due to high risk of bias, and very serious imprecision (results based on one small study with wide confidence intervals). The study narratively reported adverse events for the study as a whole, rather than by treatment group.
AUTHORS' CONCLUSIONS
Evidence about the effectiveness of acetylcholinesterase inhibitors as a medication to improve outcomes for autistic adults is lacking, and for autistic children is very uncertain. There is a need for more evidence of improvement in outcomes of relevance to clinical care, autistic people, and their families. There are a number of ongoing studies involving acetylcholinesterase inhibitors, and future updates of this review may add to the current evidence.
Topics: Child; Humans; Acetylcholine; Autism Spectrum Disorder; Cholinesterase Inhibitors; Donepezil; Galantamine; Risperidone; Rivastigmine; Child, Preschool; Adolescent
PubMed: 37267443
DOI: 10.1002/14651858.CD013851.pub2 -
Cureus Apr 2023Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that affects approximately 2% of the human population. Traditional treatment of OCD includes selective... (Review)
Review
Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that affects approximately 2% of the human population. Traditional treatment of OCD includes selective serotonin reuptake inhibitor (SSRI) or serotonin reuptake inhibitor (SRI) treatment along with cognitive behavioral therapy (CBT). Nearly 25%-30% of OCD patients do not respond to SSRIs. Glutamatergic agents are currently being studied for the treatment of OCD due to the glutamatergic pathway in the brain, related to OCD, and the role of the cortico-striato-thalamic circuit (CSTC). This review assesses the clinical effectiveness of N-methyl-D-aspartate (NMDA) antagonists, ketamine/esketamine, memantine, and amantadine, for adult patients with OCD. Inclusion criteria include human studies published within the last 15 years, with patients diagnosed with OCD, aged over 18 years, with only psychiatric comorbidities, and full-text articles. Papers that included interventions other than CBT, exposure with response prevention (ERP), and SSRI/SRI were excluded. Articles were searched for using PubMed, PubMed Central, Medical Literature Analysis and Retrieval System Online, GeorgiA LIbrary LEarning Online, EBSCO Information Services, OpenAthens, Multidisciplinary Digital Publishing Institute, and Google Scholar databases, last searched on December 2, 2022. The risk of bias was assessed using Cochrane Risk of Bias tools, the Scale for the Assessment of Narrative Review Articles (SANRA) checklist for literature reviews, and the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for quasi-experimental studies. Results were presented and synthesized by Excel spreadsheet analysis. The database search yielded 4,221 articles, which was cut down to 18 articles by inclusion/exclusion criteria, including duplications. 80% of the ketamine studies resulted in a significant reduction of obsessions and compulsions based on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and each of the memantine and amantadine studies displayed clinical effectiveness, also. Limitations include the small number of amantadine studies and the limited availability of other NMDA receptor (NMDAR) antagonist-focused studies. This systematic review shows that ketamine is an effective drug for the treatment of non-refractory, mild to moderate OCD, and memantine and amantadine are effective augmentation agents for the treatment of mild to severe OCD.
PubMed: 37213965
DOI: 10.7759/cureus.37833 -
International Journal of Molecular... Apr 2023The sleep-wake cycle is a complex multifactorial process involving several neurotransmitters, including acetylcholine, norepinephrine, serotonin, histamine, dopamine,... (Review)
Review
The sleep-wake cycle is a complex multifactorial process involving several neurotransmitters, including acetylcholine, norepinephrine, serotonin, histamine, dopamine, orexin and GABA, that can be, in turn, regulated by different nutrients involved in their metabolic pathways. Although good sleep quality in children has been proven to be a key factor for optimal cognitive, physical and psychological development, a significant and ever-increasing percentage of the pediatric population suffers from sleep disorders. In children, behavioral interventions along with supplements are recommended as the first line treatment. This systematic review was conducted, according to the PRISMA guidelines, with the purpose of assessing the principal nutrients involved in the pathways of sleep-regulating neurotransmitters in children and adolescents. Our focus was the utilization of over the counter (OTC) products, specifically iron, hydroxytryptophan, theanine and antihistamines in the management of different pediatric sleep disorders with the intention of providing a practical guide for the clinician.
Topics: Adolescent; Humans; Child; Sleep; Sleep Initiation and Maintenance Disorders; Histamine; Histamine Antagonists; Neurotransmitter Agents; Sleep Wake Disorders
PubMed: 37175525
DOI: 10.3390/ijms24097821