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The Cochrane Database of Systematic... Jul 2022Attention Deficit Hyperactivity Disorder (ADHD) can co-occur in up to 40% of people with epilepsy. There is debate about the efficacy and tolerability of stimulant and... (Review)
Review
BACKGROUND
Attention Deficit Hyperactivity Disorder (ADHD) can co-occur in up to 40% of people with epilepsy. There is debate about the efficacy and tolerability of stimulant and non-stimulant drugs used to treat people with ADHD and co-occurring epilepsy.
OBJECTIVES
To assess the effect of stimulant and non-stimulant drugs on children and adults with ADHD and co-occurring epilepsy in terms of seizure frequency and drug withdrawal rates (primary objectives), as well as seizure severity, ADHD symptoms, cognitive state, general behaviour, quality of life, and adverse effects profile (secondary objectives).
SEARCH METHODS
We searched the following databases on 12 October 2020: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 9 October 2020), CINAHL Plus (EBSCOhost, 1937 onwards). There were no language restrictions. CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy. SELECTION CRITERIA: We included randomised controlled trials of stimulant and non-stimulant drugs for people of any age, gender or ethnicity with ADHD and co-occurring epilepsy.
DATA COLLECTION AND ANALYSIS
We selected articles and extracted data according to predefined criteria. We conducted primary analysis on an intention-to-treat basis. We presented outcomes as risk ratios (RRs) with 95% confidence intervals (CIs), except for individual adverse effects where we quoted 99% CIs. We conducted best- and worst-case sensitivity analyses to deal with missing data. We carried out a risk of bias assessment for each included study using the Cochrane risk of bias tool and assessed the overall certainty of evidence using the GRADE approach.
MAIN RESULTS
We identified two studies that matched our inclusion criteria: a USA study compared different doses of the stimulant drug osmotic-release oral system methylphenidate (OROS-MPH) with a placebo in 33 children (mean age 10.5 ± 3.0 years), and an Iranian study compared the non-stimulant drug omega-3 taken in conjunction with risperidone and usual anti-seizure medication (ASM) with risperidone and ASM only in 61 children (mean age 9.24 ± 0.15 years). All children were diagnosed with epilepsy and ADHD according to International League Against Epilepsy and Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria, respectively. We assessed both studies to be at low risk of detection and reporting biases, but assessments varied from low to high risk of bias for all other domains. OROS-MPH No participant taking OROS-MPH experienced significant worsening of epilepsy, defined as: 1. a doubling of the highest 14-day or highest two-day seizure rate observed during the 12 months before the trial; 2. a generalised tonic-clonic seizure if none had been experienced in the previous two years; or 3. a clinically meaningful intensification in seizure duration or severity (33 participants, 1 study; low-certainty evidence). However, higher doses of OROS-MPH predicted an increased daily risk of a seizure (P < 0.001; 33 participants, 1 study; low-certainty evidence). OROS-MPH had a larger proportion of participants receiving 'much improved' or 'very much improved' scores for ADHD symptoms on the Clinical Global Impressions for ADHD-Improvement tool (33 participants, 1 study; low-certainty evidence). OROS-MPH also had a larger proportion of people withdrawing from treatment (RR 2.80; 95% CI 1.14 to 6.89; 33 participants, 1 study; moderate-certainty evidence). Omega-3 Omega-3 with risperidone and ASM were associated with a reduction in mean seizure frequency by 6.6 seizures per month (95% CI 4.24 to 8.96; 56 participants, 1 study; low-certainty evidence) and an increase in the proportion of people achieving 50% or greater reduction in monthly seizure frequency (RR 2.79, 95% CI 0.84 to 9.24; 56 participants, 1 study; low-certainty evidence) compared to people on risperidone and ASM alone. Omega-3 with risperidone and ASM also had a smaller proportion of people withdrawing from treatment (RR 0.65, 95% CI 0.12 to 3.59; 61 participants, 1 study; low-certainty evidence) but a larger proportion of people experiencing adverse drug events (RR 1.40, 95% CI 0.44 to 4.42; 56 participants, 1 study; low-certainty evidence) compared to people on risperidone and ASM alone.
AUTHORS' CONCLUSIONS
In children with a dual-diagnosis of epilepsy and ADHD, there is some evidence that use of the stimulant drug OROS-MPH is not associated with significant worsening of epilepsy, but higher doses of it may be associated with increased daily risk of seizures; the evidence is of low-certainty. OROS-MPH is also associated with improvement in ADHD symptoms. However, this treatment was also associated with a large proportion of treatment withdrawal compared to placebo. In relation to the non-stimulant drug omega-3, there is some evidence for reduction in seizure frequency in children who are also on risperidone and ASM, compared to children who are on risperidone and ASM alone. Evidence is inconclusive whether omega-3 increases or decreases the risk of adverse drug events. We identified only two studies - one each for OROS-MPH and omega-3 - with low to high risk of bias. We assessed the overall certainty of evidence for the outcomes of both OROS-MPH and omega-3 as low to moderate. More studies are needed. Future studies should include: 1. adult participants; 2. a wider variety of stimulant and non-stimulant drugs, such as amphetamines and atomoxetine, respectively; and 3. additional important outcomes, such as seizure-related hospitalisations and quality of life. Clusters of studies which assess the same drug - and those that build upon the evidence base presented in this review on OROS-MPH and omega-3 - are needed to allow for meta-analysis of outcomes.
Topics: Adolescent; Adult; Anticonvulsants; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Drug Resistant Epilepsy; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Iran; Quality of Life; Risperidone
PubMed: 35844168
DOI: 10.1002/14651858.CD013136.pub2 -
Cureus Aug 2023Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified... (Review)
Review
Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified approach for treating these patients in the existing literature. This study aimed to assess the effects of different treatment modalities used in calcium channel blocker poisoning, as reported by previous studies. The primary outcomes studied were mortality and hemodynamic parameters after treatment. The secondary outcomes were the length of hospital stay, length of intensive care unit stay, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. A thorough literature search was performed through Ovid, PubMed, Cochrane Library, and Google Scholar from January 2014 to December 31, 2022, to identify all studies analyzing the effects of the treatment of calcium channel blocker poisoning on the desired outcomes. Two reviewers reviewed 607 published articles from January 2014 to December 2022 to identify studies analyzing the effects of the treatment of calcium channel blocker poisoning on desired outcomes. In this review, 18 case reports, one case series, and one cohort study were included. Most patients were treated with an injection of calcium gluconate or calcium chloride. The use of calcium along with dopamine and norepinephrine was found to have lower mortality rates. A few patients were also treated with injection atropine for bradycardia. High-dose insulin therapy was used in 14 patients, of whom two did not survive. In the cohort study, 66 calcium channel blocker toxicity patients were included. These patients were treated with high-dose insulin therapy. A total of 11 patients with calcium channel blocker toxicity succumbed. Although it was found to be associated with improved hemodynamic parameters and lower mortality, side effects such as hypokalemia and hypoglycemia were noted. Intravenous lipid emulsion therapy (administered to eight patients), extracorporeal life support (used in three patients with refractory shock or cardiac arrest), injection glucagon, methylene blue, albumin infusion, and terlipressin were associated with a lower mortality rate as well as improvement in hemodynamic parameters. None of the case reports provided any information on end-organ damage on long-term follow-up.
PubMed: 37664357
DOI: 10.7759/cureus.42854 -
Tremor and Other Hyperkinetic Movements... 2024Tardive Dyskinesia (TD) is a neurological disorder characterized by involuntary movements, often caused by dopamine receptor antagonists. Vesicular Monoamine Transporter... (Comparative Study)
Comparative Study Review
BACKGROUND
Tardive Dyskinesia (TD) is a neurological disorder characterized by involuntary movements, often caused by dopamine receptor antagonists. Vesicular Monoamine Transporter 2 (VMAT2) inhibitors, such as valbenazine and deutetrabenazine, have emerged as promising therapies for TD and several clinical trials have shown their efficacy. This study aims to compare the efficacy and safety profile of VMAT2 inhibitors, focusing on a recent trial conducted in the Asian population.
METHODS
We reviewed the PubMed, Cochrane Library, Embase database, and clinicaltrials.gov between January 2017 and October 2023, using the keywords "tardive dyskinesia" AND ("valbenazine" [all fields] OR " deutetrabenazine " [all fields]) AND "clinical trial". The reviewed articles were studied for efficacy and side effects.
RESULTS
An initial search yielded 230 articles, of which 104 were duplicates. Following the title and abstract screening, 25 additional articles were excluded. A full-text review resulted in the exclusion of 96 more articles. Ultimately, four double-blind clinical trials met the inclusion criteria. The deutetrabenazine studies demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores compared to placebo, with no difference in adverse events. The valbenazine studies showed favorable results in reducing TD symptoms and were well-tolerated.
DISCUSSION
The studies reviewed in this analysis underscore the potential of deutetrabenazine and valbenazine as valuable treatment options for TD in diverse populations. Both medications demonstrated significant improvements in AIMS scores, suggesting their effectiveness in managing TD symptoms. Additionally, they exhibited favorable safety profiles, with low rates of serious adverse events and no significant increase in QT prolongation, parkinsonism, suicidal ideation, or mortality.
CONCLUSION
The studies reviewed highlight the promising efficacy and tolerability of deutetrabenazine and valbenazine as treatments for Tardive Dyskinesia, providing new hope for individuals affected by this challenging condition.
Topics: Humans; Randomized Controlled Trials as Topic; Tardive Dyskinesia; Tetrabenazine; Valine; Vesicular Monoamine Transport Proteins
PubMed: 38497033
DOI: 10.5334/tohm.842 -
Neuropsychopharmacology Reports Sep 2020Considering that the efficacy results of the Japan lurasidone phase 3 trials for acute schizophrenia were inconsistent, we conducted a systematic review and a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Considering that the efficacy results of the Japan lurasidone phase 3 trials for acute schizophrenia were inconsistent, we conducted a systematic review and a random-effect model network meta-analysis of those trials to examine whether lurasidone was beneficial for the treatment of Japanese patients with acute schizophrenia.
METHODS
The study included the double-blind, randomized trial in Japan that included patients with acute schizophrenia. Efficacy outcomes were improvement of the Positive and Negative Syndrome Scale total score (PANSS-T, primary), positive (PANSS-P), negative (PANSS-N), and general (PANSS-G) subscale scores; and Clinical Global Impression-Severity Scale (CGI-S) score and response rate. Other outcomes were discontinuation rates and incidence of individual adverse events.
RESULTS
We included four studies (n = 1,608). Although both lurasidone 40 mg/d (LUR40) and 80 mg/d (LUR80) outperformed placebo in PANSS-T [standardized mean difference (95% credible interval): LUR40 = -0.298 (-0.420, -0.176), LUR80 = -0.170 (-0.320, -0.019)], PANSS-P, and CGI-S scores, LUR40 but not LUR80 outperformed placebo in PANSS-N and PANSS-G scores and response rate. LUR40 outperformed LUR80 regarding PANSS-G score. Both LUR40 and LUR80 were associated with a higher incidence of akathisia, somnolence, and increased body weight compared with placebo. Compared with placebo, LUR40 was associated with a higher incidence of weight gain (≥7%), and LUR80 was associated with a higher incidence of dystonia and weight loss (≥7%) and higher Drug-Induced Extrapyramidal Symptoms Scale score.
CONCLUSIONS
Both LUR40 and LUR80 improved overall symptoms in Japanese patients with acute schizophrenia. However, LUR80 seemed to have a risk of extrapyramidal symptoms.
Topics: Antipsychotic Agents; Clinical Trials, Phase III as Topic; Double-Blind Method; Humans; Japan; Lurasidone Hydrochloride; Network Meta-Analysis; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome
PubMed: 32767739
DOI: 10.1002/npr2.12131 -
The British Journal of Psychiatry : the... Aug 2022Aripiprazole augmentation is proven effective for antidepressant-refractory depression, but its licensed dose range is wide and optimal dosage remains unclear. (Meta-Analysis)
Meta-Analysis Review
Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose-effect meta-analysis.
BACKGROUND
Aripiprazole augmentation is proven effective for antidepressant-refractory depression, but its licensed dose range is wide and optimal dosage remains unclear.
AIMS
To find the optimal dosage of aripiprazole augmentation.
METHOD
Multiple electronic databases were searched (from inception to 16 February 2021) to identify all assessor-masked randomised controlled trials evaluating aripiprazole augmentation therapy in adults (≥18 years old, both genders) with major depressive disorder showing inadequate response to at least one antidepressant treatment. A random-effects, one-stage dose-effect meta-analysis with restricted cubic splines was conducted. Outcomes were efficacy (treatment response: ≥50% reduction in depression severity), tolerability (drop-out due to adverse effects) and acceptability (drop-out for any reason) after 8 weeks of treatment (range 4-12 weeks).
RESULTS
Ten studies met the inclusion criteria. All were individually randomised, placebo-controlled, multi-centre, parallel studies including 2625 participants in total. The maximum target dose-efficacy curve showed an increase up to doses between 2 mg (odds ratio OR = 1.46, 95% CI 1.15-1.85) and 5 mg (OR = 1.93, 95% CI 1.33-2.81), and then a non-increasing trend through the higher licensed doses up to 20 mg (OR = 1.90, 95% CI 1.52-2.37). Tolerability showed a similar trend with greater uncertainty. Acceptability showed no significant difference through the examined dose range. Certainty of evidence was low to moderate.
CONCLUSIONS
Low-dose aripiprazole as augmentation treatment might achieve the optimal balance between efficacy, tolerability and acceptability in the acute treatment of antidepressant-refractory depression. However, the small number of included studies and the overall moderate to high risk of bias seriously compromise the reliability of the results. Further research is required to investigate the benefits of low versus high dose.
Topics: Adolescent; Adult; Antidepressive Agents; Aripiprazole; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Female; Humans; Male; Reproducibility of Results
PubMed: 35049482
DOI: 10.1192/bjp.2021.165 -
Neuropsychopharmacology Reports Dec 2020This systematic review and random-effect model, network meta-analysis of the phase 3 trials in Japan assessed the efficacy and safety profile of lurasidone compared with... (Comparative Study)
Comparative Study Meta-Analysis
AIM
This systematic review and random-effect model, network meta-analysis of the phase 3 trials in Japan assessed the efficacy and safety profile of lurasidone compared with olanzapine and quetiapine extended-release (QUE-XR) for the treatment of bipolar depression.
METHODS
The study included double-blind, randomized, placebo-controlled, phase 3 trials in Japan that included patients with bipolar depression. Outcomes included response rate (primary), remission rate (secondary), improvement of Montgomery-Åsberg Depression Rating Scale (MADRS) total score, discontinuation rates, and incidence of individual adverse events.
RESULTS
Three studies were included (n = 1223). Lurasidone and olanzapine but not QUE-XR were superior to placebo in response rate [risk ratio (95% credible interval): lurasidone = 0.78 (0.66, 0.92); olanzapine = 0.84 (0.71, 0.99); QUE-XR = 0.87 (0.73, 1.03)]. Lurasidone, olanzapine and QUE-XR were superior to placebo in remission rate [lurasidone = 0.90 (0.83, 0.98); olanzapine = 0.87 (0.77, 0.99); QUE-XR = 0.84 (0.73, 0.98)] and the improvement of MADRS total score. There were not differences in discontinuation rates between each antipsychotic and placebo. Compared with placebo, lurasidone was higher incidence of akathisia, and increased body weight and blood prolactin level; olanzapine was higher incidence of somnolence and ≥7% weight gain, and increased body weight, blood total cholesterol level, blood LDL cholesterol level, and blood triglyceride levels; QUE-XR was higher incidence of extrapyramidal symptoms, akathisia, somnolence, dry mouth, constipation and ≥7% weight gain, and increased body weight, blood total cholesterol level, blood LDL cholesterol level, and blood triglyceride levels.
CONCLUSIONS
Our results suggested although the efficacy of three SGAs was similar, there were the differences in the safety profile among the SGAs.
Topics: Antipsychotic Agents; Bipolar Disorder; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Humans; Japan; Lurasidone Hydrochloride; Network Meta-Analysis; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic
PubMed: 32902200
DOI: 10.1002/npr2.12137 -
The Cochrane Database of Systematic... May 2022Physicians often prescribe opioids for pain in the acute care setting. Nausea and vomiting are well-described adverse events, occurring in over one-third of patients.... (Review)
Review
BACKGROUND
Physicians often prescribe opioids for pain in the acute care setting. Nausea and vomiting are well-described adverse events, occurring in over one-third of patients. Prophylactic antiemetics may be one option to reduce opioid-associated nausea and vomiting. However, these medications also have their own adverse effects, so it is important to understand their efficacy and safety prior to routine use. This is a review of randomized controlled trials comparing prophylactic antiemetics versus placebo or standard care for preventing opioid-associated nausea and vomiting.
OBJECTIVES
To assess the effects of prophylactic antiemetics for nausea and vomiting in adults (aged 16 years or older) receiving intravenous opioids in the acute care setting.
SEARCH METHODS
We searched CENTRAL (the Cochrane Library), MEDLINE (OVID), Embase (OVID) from inception to January 2022, and Google Scholar (17 January 2022). We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and screened reference lists.
SELECTION CRITERIA
We included randomized controlled trials of prophylactic antiemetics versus placebo or standard care in adults prior to receiving an intravenous opioid.
DATA COLLECTION AND ANALYSIS
Two review authors (MG, JNC) independently determined the eligibility of each study according to the inclusion criteria. Two review authors (MG, GDP) then independently extracted data, assessed risk of bias, and determined the certainty of evidence using GRADE. Our primary outcomes were the occurrence of nausea, vomiting, and adverse events. Secondary outcomes included nausea severity, number of vomiting episodes, and number of participants requiring antiemetic rescue therapy. We presented outcomes as risk ratios (RR) for dichotomous data (e.g. presence of vomiting, presence of nausea, number of participants requiring rescue medication, adverse events) and mean difference (MD) or standardized mean difference for continuous data (e.g. number of vomiting episodes, nausea severity) with 95% confidence intervals (CI).
MAIN RESULTS
We included three studies involving 527 participants (187 women and 340 men) with a mean age of 42 years. All studies used intravenous metoclopramide (10 mg) as the intervention and a placebo for the comparator. No studies assessed any other antiemetic or compared the intervention to standard care. Compared to placebo, metoclopramide did not reduce vomiting (RR 1.18, 95% CI 0.26 to 5.32; low-certainty evidence) or nausea (RR 0.55; 95% CI 0.15 to 2.03; low-certainty evidence) and there was no difference in adverse events (RR 2.34, 95% CI 0.47 to 11.61; low-certainty evidence). No data were available regarding the number of vomiting episodes. Metoclopramide did reduce the severity of nausea compared with placebo (MD -0.49, 95% CI -0.75 to -0.23; low-certainty evidence) but did not reduce the need for rescue medication (RR 1.86, 95% CI 0.17 to 20.16; low-certainty evidence). Two studies were at unclear risk of bias for random sequence generation, one for blinding of outcome assessors, one for incomplete outcome data, and two for selective reporting. The studies were at low risk of bias for all remaining components.
AUTHORS' CONCLUSIONS
There was no evidence that prophylactic metoclopramide affected the risk of vomiting, nausea, or the need for rescue medication when provided prior to intravenous opioids in the acute care setting. There was a clinically insignificant difference in nausea severity when comparing prophylactic metoclopramide with placebo. Overall, the evidence was of low certainty. Future research could better delineate the effects of prophylactic antiemetics on specific populations, and new studies are needed to evaluate the use of other prophylactic antiemetic agents, for which there were no data.
Topics: Adult; Analgesics, Opioid; Antiemetics; Female; Humans; Male; Metoclopramide; Nausea; Vomiting
PubMed: 35588093
DOI: 10.1002/14651858.CD013860.pub2 -
Translational Psychiatry Dec 2022Is paliperidone palmitate (PP) a useful treatment option for adults with acute symptoms of schizophrenia? We conducted a systematic review and a random-effects pairwise... (Meta-Analysis)
Meta-Analysis
Is paliperidone palmitate (PP) a useful treatment option for adults with acute symptoms of schizophrenia? We conducted a systematic review and a random-effects pairwise and network meta-analysis that compared PP (25-150 mg equivalent) with paliperidone extended-release (PAL-ER, 3-12 mg/d) regarding their efficacy and safety in adults with acute symptoms of schizophrenia. The outcomes were the total score of the Positive and Negative Syndrome Scale (PANSS-T) at week 6 (the primary outcome for efficacy) and all-cause discontinuation(the primary outcome for acceptability), discontinuation due to inefficacy, discontinuation due to adverse events, discontinuation due to the withdrawal of consent, and the incidence of individual adverse events. Five studies on PP and seven studies on PAL-ER, which involved 4970 individuals in total, were included in this study. For the primary outcomes, we only included data from the treatment arms that used 100 or 150 mg equivalent as an initial dose of PP and data from the treatment arms that used 6, 9, or 12 mg as an initial dose of PAL-ER. The pairwise meta-analyses showed that both PP and PAL-ER outperformed placebo regarding PANSS-T at week 6 and all-cause discontinuation. However, there were no statistically significant differences in these outcomes between the effect sizes of PP and that of PAL-ER. Both PP and PAL-ER increased blood prolactin levels in both females and males compared with placebo. PAL-ER significantly increased blood prolactin in both females and males compared with PP. There were no statistically significant differences in other outcomes between the effect sizes of PP and that of PAL-ER. Similar results in all outcomes were observed in the network meta-analyses. In conclusion, PP might be a useful treatment option for adults with acute symptoms of schizophrenia. A noninferiority study that directly compares PP with PAL-ER for acute schizophrenia, conducted according to the recommended regimen, is required to provide solid evidence.
Topics: Male; Female; Adult; Humans; Paliperidone Palmitate; Schizophrenia; Network Meta-Analysis; Antipsychotic Agents; Prolactin; Isoxazoles; Pyrimidines; Delayed-Action Preparations; Treatment Outcome
PubMed: 36535950
DOI: 10.1038/s41398-022-02286-1 -
Pharmacological Research Feb 2022Antipsychotics represent the mainstay of schizophrenia pharmacological therapy, and their role has been expanded in the last years to mood disorders treatment. Although...
Antipsychotics represent the mainstay of schizophrenia pharmacological therapy, and their role has been expanded in the last years to mood disorders treatment. Although introduced in 1952, many years of research were required before an accurate picture of how antipsychotics work began to emerge. Despite the well-recognized characterization of antipsychotics in typical and atypical based on their liability to induce motor adverse events, their main action at dopamine D2R to elicit the "anti-psychotic" effect, as well as the multimodal action at other classes of receptors, their effects on intracellular mechanisms starting with receptor occupancy is still not completely understood. Significant lines of evidence converge on the impact of these compounds on multiple molecular signaling pathways implicated in the regulation of early genes and growth factors, dendritic spine shape, brain inflammation, and immune response, tuning overall the function and architecture of the synapse. Here we present, based on PRISMA approach, a comprehensive and systematic review of the above mechanisms under a translational perspective to disentangle those intracellular actions and signaling that may underline clinically relevant effects and represent potential targets for further innovative strategies in antipsychotic therapy.
Topics: Animals; Antipsychotic Agents; Brain; Chromatin Assembly and Disassembly; Epigenesis, Genetic; Gene Expression Regulation; Genes, Immediate-Early; Humans; Neuronal Plasticity; Neuroprotective Agents; Neurotransmitter Transport Proteins
PubMed: 35026403
DOI: 10.1016/j.phrs.2022.106078 -
NPJ Schizophrenia May 2021Early intervention is essential for favorable long-term outcomes in schizophrenia. However, there is limited guidance in the scientific literature on how best to choose... (Review)
Review
Early intervention is essential for favorable long-term outcomes in schizophrenia. However, there is limited guidance in the scientific literature on how best to choose between dopamine D receptor (DR) partial agonists and DR antagonists in early stages of schizophrenia. The aim of this meta-analysis was to directly compare DR partial agonists with DR antagonists for efficacy and tolerability, using randomized controlled trials (RCTs) that involved participants diagnosed with first-episode psychosis, schizophrenia, or related psychotic disorders with a duration of illness ≤5 years. Fourteen RCTs, involving 2494 patients, were included in the meta-analysis. Aripiprazole was the only identified DR partial agonist, and was not significantly different from pooled DR antagonists for overall symptom reduction or all-cause discontinuation. However, aripiprazole was more favorable than pooled DR antagonists for depressive symptoms, prolactin levels, and triglyceride levels. Specifically, aripiprazole was more favorable than paliperidone for triglyceride levels and more favorable than risperidone and olanzapine, but less favorable than ziprasidone, for weight gain. In addition, aripiprazole was less favorable for akathisia compared with second-generation DR antagonists, in particular olanzapine and quetiapine, and less favorable for discontinuation due to inefficacy than risperidone. Lastly, aripiprazole was more favorable than haloperidol for various efficacy and tolerability outcomes. In conclusion, aripiprazole's efficacy did not differ substantially from DR antagonists in the early course of schizophrenia, whereas differential tolerability profiles were noted. More double-blind RCTs are required comparing the efficacy and tolerability of aripiprazole as well as other DR partial agonists with DR antagonists in early stages of schizophrenia.
PubMed: 34035313
DOI: 10.1038/s41537-021-00158-z