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Molecular Psychiatry Feb 2022A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological... (Meta-Analysis)
Meta-Analysis
A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.
Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Carbamazepine; Female; Haloperidol; Humans; Lithium; Male; Mania; Network Meta-Analysis; Olanzapine; Paliperidone Palmitate; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Tamoxifen; Valproic Acid
PubMed: 34642461
DOI: 10.1038/s41380-021-01334-4 -
Psychiatry Research May 2022There are currently no evidence-based treatment recommendations for impulse control disorders, which include intermittent explosive disorder (IED), kleptomania and... (Review)
Review
There are currently no evidence-based treatment recommendations for impulse control disorders, which include intermittent explosive disorder (IED), kleptomania and pyromania. Therefore, this systematic review sought to identify all randomized controlled trials (RCTs) that investigated pharmacological treatments for impulse control disorders, to evaluate their efficacy and tolerability. Searches were conducted within MEDLINE, PsychINFO, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Eight studies were included, six investigated pharmacotherapies for IED, while two investigated management for kleptomania. For the treatment of IED, oxcarbazepine and fluoxetine were the most efficacious. Importantly, divalproex was not superior to placebo in decreasing IED symptoms and was associated with significant adverse effects. In the treatment of kleptomania, only naltrexone was effective. The existing data suggest that the pharmacological treatment for impulse control disorders is an understudied area of psychiatry. Much of the current research on impulse control disorders focuses on management with anticonvulsants and antidepressants. Further studies conducted on these interventions in this population may yield promising results.
Topics: Antidepressive Agents; Disruptive, Impulse Control, and Conduct Disorders; Fluoxetine; Humans; Valproic Acid
PubMed: 35305343
DOI: 10.1016/j.psychres.2022.114499 -
The Journal of Headache and Pain May 2023While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis.
METHODS
We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to August 13, 2022, for randomized trials of pharmacological treatments for migraine prophylaxis in adults. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist random-effects network meta-analysis and rated the certainty (quality) of evidence as either high, moderate, low, or very low using the GRADE approach.
RESULTS
We identified 74 eligible trials, reporting on 32,990 patients. We found high certainty evidence that monoclonal antibodies acting on the calcitonin gene related peptide or its receptor (CGRP(r)mAbs), gepants, and topiramate increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo. We found moderate certainty evidence that beta-blockers, valproate, and amitriptyline increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, and low certainty evidence that gabapentin may not be different from placebo. We found high certainty evidence that, compared to placebo, valproate and amitriptyline lead to substantial adverse events leading to discontinuation, moderate certainty evidence that topiramate, beta-blockers, and gabapentin increase adverse events leading to discontinuation, and moderate to high certainty evidence that (CGRP(r)mAbs) and gepants do not increase adverse events.
CONCLUSIONS
(CGRP(r)mAbs) have the best safety and efficacy profile of all drugs for migraine prophylaxis, followed closely by gepants.
Topics: Adult; Humans; Topiramate; Valproic Acid; Gabapentin; Calcitonin Gene-Related Peptide; Network Meta-Analysis; Amitriptyline; Antibodies, Monoclonal; Migraine Disorders
PubMed: 37208596
DOI: 10.1186/s10194-023-01594-1 -
Seizure Nov 2022Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available evidence and provide estimates of comparative effectiveness and ranking of treatment effects.
METHODS
All randomized controlled trials studying patients (>1 month of age) with benzodiazepine-resistant SE were included. Outcomes including seizure cessation within 60 min, seizure freedom for 24 h, death, respiratory depression warranting intubation and cardiovascular instability were studied. Conventional and network meta-analyses (NMA) were done.
RESULTS
Seventeen studies were included (16 in NMA). Phenobarbital and high-dose levetiracetam were significantly superior to phenytoin with respect to seizure cessation within 60 min. Network ranking demonstrated that phenobarbital had the highest probability of being the best among the studied interventions followed by high-dose levetiracetam and high-dose valproate. Network meta-analysis was limited by predominant indirect evidence and high heterogeneity.On pairwise comparisons, phenobarbital was found to be associated with a higher risk of need for intubation and cardiovascular instability. Levetiracetam had a better safety profile than fosphenytoin.
CONCLUSIONS
Based on low quality evidence, phenobarbital appears to be the most effective agent for seizure cessation within 60 min of administration in patients with benzodiazepine resistant status epilepticus. High-dose levetiracetam, high-dose valproate and fosphenytoin are probably equally effective. Choice of medication may be guided by effectiveness, safety concerns, availability, cost and systemic co-morbidities.
Topics: Adult; Child; Humans; Anticonvulsants; Benzodiazepines; Levetiracetam; Network Meta-Analysis; Phenobarbital; Phenytoin; Seizures; Status Epilepticus; Valproic Acid; Drug Resistance; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36209676
DOI: 10.1016/j.seizure.2022.09.017 -
European Journal of Investigation in... Aug 2023This review aimed to investigate the metabolic alterations associated with psychopharmacological treatment of neuropsychiatric disorders, which can significantly impact... (Review)
Review
This review aimed to investigate the metabolic alterations associated with psychopharmacological treatment of neuropsychiatric disorders, which can significantly impact patients' physical health and overall quality of life. The study utilized the PRISMA methodology and included cross-sectional, retrospective studies, and randomized clinical trials from reputable databases like SCOPUS, CLARIVATE, SCIENCE DIRECT, and PUBMED. Out of the 64 selected studies, various psychotropic drug classes were analyzed, including antidepressants, anticonvulsants, and antipsychotics. Among the antidepressants, such as amitriptyline, Imipramine, and clomipramine, weight gain, constipation, and cardiovascular effects were the most commonly reported metabolic adverse effects. SSRI antidepressants like Fluoxetine, Sertraline, Citalopram, Escitalopram, and Paroxetine exhibited a high prevalence of gastrointestinal and cardiac alterations. Regarding anticonvulsants, valproic acid and Fosphenytoin were associated with adverse reactions such as weight gain and disturbances in appetite and sleep patterns. As for antipsychotics, drugs like Clozapine, Olanzapine, and Risperidone were linked to weight gain, diabetes, and deterioration of the lipid profile. The findings of this review emphasize the importance of continuous monitoring for adverse effects, particularly considering that the metabolic changes caused by psychopharmacological medications may vary depending on the age of the patients. Future research should focus on conducting field studies to further expand knowledge on the metabolic effects of other commonly prescribed psychotropic drugs. Overall, the study highlights the significance of understanding and managing metabolic alterations induced by psychopharmacological treatment to enhance patient care and well-being.
PubMed: 37623307
DOI: 10.3390/ejihpe13080110 -
Journal of Affective Disorders Aug 2022Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the... (Review)
Review
OBJECTIVES
Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the clinician. The aim of this paper is to give an overview of the evidence-based treatment options for rapid cycling.
METHODS
A systematic search on Pubmed, Embase and Cochrane databases from inception until December 2021 was conducted according to the PRISMA guidelines. An additional search on clinicaltrials.gov was done. References of retrieved papers and key reviews were hand-searched. Randomized controlled trials including at least 10 patients with bipolar disorder, rapid cycling, reporting an objective outcome measure were selected.
RESULTS
Our search, initially revealing 1330 articles, resulted in 16 papers about treatment of an acute mood episode, relapse prevention or both. Lithium, anticonvulsants, second generation antipsychotics, antidepressants and thyroid hormone were assessed as treatment options in the presented data. Evidence supporting the use of aripiprazole, olanzapine, quetiapine, valproate and lamotrigine for treatment of rapid cycling bipolar disorder was found.
LIMITATIONS
Small sample sizes, different index episodes and variety of outcome measures.
CONCLUSION
Evidence regarding treatment of rapid cycling remains scarce. Evidence supports the use of aripiprazole, olanzapine, and valproate for acute manic or mixed episodes, quetiapine for acute depressive episodes and aripiprazole and lamotrigine for relapse prevention. Given the paucity of available evidence, and the burden that accompanies rapid cycling, future research is warranted.
Topics: Anticonvulsants; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Humans; Lamotrigine; Olanzapine; Quetiapine Fumarate; Valproic Acid
PubMed: 35545157
DOI: 10.1016/j.jad.2022.05.017 -
Journal of Clinical PsychopharmacologyHyperammonemia is an adverse effect that poses clinical uncertainty around valproic acid (VPA) use. The prevalence of symptomatic and asymptomatic hyperammonemia and its...
BACKGROUND
Hyperammonemia is an adverse effect that poses clinical uncertainty around valproic acid (VPA) use. The prevalence of symptomatic and asymptomatic hyperammonemia and its relationship to VPA concentration is not well established. There is also no clear guidance regarding its management. This results in variability in the monitoring and treatment of VPA-induced hyperammonemia. To inform clinical practice, this systematic review aims to summarize evidence available around VPA-associated hyperammonemia and its prevalence, clinical outcomes, and management.
METHODS
An electronic search was performed through Ovid MEDLINE, Ovid Embase, Web of Science, and PsycINFO using search terms that identified hyperammonemia in patients receiving VPA. Two reviewers independently performed primary title and abstract screening with a third reviewer resolving conflicting screening results. This process was repeated during the full-text review process.
RESULTS
A total of 240 articles were included. Prevalence of asymptomatic hyperammonemia (5%-73%) was higher than symptomatic hyperammonemia (0.7%-22.2%) and occurred within the therapeutic range of VPA serum concentration. Various risk factors were identified, including concomitant medications, liver injury, and defects in carnitine metabolism. With VPA discontinued, most symptomatic patients returned to baseline mental status with normalized ammonia level. There was insufficient data to support routine monitoring of ammonia level for VPA-associated hyperammonemia.
CONCLUSIONS
Valproic acid-associated hyperammonemia is a common adverse effect that may occur within therapeutic range of VPA. Further studies are required to determine the benefit of routine ammonia level monitoring and to guide the management of VPA-associated hyperammonemia.
Topics: Humans; Valproic Acid; Anticonvulsants; Epilepsy; Hyperammonemia; Ammonia; Clinical Decision-Making; Uncertainty; Drug-Related Side Effects and Adverse Reactions
PubMed: 37126830
DOI: 10.1097/JCP.0000000000001689 -
Journal of Neurology Oct 2023To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and related entities.
METHODS
Two reviewers independently searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials from December 2022 to February 2023. Studies on the efficacy and safety of ASM monotherapies or adjunctive therapies for IGEs and related entities-including juvenile myoclonic epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy, or generalized tonic-clonic seizures alone (GTCA)-were included. Efficacy outcomes were the proportions of patients remaining seizure free for 1, 3, 6, and 12 months; safety outcomes were the proportions of any treatment-emergent adverse event (TEAE) and TEAEs leading to discontinuation. Network meta-analyses were performed in a random-effects model to obtain odds ratios and 95% confidence intervals. Rankings of ASMs were based on the surface under the cumulative ranking curve (SUCRA). This study is registered with PROSPERO (No. CRD42022372358).
RESULTS
Twenty-eight randomized controlled trials containing 4282 patients were included. As monotherapies, all ASMs were more effective than placebo, and valproate and ethosuximide were significantly better than lamotrigine. According to the SUCRA for efficacy, ethosuximide ranked first for CAE, whereas valproate ranked first for other types of IGEs. As adjunctive therapies, topiramate ranked best for GTCA as well as overall for IGEs, while levetiracetam ranked best for myoclonic seizures. For safety, perampanel ranked best (measured by any TEAE).
CONCLUSIONS
All of the studied ASMs were more effective than placebo. Valproate monotherapy ranked best overall for IGEs, whereas ethosuximide ranked best for CAE. Adjunctive topiramate and levetiracetam were most effective for GTCA and myoclonic seizures, respectively. Furthermore, perampanel had the best tolerability.
Topics: Humans; Child; Valproic Acid; Topiramate; Network Meta-Analysis; Levetiracetam; Ethosuximide; Anticonvulsants; Epilepsy, Generalized; Seizures; Randomized Controlled Trials as Topic
PubMed: 37378757
DOI: 10.1007/s00415-023-11834-8 -
BMJ Open Jul 2019The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain...
OBJECTIVE
The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain injury (TBI).
METHODS
We performed a search strategy in PubMed, OvidMEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Google Scholar, Directory of Open Access Journals, LILACS, Web of Science and Prospero (up to 10 December 2018) for published and unpublished evidence on the risks and benefits of 9 prespecified medications classes used to control agitated behaviours following TBI. We included all randomised controlled trials, quasi-experimental and observational studies examining the effects of medications administered to control agitated behaviours in TBI patients. Included studies were classified into three mutually exclusive categories: (1) agitated behaviour was the presenting symptom; (2) agitated behaviour was not the presenting symptom, but was measured as an outcome variable; and (3) safety of pharmacological interventions administered to control agitated behaviours was measured.
RESULTS
Among the 181 articles assessed for eligibility, 21 studies were included. Of the studies suggesting possible benefits, propranolol reduced maximum intensities of agitation per week and physical restraint use, methylphenidate improved anger measures following 6 weeks of treatment, valproic acid reduced weekly agitated behaviour scale ratings and olanzapine reduced irritability, aggressiveness and insomnia between weeks 1 and 3 of treatment. Amantadine showed variable effects and may increase the risk of agitation in the critically ill. In three studies evaluating safety outcomes, antipsychotics were associated with an increased duration of post-traumatic amnesia (PTA) in unadjusted analyses. Small sample sizes, heterogeneity and an unclear risk of bias were limits.
CONCLUSIONS
Propranolol, methylphenidate, valproic acid and olanzapine may offer some benefit; however, they need to be further studied. Antipsychotics may increase the length of PTA. More studies on tailored interventions and continuous evaluation of safety and efficacy throughout acute, rehabilitation and outpatient settings are needed.
PROSPERO REGISTRATION NUMBER
CRD42016033140.
Topics: Antipsychotic Agents; Brain Injuries, Traumatic; Humans; Psychomotor Agitation; Psychoses, Substance-Induced; Randomized Controlled Trials as Topic
PubMed: 31289093
DOI: 10.1136/bmjopen-2019-029604 -
Journal of Clinical Medicine Sep 2023Long-term medication with valproic acid has been associated with acute pancreatitis. The purpose of this report is to gain insight into the features of this... (Review)
Review
Long-term medication with valproic acid has been associated with acute pancreatitis. The purpose of this report is to gain insight into the features of this pancreatitis. A preregistered literature search (CRD42023438294) was performed on the National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar. Patients with alcohol abuse disorder, gallstone disease, hypertriglyceridemia or hypercalcemia, patients with acute valproic acid intoxication, and patients with a pre-existing pancreatitis were excluded. For the final analysis, we retained 73 reports published between 1979 and 2023, which described 125 subjects (83 children and 42 adults predominantly affected by an epilepsy) with an acute pancreatitis related to valproic acid. The diagnosis was made 11 (3.0-24) months (median and interquartile range) after starting valproic acid. One hundred and five cases (84%) recovered and twenty (16%) died. Sex, age, dosage or circulating level of valproic acid, latency time, prevalence of intellectual disability, and antiepileptic co-medication were similar in cases with and without a lethal outcome. Nineteen subjects were rechallenged with valproic acid after recovery: sixteen (84%) cases developed a further episode of pancreatitis. In conclusion, pancreatitis associated with valproic acid presents at any time during treatment and has a high fatality rate.
PubMed: 37762984
DOI: 10.3390/jcm12186044