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General Hospital Psychiatry 2022We conducted an updated, comprehensive, and contemporary systematic review to examine the efficacy of existing pharmacologic agents employed for management of delirium... (Review)
Review
OBJECTIVE
We conducted an updated, comprehensive, and contemporary systematic review to examine the efficacy of existing pharmacologic agents employed for management of delirium symptoms among hospitalized adults.
METHODS
Searches of PubMed, Scopus, Embase, and Cochrane Library databases from inception to May 2021 were performed to identify studies investigating efficacy of pharmacologic agents for management of delirium.
RESULTS
Of 11,424 articles obtained from searches, a total of 33 articles (N = 3030 participants) of randomized or non-randomized trials, in which pharmacologic treatment was compared to active comparator, placebo, or no treatment, met all criteria and were included in this review. Medications used for management of delirium symptoms included antipsychotic medications (N = 27), alpha-2 agonists (N = 5), benzodiazepines (N = 2), antidepressants (n = 1), acetylcholinesterase inhibitors (N = 2), melatonin (N = 2), opioids (N = 1), and antiemetics (N = 2). Despite somewhat mixed findings and a relative lack of high-quality trials, it appears that antipsychotic medications (e.g., haloperidol, olanzapine, risperidone, or quetiapine) and dexmedetomidine have the potential to improve delirium outcomes.
CONCLUSIONS
Pharmacologic agents can reduce delirium symptoms (e.g., agitation) in some hospitalized patients. Additional double-blinded, randomized, placebo-controlled clinical trials are critically needed to investigate the efficacy of pharmacologic agents for diverse hospitalized populations (e.g., post-surgical patients, patients at the end-of-life, or in intensive care units).
Topics: Adult; Humans; Antipsychotic Agents; Delirium; Acetylcholinesterase; Haloperidol; Risperidone
PubMed: 36375344
DOI: 10.1016/j.genhosppsych.2022.10.010 -
Systematic Reviews Mar 2023Keloids are pathologic scars that pose a significant functional and cosmetic burden. They are challenging to treat, despite the multitude of treatment modalities... (Review)
Review
BACKGROUND
Keloids are pathologic scars that pose a significant functional and cosmetic burden. They are challenging to treat, despite the multitude of treatment modalities currently available.
OBJECTIVE
The aim of this study was to conduct an evidence-based review of all prospective data regarding keloid treatments published between 2010 and 2020.
METHODS
A systematic literature search of PubMed (National Library of Medicine), Embase (Elsevier), and Cochrane Library (Wiley) was performed in November of 2020. Search strategies with the keywords "keloid" and "treatment" were performed by a medical librarian. The search was limited to prospective studies that were peer-reviewed, reported on clinical outcomes of keloid therapies, and were published in the English language between January 1, 2010, and November 24, 2020.
RESULTS
A total of 3462 unique citations were identified, of which 108 studies met inclusion criteria. Current literature supports silicone gel or sheeting with corticosteroid injections as first-line therapy for keloids. Adjuvant intralesional 5-fluorouracil (5-FU), bleomycin, or verapamil can be considered, although mixed results have been reported with each. Laser therapy can be used in combination with intralesional corticosteroids or topical steroids with occlusion to improve drug penetration. Excision of keloids with immediate post-excision radiation therapy is an effective option for recalcitrant lesions. Finally, silicone sheeting and pressure therapy have evidence for reducing keloid recurrence.
CONCLUSIONS
This review was limited by heterogeneity of subject characteristics and study outcome measures, small sample sizes, and inconsistent study designs. Larger and more robust controlled studies are necessary to further understand the variety of existing and emerging keloid treatments, including corticosteroids, cryotherapy, intralesional injections, lasers, photodynamic therapy, excision and radiation, pressure dressings, and others.
Topics: Humans; Prospective Studies; Keloid; Fluorouracil; Adrenal Cortex Hormones; Verapamil; Treatment Outcome
PubMed: 36918908
DOI: 10.1186/s13643-023-02192-7 -
Archives of Dermatological Research Jul 2023Treatment of actinic keratoses (AKs) can help lower the risk of eventual skin cancer and address field pre-cancerization. This review compares the different therapeutic... (Review)
Review
Treatment of actinic keratoses (AKs) can help lower the risk of eventual skin cancer and address field pre-cancerization. This review compares the different therapeutic options for actinic keratosis. Databases used include Medline, EMBASE, Web of Science and the Cochrane Library from inception to December 2019. Randomized control trials that were related to any approved or recognized treatment for actinic keratosis were included. 1186 studies were found, of which 80 with 6748 patients were included in the analysis. A network meta-analysis was not possible due to interstudy heterogeneity. The greatest degree of improvement was seen with photodynamic therapy (PDT) used adjunctively with other modalities, but this was not significantly different compared to other treatments. PDT, cryotherapy, imiquimod, ingenol mebutate (IMB), 5-fluorouracil (5-FU), trichloroacetic acid (TCA), and ablative fractional laser (AFXL), were all non-inferior to one another in terms of percent clearance of AKs, but the lowest rates of clearance were seen with diclofenac sodium. When results were substratified by body site, 5-FU, combination PDT and combination 5-FU with calcipotriol were the most beneficial for AKs on the head and neck, although they often caused the highest proportion of initial side effects. Absence of randomized control trials for surgical treatments and non-ablative laser limits comparison of these treatments to other modalities. Limitations include the lack of standardized outcome reporting limited the comparability of results across trials. The results of this analysis do not account for individual patient risk or cumulative risk for development of skin cancer. At present, PDT, cryotherapy, imiquimod, IMB, 5-FU, TCA, AFXL, and combination treatments are similarly efficacious in reducing AKs in immunocompetent patients.Registration: N/A.
Topics: Humans; Keratosis, Actinic; Imiquimod; Photochemotherapy; Treatment Outcome; Skin Neoplasms; Fluorouracil
PubMed: 36454335
DOI: 10.1007/s00403-022-02490-5 -
Molecular Autism Mar 2022There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD.
METHODS
We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses.
RESULTS
We analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n = 7450 participants) in children/adolescents and 18 RCTs (n = 1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k = 6 studies in analysis, SCD: SMD = 0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k = 3, RB:0.49 [0.18, 0.80]), bumetanide (k = 4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k = 4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k = 3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k = 1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k = 1, RB: 1.04 [0.27, 1.81]), oxytocin (k = 6, RB:0.41 [0.16, 0.66]) and risperidone (k = 1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed substantially in improving associated symptoms, and in their side-effect profiles.
LIMITATIONS
Most of the studies were inadequately powered (sample sizes of 20-80 participants), with short duration (8-13 weeks), and about a third focused on associated symptoms. Networks were mainly star-shaped, and there were indications of reporting bias. There was no optimal rating scale measuring change in core symptoms.
CONCLUSIONS
Some medications could improve core symptoms, although this could be likely secondary to the improvement of associated symptoms. Evidence on their efficacy and safety is preliminary; therefore, routine prescription of medications for the core symptoms cannot be recommended. Trial registration PROSPERO-ID CRD42019125317.
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Humans; Network Meta-Analysis; Oxytocin; Risperidone
PubMed: 35246237
DOI: 10.1186/s13229-022-00488-4 -
Journal of Comparative Effectiveness... Mar 2023To summarize the evidence in terms of efficacy and safety of head-to-head studies of high-intensity statins regardless of the underlying population. A systematic... (Meta-Analysis)
Meta-Analysis Review
To summarize the evidence in terms of efficacy and safety of head-to-head studies of high-intensity statins regardless of the underlying population. A systematic review and meta-analysis was conducted to summarize the effect sizes in randomized controlled trials and cohort studies that compared high-intensity statins. Based on 44 articles, similar effectiveness was observed across the statins in reducing LDL levels from baseline. All statins were observed to have similar adverse drug reactions (ADRs), although higher dosages were associated with more ADRs. Based on a pooled quantitative analysis of atorvastatin 80 mg versus rosuvastatin 40 mg, rosuvastatin was statistically more effective in reducing LDL. This review further confirms that high-intensity statins reduce LDL by ≥50%, favoring rosuvastatin over atorvastatin. Additional data are needed to confirm the clinical significance on cardiovascular outcomes using real-world studies.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Atorvastatin; Cohort Studies
PubMed: 36847307
DOI: 10.57264/cer-2022-0163 -
Asian Journal of Psychiatry Jan 2021Antipsychotics play a crucial role in the management of behavioral problems in patients undergoing hemodialysis. Oral and injectable antipsychotics are routinely... (Review)
Review
OBJECTIVE
Antipsychotics play a crucial role in the management of behavioral problems in patients undergoing hemodialysis. Oral and injectable antipsychotics are routinely prescribed to control emergent delirium or exacerbation of previous psychiatric symptoms. However scanty literature is available on the pharmacokinetics of antipsychotics in such patients. Avoiding amisulpride and warning against increasing the dosage in renal failure is the only recommendation by drug manufacturers and clinical guidelines. Hemodialysis affects the volume of distribution (V) and blood levels of antipsychotics in a complex manner. It is hence difficult to equate data on renal failure with hemodialysis to reliably predict the treatment response.
METHOD
We systematically analyzed online data from 1981 to 2019 on the use of antipsychotics in hemodialysis. The outcome was defined as the safety and efficacy of AP, measured in terms of adverse effects and relapse of existing or new onset of behavioral symptoms in Hemodialysis.
RESULTS
The data from 182 studies revealed that only 14 case reports and 1 case series met the review criteria. Oral Risperidone, Clozapine, Aripiprazole, Ziprasidone, Haloperidol, and Long-acting Risperidone, Flupenthixol, and Paliperidone were the antipsychotics studied in terms of pharmacokinetics during hemodialysis. AP levels in the blood were found to be unaffected in two studies during HD while the other two studies recommended scheduling of AP regimen w.r.t HD session. Six reports mentioned exacerbation of pre-existing psychiatric ailments in patients undergoing HD, the most common being schizophrenia.
CONCLUSION
Findings of the review reveals modest evidence favoring multiple dosing regimens of oral aripiprazole, ziprasidone, olanzapine, and risperidone. Long-acting risperidone and paliperidone are well tolerated and half of the conventional dose may be effective in the case of paliperidone. Though CYP-3A4 remains relatively and transiently unaltered during hemodialysis, none of the antipsychotics are compromised in HD. While selecting an AP during HD, one has to consider the protein binding, clearance by dialysis, duration of an HD session, route of administration of AP, and impaired bowel absorption in HD.
Topics: Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine; Renal Dialysis; Risperidone
PubMed: 33341539
DOI: 10.1016/j.ajp.2020.102484 -
Current Psychiatry Reports Nov 2021Over the last ten years, the treatment of psychosis has seen a near explosion of creative development in both novel agents and new delivery modalities. The current... (Review)
Review
PURPOSE OF REVIEW
Over the last ten years, the treatment of psychosis has seen a near explosion of creative development in both novel agents and new delivery modalities. The current review summarizes these developments over the past decade (2011-2020). We performed a systematic review utilizing PubMed and PsychInfo with the aim of identifying all the RCT and related analyses in adults with psychosis (schizophrenia and mania).
RECENT FINDINGS
We identified 11 significant developments: the introduction of new antipsychotics cariprazine, brexpiprazole, lumateperone, and pimavanserin; introduction of new delivery methods: subcutaneous long-acting risperidone, aripiprazole lauroxil, transdermal asenapine, and inhaled loxapine; and the introduction of new approaches such as olanzapine/samidorphan for olanzapine-associated weight gain, examination of the TAAR1 agonist SEP 363,856 as a test of concept, and the combination of Xanomeline/Trospium, an M and M muscarinic receptor agonist in conjunction with a peripheral anticholinergic. Last decade has seen a tremendous development in second-generation antipsychotics which provides unprecedented treatment options for clinicians in treating psychosis.
Topics: Adult; Antipsychotic Agents; Humans; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia
PubMed: 34843030
DOI: 10.1007/s11920-021-01298-w -
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 -
BMJ Open May 2022To conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) of the effectiveness and safety of oral pre-exposure prophylaxis (PrEP) to... (Meta-Analysis)
Meta-Analysis
Oral pre-exposure prophylaxis (PrEP) to prevent HIV: a systematic review and meta-analysis of clinical effectiveness, safety, adherence and risk compensation in all populations.
OBJECTIVE
To conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) of the effectiveness and safety of oral pre-exposure prophylaxis (PrEP) to prevent HIV.
METHODS
Databases (PubMed, Embase and the Cochrane Register of Controlled Trials) were searched up to 5 July 2020. Search terms for 'HIV' were combined with terms for 'PrEP' or 'tenofovir/emtricitabine'. RCTs were included that compared oral tenofovir-containing PrEP to placebo, no treatment or alternative medication/dosing schedule. The primary outcome was the rate ratio (RR) of HIV infection using a modified intention-to-treat analysis. Secondary outcomes included safety, adherence and risk compensation. All analyses were stratified a priori by population: men who have sex with men (MSM), serodiscordant couples, heterosexuals and people who inject drugs (PWIDs). The quality of individual studies was assessed using the Cochrane risk-of-bias tool, and the certainty of evidence was assessed using GRADE.
RESULTS
Of 2803 unique records, 15 RCTs met our inclusion criteria. Over 25 000 participants were included, encompassing 38 289 person-years of follow-up data. PrEP was found to be effective in MSM (RR 0.25, 95% CI 0.1 to 0.61; absolute rate difference (RD) -0.03, 95% CI -0.01 to -0.05), serodiscordant couples (RR 0.25, 95% CI 0.14 to 0.46; RD -0.01, 95% CI -0.01 to -0.02) and PWID (RR 0.51, 95% CI 0.29 to 0.92; RD -0.00, 95% CI -0.00 to -0.01), but not in heterosexuals (RR 0.77, 95% CI 0.46 to 1.29). Efficacy was strongly associated with adherence (p<0.01). PrEP was found to be safe, but unrecognised HIV at enrolment increased the risk of viral drug resistance mutations. Evidence for behaviour change or an increase in sexually transmitted infections was not found.
CONCLUSIONS
PrEP is safe and effective in MSM, serodiscordant couples and PWIDs. Additional research is needed prior to recommending PrEP in heterosexuals. No RCTs reported effectiveness or safety data for other high-risk groups, such as transgender women and sex workers.
PROSPERO REGISTRATION NUMBER
CRD42017065937.
Topics: Anti-HIV Agents; Emtricitabine; Female; HIV Infections; Humans; Male; Pre-Exposure Prophylaxis; Tenofovir; Treatment Outcome
PubMed: 35545381
DOI: 10.1136/bmjopen-2020-048478 -
Journal of Comparative Effectiveness... Apr 2022To conduct indirect treatment comparisons between risdiplam and other approved treatments for spinal muscular atrophy (SMA). Individual patient data from risdiplam... (Review)
Review
To conduct indirect treatment comparisons between risdiplam and other approved treatments for spinal muscular atrophy (SMA). Individual patient data from risdiplam trials were compared with aggregated data from published studies of nusinersen and onasemnogene abeparvovec, accounting for heterogeneity across studies. In Type 1 SMA, studies of risdiplam and nusinersen included similar populations. Indirect comparison results found improved survival and motor function with risdiplam versus nusinersen. Comparison with onasemnogene abeparvovec in Type 1 SMA and with nusinersen in Types 2/3 SMA was challenging due to substantial differences in study populations; no concrete conclusions could be drawn from the indirect comparison analyses. Indirect comparisons support risdiplam as a superior alternative to nusinersen in Type 1 SMA.
Topics: Azo Compounds; Humans; Muscular Atrophy, Spinal; Pyrimidines; Spinal Muscular Atrophies of Childhood
PubMed: 35040693
DOI: 10.2217/cer-2021-0216