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Journal of Psychopharmacology (Oxford,... Feb 2024Medication adherence is a prerequisite to achieving beneficial treatment outcomes. In major depressive disorder, many patients fail to complete medication regimens,... (Review)
Review
BACKGROUND
Medication adherence is a prerequisite to achieving beneficial treatment outcomes. In major depressive disorder, many patients fail to complete medication regimens, raising concern for poor treatment outcomes. It is usual to experience adverse drug reactions (ADRs) while taking antidepressants, and relative discomfort is reported by patients.
AIMS
The present review focuses on the presence of antidepressant-related side effects and the subsequent relationship with medication non-adherence.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Following the preliminary research, the research question and eligibility criteria were created based on the PICO framework. All articles retrieved from the selected databases were exported to Covidence, a Systematic Review managing software tool. Two reviewers assessed the papers to identify the risk of bias using the Joanna Briggs Institute critical appraisal tool for cross-sectional studies. Seven studies with a low-moderate risk of bias fulfilled the eligibility criteria and were conducted from 2013 to 2020 in Europe, Africa and Asia.
RESULTS
The results demonstrated high levels of suboptimal adherence ranging from 46% to 83% amongst the studied population. A variety of side effects were reported by a significant number of participants predominantly with moderate severity. A correlation between the presence of ADRs and suboptimal rates of adherence to antidepressants was found. Somnolence and headaches among other unspecified ADRs were found to increase the dropout rates for selective serotonin reuptake inhibitors.
CONCLUSIONS
The present study elucidates the need for effective interventions to facilitate antidepressant adherence and enhance doctor-patient communication, benefiting both the individuals and the healthcare system and leading to better clinical outcomes and reduction of relapse-related costs.
Topics: Adult; Humans; Depressive Disorder, Major; Cross-Sectional Studies; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Drug-Related Side Effects and Adverse Reactions; Medication Adherence
PubMed: 38344912
DOI: 10.1177/02698811231224171 -
The Journal of Nutrition, Health & Aging Apr 2024To systematically review and quantitatively synthetize evidence on the use of PIPs linked to adverse health outcomes in older adults. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review and quantitatively synthetize evidence on the use of PIPs linked to adverse health outcomes in older adults.
METHODS
A Medline, Embase® and Opengrey libraries search was conducted from 2004 to February 2021, using the PICO model: older people, psychotropic drugs, inappropriate prescribing, and adverse drug events. Fixed-effects and random-effects meta-analysis were performed from 3 eligible studies using an inverse-variance method.
RESULTS
Of the 1943 originally identified abstracts, 106 met the inclusion criteria and 7 studies were included in this review. All were of good quality. The number of participants ranged from 318 to 383,150 older adults (54.5-74.4% women). Associations were found between PIPs use and decreased personal care activities of daily living (ADL), unplanned hospitalizations, falls and mortality. In the pooled analysis, association with falls was confirmed (1.23 [95%CI: 1.15;1.32]).
CONCLUSIONS
Participants of 65 years and older treated with PIPs were more at risk of adverse health outcomes than those using no PIPs, including greater risks of falls, functional disabilities, unplanned hospitalizations, and mortality. Results of the present systematic review and meta-analysis provide additional evidence for an appropriate and safe use of psychotropics in older adults.
Topics: Humans; Aged; Psychotropic Drugs; Activities of Daily Living; Inappropriate Prescribing; Accidental Falls; Female; Male; Hospitalization; Aged, 80 and over; Potentially Inappropriate Medication List
PubMed: 38341965
DOI: 10.1016/j.jnha.2024.100187 -
European Neuropsychopharmacology : the... Apr 2024The aim of the study was to assess the clinical utility of currently available pharmacogenomic (PGx) tools compared with treatment as usual (TAU), using a meta-analysis... (Meta-Analysis)
Meta-Analysis
Current level of evidence for improvement of antidepressant efficacy and tolerability by pharmacogenomic-guided treatment: A Systematic review and meta-analysis of randomized controlled clinical trials.
The aim of the study was to assess the clinical utility of currently available pharmacogenomic (PGx) tools compared with treatment as usual (TAU), using a meta-analysis of dichotomous and continuous antidepressant efficacy and tolerability data from previously published clinical trials. MEDLINE, clinicaltrial.gov, EU Clinical Trials Register, WHO ICTRP and CENTRAL were systematically searched; of the 962 results originally reviewed, 15 trials were included. Antidepressant efficacy was quantified by relative and absolute changes in symptom severity after eight weeks of treatment and by response and remission rates, while tolerability was estimated by the rate of study discontinuation for any reason. In the PGx-guided patients, symptom severity reduced by an average of 31.0% after eight weeks of treatment, compared to an average reduction of 26.8% in the TAU group. Accordingly, PGx-guided patients experienced a greater reduction in symptom severity of 3.4% (95%CI: 1.6-5.3%), which corresponded to a reduction in the Hamilton Depression score of 0.75 (0.30-1.21), a 37% (15-63%) higher remission rate, and an 18% (5-33%) higher response rate compared with TAU patients, while no difference was observed in discontinuation rate between groups. Notably, the majority of associations lost statistical significance when restricting the dataset to low risk of bias studies, while certain funnel plots suggested a potential publication bias favoring the reporting of statistically significant results. In summary, PGx tools marginally enhance antidepressant efficacy, but not antidepressant tolerability; thus, additional research and advancement of PGx tools are needed to improve integration of PGx in clinical pharmacotherapy of depression.
Topics: Humans; Pharmacogenetics; Antidepressive Agents
PubMed: 38340605
DOI: 10.1016/j.euroneuro.2024.01.005 -
BMC Psychiatry Feb 2024In recent years, accelerated transcranial magnetic stimulation (aTMS) has been developed, which has a shortened treatment period. The aim of this study was to evaluate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In recent years, accelerated transcranial magnetic stimulation (aTMS) has been developed, which has a shortened treatment period. The aim of this study was to evaluate the efficacy and long-term maintenance effects of aTMS in patients with major depressive disorder (MDD).
METHODS
We systematically searched online databases for aTMS studies in patients with MDD published before February 2023 and performed a meta-analysis on the extracted data.
RESULTS
Four randomized controlled trials (RCTs) and 10 before-and-after controlled studies were included. The findings showed that depression scores significantly decreased following the intervention (SMD = 1.80, 95% CI (1.31, 2.30), p < 0.00001). There was no significant difference in antidepressant effectiveness between aTMS and standard TMS (SMD = -0.67, 95% CI (-1.62, 0.27), p = 0.16). Depression scores at follow-up were lower than those directly after the intervention based on the depression rating scale (SMD = 0.22, 95% CI (0.06, 0.37), p = 0.006), suggesting a potential long-term maintenance effect of aTMS. Subgroup meta-analysis results indicated that different modes of aTMS may have diverse long-term effects. At the end of treatment with the accelerated repetitive transcranial magnetic stimulation (arTMS) mode, depressive symptoms may continue to improve (SMD = 0.29, 95% CI (0.10, 0.49), I = 22%, p = 0.003), while the accelerated intermittent theta burst stimulation (aiTBS) mode only maintains posttreatment effects (SMD = 0.01, 95% CI (-0.45, 0.47), I = 66%, p = 0.98).
CONCLUSIONS
Compared with standard TMS, aTMS can rapidly improve depressive symptoms, but there is no significant difference in efficacy. aTMS may also have long-term maintenance effects, but longer follow-up periods are needed to assess this possibility.
TRIAL REGISTRATION
This article is original and not under simultaneous consideration for publication. The study was registered on PROSPERO ( https://www.crd.york.ac.uk/prospero/ ) (number: CRD42023406590).
Topics: Humans; Transcranial Magnetic Stimulation; Depression; Depressive Disorder, Major; Antidepressive Agents; Research Design
PubMed: 38326789
DOI: 10.1186/s12888-024-05545-1 -
Biomedicine & Pharmacotherapy =... Mar 2024By meta-analysing pooled studies and available individual participant data, we aim to provide new insight on olanzapine therapeutic drug monitoring in schizophrenia. (Meta-Analysis)
Meta-Analysis
AIMS
By meta-analysing pooled studies and available individual participant data, we aim to provide new insight on olanzapine therapeutic drug monitoring in schizophrenia.
METHOD
We conducted a computerized search of bibliographic databases (Pubmed, Cochrane library, Web of Science and PsycINFO) to identify studies that assessed the relationship between olanzapine plasma concentration and the change in patients' clinical scores. We investigated this relationship with olanzapine plasma level 12h00 post-intake using a random-effects model.
RESULTS
7 studies were included in the pooled data analysis (781 patients). We found no difference in oral dose between responders and non-responders but a significantly higher concentration of 4.50 µg/L in responders (p < 0.01). Olanzapine concentration above the thresholds identified in each study was associated with response (odd ratio = 3.50, p = 0.0007). We identified that non-responder patients showed greater inter-individual variability than responders. In the individual data analysis (159 patients), we found no relationship between dose and clinical response but an association between plasma level and response in the shape of a parabolic curve. The Receiver Operating Characteristic curve found a threshold of 22.07 µg/L to identify responders (96% sensitivity, 86% specificity) and a threshold of 56.47 µg/L to identify a decreased probability of response.
CONCLUSION
In contrast to oral dose, our work confirmed that plasma olanzapine levels are associated with clinical response and should therefore be used to optimise treatment. We determined a treatment response threshold of 22.07 µg/L and suggest that a concentration above the therapeutic window may result in a decreased response.
Topics: Humans; Data Analysis; Odds Ratio; Olanzapine; Plasma; ROC Curve; Schizophrenia
PubMed: 38325263
DOI: 10.1016/j.biopha.2024.116236 -
Neuropsychopharmacology Reports Mar 2024To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis... (Meta-Analysis)
Meta-Analysis
AIM
To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis of double-blind, randomized, placebo-controlled trials of available antidepressants in Japan for older adults with MDD.
METHODS
Outcome measures included response rate (primary), improvement in depressive symptom scale score, remission rate, all-cause discontinuation, discontinuation due to adverse events, and at least one adverse event. A random-effects model was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (95% CI).
RESULTS
Nine double-blind, randomized, placebo-controlled trials (n = 2145) were identified. No study has been conducted in Japan. Our meta-analysis included the following antidepressants: duloxetine, escitalopram, imipramine, sertraline, venlafaxine, and vortioxetine. Antidepressants have significantly higher response rates than placebo (RR [95% CI] = 1.38 [1.04, 1.83], p = 0.02). Antidepressants outperformed placebo in terms of improving depressive symptom scale score (SMD [95% CI] = -0.62 [-0.92, -0.33], p < 0.0001). However, antidepressants were associated with a higher discontinuation rate due to adverse events (RR [95% CI] = 1.94 [1.30, 2.88], p = 0.001) and a higher incidence of at least one adverse event (RR [95% CI] = 1.11 [1.02, 1.21], p = 0.02) compared to placebo. The groups did not differ significantly in terms of remission rate or all-cause discontinuation.
CONCLUSIONS
Our meta-analysis concluded that treatment with antidepressants available in Japan is only weakly recommended for moderate to severe MDD in older adults.
Topics: Humans; Aged; Depressive Disorder, Major; Japan; Antidepressive Agents; Duloxetine Hydrochloride; Venlafaxine Hydrochloride; Randomized Controlled Trials as Topic
PubMed: 38318955
DOI: 10.1002/npr2.12422 -
Journal of the Academy of... 2024Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available... (Review)
Review
Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies.
Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available management options include de-escalation techniques and rapid tranquilization, mostly via parenteral formulations of medication. While the intramuscular route has been extensively studied in a range of clinical settings, the same cannot be said for intravenous (IV); this is despite potential benefits, including rapid absorption and complete bioavailability. This systematic review analyzed existing evidence for effectiveness and safety of IV medication for management of acute disturbances. It followed a preregistered protocol (PROSPERO identification CRD42020216456) and is reported following the guidelines set by Preferred Reporting Items for Systematic Review and Meta-Analysis. APA PsycINFO, MEDLINE, and EMBASE databases were searched for eligible interventional studies up until May 30th, 2023. Data analysis was limited to narrative synthesis since primary outcome measures varied significantly. Results showed mixed but positive results for the effectiveness of IV dexmedetomidine, lorazepam, droperidol, and olanzapine. Evidence was more limited for IV haloperidol, ketamine, midazolam, chlorpromazine, and valproate. There was no eligible data on the use of IV clonazepam, clonidine, diazepam, diphenhydramine, propranolol, ziprasidone, fluphenazine, carbamazepine, or promethazine. Most studies reported favorable adverse event profiles, though they are unlikely to have been sufficiently powered to pick up rare serious events. In most cases, evidence was of low or mixed quality, accentuating the need for further standardized, large-scale, multi-arm randomized controlled trials with homogeneous outcome measures. Overall, this review suggests that IV medications may offer an effective alternative parenteral route of administration in acute disturbance, particularly in general hospital settings.
Topics: Humans; Administration, Intravenous; Psychomotor Agitation; Aggression; Antipsychotic Agents; Prospective Studies
PubMed: 38309683
DOI: 10.1016/j.jaclp.2024.01.004 -
Journal of Managed Care & Specialty... Feb 2024Schizophrenia is a chronic, relapsing, and burdensome psychiatric disorder affecting approximately 0.25%-0.6% of the US population. Oral antipsychotic treatment (OAT)... (Review)
Review
A systematic review of the real-world effectiveness and economic and humanistic outcomes of selected oral antipsychotics among patients with schizophrenia in the United States: Updating the evidence and gaps.
BACKGROUND
Schizophrenia is a chronic, relapsing, and burdensome psychiatric disorder affecting approximately 0.25%-0.6% of the US population. Oral antipsychotic treatment (OAT) remains the cornerstone for managing schizophrenia. However, nonadherence and high treatment failure lead to increased disease burden and medical spending. Cost-effective management of schizophrenia requires understanding the value of current therapies to facilitate better planning of management policies while addressing unmet needs.
OBJECTIVE
To review existing evidence and gaps regarding real-world effectiveness and economic and humanistic outcomes of OATs, including asenapine, brexpiprazole, cariprazine, iloperidone, lumateperone, lurasidone, olanzapine/samidorphan, paliperidone, and quetiapine.
METHODS
We conducted a literature search using PubMed, American Psychological Association PsycINFO (EBSCOhost), and the Cumulative Index of Nursing and Allied Health Literature from January 2010 to March 2022 as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language articles describing adults with schizophrenia receiving at least 1 of the selected OATs and reporting real-world effectiveness, direct or indirect costs, humanistic outcomes, behavioral outcomes, adherence/persistence patterns, or product switching were identified.
RESULTS
We identified 25 studies from a total of 24,190 articles. Real-world effectiveness, cost, and adherence/persistence outcomes were reported for most OATs that were selected. Humanistic outcomes and product switching were reported only for lurasidone. Behavioral outcomes (eg, interpersonal relations and suicide ideation) were not reported for any OAT. The key economic outcomes across studies were incremental cost-effectiveness ratios, cost per quality-adjusted life-years, and health care costs. In studies that compared long-acting injectables (LAIs) with OATs, LAIs had a higher pharmacy and lower medical costs, while total health care cost was similar between LAIs and OATs. Indirect costs associated with presenteeism, absenteeism, or work productivity were not reported for any of the selected OATs. Overall, patients had poor adherence to OATs, ranging between 20% and 61% across studies. Product switching did not impact the all-cause health care costs before and after treatment.
CONCLUSIONS
Our findings showed considerable gaps exist for evidence on behavioral outcomes, humanistic outcomes, medication switching, and adherence/persistence across OATs. Our findings also suggest an unmet need regarding treatment nonadherence and lack of persistence among patients receiving OATs. We identified a need for research addressing OATs' behavioral and humanistic outcomes and evaluating the impact of product switching in adults with schizophrenia in the United States, which could assist clinicians in promoting patient-centered care and help payers understand the total value of new antipsychotic drugs.
Topics: Adult; Humans; United States; Antipsychotic Agents; Schizophrenia; Lurasidone Hydrochloride; Paliperidone Palmitate; Quetiapine Fumarate
PubMed: 38308625
DOI: 10.18553/jmcp.2024.30.2.183 -
BMC Anesthesiology Feb 2024To systematically review the evidence about the effect of haloperidol on postoperative delirium in elderly patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically review the evidence about the effect of haloperidol on postoperative delirium in elderly patients.
METHODS
PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure were used to find concerned studies for meta-analysis. The main outcome was the incidence of postoperative delirium, and the secondary outcomes were side effects of haloperidol and the length of hospital stay. The meta-analyses were conducted using the Review Manager Version 5.1. This study was conducted based on the PRISMA statement.
RESULTS
Eight RCTs (1569 patients) were included in the meta-analysis. There was a significant difference in the incidence of postoperative delirium between haloperidol and control groups (OR = 0.62, 95%CI 0.48-0.80, P = 0.0002, I = 20%). In addition, side effects of haloperidol and the duration of hospitalization were comparable (OR = 0.58, 95%CI 0.25-1.35, P = 0.21, I = 0%; MD =-0.01, 95%CI -0.16-0.15, P = 0.92, I = 28%). Subgroup analysis implied the effect of haloperidol on postoperative delirium might vary with the dose (5 mg daily: OR = 0.40, 95%CI 0.22-0.71, P = 0.002, I = 0%; <5 mg daily: OR = 0.72, 95%CI 0.42-1.23, P = 0.23, I = 0%).
CONCLUSIONS
The meta-analysis revealed perioperative application of haloperidol could decrease the occurrence of postoperative delirium without obvious side effects in elderly people, and high-dose haloperidol (5 mg daily) possessed a greater positive effect.
Topics: Humans; Aged; Haloperidol; Antipsychotic Agents; Emergence Delirium; Delirium; Hospitalization
PubMed: 38308229
DOI: 10.1186/s12871-024-02434-8 -
BMC Pregnancy and Childbirth Feb 2024Lamotrigine has become one of the most commonly prescribed antiseizure medications (ASM) in epileptic women during pregnancy and therefore requires regular updates... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lamotrigine has become one of the most commonly prescribed antiseizure medications (ASM) in epileptic women during pregnancy and therefore requires regular updates regarding its safety. The aim of this study was to estimate the association between in utero exposure to lamotrigine monotherapy and the occurrence of neurodevelopmental outcomes.
METHODS
All comparative studies assessing the occurrence of neurodevelopmental outcomes after epilepsy-indicated lamotrigine monotherapy exposure during pregnancy were searched. First, references were identified through a snowballing approach, then, through electronic databases (Medline and Embase) from 2015 to June 2022. One investigator evaluated study eligibility and extracted data and a second independent investigator reviewed the meta-analysis (MA). A systematic review and random-effects model approach were performed using a collaborative WEB-based meta-analysis platform (metaPreg.org) with a registered protocol (osf.io/u4gva).
RESULTS
Overall, 18 studies were included. For outcomes reported by at least 4 studies, the pooled odds ratios and 95% confidence interval obtained with the number of exposed (N1) and unexposed children (N0) included were: neurodevelopmental disorders as a whole 0.84 [0.66;1.06] (N1 = 5,271; N0 = 22,230); language disorders or delay 1.16 [0.67;2.00] (N1 = 313; N0 = 506); diagnosis or risk of ASD 0.97 [0.61;1.53] (N1 = at least 5,262; N0 = 33,313); diagnosis or risk of ADHD 1.14 [0.75;1.72] (N1 = at least 113; N0 = 11,530) and psychomotor developmental disorders or delay 2.68 [1.29-5.56] (N1 = 163; N0 = 220). The MA of cognitive outcomes included less than 4 studies and retrieved a significant association for infants exposed to lamotrigine younger than 3 years old but not in the older age groups.
CONCLUSION
Prenatal exposure to lamotrigine monotherapy is not found to be statistically associated with neurodevelopmental disorders as a whole, language disorders or delay, diagnosis or risk of ASD and diagnosis or risk of ADHD. However, the MA found an increased risk of psychomotor developmental disorders or delay and cognitive developmental delay in less than 3 years old children. Nevertheless, these findings were based exclusively on observational studies presenting biases and on a limited number of included children. More studies should assess neurodevelopmental outcomes in children prenatally exposed to lamotrigine.
Topics: Pregnancy; Child; Infant; Female; Humans; Aged; Child, Preschool; Lamotrigine; Prenatal Exposure Delayed Effects; Anticonvulsants; Epilepsy; Vitamins; Language Disorders
PubMed: 38308208
DOI: 10.1186/s12884-023-06242-9