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The Journal of Clinical Psychiatry Jul 2020To review the efficacy of antidepressants and other therapeutic agents for the treatment of cognitive impairment in adults with major depressive disorder (MDD).
OBJECTIVE
To review the efficacy of antidepressants and other therapeutic agents for the treatment of cognitive impairment in adults with major depressive disorder (MDD).
DATA SOURCES
We conducted a database search of MEDLINE, PsycINFO, and Embase through Ovid on May 7, 2019. The year of publication was not restricted. The search terms "Major Depressive Disorder," "depress*," "cognit*," and "therapeutics" were used.
STUDY SELECTION
The studies included in this review were clinical trials of antidepressants and other therapeutic agents in MDD populations. Participants were aged between 18 and 65 years and had a DSM-III, -IV, or -5 diagnosis of MDD. In total, 2,045 research papers were screened, 53 full-text articles were assessed, and 26 articles were eligible to be included in this systematic review.
DATA EXTRACTION
The data and quality of research papers were assessed and screened by 2 independent reviewers. Discrepancies were resolved through a third reviewer.
RESULTS
Overall, studies demonstrated that tricyclic antidepressants do not have procognitive effects, while vortioxetine and bupropion have demonstrated procognitive effects in MDD populations relative to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Several non-antidepressant agents, such as modafinil, amphetamines, and erythropoietin, have also demonstrated significant positive effects on cognition in depression.
CONCLUSIONS
Present-day antidepressants and other agents have demonstrated procognitive effects in MDD, but the findings between various agents are mixed. Further research looking at objective measures of cognitive performance would be helpful to obtain more definitive results regarding the efficacy of therapeutics for cognitive impairment in MDD.
Topics: Antidepressive Agents; Cognitive Dysfunction; Depressive Disorder, Major; Humans; Psychotropic Drugs
PubMed: 32726521
DOI: 10.4088/JCP.19r13200 -
Therapeutic Drug Monitoring Feb 2020Substance use disorder often coexists with other psychiatric disorders, resulting in the simultaneous use of recreational and prescription drugs. The authors aimed to...
PURPOSE
Substance use disorder often coexists with other psychiatric disorders, resulting in the simultaneous use of recreational and prescription drugs. The authors aimed to identify potential pharmacokinetic and pharmacodynamic interactions between new psychoactive substances of the cathinone class and specific prescription drugs.
METHODS
The authors performed a systematic literature review on interactions between synthetic cathinones (mephedrone, methylone, methylenedioxypyrovalerone, and alpha-pyrrolidinopentiophenone) and antidepressants (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine), attention deficit hyperactivity disorder (ADHD) medications (atomoxetine, dexamphetamine, methylphenidate, modafinil) or HIV medications.
RESULTS
Although no pharmacokinetic interactions have been reported in previous literatures, such interactions are likely to occur. Metabolic pathways of cathinones, antidepressants, and ADHD medications have been shown to overlap, including metabolism via cytochrome P450 enzymes and their inhibition. Consistent with this finding, interactions of bupropion (a cathinone) with antidepressants and ADHD medications have been found to increase their serum concentrations and half-lives. Additionally, limited pharmacodynamic interactions have been reported. However, as cathinones, antidepressants, and ADHD medications have been reported to increase the extracellular monoamine concentration by affecting reuptake transporters, interactions among these compounds are likely. Presumably, even higher monoamine concentrations could be observed when cathinones are combined with prescription drugs with a similar mode of action, as has been reported in animals exposed to duloxetine and bupropion. HIV medications have a different mode of action; thus, they have been reported to be less likely to have pharmacodynamic interactions with cathinones.
CONCLUSIONS
Clinicians should be aware of possible interactions between synthetic cathinones and prescription drugs, which may increase the risk of drug toxicity or reduce the therapeutic efficacy of the drugs. Qualitative drug screening for cathinones using mass spectrometry methods may aid the early detection of these agents.
Topics: Alkaloids; Anti-HIV Agents; Central Nervous System Stimulants; Cytochrome P-450 Enzyme System; Drug Interactions; Half-Life; Humans; Models, Biological; Selective Serotonin Reuptake Inhibitors
PubMed: 31425490
DOI: 10.1097/FTD.0000000000000682 -
Bipolar Disorders Mar 2020The aim of this study was to evaluate the efficacy and safety of the dopaminergic-enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study was to evaluate the efficacy and safety of the dopaminergic-enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar depression.
METHODS
A comprehensive search of major electronic databases was conducted to identify randomized controlled trials (RCTs) of adjunctive MoArm that included patients with bipolar I (BP-I) or bipolar II (BP-II) depression. Data for response/remission and all-cause discontinuation were analyzed. Effect size was summarized by relative risk (RR) using a random effect model.
RESULTS
Of 58 studies, five RCTs (N = 795 drug, N = 792 placebo) met inclusion criteria. Four armodafinil studies included only BP-I patients and one modafinil study included both bipolar subtypes with limited heterogeneity (I = 34%, P = .19; I = 18%, P = .30). Compared to placebo, augmentation with MoArm was associated with significantly greater rates of treatment response (RR, 1.18; 95% CI, 1.01-1.37; P = .03) and remission (RR, 1.38; 95% CI, 1.10-1.73; P = .005). All-cause discontinuation was not different than placebo (RR, 1.08; 95% CI, 0.89-1.30; P = .45) with no evidence of increased risk of mood switch or suicide attempts with MoArm (RR, 0.99; 95% CI, 0.39-2.5; P = .98; RR, 1.02; 95% CI, 0.37-2.85; P = .97).
CONCLUSION
This narrower scope meta-analysis of one drug for one disease suggests that adjunctive MoArm may represent a novel therapeutic intervention. Further studies delineating the subtypes of bipolar depression responsive to these novel dopaminergic-enhancing agents are encouraged.
Topics: Bipolar Disorder; Female; Humans; Modafinil; Randomized Controlled Trials as Topic
PubMed: 31643130
DOI: 10.1111/bdi.12859 -
Journal of Psychiatric Research Nov 2021Several drugs previously tested in clinical trials and approved for different indications have been repurposed for bipolar disorder. We carried out a systematic...
Several drugs previously tested in clinical trials and approved for different indications have been repurposed for bipolar disorder. We carried out a systematic meta-review of meta-analyses of randomized placebo-controlled trials investigating repurposed drugs as adjunctive treatments for mania and bipolar depression. We performed a critical appraisal using 'A MeaSurement Tool to Assess systematic Reviews' Version 2 (AMSTAR 2). We synthesized results on efficacy, tolerability, and safety, assessing evidence quality according to the 'Grading of Recommendations, Assessment, Development and Evaluations' (GRADE) approach. Our systematic search identified nine eligible studies investigating 12 drugs, four for mania and eight for bipolar depression. The quality of reporting was heterogeneous according to AMSTAR 2. In mania, allopurinol (for symptoms reduction and remission at 4-8 weeks) and tamoxifen (for response and symptoms reduction at 4-6 weeks) showed higher efficacy than placebo, with low and very low quality of evidence, respectively. Concerning bipolar depression, modafinil/armodafinil (for response, remission, and symptoms reduction at 6-8 weeks) and pramipexole (for response and symptoms reduction at 6 weeks) were superior to placebo, despite the low quality of evidence. Results on the efficacy of celecoxib and N-acetylcysteine were of low quality and limited to certain outcomes. Overall, the lack of evidence of high and moderate quality does not allow us to draw firm conclusions on the clinical utility of repurposed drugs as adjunctive treatments for mania and bipolar depression, highlighting the need for additional research.
Topics: Bipolar Disorder; Humans; Mania; Meta-Analysis as Topic; Modafinil; Pharmaceutical Preparations; Randomized Controlled Trials as Topic
PubMed: 34509090
DOI: 10.1016/j.jpsychires.2021.09.018 -
European Neuropsychopharmacology : the... Sep 2020Modafinil, methyphenidate (MPH) and d-amphetamine (d-amph) are putative cognitive enhancers. However, efficacy of cognitive enhancement has yet to be fully established.... (Meta-Analysis)
Meta-Analysis
How effective are pharmaceuticals for cognitive enhancement in healthy adults? A series of meta-analyses of cognitive performance during acute administration of modafinil, methylphenidate and D-amphetamine.
Modafinil, methyphenidate (MPH) and d-amphetamine (d-amph) are putative cognitive enhancers. However, efficacy of cognitive enhancement has yet to be fully established. We examined cognitive performance in healthy non-sleep-deprived adults following modafinil, MPH, or d-amph vs placebo in 3 meta-analyses, using subgroup analysis by cognitive domain; executive functions (updating, switching, inhibitory control, access to semantic/long term memory), spatial working memory, recall, selective attention, and sustained attention. We adhered to PRISMA. We identified k = 47 studies for analysis; k = 14 studies (64 effect sizes) for modafinil, k = 24 studies (47 effect sizes) for Methylphenidate, and k = 10 (27 effect sizes) for d-amph. There was an overall effect of modafinil (SMD=0.12, p=.01). Modafinil improved memory updating (SMD=0.28, p=.03). There was an overall effect of MPH (SMD=0.21, p=.0004) driven by improvements in recall (SMD=0.43, p=.0002), sustained attention (SMD=0.42, p=.0004), and inhibitory control (SMD=0.27, p=.03). There were no effects for d-amph. MPH and modafinil show enhancing effects in specific sub-domains of cognition. However, data with these stimulants is far from positive if we consider that effects are small, in experiments that do not accurately reflect their actual use in the wider population. There is a user perception that these drugs are effective cognitive enhancers, but this is not supported by the evidence so far.
Topics: Adult; Cognition; Dextroamphetamine; Drug Administration Schedule; Female; Healthy Volunteers; Humans; Male; Mental Recall; Methylphenidate; Modafinil; Nootropic Agents; Pharmaceutical Preparations
PubMed: 32709551
DOI: 10.1016/j.euroneuro.2020.07.002 -
Digestive Diseases and Sciences Aug 2019Fatigue is the most common complication of primary biliary cholangitis (PBC) and can be debilitating. Numerous interventions have been trialed targeting several proposed... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Fatigue is the most common complication of primary biliary cholangitis (PBC) and can be debilitating. Numerous interventions have been trialed targeting several proposed mechanisms of PBC-associated fatigue. We sought to summarize and perform a meta-analysis to determine the efficacy of these interventions.
METHODS
A comprehensive database search was conducted from inception through March 27, 2018. The primary outcome was proportion of fatigued patients or reduction in degree of fatigue. Adverse events were a secondary outcome. We assessed studies for risk of bias, graded quality of evidence, and used meta-analysis to obtain overall effect by pooling studies of the same class.
RESULTS
We identified 16 studies evaluating ursodeoxycholic acid (UDCA) (7), liver transplantation (2), serotonin reuptake inhibitors (2), colchicine (1), methotrexate (1), cyclosporine (1), modafinil (1), and obeticholic acid (1). On meta-analysis, UDCA was not associated with a reduction in risk of fatigue (RR = 0.86, 95% CI 0.69-1.08, p = 0.19, I = 56.2%). While liver transplantation did reduce degree of fatigue (SMD - 0.57, 95% CI - 0.89 to - 0.24, p = 0.001, I = 67.3%), fatigue did not return to baseline indicating the underlying cause may not be addressed.
CONCLUSIONS
While there is some improvement in fatigue with liver transplantation, there is a lack of high-quality evidence supporting the efficacy of any other intervention in the treatment of PBC-related fatigue. Further research into the underlying pathophysiology may help guide future trials.
Topics: Cholangitis; Fatigue; Humans; Liver Transplantation
PubMed: 30632051
DOI: 10.1007/s10620-019-5457-5 -
Journal of Clinical Psychopharmacology 2019The negative symptoms of schizophrenia pose a heavy burden on patients and relatives and represent an unmet therapeutic need. The observed association of negative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The negative symptoms of schizophrenia pose a heavy burden on patients and relatives and represent an unmet therapeutic need. The observed association of negative symptoms with impaired reward system function has stimulated research on prodopaminergic agents as potential adjunctive treatments.
METHODS
We conducted a systematic review and meta-analysis of published randomized controlled trials of amphetamine, methylphenidate, modafinil, armodafinil, lisdexamphetamine, L-dopa, levodopa, bromocriptine, cabergoline, quinagolide, lisuride, pergolide, apomorphine, ropinirole, pramipexole, piribedil, and rotigotine augmentation in schizophrenia and schizoaffective disorder.Medline, EMBASE, and several other databases as well as trial registries were searched for placebo-controlled trials.
RESULTS
Ten randomized controlled trials were included in the meta-analysis, 6 trials on modafinil, 2 on armodafinil, 1 on L-dopa, and 1 on pramipexole. Overall, prodopaminergic agents did not significantly reduce negative symptoms. Restricting the analysis to studies requiring a minimum threshold for negative symptom severity, modafinil/armodafinil showed a significant but small effect on negative symptoms. A subset of studies allowed for calculating specific effects for the negative symptom dimensions diminished expression and amotivation, but no significant effect was found. Prodopaminergic agents did not increase positive symptom scores.
CONCLUSIONS
The currently available evidence does not allow for formulating recommendations for the use of prodopaminergic agents for the treatment of negative symptoms. Nevertheless, the observed improvement in studies defining a minimum threshold for negative symptom severity in the absence of an increase in positive symptoms clearly supports further research on these agents.
Topics: Dopamine Agonists; Humans; Outcome Assessment, Health Care; Schizophrenia
PubMed: 31688399
DOI: 10.1097/JCP.0000000000001124 -
Wellcome Open Research 2021Shift work is essential in society but can be detrimental to health and quality of life and is associated with decreased productivity and increased risk of accidents....
A scoping review of the evidence for the impact of pharmacological and non-pharmacological interventions on shift work related sleep disturbance in an occupational setting.
Shift work is essential in society but can be detrimental to health and quality of life and is associated with decreased productivity and increased risk of accidents. Interventions to reduce these consequences are needed, but the extent and range of trial evidence for interventions for those most affected by their shift-work schedules is unclear. We therefore carried out a scoping review to assess the availability of evidence to inform the development and evaluation of future interventions. We aimed to identify clinical trials of any intervention for shift work-related sleep disturbance that included a comparator group, where the intervention was delivered in an occupational setting. We searched Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL, EMBASE, Medline and Science Citation Index from inception to 30 March 2020 for relevant citations. Citations were screened by two independent reviewers, a third reviewer resolved disagreements. Data were extracted by two independent reviewers. From 1250 unique citations, 14 studies met inclusion criteria for comparative trials of treatment in an occupational setting. There were five trials of hypnotics, five trials of stimulants, and four trials of non-pharmacological therapies (cognitive behavioural therapy, light therapy, aromatherapy and herbal medicine). Outcomes included sleep parameters, day-time sleepiness, and quality of life. There were no consistently reported outcomes across trials. Interventions fell into three distinct groups investigated in distinct time periods without progression from efficacy trials to wider-scale interventions. The lack of consistent patient-reported outcome measures limits synthesising findings. Some trials focussed on optimising sleep, others on reducing wake-time sleepiness. Adequately powered trials of existing interventions are needed, with the development and testing of novel combination treatments in patients with well-defined shift work sleep disorder. A core set of clinically relevant outcomes will develop and standardise the evidence-base for shift work sleep disorder.
PubMed: 37346814
DOI: 10.12688/wellcomeopenres.17002.2 -
Frontiers in Neurology 2024Traumatic brain injury (TBI), in any form and severity, can pose risks for developing chronic symptoms that can profoundly hinder patients' work/academic, social, and...
Traumatic brain injury (TBI), in any form and severity, can pose risks for developing chronic symptoms that can profoundly hinder patients' work/academic, social, and personal lives. In the past 3 decades, a multitude of pharmacological, stimulation, and exercise-based interventions have been proposed to ameliorate symptoms, memory impairment, mental fatigue, and/or sleep disturbances. However, most research is preliminary, thus limited influence on clinical practice. This review aims to systematically appraise the evidence derived from randomized controlled trials (RCT) regarding the effectiveness of pharmacological, stimulation, and exercise-based interventions in treating chronic symptoms due to TBI. Our search results indicate that despite the largest volume of literature, pharmacological interventions, especially using neurostimulant medications to treat physical, cognitive, and mental fatigue, as well as daytime sleepiness, have yielded inconsistent results, such that some studies found improvements in fatigue (e.g., Modafinil, Armodafinil) while others failed to yield the improvements after the intervention. Conversely, brain stimulation techniques (e.g., transcranial magnetic stimulation, blue light therapy) and exercise interventions were effective in ameliorating mental health symptoms and cognition. However, given that most RCTs are equipped with small sample sizes, more high-quality, larger-scale RCTs is needed.
PubMed: 38562423
DOI: 10.3389/fneur.2024.1321239