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Frontiers in Public Health 2022Pharmacological neuroenhancement (PN) describes the use of divergent psychoactive substances to enhance mental performance (cognition) without medical need. This kind of...
Pharmacological neuroenhancement (PN) describes the use of divergent psychoactive substances to enhance mental performance (cognition) without medical need. This kind of substance abuse takes place predominantly in stressful situations. Users implicitly-or even explicitly-describe this kind of drug abuse to be a coping strategy. Regarding the decision making process whether to use PN drugs or not, users indicate that legal aspects to be decisive. However, the legal situation has been neglected so far. To elucidate the German legal situation, PN substances have to be divided into over-the-counter drugs, prescription drugs and illegal drugs. Amphetamines have the highest cognition-enhancing potential, followed by modafinil and caffeine-containing substances. It is pointed out that the use of both freely available and prescription PN substances and narcotics without medical indication have so far been largely exempt from punishment under German law. However, individuals (physicians, bus and truck drivers, etc.) taking PN substances may expose others at risk due to wrong decisions (driving or treatment), errors based on side effects of the used substances. Therefore, the protection of life and health of others could legitimize criminal regulation.
Topics: Humans; Criminals; Substance-Related Disorders; Illicit Drugs; Amphetamines; Adaptation, Psychological
PubMed: 36388290
DOI: 10.3389/fpubh.2022.1028654 -
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 -
The Cochrane Database of Systematic... Dec 2019People with schizophrenia have a range of different symptoms, including positive symptoms (hallucinations and delusions), negative symptoms (such as social withdrawal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
People with schizophrenia have a range of different symptoms, including positive symptoms (hallucinations and delusions), negative symptoms (such as social withdrawal and lack of affect), and cognitive impairment. The standard medication for people with schizophrenia is antipsychotics. However, these medications may not be effective for all symptoms of schizophrenia, as cognitive and negative symptoms are usually hard to treat. Additional therapies or medications are available for the management of these symptoms. Modafinil, a wakefulness-promoting agent most frequently used in narcolepsy or shift work sleep disorder, is one intervention that is theorised to have an effect of these symptoms.
OBJECTIVES
The primary objective of this review was to assess the effects of modafinil for people with schizophrenia or related disorders.
SEARCH METHODS
On 27 April 2015, 24 May 2017, and 31 October 2019, we searched the Cochrane Schizophrenia Group's register of trials, which is based on regular searches of CENTRAL, MEDLINE, Embase, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials. There are no language, time, document type, or publication status limitations for the inclusion of records in the register.
SELECTION CRITERIA
We selected all randomised controlled trials comparing modafinil with placebo or other treatments for people with schizophrenia or schizophrenia-spectrum disorders.
DATA COLLECTION AND ANALYSIS
We independently extracted data from the included studies. We analysed dichotomous data using risk ratios (RR) and 95% confidence intervals (CI). We analysed continuous data using mean difference (MD) with a 95% CI. We used a random-effects model for the meta-analysis. We used GRADE to complete a 'Summary of findings' table and assessed risk of bias for the included studies.
MAIN RESULTS
Eleven studies including a total of 422 participants contributed to data analyses. Most studies had a small population size (average 38 people per study) and were of short duration. We also detected a high risk of bias for selective outcome reporting in just under 50% of the trials. We therefore rated the overall methodological quality of the included studies as low. We considered seven main outcomes of interest: clinically important change in overall mental state, clinically important change in cognitive functioning, incidence of a clinically important adverse effect/event, clinically important change in global state, leaving the study early for any reason, clinically important change in quality of life, and hospital admission. All studies assessed the effects of adding modafinil to participants' usual antipsychotic treatment compared to adding placebo to usual antipsychotic treatment. Six studies found that adding modafinil to antipsychotic treatment may have little or no effect on overall mental state of people with schizophrenia, specifically the risk of worsening psychosis (RR 0.91, 95% CI 0.28 to 2.98; participants = 209; studies = 6, low-quality evidence). Regarding the effect of modafinil on cognitive function, the trials did not report clinically important change data, but one study reported endpoint scores on the MATRICS Consensus Cognitive Battery (MCCB): in this study we found no clear difference in scores between modafinil and placebo treatment groups (MD -3.10, 95% CI -10.9 to 4.7; participants = 48; studies = 1, very low-quality evidence). Only one study (N = 35) reported adverse effect/event data. In this study one serious adverse event occurred in each group (RR 0.84, 95% CI 0.06 to 12.42; participants = 35; studies = 1, very low-quality evidence). One study measured change in global state using the Clinical Global Impression - Improvement Scale. This study found that adding modafinil to antipsychotic treatment may have little or no effect on global state (RR 6.36, 95% CI 0.94 to 43.07, participants = 21; studies = 1, very low-quality evidence). Nine studies found that modafinil has no effect on numbers of participants leaving the study early (RR 1.26, 95% CI 0.63 to 2.52 participants = 357; studies = 9, moderate-quality evidence). None of the trials reported clinically important change in quality of life, but one study did report quality of life using endpoint scores on the Quality of Life Inventory, finding no clear difference between treatment groups (MD -0.2, 95% CI -1.18 to 0.78; participants = 20; studies = 1, very low-quality evidence). Finally, one study reported data for number of participants needing hospitalisation: one participant in each group was hospitalised (RR 0.84, 95% CI 0.06 to 12.42; participants = 35; studies = 1, very low-quality evidence).
AUTHORS' CONCLUSIONS
Due to methodological issues, low sample size, and short duration of the clinical trials as well as high risk of bias for outcome reporting, most of the evidence available for this review is of very low or low quality. For results where quality is low or very low, we are uncertain or very uncertain if the effect estimates are true effects, limiting our conclusions. Specifically, we found that modafinil is no better or worse than placebo at preventing worsening of psychosis; however, we are uncertain about this result. We have more confidence that participants receiving modafinil are no more likely to leave a trial early than participants receiving placebo. However, we are very uncertain about the remaining equivocal results between modafinil and placebo for outcomes such as improvement in global state or cognitive function, incidence of adverse events, and changes in quality of life. More high-quality data are needed before firm conclusions regarding the effects of modafinil for people with schizophrenia or related disorders can be made.
Topics: Antipsychotic Agents; Cognition; Humans; Modafinil; Quality of Life; Randomized Controlled Trials as Topic; Schizophrenia; Wakefulness-Promoting Agents
PubMed: 31828767
DOI: 10.1002/14651858.CD008661.pub2 -
Psychiatrike = Psychiatriki 2016Bipolar disorder (BD) has a complex and variable clinical picture which is characterized by many different phacets and phases and as a result its therapeutical options... (Review)
Review
Bipolar disorder (BD) has a complex and variable clinical picture which is characterized by many different phacets and phases and as a result its therapeutical options are also complex and often unsatisfactory. Typically the so-called "mood stabilizers" are used in the treatment of BD and in this class lithium and specific antiepileptics are included. The present study aimed to systematically review the literature concerning the presence of randomized double blind clinical trials of 'non conventional' pharmaceutical treatment options. The present systematic review utilized the PRISMA method and searched the MEDLINE through January 1st 2015 with the use of appropriate key words. In order to identify randomized controlled trials- RCTs a combination of the words "bipolar", "manic", "mania", "manic depression" and "manic depressive" with "randomized" was used. Webpages with lists of trials were also searched including http://clinicaltrials.gov and http://www.clinicalstudyresults.org as well as the official webpages of all pharma companies with products marketed in the treatment of BD. The reference lists of various review papers were also searched. The MEDLINE was searched with the combination of the words "guidelines" or "algorithms" with "mania", "manic", "bipolar", "manicdepressive" or "manic depression" in order to identify articles with treatment guidelines. The reference list of these articles were also scanned. From 3,284 papers which were initially traced, only 47 papers were included in the present study. From those agents studied in acute mania, tamoxifen is efficacious as monotherapy and as combination therapy with lithium and other mood stabilizers, however its safety profile is relatively poor. Allopurinol manifests efficacy in combination with lithium but not with other agents and its safety profile is satisfactory. Methoxyprogesterone is efficacious in combination with mood stabilizers and its safety profile is very good. In acute bipolar depression the combinations of FEWP with carbamazepine and ketamine, modafinil, pramipexole, pregnenolone and maybe armodafinil with mood stabilizers are efficacious. The safety profile of these combinations is medium. The use of celecoxib, lisdexamfetamine and memantine have negative data. Concerning the maintenance treatment, the data are negative for memantine and for Nacetylcysteine. Although most of the data concerning the usefulness of "non-conventional" pharmacotherapeutic agents in the treatment of bipolar disorder are negative, it is encouraging that those agents who have been proven efficacious probably exert their therapeutic effect through pathways which differ from usual and probably different from those classically considered in most biological models of bipolar illness. In this way there constitute new paradigms and open new horizons in the understanding of the disease.
Topics: Antimanic Agents; Bipolar Disorder; Drug Therapy, Combination; Humans; Psychotropic Drugs; Randomized Controlled Trials as Topic
PubMed: 28114089
DOI: 10.22365/jpsych.2016.274.253 -
Current Oncology (Toronto, Ont.) Apr 2018Our objective was to determine whether, compared with control interventions, pharmacologic interventions reduce the severity of fatigue in patients with cancer or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Our objective was to determine whether, compared with control interventions, pharmacologic interventions reduce the severity of fatigue in patients with cancer or recipients of hematopoietic stem-cell transplantation (hsct).
METHODS
For a systematic review, we searched medline, embase, the Cochrane Central Register of Controlled Trials, cinahl, and Psychinfo for randomized trials of systemic pharmacologic interventions for the management of fatigue in patients with cancer or recipients of hsct. Two authors independently identified studies and abstracted data. Methodologic quality was assessed using the Cochrane Risk of Bias tool. The primary outcome was fatigue severity measured using various fatigue scales. Data were synthesized using random-effects models.
RESULTS
In the 117 included trials (19,819 patients), the pharmacologic agents used were erythropoietins ( = 31), stimulants ( = 19), l-carnitine ( = 6), corticosteroids ( = 5), antidepressants ( = 5), appetite stimulants ( = 3), and other agents ( = 48). Fatigue was significantly reduced with erythropoietin [standardized mean difference (smd): -0.52; 95% confidence interval (ci): -0.89 to -0.14] and with methylphenidate (smd: -0.36; 95% ci: -0.56 to -0.15); modafinil (or armodafinil) and corticosteroids were not effective.
CONCLUSIONS
Erythropoietin and methylphenidate significantly reduced fatigue severity in patients with cancer and in recipients of hsct. Concerns about the safety of those agents might limit their usefulness. Future research should identify effective interventions for fatigue that have minimal adverse effects.
Topics: Central Nervous System Stimulants; Erythropoietin; Fatigue; Hematopoietic Stem Cell Transplantation; Humans; Methylphenidate; Neoplasms; Severity of Illness Index
PubMed: 29719440
DOI: 10.3747/co.25.3883 -
Frontiers in Psychiatry 2019Social cognition deficits are a core feature of schizophrenia and deteriorate functionality of patients. However, evidence is sparse for the treatment effect on social...
Social cognition deficits are a core feature of schizophrenia and deteriorate functionality of patients. However, evidence is sparse for the treatment effect on social cognition impairments in the early stage of psychosis. Here, we provide a systematic review of the literature on social cognitive impairment in early psychosis in relation to its intervention. A literature search was conducted on English articles identified by Web of Science and PubMed databases, according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Five papers met the inclusion criteria. Results from two studies of cognitive training and one study of modafinil indicate positive results regarding social cognition outcomes in patients with early psychosis. On the other hand, two studies with oxytocin and modafinil did not suggest such effects. Further research is warranted to explore the benefit of early intervention into disturbances of social cognition in psychoses.
PubMed: 31156479
DOI: 10.3389/fpsyt.2019.00333 -
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