-
The Cochrane Database of Systematic... Sep 2016Cocaine dependence is a severe disorder for which no medication has been approved. Like opioids for heroin dependence, replacement therapy with psychostimulants could be... (Review)
Review
BACKGROUND
Cocaine dependence is a severe disorder for which no medication has been approved. Like opioids for heroin dependence, replacement therapy with psychostimulants could be an effective therapy for treatment.
OBJECTIVES
To assess the effects of psychostimulants for cocaine abuse and dependence. Specific outcomes include sustained cocaine abstinence and retention in treatment. We also studied the influence of type of drug and comorbid disorders on psychostimulant efficacy.
SEARCH METHODS
This is an update of the review previously published in 2010. For this updated review, we searched the Cochrane Drugs and Alcohol Group Trials Register, CENTRAL, MEDLINE, Embase and PsycINFO up to 15 February 2016. We handsearched references of obtained articles and consulted experts in the field.
SELECTION CRITERIA
We included randomised parallel group controlled clinical trials comparing the efficacy of a psychostimulant drug versus placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 26 studies involving 2366 participants. The included studies assessed nine drugs: bupropion, dexamphetamine, lisdexamfetamine, methylphenidate, modafinil, mazindol, methamphetamine, mixed amphetamine salts and selegiline. We did not consider any study to be at low risk of bias for all domains included in the Cochrane 'Risk of bias' tool. Attrition bias was the most frequently suspected potential source of bias of the included studies. We found very low quality evidence that psychostimulants improved sustained cocaine abstinence (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.05 to 1.77, P = 0.02), but they did not reduce cocaine use (standardised mean difference (SMD) 0.16, 95% CI -0.02 to 0.33) among participants who continued to use it. Furthermore, we found moderate quality evidence that psychostimulants did not improve retention in treatment (RR 1.00, 95% CI 0.93 to 1.06). The proportion of adverse event-induced dropouts and cardiovascular adverse event-induced dropouts was similar for psychostimulants and placebo (RD 0.00, 95% CI -0.01 to 0.01; RD 0.00, 95% CI -0.02 to 0.01, respectively). When we included the type of drug as a moderating variable, the proportion of patients achieving sustained cocaine abstinence was higher with bupropion and dexamphetamine than with placebo. Psychostimulants also appeared to increase the proportion of patients achieving sustained cocaine and heroin abstinence amongst methadone-maintained, dual heroin-cocaine addicts. Retention to treatment was low, though, so our results may be compromised by attrition bias. We found no evidence of publication bias.
AUTHORS' CONCLUSIONS
This review found mixed results. Psychostimulants improved cocaine abstinence compared to placebo in some analyses but did not improve treatment retention. Since treatment dropout was high, we cannot rule out the possibility that these results were influenced by attrition bias. Existing evidence does not clearly demonstrate the efficacy of any pharmacological treatment for cocaine dependence, but substitution treatment with psychostimulants appears promising and deserves further investigation.
PubMed: 27670244
DOI: 10.1002/14651858.CD007380.pub4 -
Chronic Respiratory Disease May 2017Fatigue is a common manifestation of sarcoidosis, often persisting without evidence of disease activity. First-line therapies for sarcoidosis have limited effect on... (Review)
Review
Fatigue is a common manifestation of sarcoidosis, often persisting without evidence of disease activity. First-line therapies for sarcoidosis have limited effect on fatigue. This review aimed to assess the treatment options targeting sarcoidosis-associated fatigue. Medline and Web of Science were searched in November 2015; the bibliographies of these papers, and relevant review papers, were also searched. Studies were included if they reported on the efficacy of interventions (both pharmacological and non-pharmacological) on fatigue scores in sarcoidosis patients. Eight studies were identified that fulfilled the inclusion criteria. These studies evaluated six different interventions (infliximab, adalimumab, ARA 290, methylphenidate, armodafinil and exercise programmes). There is evidence to support a treatment effect of anti-tumour necrosis factor (TNF)-αtherapies (adalimumab and infliximab) and neurostimulants (methylphenidate and armodafinil), but within five of the studies, the risk of bias was high within most domains and the remaining three studies included only small numbers of participants and were short in duration. Trial evidence for treating fatigue as a manifestation of sarcoidosis is limited and requires further investigation. Anti-TNF-α therapies may be beneficial in patients with organ-threatening disease. Neurostimulants have some trial evidence supporting improvements in fatigue but further investigation is needed before they can be recommended.
Topics: Adalimumab; Antirheumatic Agents; Benzhydryl Compounds; Central Nervous System Stimulants; Exercise Therapy; Fatigue; Humans; Infliximab; Methylphenidate; Modafinil; Oligopeptides; Sarcoidosis; Tumor Necrosis Factor-alpha
PubMed: 27507833
DOI: 10.1177/1479972316661926 -
Journal of Parkinson's Disease 2023Fatigue is one of the most common and debilitating non-motor symptoms among patients with Parkinson's disease (PD) and significantly impacts quality of life. Therefore,... (Meta-Analysis)
Meta-Analysis
Physical Exercise as a Potential Treatment for Fatigue in Parkinson's Disease? A Systematic Review and Meta-Analysis of Pharmacological and Non-Pharmacological Interventions.
BACKGROUND
Fatigue is one of the most common and debilitating non-motor symptoms among patients with Parkinson's disease (PD) and significantly impacts quality of life. Therefore, effective treatment options are needed.
OBJECTIVE
To provide an update on randomized controlled trials (RCTs) including pharmacological and non-pharmacological (but non-surgical) treatments that examine the effects of fatigue on PD patients.
METHODS
We searched the MEDLINE, EMBASE, PsycINFO, CENTRAL, and CINAHL databases for (cross-over) RCTs on pharmacological and non-pharmacological interventions for treating fatigue in PD patients until May 2021. Meta-analyses for random-effects models were calculated when two or more studies on the same treatment option were available using standardized mean differences (SMDs) with 95% confidence intervals (CIs).
RESULTS
Fourteen pharmacological and 16 non-pharmacological intervention RCTs were identified. For pharmacological approaches, a meta-analysis could only be performed for modafinil compared to placebo (n = 2) revealing a non-significant effect on fatigue (SMD = - 0.21, 95% CI - 0.74-0.31, p = 0.43). Regarding non-pharmacological approaches, physical exercise (n = 8) following different training approaches versus passive or placebo control groups showed a small significant effect (SMD = - 0.37, 95% CI - 0.69- - 0.05, p = 0.02) which could not be demonstrated for acupuncture vs. sham-acupuncture (SMD = 0.16, 95% CI - 0.19-0.50, p = 0.37).
CONCLUSION
Physical exercise may be a promising strategy to treat fatigue in PD patients. Further research is required to examine the efficacy of this treatment strategy and further interventions. Future studies should differentiate treatment effects on physical and mental fatigue as the different underlying mechanisms of these symptoms may lead to different treatment responses. More effort is required to develop, evaluate, and implement holistic fatigue management strategies for PD patients.
Topics: Humans; Parkinson Disease; Exercise; Modafinil; Quality of Life
PubMed: 37334618
DOI: 10.3233/JPD-225116 -
The Cochrane Database of Systematic... Sep 2022Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of... (Review)
Review
BACKGROUND
Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 4, 2016.
OBJECTIVES
To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and clinically significant (or high levels) of fatigue.
SEARCH METHODS
For this updated review, we searched CENTRAL, MEDLINE and Embase, and checked the reference lists of included studies in April 2022. We also searched relevant conference proceedings, and ClinicalTrials.gov for ongoing trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that investigated any pharmacological or non-pharmacological intervention in adults with PBT and fatigue, where fatigue was the primary outcome measure. We restricted inclusion specifically to studies that enrolled only participants with clinically significant levels of fatigue to improve the clinical utility of the findings.
DATA COLLECTION AND ANALYSIS
Two review authors (JD, DC) independently evaluated search results for the updated search. Two review authors (JD, SYK) extracted data from selected studies, and carried out a risk of bias assessment. We extracted data on fatigue, mood, cognition, quality of life and adverse events outcomes.
MAIN RESULTS
The original review identified one study and this update identified a further two for inclusion. One study investigated the use of modafinil, one study the use of armodafinil and one study the use of dexamfetamine. We identified three ongoing studies. In the original review, the single eligible trial compared modafinil to placebo for 37 participants with a high- or low-grade PBT. One new study compared two doses of armodafinil (150 mg and 250 mg) to placebo for 297 people with a high-grade glioma. The second new study compared dexamfetamine sulfate to placebo for 46 participants with a low- or high-grade PBT. The evidence was uncertain for both modafinil and dexamfetamine regarding fatigue outcome measures, compared to controls, at study endpoint. Two trials did not reach the planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. These trials were at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation for one study because the investigators did not analyse the impact of imputation on the results and information regarding baseline characteristics and randomisation were not clear. The certainty of the evidence measured using GRADE was very low across all three studies. There was one identified study awaiting classification once data are available, which investigated the feasibility of 'health coaching' for people with a PBT experiencing fatigue. There were three ongoing studies that may be eligible for an update of this review, all investigating a non-pharmacological intervention for fatigue in people with PBT.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.
Topics: Adult; Brain Neoplasms; Dextroamphetamine; Fatigue; Glioma; Humans; Modafinil
PubMed: 36094728
DOI: 10.1002/14651858.CD011376.pub3 -
Bipolar Disorders Jun 2022Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in... (Review)
Review
Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force.
BACKGROUND
Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations.
METHODS
The review included RCTs of candidate pro-cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials.
RESULTS
We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre-screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking.
CONCLUSIONS
Evidence for pro-cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre-screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real-world functioning, investigate multimodal interventions and include neuroimaging.
Topics: Bipolar Disorder; Cognition; Cognitive Dysfunction; Humans; Lurasidone Hydrochloride; Mood Disorders
PubMed: 35174594
DOI: 10.1111/bdi.13193 -
Revista de Neurologia Jun 2023Psychotic disorders are considered chronic mental health issues. Although it has been demonstrated that these disorders can present with a wide range of symptoms,... (Review)
Review
INTRODUCTION
Psychotic disorders are considered chronic mental health issues. Although it has been demonstrated that these disorders can present with a wide range of symptoms, pharmacological treatment is based on the use of typical and atypical antipsychotics, whose main mechanism of action is dopaminergic blockade, limiting their effect to the improvement of positive symptoms, without improving the rest of the symptoms and giving rise to a large number of serious adverse effects. For this reason, new therapeutic targets other than the dopaminergic system are being studied. The main objective of this review is to test whether these psychoactive substances used in clinical practice could provide additional benefits as an adjunctive treatment for people with psychotic disorders.
DEVELOPMENT
For this systematic review, a literature search was conducted in the databases PsycINFO, Medline, Psicodoc, PubMed and Google Scholar. Altogether 28 articles were included in the review. One of the main findings is that cannabidiol is more effective for improving positive symptoms and psychopathology; modafinil, for cognitive symptoms, motor and emotional functioning and quality of life; and ketamine, for negative symptoms. In addition, all the substances showed a good tolerability and safety profile, especially in comparison to antipsychotics.
CONCLUSION
The results obtained open up the possibility of having a guideline for clinicians/health professionals on the use of cannabidiol, modafinil and ketamine as adjunctive treatment for patients with psychotic conditions.
Topics: Humans; Antipsychotic Agents; Modafinil; Ketamine; Cannabidiol; Quality of Life; Psychotic Disorders
PubMed: 37231549
DOI: 10.33588/rn.7611.2023077 -
Journal of Clinical Sleep Medicine :... Dec 2021Excessive daytime sleepiness associated with obstructive sleep apnea affects 9%-22% of continuous positive airway pressure-treated patients. An indirect treatment... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVES
Excessive daytime sleepiness associated with obstructive sleep apnea affects 9%-22% of continuous positive airway pressure-treated patients. An indirect treatment comparison meta-analysis was performed to compare efficacy and safety of medications (solriamfetol, modafinil, and armodafinil) approved to treat excessive daytime sleepiness associated with obstructive sleep apnea.
METHODS
Efficacy and safety measures assessed in this indirect treatment comparison included Epworth Sleepiness Scale (ESS), 20-minute Maintenance of Wakefulness Test (MWT20), Clinical Global Impression of Change (CGI-C), Functional Outcomes of Sleep Questionnaire (FOSQ), and incidence of treatment-emergent adverse events (any, serious, or leading to discontinuation).
RESULTS
A systematic literature review identified 6 parallel-arm, placebo-controlled randomized controlled trials that randomized 1,714 total participants to placebo, solriamfetol, modafinil, or armodafinil. In this indirect treatment comparison, all comparators were associated with greater improvements than placebo on the ESS, MWT20, and CGI-C after 4, 8, and 12 weeks of treatment. Relative to comparators and placebo at 12 weeks, solriamfetol at 150 mg or 300 mg had the highest probabilities of improvement in the ESS, MWT20, and CGI-C. Modafinil (200 or 400 mg) and solriamfetol (150 or 300 mg) were associated with greater improvement on the FOSQ than placebo at 12 weeks. Less than 2% of patients using placebo or comparators experienced serious or discontinuation-related treatment-emergent adverse events.
CONCLUSIONS
The results of this indirect treatment comparison show 12 weeks of treatment with solriamfetol, modafinil, and armodafinil resulted in varying levels of improvement on the ESS, MWT20, and CGI-C and similar safety risks in participants with excessive daytime sleepiness associated with obstructive sleep apnea.
CITATION
Ronnebaum S, Bron M, Patel D, et al. Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea. . 2021;17(12):2543-2555.
Topics: Benzhydryl Compounds; Carbamates; Disorders of Excessive Somnolence; Double-Blind Method; Humans; Modafinil; Phenylalanine; Sleep Apnea, Obstructive; Treatment Outcome
PubMed: 34402784
DOI: 10.5664/jcsm.9610 -
European Neuropsychopharmacology : the... Jan 2024Growing evidence suggests an association between inflammatory processes and depressive disorders (DD). DD typically emerge during adolescence. Treatment effects of... (Meta-Analysis)
Meta-Analysis Review
Growing evidence suggests an association between inflammatory processes and depressive disorders (DD). DD typically emerge during adolescence. Treatment effects of agents with anti-inflammatory properties in youth DD have not been systematically reviewed. Here, the existing evidence on the use of anti-inflammatory drugs (including polyunsaturated fatty acids, nonsteroidal anti-inflammatory drugs, cytokine inhibitors, statins, pioglitazone, corticosteroids, and minocycline or modafinil) in children and adolescents with DD was synthesized using meta-analysis. The PROSPERO preregistered search yielded 22 records meeting search criteria. Of these, data from 19 primary studies (n = 1366 subjects) were subjected to meta-analysis. A significant but small effect in favor of anti-inflammatory agents in reducing depressive symptoms in youth with DD was found (SMD = -0.29, 95 % CI = -0.514; -0.063, p = 0.01). Post-hoc analyzes of drug subclasses found a significant effect of omega-3 fatty acids in reducing depressive symptoms. Results underline the importance to consider inflammatory pathways in the supplemental treatment of youth with DD. Further research is warranted, to clarify if anti-inflammatory agents are only effective in a subpopulation of patients (inflammatory biotype of depression in youth) and/or to alleviate specific symptom domains of depression (e.g., cognitive symptoms).
Topics: Child; Humans; Adolescent; Depression; Anti-Inflammatory Agents; Minocycline; Pioglitazone; Fatty Acids, Omega-3
PubMed: 37864981
DOI: 10.1016/j.euroneuro.2023.09.006 -
The Cochrane Database of Systematic... Nov 2022Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of... (Review)
Review
BACKGROUND
Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of pharmacological and non-pharmacological treatment of cognitive deficits in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 12, 2014.
OBJECTIVES
To assess the effectiveness of interventions for preventing or ameliorating cognitive deficits in adults treated with cranial irradiation.
SEARCH METHODS
For this review update we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Embase via Ovid, and PsycInfo via Ovid to 12 September 2022.
SELECTION CRITERIA
We included randomised controlled (RCTs) trials that evaluated pharmacological or non-pharmacological interventions in cranial irradiated adults, with objective cognitive functioning as a primary or secondary outcome measure.
DATA COLLECTION AND ANALYSIS
Two review authors (MK, JD) independently extracted data from selected studies and carried out a risk of bias assessment. Cognitive function, fatigue and mood outcomes were reported. No data were pooled.
MAIN RESULTS
Eight studies met the inclusion criteria and were included in this updated review. Six were from the original version of the review, and two more were added when the search was updated. Nineteen further studies were assessed as part of this update but did not fulfil the inclusion criteria. Of the eight included studies, four studies investigated "prevention" of cognitive problems (during radiotherapy and follow-up) and four studies investigated "amelioration" (interventions to treat cognitive impairment as a late complication of radiotherapy). There were five pharmacological studies (two studies on prevention and three in amelioration) and three non-pharmacological studies (two on prevention and one in amelioration). Due to differences between studies in the interventions being evaluated, a meta-analysis was not possible. Studies in early radiotherapy treatment phase (five studies) Pharmacological studies in the "early radiotherapy treatment phase" were designed to prevent or ameliorate cognitive deficits and included drugs used in dementia (memantine) and fatigue (d-threo-methylphenidate hydrochloride). Non-pharmacological studies in the "early radiotherapy treatment phase" included a ketogenic diet and a two-week cognitive rehabilitation and problem-solving programme. In the memantine study, the primary cognitive outcome of memory at six months did not reach significance, but there was significant improvement in overall cognitive function compared to placebo, with similar adverse events across groups. The d-threo-methylphenidate hydrochloride study found no statistically significant difference between arms, with few adverse events. The study of a calorie-restricted ketogenic diet found no effect, although a lower than expected calorie intake in the control group complicates interpretation of the results. The study investigating the utility of a rehabilitation program did not carry out a statistical comparison of cognitive performance between groups. Studies in delayed radiation or late effect phase (four studies) The "amelioration" pharmacological studies to treat cognitive complications of radiotherapy included drugs used in dementia (donepezil) or psychostimulants (methylphenidate and modafinil). Non-pharmacological measures included cognitive rehabilitation and problem solving (Goal Management Training). These studies included patients with cognitive problems at entry who had "stable" brain cancer. The donepezil study did not find an improvement in the primary cognitive outcome of overall cognitive performance, but did find improvement in an individual test of memory, compared to placebo; adverse events were not reported. A study comparing methylphenidate with modafinil found improvements in cognitive function in both the methylphenidate and modafinil arms; few adverse events were reported. Another study comparing two different doses of modafinil combined treatment arms and found improvements across all cognitive tests, however, a number of adverse events were reported. Both studies were limited by a small sample size. The Goal Management Training study suggested a benefit of the intervention, a behavioural intervention that combined mindfulness and strategy training, on executive function and processing speed. There were a number of limitations across studies and few were without high risks of bias.
AUTHORS' CONCLUSIONS
In this update, limited additional evidence was found for the treatment or amelioration of cognitive deficits in adults treated with cranial irradiation. As concluded in the original review, there is supportive evidence that memantine may help prevent cognitive deficits for adults with brain metastases receiving cranial irradiation. There is supportive evidence that donepezil, methylphenidate and modafinil may have a role in treating cognitive deficits in adults with brain tumours who have been treated with cranial irradiation; patient withdrawal affected the statistical power of these studies. Further research that tries to minimise the withdrawal of consent, and subsequently reduce the requirement for imputation procedures, may offer a higher certainty of evidence. There is evidence from only a single small study to support non-pharmacological interventions in the amelioration of cognitive deficits. Further research is required.
Topics: Adult; Humans; Modafinil; Donepezil; Memantine; Quality of Life; Cognitive Dysfunction; Cranial Irradiation; Cognition; Methylphenidate; Brain Neoplasms; Fatigue; Dementia
PubMed: 36427235
DOI: 10.1002/14651858.CD011335.pub3 -
Diagnostics (Basel, Switzerland) Dec 2021Sleep disorders are among the main comorbidities in patients with a Disorder of Consciousness (DOC). Given the key role of sleep in neural and cognitive functioning,... (Review)
Review
Sleep disorders are among the main comorbidities in patients with a Disorder of Consciousness (DOC). Given the key role of sleep in neural and cognitive functioning, detecting and treating sleep disorders in DOCs might be an effective therapeutic strategy to boost consciousness recovery and levels of awareness. To date, no systematic reviews have been conducted that explore the effect of sleep treatments in DOCs; thus, we systematically reviewed the existing studies on both pharmacological and non-pharmacological treatments for sleep disorders in DOCs. Among 2267 assessed articles, only 7 were included in the systematic review. The studies focused on two sleep disorder categories (sleep-related breathing disorders and circadian rhythm dysregulation) treated with both pharmacological (Modafinil and Intrathecal Baclofen) and non-pharmacological (positive airway pressure, bright light stimulation, and central thalamic deep brain stimulation) interventions. Although the limited number of studies and their heterogeneity do not allow generalized conclusions, all the studies highlighted the effectiveness of treatments on both sleep disorders and levels of awareness. For this reason, clinical and diagnostic evaluations able to detect sleep disorders in DOC patients should be adopted in the clinical routine for the purpose of intervening promptly with the most appropriate treatment.
PubMed: 35054255
DOI: 10.3390/diagnostics12010088