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Dementia & Neuropsychologia 2023Anticholinergics (ACs) are among the most prescribed drugs. Investigating the impaired cognitive domains due to individual ACs usage is associated with controversial... (Review)
Review
UNLABELLED
Anticholinergics (ACs) are among the most prescribed drugs. Investigating the impaired cognitive domains due to individual ACs usage is associated with controversial findings.
OBJECTIVE
The objective of this study was to investigate the effects of individual ACs on different aspects of cognitive function based on clinical trial studies.
METHODS
This systematic review was conducted following the PRISMA statement. A systematic search was performed in Embase, PubMed, Cochrane Library, Scopus, and Web of Science databases. Risk of bias (RoB) was assessed by the Joanna Briggs Institute checklists and the meta-analysis was performed using the CMA software.
RESULTS
Out of 3,026 results of searching, 138 studies were included. A total of 38 studies that assess the cognitive impacts of scopolamine were included in the meta-analysis. Included studies reported cognitive effects of scopolamine, mecamylamine, atropine, biperiden, oxybutynin, trihexyphenidyl, benzhexol, and dicyclomine; however, glycopyrrolate, trospium, tolterodine, darifenacin, fesoterodine, tiotropium, and ipratropium were not associated with cognitive decline. Based on the meta-analyses, scopolamine was associated with reduced recognition (SDM -1.84; 95%CI -2.48 to -1.21; p<0.01), immediate recall (SDM -1.82; 95%CI -2.35 to -1.30; p<0.01), matching to sample (SDM -1.76; 95%CI -2.57 to -0.96; p<0.01), delayed recall (SDM -1.54; 95%CI -1.97 to -1.10; p<0.01), complex memory tasks (SDM -1.31; 95%CI -1.78 to -0.84; p<0.01), free recall (SDM -1.18; 95%CI -1.63 to -0.73; p<0.01), cognitive function (SDM -0.95; 95%CI -1.46 to -0.44; p<0.01), attention (SDM -0.85; 95%CI -1.38 to -0.33; p<0.01), and digit span (SDM -0.65; 95%CI -1.21 to -0.10; p=0.02). There was a high RoB in our included study, especially in terms of dealing with possible cofounders.
CONCLUSION
The limitations of this study suggest a need for more well-designed studies with a longer duration of follow-up on this topic to reach more reliable evidence.
PubMed: 37261256
DOI: 10.1590/1980-5764-DN-2022-0053 -
Brain Sciences Nov 2022cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving... (Review)
Review
BACKGROUND
cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving efficacy of pharmacotherapies tested for cocaine use disorder, in the context of randomized-controlled clinical trials.
OBJECTIVES
we assessed the databases of the U.S. National Library of Medicine, Google Scholar, and PsycINFO, without date restrictions up to August 2022, to identify relevant studies.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
we included double-blinded randomized-controlled trials investigating pharmacotherapies for cocaine craving and/or cocaine use disorder whose outcomes included cocaine craving.
STUDY APPRAISAL AND SYNTHESIS METHODS
Two authors screened studies' titles and abstracts for inclusion, and both read all the included studies. We systematically gathered information on the following aspects of each study: title; author(s); year of publication; sample size; mean age; sample characteristics; study set-ting; whether participants were treatment-seeking; study design; craving measures; study interventions; drop-out rates; and other relevant outcomes.
RESULTS
Overall, we appraised 130 clinical trials, including 8137 participants. We further considered the drugs from the studies that scored equal to or greater than six points in the quality assessment. There was a correlation between craving and cocaine use outcomes (self-reports, timeline follow-back or urinary benzoylecgonine) in the vast majority of studies. In the short-term treatment, acute phenylalanine-tyrosine depletion, clonidine, fenfluramine, meta-chlorophenylpiperazine (m-CPP) and mecamylamine presented promising effects. In the long term, amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone presented promising anti-craving effects. Unfortunately, the highly tested medications were not successful in most of the trials, as follows: propranolol in the short term; amantadine, aripiprazole, bromocriptine, citicoline, ketamine, modafinil, olanzapine, topiramate in the long term. The remaining 52 medications had no positive anti-craving outcomes.
LIMITATIONS
Our review was limited by high heterogeneity of craving assessments across the studies and by a great range of pharmacotherapies. Further, the majority of the studies considered abstinence and retention in treatment as the main outcomes, whereas craving was a secondary outcome and some of the studies evaluated patients with cocaine use disorder with comorbidities such as opioid or alcohol use disorder, schizophrenia, bipolar disorder or attention deficit hyperactivity. Lastly, most of the studies also included non-pharmacological treatments, such as counseling or psychotherapy.
CONCLUSIONS
There is a direct association between craving and cocaine use, underscoring craving as an important treatment target for promoting abstinence among persons with cocaine use disorder. Clonidine, fenfluramine and m-CPP showed to be promising medications for cocaine craving in the short-term treatment, and amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone in the long-term treatment.
PubMed: 36421870
DOI: 10.3390/brainsci12111546 -
Frontiers in Pharmacology 2022A network meta-analysis based on randomized controlled trials was conducted to investigate the effects of pharmacological interventions on smoking cessation. English...
A network meta-analysis based on randomized controlled trials was conducted to investigate the effects of pharmacological interventions on smoking cessation. English databases were searched to obtain randomized controlled trials reporting the effect of pharmacological interventions on smoking cessation. The risk of bias for the included trials was assessed using Cochrane Handbook tool. Stata 15.1 software was used to perform network meta-analysis, and GRADE approach was used to assess the evidence credibility on the effects of different interventions on smoking cessation. A total of 159 studies involving 60,285 smokers were included in the network meta-analysis. The analysis involved 15 interventions and which yielded 105 pairs of comparisons. Network meta-analysis showed that varenicline was more helpful for smoking cessation than other monotherapies, such as nicotine replacement therapy [Odds Ratio (OR) = 1.42, 95% confidence interval (CI) (1.16, 1.73)] and bupropion [OR = 1.52, 95% CI (1.22, 1.89)]. Furthermore, combined interventions were superior to monotherapy in achieving smoking cessation, such as varenicline plus bupropion over bupropion [OR = 2.00, 95% CI (1.11, 3.61)], varenicline plus nicotine replacement therapy over nicotine replacement therapy [OR = 1.84, 95% CI (1.07, 3.18)], and nicotine replacement therapy plus mecamylamine over naltrexone [OR = 6.29, 95% CI (1.59, 24.90)]. Finally, the surface under the cumulative ranking curve value indicated that nicotine replacement therapy plus mecamylamine had the greatest probability of becoming the best intervention. Most pharmacological interventions demonstrated a benefit in smoking cessation compared with placebo, whether monotherapy or combination therapy. Moreover, confirmed evidence suggested that some combination treatments, such as varenicline plus bupropion and nicotine replacement therapy plus mecamylamine have a higher probability of being the best smoking cessation in.
PubMed: 36353488
DOI: 10.3389/fphar.2022.1012433 -
Revue Des Maladies Respiratoires Sep 2021The effectiveness of the three validated smoking cessation medications, nicotine replacement therapy, varenicline and bupropion, may be insufficient, in hard-core... (Review)
Review
INTRODUCTION
The effectiveness of the three validated smoking cessation medications, nicotine replacement therapy, varenicline and bupropion, may be insufficient, in hard-core smokers.
OBJECTIVES
This systematic review investigates the efficacy of combinations of different medications in smoking abstinence and their tolerability.
RESULTS
Three randomized controlled trials (RCTs) compared the combined medications with varenicline and nicotine patches vs. varenicline; two found an increase in abstinence rates with the combined medications. In one study, the beneficial effect was only observed in heavy smokers. The four RCTs comparing the combined medications with varenicline and bupropion (vs. varenicline) demonstrated an increase in abstinence rates with the combined medications, most often in heavy smokers who are very dependent on tobacco. The results of the three RCTs comparing the combined medications with bupropion and nicotine replacement therapy vs. varenicline were discordant. Three studies included other molecules (mecamylamine, selegiline, sertraline, buspirone). Combined medications were well tolerated.
CONCLUSION
Combination treatments can achieve higher smoking abstinence rates than monotherapies, especially in smokers who have failed to quit (Hard-core smokers). Treatment with a combination of varenicline and nicotine replacement therapy is a therapeutic option in smoking cessation.
Topics: Bupropion; Humans; Nicotine; Smoking; Smoking Cessation; Varenicline
PubMed: 34215484
DOI: 10.1016/j.rmr.2021.05.012 -
European Neuropsychopharmacology : the... May 2017Treatment of unipolar depression with currently available antidepressants is still unsatisfactory. Augmentation with lithium or second generation antipsychotics is an... (Meta-Analysis)
Meta-Analysis Review
Treatment of unipolar depression with currently available antidepressants is still unsatisfactory. Augmentation with lithium or second generation antipsychotics is an established practice in non-responders to antidepressant monotherapy, but is also associated with a substantial non-response rate and with non-tolerance. Based on a systematic review of the literature, including meta-analyses, randomized controlled trials (RCTs), non-randomized comparative studies and case studies, off-label augmentation agents (administered in addition to an antidepressant, without FDA approval for treatment of MDD) were identified and evaluated regarding their efficacy using levels of evidence. The agents had to be added to an existing antidepressant regime with the aim of achieving an improved clinical response to an ongoing antidepressant treatment (augmentation) or an earlier onset of effect when starting antidepressant and augmentation agent simultaneously (acceleration). Five substances, modafinil, ketamine, pindolol, testosterone and estrogen (the latter two in hormone-deficient patients) were shown to be clinically effective in high evidence studies. For the six drugs dexamethasone, mecamylamine, riluzole, amantadine, pramipexole and yohimbine clear proof of efficacy was not possible due to low levels of evidence, small sample sizes or discordant results. For the two agents methylphenidate and memantine only studies with negative outcomes could be found. Overall, the quality of study designs was low and results were often contradictory. However, the use of pindolol, ketamine, modafinil, estrogen and testosterone might be an option for depressed patients who are not responding to antidepressant monotherapy or established augmentation strategies. Further high quality studies are necessary and warranted.
Topics: Antidepressive Agents; Depressive Disorder; Humans; Off-Label Use
PubMed: 28318897
DOI: 10.1016/j.euroneuro.2017.03.003 -
Expert Review of Neurotherapeutics 2016Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard... (Review)
Review
Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder.
Topics: Adrenergic alpha-Agonists; Adult; Amphetamines; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Bridged Bicyclo Compounds, Heterocyclic; Bupropion; Central Nervous System Stimulants; Desipramine; Dopamine Agents; Droxidopa; Drug Combinations; Duloxetine Hydrochloride; Guanfacine; Histamine Agents; Humans; Lisdexamfetamine Dimesylate; Lithium Compounds; Lobeline; Mecamylamine; Memantine; Modafinil; Morpholines; Nicotinic Agonists; Nicotinic Antagonists; Nomifensine; Paroxetine; Pyridines; Pyridoxine; Pyrrolidonecarboxylic Acid; Quinazolinones; Reboxetine; Venlafaxine Hydrochloride; Wakefulness-Promoting Agents
PubMed: 26693882
DOI: 10.1586/14737175.2016.1135735