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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 -
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 -
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 -
The Cochrane Database of Systematic... May 2013Smoking is the leading preventable cause of illness and premature death worldwide. Some medications have been proven to help people to quit, with three licensed for this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Smoking is the leading preventable cause of illness and premature death worldwide. Some medications have been proven to help people to quit, with three licensed for this purpose in Europe and the USA: nicotine replacement therapy (NRT), bupropion, and varenicline. Cytisine (a treatment pharmacologically similar to varenicline) is also licensed for use in Russia and some of the former socialist economy countries. Other therapies, including nortriptyline, have also been tested for effectiveness.
OBJECTIVES
How do NRT, bupropion and varenicline compare with placebo and with each other in achieving long-term abstinence (six months or longer)? How do the remaining treatments compare with placebo in achieving long-term abstinence? How do the risks of adverse and serious adverse events (SAEs) compare between the treatments, and are there instances where the harms may outweigh the benefits?
METHODS
The overview is restricted to Cochrane reviews, all of which include randomised trials. Participants are usually adult smokers, but we exclude reviews of smoking cessation for pregnant women and in particular disease groups or specific settings. We cover nicotine replacement therapy (NRT), antidepressants (bupropion and nortriptyline), nicotine receptor partial agonists (varenicline and cytisine), anxiolytics, selective type 1 cannabinoid receptor antagonists (rimonabant), clonidine, lobeline, dianicline, mecamylamine, Nicobrevin, opioid antagonists, nicotine vaccines, and silver acetate. Our outcome for benefit is continuous or prolonged abstinence at least six months from the start of treatment. Our outcome for harms is the incidence of serious adverse events associated with each of the treatments. We searched the Cochrane Database of Systematic Reviews (CDSR) in The Cochrane Library, for any reviews with 'smoking' in the title, abstract or keyword fields. The last search was conducted in November 2012. We assessed methodological quality using a revised version of the AMSTAR scale. For NRT, bupropion and varenicline we conducted network meta-analyses, comparing each with the others and with placebo for benefit, and varenicline and bupropion for risks of serious adverse events.
MAIN RESULTS
We identified 12 treatment-specific reviews. The analyses covered 267 studies, involving 101,804 participants. Both NRT and bupropion were superior to placebo (odds ratios (OR) 1.84; 95% credible interval (CredI) 1.71 to 1.99, and 1.82; 95% CredI 1.60 to 2.06 respectively). Varenicline increased the odds of quitting compared with placebo (OR 2.88; 95% CredI 2.40 to 3.47). Head-to-head comparisons between bupropion and NRT showed equal efficacy (OR 0.99; 95% CredI 0.86 to 1.13). Varenicline was superior to single forms of NRT (OR 1.57; 95% CredI 1.29 to 1.91), and to bupropion (OR 1.59; 95% CredI 1.29 to 1.96). Varenicline was more effective than nicotine patch (OR 1.51; 95% CredI 1.22 to 1.87), than nicotine gum (OR 1.72; 95% CredI 1.38 to 2.13), and than 'other' NRT (inhaler, spray, tablets, lozenges; OR 1.42; 95% CredI 1.12 to 1.79), but was not more effective than combination NRT (OR 1.06; 95% CredI 0.75 to 1.48). Combination NRT also outperformed single formulations. The four categories of NRT performed similarly against each other, apart from 'other' NRT, which was marginally more effective than NRT gum (OR 1.21; 95% CredI 1.01 to 1.46). Cytisine (a nicotine receptor partial agonist) returned positive findings (risk ratio (RR) 3.98; 95% CI 2.01 to 7.87), without significant adverse events or SAEs. Across the 82 included and excluded bupropion trials, our estimate of six seizures in the bupropion arms versus none in the placebo arms was lower than the expected rate (1:1000), at about 1:1500. SAE meta-analysis of the bupropion studies demonstrated no excess of neuropsychiatric (RR 0.88; 95% CI 0.31 to 2.50) or cardiovascular events (RR 0.77; 95% CI 0.37 to 1.59). SAE meta-analysis of 14 varenicline trials found no difference between the varenicline and placebo arms (RR 1.06; 95% CI 0.72 to 1.55), and subgroup analyses detected no significant excess of neuropsychiatric events (RR 0.53; 95% CI 0.17 to 1.67), or of cardiac events (RR 1.26; 95% CI 0.62 to 2.56). Nortriptyline increased the chances of quitting (RR 2.03; 95% CI 1.48 to 2.78). Neither nortriptyline nor bupropion were shown to enhance the effect of NRT compared with NRT alone. Clonidine increased the chances of quitting (RR 1.63; 95% CI 1.22 to 2.18), but this was offset by a dose-dependent rise in adverse events. Mecamylamine in combination with NRT may increase the chances of quitting, but the current evidence is inconclusive. Other treatments failed to demonstrate a benefit compared with placebo. Nicotine vaccines are not yet licensed for use as an aid to smoking cessation or relapse prevention. Nicobrevin's UK license is now revoked, and the manufacturers of rimonabant, taranabant and dianicline are no longer supporting the development or testing of these treatments.
AUTHORS' CONCLUSIONS
NRT, bupropion, varenicline and cytisine have been shown to improve the chances of quitting. Combination NRT and varenicline are equally effective as quitting aids. Nortriptyline also improves the chances of quitting. On current evidence, none of the treatments appear to have an incidence of adverse events that would mitigate their use. Further research is warranted into the safety of varenicline and into cytisine's potential as an effective and affordable treatment, but not into the efficacy and safety of NRT.
Topics: Adult; Alkaloids; Antidepressive Agents, Second-Generation; Azocines; Benzazepines; Bupropion; Humans; Nicotinic Agonists; Nortriptyline; Quinolizines; Quinoxalines; Randomized Controlled Trials as Topic; Review Literature as Topic; Smoking; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 23728690
DOI: 10.1002/14651858.CD009329.pub2 -
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 -
The Cochrane Database of Systematic... 2000Mecamylamine is a nicotine antagonist (that is it blocks the effect of nicotine). The rationale for its use in smoking cessation is that it may block the rewarding... (Comparative Study)
Comparative Study Review
BACKGROUND
Mecamylamine is a nicotine antagonist (that is it blocks the effect of nicotine). The rationale for its use in smoking cessation is that it may block the rewarding effect of nicotine and thus reduce the urge to smoke.
OBJECTIVES
The objective of this review was to determine the effectiveness of mecamylamine in promoting smoking cessation, either alone or in combination with nicotine replacement therapy.
SEARCH STRATEGY
We searched the Cochrane Tobacco Addiction Group trials register.
SELECTION CRITERIA
Randomised trials of mecamylamine, either alone or in combination with nicotine replacement therapy, which reported smoking cessation rates at least six months after intervention.
DATA COLLECTION AND ANALYSIS
We extracted data in duplicate on the type of subjects, the dose and duration of the mecamylamine and nicotine treatments, side-effects of treatment, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was sustained abstinence from smoking (biochemically validated) after at least six months follow-up in patients smoking at baseline. Smokers lost to follow-up were regarded as being continuing smokers. Because of the preliminary nature of available data, we did not perform meta-analysis but report the results narratively.
MAIN RESULTS
We identified two studies, both from the same investigators. In a study of 48 volunteers, a combination of mecamylamine plus nicotine patch was more effective than nicotine patch alone (abstinence rate at one year 37.5% vs 4.2%). In a second study, 80 volunteers were treated for four weeks prior to cessation with one of four treatments: 1. Nicotine patch plus mecamylamine capsules 2. Nicotine alone 3. Mecamylamine alone 4. No active drug. All four groups received combination treatment with nicotine and mecamylamine after the scheduled quit date. The abstinence rates in these four groups were respectively 40%, 20%, 15% and 15%. The higher abstinence rate in the group treated with combination therapy was not statistically significant. The authors reported a statistically significant benefit of mecamylamine using Kaplan-Meier survival analysis. In the doses used, mecamylamine was well tolerated, although up to 40% of subjects required reductions in dose, usually because of constipation.
REVIEWER'S CONCLUSIONS
Data from two small studies suggest that the combination of nicotine and mecamylamine may be superior to nicotine alone in promoting smoking cessation. However, these results require confirmation in larger studies before the treatment can be recommended clinically.
Topics: Administration, Cutaneous; Drug Therapy, Combination; Humans; Mecamylamine; Nicotine; Nicotinic Antagonists; Smoking Cessation; Smoking Prevention
PubMed: 10796584
DOI: 10.1002/14651858.CD001009 -
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