Efficacy of citicoline as a supplement in glaucoma patients: A systematic review.

PURPOSE: Glaucoma is a leading cause of irreversible blindness worldwide. Retinal ganglion cells (RGC), the neurons that connect the eyes to the brain, specifically die in glaucoma, leading to blindness. Elevated intraocular pressure (IOP) is the only modifiable risk factor, however, many patients progress despite excellent IOP control. Thus, alternative treatment strategies to prevent glaucoma progression are an unmet need. Citicoline has demonstrated neuroprotective properties in central neurodegenerative diseases. However, conclusive evidence of the effect of citicoline on glaucoma progression is missing. This systematic review investigates first-time the therapeutic potential of citicoline in glaucoma patients. METHODS: The present study was conducted according to the PRISMA 2020 statement. PubMed, Web of Science, Google Scholar, and Embase were accessed in July 2023 to identify all clinical studies investigating the efficacy of citicoline on IOP, the mean deviation of the 24-2 visual field testing (MD 24-2), retinal nerve fibre layer (RNFL), and the pattern electroretinogram (PERG) P50-N95 amplitude in glaucoma patients. The risk of bias was assessed using the Review Manager 5.3 software (The Nordic Cochrane Collaboration, Copenhagen) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool. RESULTS: Ten studies were eligible for this systematic review, including 424 patients. The mean length of the follow-up was 12.1 ± 11.6 months. The overall risk of bias was low to moderate. The mean age of the patients was 56.7 years. There were no significant differences in the IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude between patients receiving citicoline and the control group. There was no improvement from baseline to the last follow-up in IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude. CONCLUSION: There is a lack of sufficient evidence to support that citicoline slows the progression of glaucoma.

Is Citicoline Effective in Preventing and Slowing Down Dementia?-A Systematic Review and a Meta-Analysis.

BACKGROUND: Cognitive impairment is a staggering personal and societal burden; accordingly, there is a strong interest in potential strategies for its prevention and treatment. Nutritional supplements have been extensively investigated, and citicoline seems to be a promising agent; its role in clinical practice, however, has not been established. We systematically reviewed studies on the effect of citicoline on cognitive performance. METHODS: We searched the PubMed and Cochrane Library databases for articles published between 2010 and 2022. Relevant information was extracted and presented following the PRISMA recommendations. Data were pooled using the inverse-variance method with random effects models. RESULTS: We selected seven studies including patients with mild cognitive impairment, Alzheimer's disease or post-stroke dementia. All the studies showed a positive effect of citicoline on cognitive functions. Six studies could be included in the meta-analysis. Overall, citicoline improved cognitive status, with pooled standardized mean differences ranging from 0.56 (95% CI: 0.37-0.75) to 1.57 (95% CI: 0.77-2.37) in different sensitivity analyses. The overall quality of the studies was poor. DISCUSSION: Available data indicate that citicoline has positive effects on cognitive function. The general quality of the studies, however, is poor with significant risk of bias in favor of the intervention. Other: PubMed and the Cochrane Library.

The acute dose and baseline amplitude-dependent effects of CDP-choline on deviance detection (MMN) in chronic schizophrenia: A pilot study.

The detection of deviant auditory features is empirically supported as impaired in schizophrenia and has been shown to associate with functional outcome. Modulated by glutamate neurotransmission, this sensory process has also been shown to relate to the α7 nicotinic acetylcholine receptor (nAChR) system, a prioritized molecular target for the development of novel cognition targeted pharmacological treatments. This pilot study assessed the acute effects of CDP-Choline, a choline supplement with α7 nAChR agonist properties, on the mismatch negativity (MMN), an event-related potential index of the detection of an acoustic change, in a sample of individuals diagnosed with chronic schizophrenia. Utilizing a randomized, placebo-controlled, double-blind design, the dose-dependent (500 mg, 1,000 mg, 2,000 mg), baseline amplitude-dependent (low vs. high), and deviant feature-dependent effects of CDP-Choline on the MMN were examined. CDP-choline's effects interacted with dosage, deviance feature, and baseline amplitude with low baseline amplitude patients demonstrating enhanced MMNs, and high baseline amplitude patients demonstrating suppressed MMNs in response to CDP-Choline. These findings offer tentative support for the involvement of the α7 nAChR system in auditory MMN abnormalities in schizophrenia and supports further research assessing the effects of long-term treatment with CDP-Choline in the personalized treatment of auditory deviance processing impairments. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Synergistic effect between imipramine and citicoline upon induction of analgesic and antidepressant effects in mice.

Imipramine is a tricyclic antidepressant (TCA) drug that is sometimes used to treat neuropathic pain. Citicoline is a dietary supplement that has been used as a neuroprotective agent for neurological disorders. Probable interaction between imipramine and citicoline on pain and depression behaviors was examined in mice using a tail-flick test, open field test (OFT), forced swimming test (FST), and tail suspension test (TST). The results indicated that the intraperitoneal (i.p.) administration of citicoline (50 mg/kg) induced analgesic and antidepressant-like behaviors in mice. Similarly, i.p. injection of imipramine (5 mg/kg) induced dose-dependent anti-nociceptive and anti-depressive effects. Co-administration of different doses of imipramine (1.25, 2.5, and 5 mg/kg) along with an ineffective dose of citicoline (6.25 mg/kg) increased tail-flick latency and decreased immobility time in the FST, suggesting an analgesic and antidepressant-like behaviors. Interestingly, there is a synergistic effect between imipramine and citicoline upon the induction of analgesic and antidepressant effects. All doses of the drugs had no significant effect on the locomotor activity. Based on these results, it can be concluded that the administration of citicoline (as an adjuvant drug) in combination with imipramine increased the efficacy of TCA drugs for modulation of pain and depression behaviors.

Effectiveness of citicoline in pediatric patients with refractive amblyopia in Surabaya, East Java, Indonesia.

OBJECTIVES: Amblyopia is a decrease of visual acuity that cannot be attributed to any structural abnormality of the eye or visual system, causing a partial or complete loss of vision due to inadequate stimulation in early life. Citicoline has been reported to improve visual acuity in amblyopic eyes as adjuvant treatment. This study was aimed to determine the effectiveness of citicoline in pediatric patients with refractive amblyopia in ophthalmology daily practices. METHODS: This was a retrospective-descriptive study with a time limited sampling method. This study was conducted at Surabaya Eye Clinic, East Java, Indonesia, by reviewing medical records for the period of January 2018 to December 2019. RESULTS: A total of 34 eyes were included in the study with the majority aged five years (41.2%) and six years (35.3%). The severity of amblyopia varied among patients, 21 eyes (61.76%) had mild amblyopia, seven eyes (20.59%) had moderate amblyopia, and two eyes (5.88%) had severe amblyopia. The duration of given therapy also varied, 18 eyes (52.94%) were given 3 months therapy, two eyes were given 4 months therapy, 12 eyes were given 6 months therapy, and two eyes were given 8 months therapy. Citicoline was found effective in mild and moderate amblyopia and for the duration of 3 and 6 months (p<0.05). In others group who did not showed statistically significant improvement was due to inadequate samples but clinically significant improvement was noted. CONCLUSIONS: Citicoline therapy resulted in a clinically and statistically improvement in refractive amblyopia patients.

Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Supplementation of citicoline (CDP-choline), a naturally occurring mononucleotide, has shown beneficial effects on memory function and behavior in populations with a wide range of impairments. However, few studies have investigated its effect in healthy older populations. OBJECTIVE: The objective of this study was to investigate the effects of citicoline (Cognizin®), on memory in healthy elderly populations with age-associated memory impairment (AAMI). METHODS: A total of 100 healthy men and women aged between 50 and 85 y with AAMI participated in this randomized, double-blind, placebo-controlled trial. Participants were randomized to receive placebo (n = 51) or citicoline (n = 49; 500 mg/d) for 12 wk. Memory function was assessed at baseline and end of the intervention (12 wk) using computerized tests (Cambridge Brain Sciences, Ontario, Canada). Safety measurements included adverse events query, body weight, blood pressure, and hematology and metabolic panel. Intent-to-treat analysis was conducted using ANCOVA for the primary and secondary outcome variables with Bonferroni correction for multiple comparisons. RESULTS: A total of 99 out of 100 participants completed the study in its entirety. After the 12-wk intervention, participants supplemented with citicoline showed significantly greater improvements in secondary outcomes of episodic memory (assessed by the Paired Associate test), compared with those on placebo (mean: 0.15 vs. 0.06, respectively, P = 0.0025). Composite memory (secondary outcome), calculated using the scores of 4 memory tests, also significantly improved to a greater extent following citicoline supplementation (mean: 3.78) compared with placebo (mean: 0.72, P = 0.0052). CONCLUSIONS: Dietary supplementation of citicoline for 12 wk improved overall memory performance, especially episodic memory, in healthy older males and females with AAMI. The findings suggest that regular consumption of citicoline may be safe and potentially beneficial against memory loss due to aging. This trial was registered at clinicaltrials.gov as NCT03369925.

[The role of citicoline in glaucoma]. / Bedeutung von Citicolin bei der Glaukomerkrankung.

BACKGROUND: In recent years, many experimental and clinical studies have shown that in glaucoma, neuronal degeneration occurs not only at the level of the retina and optic nerve, but also along the entire visual pathway and the brain. OBJECTIVE: This article presents the neuroprotective effects of citicoline and their mechanisms in glaucoma disease. MATERIALS AND METHODS: The relevance of citicoline is explained against the background of neuroanatomy, neuroimaging, and the pathogenesis of glaucoma. Data from experimental and clinical studies are presented and a conclusion is drawn for clinical application. RESULTS: Citicoline has a neuroprotective effect via mechanisms relevant to glaucoma. The neuroprotective effect of citicoline in open-angle glaucoma can be demonstrated functionally and morphologically. It is independent of the glaucoma damage and intraocular pressure, and usually occurs only after 1 year. The effects of oral citicoline occur at a daily dose of 500-1000 mg. Citicoline can be taken permanently or in cycles. No side effects occurred in the studies when taking citicoline. Citicoline can improve cognitive performance and thus treatment adherence as well as quality of life in glaucoma patients. CONCLUSION: This relatively old nootropic drug, which is now marketed as a food supplement, seems to be a valuable addition to conventional treatment and also a rational option for prophylaxis of open-angle glaucoma.

Citicoline as Adjuvant Therapy in Parkinson's Disease: A Systematic Review.

PURPOSE: Parkinson disease (PD) medications are not readily available in all countries. Citicoline increases dopamine synthesis and inhibits dopamine uptake. This systematic review aims to synthesize current existing evidence on the efficacy of citicoline adjunctive therapy in improving PD symptoms. METHODS: An extensive literature search of Scopus, Embase, PubMed, Cochrane Library, and Google Scholar was conducted for articles published on or before December 31, 2019. The studies were screened and selected by 2 independent reviewers. We included all studies that explored the efficacy of citicoline as an adjunct therapy in PD. FINDINGS: A total of 7 studies (2 crossover, 3 randomized controlled, and 2 open prospective studies) were included. Despite the varied outcome tools, this review found that patients with PD who were taking citicoline had significant improvement in rigidity, akinesia, tremor, handwriting, and speech. Citicoline allowed effective reduction of levodopa by up to 50%. Significant improvement in cognitive status evaluation was also noted with citicoline adjunctive therapy. IMPLICATIONS: Citicoline adjuvant therapy has beneficial effects as an adjuvant therapy in patients with PD. However, due to the heterogeneity of the studies, there is a need for more high-quality studies.

Protective effect of citicoline on random flap survival in a rat mode.

BACKGROUND: Medical therapy for flap survival has been extensively investigated. In this study, we explored the effect of citicoline (CDP-choline, CDPC), used for clinical treatment of cerebral trauma, on random skin flap survival in rats. MATERIALS AND METHODS: Sixty rats were divided into three groups: low-dose (CDPC-L), high-dose (CDPC-H), and control. The CDPC-L and CDPC-H groups were intraperitoneally injected with 100 mg/kg and 300 mg/kg CDPC every day, respectively; the control group was injected with an equivalent volume of normal saline. The survival region was assessed on the 7th day after the flap operation. The microvascular density and neutrophil density were measured by hematoxylin and eosin staining. Lead angiography was used to detect angiogenesis, and laser Doppler was used to detect blood perfusion. Expression levels of vascular endothelial growth factor (VEGF), interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, Toll-like receptor (TLR) 4, and nuclear factor kappa B (NF-κB) were detected by immunohistochemistry. Malondialdehyde and superoxide dismutase were used to determine the lipid peroxidation level. RESULTS: The average survival region of the flap was significantly larger in the CDPC-H group than in CDPC-L and control groups, with less ischemic necrosis. VEGF expression, microvascular density, angiogenesis, blood perfusion, and superoxide dismutase in the flap were higher in the CDPC-H group than in the CDPC-L and control groups. In addition, levels of neutrophil density, IL-1ß, IL-6, TNF-α, TLR4, NF-κB, and malondialdehyde decreased significantly in the CDPC-H group. CONCLUSION: High-dose CDPC injection after a random flap operation is beneficial for flap survival.

A novel approach in the management of hyperhomocysteinemia.

Hyperhomocysteinemia (Hhcy) is a biochemical alteration with plasma levels of homocysteine higher than 15 µmol/L, associated with atherosclerosis, and with vascular thrombosis by disrupting endothelial cells. Homocysteine is a sulfur-containing amino acid derived from methionine which is an essential amino acid. Excess homocysteine produced in the body is expelled out by liver and kidney from the systemic circulation. Hhcy is caused by the excess deficiencies of the vitamins like pyridoxine (B6), folic acid (B9), or cyanocobalamin (B12). High protein consumers are usually at risk for hyperhomocysteinemia because of low plasma B12 levels. It is approximated that mild Hhcy occurs in 5-7% of the general population and 40% in patients with vascular disease. Patients with heart failure, impaired renal function, and diabetes should be screened since the prevalence of Hhcy in these patients appears to be quite high. In this article, we hypothesise that citicoline is a novel drug for the management of Hhcy. Furthermore, the side effects of citicoline are also minimal and self-limiting. If this strategy is validated, citicoline will be the cost-effective way to be administered for Hhcy. Many evidences are available which suggest that ignoring homocysteine levels in patients with the vascular disease would be unwise. Thus, there is an urgent need for health care providers to develop effective preventions and interventions program (folic acid, Vitamin B6 and Vitamin B12 supplementation as well as lifestyle change) to reduce this disorder.

Effectiveness of acupuncture for vascular cognitive impairment no dementia: a randomized controlled trial.

OBJECTIVE:: To evaluate the effectiveness of acupuncture in patients with vascular cognitive impairment no dementia (VCIND) in comparison with citicoline, an agent for cognitive disturbances associated with chronic cerebral disorders. DESIGN:: A randomized controlled multicenter trial. SETTING:: In three hospitals in Beijing, China. SUBJECTS:: A total of 216 patients with VCIND were recruited. INTERVENTIONS:: Patients with VCIND (mean age of 65.4 years) were randomized to receive acupuncture (two sessions per week) or oral citicoline (100 mg three times daily) over three months. MAIN MEASURES:: The primary outcome was the change from baseline to three months in cognitive symptom, measured by Alzheimer's disease Assessment Scale, cognitive subscale (ADAS-cog). Secondary outcomes included changes from baseline to six months in ADAS-cog, executive function measured by the Clock Drawing Test (CDT), and functional disability measured by the Ability of Daily Living (ADL) scale at three and six months. RESULTS:: At three months, the acupuncture group had a greater decrease in mean ADAS-cog score (-2.33 ± 0.31) than the citicoline group (-1.38 ± 0.34) with a mean difference of -0.95 (95% CI, -1.84 to -0.07, P = 0.035). The mean change from baseline to six months in ADAS-cog also significantly favored acupuncture treatments (acupuncture change -2.61 vs citicoline -1.25, difference: -1.36 points; 95% CI, -2.20 to -0.51; P = 0.002). There was no difference between the two groups on CDT and ADL scores at either time point. CONCLUSION:: Compared with citicoline, acupuncture has comparable and even superior efficacy with improved cognitive and daily living performance as a complementary and alternative medicine treatment for VCIND.

A Randomized, Double-Blind, Placebo-Controlled Trial of Citicoline in Patients with Alcohol Use Disorder.

BACKGROUND: Alcohol use disorder is a major societal and individual burden that exacerbates health outcomes, decreases quality of life, and negatively affects U.S. healthcare spending. Although pharmacological treatments are available for alcohol use disorder, many of them are limited by small effect sizes and used infrequently. Citicoline is a widely available over-the-counter supplement with a favorable side effect profile. It acts through cholinergic pathways and phospholipid metabolism. The current report examines the effect of oral citicoline on alcohol use, craving, depressive symptoms, and cognitive outcomes in individuals with alcohol use disorder. METHODS: A 12-week, randomized, double-blind, parallel-group, placebo-controlled, pilot study of citicoline (titrated to 2,000 mg/d) in 62 adults (age 18 to 75) with alcohol use disorder was conducted. Alcohol use, such as number of drinking days, amount used, and number of heavy drinking days, was assessed using the Timeline Followback method and liver enzymes, while alcohol craving was measured using the Penn Alcohol Craving Scale. A neurocognitive battery (e.g., Rey Auditory Verbal Learning Test) and depressive symptoms scale (e.g., Inventory of Depressive Symptomatology Self-Report) scores were also collected. Data were analyzed using a random regression analysis. RESULTS: The primary outcome analysis was conducted in the intent-to-treat sample and consisted of 55 participants (78.2% men and 21.8% women, mean age of 46.47 ± 9.15 years). In the assessment period, the drinking days, on average, represented 77% of the assessed days. Significant between-group differences were not observed on alcohol use, craving, and cognitive or depressive symptom measures. Citicoline was well tolerated. CONCLUSIONS: This proof-of-concept study observed that citicoline was well tolerated, but was not associated with a reduction in alcohol use or other outcomes, as compared to placebo. The favorable effects reported with citicoline for cocaine use, cognitive disorders, and other conditions do not appear to extend to alcohol use disorder.

The Effect of Citicoline Supplementation on Motor Speed and Attention in Adolescent Males.

OBJECTIVE: This study assessed the effects of citicoline, a nutraceutical, on attention, psychomotor function, and impulsivity in healthy adolescent males. METHOD: Seventy-five healthy adolescent males were randomly assigned to either the citicoline group ( n = 51 with 250 or 500 mg citicoline) or placebo ( n = 24). Participants completed the Ruff 2&7 Selective Attention Test, Finger Tap Test, and the Computerized Performance Test, Second Edition (CPT-II) at baseline and after 28 days of supplementation. RESULTS: Individuals receiving citicoline exhibited improved attention ( p = 0.02) and increased psychomotor speed ( p = 0.03) compared with those receiving placebo. Higher weight-adjusted dose significantly predicted increased accuracy on an attention task ( p = 0.01), improved signal detectability on a computerized attention task ( p = 0.03), and decreased impulsivity ( p = 0.01). DISCUSSION: Adolescent males receiving 28 days of Cognizin® citicoline showed improved attention and psychomotor speed and reduced impulsivity compared to adolescent males who received placebo.

New advances in amblyopia therapy I: binocular therapies and pharmacologic augmentation.

Amblyopia therapy options have traditionally been limited to penalisation of the non-amblyopic eye with either patching or pharmaceutical penalisation. Solid evidence, mostly from the Pediatric Eye Disease Investigator Group, has validated both number of hours a day of patching and days per week of atropine use. The use of glasses alone has also been established as a good first-line therapy for both anisometropic and strabismic amblyopia. Unfortunately, visual acuity equalisation or even improvement is not always attainable with these methods. Additionally, non-compliance with prescribed therapies contributes to treatment failures, with data supporting difficulty adhering to full treatment sessions. Interest in alternative therapies for amblyopia treatment has long been a topic of interest among researchers and clinicians alike. Incorporating new technology with an understanding of the biological basis of amblyopia has led to enthusiasm for binocular treatment of amblyopia. Early work on perceptual learning as well as more recent enthusiasm for iPad-based dichoptic training have each generated interesting and promising data for vision improvement in amblyopes. Use of pharmaceutical augmentation of traditional therapies has also been investigated. Several different drugs with unique mechanisms of action are thought to be able to neurosensitise the brain and enhance responsiveness to amblyopia therapy. No new treatment has emerged from currently available evidence as superior to the traditional therapies in common practice today. But ongoing investigation into the use of both new technology and the understanding of the neural basis of amblyopia promises alternate or perhaps better cures in the future.

Intervención terapéutica farmacológica del deterioro cognitivo leve / Pharmacological therapeutic intervention in mild cognitive impairment

El deterioro cognitivo leve es un síndrome en el que, además de sintomatología cognitiva, se pueden encontrar sintomatología afectiva y conductual y diferentes subtipos. Se trata de una entidad clínica heterogénea, que tiene heterogeneidad etiológica (degenerativa, vascular, psiquiátrica, patología no neurológica), sintomatología clínica heterogénea y heterogeneidad en el curso clínico. La etiología es múltiple y, por lo mismo, el tratamiento también lo es y se debe combinar con el no farmacológico. Se describen las intervenciones farmacológicas tanto preventivas como terapéuticas: control de factores de riesgo vascular, evitar la iatrogenia, uso de suplementos nutracéuticos, la CDP-colina, el Ginkgo biloba EGb 761(R) y la mejora de órganos de los sentidos (AU)

Mild cognitive impairment (MCI) is a syndrome encompassing affective and behavioural symptoms and various subtypes. MCI is a heterogeneous clinical entity with varied causes (degenerative, vascular, psychiatric, non-neurological disorders), and there is wide variation in symptoms and clinical course. There are multiple causes and consequently various treatments can be applied and should be combined with non-pharmacological measures. This article describes both preventive and therapeutic pharmacological interventions: control of vascular risk factors, avoidance of iatrogeny, use of nutraceuticals, CDP-choline, and Ginkgo biloba EGb 761(R), and improvement in sense organs (AU)

Citicoline Combination Therapy for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Residual symptoms of major depressive disorder are a source of long-term morbidity. New therapeutic strategies are required to alleviate this morbidity and enhance patient quality of life. Citicoline has been used for vascular accidents and has been effective in cognitive rehabilitation. It has been used successfully to reduce craving in patients with substance abuse disorder and for mood management of bipolar disorder. Here, we test citicoline effectiveness as an adjuvant therapy in major depression. METHOD: A double-blind randomized trial was designed on 50 patients with major depressive disorder who were under treatment with citalopram. Patients were allocated to 2 groups and received citicoline (100 mg twice a day) or placebo as an adjuvant treatment for 6 weeks. Depressive symptoms were assessed by the Hamilton Depression Rating Scale (HDRS) at baseline and at weeks 2, 4, and 6. RESULTS: Significantly greater improvement was observed in the HDRS scores of the citicoline group compared with the placebo group from baseline to weeks 2, 4, and 6 (Ps = 0.030, 0.032, and 0.021, respectively). Repeated-measures general linear model demonstrated a significant effect for time × treatment interaction on the HDRS score (F2.10,101.22 = 3.12, P = 0.04). Remission rate was significantly higher in the citicoline group compared with the placebo group (P = 0.045). CONCLUSIONS: Citicoline was an effective adjuvant to citalopram in the therapy of major depressive disorder.

Encefalopatía tardía por monóxido de carbono de curso reversible en un paciente tratado con citicolina / Delayed-onset encephalopathy caused by carbon monoxide poisoning: Resolution in a patient treated with citicoline

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Citicoline in addictive disorders: a review of the literature.

BACKGROUND: Citicoline is a dietary supplement that has been used as a neuroprotective agent for neurological disorders such as stroke and dementia. Citicoline influences acetylcholine, dopamine, and glutamate neurotransmitter systems; serves as an intermediate in phospholipid metabolism; and enhances the integrity of neuronal membranes. Interest has grown in citicoline as a treatment for addiction since it may have beneficial effects on craving, withdrawal symptoms, and cognitive functioning, as well as the ability to attenuate the neurotoxic effects of drugs of abuse. OBJECTIVES: To review the literature on citicoline's use in addictive disorders. METHODS: Using PubMed we conducted a narrative review of the clinical literature on citicoline related to addictive disorders from the years 1900-2013 using the following keywords: citicoline, CDP-choline, addiction, cocaine, alcohol, substance abuse, and substance dependence. Out of approximately 900 first hits, nine clinical studies have been included in this review. RESULTS: Most addiction research investigated citicoline for cocaine use. The findings suggest that it is safe and well tolerated. Furthermore, citicoline appears to decrease craving and is associated with a reduction in cocaine use, at least at high doses in patients with both bipolar disorder and cocaine dependence. Limited data suggest citicoline may also hold promise for alcohol and cannabis dependence and in reducing food consumption. CONCLUSIONS: Currently, there is limited research on the efficacy of citicoline for addictive disorders, but the available literature suggests promising results. Future research should employ larger sample sizes, increased dosing, and more complex study designs.

Most effective adjuvant treatments after surgery in peripheral nerve laceration: Systematic review of the literature on rodent models.

Surgical repair alone does not lead to satisfactory recovery after nerve laceration injury, yet no adjuvant clinical treatments are available. The goal of this review is to systematically survey all adjuvant treatments after surgery investigated in rat and mouse models. Both PubMed and Embase were explored with a systematic bibliographic search algorithm. Inclusion criteria consisted of treatments applied to rats or mice after complete transection and microsurgical repair of lower-limb motor or mixed nerves. Effect size statistics enabled numerical comparison between outcomes of treated and untreated animals and ranked the best treatments. 1,553 articles were found according to our search strategies, and 22 of them corresponded to our pre-defined inclusion criteria. After data extraction and analysis, the top 3 adjuvant strategies in terms of combined average effect size were citicoline, neurotrophin-4, and nitric oxide synthesis inhibitor, with values of 5.52, 5.14 and 4.08, respectively. Definitive treatment comparison was difficult due to the lack of uniformity in outcome evaluation in the experiments performed. Animal studies, comparing treatments administered within the same experimental protocol, are needed to truly assess efficiency and to provide solid recommendations for future clinical investigation.

Nutrients for prevention and treatment of mental health disorders.

The choice of nutrients for review is based on clinical evidence of efficacy in neuropsychiatric disorders and biochemical effects that are neuroprotective or reparative. Vitamins, minerals, amino acids, and metabolites have been shown to augment antidepressants, improve symptoms in anxiety disorders, depression, neurodegenerative diseases, brain injury, ADHD, and schizophrenia, and to reduce medication side effects. Detection and correction of vitamin and mineral deficiencies can be essential for recovery. Generally low in adverse effects when taken in therapeutic doses, nutrients can be combined for greater benefits. Further studies are warranted to validate these promising treatments.