Unintentional therapeutic errors with bupropion are common. The impact of the timing of the second dose in a double dose exposure on adverse effects is not well studied. This study aims to compare adverse effects between double doses separated by <720 min and ≥720 min.

This was a retrospective cohort study of unintentional double dose bupropion ingestions in patients reported to a regional poison center between January 2018 and December 2022. Patients were included if the double dose was their own medication, unintentional, and a single substance exposure. Data collected included age, gender, bupropion formulation, prescribed home dose, dosing error details, time between doses, caller site, referral to the emergency department, patient observation at healthcare facilities, clinical effects, and outcome.

Among 663 cases screened, 294 met inclusion criteria. The majority involved extended-release preparations (69.0%). Seventy-four were observed in a healthcare facility and monitored for 24 h from initial dose. The incidence of seizures was 5.3%, including one case not observed for a full 24 h. There was no significant difference in the incidence of seizures (2.7% versus 7.7%), tachycardia (27.0% versus 30.8%), hypertension (18.9% versus 38.5%) other signs/symptoms (27.0% versus 23.1%), or any signs/symptoms (48.6% versus 61.5%) between double doses of extended release bupropion separated by <720 min and those separated by ≥720 min, respectively.

In patients with double dose exposures to extended-release bupropion, it does not appear that the timing of the second dose can be used to risk-stratify patients. Our data are limited by sample size.

In this study, the time between double doses of bupropion did not affect the incidence of seizure, tachycardia, hypertension, other signs/symptoms, or any signs/symptoms. Larger, prospective studies investigating this difference would strengthen our understanding and management of these patients.

The pursuit of linear dosage in pharmacy is essential for achieving consistent therapeutic release and enhancing patient compliance. This review provides a comprehensive summary of zero-order drug delivery systems, with a particular focus on reservoir-based systems emanated from different microfabrication technologies.

The consideration of recent advances in drug delivery systems is given to encompass the key areas including the importance of achieving a constant drug release rate for therapeutic applications. Detailed examination of reservoir-based systems, their design, mechanisms of action and materials used are highlighted. By addressing these areas, the discussion aims to provide a thorough understanding of most recent zero-order drug delivery systems, their performance advantages and methods of their manufacturing. To ensure the complete coverage of the explored research area, modern AI-assistant tools were used to find not only the most relevant, but also connected and similar articles.

Future developments in reservoir-based drug delivery systems are expected to significantly enhance therapeutic effectiveness and patient outcomes through the integration of innovative materials and technologies. The fabrication of intelligent drug delivery systems that utilize sensors and feedback mechanisms can enable real-time monitoring of drug release and patient reactions.

Pharmacotherapy for depression includes drugs such as monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), noradrenaline (NA) and serotonin (5-HT) reuptake inhibitors (NaSSAs), and atypical antidepressants; these drugs exert differentially beneficial effects on symptoms of depression after acute and chronic treatment in animal models. Said effects are established through neuroplastic mechanisms involving changes in neurogenesis and synaptogenesis as result of the activation of intracellular signaling pathways associated with neurochemical and behavioral changes. Antidepressants increase the synaptic availability of monoamines (monoaminergic hypothesis) such as 5-HT, NA, and gamma-aminobutyric acid (GABA) by inhibiting their reuptake or degradation and activating intracellular signaling pathways such as the responsive element binding protein (cAMP-CREB) cascade, which regulates the expression of genes related to neuroplasticity and neurogenesis, such as brain-derived neurotrophic factor (BDNF), in various brain structures implicated in depression. The aim of this review is to analyze the mechanisms of action of different antidepressants and to compare the effects of acute and chronic treatment on neuroplasticity in animal models of depression. A thorough search was conducted in PubMed, Scopus, and Web of Science, focusing on studies since 1996 with keywords like antidepressants, acute and chronic treatment, neuroplasticity, and experimental depression. Studies included had to investigate antidepressant effects experimentally, with full-text access, while excluding those that did not. Data extraction focused on study design, findings, and relevance to understanding treatment differences. Only high-quality, peer-reviewed studies were considered to ensure a comprehensive synthesis of current knowledge.

Bupropion is an atypical antidepressant indicated for the treatment of major depressive disorder (MDD), seasonal affective disorder (SAD), and smoking cessation. It is also used off-label for attention deficit hyperactivity disorder (ADHD). Its mechanism of action includes the selective norepinephrine and dopamine reuptake inhibitor (NDRI). The drug is available in immediate-release (IR), sustained-release (SR), and extended-release (XL) formulations. Common side effects are typically mild and include anxiety, insomnia, headache, dizziness, constipation, and nausea. Rarely, cutaneous hypersensitivity reactions may occur. We describe a 23-year-old man who developed severe and diffuse urticaria and angioedema 4 weeks after initiation of bupropion XL for MDD and ADHD. The bupropion was stopped, and he was treated with levocetirizine, diphenhydramine (oral and topical), and methylprednisolone with complete resolution of his symptoms within 2 weeks. Due to a good initial therapeutic response to the medication, a trial of bupropion SR was initiated. The patient again had a favorable therapeutic response without any dermatologic side effects.

Sexual dysfunction is common in men and women with neurological diseases. Medications used in neurology can cause sexual dysfunction independently of the disease process and this may adversely affect patients' quality of life. This review focuses on medications commonly prescribed to neurological patients that may contribute to altered sexual function, and discusses how they may differ in men and women.

Selective serotonin reuptake inhibitors are associated with high rates of nonadherence and sexual dysfunction, yet the correlation between these findings in young adult men is poorly characterized. We aimed to evaluate if young adult men are less willing to adhere to antidepressant treatment due to intolerable side effects, such as sexual dysfunction.

Deidentified, compensated survey that assessed baseline demographics, PHQ-8 and GAD-7 scores, attitudes towards antidepressant medication side effects, and perceptions of antidepressant medications including selective serotonin reuptake inhibitors, bupropion, and mirtazapine.

From 665 delivered surveys, 505 respondents completed their survey (response rate: 76%), of which 486 were included for final analysis. After seeing common side effect profiles, our sample's willingness to take sexual function-sparing agents, such as bupropion or mirtazapine, was significantly greater than selective serotonin reuptake inhibitors (p < 0.001), with no significant difference between bupropion and mirtazapine (p = 0.263). The negative influence of erectile dysfunction and anorgasmia scored significantly higher than other common antidepressant side effects like weight gain, nausea, and dry mouth (range: p < 0.001, p = 0.043). With the exception of insomnia, participants indicated that experiencing sexual dysfunction while taking an antidepressant medication would lead to nonadherence at a significantly higher frequency than any other side effect assessed (range: p < 0.001, p = 0.005).

The risk of experiencing sexual side effects when taking antidepressants could lead young adult men to become nonadherent to these medications. Strategies to augment the effectiveness of antidepressants, such as shared decision-making and the use of sexual function-sparing agents, are critical.

The global prevalence of obesity and overweight is a significant concern in the field of public health. However, addressing and combating these conditions pose considerable challenges. Numerous interventional studies have been conducted to assess the possible impact of bupropion on weight reduction. The primary objective of this study was to conduct a comprehensive investigation into the effects of bupropiona alone and in combination with naltrexone on weight, body mass index (BMI), and waist circumferences (WC).

A systematic search was conducted in five databases using established keywords. The purpose of this search was to uncover controlled trials that examined the impact of bupropion, either as a standalone intervention or in combination with naltrexone, on weight loss outcomes. The random-effects model analysis was used to provide pooled weighted mean difference and 95% confidence intervals.

Twenty five studies with 22,165 participants' were included in this article. The pooled findings showed that bupropion administration has an effect on lowering weight (WMD: -3.67 kg, 95% CI: -4.43 to -2.93) and WC (WMD: -2.98 cm, 95% CI -3.78 to -2.19) in compared with control groups. The analysis also showed that the effects of the present intervention on weight and WC during the intervention are > 26 weeks and ≤ 26 weeks compared to the other group, respectively. In addition, changes in weight loss and WC after receiving bupropion together with naltrexone were more compared to bupropion alone.

In conclusion, the addition of combination therapies like bupropion and naltrexone to lifestyle modifications including diet would cause significant weight loss.

This review discusses the safety concerns associated with diving while using psychotropic medication and the limited literature available on the topic. Despite the risks, some divers continue to dive while taking these medications, and their reasons for doing so are unclear. The exact mechanisms of action of these drugs in hyperbaric environments are poorly understood. While current standards and advice for fitness-to-dive assessments are based on limited evidence and expert opinion, developing evidence-based strategies could improve patient care and optimise diving safety. This review appraises relevant literature in diving medicine and provides clinical perspectives for diving physicians conducting fitness-to-dive assessments on patients using psychotropic medication.

The adverse effects of smoking cessation in individuals with mental health disorders have been a point of concern, and progress in the development of treatment has been slow. The primary first-line treatments for smoking cessation are Nicotine Replacement Therapy, Bupropion, Varenicline, and behavioural support. Nortriptyline and Clonidine are second-line treatments used when the first-line treatments are not effective or are contraindicated. Smoking cessation medications have been shown to be effective in reducing nicotine cravings and withdrawal symptoms and promoting smoking cessation among patients living with mental disorders. However, these medications may have implications for patients' mental health and need to be monitored closely. The efficacy and side effects of these medications may vary depending on the patient's psychiatric condition, medication regimen, substance use, or medical comorbidities. The purpose of this review is to synthesise the pharmacokinetics, pharmacodynamics, therapeutic effects, adverse effects, and pharmacological interactions of first- and second-line smoking cessation drugs, with an emphasis on patients suffering from mental illnesses. Careful consideration of the risks and benefits of using smoking cessation medications is necessary, and treatment plans must be tailored to individual patients' needs. Monitoring symptoms and medication regimens is essential to ensure optimal treatment outcomes.

Bupropion had been in use since the late 1980s as an unconventional treatment for depression. Unlike other antidepressants, bupropion has no serotonergic activity and inhibits the reuptake of norepinephrine and dopamine. The drug has been used to treat depression, Attention Deficit Hyperactivity Disorder (ADHD), and smoking cessation. This investigation reviews the pharmacokinetic and pharmacodynamic effects of bupropion and its mechanisms of action and interactions with other drugs. We evaluated the efficacy of major on and off-label uses of bupropion, focusing on the indications, benefits, and adverse effects. Our review demonstrates that bupropion is superior to placebo and non-inferior to SSRIs such as escitalopram in treating major depressive disorder. More research is needed to determine positive patient-centered outcomes such as increases in quality of life. In the case of ADHD, the evidence for efficacy is mixed with poorly conducted randomized clinical trials, small sample sizes, and a lack of long-term assessments. The same is true in the case of bipolar disorder in which there is still limited and controversial data available on bupropion's safety and efficacy. In the case of smoking cessation, bupropion is found to be an effective anti-smoking drug with synergistic benefits when used as a combination therapy. We conclude that bupropion has the potential to provide benefit for a subset of patients who do not tolerate other typical antidepressants or anti-smoking therapies or for those whose treatment goals align with bupropion's unique side effect profile, such as smokers who wish to quit and lose weight. Additional research is needed to determine the drug's full clinical potential, particularly in the areas of adolescent depression and combination therapy with varenicline or dextromethorphan. Clinicians should use this review to understand the varied uses of the drug and identify the situations and patient populations in which bupropion can lend its greatest benefit.

Bupropion is a structurally and biochemically unique antidepressant that inhibits the neuronal uptake of dopamine and norepinephrine. Often prescribed for children and adolescents, bupropion displays both neurologic and cardiac toxicities in overdose more serious than toxicities resulting from poisonings by tricyclic antidepressants and selective serotonin reuptake inhibitors. Bupropion was briefly removed from the market in the 1980s. The incidence of bupropion poisonings in the United States, and resultant morbidity and mortality in children and adolescents, has been steadily increasing since 2012. Antidepressants less toxic than bupropion in overdose should be considered in the vulnerable 6- to 19-year-old patient population. [Pediatr Ann. 2023;52(5):e178-e180.].

Fragile X syndrome (FXS) is a hereditary disease that predominantly leads to intellectual disability (ID) in boys. It is the second prominent cause of ID, which manifests as a result of the atypical development of the cytosine-guanine-guanine (CGG) region. This irregular extension of the CGG region gives rise to methylation and silencing of the fragile X mental retardation 1 (FMR1) gene, causing a loss of the fragile X mental retardation 1 protein (FMRP). This reduction or loss of FMRP is the main cause of ID. It has a multisystemic involvement showing neuropsychiatric features such as ID, speech and language delay, autism spectrum disorder, sensory hyperarousal, social anxiety, abnormal eye contact, shyness, and aggressive behaviour. It is also known to cause musculoskeletal symptoms, ocular symptoms, cardiac abnormalities, and gastrointestinal symptoms. The management is challenging, and there is no known cure for the disease; hence an early diagnosis of the condition is needed through prenatal screening offered to couples with familial history of ID before conception. The management rests on non-pharmacological modalities, including applied behaviour analysis, physical therapy, occupational therapy, speech-language therapy, and pharmacologic management through symptomatic treatment of comorbid behaviours and psychiatric problems and some forms of targeted therapy.

There is a strong evidence base for the use of existing pharmacotherapies to support tobacco cessation, alone or in combination, ideally with concurrent behavioral interventions. Future pharmacotherapies under development may assist in the most refractory cases. Incorporating current and future therapies into a longitudinal chronic care model for tobacco dependence will help a diverse range of patients achieve independence from nicotine addiction.

Bipolar depression (BD-D) is both common and incredibly challenging to treat. Even treated individuals with BD-D experience depression approximately 19% of the time, and subsyndromal depression an additional 18%. This stands in clear contrast to the approximately 10% of time spent in hypomania and 1% of time spent in mania. Despite this high illness burden, there remain relatively few treatment options approved by the US Food and Drug Administration for BD-D. Of the approved medications, four are second-generation antipsychotics (SGAs) and one is an SGA combined with an antidepressant. However, particularly when used long-term, antipsychotics can pose a significant risk of adverse effects, raising the clinical conundrum of weighing the risks associated with long-term antipsychotic use versus the risk of relapse when patients are off medications. Here, we review commonly used treatments for BD-D, including antipsychotics, classic mood stabilisers, electroconvulsive therapy and psychotherapy. We then address the somewhat controversial topic of antidepressant use in BD-D. Finally, we summarise emerging treatment options and highlight ongoing clinical trials. We hope this review will help compare the risks and benefits of several common and novel options for the treatment of patients with BD-D. In doing so, we also hope this review will aid the individualised selection of treatments based on each patient's history and treatment goals.

Seizures that occur spontaneously after termination of an electroconvulsive therapy (ECT) seizure are termed tardive seizures. They are thought to be a rare complication of ECT, influenced by risk factors that affect seizure threshold. However, there has been limited review of tardive seizures with modified ECT. We aimed to review the literature to provide clinical guidance for the use of ECT after tardive seizures.

PubMed, EMBASE, PsycInfo, and CINAHL databases were searched from inception to May 2021 to identify cases of modified ECT, with evidence of a seizure occurring within 7 days of a terminated ECT seizure. Data for demographic, medical, pharmacological, anesthetic, and ECT variables as well as management strategies were collected.

There have been 39 episodes of modified ECT-related tardive seizures published over a period of 40 years. In 97.4% of cases, there was at least 1 identified potential risk factor for seizures, including use of a seizure-lowering medication and/or preexisting neurological injury. Major complications were uncommon (<15% of cases); however, 1 fetal death and 1 subsequent suicide were reported. No case was diagnosed with epilepsy, although around 20% continued on antiepileptic medications. More than half of the included patients were retrialed on ECT, with only 15% developing further tardive seizures.

Seizures that occurred spontaneously after the termination of an ECT seizure are a rare complication of modified ECT. Recommencing ECT after a tardive seizure may occur after review of modifiable seizure risk factors and with consideration of antiepileptic medication and extended post-ECT monitoring.

Bupropion extended-release (XL; once-daily dosing) has equal efficacy with the sustained-release (SR) formulation (twice-daily dosing) for treating depression, but no studies have compared the two formulations for the treatment of smoking. In a naturalistic open-label study, we compared the effectiveness and the adverse event profiles of XL and SR in treating cancer patients for smoking.

Cancer patients (N = 648) were prescribed bupropion XL (n = 454) or SR (n = 194) alone or in combination with nicotine replacement therapy (NRT) for treating smoking from September 2006 to December 2017. We analyzed 7-day point prevalence abstinence at end-of-treatment (EOT; 3 months postmedication initiation) and evaluated for noninferiority. We also analyzed the adverse event profile differences between the medications.

There were no significant differences in abstinent rates at EOT between bupropion XL and SR when using intent-to-treat models, regardless of concomitant NRT. XL demonstrated noninferiority in treatment efficacy compared to SR when excluding those on combined treatment with NRT. Further, there were no significant differences in spontaneously reported adverse events between XL and SR.

Our data did not reveal a difference between bupropion XL and SR formulations in terms of effectiveness or adverse event profiles among cancer patients prescribed bupropion alone or in combination with NRTs to quit smoking.

In this first published direct comparison of their effectiveness and adverse event profiles, we found that bupropion XL is likely therapeutically equivalent to bupropion SR when treating smoking among cancer patients, and produces similar side effects.

Antipsychotic treatment has been documented as the mainstay for the management of schizophrenia. Evidence in literature has suggested that the management of negative symptoms of schizophrenia continues to be a treatment challenge. Therefore, residual negative symptoms can become more pervasive and visible after the treatment of positive symptoms, leading to an impaired marked deficit in the vital daily functions of patients. We present a case series of three patients with a past psychiatric history of schizophrenia who presented to the psychiatric emergency with acute symptoms of schizophrenia. Following antipsychotic treatment, all these patients showed improvement of positive symptoms, however, profound negative symptoms of schizophrenia became visible. The negative symptoms include anhedonia, amotivation, alogia, affective flattening, and passive social withdrawal. We added bupropion to manage the negative symptoms, and all three patients achieved a good treatment response. This case series suggests that the anti-depressive effects of bupropion might be a valuable treatment option in the treatment of negative symptoms of schizophrenia.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the full mutation as well as highly localized methylation of the fragile X mental retardation 1 (FMR1) gene on the long arm of the X chromosome. Children with FXS are commonly co-diagnosed with Autism Spectrum Disorder, attention and learning problems, anxiety, aggressive behavior and sleep disorder, and early interventions have improved many behavior symptoms associated with FXS. In this review, we performed a literature search of original and review articles data of clinical trials and book chapters using MEDLINE (1990-2021) and ClinicalTrials.gov. While we have reviewed the biological importance of the fragile X mental retardation protein (FMRP), the FXS phenotype, and current diagnosis techniques, the emphasis of this review is on clinical interventions. Early non-pharmacological interventions in combination with pharmacotherapy and targeted treatments aiming to reverse dysregulated brain pathways are the mainstream of treatment in FXS. Overall, early diagnosis and interventions are fundamental to achieve optimal clinical outcomes in FXS.

The dopaminergic system is involved in the regulation of immune responses in various homeostatic and disease conditions. For conditions such as Parkinson's disease and multiple sclerosis (MS), pharmacological modulation of dopamine (DA) system activity is thought to have therapeutic relevance, providing the basis for using dopaminergic agents as a treatment of relevant states. In particular, it was proposed that restoration of DA levels may inhibit neuroinflammation. We have recently reported a new class of dopamine transporter (DAT) inhibitors with high selectivity to the DAT over other G-protein coupled receptors tested. Here, we continue their evaluation as monoamine transporter inhibitors. Furthermore, we show that the urea-like DAT inhibitor (compound 5) has statistically significant anti-inflammatory effects and attenuates motor deficits and pain behaviors in the experimental autoimmune encephalomyelitis model mimicking clinical signs of MS. To the best of our knowledge, this is the first study reporting the beneficial effects of DAT inhibitor-based treatment in animals with induced autoimmune encephalomyelitis, and the observed results provide additional support to the model of DA-related neuroinflammation.

To describe polypharmacy composition, and the degree to which patients versus providers contribute to variation in medication fills, in people with epilepsy.

We performed a retrospective study of Medicare beneficiaries with epilepsy (antiseizure medication plus diagnostic codes) in 2014 (N = 78,048). We described total number of medications and prescribers, and specific medications. Multilevel models evaluated the percentage of variation in two outcomes (1. number of medications per patient-provider dyad, and 2. whether a medication was filled within thirty days of a visit) due to patient-to-patient differences versus provider-to-provider differences.

Patients filled a median of 12 (interquartile range [IQR] 8-17) medications, from median of 5 (IQR 3-7) prescribers. Twenty-two percent filled an opioid, and 61% filled at least three central nervous system medications. Levetiracetam was the most common medication (40%), followed by hydrocodone/acetaminophen (27%). The strongest predictor of medications per patient was Charlson comorbidity index (7.5 [95% confidence interval (CI) 7.2-7.8] additional medications for index 8+ versus 0). Provider-to-provider variation explained 36% of variation in number of medications per patient, whereas patient-to-patient variation explained only 2% of variation. Provider-to-provider variation explained 57% of variation in whether a patient filled a medication within 30 days of a visit, whereas patient-to-patient variation explained only 30% of variation.

Patients with epilepsy fill a large number of medications from a large number of providers, including high-risk medications. Variation in medication fills was substantially more related to provider-to-provider rather than patient-to-patient variation. The better understanding of drivers of high-prescribing practices may reduce avoidable medication-related harms.

Although few clinical trials examined the efficacy of bupropion to treat sexual dysfunction among female patients, a comprehensive and objective synthesis of the best available evidence is still lacking. To date, to the best of our knowledge, there are no published systematic reviews or meta-analyses specifically focusing on the role of bupropion in the treatment of female sexual dysfunction. The main objective of the present study was to evaluate the efficacy of bupropion in the treatment of female sexual dysfunction, and we hypothesized that bupropion is efficient in treating female patients with sexual dysfunction. This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search for published literature was performed using Ovid, Medline, Scopus, Cochrane Library, Science Direct, and PubMed databases. In our study, we found that bupropion was almost three-fold more favorable in improving problems with sexual desire (pool estimate 2.845, 95% CI: 0.215 to 5.475, I2= 95.6%, p=0.034). A meta-regression was performed to explore heterogeneity and we found that only the dosage of bupropion was statistically significant in explaining the variance, i.e., the lower the dosage (150 mg vs. 300 mg), the better the improvement in the sexual desire of women with hypoactive sexual desire disorder (HSDD). Based on the results of this systematic review and metaanalysis, there is a potential role of bupropion as an effective treatment for women with HSDD.

Antidepressants are one of the most commonly prescribed pharmaceutical classes for the treatment of psychiatric conditions. They act via modulation of brain monoaminergic signaling systems (predominantly serotonergic, adrenergic, dopaminergic) that show a high degree of structural conservation across diverse animal phyla. A reasonable assumption, therefore, is that exposed fish and other aquatic wildlife may be affected by antidepressants released into the natural environment. Indeed, there are substantial data reported for exposure effects in fish, albeit most are reported for exposure concentrations exceeding those occurring in natural environments. From a critical analysis of the available evidence for effects in fish, risk quotients (RQs) were derived from laboratory-based studies for a selection of antidepressants most commonly detected in the aquatic environment. We conclude that the likelihood for effects in fish on standard measured end points used in risk assessment (i.e., excluding effects on behavior) is low for levels of exposure occurring in the natural environment. Nevertheless, some effects on behavior have been reported for environmentally relevant exposures, and antidepressants can bioaccumulate in fish tissues. Limitations in the datasets used to calculate RQs revealed important gaps in which future research should be directed to more accurately assess the risks posed by antidepressants to fish. Developing greater certainty surrounding risk of antidepressants to fish requires more attention directed toward effects on behaviors relating to individual fitness, the employment of environmentally realistic exposure levels, on chronic exposure scenarios, and on mixtures analyses, especially given the wide range of similarly acting compounds released into the environment.

Bupropion is a widely used antidepressant that plays an essential role in treating mental disorders. Due to its structural similarities with psychostimulants, bupropion is suggested to have addictive potential. Several case reports have been published addressing its misuse in recent years, mainly through nasal insufflation and intravenous administration. Most of the reported cases cited a history of substance use disorder.

Written informed consent was obtained from the patient to write this case report.

We present a case with alcohol use disorder and attention deficit hyperactivity disorder, who developed a substance use disorder to bupropion while chewing it in doses up to 2250 mg, in an attempt to get "high" with no history of seizures.

Our case suggests that bupropion can also be misused by chewing even at high doses and that it can lead to a substance use disorder. Its use in various indications in treating mental disorders and its over-the-counter accessibility, along with a lower risk of stigmatization, could increase the prevalence of bupropion misuse. It is essential to know the medical consequences of bupropion misuse as there is increasing data on its addictive potential. More information is needed to clarify the impact of the route of administration on drug metabolism and adverse effects.

Obesity is a disease of the nervous system. While some will view this statement as provocative, others will take it as obvious. Whatever our side is, the pharmacology tells us that targeting the nervous system works for promoting weight loss. It works, but at what cost? Is the nervous system a safe target for sustainable treatment of obesity? What have we learned-and unlearned-about the central control of energy balance in the last few years? Herein we provide a thought-provoking exploration of obesity as a disorder of neurotransmission. We discuss the state of knowledge on the brain pathways regulating energy homeostasis that are commonly targeted in anti-obesity therapy and explore how medications affecting neurotransmission such as atypical antipsychotics, antidepressants, and antihistamines relate to body weight. Our goal is to provide the endocrine community with a conceptual framework that will help expending our understanding of the pathophysiology of obesity, a disease of the nervous system.

Depression is a prevalent psychiatric disorder that often leads to poor quality of life and impaired functioning. Treatment during the acute phase of a major depressive episode aims to help the patient reach a remission state and eventually return to their baseline level of functioning. Pharmacotherapy, especially selective serotonin reuptake inhibitors antidepressants, remains the most frequent option for treating depression during the acute phase, while other promising pharmacological options are still competing for the attention of practitioners. Depression-focused psychotherapy is the second most common option for helping patients overcome the acute phase, maintain remission, and prevent relapses. Electroconvulsive therapy is the most effective somatic therapy for depression in some specific situations; meanwhile, other methods have limits, and their specific indications are still being studied. Combining medications, psychotherapy, and somatic therapies remains the most effective way to manage resistant forms of depression.

Depression and anxiety are common and associated with inflammation in patients with cancer. Inflammatory indices such as albumin and neutrophil-to-lymphocyte ratio (NLR) obtained from metabolic panels and complete blood counts should be available for mental health professionals treating anxiety and depression at cancer centers. We hypothesized that albumin and NLR extrapolated from non-mental health oncology appointments would be associated with anxiety and depression and drawn close enough to psychiatry visits to be useful for the psycho-oncologist. MATERIALS & METHODS: Depression and anxiety were evaluated in patients (n = 97) referred to a cancer center psychiatric service for depression using the Patient Health Questionnaire-9 and General Anxiety Disorder-7. Albumin concentration and NLR were assessed for timing and correlation strength with anxiety and depression by setting (localized/metastatic cancer).

Most patients (96%) had albumin or NLR available at any time point of which 45% were drawn within one week of the psychiatric appointment. No significant correlations were noted when evaluating localized cancer or NLR exclusively. For patients with metastatic cancer, anxiety and depression were correlated with albumin at any time point (r = -0.28, p < 0.05; r = -0.40, p < 0.01, respectively) and within a week of psychiatry appointment (r = -0.40, p < 0.05; r = -0.68, p < 0.001, respectively). Albumin evaluated within a week predicted 32% of depression score variance (β = -0.63, p = 0.002). Hypoalbuminemia (<3.8 g/ul) was associated with anxiety (χ2 = 4.43, p = 0.04) and depression (χ2 = 11.06, p = 0.001).

Hypoalbuminemia in patients with metastatic cancer may help establish the presence or persistence of anxiety, depression, treatment refractoriness, and the use of inflammation in cancer-related psychological symptom management.

Adverse drug reactions (ADRs) are one of the major causes of morbidity and mortality worldwide. It is well-known that individual genetic make-up is one of the causative factors of ADRs. Approximately 14 million single nucleotide polymorphisms (SNPs) are distributed throughout the entire human genome and every patient has a distinct genetic make-up which influences their response to drug therapy. Cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of antiretroviral, antimalarial, anticancer, and antidepressant drugs. These drug classes are commonly in use worldwide and face specific population variability in side effects and dosing. Parts of this variability may be caused by single nucleotide polymorphisms (SNPs) in the CYP2B6 gene that are associated with altered protein expression and catalytic function. Population variability in the CYP2B6 gene leads to changes in drug metabolism which may result in adverse drug reactions or therapeutic failure. So far more than 30 non-synonymous variants in CYP2B6 gene have been reported. The occurrence of these variants show intra and interpopulation variability, thus affecting drug efficacy at individual and population level. Differences in disease conditions and affordability of drug therapy further explain why some individuals or populations are more exposed to CYP2B6 pharmacogenomics associated ADRs than others. Variabilities in drug efficacy associated with the pharmacogenomics of CYP2B6 have been reported in various populations. The aim of this review is to highlight reports from various ethnicities that emphasize on the relationship between CYP2B6 pharmacogenomics variability and the occurrence of adverse drug reactions. In vitro and in vivo studies evaluating the catalytic activity of CYP2B6 variants using various substrates will also be discussed. While implementation of pharmacogenomic testing for personalized drug therapy has made big progress, less data on pharmacogenetics of drug safety has been gained in terms of CYP2B6 substrates. Therefore, reviewing the existing evidence on population variability in CYP2B6 and ADR risk profiles suggests that, in addition to other factors, the knowledge on pharmacogenomics of CYP2B6 in patient treatment may be useful for the development of personalized medicine with regards to genotype-based prescription.

Drug repurposing, also known as drug repositioning/reprofiling, is a relatively new strategy for the identification of alternative uses of well-known therapeutics that are outside the scope of their original medical indications. Such an approach might entail a number of advantages compared to standard de novo drug development, including less time needed to introduce the drug to the market, and lower costs. The group of compounds that could be considered as promising candidates for repurposing in oncology include the central nervous system drugs, especially selected antidepressant and antipsychotic agents. In this article, we provide an overview of some antidepressants (citalopram, fluoxetine, paroxetine, sertraline) and antipsychotics (chlorpromazine, pimozide, thioridazine, trifluoperazine) that have the potential to be repurposed as novel chemotherapeutics in cancer treatment, as they have been found to exhibit preventive and/or therapeutic action in cancer patients. Nevertheless, although drug repurposing seems to be an attractive strategy to search for oncological drugs, we would like to clearly indicate that it should not replace the search for new lead structures, but only complement de novo drug development.

Attention-deficit hyperactivity disorder (ADHD), has been traditionally considered a neurodevelopmental disorder affecting children and adolescents characterized by inattention, hyperactivity, disruptive behavior, and impulsivity. Although still debated, it is evident that ADHD is also present in adulthood, but this diagnosis is rarely carried out, mainly for the frequent comorbidity with other psychiatric and/or substance abuse disorders. Given the need to shed more light on the pharmacological treatment of ADHD, we performed a naturalistic review to review and comment on the available literature of ADHD treatment across the lifespan. Indeed, stimulants are endowed of a prompt efficacy and safety, whilst non-stimulants, although requiring some weeks to be fully effective, are useful when a substance abuse history is detected. In any case, the pharmacological management of ADHD appears to be still largely influenced by the individual experience of the clinicians. Further longitudinal studies with a careful and detailed characterization of participants across different phases of the lifespan are also required to provide relevant confirmations (or denials) regarding pharmacological treatments amongst the different age groups.

In the last decades, the notion of including excipients in the formulations, as inert substances aiding production processes, has changed and they are recently viewed as multifunctional discrete entities. It is now well documented that excipients serve several roles, spreading from the stabilization and modified release, to providing biocompatible properties and targeting moieties. The aim of this study was to develop matrix-based oral drug delivery systems of bupropion hydrochloride (BUP·HCl) and naltrexone hydrochloride (NTX·HCl), suitable for releasing these active substances in a modified manner, providing a stable level of drug release, which is simultaneously therapeutically effective and non-toxic, thus reducing side effects, after a single dose administration, throughout the gastrointestinal tract. The new formulations, employing hydroxypropylmethycellulose (HPMC K15M) (a cellulosic polymer, which, generally hydrates to form a gelatinous layer that is critical to prevent wetting and rapid drug release from the matrices), poly(methacylic acid-co-ethyl acrylate) 1:1 (Eudragit^® L100-55: effective for site specific drug delivery in intestine), poly(ethylene oxide) (PEO) (7 × 10⁶: a high molecular weight polymer, water-soluble, in micro-granular powder form), as the rate controlling polymers, were chosen to lead to a "soothing out" release pattern of these drugs, at 0 ≤ t ≤ 120 min. Moreover, the release of the two drugs from the ulvan-based tablets, was found to follow the desired profile, throughout the entire course of the dissolution experiments.

Bupropion is an aminoketone antidepressant. A major concern in bupropion toxicity is seizure activity, which can occur up to 24 h from ingestion. It is difficult to predict which patients will have seizures. The purpose of this study is to identify clinical features associate with seizure after bupropion overdose.

We searched the Toxicology Investigators Consortium registry for a cases of poisoning by bupropion between January 1, 2014 and January 1, 2017 in patients aged 13-65. Demographic variables and clinical features were compared between patients who did and did not experience a seizure and presented as unadjusted odds ratios (OR). Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) between clinical features and seizures.

There were 256 cases of bupropion overdose remaining after inclusion/exclusion criteria were applied. Clinical features associated with seizure were QTc >500 (OR = 3.4, 95% CI: 1.3-8.8, p = 0.012), tachycardia (p > 140) (OR = 1.9, 95% CI: 1-3.561, p = 0.05), and age 13-18 years (2.4, 95% CI: 1.3-4.3, p = 0.005). The mean QTc value for patients experiencing a seizure was 482 ms (N = 95 IQR: 59 ms) versus 454 ms (N = 103, IQR: 43) in patients who did not experience seizure, however, it was not possible to identify a QTc cutoff with sensitivity or specificity to predict seizures.

Based on our analysis of data from the ToxIC registry, age (13-18), tachycardia (p > 140) and QTc >500 ms are associated with seizures in bupropion overdose; however, a specific QTc value may not be a useful predictor of seizures.

The noradrenaline and dopamine reuptake inhibitor bupropion is metabolized by CYP2B6 and recommended by the FDA as the only sensitive substrate for clinical CYP2B6 drug-drug interaction (DDI) studies. The aim of this study was to build a whole-body physiologically based pharmacokinetic (PBPK) model of bupropion including its DDI-relevant metabolites, and to qualify the model using clinical drug-gene interaction (DGI) and DDI data. The model was built in PK-Sim® applying clinical data of 67 studies. It incorporates CYP2B6-mediated hydroxylation of bupropion, metabolism via CYP2C19 and 11β-HSD, as well as binding to pharmacological targets. The impact of CYP2B6 polymorphisms is described for normal, poor, intermediate, and rapid metabolizers, with various allele combinations of the genetic variants CYP2B6*1, *4, *5 and *6. DDI model performance was evaluated by prediction of clinical studies with rifampicin (CYP2B6 and CYP2C19 inducer), fluvoxamine (CYP2C19 inhibitor) and voriconazole (CYP2B6 and CYP2C19 inhibitor). Model performance quantification showed 20/20 DGI ratios of hydroxybupropion to bupropion AUC ratios (DGI AUCHBup/Bup ratios), 12/13 DDI AUCHBup/Bup ratios, and 7/7 DDGI AUCHBup/Bup ratios within 2-fold of observed values. The developed model is freely available in the Open Systems Pharmacology model repository.

To develop a local consensus to guide medical practitioners and psychiatrists on the use of bupropion in different psychiatric conditions in Hong Kong.

By utilizing the modified Delphi technique, a group of 10 local physicians with extensive experience in the management of major depressive disorder (MDD) developed and voted (using an anonymous, electronic voting system) on the practicality of recommendation of a set of consensus statements on the clinical use and understanding of bupropion in Hong Kong.

There was a very high degree of agreement among the panelists on the 11 finalized consensus statements.

The present consensus statements are developed as general recommendations for medical practitioners and psychiatrists to be practically referred to in clinical settings.

The Oral route of administration forms the heartwood of the ever-growing tree of drug delivery technology. It is one of the most preferred dosage forms among patients and controlled release community. Despite the high patient compliance, the deliveries of anti-cancerous drugs, vaccines, proteins, etc. via the oral route are limited and have recorded a very low bioavailability. The oral administration must overcome the physiological barriers (low solubility, permeation and early degradation) to achieve efficient and sustained delivery. This review aims at highlighting the conventional and modern-age strategies that address some of these physiological barriers. The modern age designs include the 3D printed devices and formulations. The superiority of 3D dosage forms over conventional cargos is summarized with a focus on long-acting designs. The innovations in Pharmaceutical organizations (Lyndra, Assertio and Intec) that have taken giant steps towards commercialization of long-acting vehicles are discussed. The recent advancements made in the arena of oral peptide delivery are also highlighted. The review represents a comprehensive journey from Nano-formulations to micro-fabricated oral implants aiming at specific patient-centric designs.

The multimorbidity formed by sleep disturbances and pain conditions is highly prevalent and has a significant impact in global health and in the socioeconomic system. Although different approaches have been directed toward its management, evidence regarding an optimal treatment is lacking, and pharmacological options are often preferred. Health professionals (e.g., pain and sleep clinicians) tend to focus on their respective expertise, targeting a single symptom with a single drug. This may increase polypharmacy and the risk of drug interactions, adverse events, and mortality. Hence, the use of medications that can directly or indirectly improve sleep, pain, and other possible accompanying conditions without exacerbating them becomes especially relevant. The objectives of this comprehensive review are to: a) describe the beneficial or deleterious effects that some commonly used medications to manage pain have on sleep and sleep disorders; and b) describe the beneficial or deleterious effects that frequently prescribed medications for sleep may have on pain. Moreover, medications targeting some specific sleep-pain interactions will be suggested and future directions for improving sleep and alleviating pain of these patients will be provided with clinical and research perspectives.

Understanding the stability of analyzed drugs in biological samples is a crucial part for an appropriate interpretation of the analytical findings. Synthetic cathinones, as psychoactive stimulants, belong to a major class of new psychoactive substances. As they are subject to several degradation pathways, they are known to clinical and forensic toxicologists as unstable analytes in biological samples. When interpreting analytical data of synthetic cathinones in biological samples, analysts must be aware that the concentration of analytes may not accurately reflect the levels at the time they were acquired owing to many factors. This review provides (i) an overview of the current scientific knowledge on the stability of synthetic cathinones and/or metabolites in various human biological samples with a focus on factors that may deteriorate their stability-such as storage temperature, length of storage, matrix, pH, type of preservatives, concentration of analytes, and the chemistry of the analytes-and (ii) possible solutions on how to avoid such degradation. The PubMed database as well as Google Scholar was thoroughly searched to find published studies on the stability of synthetic cathinones since 2007 by searching specific keywords. A total of 23 articles met the inclusion criteria and were included in this review. Synthetic cathinones that carry methylenedioxy or N-pyrrolidine ring showed higher degradation resistance over other substituted groups. Acidification of samples pH plays a crucial role at increasing the stability of cathinones even with analytes that were frequently considered as poorly stable. This review also provides several recommendations for best practice in planning the experimental design, preservation, and storage conditions in order to minimize synthetic cathinones' degradation in human biological samples.

Pharmacological augmentation is a recommended strategy for patients with treatment-resistant depression. A range of guidelines provide advice on treatment selection, prescription, monitoring and discontinuation, but variation in the content and quality of guidelines may limit the provision of objective, evidence-based care. This is of importance given the side effect burden and poorer long-term outcomes associated with polypharmacy and treatment-resistant depression. This review provides a definitive overview of pharmacological augmentation recommendations by assessing the quality of guidelines for depression and comparing the recommendations made.

A systematic literature search identified current treatment guidelines for depression published in English. Guidelines were quality assessed using the Appraisal of Guidelines for Research and Evaluation II tool. Data relating to the prescription of pharmacological augmenters were extracted from those developed with sufficient rigor, and the included recommendations compared.

Total of 1696 records were identified, 19 guidelines were assessed for quality, and 10 were included. Guidelines differed in their quality, the stage at which augmentation was recommended, the agents included, and the evidence base cited. Lithium and atypical antipsychotics were recommended by all 10, though the specific advice was not consistent. Of the 15 augmenters identified, no others were universally recommended.

This review provides a comprehensive overview of current pharmacological augmentation recommendations for major depression and will support clinicians in selecting appropriate treatment guidance. Although some variation can be accounted for by date of guideline publication, and limited evidence from clinical trials, there is a clear need for greater consistency across guidelines to ensure patients receive consistent evidence-based care.

Emerging hypotheses in the pathophysiology of major depressive disorder (MDD) indicate the role of neurotrophic factors and inflammation. This study assessed the association between therapeutic response of bupropion and serum brain-derived neurotrophic factor (BDNF) and tumour necrosis factor-α (TNF-α) levels in patients with MDD.

Thirty patients (aged 18 to 60 years) with MDD diagnosed by DSM-5 criteria, with Hamilton Depression Rating scale (HAM-D) score ≥ 20 were included in the study. Patients were given bupropion sustained release (SR) in the doses of 150 mg once daily. All patients were followed up for 12 weeks.

HAM-D score at the start of the treatment was 25.57 ± 1.85 which significantly reduced to 10.8 ± 4.24 at 12 weeks of treatment. The serum BDNF level increased significantly (p < 0.05) from 2.42 ± 0.19 ng/ml to 2.97 ± 0.10 ng/ml and the levels of serum TNF-α reduced significantly (p < 0.05) from 4.45 ± 0.95 pg/ml to 2.11 ± 0.84 pg/ml at 12 weeks of treatment, in responders to treatment.

The results of our study suggest that bupropion SR monotherapy is effective and well tolerated in MDD patients with moderate to severe depression, and its therapeutic efficacy is accompanied by an increase in serum BDNF levels and a decrease in serum TNF-α levels.

The objective of the study was to characterize the prevalence of polypharmacy and central nervous system (CNS)-acting medications in patients with epilepsy, and particular types of medications.

This was a retrospective cross-sectional study using data from the nationally representative National Health and Nutrition Examination Survey (NHANES). We included patients who reported taking at least one prescription medication in order to treat seizures or epilepsy during NHANES survey years 2013-2016. We assessed the number and types of drugs and predictors of total number of medications using a negative binomial regression. We then assessed prevalence of polypharmacy (≥5 medications), CNS polypharmacy (≥3 CNS-acting medications) and additional CNS-acting medications, and drugs that lower the seizure threshold (i.e., bupropion and tramadol), and extrapolated prevalence to estimated affected US population.

The NHANES contained 20,146 participants, of whom 135 reported taking ≥1 antiseizure medication (ASM) for seizures or epilepsy representing 2,399,520 US citizens using NHANES's sampling frame. Patients reported taking a mean 5.3 (95% confidence interval (CI): 4.3-6.3) prescription medications. Adjusting for race, sex, and uninsurance, both age and number of chronic conditions predicted increased number of medications (incident rate ratio (IRR) per decade: 1.16, 95% CI: 1.04-1.28; IRR per chronic condition: 1.19, 95% CI: 1.11-1.27). Polypharmacy was reported by 47% (95% CI: 38%-57%) of patients, CNS polypharmacy by 34% (23%-47%), benzodiazepine use by 21% (14%-30%), opioid use by 16% (11%-24%), benzodiazepine plus opioid use by 6% (3%-14%), and 6% (2%-15%) reported a drug that lowers the seizure threshold. Twelve percent (7%-20%) took an opioid with either a benzodiazepine or gabapentinoid.

Polypharmacy is common in patients with epilepsy. Patients taking ASMs frequently reported also taking other CNS-acting medications (i.e., opioids, benzodiazepines, seizure threshold-lowering medications), and medication combinations with black box warnings. Central nervous system polypharmacy poses health risks. Future research is needed to explore drivers of polypharmacy and strategies to help mitigate potentially harmful prescription use in this high-risk population.

Cancer-related fatigue is a significant problem and is associated with poor quality of life. Behavioral interventions include exercise and cognitive-behavioral therapy, which survivors may be unwilling or unable to adopt. Pharmacologic interventions (e.g., selective serotonin reuptake inhibitors) have been disappointing. One potential therapy is the antidepressant bupropion, a norepinephrine-dopamine reuptake inhibitor that targets both inflammation and the hypothalamic-pituitary-adrenal axis. The current study is intended to provide a rigorous test of the efficacy and tolerability of bupropion for cancer-related fatigue.

A randomized, double-blind, placebo-controlled trial will examine the effects of bupropion on cancer-related fatigue. The trial will be conducted nationwide through the University of Rochester Medical Center (URMC) National Cancer Institute Community Oncology Research Program (NCORP). Disease-free breast cancer survivors (n = 422) who completed chemotherapy and/or radiotherapy 12-60 months previously and report significant fatigue will be randomized 1:1 to receive bupropion (300 mg/day) or placebo. Outcomes will be assessed at baseline and the 12-week follow-up. The primary outcome, fatigue, will be measured with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F). Secondary outcomes include quality of life, depression, and drug tolerability. Exploratory outcomes include cognition and symptomatology. Potential biological mechanisms and genetic moderators of cancer-related fatigue will also be explored.

This study is the first placebo-controlled trial to our knowledge to evaluate bupropion for cancer-related fatigue. Positive results could revolutionize the treatment of cancer-related fatigue, as bupropion is safe, inexpensive, widely-available, and may be more tolerable and acceptable for many patients than current, limited treatment options.