The role of sex and drug use during adolescence in determining the risk for adverse consequences of amphetamines.

Use of amphetamines during adolescence, a critical period of brain development and reorganization, may lead to particularly adverse outcomes that are long-lasting. Similarly, female users may be uniquely vulnerable to certain aspects of drug use. A recognition of the role of use during adolescence and sex on outcomes of amphetamine and methamphetamine exposure are of critical importance in understanding and treating substance use disorders. This chapter highlights what human research, which has been largely epidemiological, suggests about sex and age differences in drug use patterns and outcomes. We also discuss work in laboratory animals that has typically utilized rats or mice exposed to drugs in a non-contingent manner (i.e., involuntarily) or through volitional self-administration. Lastly, we draw attention to the fact that advancing our understanding of the effects of amphetamine and methamphetamine use, the development of problematic drug taking, and the mechanisms that contribute to relapse will require an emphasis on inclusion of age and sex as moderating factors in future studies.

Treatment with psychostimulants and atomoxetine in people with psychotic disorders: reassessing the risk of clinical deterioration in a real-world setting.

BACKGROUND: Although attention-deficit hyperactivity disorder (ADHD) is often comorbid with schizophrenia spectrum and other psychotic disorders (SZSPD), concerns about an increased risk of psychotic events have limited its treatment with either psychostimulants or atomoxetine. AIMS: To examine whether the risk of hospital admission for psychosis in people with SZSPD was increased during the year following the introduction of such medications compared with the year before. METHOD: This was a retrospective cohort study using Quebec (Canada) administrative health registries, including all Quebec residents with a public prescription drug insurance plan and a diagnosis of psychotic disorder, defined by relevant ICD-9 or ICD-10 codes, who initiated either methylphenidate, amphetamines or atomoxetine, between January 2010 and December 2016, in combination with antipsychotic medication. The primary outcome was time to hospital admission for psychosis within 1 year of initiation. State sequence analysis was also used to visualise admission trajectories for psychosis in the year following initiation of these medications, compared with the previous year. RESULTS: Out of 2219 individuals, 1589 (71.6%) initiated methylphenidate, 339 (15.3%) amphetamines and 291 (13.1%) atomoxetine during the study period. After adjustment, the risk of hospital admission for psychosis was decreased during the 12 months following the introduction of these medications when used in combination with antipsychotics (adjusted HR = 0.36, 95% CI 0.24-0.54; P < 0.0001). CONCLUSIONS: These findings suggest that, in a real-world setting, when used concurrently with antipsychotic medication, methylphenidate, amphetamines and atomoxetine may be safer than generally believed in individuals with psychotic disorders.

Psychiatric and non-psychiatric drugs causing false-positive amphetamines urine test in psychiatric patients: a pharmacovigilance analysis using FAERS.

INTRODUCTION: Immunoassay urine drug screen (UDS) is frequently used in clinical practice for initial screening process, being generally available, fast, and inexpensive. Exposure to widely prescribed drugs might determine false-positive UDS amphetamines, leading to diagnostic issues, wrong therapeutic choices, impairment of physician-patient relationship, and legal implications. AREAS COVERED: To summarize and comment on a comprehensive list of compounds responsible for UDS false positives for amphetamines, we conducted a literature review on PubMed along with a comparison with Real-World Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database analysis between 2010 and 2022. Forty-four articles and 125 Individual Case Safety Reports (ICSR) involving false-positive amphetamine UDS in psychiatric patients were retrieved from FAERS. EXPERT OPINION: False-positive results were described in literature for antidepressants, atomoxetine, methylphenidate, and antipsychotics, but also for non-psychiatric drugs of common use, such as labetalol, fenofibrate, and metformin. Immunoassay method is usually responsible for false-positive results, and in most cases, mass spectrometry (MS) does not eventually confirm the UDS positivity. Physicians should be aware of immunoassays' limitations and when turning to a confirmatory test. Any new cross-reaction should be reported to pharmacovigilance activities.

Amphetamines abuse and depression: Focus on TRPC channels.

Amphetamines, such as amphetamine (AMPH), methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA), are the psychotropic substances widely abused in the world. Amphetamines abuse can damage dopaminergic and serotonin neurons and cause neuroinflammation and neurotoxicity. Neuropsychiatric disorders induced by amphetamines abuse include depression, anxiety, auditory hallucinations, mania, and cognitive disorders, of which depression has a higher incidence. Transient receptor potential (TRP) channels can regulate the inflow and outflow of Ca2+. In TRP family, transient receptor potential canonical (TRPC) channels are closely associated with the development of some neurological diseases, such as Parkinson's disease and Alzheimer's disease. However, the correlation between TRPC channels and depression and the specific mechanism of TRPC channels in depression still haven't been fully clarified. This review elaborates the pathophysiological mechanisms of depression induced by amphetamines abuse, the functions of TRPC channels in the nervous system, and the possible correlation between TRPC channels and depression induced by amphetamines abuse, which would provide the theoretical basis for the development of the novel and effective therapeutic drugs for amphetamines abuse-induced depression.

In utero exposure to ADHD medication and long-term offspring outcomes.

Attention Deficit Hyperactivity Disorder (ADHD) medication is increasingly being used during pregnancy. Concerns have been raised as to whether ADHD medication has long-term adverse effects on the offspring. The authors investigated whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental and growth outcomes in offspring. The population-based cohort study in the Danish national registers included 1,068,073 liveborn singletons from 1998 to 2015 followed until any developmental diagnosis, death, emigration, or December 31, 2018. Children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy and children of mothers who discontinued ADHD medication before pregnancy were compared using Cox regression. Main outcomes were neurodevelopmental psychiatric disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment during childhood or adolescence. In total, 898 children were exposed to ADHD medication during pregnancy compared to 1270 children whose mothers discontinued ADHD medication before pregnancy. After adjustment for demographic and psychiatric characteristics of the mother, no increased risk of any offspring developmental disorders was found combined (aHR 0.97, 95% CI 0.81 to 1.17) or for separate subcategories. Similarly, no increased risk was found for any sub-categories of outcomes in the negative control or sibling controlled analyses. Neurodevelopment and growth in offspring do not differ based on antenatal exposure to ADHD medication. These findings provide reassurance for women with ADHD who depend on ADHD medication for daily functioning and who consider continuing medication in pregnancy.

Consumo de psicoestimulantes por estudantes de medicina em um centro universitário privado / Consumption of psychostimulants by medical students in a private university center

O consumo de psicoestimulantes tem crescido exponencialmente, sobretudo entre estudantes de medicina, na busca por aumentar o rendimento acadêmico. Atualmente, a extensa carga horária de aulas e estudos, exigências de produtividade e altos níveis de estresse podem desencadear o uso. Objetivo: Analisar o uso de psicoestimulantes por estudantes do curso de Medicina de um Centro Universitário privado em Minas Gerais. Métodos: Foi realizado um estudo descritivo, quantitativo, com delineamento transversal entre os discentes do 1° ao 5° ano do curso de Medicina no 2° semestre de 2021. Os participantes responderam ao questionário semi-estruturado elaborado pelos autores. Os dados obtidos foram tabulados no software Statistical Product and Service Solutions. Resultados: Dos 244 entrevistados, cerca de 57.4% faziam uso de algum psicoestimulante. Houve maior uso entre os estudantes do 2° ano e as principais substâncias utilizadas foram: cafeína (85%), energético (65%) e metilfenidato (60%). A melhora na concentração (97%) foi o efeito mais percebido pelos usuários, seguido de redução do sono (83%) e melhora de raciocínio (80%). Muitos consideraram que os estimulantes cerebrais têm o potencial de melhorar o rendimento acadêmico, mas pode reduzir a qualidade do sono e consequentemente torná-los susceptíveis a outras enfermidades. Conclusão: É notável que existe uso abusivo de estimulantes cerebrais, sendo fundamental o trabalho em conjunto entre instituição de ensino e familiares, em prol da prevenção e do controle de danos causados por esse hábito

The consumption of psychostimulants has grown exponentially, especially among medical students, in the quest to increase academic performance. Currently, the extensive workload of classes and studies, productivity demands and high levels of stress can trigger use. Objective: To analyze the use of psychostimulants by medical students at a private University Center in Minas Gerais. Methods: A descriptive, quantitative, cross-sectional study was carried out among students from the 1st to the 5th year of the medicine course in the 2nd semester of 2021. The participants answered the semi-structured questionnaire prepared by the authors. The data obtained were tabulated in the Statistical Product and Service Solutions software. Results: Of the 244 respondents, about 57.4% used some psychostimulant. There was greater use among 2nd year students and the main substances used were: caffeine (85%), energy drink (65%) and methylphenidate (60%). Improved concentration (97%) was the effect most perceived by users, followed by reduced sleep (83%) and improved thinking (80%). Many considered that brain stimulants have the potential to improve academic performance, but can reduce sleep quality and consequently make them susceptible to other illnesses. Conclusion: It is notable that there is abusive use of brain stimulants, and it is essential to work together between educational institutions and family members in order to prevent and control the damage caused by this habit

Early-Onset Cardiovascular Disease From Cocaine, Amphetamines, Alcohol, and Marijuana.

Cardiovascular disease (CVD), a disease typically associated with aging and the definitive leading cause of death worldwide, now threatens young and middle-aged populations. Recreational abuse of alcohol, marijuana, cocaine, and amphetamine-type stimulants has been an escalating public health problem for decades, but now use of these substances has become a significant contributor to early-onset CVD. While this remains a global phenomenon, the epicentre of substance abuse is rooted in North America, where it has been exacerbated by the response to the COVID-19 pandemic. For the first time in history, the United States crossed 100,000 overdose-related deaths in a calendar year. Sadly, Canada's recreational drug abuse problem closely mirrors that of the US. This is indicative of the larger public health crisis, as we now know that these substances are cardiotoxic and are contributing to the rising levels of premature chronic CVD, including hypertension, arrhythmias, heart failure, stroke, myocardial infarction, arterial dissection, sudden cardiac death, and early mortality.

Cardiovascular Outcomes Among Older Individuals With Depression Prescribed Amphetamines: A Retrospective Cohort Study.

BACKGROUND: Prescription amphetamines are utilized for treatment of depression in older adults, yet cardiovascular risks in this population are not well described. The purpose of this study is to evaluate risk of cardiovascular events among adults aged 65 and older with depression who were prescribed amphetamines. METHODS: We conducted a retrospective matched cohort study utilizing the TriNetx database and statistical software. The 1:1 propensity score matching technique was performed using logistic regression to balance the baseline characteristics of the population. Inclusion criteria were a diagnosis of depression and age 65 years and older. We excluded individuals with an adverse cardiovascular event or diagnosis of attention deficit and hyperactivity disorder prior to enrollment. Individuals were followed from January 1, 2018 to December 31, 2020. Those prescribed an amphetamine were considered exposed and others served as controls. We used descriptive statistics and calculated risk ratios to assess the relationship between amphetamine prescriptions and cardiovascular events in these cohorts. RESULTS: There were 4 434 included in the exposed cohort and 4 434 matched controls in the unexposed group. The cohort exposed to amphetamines had higher high-density lipoprotein along with lower low-density lipoprotein, total cholesterol, hemoglobin A1C, systolic blood pressure, and body mass index than the control group, but increased risk of cardiovascular events (risk ratio: 8.9; 95% confidence interval: 6.39, 12.48). CONCLUSIONS: Amphetamines offer potential benefits to people with depression; however, these data suggest increased risk of cardiovascular events among older individuals. Additional research is warranted to fully characterize risk among subpopulations of older adults and inform patient-provider decision making.

Stimulant Drugs of Abuse and Cardiac Arrhythmias.

Nonmedical use of prescription and nonprescription drugs is a worldwide epidemic, rapidly growing in magnitude with deaths because of overdose and chronic use. A vast majority of these drugs are stimulants that have various effects on the cardiovascular system including the cardiac rhythm. Drugs, like cocaine and methamphetamine, have measured effects on the conduction system and through several direct and indirect pathways, utilizing multiple second messenger systems, change the structural and electrical substrate of the heart, thereby promoting cardiac dysrhythmias. Substituted amphetamines and cocaine affect the expression and activation kinetics of multiple ion channels and calcium signaling proteins resulting in EKG changes, and atrial and ventricular brady and tachyarrhythmias. Preexisting conditions cause substrate changes in the heart, which decrease the threshold for such drug-induced cardiac arrhythmias. The treatment of cardiac arrhythmias in patients who take drugs of abuse may be specialized and will require an understanding of the unique underlying mechanisms and necessitates a multidisciplinary approach. The use of primary or secondary prevention defibrillators in drug abusers with chronic systolic heart failure is both sensitive and controversial. This review provides a broad overview of cardiac arrhythmias associated with stimulant substance abuse and their management.

Estudo de estabilidade de anfetaminas e produtos de biotransformação de cocaína e tetraidrocanabinol em amostras de urina seca em papel (dried urine spots) / Stability study of amphetamines, biotransformation products of cocaine and tetrahydrocannabinol in dried urine spots

O número de pessoas utilizando substâncias ilícitas de forma recreativa aumenta a cada ano, chamando a atenção de estudiosos de diversas áreas do conhecimento. Com isso, a demanda de exames toxicológicos exigida para trabalhadores, vítimas de crimes e esportistas também tem crescido. A amostra biológica mais utilizada para análises toxicológicas continua sendo a urina, visto que sua obtenção é menos invasiva, possibilita coletar grande volume de amostra e pode-se detectar substâncias até dias após ter ocorrido a exposição ou consumo. Entretanto, estas amostras necessitam de um grande volume físico para serem armazenadas e transportadas aos laboratórios, devendo ser mantidas em temperatura baixa e controlada para conservação. Outro ponto a se considerar é a quantidade de amostra insuficientemente coletada, ou extravasamento do conteúdo, contaminando outras amostras e muitas vezes, inviabilizando a análise. Uma alternativa recente para tais problemas é utilizar a técnica chamada de dried urine spots (DUS), onde poucos microlitros de urina são colocados em um papel absorvente e secos sob temperatura ambiente, preservando de agentes degradantes os componentes presentes na urina. Assim, o objetivo deste trabalho é avaliar a estabilidade das substâncias do presente estudo em alta temperatura, temperatura ambiente e em temperaturas de 4°C e -20°C. Para este fim, foi necessário desenvolver, validar e aplicar métodos de extração e determinação de anfetaminas e produtos de biotransformação de cocaína e tetraidrocanabinol carboxílico (THCCOOH) em amostras dried urine spot, utilizando cromatografia líquida acoplada à espectrometria de massas. Os picos foram identificados por UPLC-ESI-MS/MS, com tempo total de 5 mins utilizando fase A- água, formiato de amônio e 0,1% ácido fórmico, e B- metanol: acetonitrila (6:4) + 0,1% de ácido fórmico. A extração foi feita utilizando acetonitrila: metanol: acetona (1:1:1) +ácido fórmico 0,1%. Não foi possível iniciar a validação de THCCOOH, visto uma possível complexação do analito com o papel. Para as outras substâncias, o método cromatográfico desenvolvido se mostrou eficiente e seletivo, com LOD e LOQ de 10 ng/mL para todos os analitos, sendo linear até 1000 ng/mL, atendeu as especificações de precisão e exatidão e carryover. As amostras permaneceram estáveis ao longo de 32 dias nas temperaturas estudadas, demonstrando a segurança em se utilizar a técnica de DUS para armazenamento e transporte de amostras biológicas dentro da faixa de temperatura do estudo até 32 dias

The number of people using illegal substances in a recreational way increases each year, drawing the attention of scholars from different areas of knowledge. As a result, the demand for workplaces drug tests, toxicological tests for victims of crimes and dopping has also grown. The biological sample most used for toxicological tests remains urine, since obtaining it is less invasive, it is possible to collect a large volume of sample and it is possible to detect substances up to days after exposure or consumption has occurred. However, these samples require a large physical volume to be stored and transported to the laboratories, and must be kept at a low temperature for conservation. Another point to consider is the amount of sample insufficiently collected, or leakage of the content, causing contamination of other samples and often making the analysis unfeasible. A recent alternative to such problems is to use "dried urine spots" (DUS), where few microliters of urine are placed on absorbent paper and dried at room temperature, preserving the components present in the urine from degrading agents. Thus, the objective of this work is to evaluate the stability of the substances in this study at high temperature, room temperature and at temperatures of 4°C and -20°C. For this purpose, it was necessary to develop, validate and apply methods of extraction and determination of amphetamines and biotransformation products of cocaine and carboxylic tetrahydrocannabinol (THCCOOH) in dried urine spot samples, using liquid chromatography coupled to mass spectrometry (LC-MS). The peaks were identified liquid chromatography coupled to a mass spectrometer (UPLC-ESI-MS/MS), with a total time of 5 mins using phase A- water, ammonium formate and 0.1% formic acid, and B- methanol: acetonitrile (6:4) + 0.1% formic acid. Extraction was done using acetonitrile: methanol: acetone (1:1:1) + 0.1% formic acid. It was not possible to perform the validation of THCCOOH, given a possible complexation of the analyte with the paper. To the others substances, the chromatographic method developed proved to be efficient and selective, with LOD and LOQ of 10 ng/mL for all analytes, being linear up to 1000 ng/mL, meeting the specifications of precision and accuracy and carryover. The samples remained stable for 32 days at the temperatures studied, demonstrating the safety of using the DUS technique for storage and transport of biological samples until 32 days on temperature range studied

Are Amphetamines Associated with Adverse Cardiovascular Events Among Elderly Individuals?

BACKGROUND: Prescription amphetamines are the most common pharmacological treatment for attention deficit hyperactivity disorder (ADHD) and use among older age groups is increasing. The purpose of this study is to assess the risk of adverse cardiovascular events among individuals older than 65 years. METHODS: We conducted a retrospective matched cohort study using TriNetX database with propensity score matching (PSM) to assess the odds of a cardiovascular event among individuals with ADHD exposed to amphetamine compared with individuals with ADHD who were not exposed to this medication. During the index period of January 1, 2018, through December 31, 2020, 13,233 individuals older than 65 years (mean age = 69 years) met the study criteria. RESULTS: The cohort exposed to amphetamine had increased blood pressure and increased odds of cardiovascular events (odds ratio [OR], 6.16; absolute risk difference = 3.31%) compared with the control group. CONCLUSIONS: Amphetamines have clear safety data in younger age cohorts; however, this safety data may not generalize to older populations. Additional research is warranted to clarify further exposure and subpopulation-level risk factors associated with adverse cardiovascular events among older patients.

How Frequent Is Switching From an Initial Stimulant Family to the Alternative One in the Clinical Setting?: A Pilot Study of 49 Consecutively Referred Medication-Naive Adults With Attention-Deficit/Hyperactivity Disorder.

PURPOSE/BACKGROUND: This study aimed to evaluate the frequency of needing to switch the initial treatment of a stimulant to the alternative family in newly referred, medication-naive adults with attention-deficit/hyperactivity disorder (ADHD) initiating treatment with stimulants. METHODS/PROCEDURES: Subjects were 49 unmedicated adults (18-45 years old) with Diagnostic and Statistical Manual of Disorders (Fifth Edition) ADHD who initiated treatment with a stimulant. Before the clinical assessment with an expert clinician, participants completed the Adult Self-Report, Behavior Rating Inventory of Executive Function-Adult Version, Emotional Dysregulation Subscale of the Barkley Current Behavior Scale-Self-report, and Mind Wandering Questionnaire. The rate of switching was examined using information from the electronic medical record for up to three clinical follow-up visits. Comparisons were made between those who did and did not need to switch on baseline demographic and clinical characteristics. FINDINGS/RESULTS: Sixty-seven percent of ADHD patients were initially prescribed a methylphenidate product, and 33%, an amphetamine product. Forty-one percent of ADHD patients needed to switch from their initially prescribed stimulant family within 90 days of initiating treatment because of poor tolerability. Whereas the rate of switching was significantly higher in those initially prescribed methylphenidate, the rate of patients who required changes in formulation (long- to short-acting and vice versa) or additional antianxiety or antidepressant treatment ("strugglers") was higher in those taking amphetamine. Switchers were more impaired on the Adult Self-Report Intrusive scale, whereas nonswitchers were more impaired on the Behavior Rating Inventory of Executive Function Inhibit and Task Monitor scales. However, these findings were small and of unclear clinical significance. IMPLICATIONS/CONCLUSIONS: Forty-one percent of medication-naive adults with ADHD initiating stimulant treatment required a switch from the initially prescribed stimulant family to the alternative one because of poor tolerability. Switching could not be adequately predicted by baseline demographic or clinical characteristics. These findings call for improved efforts to help identify predictors of response to stimulant treatment in adults with ADHD to avoid unnecessary delays in identifying a safe and effective treatment for these patients.

Cerebral vasculitis associated with drug abuse.

PURPOSE OF REVIEW: To review understand the epidemiology, background, neuropharmacology, and histopathology of literature verified cases, and likely etiopathogenic mechanisms. RECENT FINDINGS: There are only a handful of histologically confirmed patients in the literature with cerebral vasculitis because of drug abuse. SUMMARY: There is little justification for invasive laboratory investigation given the ready availability of highly accurate vascular neuroimaging techniques to dictate management, which usually rests upon avoidance of further exposure and minimizing the secondary neurotoxic effects of the abused substances and polypharmacy use.

Adult attention deficit/hyperactivity disorder in the ambulatory care setting.

Adult attention deficit/hyperactivity disorder (ADHD) is a significant and prevalent disorder. ADHD can impair adults' quality of life, so clinicians in multiple specialties should be able to recognize and treat the disorder. Much of the current literature has focused on childhood ADHD. However, adult ADHD is a common comorbidity in patients with mental illness, and it is essential that patients diagnosed with the disorder are treated appropriately, which can significantly improve outcomes. Adults with untreated ADHD are more likely to have substance dependence, job instability, and an overall poorer quality of life. This article reviews the screening and assessment for adult ADHD along with pharmacologic and nonpharmacologic recommendations for the management of the disorder.

The association between use of opiates, cocaine, and amphetamines during pregnancy and maternal postpartum readmission in the United States: A retrospective analysis of the Nationwide Readmissions Database.

BACKGROUND: Substance use during pregnancy has increased in the United States, with adverse consequences for mother and baby. Similarly, postpartum readmission (PPR) imposes physical, emotional, and financial stressors causing disruption to family functioning and childcare. We used national data to estimate the extent to which women who used opiates, cocaine, and amphetamines during pregnancy are at increased risk of PPR. METHODS: We analyzed 2010-2014 data from the Nationwide Readmissions Database (NRD). Our exposure, drug use during pregnancy, was identified using diagnosis codes indicative of opioid, cocaine or amphetamine use, abuse, or dependence. The outcome was all-cause PPR, maternal readmission within 42 days following discharge from the delivery hospitalization. Multivariable logistic regression was used to estimate odds ratios (OR) that represented associations between drug use and PPR. RESULTS: Among 11 million delivery hospitalizations, nearly 1 % had documented use of opiates, cocaine and/or amphetamines. The crude PPR rate was nearly four times higher among users (54.6 per 1000) compared to non-users (14.0 per 1000), and 1 in 10 women who had documented use of more than one drug category experienced postpartum readmission. Even after controlling for sociodemographic and clinical confounders, we observed a two-fold increased odds of PPR among users compared to non-users (OR = 1.95; 95 % CI: 1.82, 2.07). CONCLUSIONS: The national opioid epidemic should encourage a paradigm shift in health care public policy to facilitate the management of all substance use disorders as chronic medical conditions through evidence-based public health initiatives to prevent these disorders, treat them, and promote recovery.

Clinical Trials for Stimulant Use Disorders: Addressing Heterogeneities That May Undermine Treatment Outcomes.

In recent years, use of cocaine and amphetamines and deaths associated with stimulants have been on the rise, and there are still no FDA-approved medications for stimulant use disorders. One contributing factor may involve heterogeneity. At the neurobiological level, dual dopamine dysfunction may be undermining medication efficacy, suggesting a need for combination pharmacotherapies. At the population level, individual variability is expressed in a number of ways and, if left unaddressed, may interfere with medication efficacy. This chapter reviews studies investigating medications to address dopamine dysfunction, and it also identifies several prominent heterogeneities associated with stimulant (and other substance) use disorders. The chapter has implications for improving interventions to treat stimulant use disorders, and the theme of individual heterogeneity may have broader application across substance use disorders.

Uso de testosterona en mujeres: un comentario sobre el consenso global sobre el uso de la terapia de testosterona para mujeres / Global consensus position statement on the use of testosterone therapy for women

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)

There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)

Extended release mixed amphetamine salts and topiramate for cocaine dependence: A randomized clinical replication trial with frequent users.

BACKGROUND: Cocaine use disorder (CUD) remains a substantial public health problem with no clearly effective pharmacotherapy available. In a prior trial, combined amphetamine and topiramate treatment significantly reduced cocaine use among individuals demonstrating the most frequent use at baseline. This trial targeted such frequent users. METHODS: A double-blind, randomized placebo-controlled trial, testing the combination of mixed amphetamine salts extended-release (MAS-ER) and topiramate or placebo over a 12-week medication phase was conducted. The two-site outpatient trial included 127 adults (96 males) with CUD using at least 9 days in the prior month. MAS-ER was titrated to a maximum dose of 60 mg/day and topiramate to a maximum dose of 100 mg twice/day. The primary outcome was the proportion of individuals who achieved three consecutive abstinent weeks at the end of the study (EOS) as measured by urine toxicology and self-report. RESULTS: The proportion of participants achieving three abstinent weeks at the EOS was significantly (P = .03) larger in the treatment (14.1%) compared to the placebo group (0.0%), while controlling for baseline cocaine use, sex, current alcohol use disorder, and site. Of note, due to conservative cardiac safety-parameters a considerable number of individuals in the treatment group were discontinued from study medication (20.3%). CONCLUSIONS: While these findings provide further evidence that the combination of MAS-ER and topiramate is efficacious in promoting abstinence in CUD adults with frequent use it remains possible that the combination treatment is no more effective than either treatment alone. Despite this, the study provides a valuable "proof of concept."