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1.
Psychopharmacology (Berl) ; 237(6): 1681-1689, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32125484

RESUMO

RATIONALE: A variety of neural systems are involved in drug addiction, and some of these systems are shared across different addictive drugs. We have found several different types of drug treatments that successfully reduce nicotine self-administration. OBJECTIVES: The current set of studies is the first in a series to determine if drug treatments that have been found to significantly reduce nicotine self-administration would reduce opiate self-administration. METHODS: Amitifadine, a triple reuptake inhibitor of dopamine, norepinephrine, and serotonin, was assessed in female Sprague-Dawley rats to determine whether it significantly reduces remifentanil self-administration with either acute or chronic treatment. RESULTS: Acutely, amitifadine doses of 5, 10, and 20 mg/kg each significantly reduced remifentanil self-administration. In a chronic study, repeated treatment with 10 mg/kg of amitifadine continued to reduce remifentanil self-administration, even after the cessation of treatment. However, amitifadine was not found to attenuate the rise in remifentanil self-administration with continued access. This study and our earlier one showed that the 10 mg/kg amitifadine dose did not significantly affect food motivated responding. Amitifadine did not attenuate remifentanil-induced antinociception as measured on the hot plate test but extended and maintained antinociceptive effects. CONCLUSIONS: These studies show the promise of amitifadine as a treatment for countering opiate self-administration for adjunctive use with opioids for analgesia. Further studies are needed to determine the possible efficacy of amitifadine for combating opiate addiction or preventing it in humans during adjunctive use with opioids for chronic pain.


Assuntos
Analgésicos Opioides/administração & dosagem , Compostos Aza/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Inibidores da Captação de Dopamina/uso terapêutico , Norepinefrina/antagonistas & inibidores , Remifentanil/administração & dosagem , Inibidores de Captação de Serotonina/uso terapêutico , Animais , Compostos Aza/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Dopamina/metabolismo , Inibidores da Captação de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Motivação/efeitos dos fármacos , Motivação/fisiologia , Nicotina/administração & dosagem , Norepinefrina/metabolismo , Dor/tratamento farmacológico , Dor/metabolismo , Ratos , Ratos Sprague-Dawley , Autoadministração , Serotonina/metabolismo , Inibidores de Captação de Serotonina/farmacologia , Estereoisomerismo
2.
Medicina (B Aires) ; 80 Suppl 2: 72-75, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32150718

RESUMO

Attention deficit and hyperactivity disorder (ADHD) is a neurobiological disorder frequent in childhood. The main symptoms are attention disorder and/or impulsivity and/or hyperactivity. There are different subtypes of ADHD according to the degree of presence of these three symptoms. There are different therapeutic approaches with high proved effectiveness. Methylphenidate, a stimulant that acts through the dopaminergic and adrenergic pathways, is commonly used for the treatment of ADHD. The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening instrument internationally used for the screening of mental health problems in children and adolescents. It consists in a 25 items questionnaire with 5 different scales: emotional symptoms, conduct problems, hyperactivity / inattention, peer relationship problems and prosocial behaviours. The SDQ score was collected in a sample of ADHD patients with an age between 7 and 12 years. The score obtained before starting treatment with methylphenidate was compared before and after starting treatment, every 3-6 months and up to a period of 2 years. Statistical processing was performed using R, which is a free program for statistical and graphical analysis, that allows temporary analysis. The results indicate that hyperactivity improves throughout the first year of treatment, emotional symptoms and behavioral problems improve during the first 6 months of treatment, pro-social symptoms slowly improve over 2 years. Problems with partners do not improve in the analyzed time.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Inibidores da Captação de Dopamina/uso terapêutico , Metilfenidato/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Criança , Progressão da Doença , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Visita a Consultório Médico , Análise de Regressão , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
3.
Psychopharmacology (Berl) ; 237(5): 1331-1342, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32034448

RESUMO

RATIONALE: Searches for antidotes to cocaine, and for cognition enhancers potentially applicable to Alzheimer's disease, have revealed a novel regulatory site on nicotinic acetylcholine receptors. In the presence of an agonist, inhibitors binding to this site changed the ion channel equilibrium from the open-channel form towards the closed form. Other, related, molecules could bind to the site without changing the equilibrium. These latter compounds were predicted to displace the inhibitors without affecting receptor function per se. These compounds alleviated the inhibition. One of them is ecgonine methyl ester (EME), which is generally described as inactive, but this work suggested a beneficial effect on cognition. OBJECTIVE: This in vivo study tested for cognitive enhancement by EME in scopolamine-impaired, and aged, rats. METHODS: Memory was the primary endpoint, but thigmotaxis became an important secondary endpoint in the light of observations made during the study. Impaired cognition was pharmacologically induced by scopolamine in young rats, and spontaneously present in aged rats. Learning ability before and after administration of EME was tested in Morris water maze protocols. Concentrations of EME in the brain and plasma were analyzed by gas chromatography-mass spectrometry. RESULTS: A single dose of EME reversed scopolamine impairment, indicating involvement of acetylcholine receptors. Longer-term treatment improved cognition in aged rats, with enhanced rates of learning in the absence of an exogenous cognition-impairing compound. Impairment returned with a new challenge; the improvement could be re-established with continued dosing. EME also reversed thigmotaxis seen in aged rats; thigmotaxis is believed to indicate anxiety. The concentrations of EME in the brain proved adequate drug exposure. CONCLUSIONS: Since other investigators have shown cognition impairment caused by cocaine in aged rats, this work shows that cocaine and EME have opposite effects in Morris water maze models. EME might induce cognitive enhancement and relief of anxiety in cocaine-impaired humans, and in other cognitive disorders.


Assuntos
Envelhecimento/efeitos dos fármacos , Antagonistas Colinérgicos/toxicidade , Cocaína/análogos & derivados , Cognição/efeitos dos fármacos , Entorpecentes/farmacologia , Escopolamina/toxicidade , Envelhecimento/fisiologia , Envelhecimento/psicologia , Animais , Cocaína/farmacologia , Cocaína/uso terapêutico , Cognição/fisiologia , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/psicologia , Inibidores da Captação de Dopamina/farmacologia , Inibidores da Captação de Dopamina/uso terapêutico , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Memória/fisiologia , Entorpecentes/uso terapêutico , Ratos , Ratos Sprague-Dawley
5.
Soc Sci Med ; 238: 112492, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31442849

RESUMO

In recent decades pharmaceutical consumption has skyrocketed, growing from $43 US billion in 1985 to over $1143 billion in 2017. In trying to understand the source of this growth, social scientists have identified the key actors driving medication use and the processes through which they are driving it. However, much less attention has been devoted to understanding the forces that constrain medication consumption. This information is crucial for developing a deeper understanding of medication consumption, one that explains how context mediates the ability of key actors to shape medication consumption. To address this gap, I examine France's low consumption of psychostimulants to treat ADHD symptoms. France is a strategic case to analyze because it diverges dramatically from comparative cases: while 7% of U.S. children are medicated with psychostimulants, the same is true for only 0.2% of French children. To explain the French case I use the theory of countervailing powers. Informed by interviews with key informants, the French medical literature on psychostimulants and secondary sources, I explain how the state, medical experts and consumers have acted as countervailing forces against pharmaceutical interests. In doing so, I provide deeper insight about how context can limit the pharmaceutical industry's power.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Metilfenidato/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Inibidores da Captação de Dopamina/uso terapêutico , Indústria Farmacêutica/métodos , Indústria Farmacêutica/estatística & dados numéricos , França/epidemiologia , Humanos
6.
Trials ; 20(1): 468, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362784

RESUMO

BACKGROUND: The purpose of this study was to compare the effect of 300 mg of bupropion and 8 mg of buprenorphine per day on the treatment of methamphetamine withdrawal cravings over a 2-week treatment interval. METHOD: Sixty-five methamphetamine-dependent men who met the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) criteria for methamphetamine dependence and withdrawal were randomly divided into two groups. Subjects randomly received 300 mg of bupropion or 8 mg of buprenorphine per day in a psychiatric ward. Of the 65 subjects, 35 (53.8%) received buprenorphine and 30 (46.2%) received bupropion. The subjects were assessed by using methamphetamine craving score, interview, and negative urine drug test. FINDINGS: There were no statistically significant differences between the two groups in regard to age, education, duration of methamphetamine dependency, marital status, employment, and income. The mean ages were 32.8 years (standard deviation (SD) = 7.26, range = 22 to 59) for the buprenorphine group and 32.21 years (SD = 8.45, range = 17 to 51) for the bupropion group. All 65 patients completed the 2-week study. Both medications were effective in the reduction of methamphetamine cravings. Reduction of craving in the buprenorphine group was significantly more than the bupropion group (P = 0.011). Overall, a significant main effect of day (P <0.001) and group (P = 0.011) and a non-significant group-by-day interaction (P >0.05) were detected. CONCLUSIONS: The results support the safety and effectiveness of buprenorphine and bupropion in the treatment of methamphetamine withdrawal craving. Administration of 8 mg of buprenorphine per day can be recommended for the treatment of methamphetamine withdrawal cravings. We should note that it is to be expected that craving decreases over time without any medication. So the conclusion may not be that bupropion and buprenorphine both lower the craving. As the buprenorphine is superior to bupropion, only buprenorphine does so for sure. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT) registration number: IRCT2015010320540N1 . Date registered: April 10, 2015.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Comportamento Aditivo/tratamento farmacológico , Buprenorfina/uso terapêutico , Bupropiona/uso terapêutico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Fissura/efeitos dos fármacos , Inibidores da Captação de Dopamina/uso terapêutico , Metanfetamina/efeitos adversos , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adolescente , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/diagnóstico , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Analgésicos Opioides/efeitos adversos , Comportamento Aditivo/diagnóstico , Comportamento Aditivo/psicologia , Buprenorfina/efeitos adversos , Bupropiona/efeitos adversos , Inibidores da Captação de Dopamina/efeitos adversos , Método Duplo-Cego , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Síndrome de Abstinência a Substâncias/diagnóstico , Síndrome de Abstinência a Substâncias/psicologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
J Clin Endocrinol Metab ; 104(10): 4619-4625, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265070

RESUMO

CONTEXT: The effect of antidepressant (ATD) use on mortality in patients with diabetes mellitus (DM) has not yet been sufficiently studied, although comorbid depression is common in this population. OBJECTIVE: To explore the impact of ATDs on mortality among DM patients. DESIGN: A retrospective cohort study in a national database. SETTING: This population-based study used the National Health Insurance Research Database in Taiwan. Since 2000, we identified 53,412 cases of newly diagnosed patients with DM and depression. Patient cases were followed for assessing mortality until 2013. MAIN OUTCOME MEASURE: The association between mortality and ATD use was explored adjusting for cumulative dosing. RESULTS: Using the time-dependent Cox regression model, ATD use was associated with significantly reduced mortality among patients with DM [in the highest dose group: hazard ratio (HR), 0.65; 95% CI, 0.59 to 0.71]. Further analysis showed that differences in mortality existed across ATD categories: selective serotonin reuptake inhibitors (HR, 0.63; 95% CI, 0.56 to 0.71), serotonin-norepinephrine reuptake inhibitors (HR, 0.58; 95% CI, 0.44 to 0.78), norepinephrine-dopamine reuptake inhibitors (HR, 0.20; 95% CI, 0.07 to 0.63), mirtazapine (HR, 0.60; 95% CI, 0.45 to 0.82), tricyclic/tetracyclic antidepressants (HR, 0.73; 95% CI, 0.54 to 0.97), and trazodone (HR, 0.52; 95% CI, 0.29 to 0.91). However, reversible inhibitor of monoamine oxidase A (RIMA) was found to be associated with an increase, rather than a decrease, in total mortality (HR, 1.48; 95% CI, 1.09 to 1.99). CONCLUSION: Most ATDs, but not RIMA, were associated with significantly reduced mortality among a population with comorbid DM and depression.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Mortalidade , Adolescente , Adulto , Idoso , Antidepressivos Tricíclicos/uso terapêutico , Estudos de Coortes , Comorbidade , Transtorno Depressivo/epidemiologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/epidemiologia , Inibidores da Captação de Dopamina/uso terapêutico , Transtorno Distímico/tratamento farmacológico , Transtorno Distímico/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mirtazapina/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Modelos de Riscos Proporcionais , Inibidores de Captação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Taiwan/epidemiologia , Trazodona/uso terapêutico , Adulto Jovem
9.
Expert Rev Clin Pharmacol ; 12(8): 723-728, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31215815

RESUMO

Introduction: Narcolepsy is a chronic disabling condition, excessive daytime somnolence is the main symptoms of it. There is currently no cure for narcolepsy, and hence there is a great need for new treatment options. Solriamfetol is a new selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects. The purpose of this paper is to review solriamfetol. Areas covered: The chemical property, mechanism of action, pharmacokinetics, clinical efficacy, and safety of solriamfetol are introduced in this paper. Expert opinion: Solriamfetol can bind to dopamine and norepinephrine transporters and inhibit reuptake of dopamine and norepinephrine. Clinical trials showed that solriamfetol could significantly improve the ability to stay awake and subjective symptoms of excessive sleepiness in adults with narcolepsy. Solriamfetol was well tolerated. Very common adverse reactions were headache, nausea, decreased appetite, insomnia, and anxiety.


Assuntos
Carbamatos/uso terapêutico , Distúrbios do Sono por Sonolência Excessiva/tratamento farmacológico , Narcolepsia/tratamento farmacológico , Inibidores da Captação Adrenérgica/efeitos adversos , Inibidores da Captação Adrenérgica/farmacologia , Inibidores da Captação Adrenérgica/uso terapêutico , Animais , Distúrbios do Sono por Sonolência Excessiva/fisiopatologia , Inibidores da Captação de Dopamina/efeitos adversos , Inibidores da Captação de Dopamina/farmacologia , Inibidores da Captação de Dopamina/uso terapêutico , Humanos , Narcolepsia/fisiopatologia , Fenilalanina/análogos & derivados , Resultado do Tratamento
10.
Eur Neuropsychopharmacol ; 29(6): 756-765, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064683

RESUMO

RATIONALE: the role that antidepressants play on alcohol consumption is not well understood. Previous studies have reported that treatment with a Selective Serotonin Reuptake Inhibitor (SSRIs) increases alcohol consumption in an animal model of relapse, however it is unknown whether this effect holds for other antidepressants such as the atypical dopamine/norepinephrine reuptake inhibitors (SNDRI). OBJECTIVES: the main goal of the present study was to compare the effects of two classes of antidepressants drugs, bupropion (SNDRI) and fluoxetine (SSRI), on alcohol consumption during relapse. Since glutamatergic and endocannabinoid signaling systems plays an important role in alcohol abuse and relapse, we also evaluated the effects of both antidepressants onthe expression of the main important genes and proteins of both systems in the prefrontal cortex, a critical brain region in alcohol relapse. METHODS: rats were trained to self-administered alcohol. During abstinence, rats received a 14d-treatment with vehicle, fluoxetine (10 mg/kg) or bupropion (20 mg/kg), and we evaluated alcohol consumption during relapse for 3 weeks. Samples of prefrontal cortex were taken to evaluate the mRNA and protein expression of the different components of glutamatergic and endocannabinoid signaling systems. RESULTS: fluoxetine treatment induced a long-lasting increase in alcohol consumption during relapse, an effect that was not observed in the case of bupropion treatment. The observed increases in alcohol consumption were accompanied by distinct alterations in the glutamate and endocannabinoid systems. CONCLUSIONS: our results suggest that SSRIs can negatively impact alcohol consumption in relapse while SNDRIs have no effects. The observed increase in alcohol consumption are accompanied by functional alterations in the glutamatergic and endocannabinoid systems. This finding could open new strategies for the treatment of depression in patients with alcohol use disorders.


Assuntos
Alcoolismo/tratamento farmacológico , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/efeitos adversos , Bupropiona/uso terapêutico , Inibidores da Captação de Dopamina/efeitos adversos , Inibidores da Captação de Dopamina/uso terapêutico , Consumo de Bebidas Alcoólicas , Alcoolismo/psicologia , Animais , Endocanabinoides/metabolismo , Fluoxetina/uso terapêutico , Masculino , Córtex Pré-Frontal/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Wistar , Receptores de Glutamato/biossíntese , Receptores de Glutamato/genética , Recidiva , Inibidores de Captação de Serotonina/uso terapêutico
11.
Drugs ; 79(7): 785-790, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31062265

RESUMO

Solriamfetol (Sunosi™) is an orally active, selective dopamine and norepinephrine reuptake inhibitor that was recently approved in the USA as a treatment for excessive daytime sleepiness (hypersomnia) associated with narcolepsy and obstructive sleep apnoea (OSA). Norepinephrine and dopamine influence various physiologic functions, including sleep-wake regulation, and excessive sleepiness has been linked with dysregulation of dopaminergic and norepinephrine systems. This article summarizes the milestones in the development of solriamfetol leading to this first approval as a treatment for excessive daytime sleepiness associated with narcolepsy and OSA.


Assuntos
Distúrbios do Sono por Sonolência Excessiva/tratamento farmacológico , Inibidores da Captação de Dopamina/farmacocinética , Inibidores da Captação de Dopamina/administração & dosagem , Inibidores da Captação de Dopamina/efeitos adversos , Inibidores da Captação de Dopamina/uso terapêutico , Relação Dose-Resposta a Droga , Aprovação de Drogas , Humanos , Narcolepsia/tratamento farmacológico , Inibidores da Captação de Neurotransmissores/administração & dosagem , Inibidores da Captação de Neurotransmissores/efeitos adversos , Inibidores da Captação de Neurotransmissores/farmacocinética , Inibidores da Captação de Neurotransmissores/uso terapêutico , Norepinefrina/metabolismo , Transtornos do Sono-Vigília/tratamento farmacológico , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration
12.
Rev. neurol. (Ed. impr.) ; 68(10): 417-425, 16 mayo, 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-180737

RESUMO

Introducción. El metilfenidato es un fármaco ampliamente usado como tratamiento del trastorno por déficit de atención/hiperactividad (TDAH) y otros trastornos neuropsiquiátricos. La dificultad para mantener la atención de forma prolongada y la deficiente ejecución de tareas que caracterizan a tales trastornos se han vinculado a la disfunción del circuito de activación por defecto --default mode network (DMN)--, revelado en estudios de resonancia magnética funcional. En los individuos sanos, el DMN y la red orientada a tareas (task-positive network) presentan una relación inversa. Se ha planteado que el metilfenidato revertiría la escasa desactivación del DMN durante la ejecución de tareas que caracteriza a los trastornos de la atención y del control inhibitorio, normalización que a su vez mejoraría la ejecución de las tareas. Pacientes y métodos. Con objeto de examinar la hipótesis de que este fármaco propicia tal desactivación, se llevó a cabo una revisión sistemática de la bibliografía. Resultados. Doce estudios se incluyeron finalmente en la revisión. Para ello, debían haber medido los efectos de la administración del metilfenidato sobre la actividad del DMN. Once estudios mostraron indicios de mejora atribuible al metilfenidato en áreas cerebrales vinculadas a dicho circuito. Los resultados indican la normalización de los circuitos cerebrales en los pacientes con disfunción del DMN. Conclusiones. Los hallazgos preliminares ofrecen indicios sólidos de que el metilfenidato mejora la disfunción del DMN presente en el TDAH y otros trastornos neuropsiquiátricos. Se precisan nuevos estudios que diluciden los pormenores de este efecto y mejoren la comprensión sobre los mecanismos de acción del metilfenidato


Introduction. Methylphenidate is a widely-used drug for the treatment of attention deficit/hyperactivity disorder (ADHD) and other neuropsychiatric disorders. Sustained-attention deficits and poorer task performance in these disorders have been associated with default mode network (DMN) dysfunction in fMRI studies. DMN is a set of brain areas more activated during the resting-state. Under the execution of external tasks, there is an attenuation of DMN activity. In healthy individuals DMN and task-positive network are anticorrelated. It has been suggested that methylphenidate could normalize the attenuated task-related DMN deactivation in attention- and inhibitory control-related disorders and that such normalization could improve task performance. Patients and methods. To explore the hypothesis of DMN deactivation after methylphenidate administration, we conducted a systematic review of the literature. Results. After a systematic search, 12 studies were included in this review. For eligibility, studies were required to measure the effects of methylphenidate administration on the DMN activity. Eleven studies showed evidence of MPH-induced improvements in brain areas related to DMN. The results suggest a normalization of brain circuits in individuals with DMN dysfunction. Conclusions. Our preliminary findings strongly suggest methylphenidate improves DMN dysfunction presented in ADHD and other neuropsychiatric disorders. Further studies are needed to better understand this effect and expand comprehension of methylphenidate action mechanisms


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Metilfenidato/uso terapêutico , Inibidores da Captação de Dopamina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia
14.
Neuropharmacology ; 158: 107609, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31009632

RESUMO

Substance use disorders (SUD) are serious public health problems worldwide. Although significant progress has been made in understanding the neurobiology of drug reward and the transition to addiction, effective pharmacotherapies for SUD remain limited and a majority of drug users relapse even after a period of treatment. The United States Food and Drug Administration (FDA) has approved several medications for opioid, nicotine, and alcohol use disorders, whereas none are approved for the treatment of cocaine or other psychostimulant use disorders. The medications approved by the FDA for the treatment of SUD can be divided into two major classes - agonist replacement therapies, such as methadone and buprenorphine for opioid use disorders (OUD), nicotine replacement therapy (NRT) and varenicline for nicotine use disorders (NUD), and antagonist therapies, such as naloxone for opioid overdose and naltrexone for promoting abstinence. In the present review, we primarily focus on the pharmacological rationale of agonist replacement strategies in treatment of opioid dependence, and the potential translation of this rationale to new therapies for cocaine use disorders. We begin by describing the neural mechanisms underlying opioid reward, followed by preclinical and clinical findings supporting the utility of agonist therapies in the treatment of OUD. We then discuss recent progress of agonist therapies for cocaine use disorders based on lessons learned from methadone and buprenorphine. We contend that future studies should identify agonist pharmacotherapies that can facilitate abstinence in patients who are motivated to quit their illicit drug use. Focusing on those that are able to achieve abstinence from cocaine will provide a platform to broaden the effectiveness of medication and psychosocial treatment strategies for this underserved population. This article is part of the Special Issue entitled 'New Vistas in Opioid Pharmacology'.


Assuntos
Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Inibidores da Captação de Dopamina/uso terapêutico , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Buprenorfina/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Dextroanfetamina/uso terapêutico , Proteínas da Membrana Plasmática de Transporte de Dopamina/antagonistas & inibidores , Desenvolvimento de Medicamentos , Humanos , Metadona/uso terapêutico , Metilfenidato/uso terapêutico , Modafinila/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/metabolismo , Oxalatos , Piperazinas , Receptores Opioides mu/agonistas , Tabagismo/tratamento farmacológico , Tropanos/uso terapêutico , Vareniclina/uso terapêutico
15.
Psychiatry Res Neuroimaging ; 286: 53-59, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30903953

RESUMO

We examined the effects of lisdexamfetamine (LDX) treatment on ventral prefrontal cortex (VPFC) and striatal brain activation in binge eating disorder (BED). We hypothesized that participants with BED have an abnormal brain response to palatable food cues, and that VPFC and striatal regions would respond to such cues after LDX treatment. Twenty women with moderate to severe BED consented to a 12-week, open-label trial of LDX with fMRI before and after treatment. Twenty obese women without BED served as healthy controls and received one fMRI. LDX was started at 30 mg/d with a target of 70 mg/d at week 12. At baseline, women with BED showed greater activation in ventrolateral prefrontal cortex (VLPFC), striatum, and globus pallidus to food pictures and brain activation to food pictures predicted clinical outcome at 12 weeks. After 12 weeks of LDX treatment, BED women showed significant reductions in globus pallidus activation. Reductions in ventromedial prefrontal cortex (VMPFC) and thalamus activation specifically correlated with binge eating and obsessive-compulsive symptom reductions, respectively. Results suggest that BED is characterized by an abnormally large VPFC-subcortical brain response to palatable foods that LDX treatment helps modify. Moreover, VPFC-subcortical activation at baseline is a potential biomarker of LDX response.


Assuntos
Transtorno da Compulsão Alimentar/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Inibidores da Captação de Dopamina/uso terapêutico , Dimesilato de Lisdexanfetamina/uso terapêutico , Rede Nervosa/efeitos dos fármacos , Obesidade/tratamento farmacológico , Adulto , Transtorno da Compulsão Alimentar/diagnóstico por imagem , Transtorno da Compulsão Alimentar/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiologia , Inibidores da Captação de Dopamina/farmacologia , Feminino , Humanos , Dimesilato de Lisdexanfetamina/farmacologia , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Obesidade/diagnóstico por imagem , Obesidade/fisiopatologia , Projetos Piloto , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Resultado do Tratamento
16.
Int Rev Psychiatry ; 31(4): 332-346, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30870048

RESUMO

Shared decision-making (SDM) means that clinicians and the patient make decisions about the treatment together. Regarding drug treatment in eating disorders (EDs), such decisions may include psychopharmacological treatment for the ED itself, medications for potential co-morbid psychiatric disorders, pharmacological strategies to alleviate the health consequences of an ED, or 'pro re nata' (PRN) medication which is given in acute care when required. Decisions regarding drug treatment in EDs should be specific in terms of the active pharmacological substance, its dose, its route of administration, and the duration of treatment. Decisions should be made with regard to the specific health risks of patients with EDs and the entire treatment approach, and should take alternative measures, additional therapies, and specific combinations of therapies into account. The differences in the expectations of patients, carers, and clinicians towards drug treatment, the lack of specific suggestions in clinical practice guidelines, and the lack of approved psychopharmacological treatment options make SDM necessary, but also a challenge. However, SDM may be limited due to the patient's impaired insight or limited capacity due to the ED. Thus, the legal framework must be taken into consideration.


Assuntos
Anorexia Nervosa/tratamento farmacológico , Antipsicóticos/uso terapêutico , Transtorno da Compulsão Alimentar/tratamento farmacológico , Bulimia Nervosa/tratamento farmacológico , Agonistas de Receptores de Canabinoides/uso terapêutico , Tomada de Decisão Compartilhada , Inibidores da Captação de Dopamina/uso terapêutico , Tratamento Farmacológico/normas , Agonistas de Aminoácidos Excitatórios/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Humanos
17.
Eur Neuropsychopharmacol ; 29(3): 397-404, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30595354

RESUMO

More effective, tolerable interventions for treatment-refractory obsessive-compulsive disorder (OCD) are needed. Preliminary findings encourage optimism that methylphenidate augmentation may be of benefit in the treatment of OCD. To test modulator methylphenidate (MPH) of extended-release formulations (MPH-ER) a safe and effective add-on therapy for refractory OCD, a pilot randomized, placebo-controlled, double-blind trial was conducted at an outpatient, single-center academic setting. Participants included 44 adults with serotonin reuptake inhibitor (SRI) treatment-refractory OCD and receiving a stable fluvoxamine pharmacotherapy with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores higher than 20. Data were analyzed in the intention-to-treat sample. All subjects were randomized into two parallel groups to receive fluvoxamine (250 mg daily) plus MPH-ER (36 mg daily) or fluvoxamine (250 mg daily) plus identical placebo tablets under double-blind conditions and followed for 8 weeks. Forty-four patients (29 [66%] men), with a mean (SD) age of 24.7 (6) years participated; with a mean (SD) duration of episode 5.7 (3) were randomized and forty-one finished the trial. In the intention-to-treat analysis, the improvement in the Y-BOCS total score and Y-BOCS obsession subscale score was more prominent in the fluvoxamine and MPH-ER group compared with those receiving placebo (P < .001). Additionally, cumulative response rates were higher in the MPH-ER vs placebo groups (59% vs 5%; P  < .001). MPH-ER was well tolerated; No subjects dropped out due to side effects. In summary, combined treatment with MPH-ER demonstrated an enhanced clinical rate of response compared to placebo. Further trials should examine MPH-ER efficacy in a larger sample.


Assuntos
Inibidores da Captação de Dopamina/uso terapêutico , Fluvoxamina/uso terapêutico , Metilfenidato/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Adulto , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
18.
J Child Adolesc Psychopharmacol ; 29(2): 80-89, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30694697

RESUMO

OBJECTIVE: Dasotraline is a potent inhibitor of presynaptic dopamine and norepinephrine reuptake with a pharmacokinetic profile characterized by slow absorption and a long elimination half-life. The aim of this study was to evaluate the efficacy and safety of dasotraline in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Children aged 6-12 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of ADHD were randomized to 6 weeks of double-blind once-daily treatment with dasotraline (2 or 4 mg) or placebo. The primary efficacy endpoint was change from baseline in the ADHD Rating Scale Version IV-Home Version (ADHD RS-IV HV) total score at week 6. RESULTS: A total of 342 patients were randomized to dasotraline or placebo (mean age 9.1 years, 66.7% male). Treatment with dasotraline was associated with significant improvement at study endpoint in the ADHD RS-IV HV total score for the 4 mg/day dose versus placebo (-17.5 vs. -11.4; p < 0.001; effect size [ES], 0.48), but not for the 2 mg/day dose (-11.8 vs. -11.4; ns; ES, 0.03). A regression analysis confirmed a significant linear dose-response relationship for dasotraline. Significant improvement for dasotraline 4 mg/day dose versus placebo was also observed across the majority of secondary efficacy endpoints, including the Clinical Global Impression (CGI)-Severity score, the Conners Parent Rating Scale-Revised scale (CPRS-R) ADHD index score, and subscale measures of hyperactivity and inattentiveness. Discontinuation rates due to adverse events (AEs) were higher in the dasotraline 4 mg/day group (12.2%) compared with the 2 mg/day group (6.3%) and placebo (1.7%). The most frequent AEs associated with dasotraline were insomnia, decreased appetite, decreased weight, and irritability. Psychosis-related symptoms were reported as AEs by 7/219 patients treated with dasotraline in this study. There were no serious AEs or clinically meaningful changes in blood pressure or heart rate on dasotraline. CONCLUSION: In this placebo-controlled study, treatment with dasotraline 4 mg/day significantly improved ADHD symptoms and behaviors, including attention and hyperactivity, in children aged 6-12 years. The most frequently reported AEs observed on dasotraline included insomnia, decreased appetite, decreased weight, and irritability.


Assuntos
1-Naftilamina/análogos & derivados , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Inibidores da Captação de Dopamina/uso terapêutico , 1-Naftilamina/efeitos adversos , 1-Naftilamina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Criança , Inibidores da Captação de Dopamina/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Resultado do Tratamento
19.
Clin Exp Ophthalmol ; 47(2): 259-264, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30663207

RESUMO

IMPORTANCE: The association between visual deficits and attention disorders has been reported but remains unproven. BACKGROUND: The objective of this study was to evaluate the risk of attention-deficit hyperactivity disorder (ADHD) in children with amblyopia. DESIGN: Population-based, cohort study. PARTICIPANTS: The dataset from the Taiwan National Health Insurance Research Database in 2000 to 2010. METHODS: A total of 6817 patients aged <18 years with newly diagnosed amblyopia were identified. Four age- and sex-matched controls without amblyopia were included for each patient, that is, 27268 controls. MAIN OUTCOME MEASURES: The primary outcome was the risk of ADHD. The secondary outcomes were age at ADHD onset and use of ADHD medication. RESULTS: During a mean observation period of 7.18 years, the incidence of ADHD per 1000 person-years was 7.02 in the amblyopia group and 4.61 in the control group (P < 0.0001). The ADHD risk in the amblyopia group was 1.81 times that in the control group (hazard ratio 1.81; 95% confidence interval 1.59-2.06). After stratification by amblyopia subtype, the greatest risk was in the deprivation type (hazard ratio 2.14; 95% confidence interval 1.56-2.92) followed by the strabismic (hazard ratio 2.09; 95% confidence interval 1.15-3.79) and refractive (hazard ratio 1.76; 95% confidence interval 1.54-2.02) types. Age at ADHD onset was younger in the amblyopia group (median 8.14 vs 8.45 years; P = 0.0096). The average duration of neuropsychiatric medication use was comparable between groups (P = 0.98). CONCLUSIONS AND RELEVANCE: The ADHD risk is higher in children with amblyopia.


Assuntos
Ambliopia/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Inibidores da Captação Adrenérgica/uso terapêutico , Ambliopia/diagnóstico , Ambliopia/tratamento farmacológico , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Bupropiona/uso terapêutico , Criança , Estudos de Coortes , Bases de Dados Factuais , Inibidores da Captação de Dopamina/uso terapêutico , Feminino , Humanos , Incidência , Masculino , Metilfenidato/uso terapêutico , Programas Nacionais de Saúde/estatística & dados numéricos , Fatores de Risco , Taiwan/epidemiologia , Acuidade Visual/fisiologia
20.
Curr Drug Targets ; 20(2): 210-219, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-28494748

RESUMO

Attention deficit hyperactive disorder (ADHD), a hyperactivity disorder prevalent among children may continue as an adulthood attention deficit. To date, treating an individual with an adult ADHD may be an arduous task as it involves numerous challenges, which include a need for high index of suspicion to diagnose this medical condition. Many psychiatric disorders masquerade as ADHD and delay the necessary assessment and proper treatment for this debilitating medical disorder. Adult ADHD is often misdiagnosed (or under diagnosed) due to the fact that this medical condition is being masked by the patients' high level of intellectual achievement. As the ADHD in adult persists, it may end-up with impairment in the personal-social-occupational function in which the management becomes a great challenge. The treatment of ADHD can be optimized by using various drugs targets agents like norepinephrine-dopamine reuptake inhibitor (NDRI), with or without psycho stimulants like methylphenidate, which is marketed as Ritalin. Bupropion, an NDRI has a novel effect on ADHD as the molecule exerts its effects by modulating the reward-pleasure mesolimbic dopaminergic system and at the same time regulates the elevating mood dimension of the noradrenergic neurotransmission. The role of Bupropion in the neural and psychopharmacological perspective treatment of ADHD was deliberated. The present review highlights the novel effects of Bupropion in ADHD treatment, together with the help of other successful bio-psycho-social measures. This may be of immense benefit to the psychiatrists for treating their patients.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Bupropiona/uso terapêutico , Inibidores da Captação de Dopamina/uso terapêutico , Adulto , Animais , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Ensaios Clínicos como Assunto , Diagnóstico Diferencial , Humanos , Masculino , Resultado do Tratamento
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