RESUMEN
Neuropsychiatric disorders, such as depression, bipolar disorder, schizophrenia, obsessive-compulsive disorder, and neurodevelopmental disorders such as autism spectrum disorder, are associated with significant illness burden. Accumulating evidence supports an association between these disorders and inflammation. Consequently, anti-inflammatory agents, such as the cyclooxygenase-2 inhibitors, represent a novel avenue to prevent and treat neuropsychiatric illness. In this paper, we first review the role of inflammation in psychiatric pathophysiology including inflammatory cytokines' influence on neurotransmitters, the hypothalamic-pituitary-adrenal axis, and microglial mechanisms. We then discuss how cyclooxygenase-2-inhibitors influence these pathways with potential therapeutic benefit, with a focus on celecoxib, due to its superior safety profile. A search was conducted in PubMed, Embase, and PsychINFO databases, in addition to Clinicaltrials.gov and the Stanley Medical Research Institute trial registries. The results were presented as a narrative review. Currently available outcomes for randomized controlled trials up to November 2017 are also discussed. The evidence reviewed here suggests cyclooxygenase-2 inhibitors, and in particular celecoxib, may indeed assist in treating the symptoms of neuropsychiatric disorders; however, further studies are required to assess appropriate illness stage-related indication.
RESUMEN
BACKGROUND: There is evidence that substance use disorders and other mental disorders may have shared biological mechanisms. However, the neurobiological basis of this comorbidity remains only partially explained. This review describes the historical evolution of the dual disorders concept and approach, and reviews the existing literature on neurobiological findings specifically regarding comorbid substance use and mood disorders. METHODS: Searches were conducted using PubMed and Scopus in December 2017. A Boolean search was performed using combinations of "dual diagnosis" or "dual disorder" or "depression" or "bipolar" or "affective disorder" or "mood disorder" and "substance use" or "substance abuse" and "neurobiology" or "functional neuroimaging" or "genetics" or "neurotransmitters" or "neuroendocrinology" in the title or abstract, or as keywords, using no language restriction. RESULTS: 32 studies met the inclusion criteria. We found robust evidence for involvement of the neurotransmitters dopamine, GABA and glutamate and their receptors, as well as by the central corticotrophin-releasing hormone, hypothalamic-pituitary-adrenal axis activation, oxidative stress and inflammation. Recent studies focusing on neuroimaging and genetics have not shown consistent results. LIMITATIONS: Only two search tools were used; most identified studies excluded the population of interest (comorbid mood and substance abuse disorders). CONCLUSIONS: The neurobiological relevance for the occurrence of comorbid mood and substance abuse disorders has not been fully elucidated. Considering the high levels of individuals who experience comorbidity in these areas as well as the negative associated outcomes, this is clearly an area that requires further in-depth investigation. Furthermore, findings from this area can help to inform drug abuse prevention and intervention efforts, and especially how they relate to populations with psychiatric symptoms.
Asunto(s)
Trastornos del Humor/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Comorbilidad , Diagnóstico Dual (Psiquiatría) , Femenino , Humanos , Sistema Hipotálamo-Hipofisario/fisiopatología , Masculino , Trastornos del Humor/fisiopatología , Trastornos del Humor/psicología , Neurobiología , Neuroimagen , Sistema Hipófiso-Suprarrenal/fisiopatología , Trastornos Relacionados con Sustancias/fisiopatología , Trastornos Relacionados con Sustancias/psicologíaRESUMEN
Tobacco use disorder is a chronic illness. With its high comorbidity rate, it is a major cause of years of life lost or years lived with disability; however, it is also considered the most preventable cause of death in developed countries. Since the development of nicotine replacement therapy (NRT) in 1978, treatment options have continued to evolve and expand. Despite this, currently available treatments remain insufficient, with less than 25% of smokers remaining abstinent 1 year after treatment. In this article, we review existing and emerging smoking cessation pharmacotherapies, with a special emphasis on the most promising agents that are currently being investigated. A search of the Cochrane Database of Systematic Reviews and the PubMed, Ovid, and ClinicalTrials.gov databases (August 2 to September 1, 2017) was undertaken for articles on smoking cessation pharmacotherapies, applying no language restrictions. More than 40 pharmacotherapies were reviewed including conventional pharmacotherapies-NRT, bupropion, and varenicline (all approved by the U.S. Food and Drug Administration as first-line treatment of smoking cessation)-and novel therapies: cytisine, N-acetylcysteine, cycloserine, memantine, baclofen, topiramate, galantamine, and bromocriptine. Studies of combination NRT and varenicline showed the greatest smoking cessation rates. Clonidine and nortriptyline are second-line treatments used when first-line treatments fail or are contraindicated, or by patient preference. Some novel therapies, especially acetylcholinesterase inhibitors, cytisine, and N-acetylcysteine, display promising results. Because the results of randomized clinical trials were reported using varied end points and outcome measures, direct comparisons between different pharmacotherapies cannot easily be evaluated. Additional high-quality randomized double-blind placebo-controlled trials with long-term follow-up, using validated sustained abstinence measures, are needed to find more effective smoking cessation aids.