Expert review of neurotherapeutics
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Expert Rev Neurother · May 2015
EditorialWhy have we not yet developed a simple blood test for TBI?
In recent years, traumatic brain injury (TBI) has emerged as a rapidly growing public health challenge. Annually, approximately 1.7 million people will sustain a TBI in the USA and WHO has named TBI the leading cause of death and disability in young adults worldwide, predicting it will become the third leading cause of death in the general population by 2020. ⋯ Despite decades of basic and clinical research, and the identification of hundreds of biochemical markers, presently there is no blood test to objectively assess TBI severity. Recent work suggests treatment-induced variance in the brain's glymphatic clearance may be responsible for the breakdown between biomarker discovery and clinical translation.
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Expert Rev Neurother · Nov 2014
EditorialWhat is hydroxynorketamine and what can it bring to neurotherapeutics?
(R,S)-Ketamine was initially developed as an anesthetic agent and its pharmacological properties were determined on the basis of this clinical use. However, pharmacological studies in rat led to the development of the 'Ketamine Paradigm', whereby (R,S)-ketamine and its N-demethylated metabolite (R,S)-norketamine were deemed the active compounds whereas the other ketamine metabolites were considered inactive. Recent in vivo and in vitro studies with (2S,6S)-hydroxynorketamine, a previously identified 'inactive' metabolite, have demonstrated that this compound is an active and selective inhibitor of the α7 subtype of the nicotinic acetylcholine receptor and that this activity contributes to the pharmacological responses associated with the antidepressant activity of (R,S)-ketamine. Thus, it appears that it is necessary to reassess the 'Ketamine Paradigm' in regards to the use of sub-anesthetic doses of (R,S)-ketamine in the treatment of treatment-resistant depression.
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Expert Rev Neurother · Sep 2014
EditorialCan antidepressant medication relieve agitation in Alzheimer's disease?
Neuropsychiatric symptoms (NPS) are a major concern in the treatment of Alzheimer's disease. Historically, NPS are difficult to treat effectively due to a high side-effect burden associated with commonly used medications, such as atypical antipsychotics. Non-pharmacological treatment approaches have become the first line option. ⋯ Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) have shown promise in clinical trials for alleviating the burden of NPS. Lower overall agitation and caregiver stress has been reported to correlate to treatment with the SSRI citalopram. However, certain side effects of citalopram, such as QTc interval prolongation and increased cognitive decline, carry clinical concern and should be weighed when prescribing their use.
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Expert Rev Neurother · Jun 2014
EditorialNewly identified precipitating factors in mechanical ventilation-induced brain damage: implications for treating ICU delirium.
Delirium is 1.5 to 4.1 times as likely in intensive care unit patients when they are mechanically ventilated. While progress in treatment has occurred, delirium is still a major problem in mechanically ventilated patients. ⋯ This argues for minimizing the duration and tidal volumes of mechanical ventilation and for more effectively reducing sustained D2R signaling than achieved with haloperidol alone. The latter might be accomplished by reducing D2R cell surface expression and D2R-mediated Akt inhibition by elevating protein expression of dysbindin-1C.