scholarly journals Candidate Strategies for Development of a Rapid-Acting Antidepressant Class That Does Not Result in Neuropsychiatric Adverse Effects: Prevention of Ketamine-Induced Neuropsychiatric Adverse Reactions

2020 ◽  
Vol 21 (21) ◽  
pp. 7951 ◽  
Author(s):  
Motohiro Okada ◽  
Yasuhiro Kawano ◽  
Kouji Fukuyama ◽  
Eishi Motomura ◽  
Takashi Shiroyama

Non-competitive N-methyl-D-aspartate/glutamate receptor (NMDAR) antagonism has been considered to play important roles in the pathophysiology of schizophrenia. In spite of severe neuropsychiatric adverse effects, esketamine (racemic enantiomer of ketamine) has been approved for the treatment of conventional monoaminergic antidepressant-resistant depression. Furthermore, ketamine improves anhedonia, suicidal ideation and bipolar depression, for which conventional monoaminergic antidepressants are not fully effective. Therefore, ketamine has been accepted, with rigorous restrictions, in psychiatry as a new class of antidepressant. Notably, the dosage of ketamine for antidepressive action is comparable to the dose that can generate schizophrenia-like psychotic symptoms. Furthermore, the psychotropic effects of ketamine precede the antidepressant effects. The maintenance of the antidepressive efficacy of ketamine often requires repeated administration; however, repeated ketamine intake leads to abuse and is consistently associated with long-lasting memory-associated deficits. According to the dissociative anaesthetic feature of ketamine, it exerts broad acute influences on cognition/perception. To evaluate the therapeutic validation of ketamine across clinical contexts, including its advantages and disadvantages, psychiatry should systematically assess the safety and efficacy of either short- and long-term ketamine treatments, in terms of both acute and chronic outcomes. Here, we describe the clinical evidence of NMDAR antagonists, and then the temporal mechanisms of schizophrenia-like and antidepressant-like effects of the NMDAR antagonist, ketamine. The underlying pharmacological rodent studies will also be discussed.

2016 ◽  
Vol 24 (3) ◽  
pp. 289-291 ◽  
Author(s):  
Nicholas A Keks ◽  
Judy Hope ◽  
David Castle

Author(s):  
SANTA TREASA CYRIAC ◽  
DIVYA SARA IYPE

Anti-bacterial are agents that inhibit bacterial growth or kills bacteria and are a sub-type of antimicrobials. These are drugs used to treat infections, but they sometimes pose a threat of adverse events. Some of these adverse events are neuropsychiatric, which are generally hard to diagnose and is often paid less attention. They account for about 30% of total Adverse drug reactions (ADRs) caused by drugs in patients without mental abnormalities. The spectrum ranges from episodes of seizure to acute psychosis. The article emphasizes the frequency of such adverse events and means to raise awareness among medical practitioners regarding the same. The various neuropsychiatric adverse effects and the agents responsible have been reviewed, along with their possible mechanisms and general management. The information for writing this review was selected by searching for keywords such as Neurotoxicity, GABA, Psychosis, Naranjo scale, and Antibiomania in databases such as Google Scholar, PubMed, Elsevier, etc. After searching the articles in the above-mentioned databases, the articles were screened concerning their importance with our work and according to their title and abstract. Additional articles were discovered by checking the references in the current study's citations. Using this method, the various neuropsychiatric adverse effects of Antibacterial agents were summarized in this review.


2017 ◽  
Vol 13 (1) ◽  
pp. 49-57
Author(s):  
Baikuntha Raj Adhikari ◽  
S Mishra ◽  
S Nepal ◽  
N Sapkota

Background: Psychosis in bipolar disorder is common but still not well understood. There is paucity of literature from our country and none from this institute which serves the eastern part of Nepal.Objective: To describe the hallucinations and delusions in bipolar disorders in our place.Methods: Patients-record files of bipolar disorders with psychosis discharged in two years’ time from 2012 to 2014 were analysed. Patients with unipolar depression, recurrent depressive disorder, serious organic illness, and primary substance use disorders were excluded. Information was collected in a structured performa. Association of delusion and hallucination was observed.Results: During the study period, ninety-five patients with bipolardisorder had psychosis. Hallucination was present in 29 (30.5%) cases, and out of these 23 (79.3%) were cases of mania. In 26 (89.7%) patients, the hallucinations were mood congruent. The median duration of appearance of hallucination was 10 days and appeared early in mania. Among hallucinations, auditory verbal hallucinations were present in all 29 patients. Delusions were present in 77 (81.1%) of patients, and grandiose delusions were the most common. Grandiose delusions tended to occur even in the absence of hallucinations. Conclusion: Psychosis is common in bipolar disorder. Grandiose delusions are the most common delusion and are relatively independent of hallucination. The auditory verbal hallucinations are the most common type of hallucination. Hallucinations in mania tend to manifest earlier than in bipolar depression and mixed episode, and most of the hallucinations in bipolar disorder are mood congruent. Health Renaissance 2015;13 (1): 49-57


2017 ◽  
Vol 2017 ◽  
pp. 1-12
Author(s):  
Patrick Amoateng ◽  
Dorcas Osei-Safo ◽  
Kennedy Kwami Edem Kukuia ◽  
Samuel Adjei ◽  
Obed Awintuma Akure ◽  
...  

Background. Albizia zygia is used in Ghanaian traditional medicine for the management of mental disorders. The present study tested the hypothesis that an extract of the leaves of Albizia zygia (AZE) may possess antipsychotic and antidepressant properties. Method. The novelty- and apomorphine-induced locomotor and rearing behaviours of AZE in mice were explored in an open-field observational test system. The effects of AZE in apomorphine-induced cage climbing test, extract-induced catalepsy, and haloperidol-induced catalepsy on mice were also investigated. Lastly, the forced swimming and tail suspension tests in mice were employed to screen the possible antidepressant effects of AZE. Results. AZE (100–3000 mg/kg) showed signs of central nervous system (CNS) depression under observation, with no lethality, 24 h after treatment in mice. AZE (100–1000 mg/kg) produced a significant decrease in the frequency of novelty- and apomorphine-induced locomotor activities in mice. The extract also significantly decreased the frequency and duration of apomorphine-induced climbing activities in mice. AZE, while failing to produce any cataleptic event in naïve mice, significantly enhanced haloperidol-induced catalepsy at a dose of 1000 mg/kg. However, AZE did not produce any significant antidepressant effects in the test models employed. Conclusion. The extract of Albizia zygia exhibited an antipsychotic-like activity in mice.


2020 ◽  
Author(s):  
James R Phelps ◽  
Olivia R Pipitone ◽  
Kenneth Squires ◽  
Jonathan D Bale

Abstract Background The Collaborative Care Model of psychiatric consultation in primary care has improved outcomes for unipolar depression, but bipolar depressions are challenging for providers and consultants. Although lamotrigine and lithium are both first line medications for bipolar depression, their use in primary care has been declining over the last decade. Objective Our project aimed to quantify the frequency of and adoption of recommendations for lamotrigine and lithium, and their adverse effects, in a Collaborative Care program. Methods Chart review. Results For 620 depressed adult patients (Public Health Questionnaire, 9-item ≥10), lamotrigine and lithium were recommended by psychiatric consultant for 35% and 26% of patients, respectively; and when recommended, were prescribed by primary care providers 50% and 32% of the time, respectively. Eighty-four percent of lithium dosages were 600 mg or less; average serum level 0.32 mEq/l. In follow-up up to 6 months, lithium was associated with no more weight gain than lamotrigine; but 12% of patients receiving lithium had thyroid stimulating hormone increases exceeding the upper limit of normal, occurring in an average of 32 days after the initial prescription. Conclusions (i) In a Collaborative Care program of psychiatric consultation, recommendations for lamotrigine and lithium were very frequent. (ii) Adoption of these recommendations is variable, warranting further investigation. (iii) Like higher doses, low doses of lithium induced hypothyroidism (rapidly)—but not weight gain.


Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 3 ◽  
Author(s):  
Fadwa Odeh ◽  
Hamdi Nsairat ◽  
Walhan Alshaer ◽  
Mohammad A. Ismail ◽  
Ezaldeen Esawi ◽  
...  

Soon after they were first described in 1990, aptamers were largely recognized as a new class of biological ligands that can rival antibodies in various analytical, diagnostic, and therapeutic applications. Aptamers are short single-stranded RNA or DNA oligonucleotides capable of folding into complex 3D structures, enabling them to bind to a large variety of targets ranging from small ions to an entire organism. Their high binding specificity and affinity make them comparable to antibodies, but they are superior regarding a longer shelf life, simple production and chemical modification, in addition to low toxicity and immunogenicity. In the past three decades, aptamers have been used in a plethora of therapeutics and drug delivery systems that involve innovative delivery mechanisms and carrying various types of drug cargos. However, the successful translation of aptamer research from bench to bedside has been challenged by several limitations that slow down the realization of promising aptamer applications as therapeutics at the clinical level. The main limitations include the susceptibility to degradation by nucleases, fast renal clearance, low thermal stability, and the limited functional group diversity. The solution to overcome such limitations lies in the chemistry of aptamers. The current review will focus on the recent arts of aptamer chemistry that have been evolved to refine the pharmacological properties of aptamers. Moreover, this review will analyze the advantages and disadvantages of such chemical modifications and how they impact the pharmacological properties of aptamers. Finally, this review will summarize the conjugation strategies of aptamers to nanocarriers for developing targeted drug delivery systems.


2019 ◽  
Vol 47 (20) ◽  
pp. 10489-10505 ◽  
Author(s):  
Arun Richard Chandrasekaran ◽  
Jibin Abraham Punnoose ◽  
Lifeng Zhou ◽  
Paromita Dey ◽  
Bijan K Dey ◽  
...  

Abstract MicroRNAs are involved in the crucial processes of development and diseases and have emerged as a new class of biomarkers. The field of DNA nanotechnology has shown great promise in the creation of novel microRNA biosensors that have utility in lab-based biosensing and potential for disease diagnostics. In this Survey and Summary, we explore and review DNA nanotechnology approaches for microRNA detection, surveying the literature for microRNA detection in three main areas of DNA nanostructures: DNA tetrahedra, DNA origami, and DNA devices and motifs. We take a critical look at the reviewed approaches, advantages and disadvantages of these methods in general, and a critical comparison of specific approaches. We conclude with a brief outlook on the future of DNA nanotechnology in biosensing for microRNA and beyond.


2019 ◽  
Vol 105 ◽  
pp. 03024 ◽  
Author(s):  
Valery Nesterov ◽  
Vladimir Aksenov ◽  
Vladimir Sadovets ◽  
Dmitry Pashkov ◽  
Zhadyra Beysebayeva

The article contains a method for determination of the energy capacity of face rock breaking by the knife operating element of the geokhod. In addition, the dependence of the breaking energy capacity on the pitch of the geokhod’s external propeller was revealed. The relevance of the study was considered. In order to set goals and objectives of the study, work features of new-class mining machines – geokhods and fundamental principles of geokhod technology were presented. Advantages and disadvantages of existing methods for determination of the energy capacity of rock breaking were identified, and the possibility of using them in calculation of power parameters of the geokhod’s knife operating element was assessed. Power and geometrical parameters of the geokhod’s knife operating element were determined, which affect the energy capacity of rock breaking. To determine the influence of the external propeller’s pitch on the breaking energy capacity, geometrical parameters of the knife operating element and parameters of mining conditions of workings were substantiated. As a result of the study, it was revealed that the energy capacity of rock breaking by the knife operating element decreases non-uniformly as the pitch of the external propeller increases.


2020 ◽  
pp. 026988112093690
Author(s):  
Yan-Ling Zhou ◽  
Wei-Jian Liu ◽  
Cheng-Yu Wang ◽  
Wei Zheng ◽  
Xiao-Feng Lan ◽  
...  

Background: Ketamine produces significant rapid-onset and robust antidepressant effects in patients with major depressive disorder. However, this drug also has transient cardiovascular stimulatory effects, and there are limited data about potential predictors of these cardiovascular effects. Methods: A total of 135 patients with unipolar and bipolar depression received a total of 741 ketamine infusions (0.5 mg/kg over 40 min). Blood pressure and pulse were monitored every 10 min during the infusions and 30 min after the infusions. Depressive, psychotomimetic and dissociative symptom severity was assessed at baseline and 4 hours after each infusion. Results: The maximum blood pressure and pulse values were observed at 30–40 min during infusions. The largest mean systolic/diastolic blood pressure increases were 7.4/6.0 mmHg, and the largest mean pulse increase was 1.9 beats per min. No significant change in blood pressure and pulse was found in the second to sixth infusions compared with the first infusion. Patients who were older (age⩾50 years), hypertensive and receiving infusions while exhibiting dissociative symptoms showed greater maximal changes in systolic and diastolic blood pressure than patients who were younger (age<50 years), normotensive and without dissociative symptoms (all p < 0.05). Hypertensive patients had less elevation of pulse than normotensive patients ( p < 0.05). Ketamine dosage was positively correlated with changes in systolic and diastolic blood pressure (all p < 0.05). Conclusions: Blood pressure and pulse elevations following subanaesthetic ketamine infusions are transient and do not cause serious cardiovascular events. Older age, hypertension, large ketamine dosage and dissociative symptoms may predict increased ketamine-induced cardiovascular effects.


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