Repurposing Potential of Ketamine: Opportunities and Challenges

Gautam, CS; Mahajan, Sonia; Sharma, Jatin; Singh, Harmanjit; Singh, Jagjit

doi:10.4103/ijpsym.ijpsym_228_19

Cited by 24 publications

(24 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As mentioned before [26], the improved prefrontal cortex glutamate homeostasis, increased synaptic functioning and enhanced BDNF signaling indicate that esketamine has the potential to be repurposed or further investigated as a treatment for OCD, SUD, PSTD and ED-disorders which have been recorded by some authors to meet the so-called definition of "internalising disorders". These are conditions characterized by internal distress that include the DSM-5 [99] diagnoses of generalized anxiety disorder, social anxiety disorder, MDD, panic disorder and OCD, which are all thought to share the common trait of neuroticism.…”

Section: Possible Advantages Of Ketamine and Esketamine Compared With Current Treatmentsmentioning

confidence: 88%

“…Other possible cellular targets of ketamine include opioid (mu, delta and kappa) receptors, and ketamine binding to these receptors has been proposed to contribute to its anti-suicidal and antidepressant effects [16]. A better understanding of the impact of ketamine binding on serotonin, opioid, dopamine and cholinergic receptors [22,26] is needed for a full assessment of the therapeutic potentials of ketamine, especially with regard to mental health disorders. Of note, different preclinical models reported that it is unlikely that NMDA inhibition alone could play a major role in the antidepressant effects of (R,S)-ketamine, opening the door for future studies and major developments [27].…”

Section: Ketamine's Mechanisms Of Actionmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature

et al. 2021

View full text Add to dashboard Cite

The obsessive–compulsive spectrum refers to disorders drawn from several diagnostic categories that share core features related to obsessive–compulsive disorder (OCD), such as obsessive thoughts, compulsive behaviors and anxiety. Disorders that include these features can be grouped according to the focus of the symptoms, e.g., bodily preoccupation (i.e., eating disorders, ED) or impulse control (i.e., substance use disorders, SUD), and they exhibit intriguing similarities in phenomenology, etiology, pathophysiology, patient characteristics and clinical outcomes. The non-competitive N-methyl-D-aspartate receptor (NMDAr) antagonist ketamine has been indicated to produce remarkable results in patients with treatment-resistant depression, post-traumatic stress disorder and OCD in dozens of small studies accrued over the past decade, and it appears to be promising in the treatment of SUD and ED. However, despite many small studies, solid evidence for the benefits of its use in the treatment of OCD spectrum and addiction is still lacking. Thus, the aim of this perspective article is to examine the potential for ketamine and esketamine in treating OCD, ED and SUD, which all involve recurring and intrusive thoughts and generate associated compulsive behavior. A comprehensive and updated overview of the literature regarding the pharmacological mechanisms of action of both ketamine and esketamine, as well as their therapeutic advantages over current treatments, are provided in this paper. An electronic search was performed, including all papers published up to April 2021, using the following keywords (“ketamine” or “esketamine”) AND (“obsessive” OR “compulsive” OR “OCD” OR “SUD” OR “substance use disorder” OR “addiction” OR “craving” OR “eating” OR “anorexia”) NOT review NOT animal NOT “in vitro”, on the PubMed, Cochrane Library and Web of Science online databases. The review was conducted in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The use and efficacy of ketamine in SUD, ED and OCD is supported by glutamatergic neurotransmission dysregulation, which plays an important role in these conditions. Ketamine’s use is increasing, and preliminary data are optimistic. Further studies are needed in order to better clarify the many unknowns related to the use of both ketamine and esketamine in SUD, ED and OCD, and to understand their long-term effectiveness.

show abstract

Section: Possible Advantages Of Ketamine and Esketamine Compared With Current Treatmentsmentioning

confidence: 88%

Section: Ketamine's Mechanisms Of Actionmentioning

confidence: 99%

Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The high number of articles retrieved as well as the presence of a definite trend for larger and more robust studies emphasise the interest of the scientific community to this research area, which may have significant implications for routine clinical practise. Such awareness likely stems from two important observations: firstly, statins are among the most commonly prescribed medications ( 139 ), hence the discovery that their use is associated with either antidepressant or depressogenic effects would have a very substantial impact on public health; and secondly, the relative lack of any breakthrough development of new antidepressant drugs capable of targeting alternative biological pathways ( 140 ), or that are free from concerns about adverse events and misuse [e.g., ketamine ( 141 )], immediately make the potential use of statins especially appealing.…”

Section: Discussionmentioning

confidence: 99%

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

et al. 2021

View full text Add to dashboard Cite

Background: Depression is a leading cause of disability, burdened by high levels of non-response to conventional antidepressants. Novel therapeutic strategies targeting non-monoaminergic pathways are sorely needed. The widely available and safe statins have several putative mechanisms of action, especially anti-inflammatory, which make them ideal candidates for repurposing in the treatment of depression. A large number of articles has been published on this topic. The aim of this study is to assess this literature according to evidence-based medicine principles to inform clinical practise and research.Methods: We performed a systematic review of the electronic databases MEDLINE, CENTRAL, Web of Science, CINAHL, and ClinicalTrials.gov, and an unstructured Google Scholar and manual search, until the 9th of April 2021, for all types of clinical studies assessing the effects of statins in depression.Results: Seventy-two studies were retrieved that investigated the effects of statins on the risk of developing depression or on depressive symptoms in both depressed and non-depressed populations. Fifteen studies specifically addressed the effects of statins on inflammatory-related symptoms of anhedonia, psychomotor retardation, anxiety, and sleep disturbances in depression. Most studies suggested a positive effect of statins on the occurrence and severity of depression, with fewer studies showing no effect, while a minority indicated some negative effects.Limitations: We provide a narrative report on all the included studies but did not perform any quantitative analysis, which limits the strength of our conclusions.Conclusions: Robust evidence indicates that statins are unlikely to lead to depressive symptoms in the general population. Promising data suggest a potential role for statins in the treatment of depression. Further clinical studies are needed, especially in specific subgroups of patients identified by pre-treatment assessments of inflammatory and lipid profiles.

show abstract

“…With a detailed inspection and the application of a power law fit, it is revealed (see Figure 7 ) that for ATC groups, such as J (antibacterials and antivirals), R (nasal preparations) and S (ophthalmologicals), the diversity is smaller compared to such cases as P (anti-parasitic products). The scaling exponent values for some ATC groups align with medical information about the wide range of diseases caused by parasites [ 32 ] for which drugs (with high diversity in targets) of group P are indicated, while the antibacterial and antiviral, ophthalmologic and nasal preparations groups do not follow this high diversity rate [ 33 , 34 ].…”

Section: Resultsmentioning

confidence: 94%

The Complex Structure of the Pharmacological Drug–Disease Network

López-Rodríguez

Reyes-Manzano

Guzmán‐Vargas

et al. 2021

Entropy

View full text Add to dashboard Cite

The complexity of drug–disease interactions is a process that has been explained in terms of the need for new drugs and the increasing cost of drug development, among other factors. Over the last years, diverse approaches have been explored to understand drug–disease relationships. Here, we construct a bipartite graph in terms of active ingredients and diseases based on thoroughly classified data from a recognized pharmacological website. We find that the connectivities between drugs (outgoing links) and diseases (incoming links) follow approximately a stretched-exponential function with different fitting parameters; for drugs, it is between exponential and power law functions, while for diseases, the behavior is purely exponential. The network projections, onto either drugs or diseases, reveal that the co-ocurrence of drugs (diseases) in common target diseases (drugs) lead to the appearance of connected components, which varies as the threshold number of common target diseases (drugs) is increased. The corresponding projections built from randomized versions of the original bipartite networks are considered to evaluate the differences. The heterogeneity of association at group level between active ingredients and diseases is evaluated in terms of the Shannon entropy and algorithmic complexity, revealing that higher levels of diversity are present for diseases compared to drugs. Finally, the robustness of the original bipartite network is evaluated in terms of most-connected nodes removal (direct attack) and random removal (random failures).

show abstract

Repurposing Potential of Ketamine: Opportunities and Challenges

Cited by 24 publications

References 70 publications

Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature

Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

The Complex Structure of the Pharmacological Drug–Disease Network

Contact Info

Product

Resources

About