• Considerable evidence suggests that the acute effects of antidepressant treatments on brain norepinephrine (NE) and serotonin (5-HT) systems cannot account fully for their delayed therapeutic action. This review evaluates the effects of long-term antidepressant treatment on biogenic amine metabolism and on various indexes of presynaptic and postsynaptic receptor function. In contrast to variable effects on NE and 5-HT turnover and on presynaptic receptor sensitivity, almost all long-term antidepressant treatments produce consistent alterations in a number of measures of postsynaptic amine receptor sensitivity. Longterm treatment has been found to reduce β-adrenergic sensitivity while enhancing responses to serotonergic and α-adrenergic stimulation, suggesting that modulation of receptor sensitivity may be a mechanism of action common to tricyclic antidepressants, "atypical" antidepressants, monoamine oxidase inhibitors, and electroconvulsive therapy. These findings provide support for hypotheses of amine receptor abnormalities in depression and indicate the need for expanded studies of amine receptor function in patients.

Receptor Sensitivity and the Mechanism of Action of Antidepressant Treatment: Implications for the Etiology and Therapy of Depression

Psychotropic drugs acting on monoamine neurotransmission are major pharmacological treatments for neuropsychiatric conditions such as schizophrenia, depression, bipolar disorder, Tourette syndrome, ADHD, and Alzheimer disease. Independent lines of research involving biochemical and behavioral approaches in normal and/or genetically modified mice provide converging evidence for an involvement of the signaling molecules Akt and glycogen synthase kinase-3 (GSK3) in the regulation of behavior by dopamine and serotonin (5-HT). These signaling molecules have also received attention for their role in the actions of psychoactive drugs such as antidepressants, antipsychotics, lithium, and other mood stabilizers. Furthermore, investigations of the mechanism by which D2 dopamine receptors regulate Akt/GSK3 signaling strongly support the physiological relevance of a new modality of G protein-coupled receptor (GPCR) signaling involving the multifunctional scaffolding protein beta-arrestin 2. Elucidation of the contribution of multiple signaling pathways to the action of psychotropic drugs may provide a better biological understanding of psychiatric disorders and lead to more efficient therapeutics.

/pdf/akt-gsk3-signaling-in-the-action-of-psychotropic-drugs-4dnx9cvusl.pdf

Akt/GSK3 signaling in the action of psychotropic drugs.

Objective: More than 40% of patients with major depressive disorder do not achieve remission even after two optimally delivered trials of antidepressant medications. This study compared the effectiveness of lithium versus triiodothyronine (T 3 ) augmentation as a third-step treatment for patients with major depressive disorder. Method: A total of 142 adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or who were intolerant to an initial prospective treatment with citalopram and a second switch or augmentation trial were randomly assigned to augmentation with lithium (up to 900 mg/day; N=69) or with T 3 (up to 50 μg/day; N=73) for up to 14 weeks. The primary outcome measure was whether participants achieved remission, which was defined as a score ≤7 on the 17-item Hamilton Depression Rating Scale. Results: After a mean of 9.6 weeks (SD=5.2) of treatment, remission rates were 15.9% with lithium augmentation and 24.7% with T 3 augmentation, although the difference be...

https://ajp.psychiatryonline.org/doi/pdf/10.1176/ajp.2006.163.9.1519

A Comparison of Lithium and T 3 Augmentation Following Two Failed Medication Treatments for Depression: A STAR*D Report

Article abstract Depressive disorders (DDs) are the most common type of psychiatric co-morbidity in patients with epilepsy. They are more likely to occur in patients with partial seizure disorders of temporal and frontal lobe origin and are more frequent among patients with poorly controlled seizures. Despite their relatively high prevalence, DDs remain unrecognized and untreated in a large proportion of patients. This article highlights the evidence of a close association between DDs and epilepsy, beginning with the bi-directional relationship between the two disorders. Not only are patients with epilepsy more likely to experience a DD, but a history of DD preceding the onset of the seizure disorder is more likely to be identified in patients with epilepsy than in a control group. In support of these observations, we review data from animal models of epilepsy showing that decreased activity of serotonin, norepinephrine, dopamine, and GABA facilitate the kindling process of seizure foci, worsen seizure frequency and severity, and are reversed or blocked by antidepressant drugs. Decreased activity of these neurotransmitters is a pivotal pathogenic mechanism of DDs and forms the basis of their pharmacotherapy. Thus, DDs and epilepsy may share common pathogenic mechanisms that facilitate the occurrence of one in the presence of the other. Contrary to long-held beliefs by patients and clinicians alike, in the sense that DDs are a "normal reaction" to the obstacles posed by epilepsy, we review evidence that points to their biologic or endogenous nature. We find a genetic predisposition to DDs, as evidenced by the frequent family history of mood disorders in these patients. Neuroimaging and neuropsychological data support a frontal lobe dysfunction in DDs, and a recent study documents concomitant dysfunction of mesial temporal structures. Depressive disorders have various clinical presentations, some typical of the different types of mood disorders in non-epileptic patients, others constituting rather frequent atypical presentations that can easily go unrecognized. A review of the pharmacologic treatment of DDs in epilepsy highlights the lack of scientific data and points to the empirical form in which these patients have been treated up to the present time. Contrary to clinicians' fears, most antidepressant drugs are safe in patients with epilepsy.

Depression and epilepsy: How closely related are they?

Lithium is used as treatment for bipolar disorder with particular efficacy in the treatment of mania. Lithium inhibits glycogen synthase kinase 3β (GSK-3β) directly or indirectly via stimulation of the kinase Akt-1. We therefore investigated the possibility that transgenic mice overexpressing GSK-3β could be of relevance to model bipolar disorder. Transgenic mice showed hypophagia, an increased general locomotor activity, and decreased habituation as assessed in an open field, an increased acoustic startle response, and again decreased habituation. The forced swim test revealed a reduced immobility in transgenic mice, but this is probably related to the hyperactivity of the animals. There were no differences in baseline and stress-induced increases of plasma adrenocorticotrophic hormone and corticosterone levels. Molecular analysis suggests compensatory mechanisms in the striatum of these transgenic mice for the overload of active GSK-3β by dimming the endogenous GSK-3β signaling pathway via upregulation of Akt-1 expression. Brain-derived neurotrophic factor protein levels were increased in the hippocampus of the transgenic mice. This suggests some kind of compensatory mechanism to the observed reduction in brain weight, which has been related previously to a reduced size of the somatodendritic compartment. Together, in mice overexpressing GSK-3β, specific intracellular signaling pathways are affected, which is accompanied by altered plasticity processes and increased activity and reactivity, whereas habituation processes seem to be decreased. The behavioral observations led to the suggestion that the model at hand recapitulates hyperactivity as observed in the manic phase of bipolar disorder.

https://www.jneurosci.org/content/jneuro/26/35/9022.full.pdf

Transgenic mice overexpressing glycogen synthase kinase 3beta: a putative model of hyperactivity and mania

Eight patients suffering from a major unipolar depression and having field to respond to treatment for three weeks or more with tricyclic antidepressants were given lithium. All eight patients experienced a remarkable relief of their depression within 48 hours. This rapid antidepressant effect of lithium in "treatment-resistant' patients might be due to the enhancement of the efficacy of the central serotoninergic system, unveiling the tricyclic antidepressant-induced sensitization of the serotoninergic postsynaptic receptors.

Lithium induces rapid relief of depression in tricyclic antidepressant drug non-responders.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

A Mayer

Author Tools

Chat about Author

Papers

Lithium induces rapid relief of depression in tricyclic antidepressant drug non-responders.