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Pharmaceuticals
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Lithium in Psychiatric Therapy: Celebrating 75th Anniversary
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Lithium in Psychiatric Therapy: Celebrating 75th Anniversary

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 28 August 2025 | Viewed by 18112

Special Issue Editors

Prof. Dr. Janusz K. Rybakowski

E-Mail Website
Guest Editor
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland
Interests: psychopharmacology; bipolar disorder; lithium
Dr. Ewa Ferensztajn-Rochowiak

E-Mail Website
Guest Editor
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland
Interests: bipolar disorder; lithium; temperament

Special Issue Information

Dear Colleagues,

This Special Issue celebrates the 75th anniversary of introducing lithium into modern psychiatry, hallmarked by a seminal publication of John Cade in the Medical Journal of Australia in 1949.

In such vein, we call for papers (especially review papers) demonstrating how, after three-quarters of a century, lithium has been consolidated as one of the most important drugs in psychiatry nowadays. Therefore, historical accounts showing developments in the lithium treatment of mania, depression (including the augmentation of antidepressant drugs), and lithium prophylaxis for mood disorders are welcome.

The chronicle tales of the anti-suicidal, immunomodulatory, antiviral, and neuroprotective (antidementia) effects of lithium are invited.  The papers in this Special Issue may cover a number of areas, such as the expansion of genetic studies on lithium, fluctuating views on the adverse effects of this ion (e.g., on kidney and thyroid function), or the use of lithium in pregnancy. Any other developmental stories about lithium over the past 75 years (e.g., a history of IGSLI) are welcome.

Prof. Dr. Janusz K. Rybakowski
Dr. Ewa Ferensztajn-Rochowiak
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lithium
  • bipolar disorder
  • mania
  • depression
  • the prevention of recurrences
  • suicide
  • dementia
  • immunomodulation
  • genetics
  • kidney function

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Published Papers (5 papers)

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Review

15 pages, 1007 KiB  
Review
An Overview of the Effects of Lithium on Alzheimer’s Disease: A Historical Perspective
by Marcia Radanovic, Monique Patricio Singulani, Vanessa de Jesus R. De Paula, Leda Leme Talib and Orestes Vicente Forlenza
Pharmaceuticals 2025, 18(4), 532; https://doi.org/10.3390/ph18040532 - 5 Apr 2025
Viewed by 4978
Abstract
Lithium was introduced into psychiatric practice in the late nineteenth century and has since become a standard treatment for severe psychiatric disorders, particularly those characterized by psychotic agitation. It remains the most effective agent for managing acute mania and preventing relapses in bipolar [...] Read more.
Lithium was introduced into psychiatric practice in the late nineteenth century and has since become a standard treatment for severe psychiatric disorders, particularly those characterized by psychotic agitation. It remains the most effective agent for managing acute mania and preventing relapses in bipolar disorder. Despite potential adverse effects, lithium’s use should be carefully considered relative to other treatment options, as these alternatives may present distinct safety and tolerability profiles. The World Health Organization classifies lithium salts as ‘essential’ medications for inclusion in global healthcare systems. Over the past two decades, the growing recognition of lithium’s efficacy—extending beyond mood stabilization to include reducing suicide risk and inducing neuroprotection—has led to its incorporation into clinical practice guidelines. Current research, particularly from translational models, suggests that lithium’s pleiotropic effects benefit not only mental and brain health but also other organs and systems. This supports its potential as a therapeutic candidate for neurological conditions, particularly those associated with neurodegenerative processes. This article will discuss the historical background, discovery, and early experimentation of lithium in psychiatry. We will also review its mechanisms of action and discuss its potential in the treatment and prevention of neurodegenerative disorders, focusing on Alzheimer’s disease. Full article
(This article belongs to the Special Issue Lithium in Psychiatric Therapy: Celebrating 75th Anniversary)
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Graphical abstract

20 pages, 363 KiB  
Review
The Mechanisms of Lithium Action: The Old and New Findings
by Kosma Sakrajda and Janusz K. Rybakowski
Pharmaceuticals 2025, 18(4), 467; https://doi.org/10.3390/ph18040467 - 26 Mar 2025
Viewed by 3942
Abstract
Despite lithium’s presence in modern psychiatry for three-quarters of a century, the mechanisms of its therapeutic action have not been fully elucidated. This article presents the evolution of the views on these mechanisms, and both the old and new findings are discussed. Among [...] Read more.
Despite lithium’s presence in modern psychiatry for three-quarters of a century, the mechanisms of its therapeutic action have not been fully elucidated. This article presents the evolution of the views on these mechanisms, and both the old and new findings are discussed. Among the old mechanisms, lithium’s effect on the purinergic system; electrolyte metabolism; membrane transport; and second messenger systems, namely, cyclic nucleotide and phosphatidylinositol (PI), glycogen synthase kinase-3beta (GSK-3β), brain-derived neurotrophic factor, and neurotransmitters, are discussed. The new data were obtained from in vitro studies, molecular biology, and genetic research. They showed the effects of lithium on the immune system, biological rhythms, telomere functions, and mitochondria. In this article, each lithium mechanism is considered in the light of its association with the pathogenesis of bipolar disorder or/and as a marker of the lithium response. Although not exhaustive, this review elucidates the multiple potential mechanisms of lithium action. It was also observed that many seemingly “old” mechanisms have experienced a resurgence in research conducted during the 21st century. Additionally, many studies converged on the previously postulated mechanisms of lithium inhibiting GSK-3β and PI. Full article
(This article belongs to the Special Issue Lithium in Psychiatric Therapy: Celebrating 75th Anniversary)
14 pages, 637 KiB  
Review
History of Suicide Prevention with Lithium Treatment
by Leonardo Tondo and Ross J. Baldessarini
Pharmaceuticals 2025, 18(2), 258; https://doi.org/10.3390/ph18020258 - 14 Feb 2025
Viewed by 3186
Abstract
Suicidal behavior is prevalent among individuals with psychiatric illnesses, especially mood, substance abuse, and psychotic disorders. Over the past several decades, lithium treatment in patients with mood disorders has been increasingly used to lower the risk of suicidal behavior. This overview considers that [...] Read more.
Suicidal behavior is prevalent among individuals with psychiatric illnesses, especially mood, substance abuse, and psychotic disorders. Over the past several decades, lithium treatment in patients with mood disorders has been increasingly used to lower the risk of suicidal behavior. This overview considers that lithium treatment has the most abundant evidence of reducing suicidal behavior. It also examines the hypothesis that higher natural lithium levels in drinking water correlate with reduced suicide rates. We report findings from trials comparing lithium treatment with its absence, placebos, or alternative treatments for suicide prevention and address substantial challenges in such studies. The mechanisms behind lithium’s potentially protective effects against suicidal behavior remain uncertain. However, it is believed that lithium may produce anti-aggressive/anti-impulsive effects that directly contribute to anti-suicidal outcomes and mood-stabilizing effects that indirectly lead to the same results. Anti-aggressive/anti-impulsive effects may be obtained at the very low levels of lithium present in drinking water, whereas recurrence prevention may be attained at therapeutic levels. Full article
(This article belongs to the Special Issue Lithium in Psychiatric Therapy: Celebrating 75th Anniversary)
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Figure 1

10 pages, 913 KiB  
Review
Trace Lithium for Suicide Prevention and Dementia Prevention: A Qualitative Review
by Takeshi Terao, Hirofumi Hirakawa, Masaaki Muronaga, Toshihiko Izumi and Kentaro Kohno
Pharmaceuticals 2024, 17(11), 1486; https://doi.org/10.3390/ph17111486 - 5 Nov 2024
Cited by 2 | Viewed by 2402
Abstract
Background: Anti-manic effects of lithium and the nature of trace element in lithium were first observed in 1949. In this review, we explore the potential effects of trace lithium in the prevention of suicide and dementia. Methods: This is a qualitative [...] Read more.
Background: Anti-manic effects of lithium and the nature of trace element in lithium were first observed in 1949. In this review, we explore the potential effects of trace lithium in the prevention of suicide and dementia. Methods: This is a qualitative and non-systematic review. Results: While most studies to date have been cross-sectional, limiting the establishment of causal relationships, the potential benefits of trace lithium for suicide prevention and dementia prevention are notable, especially in the absence of radical treatments for suicide and dementia. Furthermore, trace lithium appears to lack many of the adverse effects associated with so-called therapeutic lithium levels. Conclusions: The present findings suggest that trace lithium may be associated with lower suicide rates and reduced dementia rates. Probably, trace lithium may inhibit testosterone and thereby mitigate aggression and impulsivity and decrease suicide. Also, trace lithium may inhibit GSK-3β and thereby lower amyloid β and tau hyperphosphorylation and inhibit pro-inflammatory cytokines such as IL 6 and IL 8 and thereby mitigate inflammation, whereas trace lithium may promote BDNF and neurogenesis in the general population. Full article
(This article belongs to the Special Issue Lithium in Psychiatric Therapy: Celebrating 75th Anniversary)
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Graphical abstract

9 pages, 229 KiB  
Review
What Patients with Bipolar Disorder Need to Know about Lithium
by Robert M. Post and Janusz K. Rybakowski
Pharmaceuticals 2024, 17(9), 1223; https://doi.org/10.3390/ph17091223 - 17 Sep 2024
Cited by 3 | Viewed by 2691
Abstract
Lithium is the superior first-line treatment for bipolar disorder (BD). Yet the percentage of patients receiving lithium is abysmally low, especially in the US. Since psychiatrists have failed to place lithium in its appropriate role, we make the case that patients with BD [...] Read more.
Lithium is the superior first-line treatment for bipolar disorder (BD). Yet the percentage of patients receiving lithium is abysmally low, especially in the US. Since psychiatrists have failed to place lithium in its appropriate role, we make the case that patients with BD themselves need to be better educated about the unique characteristics and pre-eminence of the drug so that it can be used more often and appropriately. Lithium has a highly unfavorable popular reputation among would-be patients and many psychiatrists. Thus, a direct appeal to patients with BD appears appropriate to try to remediate this situation. The unique assets of lithium are underappreciated or not well known. Conversely, the side effects profile of lithium are overestimated. Here, we make the case that lithium’s image needs to be revised not only with better and more accurate information but also with a wholesale renaming and rebranding of the drug. We will not only outline the unique qualities and new information about the side effects of the drug but attempt to change some of the terminology conventionally used to refer to lithium so that its use may be appropriately applied earlier and at an increased frequency for patients with BD. Full article
(This article belongs to the Special Issue Lithium in Psychiatric Therapy: Celebrating 75th Anniversary)
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