Translational Psychiatry
April 21, 2026
Paul A Parcon, Amanda Bardhoshi, Amanda Olsen-Dufour et al.
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is a robust, rapid-acting antidepressant whose molecular effects have not been fully elucidated. Phosphodiesterase-4 (PDE4), which terminates cyclic adenosine monophosphate (cAMP) activity, may underlie antidepressant response. In particular, previous studies found that whole brain binding of the positron emission tomography (PET)...
Research Square
February 12, 2026
Jenessa N Johnston, Greg Jones, Shiyong Peng et al.
Rapid-acting antidepressants like ketamine and serotonergic psychedelics show promise for treatment-resistant depression (TRD), but the molecular mechanisms that contribute to their therapeutic effects remain unclear. Induced pluripotent stem cells (iPSCs) offer a platform to model human cortical neurons and investigate drug effects in a human-relevant system. Here, iPSCs from individuals with...
Translational Psychiatry
November 18, 2025
Jenessa N Johnston, Peixiong Yuan, Bashkim Kadriu et al.
2 citations
Treatment-resistant depression (TRD) is associated with worse clinical outcomes and longer course of illness. However, TRD is more difficult to model in animal phenotypes, suggesting that other experimental and translational models must be considered to properly address and research novel therapeutics. Reelin, an endogenous glycoprotein downregulated in depression, has shown rapid...
Frontiers in Psychiatry
September 2, 2025
Mina Kheirkhah, Nastasia McDonald, Julia Aepfelbacher et al.
1 citation
Introduction: This is the first randomized controlled trial to use both qualitative and quantitative methods to evaluate the effects of a combined sensory intervention that included mindfulness, music, and a light-occluding eye mask during antidepressant-dose ketamine treatment for depression. Methods: Forty-three participants with unipolar depressive disorder enrolled in the study; 22...
medRxiv
August 28, 2025
Franziska Stadler, Johan Saelens, Ioline D. Henter et al.
preprint
This international online study (N=759) examined the acute, subacute, and long-term effects of psychedelic drug use on cognitive performance and mental health. Participants completed cognitive tasks assessing working memory, selective attention, and visual/spatial perception, as well as questionnaires assessing mental health outcomes and quality of life. Based on self-reported substance use,...
Journal of Affective Disorders
December 15, 2024
Rodrigo Machado‐Vieira, Gregory H Jones, Alan C. Courtes et al.
Fatigue is a multidimensional condition that may overlap with depression. Initial studies found that fatigue responds in only a limited way to standard monoaminergic antidepressants and mood stabilizers but does respond positively to intravenous (IV) racemic (R,S)-ketamine (ketamine). However, IV ketamine's use is limited by cost and access barriers. To date, no study has evaluated intranasal...
Neuroscience and Biobehavioral Reviews
July 1, 2024
Mina Kheirkhah, Allison C. Nugent, Alicia A Livinski et al.
13 citations
Music and ketamine are both known to affect therapeutic outcomes, but few studies have investigated their co-administration. This scoping review describes the existing literature on the joint use of music and ketamine-or esketamine (the S(+) enantiomer of ketamine)-in humans. The review considers that extant studies have explored the intersection of ketamine/esketamine and music in healthy...
Pharmacology and Therapeutics
May 1, 2023
J. Johnston, Ioline D. Henter, Carlos A. Zarate
106 citations
Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist first developed as an anesthetic, has shown significant promise as a medication with rapid antidepressant properties in treatment-resistant depression. However, concerns such as adverse side effects and potential misuse liability have limited its widespread use. Racemic ketamine has two enantiomers—(S)- and (R)-ketamine—that appear...
Drug Discovery Today
February 1, 2023
J. Johnston, Maximillian Greenwald, Ioline D. Henter et al.
64 citations
Well-established animal models of depression have described a proximal relationship between stress and central nervous system (CNS) inflammation – a relationship mirrored in the peripheral inflammatory biomarkers of individuals with depression. Evidence also suggests that stress-induced proinflammatory states can contribute to the neurobiology of treatment-resistant depression. Interestingly,...
Neuropharmacology
January 13, 2023
Jenessa N Johnston, Bashkim Kadriu, Josh Allen et al.
64 citations
The discovery of ketamine as a rapid-acting antidepressant spurred significant research to understand its underlying mechanisms of action and to identify other novel compounds that may act similarly. Serotonergic psychedelics (SPs) have shown initial promise in treating depression, though the challenge of conducting randomized controlled trials with SPs and the necessity of long-term clinical...
Discover Mental Health
April 15, 2022
Mani Yavi, Holim Lee, Ioline D. Henter et al.
150 citations
-enantiomer, intranasal esketamine, for the treatment of major depressive disorder (MDD). Initial studies found that a single subanesthetic-dose IV ketamine infusion rapidly (within one day) improved depressive symptoms in individuals with MDD and bipolar depression, with antidepressant effects lasting three to seven days. In 2019, esketamine received FDA approval as an adjunctive treatment for...
CNS Drugs
May 1, 2021
Ioline D. Henter, Lawrence T. Park, Carlos A. Zarate
The efficacy of standard antidepressants is limited for many patients with mood disorders such as major depressive disorder (MDD) and bipolar depression, underscoring the urgent need to develop novel therapeutics. Both clinical and preclinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders. In particular, rapid reductions in depressive symptoms...
The International Journal of Neuropsychopharmacology
November 16, 2020
Bashkim Kadriu, Maximillian Greenwald, Ioline D. Henter et al.
98 citations
BACKGROUND: The glutamatergic modulator ketamine has created a blueprint for studying novel pharmaceuticals in the field. Recent studies suggest that "classic" serotonergic psychedelics (SPs) may also have antidepressant efficacy. Both ketamine and SPs appear to produce rapid, sustained antidepressant effects after a transient psychoactive period. METHODS: This review summarizes areas of...
Acta Psychiatrica Scandinavica
July 17, 2020
Lawrence T. Park, David A. Luckenbaugh, Steven Pennybaker et al.
23 citations
OBJECTIVE: Ketamine's effects on different dimensions of depressive symptomatology, including typical/melancholic and atypical depression, remain largely unknown. This study examined the effects of a single intravenous dose of ketamine on general depressive symptoms (measured using the Montgomery-Asberg Depression Rating Scale (MADRS), typical/melancholic symptoms (measured using the MADRS5),...
Advances in pharmacology (San Diego, Calif.)
2020
Bashkim Kadriu, Elizabeth D. Ballard, Ioline D. Henter et al.
35 citations
As a field, psychiatry is undergoing an exciting paradigm shift toward early identification and intervention that will likely minimize both the burden associated with severe mental illnesses as well as their duration. In this context, the rapid-acting antidepressant ketamine has revolutionized our understanding of antidepressant response and greatly expanded the pharmacologic armamentarium for...
The International Journal of Neuropsychopharmacology
November 14, 2018
Bashkim Kadriu, Laura Musazzi, Ioline D. Henter et al.
164 citations
The underlying neurobiological basis of major depressive disorder remains elusive due to the severity, complexity, and heterogeneity of the disorder. While the traditional monoaminergic hypothesis has largely fallen short in its ability to provide a complete picture of major depressive disorder, emerging preclinical and clinical findings suggest that dysfunctional glutamatergic...
October 23, 2018
Bashkim Kadriu, Subha Subramanian, Z. Deng et al.
preprint
Major depressive disorder (MDD) is a highly prevalent and debilitating illness and closely linked to suicide risk. Currently available antidepressants take weeks to work and have low remission rates; indeed, about a third of individuals with MDD fail to fully remit in response to these agents. Novel therapies that target the glutamatergic system—such as ketamine—offer rapid antidepressant...
Neuropsychiatric Disease and Treatment
October 1, 2018
Wallace C. Duncan, Elizabeth E. Slonena, Nadia S. Hejazi et al.
17 citations
PURPOSE: This study examined the links between 24-hour activity patterns (specifically, amplitude and timing of wrist activity) and the persisting qualities of clinical antidepressant response to the glutamatergic modulator ketamine. METHODS: Twenty-four-hour activity patterns were compared across 5 days of 24-hour activity rhythms in patients with major depressive disorder who displayed either...
Harvard Review of Psychiatry
February 21, 2018
Ioline D. Henter, Rafael Teixeira de Sousa, Carlos A. Zarate
94 citations
LEARNING OBJECTIVE: After participating in this activity, learners should be better able to evaluate the evidence supporting the antidepressant effects of glutamatergic modulators.Both preclinical and clinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders such as bipolar depression and major depressive disorder. In particular, rapid reductions...
The Annual Review of Pharmacology and Toxicology
January 6, 2014
Mark J. Niciu, Ioline D. Henter, David A. Luckenbaugh et al.
166 citations
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression. These effects are in direct contrast to the more modest effects seen after weeks of treatment with classic monoaminergic antidepressants. Numerous open-label and case studies similarly validate ketamine's antidepressant...
Harvard Review of Psychiatry
August 1, 2010
Carlos A. Zarate, Rodrigo Machado‐Vieira, Ioline D. Henter et al.
226 citations
Mood disorders such as bipolar disorder and major depressive disorder are common, chronic, and recurrent conditions affecting millions of individuals worldwide. Existing antidepressants and mood stabilizers used to treat these disorders are insufficient for many. Patients continue to have low remission rates, delayed onset of action, residual subsyndromal symptoms, and relapses. New therapeutic...
The Journal of Clinical Psychiatry
July 13, 2010
Nancy Diazgranados, Lobna Ibrahim, Nancy E. Brutsché et al.
563 citations
OBJECTIVE: Suicidal ideation is a medical emergency, especially when severe. Little research has been done on pharmacologic interventions that could address this problem. Ketamine, an N-methyl-D-asparate antagonist, has been reported to have antidepressant effects within hours. We examined the effects of a single dose of ketamine on suicidal ideation in subjects with treatment-resistant major...