Side Effects of esketamine nasal spray: A Synthesis of Findings from 14 Studies

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Original Abstract of the Article

Major Research Findings

Esketamine nasal spray has shown promise as a treatment for treatment-resistant depression. However, it’s essential to note that esketamine nasal spray may induce side effects. A study in 2 reported that side effects from esketamine nasal spray were most pronounced two weeks after treatment initiation and then gradually subsided. Research in 4 demonstrated the efficacy of esketamine nasal spray in patients with treatment-resistant depression who also have substance use disorder.

Reasons for Side Effects

Side effects associated with esketamine nasal spray are believed to stem from its inhibitory effect on NMDA receptors. These receptors play a crucial role in neurotransmitter release within the brain, and their inhibition can lead to irregularities in neurotransmission.

Common Side Effects

Dissociative Symptoms

A common side effect of esketamine nasal spray is dissociative symptoms. A study in 4 indicated that 38% of patients experienced dissociative symptoms, which can manifest as a loss of reality, sensory distortions, and altered perceptions of time.

Sedation

Esketamine nasal spray may also cause sedation. In a study in 4 , 26% of patients experienced sedation, which could present as drowsiness and fatigue.

Nausea and Vomiting

Esketamine nasal spray can lead to nausea and vomiting. A study in 7 suggested that dysgeusia (distorted taste) caused by esketamine nasal spray might contribute to nausea and vomiting.

Dysgeusia

Esketamine nasal spray may induce dysgeusia (distorted taste). According to a study in 7 , dysgeusia from esketamine nasal spray often presents as a metallic or bitter taste.

Hypertension and Tachycardia

Esketamine nasal spray can trigger hypertension and tachycardia. A study in 8 reported side effects such as hypertension, tachycardia, increased salivation, and increased intracranial pressure after intravenous administration of esketamine nasal spray.

Measures to Address Side Effects

Dissociative Symptoms

Dissociative symptoms can sometimes be alleviated by resting for a while after esketamine nasal spray administration. In some cases, medication such as anti-anxiety drugs might be prescribed.

Sedation

If sedation is severe, measures like reducing the dosage of esketamine nasal spray or extending the interval between administrations may be taken.

Nausea and Vomiting

To prevent nausea and vomiting, it is effective to take antiemetics before administering esketamine nasal spray. 7 Additionally, addressing dysgeusia as a contributing factor to nausea and vomiting might be necessary.

Dysgeusia

Dysgeusia often subsides within a few days to a few weeks after esketamine nasal spray administration. However, if dysgeusia persists, it is advisable to consult a specialist.

Comparison between Studies

Commonalities

Multiple studies have demonstrated that esketamine nasal spray is effective in treating treatment-resistant depression. It has also been established that esketamine nasal spray has the potential to induce side effects such as dissociative symptoms and sedation.

Differences

The incidence and severity of side effects from esketamine nasal spray might vary across studies. 4 indicated that esketamine nasal spray is effective even for patients with substance use disorder, while 7 suggested that dysgeusia could contribute to nausea and vomiting.

Precautions for Real-World Applications

While esketamine nasal spray is a viable treatment option for treatment-resistant depression, it is crucial to understand the associated risk of side effects. Before considering the use of esketamine nasal spray, it is essential to consult a doctor, thoroughly understand the risks and benefits, and make an informed decision regarding treatment.

Limitations of Current Research

Research on esketamine nasal spray is still in its early stages, and further investigation into its long-term safety and efficacy is necessary. Moreover, more in-depth research is needed to elucidate the mechanisms of side effect development and identify strategies to mitigate side effects.

Future Research Directions

Future research needs to include studies assessing the long-term safety and efficacy of esketamine nasal spray, unraveling the mechanisms behind side effect development, and developing methods to minimize side effects.

Conclusion

Esketamine nasal spray presents a promising treatment option for treatment-resistant depression; however, it carries the risk of side effects like dissociative symptoms and sedation. It is essential to consult with a doctor, understand the risks and benefits, and make an informed decision before considering the use of esketamine nasal spray.

Literature analysis of 14 papers
Positive Content
10
Neutral Content
2
Negative Content
2
Article Type
3
0
0
4
13
1.

Common selective serotonin reuptake inhibitor side effects in older adults associated with genetic polymorphisms in the serotonin transporter and receptors: data from a randomized controlled trial.

Author: GarfieldLauren D, DixonDavid, NowotnyPetra, LotrichFrancis E, PollockBruce G, KristjanssonSean D, DoréPeter M, LenzeEric J

Antidepressant side effects

This study investigated the relationship between antidepressant side effects and genetic variations in the serotonin system in older adults experiencing anxiety. The research aimed to understand the impact of genetic variations on the effectiveness and tolerability of escitalopram, a selective serotonin reuptake inhibitor, in this population.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

2.

Antidepressant side effects and their impact on treatment outcome in people with major depressive disorder: an iSPOT-D report.

Author: BraundTaylor A, TillmanGabriel, PalmerDonna M, GordonEvian, RushA John, HarrisAnthony W F

Depression treatment
Side effects
Treatment outcome

This study looks at the frequency, intensity, and burden of side effects associated with antidepressant medications in people with major depressive disorder (MDD). The study found that the burden of side effects was associated with poorer treatment outcomes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Access and real-world use patterns of esketamine nasal spray among patients with treatment-resistant depression covered by private or public insurance.

Author: TeepleAmanda, ZhdanavaMaryia, PilonDominic, Caron-LapointeGabrielle, LefebvrePatrick, JoshiKruti

Improved depression symptoms
Access barriers
Compliance issues

Initial access to esketamine nasal spray may be hindered by prior authorization or claim filing errors. Among patients who initiated esketamine, treatment compliance generally deviated from label recommendations; however, most of those who received induction per label successfully transitioned to maintenance with esketamine.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Esketamine in treatment-resistant depression patients comorbid with substance-use disorder: A viewpoint on its safety and effectiveness in a subsample of patients from the REAL-ESK study.

Author: ChiappiniStefania, d'AndreaGiacomo, De FilippisSergio, Di NicolaMarco, AndriolaIleana, BassettiRoberta, BarlatiStefano, PettorrusoMauro, SensiStefano, ClericiMassimo, Dell'OssoBernardo, VitaAntonio, MartinottiGiovanni

Depression treatment
Dissociative symptoms
Sedation

This study examined the effectiveness and safety of esketamine nasal spray (ESK-NS) in patients with treatment-resistant depression (TRD) who also had a substance use disorder (SUD). Despite limitations of a retrospective study with a small sample size, ESK-NS demonstrated antidepressant efficacy and safety, with the most common side effects being dissociative symptoms and sedation. No cases of abuse or misuse were reported.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.

Language : English

5.

Real-world experience of esketamine use to manage treatment-resistant depression: A multicentric study on safety and effectiveness (REAL-ESK study).

Author: MartinottiGiovanni, VitaAntonio, FagioliniAndrea, MainaGiuseppe, BertolinoAlessandro, Dell'OssoBernardo, SiracusanoAlberto, ClericiMassimo, BellomoAntonello, SaniGabriele, d'AndreaGiacomo, ChiaieRoberto Delle, ConcaAndreas, BarlatiStefano, Di LorenzoGiorgio, De FazioPasquale, De FilippisSergio, NicolòGiuseppe, RossoGianluca, ValcheraAlessandro, NuciforaDomenica, Di MauroStefania, BassettiRoberta, MartiadisVassilis, OlivolaMiriam, BellettiSandro, AndriolaIleana, Di NicolaMarco, PettorrusoMauro, McIntyreRoger S, di GiannantonioMassimo,

Esketamine effective for TRD
Safe and tolerable

This real-world study of 116 patients with treatment-resistant depression (TRD) treated with esketamine nasal spray found a significant reduction in depressive symptoms and a dramatic increase in clinical response and remission rates. No unexpected safety concerns were observed.

Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Real-world approach to managing dysgeusia following the use of esketamine nasal spray: a case report.

Author: BossallerNicholas A, SheltonRichard C

Reduced nausea
Reduced vomiting
Dysgeusia
Nausea
Vomiting

This study discusses the potential of alternative interventions to manage vomiting due to dysgeusia following administration of esketamine nasal spray in patients with depression. Esketamine nasal spray can cause dysgeusia (bad taste), which can lead to nausea and vomiting.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

8.

Therapeutic Mechanisms of Ketamine.

Author: MihaljevićSlobodan, PavlovićMatko, ReinerKrešimir, ĆaćićMarko

Depression treatment
Glutamatergic antidepressant
Emergence delirium
Psychotomimetic side effects

Ketamine, previously known for anesthesia, has shown potential as an antidepressant. It is believed to reverse synaptic stress pathology by activating glutamate, leading to improved connectivity for days or weeks. While effective, ketamine can cause side effects like increased salivation and psychotomimetic effects. Esketamine nasal spray, a safer alternative, is now widely approved and provides consistent therapeutic benefit.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

Arketamine, a new rapid-acting antidepressant: A historical review and future directions.

Author: ZhangJi-Chun, YaoWei, HashimotoKenji

Less side effects
Rapid onset antidepressant
Sustained antidepressant

This review discusses the history, molecular mechanisms, and future directions of arketamine, a novel antidepressant with potential benefits for treatment-resistant patients with major depressive disorder.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Effects of Mu-Opiate Receptor Gene Polymorphism rs1799971 (A118G) on the Antidepressant and Dissociation Responses in Esketamine Nasal Spray Clinical Trials.

Author: SaadZiad, HibarDerrek, FedgchinMaggie, PopovaVanina, FureyMaura L, SinghJaskaran B, KolbHartmuth, DrevetsWayne C, ChenGuang

Antidepressant effect
Dissociative effects

Esketamine's antidepressant and dissociative effects may be influenced by the mu-opioid receptor (MOR) through a single nucleotide polymorphism rs1799971 of OPRM1. This finding warrants further investigation into the role of MOR in esketamine's effects.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

Rapid-acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective.

Author: HashimotoKenji

Rapid antidepressant effects
Side effects

Ketamine is a drug that can quickly improve depression symptoms. Research is underway to study a version of ketamine with fewer side effects.

Historical ArticleA research paper that analyzes past events and developments using primary sources and examines them from a historical perspective.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

13.

Pharmacotherapies for Treatment-Resistant Depression: How Antipsychotics Fit in the Rapidly Evolving Therapeutic Landscape.

Author: JhaManish K, MathewSanjay J

Depression symptom improvement
Extrapyramidal symptoms
Metabolic dysfunction
Tardive dyskinesia
Weight gain

Treatment-resistant depression (TRD), affecting about one-third of adults with major depressive disorder, is associated with significant morbidity, mortality, and healthcare expenses. While atypical antipsychotics are approved for treating depression, they often provide limited remission and have concerning side effects, especially with long-term use.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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