Application of esketamine in treatment of intractable juvenile depressive disorder with suicide risk

Abstract

The invention belongs to the technical field of medicine application, and particularly discloses application of esketamine in treating teenager depressive disorder with suicide risk and refractory, so as to play a quick anti-depression effect on teenager patients, obviously reduce the suicide risk of the patients, and have the advantages of less adverse reaction, high bioavailability and no toxic or side effect. An important feasible treatment means is provided for teenager patients, and the compound has a great application prospect as a novel anti-depression drug.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical application technology, specifically relating to the application of esketamine in adolescents with suicidal risk and treatment-resistant depressive disorder. Background Technology

[0003] For adolescents, oral medication is one of the main methods of treating childhood and adolescent depression. However, adolescents respond differently to medication than adults. Many adult antidepressants are ineffective and unsafe in children and adolescents, and are not suitable for treating childhood and adolescent depression. Currently, only fluoxetine (Prozac) and escitalopram (Lexapro) are the only two medications approved by the U.S. Food and Drug Administration (FDA) for the treatment of major depressive disorder in children and adolescents. Furthermore, studies have found that early use of antidepressants increases suicidal behavior in adolescents.

[0004] Ketamine is an N-methyl-d-aspartate receptor (NMDA-R) antagonist with a high affinity for NMDA receptors, exhibiting rapid antidepressant effects (2-24 hours after infusion). It has also been reported to rapidly reduce suicidal ideation and behavior. Ketamine has an average remission rate of 67% in adults with treatment-resistant depression (TRD), significantly higher than other interventions for TRD. Esketamine, the S-enantiomer of ketamine, has an even greater affinity for NMDA receptors (NMDA-R). The FDA approved esketamine as a new antidepressant in March 2019. However, current reports lack studies on the efficacy and safety of esketamine in children and adolescents. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention proposes the application of esketamine in adolescents with suicidal risk and treatment-resistant depressive disorders, aiming to provide rapid antidepressant effects, significantly reduce suicide risk, minimize adverse reactions, and increase bioavailability. This provides an important and feasible treatment option for adolescent patients and has great application potential as a novel antidepressant.

[0006] To achieve the above objectives, the present invention is implemented through the following technical solution:

[0007] The application of esketamine in the treatment of depressive disorders in adolescents with suicide risk and treatment-resistant depressive disorders.

[0008] Esketamine is a nasal spray or injection.

[0009] The initial dose of esketamine is 0.2 mg per kilogram of body weight.

[0010] The treatment process is divided into a treatment period and a follow-up observation period. During the treatment period, the drug is administered every other day (0.2 mg / kg) for a total of 6 injections; then a 10-week follow-up observation period begins.

[0011] The treatment process may involve the combined use of other antidepressants or psychotherapy to enhance efficacy.

[0012] The other antidepressants mentioned are selective serotonin reuptake inhibitors.

[0013] The beneficial effects of this invention are:

[0014] This invention utilizes esketamine in adolescents with suicidal risk and treatment-resistant depressive disorders, providing a rapid antidepressant effect, significantly reducing suicide risk, with few adverse reactions and high bioavailability. It offers an important and feasible treatment option for adolescents and has great application potential as a novel antidepressant. Attached Figure Description

[0015] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0016] Figure 1 This is an experimental flowchart of the application of esketamine in adolescent patients with depression according to the present invention. Detailed Implementation

[0017] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0018] Example 1

[0019] See Figure 1 The flowchart shown illustrates the application experiment of esketamine:

[0020] 1. This study will conduct a randomized, placebo-controlled, double-blind clinical trial targeting hospitalized adolescents with major depressive disorder at acute suicide risk. The aim is to address the efficacy, safety, and tolerability of esketamine injection in these patients. Patients will be followed up for 10 weeks after treatment to observe the long-term efficacy and effectiveness of early esketamine use against suicidal behavior.

[0021] 2. Questionnaires were used to assess the improvement of patients' depressive symptoms and the reduction of suicide risk by combining self-rating and other-rating scales. Laboratory tests were used to further evaluate the safety of the treatment plan.

[0022] This study employed a randomized, placebo-controlled, double-blind clinical trial design to observe the efficacy, safety, and tolerability of esketamine injection in adolescents with major depressive disorder at acute suicidal risk during the first two weeks of acute treatment. Following this, a 10-week long-term efficacy observation period using esketamine was initiated.

[0023] 3. Implementation Plan:

[0024] ① Screening period (-1d to -2d): Diagnose and screen hospitalized patients, and include adolescents who meet the criteria.

[0025] ② Treatment period (2 weeks): The acute treatment period was a double-blind (DB) treatment phase. Patients were randomly assigned 1:1 to the experimental group (intravenous infusion of 0.2 mg / kg esketamine) and the control group (intravenous infusion of 0.045 mg / kg midazolam). On the first day of DB (first dose), all patients received the study drug continuously and slowly infused over 40 minutes using an electronic infusion pump.

[0026] ③ Follow-up period (10W): After completing the acute phase of treatment, patients will enter a long-term follow-up observation period for 10 weeks under the clinical guidance of physicians and researchers to observe the efficacy.

[0027] Comparison of results between the experimental group (0.2 mg / kg esketamine intravenously) and the control group (0.045 mg / kg midazolam intravenously):

[0028] Improvement in depression severity: Assessment using the Montgomery-Asperger's Depression Scale revealed that esketamine exhibited rapid and effective antidepressant effects at 4 and 24 hours after the first injection. Throughout the treatment period, at almost all assessment time points, esketamine consistently demonstrated superior improvement in depression severity compared to the control group (midazolam). The experimental group also had a higher rate of achieving clinical response and clinical remission compared to the control group.

[0029] Improvement of suicidal ideation: The MADRS score for suicidal ideation showed rapid anti-suicidal effects at 4 and 24 hours after the first dose. With the increase of treatment sessions, the severity of suicidal ideation gradually decreased. The changes in the degree of suicidal ideation in both groups were statistically significant.

[0030] Safety assessment: The most common adverse reactions in the esketamine group were dizziness, nausea and vomiting, excitement or agitation; significant dissociation symptoms were observed during treatment, peaking during use and gradually disappearing to normal after 2 hours. Regarding the effects of esketamine on blood pressure and heart rate, both systolic and diastolic blood pressure showed a transient increase followed by a gradual decrease; the trend in heart rate changes appeared erratic, therefore, no specific conclusions could be drawn about its specific impact on heart rate, but overall, no serious adverse events occurred, and the condition was well-tolerated in the adolescent population.

[0031] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not describe all details exhaustively, nor do they limit the invention to the specific implementations described. Clearly, many modifications and variations can be made based on the content of this specification.

Claims

1. The application of esketamine in adolescents with suicidal risk and treatment-resistant depressive disorder, characterized in that, Esketamine is administered as a nasal spray or injection; the initial dose of esketamine is 0.2-0.5 mg per kilogram of body weight; the treatment process is divided into a treatment period and a follow-up observation period, with administration every other day during the treatment period for a total of 6 injections; followed by a 10-week follow-up observation period; other antidepressants or psychotherapy are used in combination during the treatment process to enhance efficacy; the other antidepressants are selective serotonin reuptake inhibitors.

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