Intranasal Esketamine to Maintain the Antidepressant Response to IV Racemic Ketamine

• ClinicalTrials.gov Identifier: NCT04856124
• Recruitment Status: Completed
• First Posted: April 23, 2021
• Last Update Posted: April 23, 2021
• Sponsor: Psych Atlanta
• Information provided by (Responsible Party): michael banov, Psych Atlanta

Study Description

Brief Summary:

This study aims to assess the efficacy and safety of intranasal esketamine as maintenance antidepressant therapy in patients who have demonstrated clinical improvement with off-label intravenous racemic ketamine for treatment-resistant depression.

Condition or disease	Intervention/treatment
Treatment Resistant Depression	Drug: Intranasal esketamine

Detailed Description:

This is a retrospective case series of ten consecutive outpatients with treatment-resistant depression who all had a clinically meaningful response when treated with intravenous racemic ketamine and were then switched to intranasal esketamine for maintenance therapy. Efficacy and adverse effects were assessed at each treatment All patients underwent an extensive consenting process with a detailed discussion about the off-label use of IV racemic ketamine for TRD and known risks of the treatment. Other available approved therapies were offered including alternative medication, TMS, ECT, and VNS. All patients signed an informed consent form prior to treatment and a consent form allowing their data to be used for retrospective research reporting. All patients had baseline lab work and an electrocardiogram to determine medical stability. Patients were encouraged to undergo a series of six ketamine infusions over 14 to 21 days. If a response (>50% improvement) or partial response (25-50% improvement) occurred as determined by a reduction of Montgomery-Asberg Depression Rating Scale (MADRS), Patient Health Questionnaire-9 (PHQ9), and/or a Clinical Global Impressions - Improvement (CGI-I) rating of 3 or more and infusions were well tolerated, patients were offered weekly infusions for four weeks. Patients then had the option of receiving successive maintenance infusions with variable frequency depending on individual patient response and preference. Vital sign and clinical monitoring, dosing, and frequency of IV ketamine treatment were based on the published available data in this area.Treatment with IV ketamine was initiated at subanesthetic doses of 0.5mg/kg with flexible dosing based on response and tolerability up to 1.0mg/kg. Patient's oxygen saturation, blood pressure, and pulse were monitored continuously with pulse oximetry and Caretaker ® finger sensor. Patients that transitioned to IN esketamine received an initial dose of 28mg (n=1) or 56mg (n=9) of IN esketamine and all patients were eventually titrated up to a target dose of 84mg for the remainder of treatments. All patients were monitored as required by the REMS protocol for IN esketamine. Prior to treatment at the beginning of each clinic visit, MADRS and PHQ-9 were completed. CGI ratings were obtained by the treating physician at each treatment. All treatments were administered on-site at the clinic and any adverse effects related to treatment with IV ketamine or IN esketamine were captured through spontaneous reporting and rated as mild, moderate, and severe at the discretion of the treating psychiatrist.

Study Design

• Study Type: Observational
• Actual Enrollment: 10 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Switching to Intranasal Esketamine Maintains the Antidepressant Response to Intravenous Racemic Ketamine Administration: A Case Series of 10 Patients
• Actual Study Start Date: September 1, 2018
• Actual Primary Completion Date: December 15, 2020
• Actual Study Completion Date: March 1, 2021

Groups and Cohorts

Group/Cohort

Intervention/treatment

Treatment resistant depressed outpatients; Subjects had a clinically meaningful response to IV racemic ketamine and remained on other psychotropic medications during treatment with both IV ketamine and IN esketamine. Concomitant medication classes included CNS stimulants (n = 7), atypical antipsychotics (n = 6), selective serotonin reuptake inhibitors (n = 5), serotonin/norepinephrine reuptake inhibitors (n = 4), anticonvulsants (n = 3), antipsychotics (n = 3), mood stabilizers (n = 3), benzodiazepines (n = 2), norepinephrine/dopamine reuptake inhibitors (n = 2), alpha 2 antagonists (n=1), and sedative hypnotics (n = 1). Two patients (20%) previously underwent ECT with partial but transient relief from depressive symptoms, two (20%) failed TMS, and no patients reported any period of greater than 50% improvement during their current depressive episode prior to ketamine treatment.

Drug: Intranasal esketamine; Subjects with a clinically meaningful response to IV racemic ketamine were switched to IN esketamine; Other Name: IV racemic ketamine

Outcome Measures

Primary Outcome Measures :

1. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: 12 months ]
   Depression relapse based on MADRS

Secondary Outcome Measures :

1. Patient-Health Questionnaire-9 (PHQ-9) [ Time Frame: 12 months ]
   Depression relapse based on PHQ-9
2. Clinical Global Impression of Improvement scale- CGI-I [ Time Frame: 12 months ]
   Depression relapse based on CGI-I

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Six females and four males with a mean age of 41.1 years. Nine (90%) had one or more psychiatric diagnoses, including generalized anxiety disorder (n = 9), attention deficit hyperactivity disorder (n = 4), post-traumatic stress disorder (n = 3), and panic disorder (n = 1). Six (60%) were unemployed at baseline due to the disabling effects of their depression and five (50%) reported daily suicidal ideation prior to treatment. The duration of the current depressive episode ranged between 5 and 20 years.

Criteria

Inclusion Criteria:

Diagnosis of major depression, recurrent, severe without psychotic symptoms according to criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). Must be diagnosed with Treatment resistant depression.

18 years old and up Patients had a clinically meaningful response to a course of IV racemic ketamine

Exclusion Criteria:

Active substance abuse, psychosis, significant medical comorbidities, or axis II diagnosis that would interfere with the reliability of outcome measures or response to pharmacotherapy.

Contacts and Locations

Locations

United States, Georgia

PsychAtlanta

Marietta, Georgia, United States, 30060

Sponsors and Collaborators

Psych Atlanta

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Banov MD, Landrum RE, Moore MB, Szabo ST. Switching to Intranasal Esketamine Maintains the Antidepressant Response to Intravenous Racemic Ketamine Administration: A Case Series of 10 Patients. J Clin Psychopharmacol. 2021 Sep-Oct 01;41(5):594-599. doi: 10.1097/JCP.0000000000001456.

• Responsible Party: michael banov, Michael Banov MD, DFAPA, Psych Atlanta
• ClinicalTrials.gov Identifier: NCT04856124
• Other Study ID Numbers: #1262
• First Posted: April 23, 2021
• Last Update Posted: April 23, 2021
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Depressive Disorder, Treatment-Resistant; Depressive Disorder; Mood Disorders; Mental Disorders; Ketamine; Esketamine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antidepressive Agents; Psychotropic Drugs