# US 10,478,405 B2 · Method for treating post-traumatic stress disorder

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- Number: US 10,478,405 B2
- Document ID: US10478405B2
- Status: Granted
- Kind: B2
- Application number: 14/974,576
- Filed: 2015-12-18
- Published: 2016-04-14
- Granted: 2019-11-19
- Earliest claimed: 2013-04-12
- Assignees: Icahn School of Medicine at Mount Sinai
- Applicants: Icahn School of Medicine At Mount Sinai
- Inventors: Dennis S. Charney; Adriana Feder
- Web page: https://patentgrep.com/patent/US10478405B2

## CPC

- A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/0043: {Nose}
- A61K 31/428: condensed with carbocyclic rings
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 31/4525: containing a five-membered ring with oxygen as a ring hetero atom
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495})
- A61K 33/00: Medicinal preparations containing inorganic active ingredients
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 23/00: Anaesthetics
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/24: Antidepressants
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure provides compositions containing ketamine and methods of using those compositions for the treatment of post-traumatic stress disorder. Also provided herein is a pharmaceutical composition that comprises esketamine and a pharmaceutically acceptable carrier, excipient or diluent, for use in treatment of PTSD. In some aspects, the pharmaceutical composition is for intranasal or intravenous administration. In some aspects, the pharmaceutical composition is for use in a method of treating PTSD in a subject. In some aspects, the pharmaceutical composition is for use in a method of treating major depressive disorder in a subject that is co-morbid with the PTSD.

## Claims

### Claim 1

A method of treating post-traumatic stress disorder (PTSD) in a patient determined to be suffering from PTSD, comprising conducting a psychiatric evaluation of a patient to determine if the patient is afflicted with PTSD, and intranasally administering to a patient determined to be suffering from PTSD multiple sub-analgesic therapeutic doses of ketamine of between about 0.01 to about 3.0 mg of ketamine per kilogram of body weight of the patient (mg/kg).

### Claim 2 (depends on 1)

The method of claim 1, wherein a first dose is between about 0.01 to about 2.0 mg of ketamine per kilogram of body weight of the patient (mg/kg).

### Claim 3 (depends on 2)

The method of claim 2, wherein the first dose is between about 0.05 to about 0.5 mg/kg of ketamine.

### Claim 4 (depends on 2)

The method of claim 2, wherein the first dose is less than about 0.5 mg/kg, less that about 0.4 mg/kg or less than about 0.3 mg/kg of ketamine.

### Claim 5 (depends on 1)

The method of claim 1, which comprises administering the doses of ketamine at weekly intervals.

### Claim 6 (depends on 5)

The method of claim 5, wherein the patient is treated with one dose of ketamine per week for a period of two or more weeks.

### Claim 7 (depends on 1)

The method of claim 1, further comprising administering a second agent to treat the PTSD.

### Claim 8 (depends on 7)

The method of claim 7, wherein the second agent is an anti-depressant.

### Claim 9 (depends on 7)

The method of claim 7, wherein the second agent is selected from the group consisting of paroxetine, sertraline, lithium, riluzole, prazosin, lamotrigine and ifenprodil.

### Claim 10 (depends on 7)

The method of claim 7, wherein the second agent is used as adjunctive therapy to ketamine treatment.

### Claim 11 (depends on 7)

The method of claim 7, wherein the treatment comprises a phase wherein treatment with the second agent takes place after treatment with ketamine has ceased.

### Claim 12 (depends on 1)

The method of claim 1, wherein the ketamine is administered in a composition comprising a pharmaceutically acceptable carrier, excipient or diluent.

### Claim 13 (depends on 1)

The method of claim 1, wherein the ketamine is esketamine.

### Claim 14 (depends on 1)

The method of claim 1, wherein the total dose of ketamine is about 1.1 mg/kg.

### Claim 15 (depends on 1)

The method of claim 1 which comprises determining if the patient determined to be suffering from PTSD has responded to the first dose of ketamine, and administering to the patient a second dose of ketamine if the patient has responded to the first dose of ketamine, wherein the second dose is lower than the first dose.

### Claim 16 (depends on 1)

The method of claim 1 which comprises determining if the patient determined to be suffering from PTSD has responded to the first dose of ketamine and administering to the patient a second dose of ketamine, wherein the second dose is higher than the first dose.

### Claim 17

A method of treating post-traumatic stress disorder (PTSD) in a patient determined to be suffering from PTSD, comprising administering to a human individual suffering from PTSD a first therapeutically effective amount of ketamine between about 0.01 to about 3.0 mg of ketamine per kilogram of body weight of the patient (mg/kg) and then administering to the individual a second therapeutically effective amount of ketamine, wherein the second therapeutically effective amount of ketamine is lower or higher than the first therapeutically effective amount of ketamine.

### Claim 18 (depends on 17)

The method of claim 17 wherein the individual suffering from PTSD additionally suffers from at least one comorbid depressive condition.

### Claim 19 (depends on 18)

The method of claim 18 wherein the second therapeutically effective amount of ketamine is lower than the first therapeutically effective amount of ketamine.

### Claim 20 (depends on 17)

The method of claim 17 wherein the ketamine is esketamine.

### Claim 21 (depends on 17)

The method of claim 17 wherein the first therapeutically effective amount of ketamine is between about 0.01 to about 2.0 mg of ketamine per kilogram of body weight of the patient (mg/kg).

### Claim 22 (depends on 17)

The method of claim 17 which further comprises evaluating the patient after administering the first dose of ketamine to determine if the patient's PTSD symptoms have been alleviated.

### Claim 23 (depends on 22)

The method of claim 22 wherein the evaluating step comprises conducting at least one of the SCID-P, CAPS, CAPS-5 or TOP-8 structured interviews with the patient and scoring the test results.

### Claim 24

A method of treating post-traumatic stress disorder (PTSD) in a patient determined to be suffering from PTSD, comprising administering to a human individual suffering from PTSD a first therapeutically effective amount of ketamine between about 0.01 to about 3.0 mg of ketamine per kilogram of body weight of the patient (mg/kg), measuring the efficacy of the treatment in relieving the symptoms of PTSD after the administering step and, provided that one or more symptoms of PTSD or a comorbid depressive condition are alleviated, administering to the individual a second therapeutically effective amount of ketamine, wherein the second therapeutically effective amount of ketamine is lower or higher than the first therapeutically effective amount of ketamine.

### Claim 25 (depends on 24)

The method of claim 24 wherein the second therapeutically effective amount of ketamine is lower than the first therapeutically effective amount of ketamine.

### Claim 26 (depends on 24)

The method of claim 24 wherein the second therapeutically effective amount of ketamine is higher than the first therapeutically effective amount of ketamine.

### Claim 27 (depends on 24)

The method of claim 24 wherein the core symptoms of PTSD are relieved after administration of the first therapeutically effective amount of ketamine.

### Claim 28

A method of treating post-traumatic stress disorder (PTSD) in a patient determined to be suffering from acute symptoms of PTSD, comprising administering to a human individual suffering from acute symptoms of PTSD a first therapeutically effective amount of ketamine to treat said acute symptoms and thereafter administering to the individual a second lower amount of ketamine to treat chronic symptoms of PTSD.

### Claim 29 (depends on 28)

The method of claim 28 which comprises titrating the amount of ketamine to reach the second lower amount of ketamine.

### Claim 30 (depends on 24)

The method of claim 24 wherein the measuring step comprises conducting an interview with the human individual using at least one of the SCID-P, CAPS, CAPS-5 or TOP-8 structured interviews and scoring the test results.

### Claim 31 (depends on 24)

The method of claim 24 wherein the first therapeutically effective amount is between about 0.01 to about 2.0 mg of ketamine per kilogram of body weight of the patient (mg/kg).

### Claim 32

A method of treating post-traumatic stress disorder (PTSD) in a patient determined to be suffering from PTSD, comprising administering to a human individual suffering from PTSD a first therapeutically effective amount of ketamine between about 0.01 to about 3.0 mg of ketamine per kilogram of body weight of the patient (mg/kg), measuring the efficacy of the treatment in relieving the symptoms of PTSD after the administering step and, provided that one or more symptoms of PTSD or a comorbid depressive condition are alleviated, administering to the individual a second therapeutically effective amount of ketamine.

### Claim 33 (depends on 1)

The method of claim 1 wherein the intranasal administration comprises administering the ketamine to the olfactory epithelium at the roof of the nasal cavity.

### Claim 34 (depends on 1)

The method of claim 1 wherein the administering step bypasses the blood brain barrier.