# US 8,785,500 B2 · Intranasal administration of ketamine to treat depression

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- Number: US 8,785,500 B2
- Document ID: US8785500B2
- Status: Granted
- Kind: B2
- Application number: 11/688,603
- Filed: 2007-03-20
- Published: 2007-12-13
- Granted: 2014-07-22
- Earliest claimed: 2006-03-22
- Assignees: Icahn School of Medicine at Mount Sinai; Yale University; National Institute of Health
- Applicants: Dennis S. Charney; Sanjay J. Mathew; Husseini K. Manji; Carlos A. Zarate, Jr.; John H. Krystal
- Inventors: Dennis S. Charney; Sanjay J. Mathew; Husseini K. Manji; Carlos A. Zarate, Jr.; John H. Krystal
- Web page: https://patentgrep.com/patent/US8785500B2

## 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 9/008: {comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]}
- A61K 9/12: Aerosols; Foams {(A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015)}
- A61K 9/7023: {Transdermal patches and similar drug-containing composite devices, e.g. cataplasms (galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006)}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61M 15/0068: {Indicating or counting the number of dispensed doses or of remaining doses}
- A61M 15/08: Inhaling devices inserted into the nose
- 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)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Methods and compositions for the treatment of treatment-resistant depression are described. More specifically, the invention demonstrates that intranasal administration of ketamine is effective to ameliorate the symptoms of depression in a patient who has not responded to an adequate trial of one antidepressant in the current episode and has recurrent or chronic depressive symptoms (>2 years).

## Claims

### Claim 1

A method of treating depression, comprising intranasally administering to a patient who suffers from said depression and who has not responded to at least two adequate antidepressant treatments a composition comprising ketamine at a dosage sufficient to alleviate symptoms of said depression, wherein the adequate antidepressant treatments are selected from the group consisting of atypical antipsychotics, benzodiazepines, bupropion, electroconvulsive therapy, lamotrigine, lithium, monoamine oxidase inhibitors, selective norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, tricyclic antidepressants, valproic acid, nefazodone, trazodone, and pramipexole.

### Claim 2 (depends on 1)

The method of claim 1, wherein said ketamine is in a pharmaceutically acceptable carrier and is administered at a dose of between about 0.1 mg/kg per day to about 3.0 mg/kg/day.

### Claim 3 (depends on 1)

The method of claim 1, wherein the symptoms of said depression are alleviated within 2 hours of intranasal administration of said ketamine.

### Claim 4 (depends on 1)

The method of claim 1, wherein said method comprises intranasal administration of a single dose of said ketamine.

### Claim 5 (depends on 1)

The method of claim 1, wherein said method comprises intranasal administration of multiple doses of said ketamine.

### Claim 6 (depends on 1)

The method of claim 1, wherein a single intranasal administration of said ketamine is sufficient to alleviate said symptoms for 7 days.

### Claim 7 (depends on 1)

The method of claim 1, further comprising administering a pharmaceutically effective dose of a second agent, wherein said second agent is an antidepressant agent.

### Claim 8 (depends on 7)

The method of claim 7 wherein said antidepressant agent is selected from the group consisting of at least one member of lithium, a pharmaceutical antidepressant, an herbal antidepressant, an anticonvulsant, a mood stabilizer, an antipsychotic agent, and a benzodiazepine.

### Claim 9 (depends on 1)

The method of claim 1, wherein said two adequate antidepressant treatments comprise two adequate antidepressant treatments with medicines from two different classes of antidepressant medicines.

### Claim 10 (depends on 1)

The method of claim 1, wherein the symptoms of the depression are alleviated within one day of administering the composition.

### Claim 11 (depends on 1)

The method of claim 1, wherein at least one of the adequate treatments is selective serotonin reuptake inhibitor.

### Claim 12 (depends on 1)

The method of claim 1, wherein at least one of the adequate treatments is a selective norepinephrine reuptake inhibitor.

### Claim 13 (depends on 1)

The method of claim 1, wherein at least one of the adequate treatments is a tricyclic antidepressant.

### Claim 14 (depends on 1)

The method of claim 1, wherein at least one of the adequate treatments is a monamine oxidase inhibitor.

### Claim 15 (depends on 1)

The method of claim 1, wherein at least one of the adequate treatments is electroconvulsive therapy.

### Claim 16 (depends on 1)

The method of claim 1, wherein at least one of the adequate treatments is a benzodiazepine.

### Claim 17 (depends on 1)

The method of claim 1, wherein at least one of the adequate treatments is bupropion.

### Claim 18 (depends on 1)

The method of claim 1, wherein the adequate treatments are selected from the group consisting of selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, and electroconvulsive therapy.