Intranasal administration of ketamine to treat depression
Inventors
Charney, Dennis S. • Mathew, Sanjay J. • Manji, Husseini K. • Zarate, Carlos A. • Krystal, John H.
Assignees
Yale University • Icahn School of Medicine at Mount Sinai • US Department of Veterans Affairs • US Department of Health and Human Services
Publication Number
US-9592207-B2
Publication Date
2017-03-14
Expiration Date
2027-03-20
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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).
Core Innovation
The invention provides methods and compositions for treating treatment-resistant depression by intranasal administration of ketamine, demonstrating that such administration effectively ameliorates symptoms in patients who have not responded to adequate trials of at least one antidepressant and present recurrent or chronic depressive symptoms lasting more than two years.
The invention addresses the problem that existing antidepressant medications suffer from a delayed onset of effectiveness, typically taking weeks to months to alleviate symptoms, thereby leaving patients at risk for ongoing suffering and self-harm. Current treatments mainly augment monosynaptic monoamine neurotransmission but lack rapid action, which limits their utility especially in treatment-resistant depression.
The invention also contemplates alternative administration routes including intravenous and transdermal delivery of ketamine, with doses ranging approximately from 0.1 mg/kg per day to 3.0 mg/kg per day, achieving antidepressant effects within 2 hours of administration. The invention provides devices and formulations, including nasal inhalers and transdermal patches, allowing self-administration of metered ketamine doses effective to reduce depressive symptoms but below levels causing dysphoria or psychosis.
Claims Coverage
The patent includes one independent claim focused on a method of treating depression by intranasal administration of ketamine, with several dependent features expanding on dosing, combination therapies, and specific depression types.
Treatment of depression by intranasal administration of ketamine
A method comprising intranasal administration of a ketamine dose effective to alleviate depression in patients unresponsive to at least two adequate antidepressant treatments.
Specific dosing parameters for ketamine administration
Administering ketamine at doses between 0.13 to 0.53 mg/kg/day or up to 250 mg per day; including single or multiple dose regimens over periods such as 7 days.
Combination with a second antidepressant agent
The method optionally includes co-administration of a pharmaceutically effective dose of a second antidepressant agent, chosen from lithium, pharmaceutical or herbal antidepressants, anticonvulsants, mood stabilizers, antipsychotic agents, and benzodiazepines.
Alleviation of depression symptoms within a short timeframe
Ketamine administration results in alleviation of depressive symptoms within 2 hours to one day of administration.
The claims cover a method for treating depression resistant to prior treatments via intranasal ketamine at defined doses, optionally combined with other antidepressants, showing rapid symptom relief.
Stated Advantages
Intranasal administration of ketamine allows rapid and sustained antidepressant effects, with symptom alleviation evident within hours and lasting up to one week.
The method provides a non-invasive, self-administrable treatment option usable on an outpatient basis, improving patient acceptability and convenience compared to intravenous methods.
Ketamine is inexpensive and readily available with minor adverse side effects at therapeutic doses, potentially reducing healthcare costs.
The invention allows reduction in the dose of other antidepressant agents when used in combination, enhancing overall treatment efficacy.
Documented Applications
Treatment of chronic, treatment-resistant depression including major depressive disorder, recurrent major depressive disorder, seasonal affective disorder, bipolar depression, and depression due to general medical conditions in patients unresponsive to adequate antidepressant trials.
Outpatient depression management via intranasal ketamine self-administration.
Treatment-resistant depression therapy involving intravenous administration of ketamine repeated multiple times over periods of two to three weeks.
Transdermal ketamine administration through patches or topical forms for treatment-resistant depression with repeated dosing.
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