Compositions and methods for treatment of depression and other disorders
Inventors
Assignees
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Publication Number
US-12465611-B2
Publication Date
2025-11-11
Expiration Date
Abstract
The invention provides compositions and methods for the treatment of depression and other psychiatric disorders. In particular, the invention provides sustained- or controlled-release formulations, particularly extended or slow release formulations, which include at least one monoamine oxidase inhibitor (MAOI), as well as combination therapies that include at least one MAOI and at least one norepinephrine-reuptake-inhibitor (NRI), for use in such compositions and methods. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Core Innovation
The invention relates to depression and psychiatric disorders treated using monoamine oxidase inhibitors (MAOIs) formulated as controlled-release dosage forms in combination therapies. The disclosed approach centers on phenelzine and pharmaceutically acceptable salts as a controlled-release component, together with a norepinephrine-reuptake inhibitor (NRI) selected from protriptyline and desipramine and pharmaceutically acceptable salts.
The formulation is structured so that the NRI and phenelzine are released over different time periods while both are present in therapeutically effective amounts. The disclosure also includes controlled-release formulation performance considerations, plasma concentration exposure, and a described algorithm for personalizing NRI dosing based on required minimum NRI plasma concentrations.
The patent further describes individually dosing an NRI by using a pharmacokinetic model that relates a 6-hour post-dose concentration to a predicted steady-state concentration, with eligibility limits for the dose calculation. It also relates an overall clinical evaluation context in which phenelzine and NRIs are administered in combination with a tyramine challenge, with planned assessment of systolic blood pressure responses and tolerability outcomes following tyramine challenge under different dosing regimens.
Claims Coverage
The independent claim set centers on a controlled-release pharmaceutical composition containing phenelzine or a pharmaceutically acceptable salt and an NRI selected from protriptyline or desipramine or a pharmaceutically acceptable salt, with both components released over different time periods. It also requires that phenelzine is present in a therapeutically effective amount and excludes droxidopa. Independent and dependent claims together add controlled-release timing, dosage amount, pharmacokinetic performance constraints, and a psychiatric-disorder treatment context.
Controlled-release phenelzine and NRI with different release time periods
A pharmaceutical composition comprising phenelzine or a pharmaceutically acceptable salt and an NRI selected from protriptyline and desipramine or a pharmaceutically acceptable salt, wherein both are formulated as controlled-release dosage forms and are released over different time periods.
Therapeutically effective phenelzine amount and droxidopa exclusion
The phenelzine or pharmaceutically acceptable salt is present in a therapeutically effective amount, and the composition does not contain droxidopa.
Phenelzine controlled-release release time range
The phenelzine or pharmaceutically acceptable salt is released over a time period of about 6 to about 16 hours after administration.
Phenelzine dosage amount range
The phenelzine or pharmaceutically acceptable salt is present in an amount of about 20 mg to about 1000 mg.
NRI controlled-release pharmacokinetic performance at 24 hours
The controlled-release pharmaceutical composition delivers at least 50% of the NRI's average daily plasma concentration 24 hours after administration.
NRI limited to protriptyline
The NRI is protriptyline or a pharmaceutically acceptable salt of protriptyline.
Administration to treat a psychiatric disorder
A method of treating a psychiatric disorder in a subject in need thereof by administering the pharmaceutical composition.
The claims are directed to controlled-release co-formulation of phenelzine with a controlled-release NRI, with different release time periods, explicit phenelzine effectiveness and droxidopa exclusion, and further constraints on phenelzine release time, phenelzine dose amount, and NRI plasma exposure at 24 hours, together with treatment of psychiatric disorder.
Stated Advantages
Attenuation of tyramine pressor effects, including reduced systolic blood pressure increase associated with tyramine.
Improved tolerability, including reduced postural hypotension.
Improved tolerability, including reduced post-dosing paroxysmal hypertension.
Documented Applications
Treatment of depression and psychiatric disorders using the disclosed MAOI phenelzine controlled-release formulations combined with an NRI.
Attenuation of tyramine-evoked systolic blood pressure effects associated with MAOI therapy when the controlled-release MAOI and NRI release over different time periods.
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