U.S. patent application number 17/006714 was filed with the patent office on 2021-11-25 for combination methods and compositions including sleep therapeutics for treating mood.
The applicant listed for this patent is Seth Feuerstein. Invention is credited to Seth Feuerstein.
Application Number | 20210361607 17/006714 |
Document ID | / |
Family ID | 1000005955197 |
Filed Date | 2021-11-25 |
United States Patent
Application |
20210361607 |
Kind Code |
A9 |
Feuerstein; Seth |
November 25, 2021 |
COMBINATION METHODS AND COMPOSITIONS INCLUDING SLEEP THERAPEUTICS
FOR TREATING MOOD
Abstract
Pharmaceutical combinations and methods for using such
combinations to treat depression are disclosed. In various
embodiments (he pharmaceutical combinations include combinations of
omega-3 fatty acids, pharmacological sleep agents, and
non-pharmacological sleep therapies, and may include other
ingredients such as antidepressants. The present invention relates
pharmaceutical combinations and methods for their use to treat
depression.
Inventors: |
Feuerstein; Seth;
(Woodbridge, CT) |
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Applicant: |
Name |
City |
State |
Country |
Type |
Feuerstein; Seth |
Woodbridge |
CT |
US |
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Prior
Publication: |
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Document Identifier |
Publication Date |
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US 20210046035 A1 |
February 18, 2021 |
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Family ID: |
1000005955197 |
Appl. No.: |
17/006714 |
Filed: |
August 28, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15909923 |
Mar 1, 2018 |
10758508 |
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17006714 |
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14431399 |
Mar 26, 2015 |
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PCT/US2013/061588 |
Sep 25, 2013 |
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15909923 |
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61705669 |
Sep 26, 2012 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 45/06 20130101;
A61M 21/02 20130101; A61K 36/35 20130101; A61K 31/4985 20130101;
A61K 31/202 20130101; A61K 31/437 20130101; A61M 21/00
20130101 |
International
Class: |
A61K 31/202 20060101
A61K031/202; A61K 45/06 20060101 A61K045/06; A61K 31/437 20060101
A61K031/437; A61K 31/4985 20060101 A61K031/4985; A61M 21/00
20060101 A61M021/00; A61M 21/02 20060101 A61M021/02; A61K 36/35
20060101 A61K036/35 |
Claims
1-20. (canceled)
21. An apparatus offered or prescribed by a clinician for treating
at least one mood disorder a patient is experiencing, the apparatus
comprising: at least one processor configured to: receive at least
one interaction from the patient; receive information relating to
at least one sleep aspect from the patient and not indicating that
the patient is complaining to the clinician about any sleep aspect;
and treat the at least one mood disorder by outputting, to the
patient, information assisting in treatment of the at least one
sleep aspect based at least in part on the at least one interaction
received from the patient, wherein the information assisting in the
treatment of the at least one sleep aspect comprises at least one
element of cognitive behavioral therapy for the at least one sleep
aspect.
22. The apparatus of claim 21, wherein: the apparatus is connected
to a network, and the apparatus is configured to: send the at least
one interaction to at least one computer connected via the network;
and receive the information assisting in the treatment of the at
least one sleep aspect from the at least one computer, wherein the
information assisting in the treatment of the at least one sleep
aspect includes: psychological education material, relaxation
training, interactive multimedia content for paced breathing,
progressive muscle relaxation, imagery-induced relaxation, and/or
self-hypnosis, and/or instructions on patient monitoring of and
adjustment of thoughts of the patient.
23. The apparatus of claim 21, wherein: the at least one sleep
aspect comprises a sleep disorder, a sleep pattern, a sleep
quality, sleep timing, sleep duration, and/or a quality or quantity
of sleep disruption.
24. The apparatus of claim 21, wherein: the information relating to
the at least one sleep aspect comprises a sleep diary tracking at
least one metric related to sleep behavior of the patient.
25. The apparatus of claim 21, wherein: the at least one processor
is configured to receive information relating to the at least one
mood disorder from the patient.
26. (canceled)
27. The apparatus of claim 21, wherein: the at least one mood
disorder comprises at least moderate depression that is
treatment-resistant.
28. The apparatus of claim 21, wherein: the at least one processor
is configured to treat the at least one mood disorder by outputting
the information assisting in treatment of the at least one sleep
aspect and by causing administering to the patient an omega-3 fatty
acid formulation or an antidepressant.
29. A system for treating a patient suffering from at least one
mood disorder, the system comprising: at least one computer; and at
least one apparatus connected to the at least one computer via at
least one network, the at least one apparatus comprising: at least
one processor configured to: receive at least one interaction from
the patient; receive information relating to at least one sleep
aspect from the patient and indicating that the patient is or is
not suffering from insomnia; and treat the at least one mood
disorder by outputting, to the patient, information assisting in
treatment of the at least one sleep aspect based at least in part
on the at least one interaction received from the patient, wherein
the information assisting in the treatment of the at least one
sleep aspect comprises at least one element of cognitive behavioral
therapy for the at least one sleep aspect.
30. The system of claim 29, wherein: the information relating to
the at least one sleep aspect comprises a sleep diary tracking at
least one metric related to sleep behavior of the patient.
31. The system of claim 29, wherein: the information assisting in
the treatment of the at least one sleep aspect comprises:
psychological education material, relaxation training, interactive
multimedia content for paced breathing, progressive muscle
relaxation, imagery-induced relaxation, and/or self-hypnosis,
instructions on patient monitoring of and adjustment of thoughts of
the patient, an interactive sleep diary tracking at least one
metric related to sleep behavior of the patient, instructions on
modifying sleep behavior of the patient, information regarding
sleep hygiene and stimulus control, instructions on sleep
restriction and/or sleep windows, and/or instructions on use of
medication.
32. The system of claim 29, wherein: the at least one mood disorder
comprises at least moderate depression that is
treatment-resistant.
33. The system of claim 29, wherein: the at least one processor is
configured to treat the at least one mood disorder by outputting
the information assisting in treatment of the at least one sleep
aspect and by causing administering to the patient an omega-3 fatty
acid formulation or an antidepressant.
34. At least one non-transitory computer-readable storage medium
storing processor-executable instructions that, when executed by at
least one processor, cause the at least one processor to perform a
method for treating a patient suffering from at least one mood
disorder, the method comprising: receiving at least one interaction
from the patient; receiving information relating to at least one
sleep aspect from the patient and indicating that the patient is
not complaining about insomnia; and treating the at least one mood
disorder by outputting, to the patient, information assisting in
treatment of the at least one sleep aspect based at least in part
on the at least one interaction received from the patient, wherein
the information assisting in the treatment of the at least one
sleep aspect comprises at least one element of cognitive behavioral
therapy for the at least one sleep aspect.
35. The at least one non-transitory computer-readable storage
medium of claim 34, the method further comprising providing
training regarding: sleep hygiene, sleep restriction, stimulus
control, sleep scheduling, cognitive therapy, relaxation therapy,
and/or mindfulness therapy or training.
36. The at least one non-transitory computer-readable storage
medium of claim 34, the method further comprising: facilitating
self-administered cognitive behavioral therapy for the at least one
sleep aspect.
37. The at least one non-transitory computer-readable storage
medium of claim 36, wherein: the at least one mood disorder
responds to treatment within 3 or fewer weeks of initiation of the
treatment.
38. The at least one non-transitory computer-readable storage
medium of claim 34, wherein: the information assisting in the
treatment of the at least one sleep aspect comprises: psychological
education material, relaxation training, interactive multimedia
content for paced breathing, progressive muscle relaxation,
imagery-induced relaxation, and/or self-hypnosis, instructions on
patient monitoring of and adjustment of thoughts of the patient, an
interactive sleep diary tracking at least one metric related to
sleep behavior of the patient, instructions on modifying sleep
behavior of the patient, information regarding sleep hygiene and
stimulus control, instructions on sleep restriction and/or sleep
windows, and/or instructions on use of medication.
39. The at least one non-transitory computer-readable storage
medium of claim 34, wherein: the at least one mood disorder
comprises at least moderate depression that is
treatment-resistant.
40. The at least one non-transitory computer-readable storage
medium of claim 34, wherein: treating the at least one mood
disorder comprises treating the at least one mood disorder by
outputting, to the patient, the information assisting in treatment
of the at least one sleep aspect and by causing administering to
the patient an omega-3 fatty acid formulation or an
antidepressant.
41. The system of claim 29, wherein: the information relating to
the at least one sleep aspect indicates that the patient is not
suffering from chronic insomnia.
Description
RELATED APPLICATION DATA
[0001] The present International PCT Patent Application claims
priority to U.S. Provisional Patent Application No. 61/705,669,
filed Sep. 26, 2012, the disclosure of which is hereby incorporated
by reference in its entirety.
FIELD OF THE INVENTION
[0002] The present invention relates pharmaceutical combinations
and methods to treat depression.
BACKGROUND OF RELATED TECHNOLOGY
[0003] Antidepressants are a well-known class of pharmaceuticals.
They are generally categorized according to their mechanism of
action on neurotransmitter activity (e.g., Selective Serotonin
Reuptake Inhibitors; Serotonin and Norepinephrine Reuptake
Inhibitors; Tricyclic antidepressants; and Monoamine Oxidase
inhibitors); with a number of drugs in each category having
received marketing approval in the U.S. and elsewhere. Although
widely used, antidepressants are known to have a number of
drawbacks. For example, they are known to be plagued by long delays
in initiating response (typically 4 or more weeks), and may have
only a partial or no response.
[0004] Certain natural compounds have also been investigated for
their effectiveness in treating depression. For example,
substantial work has been done to study the effectiveness of
various omega-3 fatty acids in treating depression (See, for
example, Carlezon et al., 2005; Marangell et al., 2003; U.S. Pat.
Nos. 6,852,870, 8,071,646, and 8,372,451; and U.S. Patent Publ.
Nos. 2005/0267212 and 2011/0200690).
[0005] Despite this work, however, the use of omega-3 fatty acids
in treating depression has failed in clinical trials (e.g.,
VASCEPA.RTM. (icospent ethyl), an EPA-only omega-3 fatty acid,
failed in depression clinical trials), and currently no omega-3
fatty acid formulation has been approved by the U.S. Food and Drug
Administration (FDA) for use in treating depression. In fact,
recent meta-analyses suggest omega-3 fatty acids, on a population
level, have mixed results (See, for example, Mischoulon, 2011;
Appleton et al., 2010; Martins, 2009; and Young and Conquer.
2005).
[0006] Insomnia has traditionally been thought to be associated
with depression. As such, certain sleep medications have been used
to treat sleep difficulties associated with depression. However,
not only do these medications not treat the depression itself,
findings suggest that they may actually cause and/or exacerbate
depression (Kripke, 2007; and Walling, 2010).
[0007] In this regard, the FDA has required the side effect
"worsening of depression" to be included on the label of certain
sleep medications (such as zolpidem), and this side effect known to
be associated with the use of sleeping pills has been receiving
increased attention in the media (See, for example, Rabin, 2012).
In fact, sleep deprivation--rather than sleep inducement--has been
shown to help alleviate depression (See, for example, Giedke, 2002
which teaches that sleep deprivation may be help depression; See
also, Giedke et al., 2003; Wirz-Justice, 1999; Adrien, 2002;
Letemendia, 1986; and Wu, 1990). As such, sleep-inducing
medications may be contraindicated in patients suffering from
depression.
[0008] Thus, there is a need in the art for new treatments for
depression, in particular for new pharmaceutical combinations to
provide more robust treatments for depression with faster
onset.
SUMMARY OF THE INVENTION
[0009] Accordingly, the present invention provides compositions,
combinations and methods that overcome these and other problems,
and provide a more robust treatment for depression with faster
onset.
[0010] In certain exemplary, non-limiting embodiments, the present
invention is directed to a pharmaceutical composition comprising an
omega-3 fatty acid formulation and a sleep-inducing agent.
[0011] In certain exemplary, non-limiting embodiments, the omega-3
fatty acid formulation has greater than 90% purity.
[0012] In certain exemplary, non-limiting embodiments, the present
invention is directed to a pharmaceutical composition comprising an
omega-3 fatty acid formulation and a sleep-inducing agent, wherein
the composition is substantially free of an antidepressant.
[0013] In certain exemplary, non-limiting embodiments, the present
invention is directed to a combined pharmaceutical product for the
treatment of depression, the product comprising, in combination:
(i) first dose of an omega-3 fatty acid formulation and (ii) a
second dose of a sleep-inducing agent, wherein the combination of
the doses is effective for the treatment of depression in a patient
in need thereof.
[0014] In certain 7exemplary, non-limiting embodiments, the present
invention is directed to a combined pharmaceutical product for the
treatment of depression, the product comprising, in combination:
(i) first dose of an omega-3 fatty acid formulation and (ii) a
second dose of a sleep-inducing agent, wherein the combination of
the doses is effective for the treatment of depression in a patient
in need thereof, and further wherein the combined pharmaceutical
product further comprises instructions for administering each of
the first dose and the second dose.
[0015] In certain exemplary, non-limiting embodiments, the present
invention is directed to a method of treating depression comprising
the administration of an anti-depressant effective amount of a
combination of an omega-3 fatty acid formulation and a
sleep-inducing agent to a patient in need thereof.
[0016] In certain exemplary, non-limiting embodiments, the present
invention is directed to a method of treating depression comprising
the administration of an anti-depressant effective amount of a
combination of an omega-3 fatty acid formulation and a
sleep-inducing agent to a patient in need thereof in the absence of
an antidepressant.
[0017] In certain exemplary, non-limiting embodiments, the present
invention is directed to a method of treating depression comprising
the administration of an anti-depressant effective amount of a
combination of an omega-3 fatty acid formulation and a
sleep-inducing agent to a patient in need thereof, wherein the
combination is effective for the treatment of depression even in
the absence of an antidepressant.
[0018] In other certain exemplary, non-limiting embodiments, the
present invention is directed to a pharmaceutical composition
comprising an antidepressant and a sleep-inducing agent.
[0019] In other certain exemplary, non-limiting embodiments, the
present invention is directed to a pharmaceutical composition
comprising an antidepressant and a sleep-inducing agent which is
substantially free of an omega-3 fatty acid formulation.
[0020] In other certain exemplary, non-limiting embodiments, the
present invention is directed to a combined pharmaceutical product
fur the treatment of depression, the product comprising, in
combination: (i) first dose of an antidepressant and (ii) a second
dose of a sleep-inducing agent, wherein the combination of the
doses is effective for the treatment of depression in a patient in
need thereof.
[0021] In other certain exemplary, non-limiting embodiments, the
present invention is directed to a combined pharmaceutical product
for the treatment of depression, the product comprising, in
combination: (i) first dose of an antidepressant and (ii) a second
dose of a sleep-inducing agent, wherein the combination of the
doses is effective for the treatment of depression in a patient in
need thereof, and further wherein the combined pharmaceutical
product further comprises instructions fur administering each of
the first dose and the second dose.
[0022] In certain exemplary, non-limiting embodiments, the present
invention is directed to a method of treating depression comprising
the administration of an anti-depressant effective amount of a
combination of an antidepressant and a sleep-inducing agent to a
patient in need thereof.
[0023] In certain exemplary, non-limiting embodiments, the present
invention is directed to a method of treating depression comprising
the administration of an anti-depressant effective amount of a
combination of an antidepressant and a sleep-inducing agent to a
patient in need thereof in the absence of an omega-3 fatty acid
formulation.
[0024] In certain exemplary, non-limiting embodiments, the present
invention is directed to a method of treating depression comprising
the administration of an anti-depressant effective amount of a
combination of an antidepressant and a sleep-inducing agent to a
patient in need thereof, wherein the combination is effective for
the treatment of depression even in the absence of an omega-3 fatty
acid formulation.
[0025] In certain exemplary, non-limiting embodiments, the
antidepressant is selected from the group consisting of tricyclic
antidepressants, selective serotonin reuptake inhibitors (SSRI's),
selective serotonin norepinephrine reuptake inhibitors,
norepinephrine dopamine reuptake inhibitors and alpha-2
antagonist/serotonin 5HT2-3 receptor antagonists.
[0026] In certain exemplary, non-limiting embodiments, the
antidepressant is a tricyclic antidepressant selected from the
group consisting of selected from the group consisting trazodone,
doxepin, amitriptyline, amoxapine, clomipramine, desipramine,
doxepin, imipramine, maprotiline, nortriptyline, protriptyline and
trimipramine, provided that if the antidepressant is trazodone it
cannot also comprise the sleep-inducing agent.
[0027] In certain exemplary, non-limiting embodiments, the
tricyclic antidepressant is selected from the group consisting of
doxepin, amitriptyline, amoxapine, clomipramine, desipramine,
doxepin, imipramine, maprotiline, nortriptyline, protriptyline and
trimipramine.
[0028] In certain exemplary, non-limiting embodiments, the
antidepressant is a selective serotonin reuptake inhibitor selected
from the group consisting of citalopram, escitalopram, femoxetine,
fluoxetine, fluvoxamine, paroxetine, sertraline and zimeldine.
[0029] In certain exemplary, non-limiting embodiments, the
antidepressant is a selective serotonin reuptake inhibitor selected
from the group consisting of duloxetine, venlafaxine,
desvenlafaxine, milnacipran and clovoxamine.
[0030] In certain exemplary non-limiting embodiments, the
antidepressant is a norepinephrine dopamine reuptake inhibitor.
[0031] In certain exemplary, non-limiting embodiments,
norepinephrine dopamine reuptake inhibitor antidepressant is
bupropion.
[0032] In certain exemplary, non-limiting embodiments, the
antidepressant is a alpha-2 antagonist/serotonin 5HT2-3 receptor
antagonist.
[0033] In certain exemplary, non-limiting embodiments, the alpha-2
antagonist/serotonin 5HT2-3 receptor antagonist antidepressant is
mirtazapine.
[0034] In certain exemplary, non-limiting embodiments, the
sleep-inducing agent is selected from the group consisting of
antihistamines, hypnotics, trazadone tricyclic antidepressant,
melatonin, melatonin receptor agonists, tryptophan and Valerian
root.
[0035] In certain exemplary, non-limiting embodiments, the
sleep-inducing agent is selected from the group consisting
antihistamines, hypnotics, trazadone tricyclic antidepressants,
melatonin, melatonin receptor agonists and Valerian root.
[0036] In certain exemplary, non-limiting embodiments, the
sleep-inducing agents are selected from the group consisting of
antihistamines, hypnotics, melatonin, melatonin receptor agonists,
and Valerian root.
[0037] In certain exemplary, non-limiting embodiments, the
sleep-inducing agent is selected from the group consisting of
hypnotics, melatonin, melatonin receptor agonists, and Valerian
root.
[0038] In certain exemplary, non-limiting embodiments, the
sleep-inducing agent is selected from the group consisting of
hypnotics, melatonin and melatonin receptor agonists.
[0039] In certain exemplary, non embodiments, the sleep-inducing
agent is a hypnotic.
[0040] In certain exemplary, non-limiting embodiments, the
hypnotics are selected from the group consisting of benzodiazepine
hypnotics and non-benzodiazepine hypnotics.
[0041] In certain exemplary, non-limiting embodiments, the
benzodiazepine hypnotics are selected from the group consisting of
alprazolam, brotizolam, clonazepam, cinolazepam, diazepam,
estazolam, etizolam, flunitrazepam, flurazepam, loprazolam,
lormetazepam, nimetazepam, qauzepam temazepam and triazolam.
[0042] In certain exemplary, non-limiting embodiments, the
non-benzodiazepine hypnotics are selected from the group consisting
of imidazopyridines non-benzodiazepine hypnotics,
pyrazolopyrimidines non-benzodiazepine hypnotics, cycloprrolones
non-benzodiazepine hypnotics and .beta.-carboline
non-benzodiazepine hypnotics.
[0043] In certain exemplary non-limiting embodiments, the
imidazopyridines non-benzodiazepine hypnotics are selected from the
group consisting of zolpidem (tartrate), alpidem, necopidem and
saripidem.
[0044] In certain exemplary, non-limiting embodiments, the
pyrazolopyrimidines non-benzodiazepine hypnotics selected from the
group consisting of zaleplon, divaplon, fasiplon, indiplon,
lorediplon, ocinaplon, panadiplon and taniplon.
[0045] In certain exemplary, non-limiting embodiments, the
cyclopyrrolones non-zodiazepine hypnotics are selected from the
group consisting of eszopiclone, zopiclone, pagoclone, pazinaclone,
suproclone and suriclone.
[0046] In certain exemplary, non-limiting embodiments, the
.beta.-carboline non-benzodiazepine hypnotics are selected from the
group consisting of abecarnil and gedocarnil.
[0047] In certain exemplary, non-limiting embodiments, the omega-3
fatty acid formulation comprise EPA and DHA in a weight to weight
ratio from about 3.5:1 to about 699 to 1.
[0048] In certain exemplary, non-limiting embodiments, the omega-3
fatty acid formulation comprise EPA and DHA in a weight to weight
ratio from about 4.01:1 to about 6.99:1.
[0049] In certain exemplary, non-limiting embodiments, the omega-3
fatty acid formulation comprise EPA and DHA in a weight to weight
ratio from about 4.01:1 to about 5:1.
[0050] In certain exemplary, non-limiting embodiments, the omega-3
fatty acid formulation comprise EPA and DHA in a weight to weight
ratio of EPA:DHA is approximately 4.09:1.
[0051] In certain exemplary, non-limiting embodiments, the omega-3
fatter acid formulation comprise EPA and DHA, when taken together,
is greater than 90% of the formulation by weight.
[0052] In certain exemplary, non-limiting embodiments, the omega-3
fatty acid formulation comprise EPA and DHA, when taken together,
is greater than 91% of the formulation by weight.
[0053] In certain exemplary, non-limiting embodiments, the present
invention is directed to a method of treating depression comprising
the administration of an insomnia therapy program to a patient
suffering from depression.
[0054] In certain exemplary, non-limiting embodiments, the present
invention is directed to a method of treating depression comprising
the administration of an insomnia, therapy program to a patient
suffering from depression and further comprising administration to
the patient an antidepressant in an amount effective to treat
depression in combination with the insomnia therapy program.
[0055] In certain exemplary, non-limiting embodiments, the present
invention is directed to a method of treating depression comprising
the administration of an insomnia therapy program for to a patient
suffering from depression and further comprising administration to
the patient an omega-3 fatty acid formulation in an amount
effective to treat depression in combination with the insomnia
therapy program.
[0056] In certain exemplary, non-limiting embodiments, the present
invention is directed to a method of treating depression comprising
the administration of an insomnia therapy program to a patient
suffering from depression and further comprising administration to
the patient an antidepressant in an amount effective to treat
depression in combination with the insomnia therapy program in the
absence of administering a omega-3 fatty acid formulation.
[0057] In certain exemplary, non-limiting embodiments, the present
invention is directed to a method of treating depression comprising
the administration of an insomnia therapy program for to a patient
suffering from depression and further comprising administration to
the patient an omega-3 fatty acid formulation in an amount
effective to treat depression in combination with the insomnia
therapy program in the absence of administering an
antidepressant.
[0058] In certain exemplary, non-limiting embodiments, the present
invention is directed to a method of treating depression comprising
the administration of an insomnia, therapy program to a patient
suffering from depression, either alone or in combination with
administration of one or more antidepressants and/or an omega-3
fatty acid formulation to the patient.
[0059] In certain exemplary, non-limiting embodiments, depression
is treatment resistant depression.
[0060] In certain exemplary, non-limiting embodiments, treatment of
depression or treatment-resistant depression is a 50% or greater
reduction in a depression ratings scale score over the course of
clinical treatment from starting point to endpoint depression
symptoms rating scales.
[0061] In certain exemplary, non-limiting embodiments, depression
symptoms rating scales are selected from the group consisting of
HRSD.sub.17, QIDS-SR.sub.16 and MADRS.
[0062] In certain exemplary, non-limiting embodiments, the
treatment of depression or treatment resistant depression comprises
the depression going into remission.
[0063] In certain exemplary, non-limiting embodiments, the
treatment of depression or treatment resistant depression comprises
the patient achieving less than or equal to 7 on the HRSD.sub.17
scale.
[0064] In certain exemplary, non-limiting embodiments, the
treatment of depression or treatment resistant depression comprises
the patient achieving less than or equal to 5 on the
AIDS-SR.sub.16.
[0065] In certain exemplary, non-limiting embodiments, the
treatment of depression or treatment resistant depression comprises
the patient achieving than or equal to 10 on the MADRS.
[0066] In certain exemplary, non-limiting embodiments, the patient
is pregnant.
[0067] In certain exemplary, non-limiting embodiments, the
treatment of depression or treatment-resistant depression occurs
within about 8 weeks of first treatment, about 7 weeks of first
treatment, about 6 weeks of first treatment, about 5 weeks of first
treatment, about 4 weeks of first treatment, about 3 weeks of first
treatment, about 2 weeks of first treatment or about 1 week of
first treatment.
[0068] In certain exemplary, non-limiting embodiments, onset of the
attenuation of depression or treatment-resistant depression occurs
within about 8 weeks of first treatment, about 7 weeks of first
treatment, about 6 weeks of first treatment, about 5 weeks of first
treatment, about 4 weeks of first treatment, about 3 weeks of first
treatment, about 2 weeks of first treatment or about 1 week of
first treatment.
[0069] Other exemplary, non-limiting embodiments provide a
pharmaceutical combination comprising an omega-3 fatty acid and a
sleep-inducing agent. The combination includes embodiments in which
the omega-3 fatty acid and sleep-inducing agent are in separate
dosage forms, but provided together, for example in a single
package.
[0070] In certain embodiments the purity of the omega-3 fatty acid
is greater than 90%. The disclosure also provides pharmaceutical
combination comprising an antidepressant and a sleep-inducing
agent. The antidepressant and sleep-inducing agent may be provided
together, but as separate dosage forms, or may comprise a single
dosage form, e.g. as a pharmaceutical formulation.
[0071] In certain exemplary, non-limiting embodiments, the present
invention is directed to methods of treating depression comprising
the administration of a non-benzodiazepine hypnotic to a patient in
need thereof.
[0072] In certain exemplary, non-limiting embodiments, the present
invention is directed to methods of treating depression comprising
the administration of a non-benzodiazepine hypnotic to a patient in
need thereof wherein said a non-benzodiazepine hypnotic is selected
from the group consisting of zolpidem (tartrate) and
eszopiclone.
[0073] In certain exemplary, non-limiting embodiments the
sleep-inducing agent is selected from trazodone, diphenhydramine,
zolpidem, eszopiclone, tryptophan, and melatonin. In other
embodiments the sleep-inducing agent is a benzodiazepine.
[0074] In other exemplary, non-limiting embodiments, one or more of
the above embodiments (or elements within the embodiments) are
suitably combined. By way of illustration, such an embodiment could
reflect the combination of the embodiment directed to "a method of
treating depression comprising the administration of an
anti-depressant effective amount of a combination of an omega-3
fatty acid formulation and a sleep-inducing agent to a patient in
need thereof" and the embodiment directed to "the treatment of
depression or treatment resistant depression comprises the patient
achieving less than or equal to 7 on the HRSD.sub.17 scale."
[0075] In other exemplary, non-limiting embodiments, the elements
comprising one or more of the embodiments herein are independent of
each other such that one or more of the elements may be suitably
excluded to comprise an additional embodiment thereof that is a
subset of the original embodiment. By way of illustration, the
embodiments recited herein defining benzodiazepine hypnotics as
being "selected from the group consisting of alprazolam,
brotizolam, clonazepam, cinolazepam, diazepam, estazolam, etizolam,
flunitrazepam, flurazepam, loprazolam, lormetazepam, nimetazepam,
qauzepam temazepam and triazolam" also represent an embodiment to a
subset or sub-combination thereof, e.g. "selected from the group
consisting of alprazolam, brotizolam and clonazepam" or any other
suitable subset.
DETAILED DESCRIPTION OF THE INVENTION
[0076] Generally speaking, and as discussed in greater detail in
the illustrative and non-limiting Examples provided herein, the
present invention is directed to pharmaceutical compositions and
methods for their use to treat depression. In various described
exemplary, non-limiting embodiments, the pharmaceutical
compositions include combinations of omega-3 fatty acids,
pharmacological sleep agents, and non-pharmacological sleep
therapies, and may include other ingredients such as
antidepressants. For example, certain exemplary, non-limiting
embodiments, the present invention include (1) a pharmaceutical
composition comprising an omega-3 fatty acid formulation and a
sleep-inducing agent (2) a pharmaceutical composition comprising an
omega-3 fatty acid formulation and a sleep-inducing agent, wherein
the composition is substantially free of an antidepressant (3) a
pharmaceutical composition comprising an omega-3 fatty acid
formulation and a sleep-inducing agent, wherein the composition
further comprises an antidepressant (4) a pharmaceutical
composition comprising an an antidepressant and a sleep-inducing
agent (5) a pharmaceutical composition comprising an an
antidepressant and a sleep-inducing agent, wherein the composition
is substantially free of an omega-3 fatty acid formulation (6) a
pharmaceutical composition comprising an antidepressant and a
sleep-inducing agent, wherein the composition further comprises an
omega-3 fatty acid formulation (7) methods of treating depression
comprising the administration of the above examples to a patient in
need thereof (8) a method of treating depression comprising the
administration of an insomnia therapy program to a patient
suffering from depression (9) a method of treating depression
comprising the administration of an insomnia therapy program to a
patient suffering from depression further comprising administration
to the patient an antidepressant in an amount effective to treat
depression in combination with said insomnia therapy program (10) a
method of treating depression comprising the administration of an
insomnia, therapy program to a patient suffering from depression
further comprising administration to the patient an omega-3 fatty
acid formulation in an amount effective to treat depression in
combination with said insomnia therapy program and (11) a method of
treating depression comprising the administration of an insomnia
therapy program to a patient suffering from depression further
comprising administration to the patient an omega-3 fatty acid
formulation and an antidepressant in an amount effective to treat
depression in combination with said insomnia therapy program.
[0077] Various definitions are provided herein, explicitly and/or
through usage, and it is understood that such definitions will be
applied by those of skill in the art in understanding the present
invention.
[0078] The terms "a" and "an" do not denote a limitation of
quantity, but rather denote the presence of at least one of the
referenced item.
[0079] An "active agent" means any compound, element, or mixture
that when administered to a patient alone or in combination with
another agent confers, directly or indirectly, a physiological
effect on the patient. When the active agent is a compound, salts,
solvates (including hydrates) of the free compound or salt,
crystalline and non-crystalline forms, as well as various
polymorphs of the compound are included. Compounds may contain one
or more asymmetric elements such as stereogenic centers,
stereogenic axes and the like, e.g. asymmetric carbon atoms, so
that the compounds can exist in different stereoisomeric forms.
These compounds can be, for example, racemates or optically active
forms. All stereoisomers, diastereomers, Z- and E-forms, in
purified and mixture forms are included. Accordingly, when a
compound is recited by specific name or a class of compounds is
recited, all these forms are intended to be included. By
illustration, active agents as provided herein include, for
example, antidepressants, omega-3 fatty acid formulations and
sleep-inducing agents.
[0080] A "dosage form" is any unit of administration ("unit dose")
of one or more active agents. As such, a "pharmaceutical
composition" as used herein may be presented in the form of a
dosage form or unit dose and may comprise one or more active
agents. Thus, a pharmaceutical composition as used herein could,
for example, provide two active agents admixed together in a unit
dose or provide two active agents combined in a dosage form wherein
the active agents are physically separated and/or have different
release rates. Pharmaceutical compositions include any suitable
formulation including, for example, capsules, tablets, injections
and liquids and may be administered through any suitable route
including oral, buccal, parenteral, intravenous, intramuscular,
rectal, transdermal and the like. Excipients used to formulate the
pharmaceutical formulations may be any of those suitable for the
respective dosage form such as fillers, stabilizers, extenders,
binders, humidifiers, surfactants, lubricants, and the like. A
"combined pharmaceutical product" as used herein is a combination
of two more doses of two or more different active agents combined
in separate dosage forms which are not admixed.
[0081] "Therapeutically effective amount" and/or "effective amount"
means an amount effective, when administered to a human or
non-human patient, to provide any therapeutic benefit. A
therapeutic benefit may be an amelioration of symptoms, e.g., an
amount effective to decrease the symptoms of binge-eating disorder
or a major depressive disorder. In certain circumstances a patient
may not present symptoms of a condition for which the patient is
being treated. Thus a therapeutically effective amount of a
compound is also an amount sufficient to provide a significant
positive effect on any indicia of a disease, disorder or condition
e.g. an amount sufficient to significantly reduce the frequency and
severity of binge eating behavior or depressive symptoms. A
significant effect on an indicia of a disorder or condition
includes a statistically significant in a standard parametric test
of statistical significance such as Student's T-test, where
p<0.05; though the effect need not be significant in some
embodiments. "Patient" as used herein means human or non-human
animals.
[0082] Frequency of dosage may vary depending on the compound used
and the particular type of depression treated. For most disorders a
dosage regimen of once per day is preferred. Dosage regimens in
which the active agent, whether omega-3 fatty acid, antidepressant,
or sleep-inducing agent is administered 2 times daily may
occasionally be more helpful.
[0083] It will be understood, however, that the specific dose level
for any particular patient will depend upon a variety of factors
including the activity of the specific compound employed, the age,
body weight, general health, sex, diet, time of administration,
route of administration, rate of excretion, drug combination and
the severity of the particular disease in the patient undergoing
therapy. Patients may generally be monitored for therapeutic
effectiveness using assays suitable for the condition being treated
or prevented, which will be familiar to those of ordinary skill in
the art.
[0084] Moreover, for each of the sleep-inducing agent(s),
antidepressant(s) and omega-3 fatty acid formulation(s), the dose
needed for use in the inventive compositions and combinations to
effectively treat depression may, in certain embodiments, be lower
than the dose needed to effectively treat depression when used
alone (this lower dose may be referred to herein as a "suboptimal"
dose, in that it is below an amount that is required for each of
these ingredients to reach optimal therapeutic effect for any given
patient when used alone). For example, in certain embodiments of
the present invention, the dose of an antidepressant needed to
effectively treat a patient's depression is lower when the
antidepressant is used together with a non-benzodiazepine hypnotic
(in a composition or combination, as taught herein) than when the
antidepressant is used alone. Similarly, for each of the
sleep-inducing agent(s), antidepressant(s) and omega-3 fatty acid
formulation(s), the dose needed for use in combination with an
insomnia therapy program to effectively treat depression may be
lower than the dose needed to effectively treat depression when
used alone. Thus, without being bound to any particular theory, the
use of two or more of the following: sleep-inducing agent(s),
antidepressant(s), omega-3 fatty acid formulation(s) and insomnia
sleep therapy program(s), in various embodiments of the present
invention has been found to be surprisingly effective in treating
depression.
[0085] Depression includes depressive disorders listed in the
American Psychiatric Association's Diagnostic and Statistical
Manual of Mental Disorders (DSM-V); such as major depressive
disorder, dysthymic disorder, and depressive disorder not otherwise
specified (for instance, premenstrual dysphoric disorder). In
certain embodiments the depression is treatment-resistant
depression. "Treatment-resistant depression" as used herein
indicates patients who do not respond to two separate trials of
different antidepressants of adequate dose and duration in the
current episode.
[0086] Depression may be considered effectively treated when a
patient's symptoms, as measured by a depression symptom rating
scale, improve.
[0087] "Depression symptoms rating scale" refers to any one of a
number of standardized questionnaires, clinical instruments, or
symptom inventories utilized to measure symptoms and symptom
severity in depression. Such rating scales are often used in
clinical studies to define treatment outcomes, based on changes
from the study's entry point(s) to endpoint(s). Such depression
symptoms rating scales include, but are not limited to, The Quick
Inventory of Depressive-Symptomatology Self-Report
(QIDS-SR.sub.16), the 17-Item Hamilton Rating Scale of Depression
(HRSD.sub.17), the 30-Item Inventory of Depressive Symptomatology
(IDS-C.sub.30), or The Montgomery-Asperg Depression Rating Scale
(MADRS) and Beckman Depression Inventory II. Such ratings scales
may involve patient self-report or be clinician rated. A 50% or
greater reduction in a depression ratings scale score over the
course of a clinical trial (starting point to endpoint) is
typically considered a favorable response for most depression
symptoms rating scales. "Remission" in clinical studies of
depression often refers to achieving at, or below, a particular
numerical rating score on a depression symptoms rating scale, i.e.,
less than or equal to 7 on the HRSD.sub.17; or less than or equal
to 5 on the QIDS-SR.sub.16; or less than or equal to 10 on the
MADRS or less than or equal to 9 on the Beck Depression Inventory
II. An alternative measure commonly used to assess depression and
response is the Patient Health Questionnaire No. 9 (PHQ-9). A
reduction in the score is generally used as a measure of
improvement and the score level is used to estimate none, mild,
moderate or severe disease categories. Moving from one category to
another is generally considered significant change. As such
treatment of depression or treatment-resistant depression may be
evidenced by an improvement to the patient progressing to next less
severe PHQ-9 category after treatment which is termed "PHQ-9
categorical improvement" as used herein.
[0088] As used herein, "sleep-inducing compounds" and/or
"sleep-inducing agents" include the following: (1) antihistamines
such as BENADRYL.RTM. (diphenhydramine), (2) "hypnotics" which
include (a) benzodiazepines such as alprazolam, brotizolam,
clonazepam, cinolazepam, diazepam, estazolam, etizolam,
flunitrazepam, flurazepam, loprazolam, lormetazepam, nimetazepam,
qauzepam temazepam, and HALCION.RTM. (triazolam), (b)
"non-benzodiazepine hypnotics" also known as Z-drugs such as (i)
"imidazopyridines" including AMBIEN (CR).RTM. zolpidem (tartrate),
alpidem, necopidem and saripidem (ii) "pyrazolopyrimidines" such as
zaleplon, divaplon, fasiplon, indiplon, lorediplon, ocinaplon,
panadiplon and taniplon (iii) "cyclopyrrolones" such as
LUNESTA.RTM. (eszopiclone), IMOVANE.RTM. (zopiclone), pagoclone,
pazinaclone, suproclone and suriclone and (iv) .beta.-carbolines
such as abecarnil, gedocarnil (3) certain tricyclic antidepressants
including DESYREL.RTM. (trazodone), (4) melatonin and melatonin
receptor agonists such as ramelteon and (5) other sleep-inducing
agents such as tryptophan and Valerian root and melatonin.
[0089] The term "antidepressant" as used herein includes (1)
tricyclic antidepressants including DESYREL.RTM. (trazodone),
doxepin, amitriptyline, amoxapine, clomipramine, desipramine,
doxepin, imipramine, maprotiline, nortriptyline, protriptyline, and
trimipramine; (2) selective serotonin reuptake inhibitors (SSRIs)
including citalopram, escitalopram, femoxetine, fluoxetine,
fluvoxamine, paroxetine, sertraline, and zimeldine; selective
serotonin norepinephrine reuptake inhibitors including duloxetine,
venlafaxine, desvenlafaxine, milnacipran, and clovoxamine; (3)
norepinephrine dopamine reuptake inhibitors such as bupropion; and
(4) alpha-2 antagonist/serotonin 5HT2-3 receptor antagonists such
as mirtazapine.
[0090] Wherein embodiments of the present invention comprise both
an antidepressant and a sleep-inducing agent, the antidepressant
and the sleep-inducing agent are different compounds. For example,
trazadone is known in the art both as an antidepressant and as a
sleep-inducing agent. Accordingly, an embodiment of the present
invention that is directed to a pharmaceutical composition
including both an antidepressant and a sleep-inducing agent may
include trazadone as either the antidepressant or as the
sleep-inducing agent, but not both.
[0091] As used herein, an "omega-3 fatty acid formulation" includes
EPA and/or DHA. More particularly, an omega-3 fatty acid
formulation according to the present invention may comprise EPA and
DHA in a weight to weight ratio from about 3.5:1 to about 6.99 to
1, from about 4.01:1 to about 6.99:1, or from about 4.01:1 to about
5:1. The present invention also provides a highly purified omega-3
fatty acid formulation in which the weight to weight ratio of
EPA:DHA is approximately 4.09:1. The EPA and DHA may be present in
the formulation in either the triglyceride form or in the form of
esterified fatty acid. Capsules typically contain the ethyl esters
forms of EPA and DHA. Candy formulations typically contain the
triglyceride forms of EPA and DHA.
[0092] The present invention also provides highly purified omega-3
fatty acid formulations in which the content of EPA and DHA, taken
together, is greater than about 70%, greater than about 75%,
greater than about 84%, or greater than about 85% of the
formulation by weight, and the omega-3 fatty acids comprise greater
than about 85%, greater than about 90%, or greater than about 91%
of the formulation by weight. Additionally the present invention
provides omega-3 fatty acid formulations in which the amount of
cholesterol in the formulation is less than about 5% by weight,
less than about 2.5% by weight, or less than about 1% by weight.
The present invention also includes omega-3 fatty acid formulations
in which the formulation comprises less than about 20
milliequivalents per kg peroxides, less than about 10
milliequivalents per kg peroxides, or less than about 5
milliequivalents per kg peroxides. See also U.S. Pat. No.
8,071,646, incorporated in its entirety by reference herein.
[0093] As discussed herein, in certain embodiments the present
invention is directed methods of treating depression by
administering an insomnia therapy program to a patient suffering
from depression (alone or in combination with one or more
antidepressants and/or an omega-3 fatty acid formulation).
[0094] As used herein, the term "insomnia therapy program" refers
to a non-pharmacological, computer-implemented cognitive behavioral
therapy program useful for treating insomnia in a patient. The
terms "insomnia, therapy program," "insomnia talk therapy program,"
and "talk therapy program for insomnia" may be used interchangeably
herein.
[0095] One example of an insomnia therapy program that may be used
in the present invention includes the program described in Vincent
and Lewycky, 2009 and Vincent et al., 2009, the entirety of each of
which is hereby incorporated by reference. While such programs have
been shown to be effective for treating insomnia (See, for example,
Vincent, 2009), they have not been used to treat depression.
[0096] In one embodiment, an insomnia therapy program used in the
present invention includes a plurality of software modules with
which the patient interacts over a network. The software modules
are stored in a computer system which includes non-transitory
computer readable medium for storing the software, and one or more
processors for executing instructions contained in the software.
The software modules may be web-based such that the patient
interacts with the software modules over the Internet.
[0097] As set forth in Table 1, each software module is intended to
affect a cognitive and/or behavioral change in the patient.
TABLE-US-00001 TABLE 1 Insomnia Therapy Program: Software Modules
Module Includes psychoeducation about insomnia (e.g., information 1
about normal sleep, types of sleep disorders). Presents the
cognitive behavioral model of insomnia (Morin, 1993). Patient is
instructed to avoid clock-watching to reduce hyperarousal in the
bedroom. Module Includes information regarding sleep hygiene (e.g.,
implication 2 of daytime napping for sleep, information regarding
effects of alcohol consumption on sleep) and stimulus control
(e.g., encouragement to avoid engendering arousal in the bedroom
environment, removing of oneself from bed if unable to sleep, going
to bed only when sleepy). Patient is instructed to chose two habits
to change. Module Presents relaxation training and provides MP3
audio files for 3 paced breathing, progressive muscle relaxation,
imagery-induced relaxation, and self-hypnosis. Patient is
instructed to practice relaxation strategies on daily basis, as
well as to continue practicing sleep hygiene and stimulus control.
Patient is asked to choose the relaxation exercises that they most
liked and to practice with those. There is no demand to work on all
4 relaxation exercises concurrently. Module Teaches sleep
restriction (Spielman et al., 1987) and discusses 4 how to
gradually taper off hypnotic medications only under the direction
of a physician. Patient is against tapering if they had comorbid
medical conditions as a safety precaution. For SRT, patient is
informed about how to calculate a sleep window but is discouraged
from using this strategy if currently sleeping less than 4 hours
per night. Module Cognitive therapy, including instruction and
modeling regarding 5 the identification and correction of automatic
thoughts that may increase arousal (Morin, 1993); instruction
regarding scheduled problem solving (Dugas, 2003); and instruction
and modeling regarding the downward arrow technique (Burns, 1980).
Patient has the opportunity to listen to audio files of cognitive
therapy between actors portraying patients with insomnia and the
first author acting as cognitive therapist. Patient is instructed
to monitor thoughts and attempt to replace anxiety-provoking
thoughts with more realistic alternatives.
[0098] The discussion herein and the following Examples set forth
and illustrate various exemplary embodiments of the present
invention, which are understood to be illustrative and
non-limiting.
EXAMPLE 1
Case Study 1: 38 Year Old Male
[0099] A 38 year old male patient seen for depression had taken a
serotonin specific reuptake inhibitor, fluoxetine for four weeks
without improvement. The patient was started on 20 mg daily for one
month and this was increased to a maximum dose of 60 mg daily over
the subsequent two months. The higher doses improved depression
minimally Beck Depression Inventory II score change from 28 to 26
over three months of fluoxetine monotherapy.
[0100] Subsequently, addition of AMBIEN.RTM. at only 2.5 mg (one
half of a 5 mg tablet) led to improvement in depression rating
scales of 38% in 4 days after addition to the medical regimen. In
this case, the depression was rated with the Beck Depression
inventory II and at first visit the patient's score was 28 and at
the upper end of the moderate range.
[0101] Over the course of the patient's treatment with fluoxetine
as monotherapy, the patient's mood remained depressed with mild
improvement to a Beck Depression Inventory II score of 26 after
dose increases. When the AMBIEN.RTM. was added, the score improved
an additional 8 points to 18, and the score for sleep was
unchanged. At the time of this treatment course, the patient was
also taking albuterol inhaler as needed for asthma and had no other
active medical conditions or medications.
EXAMPLE 2
Case Study 2: 44 Year Old Female
[0102] A 44 year old female patient presented with depression that
had been unresponsive to three known antidepressants over the
preceding year (fluoxetine; venlafaxine; and the tricyclic
amitryptiline). A new trial of fluoxetine at 20 mg was started
concurrently with LUNESTA.RTM. (dose: 2 mg at bedtime). Mood
returned to normal/mild depression range based on PHQ-9 score. This
showed efficacy because the PHQ-9 score before treatment initiation
was 17 (indicating "moderately severe depression") and had dropped
to 7 (indicating "mild depression") in six days at subsequent
visit. This showed a shift of two categories in the PHO-9 scale. On
the PHQ the patient rated their sleep problems as "not at all" when
asked about trouble falling or staying asleep, or sleeping too
much. Antidepressant effects are known to occur in 2-6 weeks when
used as previously studied.
[0103] During the course of treatment this patient was utilizing
birth control via NUVARING .RTM. monthly and was also prescribed
alprazolam as needed for anxiety. Use of alprazolam was limited to
plane flights and attending crowded social events.
EXAMPLE 3
Case Study 3: 41 Year Old Male
[0104] A 41 year old male patient presented with no complaints of
sleep difficulties but with complaints of depression that had been
unresponsive to fluoxetine and citalopram. An omega-3 fatty acid
formulation was started at 2 grams daily composed of a >90% pure
omega-3 fatty acid formulation with a ratio of EPA:DHA of
approximately 4:1 with AMBIEM.RTM. (5 mg at bedtime) and in 5 days
mood showed significant improvement by patient report (patient
reported no longer feeling depressed).
[0105] Questioning the patient evidenced no difficulty
sleeping--either too much or too little--before the AMBIEN.RTM. is
started. There remained no sleep complaints throughout the
treatment course--either of which can occur with depression. During
the course of treatment patient was also taking atorvastatin, 10 mg
daily.
[0106] The above Examples surprisingly show and suggest inter alia
that non-benzodiazepine hypnotics (which are known in the art to
exacerbate depression) are effective in treating depression
(including treatment-resistant depression) when combined with
antidepressant(s) or omega-3 fatty acid(s).
EXAMPLE 4
Case Study 4: 62 Year Old Male
[0107] A 62 year old male patient suffering from depression had
failed trials of several medications including fluoxetine,
citalopram, trazodone. In addition, the patient had taken
ATIVAN.RTM. (lorazepam) on rare occasions related to anxiety
inducing situations which also did not improve the patient's
depression.
[0108] The patient was started on a trial of fluoxetine and
ATIVAN.RTM. (lorazepam) regularly at bedtime (0.5 mg and an
additional 0.5 mg as needed for dose of 1.0 mg) (Riemann, 2009) and
the patient's mood improved, with rating scale improvements (PHQ-9
score from 22 to 10) of greater than 50% in one week of
treatment.
[0109] This example surprisingly shows and suggests inter alia that
benzodiazepine hypnotics (which have been shown in the art to have
no significant effect in treating depression) are effective in
treating depression (including treatment-resistant depression) when
combined with antidepressant(s).
EXAMPLE 5
Case Study 5: 35 Year Old Female
[0110] A 35 year old female patient with onset of depression in
pregnancy was interested in natural remedies. The patient was
started on an omega-3 fatty acid (OMAX-3.RTM.) with minimal effect
after 4 weeks PHQ-9 score went from 17 to 16.
[0111] Two weeks later the patient's PHQ-9 remained at 16. The
patient was not complaining of sleep difficulties, in fact
described increased sleep. Despite this, Valerian (obtained from
GNC.RTM.--which is known to help induce sleep (Gyllenhaal,
2000)--was added to the regimen (of OMAX-3.RTM.) at 500 mg one hour
before bed. The patient described a desired bed time of ten PM and
dose was taken at 9 PM.
[0112] One week later the patient described improved mood and the
patient's PHQ-9 score improved to 11 despite the fact Valerian is a
central nervous system depressant and is believed to cause mild
depression (Houghton, 1999).
[0113] The above Example surprisingly shows and suggests inter
cilia that sleep-inducing agents such as Valerian (which have not
been shown in the art to be effective in treating depression) are
effective in treating depression (including treatment-resistant
depression) when combined with omega-3 fatty acid(s).
EXAMPLE 6
Case Study 6: 36 Year Old Female
[0114] Onset of depression in pregnancy is common. In this 36 year
old pregnant female patient who presented with new onset of
depression, the patient's PHQ-9 score was 1.5 and the patient
detailed no sleep complaints. The patient was concerned about
taking any pharmaceutical and was initiated on an omega-3 fatty
acid with high purity (>90% omega-3 and a ratio of EPA to DHA of
approximately 4:1, sold as OMAX-3.RTM. and simultaneously started
on an insomnia therapy program as described herein that provided
cognitive behavioral therapy for insomnia over six weeks, despite a
lack of insomnia complaints.
[0115] Specifically, the insomnia therapy program was organized
into modules, and was offered as an internet-based application as a
mix of interactive multimedia content, an interactive sleep diary,
sleep restriction, and relaxation training. Module 1 included
psychoeducation about insomnia (e.g., information about normal
sleep, types of sleep disorders) and presented the cognitive
behavioral model of insomnia. Module 2 included information
regarding sleep hygiene (e.g., implication of daytime napping for
sleep, information regarding effects of alcohol consumption on
sleep) and stimulus control (e.g., encouragement to avoid
engendering arousal in the bedroom environment, removing of oneself
from bed if unable to sleep, going to bed only when sleepy). Module
3 presented relaxation, passive muscle relaxation, imagery-induced
relaxation, and self-hypnosis. Participants were asked to choose
the relaxation exercises that they most liked and to practice with
those. There was no demand to work on all four relaxation exercises
concurrently. Module 4 introduced the concept of sleep restriction.
Module 5 introduced cognitive therapy, including correction of
automatic thoughts that may increase arousal, instruction regarding
scheduled problem solving, and instruction and modeling regarding
the downward arrow technique. Module 6 were exercises in
mindfulness meditation.
[0116] The patient's depression improved after 3 weeks to a PHQ-9
score of 4.
[0117] The above Example surprisingly shows and suggests inter alia
that insomnia therapy programs when combined with omega-3 fatty
acid(s) (which have not been shown in clinical trials to be
effective in treating depression when administered independently)
are effective in treating depression (including treatment-resistant
depression) when co-administered.
EXAMPLE 7
Case Study 7: Insomnia Therapy Program to Treat Depression in a
Male Patient
[0118] A male patient with a history of depression presented and
described a history of trying several antidepressants without
success. The patient's PHQ-9 was 16 and the patient endorsed 9
hours of sleep, and rated the PHQ-9 sleep question at 0. The
patient did, however, describe sleeping about 4 hours during the
day and 5 hours at night. The patient was given a regimen of sleep
hygiene and sleep restriction from an interactive insomnia therapy
program as described herein.
[0119] Specifically, the program was a six module program which
also tracked sleep metrics in a sleep diary. The modules focused on
insomnia and goal setting, relaxation exercises, sleep restriction,
mindfulness, cognitive restructuring and sleep hygiene. The patient
continued to sleep 9 hours, but this shifted to all being at night
as a result of the intervention. The patient's PHQ-9 score dropped
to 4.
[0120] The above Example surprisingly shows and suggests inter alia
that insomnia therapy programs (which have not been shown in the
art to be effective in treating depression) are effective in
treating depression (including treatment-resistant depression).
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[0150] The present invention may be embodied in other forms or
carried out in other ways without departing from the spirit or
essential characteristics thereof. The present disclosure is
therefore to be considered as in all aspects illustrated and not
restrictive, the scope of the invention being indicated by the
appended Claims, and all changes which come within the meaning and
range of equivalency are intended to be embraced therein.
[0151] Various references are cited throughout the Specification
and provided in a list of references above, each of which is
incorporated herein by reference in its entirety. The citation of
references herein shall not be construed as an admission that such
is prior art to the present invention.
* * * * *
References