Combination treatment for impaired motor function in parkinson's disease
The invention provides a method, and dosage form therefor, of treating impaired motor function associated with Parkinson's disease, anti-Parkinson's drug treatment, e.g. L-Dopa therapy, and/or dementia associated with Parkinson's disease. The invention includes the combined administration of an NMDA receptor antagonist and an antidepressant, e.g., the combination of amantadine and citalopram or venlafaxine, or an NMDA receptor antagonist and an anxiolytic agent, e.g., amantadine and buspirone or trazodone, for the amelioration of undesired tremors, akinesia, dyskinesia, or bradykinesia associated with one or more different disorders or diseases. The drugs can be included in a single dosage form. One embodiment includes a combination dosage form containing each drug in controlled release forms. Another embodiment includes a combination dosage form providing a controlled release of an NMDA receptor antagonist and a rapid release of a neuroactive agent after administration to a subject.
1 . A method of treating or improving the clinical status of a patient suffering from undesired motor movement symptoms associated with one or more of Parkinson's disease, anti-Parkinson's disease drug therapy, and dementia associated with Parkinson's disease, by reducing the occurrence, frequency or severity of the one or more motor movement symptoms or by substantially eliminating the occurrence of the one or more motor movement symptoms, the method comprising the steps of:
a. administering an amount of NMDA-RA to a subject suffering from one or more motor movement symptoms associated with one or more disorders; and
b. administering to the subject an amount of neuroactive agent selected from the group consisting of a selective serotonin reuptake inhibitor, a serotonin norepinephrine reuptake inhibitor, and an anxiolytic agent;
c. wherein the drugs are administered for a period of time sufficient to reduce the occurrence, frequency or severity of the one or more motor movement symptoms or to substantially eliminate the occurrence of the one or more motor movement symptoms.
2 . The method of claim 1 , wherein the motor movement disorder is selected from the group consisting of tremors, dyskinesia, akinesia, rigidity and bradykinesia.
3 . The method of claim 1 , wherein the NMDA-RA is selected from the group consisting of amantadine, memantine, budipine and ifenprodil.
4 . The method of claim 3 , wherein the selective serotonin reuptake inhibitor is selected from the group consisting of fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram.
5 . The method of claim 3 , wherein the serotonin norepinephrine reuptake inhibitor is selected from the group consisting of venlafaxine, milnacipran, and duloxetine.
6 . The method of claim 3 , wherein the anxiolytic agent is of the benzodiazepine class.
7 . The method of claim 6 , wherein the anxiolytic agent is selected from the group consisting of lorazepam and oxazepam.
8 . The method of claim 3 , wherein the anxiolytic agent is of the nonbenzodiazepine class.
9 . The method of claim 8 , wherein the anxiolytic agent is selected from the group consisting of buspirone and trazodone.
10 . The method of claim 1 , wherein the selective serotonin reuptake inhibitor is selected from the group consisting of fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram.
11 . The method of claim 1 , wherein the serotonin norepinephrine reuptake inhibitor is selected from the group consisting of venlafaxine, milnacipran, and duloxetine.
12 . The method of claim 1 , wherein the anxiolytic agent is of the benzodiazepine class.
13 . The method of claim 12 , wherein the anxiolytic agent is selected from the group consisting of lorazepam and oxazepam.
14 . The method of claim 1 , wherein the anxiolytic agent is of the nonbenzodiazepine class.
15 . The method of claim 14 , wherein the anxiolytic agent is selected from the group consisting of buspirone and trazodone.
16 . The method of claim 1 , wherein the NMDA-RA is amantadine and the selective serotonin reuptake inhibitor is citalopram.
17 . The method of claim 1 , wherein the NMDA-RA and the neuroactive agent are administered in the same dosage form.
18 . The method of claim 1 , wherein the NMDA-RA and the neuroactive agent are administered in separate dosage forms.
19 . The method of claim 1 , wherein the NMDA-RA and the neuroactive agent are administered simultaneously or in an overlapping manner.
20 . The method of claim 1 , wherein the NMDA-RA and the neuroactive agent are administered sequentially.
21 . The method of claim 1 , wherein the NMDA-RA is present in a therapeutically effective or sub-therapeutically effective amount.
22 . The method of claim 21 , wherein the neuroactive agent is present in a therapeutically effective or sub-therapeutically effective amount.
23 . The method of claim 1 , wherein the neuroactive agent is present in a therapeutically effective or sub-therapeutically effective amount.
24 . The method of claim 1 , wherein the NMDA-RA and the neuroactive agent are administered via different routes.
25 . The method of claim 1 , wherein the NMDA-RA and the neuroactive agent are administered via the same route.
26 . A method of treating or improving the clinical status of a patient suffering from undesired motor movement symptoms associated with one or more of Parkinson's disease, anti-Parkinson's disease drug therapy, and dementia associated with Parkinson's disease, the method comprising the steps of:
a. orally administering an amount of NMDA-RA to a subject suffering from one or more motor movement symptoms associated with one or more disorders; and
b. orally administering to the subject an amount of neuroactive agent selected from the group consisting of a selective serotonin reuptake inhibitor, a serotonin norepinephrine reuptake inhibitor, and an anxiolytic agent; wherein
c. the NMDA-RA and neuroactive agent are administered in a combined amount effective to and for a period of time sufficient to reduce the occurrence, frequency or severity of the one or more motor movement symptoms or to substantially eliminate the occurrence of the one or more motor movement symptoms;
d. the motor movement disorder is selected from the group consisting of tremor, dyskinesia, akinesia, rigidity and bradykinesia.
27 . The method of claim 26 , wherein the NMDA-RA is selected from the group consisting of amantadine, memantine, budipine and ifenprodil.
28 . The method of claim 27 , wherein the selective serotonin reuptake inhibitor is selected from the group consisting of fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram.
29 . The method of claim 27 , wherein the serotonin norepinephrine reuptake inhibitor is selected from the group consisting of venlafaxine, milnacipran, and duloxetine.
30 . The method of claim 27 , wherein the anxiolytic agent is of the benzodiazepine class.
31 . The method of claim 30 , wherein the anxiolytic agent is selected from the group consisting of lorazepam and oxazepam.
32 . The method of claim 27 , wherein the anxiolytic agent is of the nonbenzodiazepine class.
33 . The method of claim 32 , wherein the anxiolytic agent is selected from the group consisting of buspirone and trazodone.
34 . The method of claim 26 , wherein the selective serotonin reuptake inhibitor is selected from the group consisting of fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram.
35 . The method of claim 26 , wherein the serotonin norepinephrine reuptake inhibitor is selected from the group consisting of venlafaxine, milnacipran, and duloxetine.
36 . The method of claim 26 , wherein the anxiolytic agent is of the benzodiazepine class.
37 . The method of claim 36 , wherein the anxiolytic agent is selected from the group consisting of lorazepam and oxazepam.
38 . The method of claim 26 , wherein the anxiolytic agent is of the nonbenzodiazepine class.
39 . The method of claim 38 , wherein the anxiolytic agent is selected from the group consisting of buspirone and trazodone.
40 . The method of claim 26 , wherein the NMDA-RA is amantadine and the selective serotonin reuptake inhibitor is citalopram.
41 . The method of claim 26 , wherein the NMDA-RA and the neuroactive agent are administered simultaneously or in an overlapping manner.
42 . The method of claim 26 , wherein the NMDA-RA and the neuroactive agent are administered sequentially.
43 . The method of claim 26 , wherein the NMDA-RA is present in a therapeutically effective or sub-therapeutically effective amount.
44 . The method of claim 43 , wherein the neuroactive agent is present in a therapeutically effective or sub-therapeutically effective amount.
45 . The method of claim 26 , wherein the neuroactive agent is present in a therapeutically effective or sub-therapeutically effective amount.
46 . The method of claim 26 , wherein the NMDA-RA and the neuroactive agent are administered in the same dosage form.
47 . The method of claim 26 , wherein the NMDA-RA and the neuroactive agent are administered in separate dosage forms.
48 . A method of improving the clinical status of a subject suffering from undesired motor movement symptoms associated with one or more of Parkinson's disease, anti-Parkinson's disease drug therapy, and dementia associated with Parkinson's disease, the method comprising the step of:
a. orally administering to the subject on a once or twice daily basis an oral dosage form comprising a therapeutically effective or sub-therapeutically effective amount of an NMDA-RA; a therapeutically effective or sub-therapeutically effective amount of a neuroactive agent selected from the group consisting of a selective serotonin reuptake inhibitor, a serotonin norepinephrine reuptake inhibitor, and an anxiolytic agent; and one or more pharmaceutically acceptable excipients;
b. wherein, when the dosage form is administered to the subject, the NMDA-RA is released according to an immediate, rapid, controlled or sustained release profile, the neuroactive agent is released according to an immediate, rapid, controlled or sustained release profile, and release of one or both the NMDA-RA and the neuroactive agent is optionally delayed a lag period,
c. whereby the occurrence, frequency or severity of the one or more motor movement symptoms is reduced or substantially eliminated.
49 . The method of claim 48 , wherein the motor movement symptom is selected from the group consisting of tremors, dyskinesia, akinesia, rigidity and bradykinesia.
50 . The method of claim 48 , wherein the NMDA-RA is selected from the group consisting of amantadine, memantine, budipine and ifenprodil.
51 . The method of claim 50 , wherein the selective serotonin reuptake inhibitor is selected from the group consisting of fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram.
52 . The method of claim 50 , wherein the serotonin norepinephrine reuptake inhibitor is selected from the group consisting of venlafaxine, milnacipran, and duloxetine.
53 . The method of claim 50 , wherein the anxiolytic agent is of the benzodiazepine class.
54 . The method of claim 53 , wherein the anxiolytic agent is selected from the group consisting of lorazepam and oxazepam.
55 . The method of claim 50 , wherein the anxiolytic agent is of the nonbenzodiazepine class.
56 . The method of claim 55 , wherein the anxiolytic agent is selected from the group consisting of buspirone and trazodone.
57 . The method of claim 48 , wherein the selective serotonin reuptake inhibitor is selected from the group consisting of fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram.
58 . The method of claim 48 , wherein the serotonin norepinephrine reuptake inhibitor is selected from the group consisting of venlafaxine, milnacipran, and duloxetine.
59 . The method of claim 48 , wherein the anxiolytic agent is of the benzodiazepine class.
60 . The method of claim 59 , wherein the anxiolytic agent is selected from the group consisting of lorazepam and oxazepam.
61 . The method of claim 48 , wherein the anxiolytic agent is of the nonbenzodiazepine class.
62 . The method of claim 61 , wherein the anxiolytic agent is selected from the group consisting of buspirone and trazodone.
63 . The method of claim 48 , wherein the NMDA-RA is amantadine and the selective serotonin reuptake inhibitor is citalopram.
64 . The method of claim 48 , wherein the NMDA-RA and the neuroactive agent are administered simultaneously or in an overlapping manner.
65 . The method of claim 48 , wherein the NMDA-RA and the neuroactive agent are administered sequentially.