Antidepressant therapy
The invention relates to the treatment of depressive and anxiety disorders, specifically to improved therapy for patients afflicted with post-stroke depression and/or anxiety, or with major depressive disorder. More specifically, the invention relates to the use of chemokine receptor (CCR5) inhibitors, either alone or in combination with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), in treating depression and anxiety, as well as certain post-stroke complications that may include cognitive impairment. Compositions and methods according to embodiments of the invention are advantageously useful in the treatment of patients with treatment-resistant depression and other patient populations in which conventional antidepressant therapy is inadequate or insufficient.
1 . A method of treating or inhibiting the symptoms of a depressive and/or anxiety disorder selected from the group consisting of post-stroke depression (PSD), post-stroke anxiety (PSA), treatment resistant depression (TRD), and major depressive disorder (MDD), in a subject diagnosed with a cerebral infarction or a transient ischemic attack for 4-24 months, the method comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of maraviroc or a derivative thereof.
2 . The method of claim 1 , wherein the therapeutically effective amount of maraviroc is 100 mg per day to 300 mg per day, and the subject manifests both depressive and anxiety symptoms.
3 . The method of claim 1 , wherein the subject is at high risk of suicidal behavior evaluated by the Columbia Suicide Severity Rating Scale (C-SSRS); the subject is a human female; or wherein said subject is over 50 years of age or over 65 years of age.
4 . The method of claim 1 , wherein the subject is diagnosed as being afflicted with post-stroke depression and/or post-stroke anxiety.
5 . The method of claim 4 , wherein said subject is further diagnosed with post-stroke cognitive impairment (PSCI); or said subject is diagnosed with mild to moderate white matter lesions (WMLs) load or with severe WML load as evaluated by the Fazekas score prior to treatment.
6 . The method according to claim 1 , comprising administering to said subject maraviroc in concurrent or sequential combination with at least one antidepressant selected from the group consisting of a selective serotonin reuptake inhibitor (SSRI) and a serotonin-norepinephrine reuptake inhibitor (SNRI).
7 . The method according to claim 1 , comprising administering to said subject maraviroc as a sole active ingredient.
8 . A method for treating treatment-resistant depression (TRD) in a human subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a CCR5 inhibitor or antagonist, wherein the CCR5 inhibitor is maraviroc or a derivative thereof.
9 . The method of claim 8 , comprising administering to said subject maraviroc in concurrent or sequential combination with at least one antidepressant selected from the group consisting of a selective serotonin reuptake inhibitor (SSRI) and a Serotonin-Norepinephrine Reuptake Inhibitor (SNRI).
10 . The method of claim 8 , wherein said subject is resistant to treatment with at least one of citalopram, escitalopram, sertraline, mirtazapine, and combinations thereof, or the subject is at high risk of suicidal behavior evaluated by the Columbia Suicide Severity Rating Scale (C-SSRS).
11 . The method of claim 8 , comprising administering to said subject maraviroc in combination with citalopram, escitalopram, sertraline, mirtazapine, or combinations thereof; or administering to said subject maraviroc as a sole active ingredient.
12 . A method of treating post-stroke cognitive impairment (PSCI) in a subject diagnosed with established PSCI, comprising administering to the subject Maraviroc in a therapeutically effective amount of 100 mg per day to 600 mg per day, wherein treating comprises improving the cognitive impairment of the subject characterized by an improved cognitive score of at least two points compared to the score determined prior to treatment.
13 . The method of claim 12 , wherein treating said subject has been diagnosed with cerebral infarction or transient ischemic attack 4-24 months prior to administration of the maraviroc.
14 . The method of claim 12 , wherein treating comprises eliminating or reducing the severity of a symptom or clinical sign associated with PSCI compared to its level as determined prior to treatment.
15 . The method of claim 12 , wherein the subject is further diagnosed with depression and/or anxiety within one month to two years of stroke occurrence.
16 . The method of claim 12 , wherein said subject is diagnosed with white matter lesions (WMLs) prior to treatment, wherein said subject is diagnosed with mild to moderate WML load or with severe WML load as evaluated by the Fazekas score.
17 . The method of claim 12 , wherein the improvement in cognitive score is assessed using the Toronto Cognitive Assessment (TorCA) test.