PSILOCYBIN AND AN ADJUNCTIVE SEROTONIN REUPTAKE INHIBITOR FOR USE IN THE TREATMENT OF TREAMENT- RESISTANT DEPRESSION
The disclosure provides methods for treating a subject in need thereof comprising administering to the subject a therapeutically-effective dose of psilocybin. The methods described herein may be used to treat a variety of diseases, disorders, and conditions. For example, the methods may be used to treat depression, neurocognitive disorders, autism spectrum disorder, and/or attention-deficit/hyperactivity disorder.
1 . A method of treating treatment-resistant depression in a subject in need thereof, the method comprising administering an effective amount of psilocybin or an active metabolite thereof to the subject as an adjunctive to Selective Serotonin Reuptake Inhibitor (SSRI) therapy.
2 . The method of claim 1 , wherein the SSRI is selected from the group consisting of escitalopram, sertraline, fluoxetine, vilazodone, vortioxetine, paroxetine and citalopram.
3 . The method of claim 1 , wherein the SSRI is administered prior to administration of psilocybin.
4 . The method of claim 1 , wherein the SSRI is administered after administration of psilocybin.
5 . The method of claim 1 , wherein the SSRI is administered on the same day as the psilocybin.
6 . The method of claim 1 , wherein about 25 mg of psilocybin or an active metabolite thereof is administered to the subject.
7 . The method of claim 1 , wherein at least one sign or symptom of depression is reduced by the administration of psilocybin.
8 . The method of claim 7 , wherein the sign or symptom of depression is depressed mood, diminished interest in activities, weight loss or gain, decrease or increase in appetite, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or excessive or inappropriate guilt, diminished ability to concentrate or indecisiveness, or suicidal ideation or behavior.
9 . The method of claim 7 , wherein the sign or symptom of depression is measured according to a diary assessment, an assessment by clinician or caregiver, a clinical rating scale, or by functional MRI.
10 . The method of claim 9 , wherein the clinical rating scale is a Quick Inventory of Depressive Symptomatology (QIDS)-16 scale, a QIDS-16 daily scale, a Hamilton Depression Rating scale, a Beck Depression Inventory scale, a Montgomery-Åsberg Depression Rating Scale (MADRS), a Clinical Global Impression Scale, a Zung Self-Rating Depression Scale, a Raskin Depression Rating Scale, Young Mania Rating Scale, or combinations thereof.
11 . The method of claim 9 , wherein the clinical rating scale is MADRS.
12 . The method of claim 11 , wherein the administration of psilocybin provides an about 50% reduction in patient's MADRS total score compared to prior to treatment with psilocybin.
13 . The method of claim 11 , wherein the administration of psilocybin provides a reduction in the patient's MADRS total score to ≤10.
14 . The method of claim 9 , wherein the clinical rating scale is Clinical Global Impression-Severity scale (CGI-S).
15 . The method of claim 14 , wherein the administration of psilocybin provides a reduction in the patient's CGI-S score to ≤2.
16 . The method of claim 9 , wherein the clinical rating scale is Clinical Global Impression-Improvement scale (CGI-I).
17 . The method of claim 16 , wherein the administration of psilocybin provides a reduction in the patient's CGI-I score reported as “very much improved” or “much improved” compared to prior to treatment with psilocybin.
18 . The method of claim 1 , wherein the administration of psilocybin provides a reduction in the patient's anxiety compared to prior to treatment with psilocybin.
19 . The method of claim 18 , wherein the administration of psilocybin provides a reduction in the patient's Generalised Anxiety Disorder-7 item scale (GAD-7) total score compared to prior to treatment with psilocybin.
20 . The method of claim 1 , wherein at least one sign or symptom of depression is alleviated within 24 hours of administration of the psilocybin.
21 . The method of claim 1 , wherein at least one symptom of depression is alleviated within 1 week of administration of the psilocybin.
22 . The method of claim 1 , wherein at least one symptom of depression is alleviated for a period of at least 1 month, at least 3 months, or at least 12 months after administration of the psilocybin.
23 . (canceled)
24 . (canceled)
25 . The method of claim 1 , wherein at least two doses of psilocybin are administered to the subject.
26 . The method of claim 1 , wherein the psilocybin is administered once per day.
27 . The method of claim 25 , wherein the psilocybin is administered at least once or twice per week.
28 . (canceled)
29 . The method of claim 25 , wherein the psilocybin is administered at least once per month, at least twice per month, at least once every three months, at least once every six months, or at least once every 12 months.
30 . (canceled)
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34 . The method of claim 25 , wherein each dose of psilocybin administered is about 25 mg.
35 . The method of claim 1 , wherein the psilocybin is administered by one of the following routes: oral, intravenous, intramuscular, parenteral, topical, inhalation, rectal, transmucosal, intranasal, buccal, vaginal, intrathecal, intraocular, transdermal, in utero, intralymphatic, or by direct tissue or organ injection.
36 . The method of claim 35 , wherein the psilocybin is administered orally.
37 . The method of claim 1 , wherein the psilocybin comprises a crystalline psilocybin.
38 . (canceled)
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46 . The method of claim 37 , wherein the crystalline psilocybin is characterized by an X-ray powder diffraction (XRPD) peak at 17.5±0.1 and one or more XRPD peaks selected from 11.5±0.1, 12.0±0.1, 14.5±0.1, and 19.7±0.1 °2θ.
47 . The method of claim 37 , wherein the crystalline psilocybin is characterized by an X-ray powder diffraction (XRPD) peak at 19.7±0.1 and one or more XRPD peaks selected from 11.5±0.1, 12.0±0.1, 14.5±0.1, and 17.5±0.1 °2θ.