Method of treating or preventing attention defecit hyperactivity disorder

Abstract

Methods and compositions for treating humans suffering from, or preventing a human from suffering, a physiological or psychiatric disease, disorder, or a condition where inhibiting reuptake of norepinephrine is a benefit are disclosed. The compositions comprise a compound having a pharmacological selectivity of serotonin (K ┐ )/norepinephrine (K ┐ ) of at least about 5000. Examples of such compounds include reboxetine, and more preferably optically pure (S,S) enantiomer of reboxetine. The methods generally include administration of a therapeutic amount of such compositions. Also disclosed are preparations of a medicament from the composition, and uses of the composition in a manufacture of the medicament to treat a human suffering from, or preventing a human from suffering, a physiological or psychiatric disease, disorder, or condition.

What is claimed is:  
     
         1 . A method of selectively inhibiting reuptake of norepinephrine, the method comprising the step of administering a therapeutically effective amount of a composition to an individual, the composition comprising a compound having a pharmacological selectivity of serotonin (K ┐ )/norepinephrine (K ┐ ) of at least about 5000.  
     
     
         2 . The method of  claim 1  wherein said composition is administered in an amount of about 0.1 to about 10 mg/day.  
     
     
         3 . The method of  claim 2  wherein said composition is administered in an amount of about 0.5 to about 8 mg/day.  
     
     
         4 . The method of  claim 3  wherein said composition is administered in an amount of about 0.5 to about 5 mg/day.  
     
     
         5 . The method of  claim 4  wherein said composition is administered in an amount of about 0.5 to about 2.5 mg/day.  
     
     
         6 . The method of  claim 5  wherein said composition is administered in an amount of about 0.5 to about 0.9 mg/day.  
     
     
         7 . The method of  claim 6  wherein said composition is administered in an amount of about 0.5 to about 0.8 mg/day.  
     
     
         8 . The method of  claim 7  wherein said composition is administered in an amount of about 0.5 to about 0.75 mg/day.  
     
     
         9 . The method of  claim 1  wherein said composition is administered orally, topically, parenterally, transdermally, rectally or vaginally.  
     
     
         10 . The method of  claim 9  wherein said composition is orally administered, and further comprising a pharmaceutically acceptable carrier selected from the group consisting of a binder, diluent, lubricant, disintegrating agent, effervescing agent, dyestuff, sweetener, wetting agent, and mixtures thereof.  
     
     
         11 . The method of  claim 10  wherein the oral administration is by a sachet, capsule, tablet, or aerosol spray.  
     
     
         12 . The method of  claim 9  wherein said composition is parenterally administered subcutaneously, intraveously, or intramuscularly.  
     
     
         13 . The method of  claim 1  wherein said compound comprises an optically pure (S,S) reboxetine, or a pharmaceutically acceptable salt thereof, said compound being substantially free of (R,R) reboxetine.  
     
     
         14 . The method of  claim 13  wherein the pharmaceutically acceptable salt is a methanesulfonate salt.  
     
     
         15 . The method of  claim 13  wherein the optically pure (S,S) reboxetine or pharmaceutically acceptable salt thereof comprises at least about 90 wt. % of (S,S) reboxetine, and less than about 10 wt. % of (R,R) reboxetine, based on the total weight of the (S,S) and (R,R) reboxetine present.  
     
     
         16 . The method of  claim 15  wherein the optically pure (S,S) reboxetine or pharmaceutically acceptable salt thereof comprises at least about 97 wt. % of (S,S) reboxetine and less than about 3 wt. % of (R,R) reboxetine, based on the total weight of the (S,S) and (R,R) reboxetine present.  
     
     
         17 . The method of  claim 16  wherein the optically pure (S,S) reboxetine or pharmaceutically acceptable salt thereof comprises at least about 99 wt. % of (S,S) reboxetine and less than about 1 wt. % of (R,R) reboxetine, based on the total weight of the (S,S) and (R,R) reboxetine present.  
     
     
         18 . The method of  claim 1  wherein said condition is selected from the group consisting of at least one of an addictive disorder and withdrawal syndrome, an adjustment disorder, an age-associated learning and mental disorder, anorexia nervosa, apathy, an attention-deficit disorder due to general medical conditions, attention-deficit hyperactivity disorder, bipolar disorder, bulimia nervosa, chronic fatigue syndrome, chronic or acute stress, chronic pain, conduct disorder, cyclothymic disorder, depression, dysthymic disorder, fibromyalgia and other somatoform disorders, generalized anxiety disorder, incontinence, an inhalation disorder, an intoxication disorder, mania, migraine headaches, obesity, obsessive compulsive disorders and related spectrum disorders, oppositional defiant disorder, panic disorder, peripheral neuropathy, post-traumatic stress disorder, premenstrual dysphoric disorder, a psychotic disorder, seasonal affective disorder, a sleep disorder, social phobia, a specific developmental disorder, selective serotonin reuptake inhibition (SSRI) “poop out” syndrome, and TIC disorders.  
     
     
         19 . The method of  claim 18  wherein the addictive disorder comprises an addiction to at least one of alcohol, nicotine, and other psychoactive substance.  
     
     
         20 . The method of  claim 18  wherein the adjustment disorder comprises depressed mood, anxiety, mixed anxiety and depressed mood, disturbance of conduct, or mixed disturbance of conduct or mood.  
     
     
         21 . The method of  claim 18  wherein the age-associated learning and mental disorder comprises Alzheimer's disease.  
     
     
         22 . The method of  claim 18  wherein the depression comprises adolescent depression or minor depression.  
     
     
         23 . The method of  claim 18  wherein the premenstrual dysphoric disorder comprises premenstrual syndrome or late luteal phase dysphoric disorder.  
     
     
         24 . The method of  claim 18  wherein the psychotic disorder comprises schizophrenia, schizoaffective, or a schizophreniform disorder.  
     
     
         25 . The method of  claim 18  wherein social phobia comprises social anxiety disorder.  
     
     
         26 . The method of  claim 18  wherein the sleep disorder comprises narcolepsy or enuresis.  
     
     
         27 . The method of  claim 18  wherein somatoform disorders comprise somatization disorder, conversion disorder, pain disorder, hypochondriasis, body dysmorphic disorder, undifferentiated somatoform disorder, or somatoform NOS.  
     
     
         28 . The method of  claim 18  wherein incontinence comprises stress incontinence, genuine stress incontinence, or mixed incontinence.  
     
     
         29 . The method of  claim 18  wherein TIC disorders comprise Tourette's Disease.  
     
     
         30 . The method of  claim 18  wherein said condition is selected from the group consisting of at least one of an adjustment disorder, an age-associated learning or mental disorder, apathy, attention-deficit hyperactivity disorder, attention-deficit disorder caused by medical conditions, bulimia nervosa, chronic fatigue syndrome, chronic or acute stress, chronic pain, cyclothymic disorder, depression, dysthymic disorder, generalized anxiety disorder, nicotine addiction, post-traumatic stress disorder, premenstrual dysphoric disorder, a psychotic disorder, and SSRI “poop out” syndrome.  
     
     
         31 . The method of  claim 30  wherein said condition is selected from the group consisting of at least one of apathy, attention-deficit hyperactivity disorder, attention-deficit disorder caused by medical conditions, chronic fatigue, cyclothymic disorder, depression, nicotine addiction, post-traumatic stress disorder, and SSRI “poop out” syndrome.  
     
     
         32 . The method of  claim 1  wherein the compound has a pharmacological selectivity of serotonin (K ┐ )/norepinephrine (K ┐ ) of at least about 10,000.  
     
     
         33 . The method of  claim 32  wherein the compound has a pharmacological selectivity of serotonin (K ┐ )/norepinephrine (K ┐ ) of at least about 12,000.  
     
     
         34 . The method of  claim 33  wherein the compound has a pharmacological selectivity of serotonin (K ┐ )/norepinephrine (K ┐ ) of at least about 25,000.  
     
     
         35 . The method of  claim 34  wherein the compound has a pharmacological selectivity of serotonin (K ┐ )/norepinephrine (K ┐ ) of at least about 50,000.  
     
     
         36 . The method of  claim 35  wherein the compound has a pharmacological selectivity of serotonin (K ┐ )/norepinephrine (K ┐ ) of at least about 75,000.  
     
     
         37 . The method of  claim 36  wherein the compound has a pharmacological selectivity of serotonin (K ┐ )/norepinephrine (K ┐ ) of at least about 100,000.  
     
     
         38 . A method of treating a human suffering from a condition, or preventing said condition, wherein inhibiting reuptake of norepinephrine provides a benefit, the method comprising the step of administering a therapeutically effective amount of a composition comprising a compound having a pharmacological selectivity of serotonin (K ┐ )/norepinephrine (K ┐ ) of at least about 5000.  
     
     
         39 . A method of treating a human suffering from a condition, or preventing said condition, wherein inhibiting reuptake of norepinephrine provides a benefit, while diminishing adverse side effects, the method comprising the step of administering a total dose of about 0.1 to about 10 mg/day of an optically pure (S,S) reboxetine, or a pharmaceutically acceptable salt thereof, to an individual, said optically pure (S,S) reboxetine being substantially free of (R,R) reboxetine.  
     
     
         40 . The method of  claim 39  wherein said adverse side effects comprise dizziness, insomnia, lightheadedness, changes in blood pressure, sweating, gastrointestinal disturbances, sexual dysfunction in males. anticholinergic-like effects, and side effects with drug-drug interactions.  
     
     
         41 . A method of treating or preventing a nervous system disorder comprising the step of administering a therapeutically effective dose of racemic reboxetine or a pharmaceutically acceptable salt thereof to an individual, wherein said disorder is selected from the group consisting of at least one of an adjustment disorder, an age-associated learning and mental disorder, anorexia nervosa, apathy, an attention-deficit disorder due to general medical conditions, bipolar disorder, bulimia nervosa, chronic fatigue syndrome, chronic or acute stress, chronic pain, cyclothymic disorder, dysthymic disorder, fibromyalgia and other somatoform disorders, incontinence, mania, migraine headaches, obesity, peripheral neuropathy, post-traumatic stress disorder, premenstrual dysphoric disorder, a psychotic disorder, seasonal affective disorder, a sleep disorders, a specific developmental disorders, SSRI “poop out” syndrome, and TIC disorders.  
     
     
         42 . The method of  claim 41  wherein said disorder is selected from the group consisting of at least one of an adjustment disorder, an age-associated learning or mental disorder, apathy, bulimia nervosa, chronic fatigue syndrome, chronic or acute stress, cyclothymic disorder, dysthymic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, a psychotic disorder, and SSRI “poop out” syndrome.  
     
     
         43 . The method of  claim 42  wherein said disorder is selected from the group consisting of at least one of apathy, chronic fatigue syndrome, chronic or acute stress, cyclothymic disorder, post-traumatic stress disorder, and SSRI “poop out” syndrome  
     
     
         44 . The method of  claim 41  wherein the reboxetine is administered to the individual in an amount of about 2 to about 20 mg/day.  
     
     
         45 . The method of  claim 44  wherein the reboxetine is administered to the individual in an amount of about 4 to about 10 mg/day.  
     
     
         46 . The method of  claim 45  wherein the reboxetine is administered to the individual in an amount of about 6 to about 10 mg/day.  
     
     
         47 . The method of  claim 41  wherein said reboxetine is administered orally, parenterally, topically, transdermally, rectally, or vaginally.  
     
     
         48 . The method of  claim 47  wherein said reboxetine is orally administered with a pharmaceutically acceptable carrier comprising at least one of a binder, diluent, lubricant, disintegrating agent, effervescing agent, dyestuff, sweetener, and wetting agent.  
     
     
         49 . The method of  claim 48  wherein the oral administration is by a sachet, capsule, tablet, or aerosol spray.  
     
     
         50 . The method of  claim 47  wherein said reboxetine is parentarally administered subcutaneously, intraveously, or intramuscularly.  
     
     
         51 . The method of  claim 41  wherein the pharmaceutically acceptable salt is methanesulfonate salt.  
     
     
         52 . A preparation of a medicament from a composition comprising a compound having a pharmacological selectivity of serotonin (K ┐ )/norepinephrine (K ┐ ) of at least about 5000 to treat or prevent at least one nervous system condition selected from the group consisting of an addictive disorder and withdrawal syndrome, an adjustment disorder, an age-associated learning and mental disorder, anorexia nervosa, apathy, an attention-deficit disorder due to general medical conditions, attention-deficit hyperactivity disorder, bipolar disorder, bulimia nervosa, chronic fatigue syndrome, chronic or acute stress, chronic pain, conduct disorder, cyclothymic disorder, depression, dysthymic disorder, fibromyalgia and other somatoform disorders, generalized anxiety disorder, incontinence, an inhalation disorder, an intoxication disorder, mania, migraine headaches, obesity, obsessive compulsive disorders and related spectrum disorders, oppositional defiant disorder, panic disorder, peripheral neuropathy, post-traumatic stress disorder, premenstrual dysphoric disorder, a psychotic disorder, seasonal affective disorder, a sleep disorder, social phobia, a specific developmental disorder, selective serotonin reuptake inhibition (SSRI) “poop out” syndrome, and TIC disorders.  
     
     
         53 . A preparation of a medicament from a composition comprising reboxetine to treat or prevent at least one nervous system disorder selected from the group consisting of an adjustment disorder, an age-associated learning and mental disorder, anorexia nervosa, apathy, an attention-deficit disorder due to general medical conditions, bipolar disorder. bulimia nervosa, chronic fatigue syndrome, chronic or acute stress, chronic pain, cyclothymic disorder, dysthymic disorder, fibromyalgia and other somatoform disorders, incontinence, mania, migraine headaches, obesity. peripheral neuropathy, post-traumatic stress disorder, premenstrual dysphoric disorder a psychotic disorder, seasonal affective disorder, a sleep disorders, a specific developmental disorders, SSRI “poop out” syndrome, and TIC disorders.