Droxidopa and pharmaceutical composition thereof for the treatment of mood disorders, sleep disorders, or attention deficit disorders

Abstract

The present invention provides pharmaceutical compositions comprising droxidopa alone, or in combination with one or more further active ingredients, for the treatment of conditions, such as mood disorders, sleep disorders, or attention deficit disorders. In certain embodiments, the compositions useful in the methods of the invention comprise droxidopa and a compound selected from the group consisting of DOPA decarboxylase inhibiting compounds, catechol-O-methyltransferase inhibiting compounds, cholinesterase inhibiting compounds, monoamine oxidase inhibiting compounds, norepinephrine reuptake inhibiting compounds, selective serotonin reuptake inhibiting compounds, tricyclic antidepressant compounds, serotonin norepinephrine reuptake inhibiting compounds, norepinephrine dopamine reuptake inhibiting compound, noradrenergic and specific serotonergic antidepressants, and combinations thereof. The inventive compositions are particularly useful in the treatment of depression, narcolepsy, insomnia, and Attention Deficit / Hyperactivity Disorder (AD / HD).

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application is a division of U.S. patent application Ser. No. 12 / 116,560, filed May 7, 2008, which claims priority to U.S. Provisional Pat. App. No. 60 / 916,497, filed May 7, 2007, both of which are incorporated herein by reference in their entireties.FIELD OF THE INVENTION[0002]The present application is directed to methods of treatment of various conditions. In particular, the application is directed to the use of droxidopa, alone or in combination with one or more additional components, for the treatment of various conditions, such as mood disorders, sleep disorders, or attention deficit disorders.BACKGROUND[0003]Droxidopa is a known synthetic amino acid precursor of norepinephrine that is converted directly to norepinephrine via the action of dopa decarboxylase (DDC). Droxidopa is generally used to treat orthostatic hypotension (OH) and can be categorized as an antiparkinsonian agent; however, multiple pharmacological activ...

AI Technical Summary

Problems solved by technology

Symptoms may include: persistent feelings of sadness; feeling hopeless or helpless; having low self-esteem; feeling inadequate; excessive guilt; feelings of wanting to die; loss of interest in usual activities or activities once enjoyed; difficulty with relationships; sleep disturbances; changes in appetite or weight; decreased energy; difficulty concentrating; a decrease in the ability to make decisions; suicidal thoughts or attempts; frequent physical complaints (i.e., headache, stomach ache, fatigue); running away or threats of running away from home; hypersensitivity to failure or rejection; and irritability, hostility, or aggression.

In mood disorders, these feelings appear more intense than what a person may normally feel from time to time, and these feelings tend to continue over a period of time or interfere with an individual's interest in family, friends, community, or work.

Moreover, all three classes of medications are known to cause varying, undesirable side effects.

Narcolepsy, in particular, is known to adversely affect an individual's ability to function in daily life.

At best, known medications reduce the symptoms, but do not eliminate them entirely.

Moreover, such pharmaceutical treatments often have undesirable side effects.

Idiopathic insomnia is a long-term (often lifelong) inability to obtain adequate sleep that is presumably due to an abnormality of the neurological control of the sleep-wake system.

Over-the-counter sleep aids typically include antihistamines (e.g., diphenhydramine or doxylamine), which have the side effect of causing sleepiness.

The three subtypes take into account that some patients with AD / HD have little or no trouble sitting still or inhibiting behavior, but may be predominantly inattentive and, as a result, have great difficulty getting or staying focused on a task or activity.

Others with AD / HD may be able to pay attention to a task but lose focus because they may be predominantly hyperactive-impulsive and, thus, have trouble controlling impulse and activity.

Some evidence suggests that the disorder is genetically transmitted in many cases and results from a chemical imbalance or deficiency in certain neurotransmitters.

Symptoms of inattention, as listed in the DSM-IV, include: often failing to give close attention to details or making careless mistakes in schoolwork, work, or other activities; often having difficulty sustaining attention in tasks or play activities; often not seeming to listen when spoken to directly; often not following through on instructions and failing to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions); often having difficulty organizing tasks and activities; often avoiding, disliking, or being reluctant to engage in tasks that require sustained mental effort (such as schoolwork or homework); often losing things necessary for tasks or activities (e.g., toys, school assignments, pencils, books, or tools); often being easily distracted by extraneous stimuli; and often being forgetful in daily activities.

Symptoms of hyperactivity, as listed in the DSM-IV, include: often fidgeting with hands or feet or squirming in seat; often leaving seat in classroom or in other situations in which remaining seated is expected; often running about or climbing excessively in situations in which it is inappropriate (in adolescents or adults, may be limited to subjective feelings of restlessness); often having difficulty playing or engaging in leisure activities quietly; often being “on the go” or often acting as if “driven by a motor;” and often talking excessively.

Although such behavior is risky, the patient is not really a risk-taker but, rather, has great difficulty controlling impulse.

Symptoms of impulsivity, as listed in the DSM-IV, include: often blurting out answers before questions have been completed; often having difficulty awaiting turn; and often interrupting or intruding on others.

AD / HD is most prevalent in children, and many parents find it undesirable to treat their children through administering stimulants.

Moreover, there can be undesirable side effects, such as decreased appetite, insomnia, increased anxiety, and / or irritability.

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