MXPA97005117A - Use of tomoxetine for the manufacture of a medicine for the treatment of the disorder of deficitde the attention / hyperactivi - Google Patents

Abstract

Tomoxetine, an inhibitor of norepinephrine uptake, is used to treat attention deficit / hyperactivity disorder

Description

USE OF TOMOXETINE FOR THE MANUFACTURE OF A MEDICINE FOR THE TREATMENT OF DEFICIT DISORDER OF THE ATTENTION / HYPERACTIVITY DESCRIPTION OF THE INVENTION The invention pertains to the fields of pharmaceutical chemistry and psychiatric medicine, and provides a method for the treatment of the psychiatric disorder known as attention deficit / hyperactivity disorder.

Background of the Invention For a few decades it has been recognized that a significant number of children are persistently hyperactive and have such a short attention span that it disables them in school and in many personal relationships. Such children for many years would no doubt have been considered incorrigible and punished, or even confined in an institution. A long time ago, however, it was noted that these children can not control their hyperactivity and lack of attention, and the medical professions began to try to help them. Methylphenidate (Ritalin *) has been used for some time to treat such children and it often significantly improves their ability to function and coexist with other people.

REF: 25017 at school and at home. However, the drug has the disadvantages of requiring several doses per day, and producing a rebound effect as the effect of each dose disappears. In addition, the drug causes drowsiness and lack of appetite in some patients. Methylphenidate has noradrenergic and dopaminergic activities. Imipramine, desiprate, nortriptyline, amy triptiline, and clomipramine are also used in some cases of attention deficit / hyperactivity disorder (ADHD). These tricyclic drugs, however, have a number of physiological mechanisms and, as a class, tend to produce a number of side effects and require careful monitoring and titration of the dose. In the last decade, psychiatrists have realized that ADHD is not only a disorder of children, but often continues into adulthood. It is obvious that hyperactivity and short attention span cause serious disturbances in the life of an adult, but it is only recently that such patients have been able to obtain any treatment. The need for a safe and convenient treatment for ADHD, applicable to children and adults and without the disadvantages possessed by methylphenidate, continues to be a concern of the psychiatric profession. The present invention provides a method for the treatment of attention deficit / hyperactivity disorder, comprising the administration to a patient in need of such treatment, of an effective amount of tomoxetine. The invention also provides the use of tomoxetine for the manufacture of a medicament for the treatment of attention deficit / hyperactivity disorder; and the use of tomoxetine for the treatment of the deficit disorder of ation / hyperactivity. Tomoxetine is a well-known drug, the chemical name of which is (R) - (-) - N -methyl-3- (2-methylphenoxy) -3-phenylpropylamine. This is regularly used as a salt, and the salts are included in the term tomoxetine as used herein. See, for example, Gehlert et al., Neuroscience Letters 157, 203-06 (1993), for a discussion of the mechanism of activity of tomoxetine as an inhibitor of norepinephrine reuptake. The tomoxetina is very active in that function, and in addition it is substantially free of other activities of the central nervous system at the concentrations or doses to which it effectively inhibits the reuptake of norepinephrine. In this way, it is very free of side effects and is properly considered a selective drug. Tomoxetine is a remarkably safe drug, and its use in ADHD, whether in adults and children, is a superior treatment for that disorder because of its improved safety. further, tomoxetine is effective at relatively low doses, as discussed below, and can be safely and effectively administered once a day. In this way, the difficulties created by the multiple dosing of patients, particularly disorganized children and adults, are completely avoided. The effective dose of tomoxetine for ADHD is in the range of about 5 mg / day to about 100 ms / day. The preferred dose for adult is in the range of about 10 to about 80 mg / day, and a more highly preferred adult dose is from about 20 to 60 mg / day. The dose for children is of course smaller, in the range of from about 5 to about 70 mg / day, more preferably from about 10 to about 60 mg / day and still more preferably from about 10 to about 50 mg / day. The optimal dose for each patient, as always, must be adjusted by the doctor in charge of the case, taking into account the size of the patient, other medications that the patient requires, the severity of the disorder and all the other circumstances of the patient. Since tomoxetine is easily absorbed orally and requires once-a-day administration, there is little or no reason to administer it in any other way than orally. This can be produced in the form of a stable, clean crystal, and is thus easily formulated in the usual oral dosage forms, such as tablets, capsules, suspensions, and the like. The usual methods of pharmaceutical scientists are applicable. This can be usefully administered, if there is any reason to do so in a particular circumstance, in other pharmaceutical forms, such as injectable solutions, depot injections, suppositories and the like, which are well known and understood by pharmaceutical scientists. It will be substantially preferred, however, to administer tomoxetine as a tablet or capsule, and such dosage forms are recommended. The patient with ADHD is rather easily recognized, and most people have been in contact with children, if not adults, who show some or all of the symptoms of the disorder. The best description of the disorder is the diagnostic criteria for ADHD, published by the American Psychiatric Association in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Version (1994), as follows.

Diagnostic criteria for Attention Deficit / Hyperactivity Disorder A. Any of (1) or (2): (1) Six (or more) of the following symptoms of inattention have persisted for at least 6 months to a degree that is poorly adapted and inconsistent with the level of development: Care failure a) frequently does not pay close attention to details or makes mistakes due to lack of care in school work, at work, or in other activities b) frequently has difficulty paying attention to tasks or play activities c ) frequently does not seem to listen when spoken directly d) frequently does not follow instructions and fails to finish school work, housework or homework duties (not due to oppositional behavior or deficiency to understand instructions) ) frequently has difficulty organizing tasks and activities f) frequently avoids, dislikes or is reluctant to engage in tasks that require sustained mental effort (such as work schoolwork or homework) g) frequently loses the things necessary for tasks or activities (eg, toys, homework, pencils, books or tools) h) is often easily distracted by strange stimuli "i) ^ is often forgetful in daily activities (2) six (or more) of the following symptoms of hyperactivity-impulsivity have persisted for at least 6 months to a degree that is maladaptive and inconsistent with the level of development: Hiper ac ti vi da da) frequently restless with hands or feet or writhing in seat b) frequently leaves the seat in the classroom or in other situations where he is expected to remain seated c) frequently runs around or jumps excessively in situations in which is inappropriate (in adolescents and adults, may be limited to subjective feelings of restlessness or discomfort) d) frequently has difficulty playing or engaging calmly in leisure or leisure activities e) frequently is "on the move" or frequently acts as if "was driven by a motor" f) frequently speaks excessively ^^ Impulse g) often says without answers the answers before that the questions have been completed h) frequently has difficulty waiting for his turn i) frequently interrupts or annoys others (for example, intrudes into conversations or games) B. Some hyperactive-impulsive or inattentive symptoms that caused deterioration were present before 7 years of age.

C. Some deterioration is present from the symptoms in two or more environments (for example, at school [or at work] and at home).

D. There must be clear evidence of clinically significant impairment in social, academic, or occupational functioning.

E. Symptoms do not occur exclusively during the course of a Developmental Penetrating Disorder, Schizophrenia, or other Psychotic Disorder, and are not better explained by another mental disorder (eg, Disorder of Humor, Disorder of Anxiety, Dissociative Disorder, or a Disorder of the Personality). It will be noted that ADHD is a disorder composed of two components, the component of lack or deficit of attention and the component of hyperactivity, which are to an independent degree. Treatment with tomoxetine is effective in patients who suffer mainly from any component or from the combined disorder.

While ADHD is still primarily considered as a disorder of children, it is now understood that many patients with ADHD, as many as 50%, continue to suffer from the disorder when they grow through adolescence into adulthood. Biederman and associates have extensively studied the adult patient with ADHD, and have found numerous cases. See, for example, Biederman et al., Am. J. Psychiatry 150, 1792-98 (1993). They found that adult ADHD cases were frequently found among parents and adult siblings of. Children with ADHD. In this way, it seems that the disease is not only carried to adulthood, but it is heritable. The recently cited article by Biederman and colleagues, as well as another article by the same authors, Am. J. Psychiatry 148, 564-77 (1991), reports studies of patients with ADHD who also have one or more other psychiatric disorders. The authors indicate that such co-morbidity is very common among patients with ADHD and, naturally, tarnishes the diagnosis and treatment of such patients. The tomoxetina is effective in the treatment of ADHD although the situation of the treated patient can be complicated by the co-morbidity with one or more additional disorders.

The mere listing of the above diagnostic criteria indicates the seriousness of the ADHD and the damage it does to the patient. A person who has a moderately severe case of ADHD is substantially completely unable to concentrate, and hence is unable to perform significant work or study; it is a distraction and a continuous annoyance to those around him, due to the uselessly impulsive activity that causes the disorder; and consumes his family in cleaning and repairing the damage and deterioration that these people cause. Such a school-age patient can substantially damage the teacher's ability to achieve the goals of the class, because the child with ADHD will continuously interrupt the class, distract the other children, and consume the teacher's effort. Thus, it is readily apparent that an improved treatment of ADHD is needed, and that the present invention is consequently important to many people. The method of the present invention is effective in the treatment of patients who are children, adolescents and adults, and there is no significant difference in the symptoms or details of the manner of treatment among patients of different ages. Generally speaking, however, for purposes of the present invention, a child is considered a patient below the age of puberty, a teenager is considered a patient from the age of puberty to about 18 years of age , and an adult is coi as a patient of 13 years or older It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. Having described the invention as above, property is claimed as contained in the following:

Claims (16)

1. A method for the treatment of attention deficit / hyperactivity disorder, characterized in that it comprises administering to a patient in need of such treatment, an effective amount of tomoxetine.

2. A method according to claim 1, characterized in that the type of attention deficit disorder of attention / hyperactivity disorder is predominantly treated.

3. A method according to claim 1, characterized in that the predominantly hyperactive-impulsive type of attention deficit / hyperactivity disorder is treated.

4. A method according to claim 1, characterized in that the combined type of attention deficit / hyperactivity disorder is treated.

5. A method according to claim 1, characterized in that the patient is an adult.

6. A method of compliance with .. claim 5, characterized in that the predominantly inattentive type of attention deficit / hyperactivity disorder is treated.

7. A method according to claim 5, characterized in that the predominantly hyperactive-impulsive type of attention deficit / hyperactivity disorder is treated.

8. A method according to claim 5, characterized in that the combined type of attention deficit / hyperactivity disorder is treated.

9. A method c according to claim 1, characterized in that the patient is a teenager.

10. A method according to claim 9, characterized in that the predominantly inattentive type of attention deficit / hyperactivity disorder is treated.

11. A method according to claim 9, characterized in that the predominantly hyperactive-impulsive type of attention deficit / hyperactivity disorder is treated.

12. A method according to claim 9, characterized in that the combined type of attention deficit / hyperactivity disorder is treated.

13. A method according to claim 1, characterized in that the patient is a child.

14. A method according to claim 13, characterized in that the predominantly inattentive type of attention deficit / hyperactivity disorder is treated.

15. A method according to claim 13, characterized in that the predominantly hyperactive-impulsive type of attention deficit / hyperactivity disorder is treated.

16. A method according to claim 13, characterized in that the combined type of attention deficit / hyperactivity disorder is treated.