Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2002-07-25
2004-12-14
Henley, III, Raymond J. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S211110
Reexamination Certificate
active
06831077
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to pharmaceutical compositions comprising an atypical antipsychotic agent in combination with a chromium salt, which are used for minimizing side effects in a patient taking an atypical antipsychotic agent. The present invention also relates to a treatment for atypical depression generally, and in particular to a method of improving the effectiveness of an atypical antipsychotic agent by administering a chromium salt to a patient concurrently with the administration of the atypical antipsychotic agent.
BACKGROUND OF THE INVENTION
Those having ordinary skill in the art will appreciate that atypical depression is a difficult mental disorder to treat. Patients having such a disorder are often reluctant to seek the medical attention necessary to diagnose the disorder. Such reluctance is often related to the patient's fear of the stigma associated with seeking psychiatric help or to the patient's feelings of worthlessness associated with depression. Moreover, once patients seek competent psychiatric help, it is difficult to successfully treat the disorder through psychoanalytic approaches alone.
Presently, several pharmaceutical agents have been developed which aid in the treatment of atypical depression. Clinical experience and published studies indicate the effectiveness of olanzapine as one such agent effective in the treatment of atypical depression.
However, the use of these pharmaceutical agents, such as olanzapine, produces numerous side effects in patients. One such common side effect is significant weight gain.
Although not all patients experience this weight gain side effect, in those that do, the weight gain can be considerable, as much as 40-50 pounds. This side effect presents a number of patient issues, both medical and psychological, for the treating physician to consider. Such a marked weight gain can place a significant burden on the heart and circulatory system of the patient. In addition, particularly in patients suffering from depression, such weight gain can hurt self-image and adversely impact the depressed state. Additionally, and perhaps most importantly, such side effects can reduce treatment adherence to the therapy regimen, thereby resulting in ineffective treatment for the primary disorder. Finally, significant weight gain increases the risk for diabetes mellitus, hypertriglyceridemia, and long-term cardiovascular risk. Accordingly, the incidence of non-insulin dependent diabetes mellitus (NIDDM) and hyperglycemia is higher in patients suffering from atypical depression, such as schizophrenic patients, than in the general population.
It has been suggested that the antipsychotic agents themselves, and olanzapine in particular, are part of the problem as these agents not only increase adiposity, which in itself can decrease insulin sensitivity, but also can impact glucose regulation independently of increases in adiposity. In fact, treatment of non-diabetic patients suffering from schizophrenia with olanzapine and other atypical antipsychotic agents has been associated with negative effects on glucose regulation, which can vary in severity independent of adiposity. For example, olanzapine treatment has been associated with elevated levels of insulin, leptin, and blood lipids, as well as insulin resistance. As such, it is recognized in the art that clinicians should monitor blood glucose concentrations periodically in patients taking olanzapine, especially in those patients with risk factors for diabetes mellitus.
Identification of a means to counteract these side effects partially or completely is, therefore, important. There is at present no way to prevent or treat obesity associated with the use of these atypical antipsychotic agents, except through behavioral changes such as increased physical activity or decreased caloric intake. Accordingly, there remains a need for a method of administering an atypical antipsychotic agent to treat a patient suffering from atypical depression without causing side effects such as weight gain and diabetes mellitus in the patient.
Chromium, in its pharmaceutically acceptable trivalent form, has been used in the treatment of overeating as it is documented to control appetite. Trivalent chromium is commercially available as chromium picolinate. As such, toxicity concerns relating to pharmaceutically acceptable forms of chromium have been demonstrated to be quite low.
A method of using chromium to treat neurological and mental disorders was described in Sandyk U.S. Pat. No. 5,470,846. However, the method of this reference includes the application to the brain of a patient of a sufficient amount of an AC pulsed magnetic field of proper intensity and frequency to treat the disorder. In conjunction with the application of the AC pulsed magnetic field, a stimulant to facilitate the transport of tryptophan into the brain is administered. Chromium, preferably in the form of chromium picolinate, is described as the stimulant. However, when the disclosure of this application of chromium is taken as a whole, the deficiencies become apparent. First of all, the application of the AC pulsed magnetic field is required in the method. Additionally, patients, particularly in the case of depression, are known to be resistant to accepting such complex treatments.
Another method of using chromium to reduce hyperglycemia and stabilize levels of serum glucose was described in U.S. Pat. No. 5,789,401. However, the method of this reference includes the co-administration of biotin with chromium tripicolinate to reduce the hyperglycemia.
Yet another method of using chromium to reduce hyperglycemia and stabilize levels of serum glucose was described in U.S. Pat. No. 6,329,361. However, the method of this reference indicates that chromium tripicolinate should be used alone to reduce the hyperglycemia.
U.S. Pat. No. 5,898,036 discloses the ability of chromium to improve the effectiveness of an antidepressant composition. In particular, this patent relates to the ability of chromium to improve the effectiveness of selective serotonin reuptake inhibitors.
Similarly, U.S. Pat. No. 6,034,125 relates to the ability of chromium itself to relieve symptoms of depression in a patient. However, the method of this reference indicates that chromium should be used alone to treat depression.
Chromium has also long been recognized as being nutritionally essential and in particular it is widely considered necessary for optimum insulin activity (see
Present Knowledge in Nutrition
, The Nutrition Foundation, Washington D.C., 1984, p. 571; Boyle et al.,
Southern Med. J
., 70:1449-1453, 1977, the contents of which are hereby incorporated by reference in their entirety). Chromium improves the glucose/insulin system in subjects with hypoglycemia, hyperglycemia, diabetes, and hyperlipidemia by affecting all key parameters: insulin binding, insulin receptor number, insulin internalization, beta cell sensitivity, and insulin receptor enzymes (see Anderson R A, “Nutritional factors influencing the glucose/insulin system: chromium”,
J. Am. Coll. Nutr
., 16(5): 404-10, October 1997, the contents of which is hereby incorporated by reference in its entirety).
Most of the several studies involving chromium supplementation of subjects with NIDDM and/or lipidemia were performed with chromium picolinate and have reported beneficial effects of chromium supplementation on the glucose/insulin system. Chromium picolinate was shown to be effective on glycemic and lipemic parameters both in healthy volunteers given 200 &mgr;g chromium picolinate per day (fasting blood glucose decreased by 24%, glycosylated hemoglobin decreased by 19%, total cholesterol decreased by 13%, and LDL cholesterol decreased by 11%) and in obese Caucasian patients with type-II diabetes receiving sulphonylurea and metformin (lowering fasting insulin levels without impairing glucose control).
In addition to its effects on glycemia, chromium has been implicated as a cofactor in the maintenance of normal lipid metabolism. Further, the bioavailable conjug
Comprehensive Neuroscience, Inc.
Goldberg Joshua B.
Henley III Raymond J.
Nath Gary M.
Nath & Associates PLLC
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