GB2133285A

GB2133285A - Pharmaceutical compositions

Info

Publication number: GB2133285A
Application number: GB08300767A
Authority: GB
Inventors: Alec James Coppen
Original assignee: Individual
Current assignee: Individual
Priority date: 1983-01-12
Filing date: 1983-01-12
Publication date: 1984-07-25
Also published as: GB8300767D0

Abstract

A pharmaceutical composition contains a lithium salt and an antidepressant which is not a lithium salt, the lithium salt and the said antidepressant being present in a ratio of 400 to 800 mg lithium carbonate (or the lithium equivalent amount of another lithium salt) to the daily dose of the said antidepressant. The antidepressant may be amitriptyline, imipramine, zimelidine, fluvoxamine, femoxetine, phenelzine, tranylcypromine or mianserin.

Description

SPECIFICATION Pharmaceutical compositions This invention relates to antidepressant pharmaceutical compositions.

The use of antidepressant pharmaceutical compositions in the treatment of depressive patients is well known. The action of antidepressant pharmaceuticals is not yet fully understood. Some, such as anitriptyline, imipramine, zimelidine, fluvoxamine, femoxetine, are believed to act by inhibiting the reuptake of monoamines by the neurone and others, e.g.

pheneizine and tranylcypromine, act as monoamine oxidase inhibitors. Monoamines, in particular the neurotransmitter 5hydroxytryptamine, are generally considered to be essential for the normal maintenance of mood and it is postulated that a relative deficiency of this neurotransmitter is one of the important causes of mental depression. The mode of action of newer antidepressants such as mianserin has not yet been determined. In most cases however the patient usually takes antidepressants two or three times a day.

Lithium salts (e.g. lithium carbonate, lithium sulphate or lithium citrate) have been successfully used in the treatment and prophylaxis of manic and depressive states. Usually lithium salts are administred twice a day at a dosage such that the plasma lithium concentration 1 2 hours after the last dose of lithium is between 0.8 and 1.2 mmol/l. There is considerable evidence that higher doses giving a 12 hour plasma lithium concentration of more than 1.5 mmol/l are toxic especially to the kidneys.

According to the present invention there is provided a pharmaceutical composition containing a lithium salt and an antidepressant which is not a lithium salt, the lithium salt and antidepressant, which is not a lithium salt, being present in a ratio of 400 to 800 mg, preferably approximately 650 mg, lithium carbonate or the lithium equivalent amount of another lithium salt to the daily dose of the said antidepressant.

I have found that a satisfactory therapeutic response may be achieved by administration of the pharmaceutical compositions according to the invention. I have found that this combination of a lithium salt and antidepressant can be administered just once or twice a day at the rate of 400 to 800, preferably approximately 650, mg lithium carbonate or its lithium equivalent together with the daily dose of the antidepressant to give a more effective antidepressant action than either ingredient given alone. The amount of lithium in such a combination is generally such as to achieve a plasma lithium concentration 12 hours after the last dose of between 0.4 and 1.2 mmol/l. Further the pharmaceutical composition according to the present invention can be used to treat a broader spectrum of depressive patients than those normally treatable by either ingredient alone.In particular, the composition is particularly effective against patients suffering from the depression of the depressive phase of manicdepressive disorder (bipoiar affective disorder).

With conventional antidepressants used alone these patients are often precipitated from the depressive phase into the manic phase of the illness and are particularly difficult to treat.

Antidepressants usable, with lithium salts, in the compositions according to the present invention include those thought to act by inhibition of the reuptake of monoamine and monoamine oxidase inhibitors as well as newer antidepressants such as mianserin whose mode of action is as yet unknown.

The daily dose of a particular antidepressant ingredient depends upon the actual antidepressant used. However for each antidepressant there is a recommended daily dose and it is this recommended daily dose to which is referred in the present specification.

The lithium salt used in the present composition is preferably lithium carbonate.

Lithium carbonate is already well known for use in medical treatment as an antidepressant and therefore is readily available in pharmaceutically pure form. Lithium sulphate or lithium citrate for example may also be used.

The pharmaceutical composition according to the present invention may be in any suitable form.

Preferably it will be in an orally administrable form e.g. in the form of tablets or capsules, in which case the compositions, in addition to the active ingredients, will generally also contain an inert, physiologically acceptable carrier or diluent in conventional manner.

As mentioned above, with the compositions according to the present invention, the patient may be treated just once or twice a day. The compositions according to the present invention may be such that-the patient has to take a plurality of tablets or capsules. Then each tablet or capsule according to the present invention will contain a portion of the lithium carbonate (or lithium equivalent of another lithium salt) together with a portion of the daily dose of the antidepressant. Thus, for example if the patient is to take a total of three tablet, each tablet will contain one third of the amount of lithium carbonate (i.e. one third of 400 to 800 mg), preferably approximately 21 7 mg lithium carbonate, and one third of the daily dose of the antidepressant.

An example of such a tablet or capsule would be one containing 650 mg of lithium carbonate together with the standard daily dose of amitriptyline which is 1 50 mg.

Claims (Filed on 10.1.84) 1. A pharmaceutical composition containing a lithium salt and an antidepressant which is not a lithium salt, the lithium salt and antidepressant, which is not a lithium salt, being present in a ratio of 400 to 800 mg lithium carboante or the lithium equivalent amount of another lithium salt to the daily dose of the said antidepressant.

2. A pharmaceutical composition according to

**WARNING** end of DESC field may overlap start of CLMS **.

Claims

**WARNING** start of CLMS field may overlap end of DESC **. SPECIFICATION Pharmaceutical compositions This invention relates to antidepressant pharmaceutical compositions. The use of antidepressant pharmaceutical compositions in the treatment of depressive patients is well known. The action of antidepressant pharmaceuticals is not yet fully understood. Some, such as anitriptyline, imipramine, zimelidine, fluvoxamine, femoxetine, are believed to act by inhibiting the reuptake of monoamines by the neurone and others, e.g. pheneizine and tranylcypromine, act as monoamine oxidase inhibitors. Monoamines, in particular the neurotransmitter 5hydroxytryptamine, are generally considered to be essential for the normal maintenance of mood and it is postulated that a relative deficiency of this neurotransmitter is one of the important causes of mental depression. The mode of action of newer antidepressants such as mianserin has not yet been determined. In most cases however the patient usually takes antidepressants two or three times a day. Lithium salts (e.g. lithium carbonate, lithium sulphate or lithium citrate) have been successfully used in the treatment and prophylaxis of manic and depressive states. Usually lithium salts are administred twice a day at a dosage such that the plasma lithium concentration 1 2 hours after the last dose of lithium is between 0.8 and 1.2 mmol/l. There is considerable evidence that higher doses giving a 12 hour plasma lithium concentration of more than 1.5 mmol/l are toxic especially to the kidneys. According to the present invention there is provided a pharmaceutical composition containing a lithium salt and an antidepressant which is not a lithium salt, the lithium salt and antidepressant, which is not a lithium salt, being present in a ratio of 400 to 800 mg, preferably approximately 650 mg, lithium carbonate or the lithium equivalent amount of another lithium salt to the daily dose of the said antidepressant. I have found that a satisfactory therapeutic response may be achieved by administration of the pharmaceutical compositions according to the invention. I have found that this combination of a lithium salt and antidepressant can be administered just once or twice a day at the rate of 400 to 800, preferably approximately 650, mg lithium carbonate or its lithium equivalent together with the daily dose of the antidepressant to give a more effective antidepressant action than either ingredient given alone. The amount of lithium in such a combination is generally such as to achieve a plasma lithium concentration 12 hours after the last dose of between 0.4 and 1.2 mmol/l. Further the pharmaceutical composition according to the present invention can be used to treat a broader spectrum of depressive patients than those normally treatable by either ingredient alone.In particular, the composition is particularly effective against patients suffering from the depression of the depressive phase of manicdepressive disorder (bipoiar affective disorder). With conventional antidepressants used alone these patients are often precipitated from the depressive phase into the manic phase of the illness and are particularly difficult to treat. Antidepressants usable, with lithium salts, in the compositions according to the present invention include those thought to act by inhibition of the reuptake of monoamine and monoamine oxidase inhibitors as well as newer antidepressants such as mianserin whose mode of action is as yet unknown. The daily dose of a particular antidepressant ingredient depends upon the actual antidepressant used. However for each antidepressant there is a recommended daily dose and it is this recommended daily dose to which is referred in the present specification. The lithium salt used in the present composition is preferably lithium carbonate. Lithium carbonate is already well known for use in medical treatment as an antidepressant and therefore is readily available in pharmaceutically pure form. Lithium sulphate or lithium citrate for example may also be used. The pharmaceutical composition according to the present invention may be in any suitable form. Preferably it will be in an orally administrable form e.g. in the form of tablets or capsules, in which case the compositions, in addition to the active ingredients, will generally also contain an inert, physiologically acceptable carrier or diluent in conventional manner. As mentioned above, with the compositions according to the present invention, the patient may be treated just once or twice a day. The compositions according to the present invention may be such that-the patient has to take a plurality of tablets or capsules. Then each tablet or capsule according to the present invention will contain a portion of the lithium carbonate (or lithium equivalent of another lithium salt) together with a portion of the daily dose of the antidepressant. Thus, for example if the patient is to take a total of three tablet, each tablet will contain one third of the amount of lithium carbonate (i.e. one third of 400 to 800 mg), preferably approximately 21 7 mg lithium carbonate, and one third of the daily dose of the antidepressant. An example of such a tablet or capsule would be one containing 650 mg of lithium carbonate together with the standard daily dose of amitriptyline which is 1 50 mg. Claims (Filed on 10.1.84)

1. A pharmaceutical composition containing a lithium salt and an antidepressant which is not a lithium salt, the lithium salt and antidepressant, which is not a lithium salt, being present in a ratio of 400 to 800 mg lithium carboante or the lithium equivalent amount of another lithium salt to the daily dose of the said antidepressant.

2. A pharmaceutical composition according to claim 1 wherein the lithium salt and the said antidepressant are present in a ratio of approximately 650 mg lithium carbonate or the lithium equivalent amount of another lithium salt to the daily dose of the said antidepressant.

3. A pharmaceutical composition according to claim 1 or 2 wherein the lithium salt is lithium carbonate.

4. A pharmaceutical composition according to any one of caims 1 to 3 wherein the said antidepressant is a monoamine oxidase inhibitor.

5. A pharmaceutical composition according to any one of claims 1 to 3 wherein the said antidepressant is amitriptyline.

6. A pharmaceutical composition according to any one of claims 1 to 5 in the form of a tablet or capsule.