it has been unexpectedly been found that benzamide derivatives such as amisulpride , sulpiride or sultopride , or pharmaceutically acceptable salts and mixtures thereof are effective treatments for depressive patients suffering from bipolar disorders not responding or partially responding to drugs widely used for this condition , including but not limited to lithium , divalproate , clomipramine , fluoxetine and paroxetine . more particularly , it has now been discovered that amisulpride or a pharmaceutically acceptable salt thereof is an effective treatment for depressive patients suffering from bipolar disorders not responding or partially responding to drugs widely used for this condition , including but not limited to lithium , divalproate , clomipramine , fluoxetine , and paroxetine . according to the present invention is disclosed a method of treating bipolar depression in patients suffering from bipolar i or bipolar ii disorders , comprising administering to a patient a therapeutically effective amount of benzamide derivatives of the general formula ( i ). specific benzamide derivatives include , but are not limited to amisulpride ( ia ), or 4 - amino - n -[( 1 - ethylpyrrolidin - 2 - yl ) methyl ]- 5 -( ethylsulfonyl )- 2 - methoxybenzamide ; sulpiride ( ib ) or n -[( 1 - ethylpyrrolidin - 2 - yl ) methyl ]- 2 - methoxy - 5 - sulfamoyl - benzamide ; sultopride ( ic ) or n -[( 1 - ethylpyrrolidin - 2 - yl ) methyl ]- 5 -( ethylsulfonyl )- 2 - methoxybenzamide ; the present invention provides a method of treating bipolar depression by orally administering to a patient benzamide derivatives , preferably selected from the group consisting of amisulpride , sulpiride and sultopride or pharmaceutically acceptable salts thereof . other embodiments of the method include the use of a compound of benzamide derivatives and more particularly amisulpride or a pharmaceutically acceptable salt thereof , for the preparation of a medicament for treating bipolar depression in a patient suffering from bipolar disorders . another embodiment of the method include the use of a compound of benzamide derivatives and more particularly amisulpride or a pharmaceutically acceptable salt thereof , for the preparation of a medicament for treating bipolar depression in a patient suffering from bipolar disorder i . another embodiment of the method include the use of a compound of benzamide derivatives and more particularly amisulpride or a pharmaceutically acceptable salt thereof , for the preparation of a medicament for treating bipolar depression in a patient suffering from bipolar disorder ii . another embodiment of the invention provides a method of treating bipolar depression in patients , suffering from bipolar disorder i or bipolar disorder ii by oral administration of amisulpride . bipolar depressive patient is here defined as a patient with either bipolar i disorder , most recent episode depressed ; bipolar i disorder , most recent episode mixed or bipolar ii disorder ( recurrent major depressive episodes with hypomanic episodes ) ( classification 296 . 5 ×, 296 . 6 ×, and 296 . 89 respectively of dsm - iv ). administration for gastrointestinal absorption can be by the oral or rectal route , such as by tablets and suppositories , respectively . it is also within the scope of the invention to provide liquid formulations , in particular aqueous formulations , for oral administration . a further route of administration is by intravenous or intramuscular injection in a liquid carrier such as physiological saline . pharmaceutical compositions of the compounds of the invention suitable in the treatment of bipolar depression are described in literature and are marketed , albeit for different indications , in various countries . the term “ therapeutically effective amount ” as defined in this invention means an amount of the compound which is effective in treating a patient for the named disorder or condition . in one embodiment , bipolar depression may be treated by administering amisulpride to a patient in a dosage ranging from about 20 mg / day to about 800 mg / day . in another embodiment , bipolar depression may be treated by administering amisulpride to a patient in a dosage ranging from about 50 mg / day to about 300 mg / day . when given in such a dose , amisulpride exerts a clinically beneficial effect on bipolar depression . no deterioration of any other aspect of bipolar disorder , such as treatment - emergent mania was observed . the following examples are intended for illustrative purposes only and are not meant to limit the invention in any manner : female subject ( 42y ) diagnosed with bipolar ii disorder , recurrent major depressive episodes with hypomanic episodes ). she is admitted for bipolar depression and amisulpride treatment of 200 mg / d is initiated . after 4 weeks of treatment with amisulpride , the depressive state started to markedly decrease and after 6 weeks it had disappeared completely . after 3 years of treatment with amisulpride 100 mg / d no manic or depressive recurrence had occurred . female subject ( 36y ) diagnosed with bipolar ii disorder , recurrent major depressive episodes with hypomanic episodes ). she is admitted for bipolar depression and amisulpride treatment of 100 mg / d is initiated . after 3 weeks of treatment with amisulpride the patient &# 39 ; s depressive condition improved . after 4 years of treatment with amisulpride 100 mg / d any relapse has still not occurred . male subject ( 32y ), diagnosed with bipolar disorder i , most recent episode depressed . upon admission at the hospital a treatment with amisulpride 100 mg / g was initiated . after 3 weeks of treatment , a significant improvement of the depressive disorder was observed . after 4 years of treatment with amisulpride 50 mg / d still no relapse has occurred . male subject ( 27y ) diagnosed with bipolar i disorder , most recent episode mixed . the patient is hospitalised for bipolar depression and treatment with amisulpride 150 mg / g initiated . the depressive disorder rapidly improved and had disappeared after 4 weeks . after 4 years of treatment with amisulpride 150 mg / d still no relapse has occurred . female subject ( 54y ), diagnosed with bipolar i disorder , most recent episode depressed , for the first time at the age of 47 . the patient has been on lithium for about 3 years . she is compliant with her treatment and lithium serum levels remains stable around 0 . 7 - 0 . 9 meq / l . she is admitted for bipolar depression with lithium serum level were 0 . 8 meq / l . the day after she received an amisulpride treatment of 100 mg / d . after 3 weeks of treatment with amisulpride , the depressive state had started to vanish progressively and had disappeared completely after 6 weeks . after 3 years of treatment no manic or depressive recurrence had occurred . male subject ( 35y ), diagnosed with bipolar disorder i , most recent episode depressed , is hospitalized for manic state . his illness started 4 years ago . the patient suffers bipolar disorder type i . the patient has already shown two manic episodes . at entrance , he received divalproate at a dose of 1250 mg / d . after one month of treatment , the manic symptoms have disappeared , but suicidal thoughts , a lack of interest for own state and his family , a lack of projection in the future took place . the patient was diagnosed with major depression . then , a treatment with amisulpride ( 150 mg / d ) is established . the depressive disorders improved rapidly to disappear after 3 weeks of the treatment . male subject ( 38y ) diagnosed with bipolar i disorder , most recent episode depressed . his family informed the therapist of a dramatic decrease of his professional performance since 6 months . the patient is admitted for bipolar depression and amisulpride 250 mg / d is initiated . the anxio - depressive element disappears after 3 weeks of treatment . after 2 years treatment with amisulpride 250 mg / d , the patient has still not been subject to any recurrent manic or depressive episode . female subject ( 47y ) diagnosed with bipolar ii disorder , recurrent major depressive episodes with hypomanic episodes ). prescription by her personal doctor of a treatment of clomipramine 100 mg / d seems , according to her family , to have her condition deteriorated with increased anxiety and agitation and provoking sleep disorders . the patient &# 39 ; s chart improved after switching to amisulpride 200 mg / d . after 6 months no relapse has occurred . female subject ( 51y ) diagnosed with bipolar i disorder , most recent episode depressed . after a first therapeutic failure with lithium because of non - compliance she has been treated successfully for 5 years with carbamazepine 800 mg / d . the patient is admitted for bipolar depression with serum level of carbamazepine of 8 mg / l . after 3 weeks of treatment with fluoxetine 20 mg / d only a small improvement is observed . a treatment with amisulpride 150 mg / d is then initiated . after 2 weeks of amisulpride treatment , the patient &# 39 ; s depressive condition has almost disappeared . retrospectively , after 3 years no relapse of depressive or manic episodes have been observed with amisulpride 100 mg / d . male subject ( 25y ) diagnosed with bipolar i disorder , most recent episode mixed . the manic episode had been treated successfully with an antipsychotic treatment consisting of haloperidol and levomepromazine . the patient however refused to follow a long course treatment because he seemed not , according to himself and his family , present severe symptoms . a treatment of amisulpride 300 mg / d resolved the patient &# 39 ; s chart after only one month . after 7 months of treatment with amisulpride any relapse has still not occurred . female subject ( 51y ) diagnosed with bipolar i disorder , most recent episode depressed . after not responding properly when taking lithium as a monotherapy treatment she has been staying for 4 years on a combination of lithium 1200 mg / d and divalproate 750 mg / d . at admission , her lithium serum level was 0 . 7 meq / l and her valproate serum level was 100 mg / ml . the amount of lithium was increased in order to obtain a blood level of 0 . 9 meq / l . despite this modification , her depressive condition continued . a treatment with amisulpride 50 mg / d has then being given to her . after 15 days of treatment , the patient &# 39 ; s depressive condition improved . after 4 years with amisulpride , still no manic or depressive relapses have occurred . case 12 . female subject ( 36y ) diagnosed with bipolar i disorder , most recent episode depressed . the patient &# 39 ; s chart showed the existence of a reactive depressive condition which responded only moderately to viloxazine during adolescence . prescription of 150 mg of amisulpride led to a recovery of the depressive condition after 4 weeks . no relapse had been observed with the patient after one year of treatment with 50 mg amisulpride . male subject ( 19y ) diagnosed with bipolar i disorder , most recent episode depressed . the prescription of amisulpride 100 mg / d has shown a progressive improvement and the disappearance of the catatonic condition after 6 weeks of treatment . no relapse had been observed with the patient after two years of treatment with 100 mg / d amisuipride . male subject ( 62y ) diagnosed with bipolar i disorder , most recent episode depressed . after several manic and depressive episodes the patient seems stabilised with a combination of lithium 1600 mg / d and paroxetine 40 mg / d . upon admission at the hospital the lithium serum level are controlled and the treatment with paroxetine is stopped . a treatment with amisulpride 100 mg / d is established . after 3 weeks of treatment , a considerable improvement is obtained allowing the patient to go home . after 3 years of treatment amisulpride 200 mg / d the patient still remains stable .
a benzamide derivative , especially amisulpride , is used to prevent or treat bipolar depression of a patient suffering from bipolar disorder i or bipolar disorder ii .