human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Prolactin ( PRL ) and Cortisol ( CORT ) responses to d , l-fenfluramine ( FEN ) challenge ( 60 mg ) were examined in patients with affective disorders on two occasions under euthymic conditions : drug-free before admission to prophylactic treatment and after about 9 months of medication with lithium or carbamazepine .  Response to treatment was assessed by a complex algorithm using continuous ratings in outpatient clinic over a period of 2 years . In general , treatment result ed in a delayed and diminished CORT release ( n.s . ) ; subgroup analysis revealed an attenuated CORT response ( P < 0.05 ) in responders , whereas nonresponders showed no change in CORT secretion pattern except an enhanced CORT baseline value ( P < 0.05 ) . Cross-sectional comparison of responders with nonresponders under medication yielded a trend for greater CORT stimulation in nonresponders . This result was not affected by  FEN/NorFEN or lithium/carbamazepine serum levels , baseline CORT values , age , sex , diagnostic distribution , number of appointments to the outpatient clinic or duration of medication at the time of FEN test session . Before onset of prophylactic medication responders and nonresponders could not be discriminated significantly regarding stimulated hormone release , probably due to the small sample size ( n = 17 ) . CORT response to FEN was increased in drugfree unipolar patients compared to bipolar ( P < 0.05 ) and to schizoaffective patients ( P < 0.1 ) . In accordance with its well-documented presynaptic 5-HT-agonistic action lithium medication result ed in a significantly greater increase in CORT release than carbamazepine ( P < 0.05 ) . Evaluation of PRL stimulation showed patterns of secretion quite similar to those of CORT , without reaching statistical significance in most cases . Perhaps due to method ological differences in assessing treatment response , these data do not confirm former results , which supposed an enhanced 5-HT net activity in long-term prophylactic lithium treatment . Because of high interindividual variances of hormone parameters , the FEN-test procedure is not a useful tool for the prediction of therapeutical outcome in terms of clinical routine use . Relations of stimulated hormone response as a marker of central serotoninergic activity and clinical outcome are discussed Relapse  rates of the first 35 unipolar and bipolar II manic-depressive patients who entered the controlled phase of a continuing evaluation of the prophylactic value of  lithium alone or in combination with imipramine were analyzed . Lithium had a prophylactic effect in unipolar patients and possibly in bipolar II patients . Imipramine did not have a prophylactic effect in either group of patients In two r and omized double-blind controlled trials on 63 depressed female in- patients subject to recurrent affective disorder ( bipolar and unipolar manic-depressive psychosis )  lithium was shown to have major acute antidepressant effects . At the end of three weeks lithium produced more uniform improvement than did imipramine ; lithium in combination with tryptophan ( in the form of Optimax ) was superior to tryptophan alone -- the latter drug having no discernible antidepressant activity in this group of patients . Lithium did not produce an antidepressant effect until the second and third week of both trials Abstract The prophylactic effect of lithium was studied in a group of sixty-five patients with recurrent affective disorders in four centres . Patients were r and omly allocated to lithium or identical-looking placebo tablets for periods of up to 112 weeks . In addition , patients received any further medication or treatment which the psychiatrist in charge of the case thought was necessary . Patients receiving lithium had very significantly less affective illness than patients receiving placebo tablets , whether this was measured by time spent as an inpatient or by the duration of outpatient episodes . The amount of antidepressant or of antimanic medication prescribed was also significantly less in the lithium group . No patient on lithium was given  electroconvulsive therapy  ( E.C.T. ) , whereas 43 % of the placebo group received one or more courses of E.C.T. A global rating was made independently by two assessors who did not know whether the patient was in the lithium or in the placebo group . These assessors , the psychiatrist in charge of the case and a psychiatric social worker , showed a very high concordance in their ratings . 86 % of patients on lithium were rated as showing little or no affective disorders ( global rating 1 and 2 ) during the trial , as compared to only 8 % of the placebo group . Only 11 % of the lithium group was rated as unchanged or worse than during the 2 years previous to the trial , as compared with 75 % of the placebo group . Lithium seemed to be as effective in patients with unipolar recurrent depressive illness as in patients with both mania and depression Depressed out patients ( n = 51 ) resistant to treatment with maprotiline were treated in a blind , r and omized , single-centre study , for 6 weeks with either the reversible and selective monoamine oxidase A-inhibitor ( MAO-A-I ) , brofaromine or lithium addition to maprotiline . The Hamilton Rating Scale for Depression was scored by an independent rater before and after the 6 week treatment period . No significant differences in efficacy were found between the two treatment regimes . In the patients who completed the trial , brofaromine was well tolerated with the exception of insomnia . Anticholinergic effects as well as thyroid dysfunctions ( 17 out of 20 ) were more frequent in the maprotiline/lithium group The authors compared rates of new episodes in a sample of 64 unipolar subjects treated with fluvoxamine ( n = 32 ) and lithium ( n = 32 ) during a follow-up period of 24 months . Unipolar patients on lithium treatment had a worse outcome with a higher frequency of new recurrences compared with of new recurrences compared with patients on fluvoxamine during the course of preventive treatment The paper reports on the process of patient recruitment for a controlled clinical multicenter study on the treatment of affective disorders . Two thirds of the patients screened did not participate because prophylactic treatment was either unnecessary or not justified for medical reasons . Further , a number of patients equal to that eventually allocated to the trial refused to participate for personal , idiosyncratic reasons . In spite of this , the patients in the trial were very similar to those not participating with respect to relevant variables such as age , sex , number of and intervals between previous episodes or severity of the present episode Mixed mania ( i.e. , a manic syndrome accompanied by depressive symptoms ) and its response to long-term preventive drug treatment was studied as part of a larger NIMH collaborative study . Following recovery from a manic episode , patients received either lithium , imipramine , or the combination of lithium and imipramine for a 2-year period . It was found that patients who had recovered from a mixed manic state were at significantly higher risk for recurrences than patients who had recovered from a pure ( non-mixed ) manic state . Lithium and the combination of lithium and imipramine were highly effective preventive treatments for the pure manic group and poor treatments for the mixed group . Imipramine was ineffective for both the pure and mixed groups . The need for identifying mixed mania in therapeutic trials and in evaluating alternative treatments for lithium with this subgroup is discussed Forty-one out- patients with a history of at least three attacks of depressive illness were r and omly allocated to treatment on a double-blind basis for one year with either mianserin 20 mg three times daily plus placebo lithium tablets , or to lithium tablets once daily plus placebo mianserin tablets . After one year , the dosage of mianserin was increased to 30 mg t.d.s . for a further six months . All but three of the patients had previously been stabilized on prophylactic lithium therapy . Lithium was found to be significantly superior to mianserin in avoiding admission to hospital or ECT . The overall affective morbidity index , calculated from global rating , showed no significant difference between drugs , but the index of the mianserin group was higher in the second six months than in the first . The lithium group showed no such change .  Lithium remains the choice for the prophylaxis of unipolar recurrent depressive illness In an 18 hospital study , 205 patients hospitalized with a diagnosis of manic-depressive illness , manic type , were treated upon discharge with lithium carbonate or placebo for a two-year period . Lithium carbonate was significantly more effective than placebo in preventing relapses ( ie , affective episodes severe enough to require hospitalization or use of non study drugs ) . The difference in treatment outcome between lithium carbonate and placebo was due mainly to the lower incidence of manic relapses on lithium carbonate . Patients on lithium carbonate also had a lower incidence of depressive relapses than patients on placebo but the limited incidence of severe depression in this sample makes it difficult to draw any conclusions regarding the prophylactic efficacy of lithium carbonate in depressive illness . The results from this trial coupled with those from other studies indicate that lithium carbonate combined with regular clinical appraisal s is a safe and effective treatment for preventing relapse in manic-depressive illness Early morning sleep deprivation ( patient awake from 0200 to 2200 hours ) produces a same-day antidepressant effect in approximately one-half of patients with major depression . Unfortunately , these antidepressant effects are short-lived and patients usually relapse to baseline depression levels within 48 hours . Recent work suggests , however , that the use of lithium with early morning sleep deprivation sustains this rapid antidepressant effect and makes it clinical ly useful . In a 30-day study , we compared the abilities of four different treatments ( lithium plus early morning sleep deprivation , lithium plus a control sleep deprivation procedure , and desipramine with either of the two sleep manipulations ) to induce a rapid ( next-day ) and sustained antidepressant response in 16 depressed patients .  Lithium plus early morning sleep deprivation produced a quicker response than lithium with the control sleep deprivation , and the response was sustained for at least 30 days . In this design , however , lithium/early morning sleep deprivation was no faster than either of the two desipramine/sleep deprivation conditions in inducing remission . These results support the results of previous studies and suggest further investigation of this novel sleep/pharmacologic intervention is warranted OBJECTIVES To compare the relapse rate of elderly depressed patients taking low dose lithium as an additional therapy with antidepressant medication  to those receiving antidepressant medication alone . METHODS Fifty elderly subjects recovering from a major depressive illness taking continuation antidepressants  were r and omised , in a double blind study , to receive additional lithium carbonate or placebo and followed up over a two year period for evidence of relapse . RESULTS Relapse rate was significantly greater in those subjects taking antidepressant medication alone compared to subjects taking additional lithium therapy . After six months four ( 17 % ) subjects taking antidepressant medication alone had relapsed , whereas none of the subjects taking additional lithium had relapsed . After two years eight ( 33 % ) subjects taking antidepressant medication alone had relapsed , whereas only one ( 4 % ) of the subjects taking additional lithium had relapsed . CONCLUSION This preliminary study suggests that long-term low dose lithium therapy is well tolerated and protects elderly patients from a relapse of depressive illness A double-blind prospect i ve study was carried out comparing the prophylactic effect of maprotiline and lithium carbonate over a period of one year in patients suffering from recurrent affective disorders . The average Affective Morbidity Index was lower , but not significantly so , in patients treated with lithium .  A further analysis , based on dividing patients into those with no affective morbidity and those who showed some affective morbidity during the study , demonstrated lithium carbonate to be significantly superior to maprotiline both in the group as a whole and in unipolar depressives . A correlation between high plasma maprotiline concentration and low morbidity was observed and was in line with an earlier report . A highly significant negative correlation ( r=-0 - 97 ; p less than 0 - 001 ) was found between plasma maprotiline concentration and body weight . Although the results showed lithium carbonate to be superior to maprotiline in the study , it should be emphasized that the plasma levels of lithium  were constantly monitored and maintained at what is considered to be its optimum concentration , whereas the maprotiline treated patients were kept on a fixed dosage regime irrespective of plasma levels OBJECTIVE Use of lithium to augment antidepressant medication has been shown to be beneficial in the acute treatment of depression . The authors examined the efficacy of lithium augmentation in the continuation treatment of unipolar major depressive disorder . METHOD Thirty patients with a refractory major depressive episode who had responded to acute lithium augmentation during an open 6-week study participated in a r and omized , parallel-group , double-blind , placebo-controlled trial of lithium augmentation during continuation treatment . After a 2 - 4-week stabilization period following remission , patients were r and omly assigned to receive either lithium or placebo for a 4-month period . Antidepressant medication was continued throughout the study . RESULTS Relapses ( including one suicide ) occurred in seven ( 47 % ) of the 15 patients who received placebo in addition to antidepressants . None ( 0 % ) of the 14 patients who received lithium augmentation with antidepressants suffered a relapse during the double-blind phase of the study . Five of the seven relapsing patients in the placebo group developed a depressive episode , and the other two experienced a 
    Output:
    
agent
There were no other statistically significant differences between lithium and antidepressants according to all other outcomes considered .
AUTHORS ' CONCLUSIONS There was adequate efficacy evidence for lithium or antidepressants preventing relapse in unipolar affective disorder , however their relative efficacy was unknown .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Prolactin ( PRL ) and Cortisol ( CORT ) responses to d , l-fenfluramine ( FEN ) challenge ( 60 mg ) were examined in patients with affective disorders on two occasions under euthymic conditions : drug-free before admission to prophylactic treatment and after about 9 months of medication with lithium or carbamazepine .  Response to treatment was assessed by a complex algorithm using continuous ratings in outpatient clinic over a period of 2 years . In general , treatment result ed in a delayed and diminished CORT release ( n.s . ) ; subgroup analysis revealed an attenuated CORT response ( P < 0.05 ) in responders , whereas nonresponders showed no change in CORT secretion pattern except an enhanced CORT baseline value ( P < 0.05 ) . Cross-sectional comparison of responders with nonresponders under medication yielded a trend for greater CORT stimulation in nonresponders . This result was not affected by  FEN/NorFEN or lithium/carbamazepine serum levels , baseline CORT values , age , sex , diagnostic distribution , number of appointments to the outpatient clinic or duration of medication at the time of FEN test session . Before onset of prophylactic medication responders and nonresponders could not be discriminated significantly regarding stimulated hormone release , probably due to the small sample size ( n = 17 ) . CORT response to FEN was increased in drugfree unipolar patients compared to bipolar ( P < 0.05 ) and to schizoaffective patients ( P < 0.1 ) . In accordance with its well-documented presynaptic 5-HT-agonistic action lithium medication result ed in a significantly greater increase in CORT release than carbamazepine ( P < 0.05 ) . Evaluation of PRL stimulation showed patterns of secretion quite similar to those of CORT , without reaching statistical significance in most cases . Perhaps due to method ological differences in assessing treatment response , these data do not confirm former results , which supposed an enhanced 5-HT net activity in long-term prophylactic lithium treatment . Because of high interindividual variances of hormone parameters , the FEN-test procedure is not a useful tool for the prediction of therapeutical outcome in terms of clinical routine use . Relations of stimulated hormone response as a marker of central serotoninergic activity and clinical outcome are discussed Relapse  rates of the first 35 unipolar and bipolar II manic-depressive patients who entered the controlled phase of a continuing evaluation of the prophylactic value of  lithium alone or in combination with imipramine were analyzed . Lithium had a prophylactic effect in unipolar patients and possibly in bipolar II patients . Imipramine did not have a prophylactic effect in either group of patients In two r and omized double-blind controlled trials on 63 depressed female in- patients subject to recurrent affective disorder ( bipolar and unipolar manic-depressive psychosis )  lithium was shown to have major acute antidepressant effects . At the end of three weeks lithium produced more uniform improvement than did imipramine ; lithium in combination with tryptophan ( in the form of Optimax ) was superior to tryptophan alone -- the latter drug having no discernible antidepressant activity in this group of patients . Lithium did not produce an antidepressant effect until the second and third week of both trials Abstract The prophylactic effect of lithium was studied in a group of sixty-five patients with recurrent affective disorders in four centres . Patients were r and omly allocated to lithium or identical-looking placebo tablets for periods of up to 112 weeks . In addition , patients received any further medication or treatment which the psychiatrist in charge of the case thought was necessary . Patients receiving lithium had very significantly less affective illness than patients receiving placebo tablets , whether this was measured by time spent as an inpatient or by the duration of outpatient episodes . The amount of antidepressant or of antimanic medication prescribed was also significantly less in the lithium group . No patient on lithium was given  electroconvulsive therapy  ( E.C.T. ) , whereas 43 % of the placebo group received one or more courses of E.C.T. A global rating was made independently by two assessors who did not know whether the patient was in the lithium or in the placebo group . These assessors , the psychiatrist in charge of the case and a psychiatric social worker , showed a very high concordance in their ratings . 86 % of patients on lithium were rated as showing little or no affective disorders ( global rating 1 and 2 ) during the trial , as compared to only 8 % of the placebo group . Only 11 % of the lithium group was rated as unchanged or worse than during the 2 years previous to the trial , as compared with 75 % of the placebo group . Lithium seemed to be as effective in patients with unipolar recurrent depressive illness as in patients with both mania and depression Depressed out patients ( n = 51 ) resistant to treatment with maprotiline were treated in a blind , r and omized , single-centre study , for 6 weeks with either the reversible and selective monoamine oxidase A-inhibitor ( MAO-A-I ) , brofaromine or lithium addition to maprotiline . The Hamilton Rating Scale for Depression was scored by an independent rater before and after the 6 week treatment period . No significant differences in efficacy were found between the two treatment regimes . In the patients who completed the trial , brofaromine was well tolerated with the exception of insomnia . Anticholinergic effects as well as thyroid dysfunctions ( 17 out of 20 ) were more frequent in the maprotiline/lithium group The authors compared rates of new episodes in a sample of 64 unipolar subjects treated with fluvoxamine ( n = 32 ) and lithium ( n = 32 ) during a follow-up period of 24 months . Unipolar patients on lithium treatment had a worse outcome with a higher frequency of new recurrences compared with of new recurrences compared with patients on fluvoxamine during the course of preventive treatment The paper reports on the process of patient recruitment for a controlled clinical multicenter study on the treatment of affective disorders . Two thirds of the patients screened did not participate because prophylactic treatment was either unnecessary or not justified for medical reasons . Further , a number of patients equal to that eventually allocated to the trial refused to participate for personal , idiosyncratic reasons . In spite of this , the patients in the trial were very similar to those not participating with respect to relevant variables such as age , sex , number of and intervals between previous episodes or severity of the present episode Mixed mania ( i.e. , a manic syndrome accompanied by depressive symptoms ) and its response to long-term preventive drug treatment was studied as part of a larger NIMH collaborative study . Following recovery from a manic episode , patients received either lithium , imipramine , or the combination of lithium and imipramine for a 2-year period . It was found that patients who had recovered from a mixed manic state were at significantly higher risk for recurrences than patients who had recovered from a pure ( non-mixed ) manic state . Lithium and the combination of lithium and imipramine were highly effective preventive treatments for the pure manic group and poor treatments for the mixed group . Imipramine was ineffective for both the pure and mixed groups . The need for identifying mixed mania in therapeutic trials and in evaluating alternative treatments for lithium with this subgroup is discussed Forty-one out- patients with a history of at least three attacks of depressive illness were r and omly allocated to treatment on a double-blind basis for one year with either mianserin 20 mg three times daily plus placebo lithium tablets , or to lithium tablets once daily plus placebo mianserin tablets . After one year , the dosage of mianserin was increased to 30 mg t.d.s . for a further six months . All but three of the patients had previously been stabilized on prophylactic lithium therapy . Lithium was found to be significantly superior to mianserin in avoiding admission to hospital or ECT . The overall affective morbidity index , calculated from global rating , showed no significant difference between drugs , but the index of the mianserin group was higher in the second six months than in the first . The lithium group showed no such change .  Lithium remains the choice for the prophylaxis of unipolar recurrent depressive illness In an 18 hospital study , 205 patients hospitalized with a diagnosis of manic-depressive illness , manic type , were treated upon discharge with lithium carbonate or placebo for a two-year period . Lithium carbonate was significantly more effective than placebo in preventing relapses ( ie , affective episodes severe enough to require hospitalization or use of non study drugs ) . The difference in treatment outcome between lithium carbonate and placebo was due mainly to the lower incidence of manic relapses on lithium carbonate . Patients on lithium carbonate also had a lower incidence of depressive relapses than patients on placebo but the limited incidence of severe depression in this sample makes it difficult to draw any conclusions regarding the prophylactic efficacy of lithium carbonate in depressive illness . The results from this trial coupled with those from other studies indicate that lithium carbonate combined with regular clinical appraisal s is a safe and effective treatment for preventing relapse in manic-depressive illness Early morning sleep deprivation ( patient awake from 0200 to 2200 hours ) produces a same-day antidepressant effect in approximately one-half of patients with major depression . Unfortunately , these antidepressant effects are short-lived and patients usually relapse to baseline depression levels within 48 hours . Recent work suggests , however , that the use of lithium with early morning sleep deprivation sustains this rapid antidepressant effect and makes it clinical ly useful . In a 30-day study , we compared the abilities of four different treatments ( lithium plus early morning sleep deprivation , lithium plus a control sleep deprivation procedure , and desipramine with either of the two sleep manipulations ) to induce a rapid ( next-day ) and sustained antidepressant response in 16 depressed patients .  Lithium plus early morning sleep deprivation produced a quicker response than lithium with the control sleep deprivation , and the response was sustained for at least 30 days . In this design , however , lithium/early morning sleep deprivation was no faster than either of the two desipramine/sleep deprivation conditions in inducing remission . These results support the results of previous studies and suggest further investigation of this novel sleep/pharmacologic intervention is warranted OBJECTIVES To compare the relapse rate of elderly depressed patients taking low dose lithium as an additional therapy with antidepressant medication  to those receiving antidepressant medication alone . METHODS Fifty elderly subjects recovering from a major depressive illness taking continuation antidepressants  were r and omised , in a double blind study , to receive additional lithium carbonate or placebo and followed up over a two year period for evidence of relapse . RESULTS Relapse rate was significantly greater in those subjects taking antidepressant medication alone compared to subjects taking additional lithium therapy . After six months four ( 17 % ) subjects taking antidepressant medication alone had relapsed , whereas none of the subjects taking additional lithium had relapsed . After two years eight ( 33 % ) subjects taking antidepressant medication alone had relapsed , whereas only one ( 4 % ) of the subjects taking additional lithium had relapsed . CONCLUSION This preliminary study suggests that long-term low dose lithium therapy is well tolerated and protects elderly patients from a relapse of depressive illness A double-blind prospect i ve study was carried out comparing the prophylactic effect of maprotiline and lithium carbonate over a period of one year in patients suffering from recurrent affective disorders . The average Affective Morbidity Index was lower , but not significantly so , in patients treated with lithium .  A further analysis , based on dividing patients into those with no affective morbidity and those who showed some affective morbidity during the study , demonstrated lithium carbonate to be significantly superior to maprotiline both in the group as a whole and in unipolar depressives . A correlation between high plasma maprotiline concentration and low morbidity was observed and was in line with an earlier report . A highly significant negative correlation ( r=-0 - 97 ; p less than 0 - 001 ) was found between plasma maprotiline concentration and body weight . Although the results showed lithium carbonate to be superior to maprotiline in the study , it should be emphasized that the plasma levels of lithium  were constantly monitored and maintained at what is considered to be its optimum concentration , whereas the maprotiline treated patients were kept on a fixed dosage regime irrespective of plasma levels OBJECTIVE Use of lithium to augment antidepressant medication has been shown to be beneficial in the acute treatment of depression . The authors examined the efficacy of lithium augmentation in the continuation treatment of unipolar major depressive disorder . METHOD Thirty patients with a refractory major depressive episode who had responded to acute lithium augmentation during an open 6-week study participated in a r and omized , parallel-group , double-blind , placebo-controlled trial of lithium augmentation during continuation treatment . After a 2 - 4-week stabilization period following remission , patients were r and omly assigned to receive either lithium or placebo for a 4-month period . Antidepressant medication was continued throughout the study . RESULTS Relapses ( including one suicide ) occurred in seven ( 47 % ) of the 15 patients who received placebo in addition to antidepressants . None ( 0 % ) of the 14 patients who received lithium augmentation with antidepressants suffered a relapse during the double-blind phase of the study . Five of the seven relapsing patients in the placebo group developed a depressive episode , and the other two experienced a 
    Output:
    