title: 5-HT brain function in affective disorder: d,l-fenfluramine-induced hormone release and clinical outcome in long-term lithium/carbamazepine prophylaxis. Prophylactic effect of lithium and imipramine in unipolar and bipolar II patients: a preliminary report. Controlled studies of the acute antidepressant effects of lithium. Prophylactic lithium in affective disorders. Controlled trial. Brofaromine versus lithium addition to maprotiline. A double-blind study in maprotiline refractory depressed outpatients. A 24-month follow-up study of unipolar subjects: a comparison between lithium and fluvoxamine. The recruitment process for a multicenter study on the long-term prophylactic treatment of affective disorders. Treatment of mixed mania. Mianserin and lithium in the prophylaxis of depression. Prophylactic efficacy of lithium carbonate in manic-depressive illness. Report of the Veterans Administration and National Institute of Mental Health collaborative study group. Lithium sustains the acute antidepressant effects of sleep deprivation: Preliminary findings from a controlled study Prophylactic therapy with lithium in elderly patients with unipolar major depression. A double-blind comparison of lithium carbonate and maprotiline in the prophylaxis of the affective disorders. Double-blind, placebo-controlled trial of the use of lithium to augment antidepressant medication in continuation treatment of unipolar major depression. Lithium as a prophylactic agent in unipolar affective illness: comparison with cyclic antidepressants. Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders. Report of the NIMH Collaborative Study Group comparing lithium carbonate, imipramine, and a lithium carbonate-imipramine combination. Continuation therapy with lithium and amitriptyline in unipolar depressive illness: a randomized, double-blind, controlled trial. Methodologic issues in maintenance therapy clinical trials. Acute antidepressant effect of lithium is associated with fluctuation of calcium and magnesium in plasma Effect of prophylactic treatment on suicide risk in patients with major affective disorders. Data from a randomized prospective trial. THE EFFECT OF LITHIUM CARBONATE IN COMBINATION WITH TRICYCLIC ANTIDEPRESSANTS IN ENDOGENOUS DEPRESSION: A double‐blind, multicenter trial Response to maintenance therapy in bipolar illness. Effect of index episode. Lithium prophylaxis in recurrent affective illness. Prophylactic lithium: a double-blind trial in recurrent affective disorders. Lithium carbonate and imipramine in prevention of affective episodes. A comparison in recurrent affective illness. Five antidepressant treatments in depressed patients. Effects on urinary serotonin and 5-hydroxyindoleacetic acid output. The use of lithium in affective disorders. II. Prophylaxis of depression in chronic recurrent affective disorder. Flupenthixol decanoate in recurrent manic‐depressive illness Comparative efficacy of lithium and amitriptyline in the maintenance treatment of recurrent unipolar depression: a randomised study. Gradual discontinuation of lithium augmentation in elderly patients with unipolar depression. The use of lithium in affective disorders. 3. A double-blind study of prophylaxis in bipolar illness. Lithium carbonate and imipramine in the prophylaxis of unipolar and bipolar II illness: a prospective, placebo-controlled comparison. Double-blind comparison of lithium carbonate and imipramine in treatment of depression. A controlled study of the antidepressant effects of lithium carbonate. Continuation drug therapy for major depressive episodes: how long should it be maintained? Prophylactic lithium: double blind discontinuation in manic-depressive and recurrent-depressive disorders.
abstract: 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 manic episode . CONCLUSIONS Lithium augmentation in the continuation phase of treatment of unipolar major depressive disorder effectively protects patients against a relapse .  Patients who respond to lithium augmentation  should be maintained on lithium augmentation for a minimum of 6 months or even longer As reported by Prien ( see p 847 ) , two United States committees concluded in 1975 that lithium is prophylactically efficacious , ie , significantly better than placebo , in recurrent bipolar affective illness . The committees felt , however , that they could not recommend the prophylactic use of lithium in recurrent unipolar affective illness ( 1 ) because there is uncertainty as to what a unipolar disorder represents and ( 2 ) because the evidence for the efficacy of lithium in this disease type is based on a relatively small number of patients . With the first reason given , the committees more or less acknowledge that lack of trust in the psychiatrists ' ability to diagnose recurrent unipolar affective illness played a role in their decision . I have no comment to offer on this . As regards the second reason : It might be worth comparing the evidence now available for prophylactic efficacy of lithium and of cyclic antidepressants  in unipolar affective illness . In a double-blind , long-term follow-up study , 117 bipolar patients received lithium carbonate , imipramine hydrochloride , or both and 150 unipolar patients received lithium carbonate , imipramine , both lithium carbonate and imipramine , or placebo . With bipolar patients , lithium carbonate and the combination treatment were superior to imipramine in preventing manic recurrences and were as effective as imipramine in preventing manic recurrences and were as effective as imipramine in preventing depressive episodes . The combination treatment provided no advantage over lithium carbonate alone . With unipolar patients , imipramine and the combination treatment were more effective than lithium carbonate and placebo in preventing depressive recurrences . The combination treatment provided no advantage over imipramine alone . The lithium carbonate-treated group had fewer manic episodes than the other groups . Treatment outcome , which was evaluated primarily in terms of the occurrence of major depression or manic episodes , was significantly related to characteristics of the index episode , ie , the episode that brought the patient into the study A detailed analysis of the results of a multi-centre clinical trial shows that , while the relapse rate following recovery from an operationally defined depressive illness was smaller among patients subsequently treated with either amitryptiline or lithium  than with a placebo , there was no clinical ly significant difference between the prophylactic efficacy of the 2 antidepressants . An account is given of the relative adverse effects of the treatments , and the implication s of the findings are discussed In the early 1980s , the National Institute of Mental Health supported a multicenter , r and omized , controlled , clinical trial on unipolar and bipolar disorder to evaluate the comparative efficacies of lithium carbonate , imipramine hydrochloride , a lithium-imipramine combination , and placebo in preventing the recurrence of affective disorders . The objective of this report is to present a re analysis of the relative efficacies of these treatments in patients with unipolar disorder to focus attention on general issues related to the design and conduct of maintenance therapy trials . We show that the earlier conclusions of that study that imipramine and the combination therapy are more effective than lithium and placebo in preventing the recurrence of depression in unipolar patients can be accounted for by alternative explanations that are a consequence of the design of the study . Our findings have important implication s for the design , conduct , and interpretation of results of maintenance therapy clinical trials in general In a double‐blind study on 22 patients with major depressive disorder the effects of lithium and clomipramine on signs and symptoms and on calcium and magnesium in plasma were compared . Ratings of antidepressant and side effects were performed by 2 psychiatrists at the end of a placebo period of 5–7 days and after treatment for 2 and 4 weeks . Psychopathology was rated by 15 reported and 4 observed items from the Comprehensive Psycho pat ho logical Rating Scale ( CPRS ) . Eleven items present in 72–100 % of the patients were used to evaluate the effect of the two drugs . After 2 weeks of treatment the rated scores dropped for more than half of the CPRS items . After 4 weeks the scores for all but one item were reduced in both groups . The sums of scores were significantly reduced after 2 weeks in both groups and after 4 weeks global scores were reduced as well . The drugs had notable and similar antidepressant effects . Lithium treatment was associated with fluctuations in calcium and magnesium levels in plasma not seen during clomipramine treatment . Serum prolactin increased during clomipramine treatment but was unaffected by lithium treatment . No correlations were found between the sum of rating scores and blood levels of drugs , prolactin , calcium or magnesium Recent findings have indicated that lithium treatment markedly reduces  suicide risk in major affective disorders . To compare the effect of lithium with carbamazepine and amitriptyline , suicidal behavior was analyzed during the r and omized prospect i ve long-term MAP study ( N = 378 ; duration 2.5 years ) . Of the nine suicides and five attempted suicides , none took place during lithium treatment . The findings support the view that lithium has a specific antisuicidal effect over and above its prophylactic benefit Forty‐five endogenously depressed patients in nine different hospitals were given , r and omly , tricyclic antidepressants plus placebo , or tricyclic antidepressants plus lithium carbonate , for a minimum of 4 weeks . At the hospital with the largest single material , the six patients in the lithium group showed significantly greater improvement after 1 and 4 weeks than the seven patients in the placebo group . At the other hospitals , a total of 14 patients received lithium and 18 placebo , with no significant difference in outcome . However , the heterogeneity of this part of the material might easily have obscured any real difference in treatment outcome . Treatment response in the total material did not correlate significantly with diagnosis ( e.g. , whether unipolar or bipolar affective illness ) , age or sex . No significant side effects were reported Most previous studies of long-term maintenance therapy for bipolar illness simply compared proportions of patients experiencing recurrences . This method is inadequate because the length of time until a recurrence is not taken into account and because data from patients who withdraw prematurely from the study without a recurrence are either ignored or analyzed improperly . More appropriate survival analytic techniques were applied to the data from the National Institute of Mental Health Collaborative Study of bipolar patients treated with lithium carbonate , imipramine hydrochloride , or both . An interaction between treatment and the nature of the index episode ( the episode that brought the patients into the study ) was found . In patients with manic index episodes , both lithium and the combination were superior to imipramine . In patients with depressive index episodes , the combination was significantly superior to imipramine , whereas lithium was indistinguishable from imipramine . The latter finding differs from the original analysis , which found the combination to be no different from the other two treatments for patients with a depressive index episode The authors report on two recent two-year studies that attempted to determine the effectiveness of lithium carbonate  in treating recurrent affective illness . In study I , 205 bipolar ( manic-depressive ) patients were r and omly assigned to lithium or placebo ; in study 2 , 44 bipolar and 78 unipolar ( depressive ) patients were r and omly assigned  lithium , imipramine , or placebo . The results showed lithium to be effective in treating both manic and depressive episodes and imipramine to be effective in treating depressive episodes . The findings emphasize the importance of considering the patient 's previous course of illness in selecting a program of maintenance treatment The criteria required for the inclusion of patients into the group studied are described . The 29 patients suffered from recurrent affective disorders . No patient satisfying the criteria for selection was excluded . Reasons why 11 of the 29 patients could not be included in the double-blind trial are given . The double-blind trial was performed on the remaining 18 patients . The significance of the difference between the lengths of remissions achieved by the lithium group and the dummy group was measured by the Mann-Whitney U-test . The superiority of lithium over the dummy just failed to be significant at the 5 per cent level , 0.10>p>0.05 . One case of serious toxicity occurred . The patient recovered rapidly and completely . The design and result of the trial is discussed Patients with recurrent affective illness ( N-122 ) were r and omly assigned to lithium carbonate , imipramine , or placebo therapy for two years following discharge from hospitalization for acute depression . Patients were classified as bipolar or unipolar based on the presence or absence of a history of mania . With bipolar patients lithium carbonate was significantly more effective than imipramine or placebo in preventing affective episodes ( ie , manic or depressive attacks severe enough to require hospitalization or use of non study drugs ) . There was a relatively high incidence of manic episodes on imipramine . Unipolar patients responded equally well to lithium carbonate or imipramine . Both treatments were significantly more effective than placebo . The difference between treatments was due primarily to depressive episodes ; manic episodes occurred infrequently and were evenly distributed across treatment groups . There was no significant difference between  lithium carbonate and imipramine  among unipolar patients The 24-hour urinary serotonin ( 5-HT ) and 5-hydroxyindoleacetic acid ( 5-HIAA ) outputs were repeatedly measured in 21 patients with major affective disorders after a minimum of three weeks free of drug treatments and at steady state during subsequent antidepressant treatments or during the second week after a series of electroconvulsive treatments ( ECTs ) .  The 5-HIAA outputs were more variable over time than the outputs of major catecholamine metabolites , previously studied by us . Patients with rapid mood cycles excreted large amounts of 5-HT .  Lithium carbonate and ECTs  reduced the outputs of 5-HT and 5-HIAA , respectively . Lithium carbonate also stabilized the output of 5-HT . No common effect of different antidepressant treatments on indole outputs was found In a longitudinal outpatient study , the authors found that lithium produced a mild decrease in depth of depression scores among patients who had been on the drug for more than seven months , as compared with patients who had been receiving lithium less than seven months . They assess the factors contributing to reported positive clinical results of maintenance lithium treatment in recurrent affective disorder The hypothesis that flupenthixol decanoate may serve as an alter‐native to prophylactically administered lithium in recurrent manicdepressive illness , bipolar and unipolar type , was tested in two groups of patients . In Group I the patients were allocated r and omly to maintenance treatment with either lithium or flupenthixol decanoate . The patients in Group II had previously been given lithium and were switched to flupenthixol decanoate because of unsatisfactory prophylactic effect of lithium , doubtful tablet compliance , troublesome side effects , or fear of later harmful effects . The flupenthixol decanoate dosage was 20 mg every 2–3 weeks . The study was not blind The present study , including 81 depressive patients , compares the prophylactic efficacy of lithium and amitriptyline in recurrent unipolar depression over a treatment period of 2.5 years in a r and omised multicentre design .  Hospitalisation , re-emergence of depressive or subdepressive recurrences , unwanted side-effects and need of concomitant psychotropic medication were considered to indicate treatment failures . Average dosage for amitriptyline  was 98 + /- 37 mg/day , average  lithium blood level was 0.59 + /- 0.12 mmol/l . Survival analyses demonstrated a significant superiority of lithium ( P = 0.015 ) regarding the outcome criteria ' recurrences and /or sub clinical recurrences ' and non-significantly better results of lithium compared to amitriptyline concerning ' recurrence ' ( P = 0.059 ) or ' recurrence and /or concomitant medication ' ( P = 0.066 ) Recently , the therapeutic benefit of lithium augmentation in old age has come into question . These data , in light of the documented high incidence of side effects after lithium use in elderly patients , result ed in the design of a prospect i ve , placebo-controlled lithium augmentation withdrawal study in elderly patients with unipolar depression . Twelve eligible geriatric patients ( 10 women and 2 men ; mean [ + /-SD ] age , 76.2 + /- 5.7 years ) with DSM-III-R unipolar depression receiving adjunct lithium therapy  were r and omized to receive continued lithium augmentation or matching placebo ( withdrawal rate 150 mg/day/wk ) . At each clinic visit , patients were assessed for depression ( Montgomery-Asberg Depression Rating Scale and Geriatric Depression Rating Scale ) and  lithium-induced toxicities ( a 21-item side-effect checklist , renal and thyroid biochemistry ) . Over the 2-year observation period , the placebo group reported a decrease in composite 21-item side-effect score and specific lithium toxicities ( e.g. , urinary urgency , h and tremor , and renal/thyroid abnormalities ) . Two patients in the lithium maintenance group had a recurrence of depression at 61 and 96 weeks , respectively , immediately after a stressful life event ( cerebrovascular accident [ CVA ] or death of spouse ) , and two patients had a recurrence in the placebo group at 7 and 92 weeks , respectively , without any apparent changes in life stresses . No other prognostic risk factors for recurrence were identified . Depression that recurred in patients who were receiving placebo was relatively resistant to reinstitution of lithium augmentation therapy . In otherwise stable geriatric patients with unipolar depression , the documented benefits of reduced side effects should be weighed against the risk of recurrence and subsequent lithium resistance before withdrawal of lithium augmentation The authors studied 52 manic-depressive patients who were assigned to either lithium or placebo during their normal interval phases for periods up to 28 months . Patients receiving lithium had fewer manic and depressive episodes per patient-year than placebo patients . However , this difference may have been due to a sample bias produced by a large dropout rate among patients who had manic episodes . The findings also suggest a relationship between response to lithium and family history of bipolar illness Twenty-seven patients with recurrent unipolar depression and 22 with bipolar II illness in remission for at least six months were r and omly assigned on a double-blind basis to treatment regimens using lithium carbonate , imipramine hydrochloride , lithium carbonate plus imipramine , or placebo . Lithium carbonate was found to help prevent depressive relapse among patients with unipolar disease , and relapse of any type among those with bipolar II disease . No effect or interaction of imipramine  was found in either group . These results add to a growing body of data that suggest the usefulness of lithium carbonate in the prophylaxis of unipolar depressive illness . The relative usefulness of lithium carbonate and imipramine requires further study The effect of lithium carbonate therapy on patients with depression is still unconfirmed . Our past studies have shown a favorable response to the drug in patients with depression of mild or moderate severity . Therefore , we performed a controlled double-blind study of lithium carbonate and imipramine hydrochloride in 64 patients with depression . No significant differences were noted in the overall therapeutic response , depression scale scores , or clinical effects between the two drug groups In a double-blind crossover study comparing lithium carbonate with desimipramine in the treatment of selected depressed patients , there was considerable improvement in both groups of patients , with no statistically significant difference between the effectiveness of the two drugs . This finding , together with other reports , raises the question of whether lithium carbonate might be effective in the treatment of selected depressed patients . Consideration is also given to the implication s of our observations and findings for the bipolar concept of mania and depression . Evidence is considered for an alternative model which highlights some of the similarities between these two clinical states A major problem for the practitioner is the lack of satisfactory guidelines as to how long continuation drug treatment of depressive episodes must be maintained to ensure that the episode is over . This often leads to either premature withdrawal of the drug and subsequent relapse or unnecessarily prolonged treatment . Results from a collaborative project of the National Institute of Mental Health provide the first study -derived guidelines on the length of continuation therapy .  Findings indicate that withdrawal of such therapy is safe only after the patient has been free of significant symptoms for 16 to 20 weeks and that focusing on mild as well as severe symptoms is critical in this decision Abstract Fifty manic-depressive patients and thirty-four patients with recurrent endogenous depression who had been on open lithium treatment for at least a year took part in double-blind discontinuance studies to compare lithium carbonate and placebo . Within each diagnostic group matched pairs were allocated at r and om to lithium carbonate or placebo .  Relapses occurring first in the lithium partners constituted placebo preferences and those occurring first in the placebo parners lithium preferences . Relapses were recorded when requiring hospital admission or supervision with additional therapy at home . Serum-lithium levels were monitored . The trials terminated in significant preference for lithium both in manic-depressive and in recurrent-depressive disorder ; this happened when nine patients in each group had relapsed on placebo and none on lithium . During the whole trial , which lasted five months , twenty-one placebo patients relapsed and none of the lithium patients . Before the trials , patients had been on lithium for up to 7 years ; even after this long period there was still risk of relapse on withdrawal of the drug
target: 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 .
background: BACKGROUND The main rationale for the use of lithium in the long-term treatment of unipolar affective disorder is its efficacy in treating bipolar affective disorder and resistant depression .
  However , there is considerable uncertainty about which pharmacological intervention is most effective in the long-term treatment of recurrent unipolar affective disorder .
  OBJECTIVES To assess the effects of lithium versus antidepressants for the long-term treatment of recurrent affective disorder .