Abstract
The idea of lithium's specificity for bipolar disorder was proposed in Cade's original work in 1949. Since then, many controlled studies have been performed, examining lithium for treatment of bipolar disorder and other psychiatric conditions. This review was undertaken to determine if the suggestion of lithium's specificity has support in the controlled studies conducted after Cade's initial proposal. Studies were selected in a Medline search, dating back to 1966 and also identified from the bibliography of some of these papers. The controlled trials with lithium for the treatment of mania and bipolar depression, unipolar depression, schizophrenia, and schizoaffective disorder were reviewed. The published studies with lithium in other neuropsychiatric conditions were also considered. Additionally, we reviewed literature on other therapeutic agents proposed for bipolar disorder, looking at their comparative effectiveness to lithium. The data analyzed give strong support for lithium's being most effective in bipolar disorder, with minimal or no therapeutic effects in other neuropsychiatric disorders. The neurochemical underpinnings of this specificity are being investigated, without conclusive findings to date. The study of this paradigm of specificity in neuropsychopharmacology research may lead to meaningful contributions to understanding the pathophysiology of bipolar disorder and may help to develop newer treatments for this condition.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Abe K . (1977): Lithium prophylaxis of periodic hypersomnia. Brit J Psychiat 130: 312–316
Abou-Saleh MT . (1983): Platelet MAO: Personality and response to lithium prophylaxis. J Aff Dis 5: 55–65
Abou-Saleh MT, Coppen A . (1986): Who responds to prophylactic lithium? J Aff Dis 10: 115–125
Abrams T, Taylor MA . (1976): Mania and schizo-affective disorder, manic type: A comparison. Am J Psychiat 133: 1445–1447
Albright PS, Burnham WM . (1980): Development of a new pharmacological seizure model: Effects of anticonvulsants on cortical and amygdala-kindled seizures in the rat. Epilepsia 21: 681–689
Alexander PE, van Kammen DP, Bunney WE Jr . (1979): Antipsychotic effects of lithium in schizophrenia. Am J Psychiat 136: 283–287
Altshuler KZ, Abdullah S, Rainer JD . (1977): Lithium and aggressive behavior in patients with early total deafness. Dis Nerv Syst 38: 521–524
Antelman SM, Caggiula AR, Kiss S, Edwards DJ, Kocan D, Stiller R . (1995): Neurochemical and physiological effects of cocaine oscillate with sequential drug treatment: Possibly a major factor in drug variability. Neuropsychopharmacology 12: 297–306
Atack JR, Broughton HB, Pollack SJ . (1995): Inositol monophosphatase—A putative target for Li+ in the treatment of bipolar disorder. Trend Neurosci 18: 343–349
Atre-Vaidya N, Taylor MA . (1989): Effectiveness of lithium in schizophrenia: Do we really have an answer? J Clin Psychiat 50: 170–173
Baastrup PC . (1964): The use of lithium in manic depressive psychosis. Comp Psychiat 5: 396–408
Baastrup PC, Schou M . (1967): Lithium as a prophylactic agent. Arch Gen Psychiat 16: 162–172
Baastrup PC, Poulsen JC, Schou M, Thomsen K, Amdisen A . (1970): Prophylactic lithium: Double-blind discontinuation in manic-depressive and recurrent-depressive disorders. Lancet 2: 326–330
Ballenger JC . (1988): The use of anticonvulsants in manic-depressive illness. J Clin Psychiat 49: 21–25
Ballenger JC, Post RM . (1980): Carbamazepine in manic-depressive illness: A new treatment. Am J Psychiat 137(7):782–790
Baraban JM, Worley PF, Snyder SH . (1989): Second messenger systems and psychoactive drug action: Focus on the phosphoinositide system and lithium. Am J Psychiat 146: 1251–1260
Baron M, Gershon ES, Rudy V, Jonas WZ, Buchsbaum M . (1975): Lithium carbonate response in depression. Prediction by unipolar-bipolar illness, average-evoked response, catechol-O-methyl transferase, and family history. Arch Gen Psychiat 32: 1107–1111
Black DW, Winokur G, Nasrallah A . (1987): Treatment of mania: A naturalistic study of electroconvulsive therapy versus lithium in 438 patients. J Clin Psychiat 48: 132–139
Bowden CL, Brugger AM, Swann AC, Calabrese JR, Janicak PG, Petty F, Dilsaver SC, Davis JM, Rush AJ, Small JG, Garza-Trevino ES, Risch SC, Goodnick PJ, Morris DD . (1994): Efficacy of divalproex vs. lithium and placebo in the treatment of mania. The Depakote Mania Study Group. JAMA 271: 918–924
Bowden CL . (1995): Predictors of response to divalproex and lithium. J Clin Psychiat 56: 25–30
Braden W . (1977): Response to lithium in a case of L-dopa-induced psychosis. Am J Psychiat 134: 808–809
Braden W, Fink EB, Qualls CB, Ho CK, Samuels WO . (1982): Lithium and chlorpromazine in psychotic inpatients. Psychiat Res 7: 69–81
Brockington IF, Kendell RE, Kellett JM, Curry SH, Wainwright S . (1978): Trials of lithium, chlorpromazine, and amitriptyline in schizoaffective patients. Brit J Psychiat 133: 162–168
Brockington IF, Wainwright S, Kendell RE . (1980): Manic patients with schizophrenic or paranoid symptoms. Psycholog Med 10: 73–83
Cade JFJ . (1949): Lithium salts in the treatment of psychotic excitement. Med J Australia 14: 349–352
Calabrese JR, Delucchi GA . (1990): Spectrum of efficacy of valproate in 55 patients with rapid-cycling bipolar disorder. Am J Psychiat 147: 431–434
Calabrese JR, Markovitz PJ, Kimmel SE, Wagner SC . (1992): Spectrum of efficacy of valproate in 78 rapid-cycling bipolar patients. J Clin Psychopharmacol 12: 53–56
Campbell M, Adams PB, Small AM, Kafantaris V, Silva RR, Shell J, Perry R, Overall JE . (1995a): Lithium in hospitalized aggressive children with conduct disorder. A double-blind and placebo-controlled study. J Am Acad Child Adolesc Psychiat 34: 445–453
Carpenter WT, Kurz R, Kirkpatrick B, Hanlon TE, Summerfelt T, Buchanan RW, Waltrip RW, Breier A . (1991): Carbamazepine maintenance treatment in outpatient schizophrenics. Arch Gen Psychiat 48: 69–72
Clothier J, Swann AC, Freeman T . (1992): Dysphoric mania. J Clin Psychopharmacol 12: 13S–16S
Coppen A, Noguera R, Bailey J, Burns BH, Swani MS, Hare EH, Gardner R, Maggs R . (1971): Prophylactic lithium in affective disorders—Controlled trial. Lancet, August, 275–279
Coryell W, Endicott J, Maser JD, Mueller T, Lavori P, Keller M . (1995): The likelihood of recurrence in bipolar affective disorder: The importance of episode recency. J Aff Dis 33: 201–206
Coxhead N, Silverstone T, Cookson J . (1992): Carbamazepine versus lithium in the prophylaxis of bipolar affective disorder. Acta Psychiat Scand 85: 114–118
Craft M, Ismail IA, Krishnamurti D, Mathews J, Regan A, Seth RV, North PM . (1987): Lithium in the treatment of aggression in mentally handicapped patients. A double-blind trial. Brit J Psychiat 150: 685–689
Cronson AJ, Flemenbaum A . (1978): Antagonism of cocaine highs by lithium. Am J Psychiat 135: 856–857
Crow TJ . (1990): Continuum of psychoses and its genetic origins. The Sixty-Fifth Maudsley Lecture. Brit J Psychiat 150: 788–797
Cundall RL, Brooks PW, Murray LG . (1972): A controlled evaluation of lithium prophylaxis in affective disorders. Psycholog Med 2: 308–311
Dardennes R, Even C, Bange F, Heim A . (1995): Comparison of carbamazepine and lithium in the prophylaxis of bipolar disorders—A meta-analysis. Brit J Psychiat 166: 378–381
DeLong GR . (1978): Lithium carbonate treatment of select behavior disorders in children suggesting manic-depressive illness. J Pediat 93: 689–694
DeLong GR, Nieman GW . (1983): Lithium-induced behavioral changes in children with symptoms suggesting manic-depressive illness. Psychopharmacol Bull 19: 258–265
Delve NJ, Letemendia FJJ . (1982): Lithium treatment in schizophrenia and schizo-affective disorders. Brit J Psychiat 141: 387–400
de Montigny C . (1994): Lithium addition in treatment-resistant depression. Int Clin Psychopharmacol 9: 31–35
DePetrillo PB, Abernethy DR, Wainer IW, Andrawis NS . (1994): Verapamil decreases lymphocyte protein kinase C activity in humans. Clin Pharmacol Therapeu 55: 44–49
Dickson WE, Kendell RE . (1986): Does maintenance lithium therapy prevent recurrences of mania under ordinary clinical conditions? Psycholog Med 16: 521–530
Di Constanzo E, Schifano F . (1991): Lithium alone or in combination with carbamazepine for the treatment of rapid-cycling bipolar affective disorder. Acta Psychiat Scand 83: 456–459
Dilsaver SC, Swann AC, Shoaib AM, Bowers TC, Halle MT . (1993): Depressive mania associated with response to antimanic agent. Am J Psychiat 150: 1548–1551
Dinsmore PR, Ryback R . (1972): Lithium in schizo-affective disorders. Dis Nerv Syst December, 771–776
Dorus W, Ostrow DG, Anton R, Cushman P, Collins JF, Schaefer M, Charles HL, Desai P, Hayashida M, Malkerneker U, Willenbring M, Fiscella R, Sather MR . (1989): Lithium treatment of depressed and nondepressed alcoholics. JAMA 262: 1646–1652
Dostal T, Zvolsky P . (1970): Antiaggressive effect of lithium salts in severe mentally retarded adolescents. Int Pharmacopsychiat 5: 203–207
Dubovsky SL, Christiano J, Daniell LC, Franks RD, Murphy J, Adler L, Baker N, Harris A . (1989): Increased platelet intracellular calcium concentration in patients with bipolar affective disorder. Arch Gen Psychiat 46: 632–638
Dubovsky SL, Lee C, Christiano J, Murphy J . (1991): Elevated platelet intracellular calcium concentration in bipolar depression. Biolog Psychiat 29: 441–450
Dubovsky SL, Murphy J, Thomas M, Rademacher J . (1992): Abnormal intracellular calcium ion concentration in platelets and lymphocytes of bipolar patients. Am J Psychiat 149: 118–120
Dubovsky SL, Thomas M, Hijazi A, Murphy J . (1994): Intracellular calcium signalling in peripheral cells of patients with bipolar affective disorder. Eur Arch Psychiat Clin Neurosci 243: 229–234
Dunner DL, Stallone F, Fieve RR . (1976): Lithium carbonate and affective disorders. V: A double-blind study of prophylaxis of depression in bipolar illness. Arch Gen Psychiat 33: 117–120
Ebert D, Jaspert A, Murata H, Kaschka WP . (1995): Initial lithium augmentation improves the antidepressant effects of standard TCA treatment in nonresistant depressed patients. Psychopharmacology 118: 223–225
Elphick M . (1985): An open trial of carbamazepine in treatment-resistant bipolar and schizo-affective psychotics. Brit J Psychiat 147: 198–200
Emrich HM, Dose M, von Zerssen D . (1985): The use of sodium valproate, carbamazepine, and oxcarbazepine in patients with affective disorders. J Aff Dis 8: 243–250
Faedda GL, Baldessarini RJ, Tohen N, Strakowski SM, Waternaux C . (1991): Episode sequence in bipolar disorder and response to lithium treatment. Am J Psychiat 148: 1237–1239
Fava M, Rosenbaum JF, McGrath PJ, Stewart JW, Amsterdam JD, Quitkin FM . (1994): Lithium and tricyclic augmentation of fluoxetine treatment for resistant major depression: A double-blind, controlled study. Am J Psychiat 155: 1372–1374
Fawcett J, Clark DC, Aagesen CA, Pisani VD, Tilkin JM, Sellers D, McGuire M, Gibbons RD . (1987): A double-blind, placebo-controlled trial of lithium carbonate therapy for alcoholism. Arch Gen Psychiat 44: 248–256
Fieve RR, Dunner DL, Kumbarachi T, Stallone F . (1975): Lithium carbonate in affective disorders. IV. A double-blind study of prophylaxis unipolar recurrent depression. Arch Gen Psychiat 32: 1541–1544
Fieve RR, Dunner DL, Kumbaraci T, Stallone F . (1976): Lithium carbonate prophylaxis of depression in three subtypes in primary affective disorder. Pharmakopsychiat Neuro-Psychopharmakol 9: 100–107
Folks DG, King LD, Dowdy SB, Petrie WM, Jack RA, Kooman JC, Swenson BR, Edwards P . (1982): Carbamazepine treatment of affectively disordered inpatients. Am J Psychiat 139(1):115–117
Freeman TW, Clothier JL, Passaglia P, Lesem MD, Swann AC . (1992): A double-blind comparison of valproate and lithium in the treatment of acute mania. Am J Psychiat 149: 108–111
Fogelson DL, Jacobson S, Sternbach H . (1991): A retrospective study of valproate in private psychiatric practice. Ann Clin Psychiat 3: 315–320
Forstner U, Bohus M, Gebicke-Harter PJ, Baumer B, Berger M, van Calker D . (1994): Decreased agonist-stimulated Ca2+ response in neutrophils from patients under chronic lithium therapy. Eur Arch Psychiat Clin Neurosci 243: 240–243
Friedman E, Wang HY, Levinson D, Connell TA, Singh H . (1993): Altered platelet protein kinase C activity in bipolar affective disorder, manic episode. Biolog Psychiat 33: 520–525
Garfinkel PE, Stancer HC, Persad E . (1980): A comparison of haloperidol, lithium carbonate, and their combination in the treatment of mania. J Aff Dis 2: 279–288
Garver DL, Hirschowitz J, Fleischman R, Djuric PE . (1984): Lithium response and psychosis: A double-blind placebo-controlled study. Psychiat Res 12(1):S7–S8
Gaviria M, Flaherty J, Val E . (1982): A comparison of bipolar patients with and without a borderline personality disorder. Psychiatric J Univ Ottawa 7: 190–195
Geisler A, Schou M . (1973): Lithium treatment of obsessive-compulsive neurosis: A double-blind therapeutic trial with negative result. Foreign Psychiat 2: 90–94
Gershon S, Trautner EM . (1956): The treatment of shock dependency by pharmacological agents. Med J Australia 12(7):S2–S12
Gershon S, Yuwiler A . (1960): Lithium ion: A specific psychopharmacological approach to the treatment of mania. J Neuropsychiat 1: 229–241
Gershon S . (1970): Lithium in mania. Clin Pharmacol Therapeu 11: 168–187
Gershon S, Soares JC . (1997). Current therapeutic profile of lithium. Arch Gen Psychiat 54: 16–20
Glen AI, Johnson AL, Shepherd M . (1984): Continuation therapy with lithium and amitriptyline in unipolar depressive illness: A randomized, double-blind, controlled trial. Psycholog Med 14: 37–50
Goetzl U, Gruenberg F, Berkowit B . (1977): Lithium carbonate in management of hyperactive aggressive behavior of mentally retarded. Comp Psychiat 18: 599–606
Goodwin FK, Murphy DL, Dunner DL, Bunney WE Jr . (1972): Lithium response in unipolar versus bipolar depression. Am J Psychiat 129: 44–47
Goodwin FK, Zis AP . (1979): Lithium in the treatment of mania—Comparisons with neuroleptics. Arch Gen Psychiat 36: 840–844
Goodwin FK, Jamison KR . (1990): Manic-Depressive Illness. New York, Oxford University Press
Goodwin GM . (1994): Recurrence of mania after lithium withdrawal—Implications for the use of lithium in the treatment of bipolar affective disorder. Brit J Psychiat 164: 149–152
Goodwin GM . (1995): Lithium revisited—A reply. Brit J Psychiat 167: 573–574
Grof P, Alda M, Grof E, Fox D, Cameron P . (1993): The challenge of predicting response to stabilizing lithium treatment. The importance of patient selection. Brit J Psychiat 21: 16–19
Growe GA, Crayton JW, Klass DB, Evans H, Strizich M . (1979): Lithium in chronic schizophrenia. Am J Psychiat 136: 454–455
Guscott R, Taylor L . (1994): Lithium prophylaxis in recurrent affective illness. Efficacy, effectiveness, and efficiency. Brit J Psychiat 164: 741–746
Harrow M, Goldberg JF, Grossman LS, Meltzer HY . (1990): Outcome in manic disorders: A naturalistic follow-up study. Arch Gen Psychiat 47: 665–671
Hartigan GP . (1963): The use of lithium salts in affective disorders. Brit J Psychiat 109: 810–814
Hayes SG . (1992): Long-term valproate prophylaxis in refractory affective disorders. Ann Clin Psychiat 4: 55–63
Heninger GR, Charney DS, Sternberg DE . (1983): Lithium carbonate augmentation of antidepressant treatment. An effective prescription for treatment-refractory depression. Arch Gen Psychiat 40: 1335–1342
Himmelhoch JM, Mulla D, Neil JF, Detre TP, Kupfer DJ . (1976): Incidence and significance of mixed affective states in a bipolar population. Arch Gen Psychiat 33: 1062–1066
Himmelhoch JM, Thase MF, Mallinger AG, Houck P . (1991): Tranylcypromine versus imipramine in anergic bipolar depression. Am J Psychiat 148: 910–916
Hirschowitz J, Casper R, Garver DL, Chang S . (1980): Lithium response in good prognosis schizophrenia. Am J Psychiat 137: 916–920
Hirschowitz J, Zemlan FP, Garver DL . (1982): Growth hormone levels and lithium ratios as predictors of success of lithium therapy in schizophrenia. Am J Psychiat 139: 646–649
Horowitz HA . (1975): The use of lithium in the treatment of the drug-induced psychotic reaction. Dis Nerv Syst 36: 159–163
Hullin RP, McDonald R, Allsopp MNE . (1972): Prophylactic lithium in recurrent affective disorders. Lancet ii: 1044–1046
Jeffries JJ, Lefebvre A . (1973): Depression and mania associated with Kleine–Levin–Critchley syndrome. Can Psychiatric Ass J 18: 439–444
Joffe RT, Singer W, Levitt AJ, MacDonald C . (1993): A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression. Arch Gen Psychiat 50: 387–393
Johnson G, Gershon S, Hekimian LJ . (1968): Controlled evaluation of lithium and chlorpromazine in the treatment of manic states: An interim report. Comp Psychiat 9: 563–573
Johnson G . (1970): Differential response to lithium carbonate in manic depressive and schizo-affective disorders. Dis Nerv Syst, September 613–615
Johnson G, Gershon S, Burdock EI, Floyd A, Hekimian L . (1971): Comparative effects of lithium and chlorpromazine in the treatment of acute manic states. Brit J Psychiat 119: 267–276
Johnson G . (1974): Antidepressant effect of lithium. Comp Psychiat 15: 43–47
Judd LL, Huey LY . (1984): Lithium antagonizes ethanol intoxication of alcoholics. Am J Psychiat 141: 1517–1521
Kane JM, Quitkin FM, Rifkin A, Ramos-Lorenzi JR, Nayak DD, Howard A . (1982): Lithium carbonate and imipramine in the prophylaxis of unipolar and bipolar II illness: A prospective, placebo-controlled comparison. Arch Gen Psychiat 39: 1065–1069
Keck PE Jr, McElroy SL, Nemeroff CB . (1992): Anticonvulsants in the treatment of bipolar disorder. J Neuropsychiatry Clin Neurosci 4: 395–405
Keller MB, Lavori PW, Coryell W, Endicott J, Mueller TI . (1993): Bipolar I: A five-year prospective follow-up. J Nervous Mental Dis 181: 238–245
Kendell RE . (1985): The diagnosis of mania. J Aff Dis 8: 207–213
Khan MC, Wickham EA, Reed JV . (1987): Lithium versus placebo in acute depression: A clinical trial. Int Clin Psychopharmacol 2: 47–54
Kofman O, Belmaker RH . (1993): Ziskind–Somerfeld Research Award 1993. Biochemical, behavioral, and clinical studies of the role of inositol in lithium treatment and depression. Biolog Psychiat 34: 839–852
Krauthammer C, Klerman GL . (1978): Secondary mania—Manic syndromes associated with antecedent physical illness or drugs. Arch Gen Psychiat 35: 1333–1339
Kutcher SP, Marton P, Korenblum M . (1990): Adolescent bipolar illness and personality disorder. J Am Acad Child Adoles Psychiat 29: 355–358
Lambert PA, Carraz G, Borselli S, Carrel MS . (1966): Action neuropsychotrope d'un nouvel anti-épileptique: le dépamide. Ann M Psychol 1: 707–710
Lambert PA . (1984): Acute and prophylactic therapies of patients with affective disorders using valpromide (dipropylacetamide). In Emrich HM, Okuma T, Muller AA (eds), Anticonvulsants in Affective Disorders. Amsterdam, Excerpta Medica, pp 33–44
Lejoyeux M, Ades J . (1993): Evaluation of lithium treatment in alcoholism. Alcohol Alcoholism 28: 273–279
Lerer B . (1985): Studies on the role of brain cholinergic systems in the therapeutic mechanisms and adverse effects of ECT and lithium. Biolog Psychiat 20: 20–40
Lerer B, Moore N, Meyendorff E, Cho SR, Gershon S . (1987): Carbamazepine versus lithium in mania: A double-blind study. J Clin Psychiat 48: 89–93
Linder J, Fyro B, Pettersson U, Werner S . (1989): Acute antidepressant effect of lithium is associated with fluctuation of calcium and magnesium in plasma. A double-blind study on the antidepressant effect of lithium and clomipramine. Acta Psychiat Scand 80: 27–36
Lingjaerde O, Edlund AH, Gormsen CA, Gottfries CG, Haugstad A, Hermann IL, Hollnagel P, Makimattilla A, Rasmussen KE, Remvig J, Robak OH . (1974): The effects of lithium carbonate in combination with tricyclic antidepressants in endogenous depression. A double-blind, multicenter trial. Acta Psychiat Scand 50: 233–242
Lusznat RM, Murphy DP, Nunn CM . (1988): Carbamazepine vs. lithium in the treatment and prophylaxis of mania. Brit J Psychiat 153: 198–204
Maj M . (1984): Effectiveness of lithium prophylaxis in schizoaffective psychosis: Application of a polydiagnostic approach. Acta Psychiat Scand 70: 228–234
Maj M . (1988): Lithium prophylaxis of schizoaffective disorders: A prospective study. J Aff Dis 14: 129–135
Maj M, Pirozzi R, Starace F . (1989): Previous pattern of course of the illness as a predictor of response to lithium prophylaxis in bipolar patients. J Aff Dis 17: 237–241
Maj M, Pirozzi R, Kemali D . (1991): Long-term outcome of lithium prophylaxis in bipolar patients. Arch Gen Psychiat 48: 772
Mander AJ . (1986): Is there a lithium withdrawal syndrome? Brit J Psychiat 149: 498–501
Mander AJ, Loudon JB . (1988): Rapid recurrence of mania following abrupt discontinuation of lithium. Lancet 2: 15–17
Manji HK, Lenox RH . (1994): Long-term action of lithium: A role for transcriptional and postranscriptional factors regulated by protein kinase C. Synapse 16: 11–28
Manji HK, Potter WZ, Lenox RH . (1995): Signal transduction pathways. Molecular targets for lithium's action. Arch Gen Psychiat 52: 531–543
Marini JI, Sheard MH . (1977): Antiaggressive effect of lithium ion in man. Acta Psychiat Scand 55: 269–286
Mattsson B, von Schoultz B . (1974): A comparison between lithium, placebo, and a diuretic in premenstrual tension. Acta Psychiat Scand 255: 75–84
McCoy L, Votolato NA, Schwarzkopf SB, Nasrallah HA . (1993): Clinical correlates of valproate augmentation in refractory bipolar disorder. Ann Clin Psychiat 5: 29–33
McDougle CJ, Price LH, Goodman WK, Charney DS, Heninger GR . (1991): A controlled trial of lithium augmentation in fluvoxamine-refractory obsessive-compulsive disorder: Lack of efficacy. J Clin Psychopharmacol 11: 175–184
McElroy SL, Keck PE Jr, Pope HG Jr . (1987): Sodium valproate: its use in primary psychiatric disorders. J Clin Psychopharmacol 7: 16–24
McElroy SL, Keck PE, Pope HG, Hudson JI . (1988): Valproate in the treatment of rapid cycling bipolar disorder. J Clin Psychopharmacol 8: 275–278
McElroy SL, Keck PE Jr, Pope HG Jr, Hudson JI, Faedda GL, Swann AC . (1992a): Clinical and research implications of the diagnosis of dysphoric or mixed mania or hypomania. Am J Psychiat 149: 1633–1644
McElroy SL, Keck PE Jr, Pope HG Jr, Hudson JI . (1992b): Valproate in the treatment of bipolar disorder: Literature review and clinical guidelines. J Clin Psychopharmacol 12: 42S–52S
Mehta DB . (1976): Lithium and affective disorders associated with organic brain impairment. Am J Psychiat 133: 236
Mendels J, Secunda SK, Dyson WL . (1972): A controlled study of the antidepressant effect of lithium carbonate. Arch Gen Psychiat 26: 154–157
Mendels J . (1979): Lithium in the treatment of depression. Am J Psychiat 133: 373–378
Mendlewicz J, Stallone F . (1975): Genetic factors and lithium response in manic-depressive illness. Mod Prob Pharmacopsychiat 10: 23–29
Merry J, Reynolds CM, Bailey J, Coppen A . (1976): Prophylactic treatment of alcoholism by lithium carbonate. A controlled study. Lancet 1: 481–482
Miller FT, Libman H . (1979): Lithium carbonate in the treatment of schizophrenia and schizo-affective disorder: Review and hypothesis. Biol Psychiat 14: 705–710
Moskowitz IA . (1980): Lithium and lady luck: Use of lithium carbonate in compulsive gambling. NY State J Med 80: 785–788
Moncrieff J . (1995): Lithium revisited—A re-examination of the placebo-controlled trials of lithium prophylaxis in manic-depressive disorder. Brit J Psychiat 167: 569–574
Naylor GJ, Donald JM, Le Poidevin D, Reid AH . (1974): A double-blind trial of long-term lithium therapy in mental defectives. Brit J Psychiat 124: 52–57
Neppe VM . (1988): Carbamazepine in nonresponsive psychosis. J Clin Psychiat 49: 22–28
Noack CH, Trautner EM . (1951): Lithium treatment of maniacal psychosis. Med J Australia 18: 219–222
Noyes R Jr, Dempsey M, Blum A, Cavanaugh GL . (1974): Lithium treatment of depression. Comp Psychiat 15: 187–193
O'Connell RA, Mayo JA, Flatow L, et al. . (1991): Outcome of bipolar disorder on long-term treatment with lithium. Brit J Psychiat 159: 123–129
Ogura C, Okuma T, Nakazawa K, et al. . (1976): Treatment of periodic somnolence with lithium carbonate. Arch Neurol 33: 143–
Okuma T, Inanaga K, Otsuki S, et al. . (1979): Comparison of the antimanic efficacy of carbamazepine and chlorpromazine: A double-blind controlled study. Psychopharmacology 66: 211–217
Okuma T, Inanaga K, Otsuki S, et al. . (1981): A preliminary double-blind study on the efficacy of carbamazepine in prophylaxis of manic-depressive illness. Psychopharmacology 73: 95–96
Okuma T . (1983): Therapeutic and prophylactic effects of carbamazepine in bipolar disorders. Psychiat Clin North Am 6: 157–174
Okuma T, Yamashita I, Takahashi R, Itoh H, Otsuki S, Watanabe S, Sarai K, Hazama H, Inanaga K . (1990): Comparison of the antimanic efficacy of carbamazepine and lithium carbonate by double-blind controlled study. Pharmacopsychiatry 23: 143–150
Perris C . (1978): Morbidity suppressive effect of lithium carbonate in cycloid psychosis. Arch Gen Psychiat 35: 328–331
Peselow ED, Fieve RR, Difiglia C, et al. . (1994): Lithium prophylaxis of bipolar illness. Brit J Psychiat 164: 208–214
Petty F . (1995): GABA and mood disorders: A brief review and hypothesis. J Aff Dis 34: 275–281
Placidi GF, Lenzi A, Lazzerini F, Cassano GB, Akiskal HS . (1986): The comparative efficacy and safety of carbamazepine versus lithium: A randomized, double-blind 3-year trial in 83 patients. J Clin Psychiat 47: 490–494
Platman SR . (1970): A comparison of lithium carbonate and chlorpromazine in mania. Am J Psychiat 127: 351–353
Pond SM, Becker CE, Vandervoort R, Phillips M, Bowler RM, Peck CC . (1981): An evaluation of the effects of lithium in the treatment of chronic alcoholism. I. Clinical results. Alcohol Clin Exper Res 5: 247–251
Pope HG Jr, Lipinski JF, Cohen BM, Axelrod DT . (1980): “Schizoaffective disorder”: An invalid diagnosis? A comparison of carbamazepine disorder, schizophrenia, and affective disorder. Am J Psychiat 137: 921–927
Post RM . (1982): The use of the anticonvulsant carbamazepine in primary and secondary affective illness: Clinical and theoretical implications. Psycholog Med 12: 701–704
Post RM, Uhde TW, Ballenger JC, Squillace KM . (1983): Prophylactic efficacy of carbamazepine in manic-depressive illness. Am J Psychiat 140: 1602–1604
Post RM, Uhde TW, Roy-Byrne PP, Joffe RT . (1987): Correlates of antimanic response to carbamazepine. Psychiat Res 21: 71–83
Post RM, Altshuler LL, Ketter TA, Denicoff K, Weiss SR . (1991): Antiepileptic drugs in affective illness. Clinical and theoretical implications. Adv Neurol 55: 239–277
Post RM, Weiss SR, Chuang DM . (1992): Mechanisms of action of anticonvulsants in affective disorders: comparisons with lithium. J Clin Psychopharmacol 12: 23S–35S
Potter WZ, Bowden CL . (1992): Valproate and mood disorders: Perspectives. Introduction. J Clin Psychopharmacol 12: 2S–6S
Price LH, Henninger GR . (1994): Lithium in the treatment of mood disorders. N Engl J Med 331: 591–598
Prien RF, Caffey EM, Klett CJ . (1972a): Comparison of lithium carbonate and chlorpromazine in the treatment of mania. Arch Gen Psychiat 26: 146–153
Prien RF, Caffey EM Jr, Klett CJ . (1972b): A comparison of lithium carbonate and chlorpromazine in the treatment of excited schizo-affectives. Report of the Veterans Administration and National Institute of Mental Health collaborative study group. Arch Gen Psychiat 27: 182–189
Prien RF, Caffey EM, Klett CJ . (1973a): Prophylactic efficacy of lithium carbonate in manic-depressive illness. Report of the Veterans Administration and National Institute of Mental Health Collaborative Study Group. Arch Gen Psychiat 28: 337–341
Prien RF, Klett J, Caffey EM . (1973b): Lithium carbonate and imipramine in prevention of affective episodes. A comparison in recurrent affective illness. Report of the Veterans Administration and National Institute of Mental Health Collaborative Study Group. Arch Gen Psychiat 29: 420–425
Prien RF, Klett CJ, Caffey EM Jr . (1974): Lithium prophylaxis in recurrent affective illness. Am J Psychiat 131: 198–203
Prien RF, Kupfer DJ, Mansky PA, Small JG, Tuason VB, Voss CB, Johnson WE . (1984): 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. Arch Gen Psychiat 41: 1096–1104
Prien RF, Himmelhoch JM, Kupfer DJ . (1988a): Treatment of mixed mania. J Aff Dis 15: 9–15
Prien RF . (1988b): Maintenance treatment of depressive and manic states. In Georgotas A, Cancro R (eds), Depression and Mania. New York, Elsevier Science, pp 439–451
Prien RF, Gelenberg AJ . (1989): Alternatives to lithium for preventive treatment of bipolar disorder. Am J Psychiat 146: 840–848
Prien RF, Potter WZ . (1990): NIMH workshop report on treatment of bipolar disorder. Psychopharmacol Bull 26: 409–427
Puzynski S, Klosiewicz L . (1984): Valproic acid amide in the treatment of affective and schizoaffective disorders. J Aff Dis 6: 115–121
Quitkin FM, Kane J, Rifkin A, Ramos-Lorenzi JR, Nayak DV . (1981a): Prophylactic lithium carbonate with and without imipramine for bipolar 1 patients. A double-blind study. Arch Gen Psychiat 38: 902–907
Quitkin FM, Kane JM, Rifkin A, Ramos-Lorenzi JR, Saraf K, Howard A, Klein D . (1981b): Lithium and imipramine in the prophylaxis of unipolar and bipolar II depression: A prospective, placebo-controlled comparison. Psychopharmacol Bull 17: 142–144
Ryback RS, Schwab RS . (1971): Manic response to levodopa therapy: Report of a case. N Engl J Med 825: 788–789
Sarantidis D, Waters B . (1981): Predictors of lithium prophylaxis effectiveness. Prog Neuropsychopharmacol Biol Psychiat 5: 507–510
Sautter F, Garver D . (1985): Familial differences in lithium responsive versus lithium nonresponsive psychoses. J Psychiat Res 19: 1–8
Sautter FJ, McDermott BE, Garver DL . (1990): A family study of lithium-responsive psychosis. J Aff Dis 20: 63–69
Schexnayder LW, Hirschowitz J, Sautter FJ, Garver DL . (1995): Predictors of response to lithium in patients with psychoses. Am J Psychiat 152: 1511–1513
Schnur DB, Mukherjee S, Sackeim HA, Lee C, Roth SD . (1992): Symptomatic predictors of ECT response in medication-nonresponsive manic patients. J Clin Psychiat 53: 63–66
Schopf J, Baumann P, Lemarchand T, Rey M . (1989): Treatment of endogenous depressions resistant to tricyclic antidepressants or related drugs by lithium addition. Results of a placebo-controlled double-blind study. Pharmacopsychiatry 22: 183–187
Schou M . (1963): Normothymotics, “Mood-normalizers”—Are lithium and the imipramine drugs specific for affective disorders? Brit J Psychiat 109: 803–809
Schou M . (1979): Lithium in the treatment of other psychiatric and nonpsychiatric disorders. Arch Gen Psychiat 36: 856–859
Schou M . (1991): Lithium and electroconvulsive therapy: Adversaries, competitors, allies? Acta Psychiat Scand 84: 435–438
Scott ME, Mullaly RW . (1981): Lithium therapy for cocaine-induced psychosis: A clinical perspective. Southern Med J 74: 1475–1477
Secunda SK, Katz MM, Swann A, Koslow SH, Maas JW, Chuang S, Croughan J . (1985): Mania diagnosis state measurement and prediction of treatment response. J Aff Dis 8(2):113–121
Shapiro DR, Quitkin FM, Fleiss JL . (1989): Response to maintenance therapy in bipolar illness. Arch Gen Psychiat 46: 401–405
Sharma V, Persad E . (1994): Pharmacotherapy of rapid cycling bipolar disorder: A review. Lithium 5: 117–125
Sheard MH, Marini JL, Bridges CI, Wagner E . (1976): The effect of lithium on impulsive aggressive behavior in man. Am J Psychiat 133: 1409–1413
Shopsin B, Kim SS, Gershon S . (1971): A controlled study of lithium versus chlorpromazine in acute schizophrenics. Brit J Psychiat 119: 435–440
Shopsin B, Gershon S, Thompson H, Collins P . (1975): Psychoactive drugs in mania. A controlled comparison of lithium carbonate, chlorpromazine, and haloperidol. Arch Gen Psychiat 32: 34–42
Siassi I . (1982): Lithium treatment of impulsive behavior in children. J Clin Psychiat 43: 482–484
Singer H, Cheng R, Schou M . (1974): A controlled evaluation of lithium in the premenstrual tension syndrome. Brit J Psychiat 124: 5–15
Sletten IW, Gershon S . (1966): The premenstrual syndrome: A discussion of its pathophysiology and treatment with lithium ion. Comp Psychiat 7: 197–206
Small JG, Small IF, Milstein V, Kellams JJ, Klapper MH . (1985): Manic symptoms: An indication for bilateral ECT. Biolog Psychiat 20: 125–134
Small JG, Klapper MH, Kellams JJ, Miller MJ, Milstein V, Sharpley PH, Small IF . (1988): Electroconvulsive treatment compared with lithium in the management of manic states. Arch Gen Psychiat 45: 727–732
Small JG, Klapper MH, Milstein V, Kellams JJ, Miller MJ, Marhenke JD, Small TF . (1991): Carbamazepine compared with lithium in the treatment of mania. Arch Gen Psychiat 48: 915–921
Smulevitch AB, Zavidovskaya GI, Igonin AL, Mikhailova NM . (1974): The effectiveness of lithium in affective and schizoaffective psychosis. Brit J Psychiat 125: 65–72
Solomon DA, Keitner GI, Miller IW, Shea MT, Keller MB . (1995): Course of illness and maintenance treatments for patients with bipolar disorder. J Clin Psychiat 56: 5–13
Spring G, Schweid D, Gray C, Steinberg J, Horwitz M . (1970): A double-blind comparison of lithium and chlorpromazine in the treatment of manic states. Am J Psychiat 126: 1306–1310
Stallone F, Shelley E ., Mendlewicz J, Fieve RR . (1973): The use of lithium in affective disorders. 3. A double-blind study of prophylaxis in bipolar illness. Am J Psychiat 130: 1006–1010
Stein G, Bernadt M . (1993): Lithium augmentation therapy in tricyclic-resistant depression. A controlled trial using lithium in low and normal doses. Brit J Psychiat 162: 634–640
Stoll AL, Banov M, Kolbrener M, Mayer PV, Tohen M, Strakowski SM, Castillo J, Suppes T, Cohen BM . (1994): Neurologic factors predict a favorable valproate response in bipolar schizoaffective disorder. J Clin Psychopharmacol 14: 311–313
Suppes T, Baldessarini RJ, Faedda GL, Tohen M . (1991): Risk of recurrence following discontinuation of lithium treatment in bipolar disorder. Arch Gen Psychiat 48: 1082–1088
Swann AC, Secunda SK, Katz MM, Koslow SH, Maas JW, Chang S, Robins E . (1986): Lithium treatment of mania: Clinical characteristics, specificity of symptom change, and outcome. Psychiat Res 18: 127–141
Takahashi R, Sakuma A, Itoh H, Kurihara M . (1975): Comparison of efficacy of lithium carbonate and chlorpromazine in mania. Report of collaborative study group on treatment of mania in Japan. Arch Gen Psychiat 32: 1310–1318
Thomas J, Reddy B . (1982): The treatment of mania. A retrospective evaluation of the effects of ECT, chlorpromazine, and lithium. J Aff Dis 4: 85–92
Tohen M, Waternaux CM, Tsuang MT, Hunt AT . (1990a): Four-year follow-up of twenty-four first-episode manic patients. J Aff Dis 19: 79–86
Tohen M, Waternaux CM, Tsuang MT . (1990b): A 4-year prospective follow-up of 75 patients utilizing survival analysis. Arch Gen Psychiat 47: 1106–1111
Tupin J . (1972): Lithium use in nonmanic depressive conditions. Comp Psychiat 13: 209–214
Tyrer SP, Walsh A, Edwards DE, Berney TP, Stephens DA . (1984): Factors associated with a good response to lithium in aggressive mentally handicapped subjects. Prog Neuro-Psychopharm Biol Psychiat 8: 751–755
van Calker D, Forstner U, Bohus M, Gebicke-Harter P, Hecht H, Wark HJ, Berger M . (1993): Increased sensitivity to agonist stimulation of the Ca2+ response in neutrophils of manic-depressive patients: Effect of lithium therapy. Neuropsychobiology 27: 180–183
van Woert MH, Ambani LM, Weintraub MI . (1971): Manic behavior and levodopa. N Engl J Med 285: 1326
Vadnal R, Parthasarathy R . (1995): Myo-inositol monophosphatase: Diverse effects of lithium, carbamazepine, and valproate. Neuropsychopharmacology 12: 277–285
Watanabe S, Ishino H, Otsuki S . (1974): Lithium and affective psychoses. Folia Psychiatrica et Neurologica Japonica 28: 267–305
Watanabe S, Ishino H, Otsuki S . (1975): Double-blind comparison of lithium carbonate and imipramine in treatment of depression. Arch Gen Psychiat 32: 659–668
Watkins SE, Callender K, Thomas DR, Tidmarsh SF, Shaw DM . (1987): The effect of carbamazepine and lithium on remission from affective illness. Brit J Psychiat 150: 180–182
Wehr TA, Goodwin FK . (1987): Can antidepressants cause mania and worsen the course of affective illness? Am J Psychiat 144: 1403–1411
Will RG, Young JP, Thomas DJ . (1988): Kleine–Levin syndrome: Report of two cases with onset of symptoms precipitated by head trauma. Brit J Psychiat 152: 410–412
Wilson KCM, Scott M, Abou-Saleh M, Burns R, Copeland JRM . (1995): Long-term effects of cognitive-behavioral therapy and lithium therapy on depression in the elderly. Brit J Psychiat 167: 653–658
Worrall EP, Moody JP, Peet M, Dick P, Smith A, Chambers C, Adams M, Naylor GJ . (1979): Controlled studies of the acute antidepressant effects of lithium. Brit J Psychiat 135: 255–262
Wren JC, Kline NS, Cooper TB, Varga E, Canal O . (1974): Evaluation of lithium therapy in chronic alcoholism. Clin Med 81: 33–36
Young LD, Taylor I, Holmstrom V . (1977): Lithium treatment of patients with affective illness associated with organic brain symptoms. Am J Psychiat 134: 1405–1407
Zemlan FP, Hirschowitz J, Sautter FJ, Garver DL . (1984a): Impact of lithium therapy on core psychotic symptoms of schizophrenia. Brit J Psychiat 144: 64–69
Zemlan FP, Hirschowitz J, Garver DL . (1984b): Mood-incongruent versus mood-congruent psychosis: Differential antipsychotic response to lithium therapy. Psychiat Res 11: 317–328
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Soares, J., Gershon, S. The Lithium Ion: A Foundation for Psychopharmacological Specificity. Neuropsychopharmacol 19, 167–182 (1998). https://doi.org/10.1016/S0893-133X(98)00022-0
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1016/S0893-133X(98)00022-0
Keywords
This article is cited by
-
Integrative analysis of lithium treatment associated effects on brain structure and peripheral gene expression reveals novel molecular insights into mechanism of action
Translational Psychiatry (2020)
-
Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry
EPMA Journal (2017)
-
The Toxic Effect of Lithium Ion on Neurons (PC12 cells) and Aβ42 Molecules
Biological Trace Element Research (2014)
-
The phenotypes of bipolar disorder: relevance for genetic investigations
Molecular Psychiatry (2005)
-
1H MRS Study of Dorsolateral Prefrontal Cortex in Healthy Individuals before and after Lithium Administration
Neuropsychopharmacology (2004)
