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January 1997, Vol 54, No. 1 >
Article | January 1997

Forty Years of Lithium Treatment

Mogens Schou, MD, DrMed, DrHCMult
Arch Gen Psychiatry. 1997;54(1):9-13. doi:10.1001/archpsyc.1997.01830130013002
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This review is based on a lecture in which I was requested to present my personal experiences and views. Since its introduction into psychiatry more than 40 years ago, lithium treatment has in most countries gained wide acceptance in the prophylaxis of unipolar and bipolar affective disorders. At one time it was feared that lithium treatment might lead to a decrease in the glomerular filtration rate, but systematically collected data indicate that even long-term treatment does not induce renal insufficiency. During treatment, regular laboratory monitoring of serum lithium and creatinine concentrations is recommended. Recent studies suggest that long-term lithium treatment does not raise the mortality of manic-depressive patients and indeed may have a mortality-lowering and antisuicidal effect. Despite the availability of alternative therapies, lithium remains the treatment of choice for the prophylaxis of recurrent manic-depressive illness.

REFERENCES

1 +
Schou M.  Lithium prophylaxis: about 'naturalistic' or 'clinical practice' studies . Lithium . 1993;;4:77-81.
2 +
Baastrup PC, Schou M.  Lithium as a prophylactic agent: its effect against recurrent depressions and manic-depressive psychosis . Arch Gen Psychiatry . 1967;;16:162-172.
3 +
Baastrup PC, Poulsen JC, Schou M, Thomsen K, Amdisen A.  Prophylactic lithium: doubleblind discontinuation in manic-depressive and recurrent-depressive disorders . Lancet . 1970;;2:326-330.
4 +
Souza FGM, Mander AJ, Goodwin GM.  The efficacy of lithium prophylaxis of unipolar depression: evidence from its discontinuation . Br J Psychiatry . 1990;;157:718-722.
5 +
Souza FGM, Goodwin GM.  Lithium treatment and prophylaxis in unipolar depression: a metaanalysis . Br J Psychiatry . 1991;;158:666-675.
6 +
Nobler MS, Sackeim HA.  Pharmacotherapy and electroconvulsive therapy for mood disorders . Curr Opin Psychiatry . 1993;;6:10-15.
7 +
Kupfer DJ.  Management of recurrent depression . J Clin Psychiatry . 1993;;54( (suppl 2) ):29-33.
8 +
Thase ME.  Maintenance treatments of recurrent affective disorders . Curr Opin Psychiatry . 1993;;6:16-21.
9 +
Johnstone EC, Owens DGC, Lambert MT, Crow TJ, Frith CD, Done DJ.  Combination tricyclic antidepressant and lithium maintenance medication in unipolar and bipolar depressed patients . J Affect Dis . 1990;;20:225-233.
10 +
Prien RF, Kupfer DJ, Mansky PA, Small JG, Tuason VB, Voss CB, Johnson WE.  Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders . Arch Gen Psychiatry . 1984;;41:1096-1104.
11 +
Goodwin FK, Jamison KR. Manic-Depressive Illness . Oxford, England: Oxford University Press; 1990;.
12 +
Davis JM, Wang Z, Janicak PG.  A quantitative analysis of clinical drug trials for the treatment of affective disorders . Psychopharmacol Bull . 1993;;29:175-181.
13 +
Frank E, Kupfer DJ, Perel JM, Cornes C, Jarrett DB, Mallinger AG, Thase ME, McEachran AB, Grochocinski VJ.  Three-year outcomes for maintenance therapies in recurrent depression . Arch Gen Psychiatry . 1990;;47:1093-1099.
14 +
Kupfer DJ, Frank E, Perel JM, Cornes C, Mallinger AG, Thase ME, McEachran AB, Grochocinski VJ.  Five-year outcome for maintenance therapies in recurrent depression . Arch Gen Psychiatry . 1992;;49:769-773.
15 +
Greil W, Ludwig-Mayerhofer W, Steller B, Czernik A, Giedke H, Müller-Oerlinghausen B, Osterheider M, Rudolf GAE, Sauer H, Tegeler J, Wetterling T.  Lithium-oder Carbamazepinprophylaxe bei affektiven Psychosen? Ergebnisse einer kontrollierten, multizentrischen Studie . In: Müller Oerlinghausen B, Berghüfer A, eds. Ziele und Ergebnisse der medikamentösen Prophylaxe affektiver Psychosen . Stuttgart, Germany: Thieme; 1994;:113-119.
16 +
Schou M.  Effects of long-term lithium treatment on kidney function: an overview . J Psychiatr Res . 1988;;22:287-296.
17 +
Waller DG, Edwards JG.  Lithium and the Kidney: an update . Psychol Med . 1989;;19:825-831.
18 +
von Knorring L, Wahlin A, Nyström K, Bohman SO.  Uraemia induced by long-term lithium treatment . Lithium . 1990;;1:251-253.
19 +
Gitlin MJ.  Lithium-induced renal insufficiency . J Clin Psychopharmacol . 1993;;13:276-279.
20 +
Kallner G, Petterson U.  Renal, thyroid and parathyroid function during lithium treatment: laboratory test in 207 people treated for 1-30 years . Acta Psychiatr Scand . 1995;:91:48-51.
21 +
Aronson JK, Reynolds DJM.  ABC of monitoring drug therapy: lithium . BMJ . 1992;;305:1273-1276.
22 +
Hullin RP, Srinivasan DP, Birch NJ.  Monitoring lithium treatment . BMJ . 1993;;306:269.
23 +
Kehoe RF.  Monitoring lithium treatment . BMJ . 1993;;36:269-270.
24 +
Aronson JK, Reynolds DJM.  Monitoring lithium treatment . BMJ . 1993;;306:270.
25 +
Guscott R, Taylor L.  Monitoring of lithium treatment . Can J Psychiatry . 1993;;38:74.
26 +
Schou M.  Monitoring of lithium treatment: reply to Guscott and Taylor . Can J Psychiatry . 1993;;38:74.
27 +
Schou M.  Relapse prevention in manic-depressive illness: important and unimportant factors . Can J Psychiatry . 1991;;36:502-506.
28 +
Schou M. Lithium Treatment of Manic Depressive Illness: A Practical Guide . 5th ed. revised. Basel, Switzerland: Karger; 1993;.
29 +
Birch NJ, Grof P, Hullin RP, Kehoe RF, Schou M, Srinivasan DP.  Lithium prophylaxis: Proposed guidelines for good clinical practice . Lithium . 1993;;4:225-230.
30 +
Gelenberg AJ, Kane JM, Keller MB, Lavori P, Rosenbaum JF, Cole K, Lavalle J.  Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder . N Engl J Med . 1989;;321:1489-1493.
31 +
Norton B, Whalley LJ.  Mortality of a lithiumtreated population . Br J Psychiatry . 1984;;146:277-282.
32 +
Coppen A, Standish-Barry H, Bailey J, Houston G, Silcocks P, Hermon C.  Long-term lithium and mortality . Lancet . 1990;;335:1347.
33 +
Coppen A, Standish-Barry H, Bailey J, Houston G, Silcocks P, Hermon C.  Does lithium reduce the mortality of recurrent mood disorders? J Affect Dis . 1991;;23:1-7.
34 +
Müller-Oerlinghausen B, Ahrens B, Volk J, Grof P, Grof E, Schou M, Vestergaard P, Lenz G, Simhandl C, Thau K, Wolf R.  Reduced mortality of manic-depressive patients in long-term lithium treatment: an international collaborative study by IGSLI . Psychiatry Res . 1991;;36:329-331.
35 +
Müller-Oerlinghausen B, Ahrens B, Grof E, Grof P, Lenz G, Schou M, Simhandl C, Thau K, Volk J, Wolf R, Wolf T.  The effect of long-term lithium treatment on the mortality of patients with Manic-depressive or schizo-affective illness . Acta Psychiatr Scand . 1992;;86:218-222.
36 +
Ahrens B, Müller-Oerlinghausen B, Schou M, Wolf T, Alda M, Grof E, Grof P, Lenz G, Simhandl C, Thau K, Vestergaard P, Wolf R, Möller H.  Cardiovascular and suicide mortality of affective disorders may be reduced by lithium prophylaxis . J Affect Dis . 1995;;33:67-75.
37 +
Nilsson A.  Mortality in recurrent mood disorders during periods on and off lithium: a complete population study in 362 patients . Pharmacopsychiatry . 1995;;28:8-13.
38 +
Müller-Oerlinghausen B, Müser-Causemann B, Volk J.  Suicides and parasuicides in a high-risk patient group on and off lithium long-term medication . J Affect Dis . 1992;;25:261-270.
39 +
Lenz G, Ahrens B, Denk E, Müller-Oerlinghausen B, Schratzberger-Topitz A, Simhandl C, Wancata J.  Mortalität nach Ausscheiden aus der Lithiumambulanz . In: Müller-Oerlinghausen B, Berghöfer A, eds. Ziele und Ergebnisse der medikamentösen Prophylaxe affektiver Psychosen . Stuttgart, Germany: Thieme; 1994;:49-52.
40 +
Felber W, Kyber A.  Suizide und Parasuizide Wöhrend und auβdserhalb einer Lithiumprophylaxe . In: Müller-Oerlinghausen B, Berghöfer A, eds. Ziele und Ergebnisse der medikamentösen Prophylaxe affektiver Psychosen . Stuttgart, Germany: Thieme; 1994;:53-59.
41 +
Thies-Flechtner K, Seibert W, Walther A, Greil W, Müller-Oerlinghausen B.  Suizide bei rezidivprophylaktisch behandelten Patienten mit affektiven Psychosen . In: Müller-Oerlinghausen B, Berghöfer A, eds. Ziele und Ergebnisse der medikamentösen Prophylaxe affektiver Psychosen . Stuttgart, Germany: Thieme; 1994;:61-64.
42 +
Schou M.  Mortality-lowering effect of prophylactic lithium treatment: a look at the evidence . Pharmacopsychiatry . 1995;;28:1.

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1 +
Schou M.  Lithium prophylaxis: about 'naturalistic' or 'clinical practice' studies . Lithium . 1993;;4:77-81.
2 +
Baastrup PC, Schou M.  Lithium as a prophylactic agent: its effect against recurrent depressions and manic-depressive psychosis . Arch Gen Psychiatry . 1967;;16:162-172.
3 +
Baastrup PC, Poulsen JC, Schou M, Thomsen K, Amdisen A.  Prophylactic lithium: doubleblind discontinuation in manic-depressive and recurrent-depressive disorders . Lancet . 1970;;2:326-330.
4 +
Souza FGM, Mander AJ, Goodwin GM.  The efficacy of lithium prophylaxis of unipolar depression: evidence from its discontinuation . Br J Psychiatry . 1990;;157:718-722.
5 +
Souza FGM, Goodwin GM.  Lithium treatment and prophylaxis in unipolar depression: a metaanalysis . Br J Psychiatry . 1991;;158:666-675.
6 +
Nobler MS, Sackeim HA.  Pharmacotherapy and electroconvulsive therapy for mood disorders . Curr Opin Psychiatry . 1993;;6:10-15.
7 +
Kupfer DJ.  Management of recurrent depression . J Clin Psychiatry . 1993;;54( (suppl 2) ):29-33.
8 +
Thase ME.  Maintenance treatments of recurrent affective disorders . Curr Opin Psychiatry . 1993;;6:16-21.
9 +
Johnstone EC, Owens DGC, Lambert MT, Crow TJ, Frith CD, Done DJ.  Combination tricyclic antidepressant and lithium maintenance medication in unipolar and bipolar depressed patients . J Affect Dis . 1990;;20:225-233.
10 +
Prien RF, Kupfer DJ, Mansky PA, Small JG, Tuason VB, Voss CB, Johnson WE.  Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders . Arch Gen Psychiatry . 1984;;41:1096-1104.
11 +
Goodwin FK, Jamison KR. Manic-Depressive Illness . Oxford, England: Oxford University Press; 1990;.
12 +
Davis JM, Wang Z, Janicak PG.  A quantitative analysis of clinical drug trials for the treatment of affective disorders . Psychopharmacol Bull . 1993;;29:175-181.
13 +
Frank E, Kupfer DJ, Perel JM, Cornes C, Jarrett DB, Mallinger AG, Thase ME, McEachran AB, Grochocinski VJ.  Three-year outcomes for maintenance therapies in recurrent depression . Arch Gen Psychiatry . 1990;;47:1093-1099.
14 +
Kupfer DJ, Frank E, Perel JM, Cornes C, Mallinger AG, Thase ME, McEachran AB, Grochocinski VJ.  Five-year outcome for maintenance therapies in recurrent depression . Arch Gen Psychiatry . 1992;;49:769-773.
15 +
Greil W, Ludwig-Mayerhofer W, Steller B, Czernik A, Giedke H, Müller-Oerlinghausen B, Osterheider M, Rudolf GAE, Sauer H, Tegeler J, Wetterling T.  Lithium-oder Carbamazepinprophylaxe bei affektiven Psychosen? Ergebnisse einer kontrollierten, multizentrischen Studie . In: Müller Oerlinghausen B, Berghüfer A, eds. Ziele und Ergebnisse der medikamentösen Prophylaxe affektiver Psychosen . Stuttgart, Germany: Thieme; 1994;:113-119.
16 +
Schou M.  Effects of long-term lithium treatment on kidney function: an overview . J Psychiatr Res . 1988;;22:287-296.
17 +
Waller DG, Edwards JG.  Lithium and the Kidney: an update . Psychol Med . 1989;;19:825-831.
18 +
von Knorring L, Wahlin A, Nyström K, Bohman SO.  Uraemia induced by long-term lithium treatment . Lithium . 1990;;1:251-253.
19 +
Gitlin MJ.  Lithium-induced renal insufficiency . J Clin Psychopharmacol . 1993;;13:276-279.
20 +
Kallner G, Petterson U.  Renal, thyroid and parathyroid function during lithium treatment: laboratory test in 207 people treated for 1-30 years . Acta Psychiatr Scand . 1995;:91:48-51.
21 +
Aronson JK, Reynolds DJM.  ABC of monitoring drug therapy: lithium . BMJ . 1992;;305:1273-1276.
22 +
Hullin RP, Srinivasan DP, Birch NJ.  Monitoring lithium treatment . BMJ . 1993;;306:269.
23 +
Kehoe RF.  Monitoring lithium treatment . BMJ . 1993;;36:269-270.
24 +
Aronson JK, Reynolds DJM.  Monitoring lithium treatment . BMJ . 1993;;306:270.
25 +
Guscott R, Taylor L.  Monitoring of lithium treatment . Can J Psychiatry . 1993;;38:74.
26 +
Schou M.  Monitoring of lithium treatment: reply to Guscott and Taylor . Can J Psychiatry . 1993;;38:74.
27 +
Schou M.  Relapse prevention in manic-depressive illness: important and unimportant factors . Can J Psychiatry . 1991;;36:502-506.
28 +
Schou M. Lithium Treatment of Manic Depressive Illness: A Practical Guide . 5th ed. revised. Basel, Switzerland: Karger; 1993;.
29 +
Birch NJ, Grof P, Hullin RP, Kehoe RF, Schou M, Srinivasan DP.  Lithium prophylaxis: Proposed guidelines for good clinical practice . Lithium . 1993;;4:225-230.
30 +
Gelenberg AJ, Kane JM, Keller MB, Lavori P, Rosenbaum JF, Cole K, Lavalle J.  Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder . N Engl J Med . 1989;;321:1489-1493.
31 +
Norton B, Whalley LJ.  Mortality of a lithiumtreated population . Br J Psychiatry . 1984;;146:277-282.
32 +
Coppen A, Standish-Barry H, Bailey J, Houston G, Silcocks P, Hermon C.  Long-term lithium and mortality . Lancet . 1990;;335:1347.
33 +
Coppen A, Standish-Barry H, Bailey J, Houston G, Silcocks P, Hermon C.  Does lithium reduce the mortality of recurrent mood disorders? J Affect Dis . 1991;;23:1-7.
34 +
Müller-Oerlinghausen B, Ahrens B, Volk J, Grof P, Grof E, Schou M, Vestergaard P, Lenz G, Simhandl C, Thau K, Wolf R.  Reduced mortality of manic-depressive patients in long-term lithium treatment: an international collaborative study by IGSLI . Psychiatry Res . 1991;;36:329-331.
35 +
Müller-Oerlinghausen B, Ahrens B, Grof E, Grof P, Lenz G, Schou M, Simhandl C, Thau K, Volk J, Wolf R, Wolf T.  The effect of long-term lithium treatment on the mortality of patients with Manic-depressive or schizo-affective illness . Acta Psychiatr Scand . 1992;;86:218-222.
36 +
Ahrens B, Müller-Oerlinghausen B, Schou M, Wolf T, Alda M, Grof E, Grof P, Lenz G, Simhandl C, Thau K, Vestergaard P, Wolf R, Möller H.  Cardiovascular and suicide mortality of affective disorders may be reduced by lithium prophylaxis . J Affect Dis . 1995;;33:67-75.
37 +
Nilsson A.  Mortality in recurrent mood disorders during periods on and off lithium: a complete population study in 362 patients . Pharmacopsychiatry . 1995;;28:8-13.
38 +
Müller-Oerlinghausen B, Müser-Causemann B, Volk J.  Suicides and parasuicides in a high-risk patient group on and off lithium long-term medication . J Affect Dis . 1992;;25:261-270.
39 +
Lenz G, Ahrens B, Denk E, Müller-Oerlinghausen B, Schratzberger-Topitz A, Simhandl C, Wancata J.  Mortalität nach Ausscheiden aus der Lithiumambulanz . In: Müller-Oerlinghausen B, Berghöfer A, eds. Ziele und Ergebnisse der medikamentösen Prophylaxe affektiver Psychosen . Stuttgart, Germany: Thieme; 1994;:49-52.
40 +
Felber W, Kyber A.  Suizide und Parasuizide Wöhrend und auβdserhalb einer Lithiumprophylaxe . In: Müller-Oerlinghausen B, Berghöfer A, eds. Ziele und Ergebnisse der medikamentösen Prophylaxe affektiver Psychosen . Stuttgart, Germany: Thieme; 1994;:53-59.
41 +
Thies-Flechtner K, Seibert W, Walther A, Greil W, Müller-Oerlinghausen B.  Suizide bei rezidivprophylaktisch behandelten Patienten mit affektiven Psychosen . In: Müller-Oerlinghausen B, Berghöfer A, eds. Ziele und Ergebnisse der medikamentösen Prophylaxe affektiver Psychosen . Stuttgart, Germany: Thieme; 1994;:61-64.
42 +
Schou M.  Mortality-lowering effect of prophylactic lithium treatment: a look at the evidence . Pharmacopsychiatry . 1995;;28:1.

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