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

Unanswered Questions, Unknown Future for One of Our Oldest Medications

Michael J. Gitlin, MD; Lori L. Altshuler, MD
Arch Gen Psychiatry. 1997;54(1):21-23. doi:10.1001/archpsyc.1997.01830130025005
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A S one of the oldest pillars of modern psychopharmacology, lithium remains a treatment toward which all psychiatrists should feel a deep indebtedness. The decreased morbidity associated with its demonstrated efficacy in both the acute and maintenance phases of bipolar disorder has provided greatly needed relief and hope for patients and their families. More than any other individual, Dr Mogens Schou has been responsible for demonstrating lithium's efficacy and promoting its use. Now, 40 years after lithium's introduction into psychiatry, he reviews some of the current controversies about this remarkable drug.2

LITHIUM AS A Maintenance TREATMENT  One of Schou's concerns is the underappreciation of lithium's capacity as a maintenance treatment for bipolar disorder. He alludes to the recent naturalistic studies that suggest that lithium seems less effective in these samples than in the many controlled studies. In a previous publication,3 he concluded that the results of these naturalistic

REFERENCES

1 +
Goodwin FK, Jamison KR. Manic Depressive Illness . New York, NY: Oxford University Press; 1990;.
2 +
Schou M.  Forty years of lithium treatment . Arch Gen Psychiatry . 1997;;54:9-13.
3 +
Schou M.  Lithium prophylaxis: about 'naturalistic' or 'clinical practice' studies . Lithium . 1993;;4:77-81.
4 +
Brady JT, Sonne SC.  The relationship between substance abuse and bipolar disorder . J Clin Psychiatry . 1995;;56:19-24.
5 +
Sonne SC, Brady KT, Morton WA.  Substance abuse and bipolar affective disorder . J Nerv Ment Dis . 1994;;182:349-352.
6 +
Winokur G, Coryell W, Akiskal HS, Maser JD, Keller MB, Endicott J, Mueller T.  Alcoholism in manic-depressive (bipolar) illness: familial illness, course of illness, and the primarysecondary distinction . Am J Psychiatry . 1995;;152:365-372.
7 +
Keck PE, McElroy SL, Strakowski SM, West SA, Hawkins JM, Huber TJ, Newman RM, DePriest N.  Outcome and comorbidity in first- compared with multiple-episode mania . J Nerv Ment Dis . 1995;;183:320-324.
8 +
Chen Y-W, Dilsaver SC.  Comorbidity of panic disorder in bipolar illness: evidence from the Epidemiologic Catchment Area survey . Am J Psychiatry . 1995;;152:280-282.
9 +
Strakowski SM, Tohen M, Stoll AL, Faedda GL, Goodwin DC.  Comorbidity in mania at first hospitalization . Am J Psychiatry . 1992;;149:554-556.
10 +
Pica S, Edwards J, Jackson HJ, Bell RC, Bates GW, Rudd RP.  Personality disorders in recentonset bipolar disorder . Compr Psychiatry . 1990;;31:499-510.
11 +
O'Connell RW, Mayo JA, Sciutto MS.  PDQ-R personality disorders in bipolar patients . J Affect Disord . 1991;;23:217-221.
12 +
Tohen M, Waternaux CM, Tsuang MT.  Outcome in mania: a 4-year prospective follow-up of 75 patients utilizing survival analysis . Arch Gen Psychiatry . 1990;;47:1106-1111.
13 +
Gitlin M, Cochran S, Jamison K.  Maintenance lithium treatment: side effects and compliance . J Clin Psychiatry . 1989;;50:127-131.
14 +
Pope HG, McElroy SL, Keck PE, Hudson JI.  Valproate in the treatment of acute mania: a placebo-controlled study . Arch Gen Psychiatry . 1991;;48:62-68.
15 +
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, for the Depakote Mania Study Group.  Efficacy of divalproex vs lithium and placebo in the treatment of mania . JAMA . 1994;;271:918-924.
16 +
Small JG, Klapper MH, Milstein V, Kellams JJ, Miller MJ, Marhenke JD, Small IF.  Carbamazepine compared with lithium in the treatment of mania . Arch Gen Psychiatry . 1991;;48:915-921.
17 +
Souza FGM, Mander AJ, Goodwin GM.  The efficacy of lithium in prophylaxis of unipolar depression: evidence from its discontinuation . Br J Psychiatry . 1990;;157:718-722.
18 +
Souza FGM, Goodwin GM.  Lithium treatment and prophylaxis in unipolar depression: a metaanalysis . Br J Psychiatry . 1991;;158:666-675.
19 +
Keller MB.  Diagnostic and course-of-illness Variables pertinent to refractory depression . In: Tasman A, Goldfinger SM, Kaufmann CA, eds. American Psychiatric Press Review of Psychiatry . Washington, DC: American Psychiatric Press; 1990;;9:10-32.
20 +
Oldham JM, Skodol AE.  Personality disorders and mood disorders . In: Tasman A, Riba MB, eds. American Psychiatric Press Review of Psychiatry . Washington, DC: American Psychiatric Press; 1992;;11:418-435.
21 +
Robins LN, Locke BZ, Regier DA.  An overview of psychiatric disorders in America . In: Robins LN, Regier DA, eds. Psychiatric Disorders in America . New York, NY: The Free Press; 1991;: 328-366.
22 +
Jefferson JW.  Lithium: a therapeutic magic wand . J Clin Psychiatry . 1989;;50:81-86.
23 +
Gitlin M.  Lithium-induced renal insufficiency . J Clin Psychopharmacol . 1993;;13:276-279.
24 +
Bendz H, Aurell M, Balldin J, Mathe AA, Sjodin I.  Kidney damage in long-term lithium patients: a cross-sectional study of patients with 15 years or more on lithium . Nephrol Dial Transplant . 1994;;9:1250-1254.
25 +
American Psychiatric Association.  Practice guidelines for the treatment of patients with bipolar disorder . Am J Psychiatry . 1994;;151( (suppl) ):1-36.
26 +
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.
27 +
Ellicott A, Hammen C, Gitlin M, Brown G, Jamison K.  Life events and the course of bipolar disorder . Am J Psychiatry . 1990;;147:1194-1198.
28 +
Hunt N, Bruce-Jones W, Silverstone T.  Life events and relapse in bipolar affective disorder . J Affect Disord . 1992;;25:13-20.
29 +
Post RN.  Transduction of psychosocial stress into the neurobiology of recurrent affective disorder . Am J Psychiatry . 1992;;149:999-1010.
30 +
Cochran S.  Preventing medical noncompliance in the outpatient treatment of bipolar affective disorders . J Consult Clin Psychol . 1984;;52:873-878.

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1 +
Goodwin FK, Jamison KR. Manic Depressive Illness . New York, NY: Oxford University Press; 1990;.
2 +
Schou M.  Forty years of lithium treatment . Arch Gen Psychiatry . 1997;;54:9-13.
3 +
Schou M.  Lithium prophylaxis: about 'naturalistic' or 'clinical practice' studies . Lithium . 1993;;4:77-81.
4 +
Brady JT, Sonne SC.  The relationship between substance abuse and bipolar disorder . J Clin Psychiatry . 1995;;56:19-24.
5 +
Sonne SC, Brady KT, Morton WA.  Substance abuse and bipolar affective disorder . J Nerv Ment Dis . 1994;;182:349-352.
6 +
Winokur G, Coryell W, Akiskal HS, Maser JD, Keller MB, Endicott J, Mueller T.  Alcoholism in manic-depressive (bipolar) illness: familial illness, course of illness, and the primarysecondary distinction . Am J Psychiatry . 1995;;152:365-372.
7 +
Keck PE, McElroy SL, Strakowski SM, West SA, Hawkins JM, Huber TJ, Newman RM, DePriest N.  Outcome and comorbidity in first- compared with multiple-episode mania . J Nerv Ment Dis . 1995;;183:320-324.
8 +
Chen Y-W, Dilsaver SC.  Comorbidity of panic disorder in bipolar illness: evidence from the Epidemiologic Catchment Area survey . Am J Psychiatry . 1995;;152:280-282.
9 +
Strakowski SM, Tohen M, Stoll AL, Faedda GL, Goodwin DC.  Comorbidity in mania at first hospitalization . Am J Psychiatry . 1992;;149:554-556.
10 +
Pica S, Edwards J, Jackson HJ, Bell RC, Bates GW, Rudd RP.  Personality disorders in recentonset bipolar disorder . Compr Psychiatry . 1990;;31:499-510.
11 +
O'Connell RW, Mayo JA, Sciutto MS.  PDQ-R personality disorders in bipolar patients . J Affect Disord . 1991;;23:217-221.
12 +
Tohen M, Waternaux CM, Tsuang MT.  Outcome in mania: a 4-year prospective follow-up of 75 patients utilizing survival analysis . Arch Gen Psychiatry . 1990;;47:1106-1111.
13 +
Gitlin M, Cochran S, Jamison K.  Maintenance lithium treatment: side effects and compliance . J Clin Psychiatry . 1989;;50:127-131.
14 +
Pope HG, McElroy SL, Keck PE, Hudson JI.  Valproate in the treatment of acute mania: a placebo-controlled study . Arch Gen Psychiatry . 1991;;48:62-68.
15 +
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, for the Depakote Mania Study Group.  Efficacy of divalproex vs lithium and placebo in the treatment of mania . JAMA . 1994;;271:918-924.
16 +
Small JG, Klapper MH, Milstein V, Kellams JJ, Miller MJ, Marhenke JD, Small IF.  Carbamazepine compared with lithium in the treatment of mania . Arch Gen Psychiatry . 1991;;48:915-921.
17 +
Souza FGM, Mander AJ, Goodwin GM.  The efficacy of lithium in prophylaxis of unipolar depression: evidence from its discontinuation . Br J Psychiatry . 1990;;157:718-722.
18 +
Souza FGM, Goodwin GM.  Lithium treatment and prophylaxis in unipolar depression: a metaanalysis . Br J Psychiatry . 1991;;158:666-675.
19 +
Keller MB.  Diagnostic and course-of-illness Variables pertinent to refractory depression . In: Tasman A, Goldfinger SM, Kaufmann CA, eds. American Psychiatric Press Review of Psychiatry . Washington, DC: American Psychiatric Press; 1990;;9:10-32.
20 +
Oldham JM, Skodol AE.  Personality disorders and mood disorders . In: Tasman A, Riba MB, eds. American Psychiatric Press Review of Psychiatry . Washington, DC: American Psychiatric Press; 1992;;11:418-435.
21 +
Robins LN, Locke BZ, Regier DA.  An overview of psychiatric disorders in America . In: Robins LN, Regier DA, eds. Psychiatric Disorders in America . New York, NY: The Free Press; 1991;: 328-366.
22 +
Jefferson JW.  Lithium: a therapeutic magic wand . J Clin Psychiatry . 1989;;50:81-86.
23 +
Gitlin M.  Lithium-induced renal insufficiency . J Clin Psychopharmacol . 1993;;13:276-279.
24 +
Bendz H, Aurell M, Balldin J, Mathe AA, Sjodin I.  Kidney damage in long-term lithium patients: a cross-sectional study of patients with 15 years or more on lithium . Nephrol Dial Transplant . 1994;;9:1250-1254.
25 +
American Psychiatric Association.  Practice guidelines for the treatment of patients with bipolar disorder . Am J Psychiatry . 1994;;151( (suppl) ):1-36.
26 +
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.
27 +
Ellicott A, Hammen C, Gitlin M, Brown G, Jamison K.  Life events and the course of bipolar disorder . Am J Psychiatry . 1990;;147:1194-1198.
28 +
Hunt N, Bruce-Jones W, Silverstone T.  Life events and relapse in bipolar affective disorder . J Affect Disord . 1992;;25:13-20.
29 +
Post RN.  Transduction of psychosocial stress into the neurobiology of recurrent affective disorder . Am J Psychiatry . 1992;;149:999-1010.
30 +
Cochran S.  Preventing medical noncompliance in the outpatient treatment of bipolar affective disorders . J Consult Clin Psychol . 1984;;52:873-878.

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