Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-15T01:48:22.180Z Has data issue: false hasContentIssue false

Lithium Plus Valproate as Maintenance Polypharmacy for Patients With Bipolar I Disorder: A Review

Published online by Cambridge University Press:  07 November 2014

David A. Solomon
Affiliation:
Mood Disorders Program, Rhode Island Hospital, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island
Gabor I. Keitner
Affiliation:
Mood Disorders Program, Rhode Island Hospital, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island
Christine E. Ryan
Affiliation:
Mood Disorders Program, Rhode Island Hospital, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island
Ivan W. Miller
Affiliation:
Mood Disorders Program, Rhode Island Hospital, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island

Extract

Standard pharmacotherapy for the maintenance of treatment of patients with bipolar I disorder consists of lithium, valproate, or carbamazepine. However, many patients fail to respond to monotherapy with any of these agents, and as a result, psychiatrists often resort to polypharmacy. Findings from some open-label trials and retrospective chart reviews suggest this approach may be useful, but in the few controlled trials that have been conducted, the results have been negative. One drug combination that warrants further study as maintenance therapy is lithium plus valproate. Each is approved by the U.S. Food and Drug Administration for treatment of acute mania, and lithium has demonstrated efficacy for maintenance treatment as well. Some preliminary evidence suggests that the combination can be effective for patients who do not respond to monotherapy, and it seems to be no more dangerous than monotherapy. Concomitant administration of lithium plus valproate does not significantly alter lithium pharmacokinetics, and statistically significant changes that arise in valproate pharmacokinetics are not clinically significant. Although it is not known whether the drugs interact to augment response, many of their effects in the central nervous system do differ, and there is no indication of pharmacodynamic interactions that oppose each other. Finally, some evidence suggests that lithium and valproate may differ with regard to clinical variables that predict response to treatment. (J Clin Psychopharmacol 1998;18:38–49)

Bipolar I disorder afflicts approximately 1% of the U.S. adult population, with a median age at onset of 19 years. In many respects, it is a disabling disease. Acute episodes of mania and depression are often protracted with 24% of patients still acutely ill after 1 year has elapsed, 16% after 2 years, and 9% after 5 years. Subsyndromal symptoms, which impose significant morbidity that falls short of meeting full criteria for a mood episode, may occur frequently. Patients with bipolar I disorder are more likely than not to be unemployed or underemployed, less likely to marry and more likely to divorce than matched control subjects, and almost every family perceives the illness as a burden. Even remitted patients manifest poor psychosocial functioning, Ultimately, nearly 19% of patients die from suicide.

Type
Academic Supplement
Copyright
Copyright © Cambridge University Press 2000

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Weissman, MM, Leaf, PJ, Tischler, GL, Blazer, DG. Karno, M, Bruce, ML, Florio, LP. Affective disorders in five United States communities. Psychol Med. 1988;18:141153.CrossRefGoogle ScholarPubMed
2.Burke, KC, Burke, JD Jr, Regier, DA, Rae, DS. Age at onset of selected mental disorders in five community populations. Arch Gen Psychiatry. 1990;47:511518.CrossRefGoogle ScholarPubMed
3.Keller, MB, Lavori, PW, Coryell, W, Endicott, J, Mueller, TJ. Bipolar I: a five-year prospective follow-up. J Nerv Ment Dis. 1993;131:238245.CrossRefGoogle Scholar
4.Keller, MB, Lavori, PW, Kane, JM, Gelenberg, AJ, Rosenbaum, JF, Walzer, EA, Baker, LA. Subsyndromal symptoms in bipolar disorder: a comparison of standard and low serum levels of lithium. Arch Gen Psychiatry. 1992;49:371376.CrossRefGoogle ScholarPubMed
5.Carlson, GA, Korin, J, Davenport, YB, Adland, M. Follow-up of 53 bipolar manic-depressive patients. Br J Psychiatry. 1974;124:134139.CrossRefGoogle ScholarPubMed
6.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;47:11061111.CrossRefGoogle Scholar
7.Coryell, W, Scheftner, W, Keller, M, Endicott, J, Maser, J, Klerman, GL. The enduring psychosocial consequences of mania and depression. Am J Psychiatry. 1993;150:720727.Google ScholarPubMed
8.Chakrabarti, S, Kulhara, F, Verma, SK. Extent and determinants of burden among families of patients with affective disorders. Acta Psychiatr Scand. 1992;86:247252.CrossRefGoogle ScholarPubMed
9.Bauwens, F, Tracy, A, Pardoen, D, VanderElst, M, Mendlewicz, J. Social adjustment of remitted bipolar and unipolar out-patients: a comparison with age- and sex-matched controls. Br J Psychiatry. 1991;159:239244.CrossRefGoogle ScholarPubMed
10.Goodwin, FK, Jamison, KR. Suicide. In: Goodwin, FK, Jamison, KR. Manic-depressive illness. New York, NY: Oxford University Press; 1990:227244.Google Scholar
11.Zis, AP, Goodwin, FK. Major affective disorder as a recurrent illness: a critical review. Arch Gen Psychiatry. 1979;36:835839.CrossRefGoogle ScholarPubMed
12.Winokur, G, Coryell, W, Keller, M, Endicott, J, Askikal, H. A prospective follow-up of patients with bipolar and primary unipolar affective disorder. Arch Gen Psychiatry. 1993;50:457465.CrossRefGoogle ScholarPubMed
13.Prien, RF. Maintenance treatment of depressive and manic states. In: Georgotas, A, Cancro, R, eds. Depression and mania. New York, NY: Elsevier; 1988:439451.Google Scholar
14.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: report of the NIMH collaborative study group comparing lithium carbonate, imipramine, and a lithium carobonate-imipramine combination. Arch Gen Psychiatry. 1984;41:10961104.CrossRefGoogle Scholar
15.Shapiro, DR, Quitkin, FM, Fleiss, JL. Response to maintenance therapy in bipolar illness: effect of index episode. Arch Gen Psychiatry. 1989;46:401405.CrossRefGoogle ScholarPubMed
16.Harrow, M, Goldberg, JF, Grossman, LS, Meltzer, HY. Outcome in manic disorders: a naturalistic follow-up study. Arch Gen Psychiatry. 1990;47:665671.CrossRefGoogle ScholarPubMed
17.Maj, M, Pirozzi, R, Kemali, D. Long-term outcome of lithium prophylaxis in bipolar patients [letter]. Arch Gen Psychiatry. 1991;48:772.CrossRefGoogle ScholarPubMed
18.Gelenberg, AJ, Kane, JM, Keller, MB, Lavori, P, Rosenbaum, JF, Cole, K, Lavelle, J. Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder. N Engl J Med. 1989;321:14891493.CrossRefGoogle ScholarPubMed
19.Dunner, DJ, Fleve, RR. Clinical factors in lithium carbonate prophylaxis failure. Arch Gen Psychiatry. 1974;30:229233.CrossRefGoogle ScholarPubMed
20.Prien, RF, Himmelhoch, JM, Kupfer, DJ. Treatment of mixed mania. J Affect Disord. 1988;15:915.CrossRefGoogle ScholarPubMed
21.Post, RM, Rubinow, DR, Uhde, TW, Roy-Durne, RP, Linnolla, M, Rosoff, A, Cowdry, R. Dysphoric mania: clinical and biological correlates. Arch Gen Psychiatry. 1989;46:353358.CrossRefGoogle ScholarPubMed
22.Faedda, GL, Baldessarini, RJ, Tohen, M, Strakowski, SM, Waternaux, CM. Episode sequence in bipolar disorder and reponse to lithium treatment. Am J Psychiatry. 1991;148:12371239.Google Scholar
23.Tohen, M, Waternaux, CM, Tsuang, MT, Hunt, AT. Four-year follow-up of twenty-four first-episode manic patients. J Affect Disord. 1990;19:7986.CrossRefGoogle ScholarPubMed
24.Abou-Saleh, MT, Coppen, A. Who responds to prophylactic lithium? J Affect Disord. 1986;10:115125.CrossRefGoogle ScholarPubMed
25.Stallone, F, Shelley, E, Mendlewicz, J, Fieve, RR. The use of lithium in affective disorders III: a double-blind study of prophylaxis in bipolar disorder. Am J Psychiatry. 1973;130:10061010.CrossRefGoogle Scholar
26.O'Connell, RA, Mayo, JA, Eng, LK, Jones, JS, Gabel, RH. Social support and long-term lithium outcome. Br J Psychiatry. 1985;147:272275.CrossRefGoogle ScholarPubMed
27.Miklowitz, DJ, Goldstein, MJ, Nuechterlein, KH, Snyder, KS, Mintz, J. Family factors and the course of bipolar affective disorder. Arch Gen Psychiatry. 1988;45:225231.CrossRefGoogle ScholarPubMed
28.Pope, HG, McElroy, SL, Keck, PE, Hudson, JL. Valproate in the treatment of acute mania: a placebo-controlled study. Arch Gen Psychiatry. 1991;48:6268.CrossRefGoogle Scholar
29.Lambert, PA. 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: Elsevier, 1984:3344.Google Scholar
30.Puzynski, S, Klosiewicz, L. Valproic acid amide in the treatment of rapid-cycling bipolar disorder. J Clin Psychopharmacol. 1988;8:275279.Google Scholar
31.Emrich, HM, Dose, M, von Zerssen, D. The use of sodium valproate, carbamazepine and oxcarbazepine in patients with affective disorders. J Affect Disord. 1985;8:243250.CrossRefGoogle ScholarPubMed
32.McElroy, SL, Keck, PE Jr, Pope, HG Jr, Hudson, JI. Valproate in the treatment of rapid-cycling bipolar disorder. J Clin Psychopharmacol. 1988;8:275279.CrossRefGoogle ScholarPubMed
33.Hayes, SG. Long-term use of valproate in primary psychiatric disorders. J Clin Psychiatry. 1989;50(suppl 3):3539.Google ScholarPubMed
34.Fogelson, DI, Jacobson, S, Sternbach, H. A retrospective study of valproate in private psychiatric practice. Ann Clin Psychiatry. 1991;3:315320.Google Scholar
35.Guscott, R. Clinical experience with valproic acid in 22 patients with refractory bipolar mood disorder [letter]. Can J Psychiatry. 1992;37:590.CrossRefGoogle ScholarPubMed
36.Calabrese, JR, Woyshville, MJ, Kimmel, SE, Rapport, DJ. Predictors of valproate response in bipolar rapid cycling. J Clin Psychopharmacol. 1993;13:280283.CrossRefGoogle ScholarPubMed
37.Schaff, MR, Fawcett, J, Zajecka, JM. Divalproex sodium in the treatment of refractory mood disorders. J Clin Psyhiatry. 1993;54:380384.Google Scholar
38.Post, RM, Leverisch, GS, Rosoff, AS, Altshuler, LL. Carbamazepine prophylaxis in refractory affective disorders: a focus on long-term follow-up. J Clin Psychopharmacol. 1990;10:318327.CrossRefGoogle ScholarPubMed
39.Frankenburg, FR, Tohen, M, Cohen, BM, Lipinski, JF. Long-term response to carbamazepine: a retrospective study. J Clin Psychopharmacol. 1988;8:130132.CrossRefGoogle ScholarPubMed
40.Okuma, T, Inanga, K, Otsuki, S, Sarai, K, Takahashi, R, Hazarna, H, Mori, A, Watanabe, S. A preliminary double-blind study on the efficacy of carbamazepine in prophylaxis of manic-depressive illness. Psychopharmacology (Berlin). 1981;73:9596.CrossRefGoogle ScholarPubMed
41.Lusznar, RM, Murphy, DP, Nunn, CMH. Carbamazepine vs lithium in the treatment and prophylaxis of mania. Br J Psychiatry. 1988;153:198204.CrossRefGoogle Scholar
42.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;48:915921.CrossRefGoogle ScholarPubMed
43.Coxhead, N, Silverstone, R, Cookson, J. Carbamazepine versus lithium in the prophylaxis of bipolar affective disorder. Acta Psychiatr Scand. 1992;85:114118.CrossRefGoogle ScholarPubMed
44.Practice guideline for the treatment of patients with bipolar disorder. American Psychiatric Association. Am J Psychiatry. 1994;151(suppl 12):136.CrossRefGoogle Scholar
45.The Expert Consensus Guideline Series. Treatment of bipolar disorder. Steering Committee. American Psychiatric Association. J Clin Psychiatry. 1996;57(suppl 12A):388.Google Scholar
46.Hortobagyl, GN, Theriault, RL, Porter, L, et al.Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastses. N Engl J Med. 1996;335:17851791.CrossRefGoogle Scholar
47.Alberts, DS, Liu, PY, Hannigan, EV, et al.Intraperitoneal cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996;335:19501955.CrossRefGoogle ScholarPubMed
48.Eron, JJ, Benoit, SL, Jemsek, J, et al.Treatment with lamivudine, zidovudine, or both in HIV-positive patients with 200 to 500 CD4+ cells per cubic millimeter. North American HIV Working Party. N Engl J Med. 1995;333:16621669.CrossRefGoogle ScholarPubMed
49.Olanow, CS, HAuser, RA, Gauger, L, et al.The effect of deprenyl and levodopa on the progression of Parkinson's disease. Ann Neurol. 1995;38:771777.CrossRefGoogle ScholarPubMed
50.Ferrendelli, JA. Relating pharmacology to clinical practice: the pharmacologic basis of rational polypharmacy. Neuropoly. 1995;45(suppl 2):S12S16.Google ScholarPubMed
51.Speroff, L, Rowan, J, Symons, J, Genant, H, Wilborn, W. The comparative effect on bone density, endometrium, and lipids of continuous hormones as replacement therapy (CHART study). JAMA. 1996;276:13971403.CrossRefGoogle Scholar
52.Vigneri, S, Termini, R, Leandro, G, et al.A comparison of five maintenance therapies for reflux esophagitis. N Engl J Med. 1995;333:11061110.CrossRefGoogle ScholarPubMed
53.Nichol, MB, Stimmel, GL, Lange, SC. Factors predicting the use of multiple psychotropic medications. J Clin Psychiatry. 1995;56:6066.Google ScholarPubMed
54.Johnson, RE, McFarland, BH. Lithium use and discontinuation in a health maintenance organization. Am J Psychiatry. 1996;153:9931000.Google Scholar
55.Denicoff, KD, Blake, RD, Smith-Jackson, EE, Jacob, PA, Leverich, G, Post, RM. Morbidity in treated bipolar disorder: a one-year prospective study using daily life charts. Depression. 1994;2:95104.CrossRefGoogle Scholar
56.Sachs, GS. Use of clonazepam for bipolar affective disorder. J Clin Psychiatry. 1990;51(suppl):3134.Google ScholarPubMed
57.Prien, RF, Potter, WZ. NIMH workshop report on treatment of bipolar disorder. Psychopharmacol Bull. 1990;26:409427.Google ScholarPubMed
58.Keck, PE, McElroy, SL, Stratkowski, SM, Balistreri, TM, Kizer, DL, West, SA. Factors associated with maintenance antipsychotic treatment of patients with bipolar disorder. J Clin Psychiatry. 1996;57:147151.Google ScholarPubMed
59.Sernyak, MJ, Griffin, RA, Johnson, RM, Pearsall, HR, Wexler, BE, Woods, SW. Neuropleptic exposure following inpatient treatment of acute mania with lithium and neuroleptic. Am J Psychiatry. 1994;151:133135.Google Scholar
60.Anderson, DN. A comparison of in-patient and out-patient prescribing. Br J Psychiatry. 1989;154:644649.CrossRefGoogle ScholarPubMed
61.Rosholm, JU, Hallas, J, Gram, LF. Concurrent use of more than one major psychotropic drug (polypsychopharmacy) in out-patients–a prescription database study. Br J Clin Pharmacol. 1994;37:533538.CrossRefGoogle ScholarPubMed
62.Inoue, K, Arima, S, Tanaka, K, Kukui, Y, Kato, N. A lithium and carbamazepine combination in the treatment of bipolar disorder—a preliminary report. Folia Psychiatr Neurol Jpn. 1981;35:465–76.Google ScholarPubMed
63.Shukla, S, Cook, BL, Miller, MG. Lithium-carbamazepine versus lithium-neuroleptic prophylaxis in bipolar illness. J Affect Disord. 1985;9:219222.CrossRefGoogle ScholarPubMed
64.Kishimoto, A. The treatment of affective disorder with cabamazepine: prophylactic synergism of lithium and carbamazepine combination. Prog Neuropsychopharmacol Biol Psychiatry. 1992;16:483493.Google Scholar
65.Bocchetta, A, Chillotti, C, Severino, G, Ardau, R, Del Zompo, M. Carbamazepine augmentation in lithium-refractory bipolar patients: a prospective study on long-term prophylactic effectiveness. J Clin Psychopharmacol. 1997;17:9296.CrossRefGoogle Scholar
66.Sachs, GS, Rosenbaum, JF, Jones, L. Adjunctive clonazepam for maintenance treatment of bipolar affective disorder. J Clin Psychopharmacol. 1990;10:4247.CrossRefGoogle ScholarPubMed
67.Lowe, MR, Batchelor, DH. Depot neuroleptics and manic depressive psychosis. Int Clin Psychopharmacol. 1986;1:5362.Google ScholarPubMed
68.Peselow, ED, Fieve, RR, Difiglia, C, Sanfilipo, MP. Lithium prophylaxis of bipolar illness: the value of combination treatment. Br J Psychiatry. 1994;164:208214.CrossRefGoogle ScholarPubMed
69.Calabrese, JR, Delucchi, GA. Phenomenology of rapid cycling manic depression and its treatment with valproate. J Clin Psychiatry. 1989;50(suppl 3):3034.Google ScholarPubMed
70.Keck, PE, McElroy, SL, Vukovic, A, Friedman, LM. Combined valproate and carbamazepine treatment of bipolar disorder. J Neuropsychiatry Clin Neurosci. 1992;4:319322.Google ScholarPubMed
71.Del Zompo, M, Burrai, C, Piccardi, MP, Marelli, A, Corsini, GU. Prophylactic efficacy of carbamazepine in lithium-resistant affective disorder. In: Corsini, GU, ed. Current trends in lithium and rubidium therapy. Lancaster, England: MTP Press; 1984:325–30.CrossRefGoogle Scholar
72.Bauer, MS, Whybrow, PC. Rapid cycling bipolar affective disorder. Arch Gen Psychiatry. 1990;47:435440.CrossRefGoogle ScholarPubMed
73.White, E, Cheung, P, Silverstone, T. Depot antipsychotics in bipolar affective disorder. Int Clin Psychopharmacol. 1993;8:119122.CrossRefGoogle ScholarPubMed
74.Banov, MD, Zarate, CA, Tohen, M, et al.Clozapine therapy in refractory affective disorders: polanty predicts response in long-term follow-up. J Clin Psychiatry. 1994;55:295300.Google ScholarPubMed
75.Suppes, T, Phillips, KA, Judd, CR. Clozapine treatment of nonpsychotic rapid cycling bipolar disorder: a report of three cases. Biol Psychiatry. 1994;36:333340.CrossRefGoogle ScholarPubMed
76.Joyce, PR. Carbamazepine in rapid cycling bipolar affective disorder. Int Clin Psychopharmacol. 1988;3:123129.CrossRefGoogle ScholarPubMed
77.DiCostanzo, E, Schifano, F. Lithium alone or in combination with carbamazepine for the treatment of rapid-cycling bipolar affective disorder. Acta Psychiatr Scand. 1991;83:456459.CrossRefGoogle Scholar
78.Aronson, TA, Shukla, S, Hirschowitz, J. Clonazepam treatment of five lithium-refractory patients with bipolar disorder. Am J Psychiatry. 1989;146:7780.Google ScholarPubMed
79.Quitkin, FM, Kane, J, Rifkin, A, Ramos-Lorenzi, JR, Nayak, DV. Prophylactic lithium carbonate with and without imipramine for bipolar I patients. A double-blind study. Arch Gen Psychiatry. 1981;38:902907.CrossRefGoogle ScholarPubMed
80.Small, JG, Klapper, MH, Marhenke, JD, Milstein, V, Woodham, GC, Kellarns, JJ. Lithium combined with carbamazepine or haloperidol in the treatment of mania. Psychopharmacol Bull. 1995;31:265272.Google ScholarPubMed
81.Esparon, J, Kolloori, J, Naylor, GJ, McHarg, AM, Smith, AHW, Hopwood, SE. Comparison of the prophylactic action of flupenthixol with placebo in lithium treated manic-depressive patients. Br J Psychiatry. 1986;148:723725.CrossRefGoogle ScholarPubMed
82.Suppes, T, Calabrese, JR, Mitchell, PB, Pazzaglia, PJ, Potter, WZ, Zarin, DA. Algorithms for the treatment of bipolar, manic-depressive illness. Psychopharmacol Bull. 1995;31:469474.Google ScholarPubMed
83.Prien, RF, Rush, AJ. National Institute of Mental Health workshop report on the treatment of bipolar disorder. Biol Psychiatry. 1996;40:215220.CrossRefGoogle ScholarPubMed
84.Solomon, DA, Ryan, CE, Keitner, GI, Miller, IW, Shea, MT, Kazim, A, Keller, MB. A pilot study of lithium carbonate plus divalproex sodium for the continuation and maintenance treatment of patients with bipolar I disorder. J Clin Psychiatry. 1997;58:9599.CrossRefGoogle ScholarPubMed
85.Berry, KJ, Mielke, PW Jr.R by c chi-square analyses with small expected cell frequencies. Educ Psychol Meas. 1986;46:169173.CrossRefGoogle Scholar
86.Sharma, V, Persad, E, Mazmanian, D, Karunaraine, K. Treatment of rapid cycling bipolar disorder with combination therapy of valproate and lithium. Can J Psychiatry. 1993;38:137139.CrossRefGoogle ScholarPubMed
87.Sharma, V, Persad, E. Augmentation of valproate with lithium in a case of rapid cycling bipolar disorder. Can J Psychiatry. 1992;37:584585.CrossRefGoogle Scholar
88.Mitchell, P, Withers, K, Jacobs, G, Hickie, I. Combining lithium and sodium valproate for bipolar disorder. Aust N Z J Psychiatry. 1994;28:141143.CrossRefGoogle ScholarPubMed
89.Fenn, HH, Robinson, D, Luby, V, Dangel, C, Buxton, E, Beattie, M, Kraemer, H, Yesavage, JA. Trends in pharmacotherapy of schizoaffective and bipolar affective disorders: a 5-year naturalistic study. Am J Psychiatry. 1996;158:711713.Google Scholar
90.Preskorn, SH, Lacey, RL. Polypharmacy: when is it rational? J Pract Psychiatry Behav Health. 1995;1:9298.Google Scholar
91.Pope, HG, McElroy, SC, Satlin, A, Hudson, JI, Keck, PE, Kalish, SR. Head injury, bipolar disorder, and response to valproate. Compr Psychiatry. 1988;29:3438.CrossRefGoogle ScholarPubMed
92.Granneman, GR, Schneck, DW, Cavanaugh, JH, Witt, GF. Pharmacokinetic interactions and side effects resulting from concomitant administration of lithium and divalproex sodium. J Clin Psychiatry. 1996;57:204206.Google ScholarPubMed
93.Hardman, JG, Limbird, LE. Goodman and Gilman's the pharmacological basis of therapeutics, 9th ed. New York: McGraw-Hill; 1996.Google Scholar
94.Schatzberg, AF, Nemeroff, CB. The American Psychiatric Press textbook of psychopharmacology. Wahington, DC: American Psychiatric Press; 1995.Google Scholar
95.Lenox, RH, McNamara, RK, Watterson, JM, Watson, DG. Myristoylated alanine-rich C kinase substrate (MARCKS): a molecular target for the therapeutic action of stabilizers in the brain? J Clin Psychiatry. 1996;57(suppl 13):2331.Google ScholarPubMed
96.Bowden, CL. Predictors of response to divalproex and lithium. J Clin Psychiatry. 1995;56(suppl 3):2530.Google ScholarPubMed
97.Bowden, CL, Brugger, AM, Swann, AC, et al.Efficacy of divalproex vs lithium and placebo in the treatment of mania. JAMA. 1994;271:918924.CrossRefGoogle ScholarPubMed
98.Swann, AC, Bowden, CL, Morris, D, et al.Depression during mania: treatment response to lithium or divalproex. Arch Gen Psychiatry. 1997;54:3742.CrossRefGoogle ScholarPubMed
99.Brady, KT, Sonne, SC, Anton, R, Ballenger, JC. Valproate in the treatment of acute bipolar affective episodes complicated by substance abuse: a pilot study. J Clin Psychiatry. 1996;56:118121.Google Scholar