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The “Good Enough” Mood Stabilizer: A Review of the Clinical Evidence

  • David Kahn and Rebecca Chaplan

Abstract

A growing family of medications is used for mood stabilization in bipolar disorder. These medications fall into two broad categories according to likely mechanisms of action. Within the categories, specific drugs may vary in their efficacy for different phases of the disorder. The first category, including lithium, anticonvulsants, and some novel treatments, appears to have mechanisms related to intracellular second messengers. These medications have more pronounced antimanic than antidepressant effects, except for lamotrigine, which has antidepressant effects without precipitating mania. The second group of mood stabilizers is the atypical antipsychotics, which act through dopamine and other monoamines. Olanzapine and in all likelihood other drugs in the class possess marked, acute antimanic properties and possible antidepressant properties, but require further study before they can be used as routine options in long-term care. It is clear that the advent of multiple mood stabilizer candidates has not yet led to a single ideal therapy for bipolar disorder, but rather to options that can be flexibly tailored to the lifetime needs of individual patients, in sequences or combinations, and perhaps in conjunction with other classes of psychotropics.

Copyright

Corresponding author

Please direct correspondence to: David Kahn, MD, New York Presbyterian Hospital, 180 Fort Washington Avenue, HP 240, New York, NY 10032. Tel: 212-305-5464; Fax: 212-305-3111; E-mail: kahndav@pi.cpmc.columbia.edu.

References

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1.Sachs, GS, Printz, DJ, Kahn, DA, Carpenter, D, Docherty, JP. The expert consensus guideline series: medication treatment of bipolar disorder. Postgrad Med. 2000;4:1104.
2.West, JC, Das, A, Kahn, DA, et al. The treatment of bipolar disorder in routine practice. Paper presented at: Annual Meeting of the American Psychiatric Association; May 2001; New Orleans, La.
3.Sachs, GS. Treatment-resistant bipolar depression. Am J Psychiatry. 1996;19:215236.
4.American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder. Am J Psychiatry. 1994;151(suppl 12):136.
5.Post, RM. Comparative pharmacology of bipolar disorder and schizophrenia. Schizophr Res. 1999;39:153158.
6.Ghaemi, SN, Boiman, EE, Goodwin, FK. Kindling and second messengers: an approach to the neurobiology of recurrence in bipolar disorder. Biol Psychiatry. 1999;45:137144.
7.Bazil, CW, Pedley, TA. Advances in the medical treatment of epilepsy. Annu Rev Med. 1998;49:135162.
8.Ure, JA, Perassolo, M. Update on the pathophysiology of the epilepsies. J Neurol Sci. 2000;177:117.
9.Manji, HK, Lenox, RH. Signaling: cellular insights into the pathophysiology of bipolar disorder. Biol Psychiatry. 2000;48:518530.
10.Devanand, DP, Polanco, P, Cruz, R, et al.The efficacy of ECT in mixed affective states. J ECT. 2000;16:3237.
11.Rush, AJ, Post, RM, Nolen, WA, et al.Methodological issues in developing new acute treatments for patients with bipolar illness. Biol Psychiatry. 2000;48:615624.
12.French, JA. The art of antiepileptic trial design. Adv Neurol. 1998;76:113123.
13.Kupka, RW, Nolen, WA, Altshuler, LL, et al.The Stanley Foundation Bipolar Network: 2. Preliminary comment of demographics, course of illness and response to novel treatments. Br J Psychiatry. 2001;178:S177S183.
14.Young, LT, Joffe, RT, Robb, JC, MacQueen, GM, Marriott, M, Patelis-Siotis, I. Double-blind comparison of addition of a second mood stabilizer versus an antidepressant to an initial mood stabilizer for treatment of patients with bipolar depression. Am J Psychiatry. 2000;157:124126.
15.Nemeroff, CB, Evans, DL, Gyulai, L, et al.Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression. Am J Psychiatry. 2001;158:906912.
16.Goodwin, FK, Jamison, KR. Medical treatment of manic episodes. In: Goodwin, FK, Jamison, KR, eds. Manic-Depressive Illness. New York, NY: Oxford University Press; 1990:603629.
17.Prien, RF, Himmelhoch, JM, Kupfer, DJ. Treatment of mixed mania. J Affect Disord. 1988;15:915.
18.Goodwin, FK, Jamison, KR. Medical treatment of acute bipolar depression. In: Goodwin, FK, Jamison, KR, eds. Manic-Depressive Illness. New York, NY: Oxford University Press; 1990:630664.
19.Prien, RF, Caffey, EM Jr, Klett, CJ. 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 Psychiatry. 1973;28:337341.
20.Prien, RF, Klett, CJ, Caffey, EM Jr. Lithium carbonate and imipramine in prevention of affective episodes. A comparison in recurrent affective illness. Arch Gen Psychiatry. 1973;29:420425.
21.Davis, JM. Overview: maintenance therapy in psychiatry: II. Affective disorders. Am J Psychiatry. 1976;133:113.
22.Dunner, DL, Stallone, F, Fieve, RR. Prophylaxis with lithium carbonate: an update. Arch Gen Psychiatry. 1982;39:13441345.
23.Dunner, DL, Fieve, RR. Clinical factors in lithium carbonate prophylaxis failure. Arch Gen Psychiatry. 1974;30:229233.
24.Dunner, DL, Patrick, V, Fieve, RR. Rapid cycling manic depressive patients. Compr Psychiatry. 1977;18:561566.
25.Swann, AC, Bowden, CL, Morris, D, et al.Depression during mania. Treatment response to lithium or divalproex. Arch Gen Psychiatry. 1997;54:3742.
26.Calabrese, JR, Markovitz, PJ, Kimmel, SE, Wagner, SC. Spectrum of efficacy of valproate in 78 rapid-cycling bipolar patients. J Clin Psychopharmacol. 1992;12(suppl 1):53S56S.
27.Winsberg, ME, De Golia, SG, Strong, CM, et al. Divalproex in medicationnaïve bipolar II depression. Paper presented at: the Annual Meeting of the American Psychiatric Association; May 1997; San Diego, Calif.
28.Bowden, CL, Calabrese, JR, McElroy, SL, et al.A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Divalproex Maintenance Study Group. Arch Gen Psychiatry. 2000;57:481489.
29.Orsini, CMJ, Frankle, WG, Grandin, LD, et al. Lithium versus valproic acid: a comparison of the long-term treatment of bipolar illness. Paper presented at: the Annual Meeting of the American Psychiatric Association; May 2001; New Orleans, La.
30.Calabrese, JR, Shelton, MD, Bowden, CL, et al.Bipolar rapid cycling: focus on depression as its hallmark. J Clin Psychiatry. 2001;62(suppl 14):3441.
31.Ballenger, JC, Post, RM. Therapeutic effects of carbamazepine in affective illness: a preliminary report. Commun Psychopharmacol. 1978;2:159175.
32.Keck, PE Jr, McElroy, SL, Nemeroff, CB. Anticonvulsants in the treatment of bipolar disorder. J Neuropsychiatry Clin Neurosci. 1992;4;395405.
33.Post, RM, Uhde, TW, Roy-Byrne, PP, Joffe, RT. Correlates of antimanic response to carbamazepine. Psychiatry Res. 1987;21:7183.
34.Kahn, D. Carbamazepine and other antiepileptic drugs in refractory depression. In: Roose, SP, Glassman, AH, eds. Treatment Strategies for Refractory Depression. Washington, DC: American Psychiatric Press; 1990:75108.
35.Keck, PE, McElroy, SL. Antiepileptic drugs. In: Textbook of Psychopharmacology. 2nd ed. Washington, DC: American Psychiatric Press; 1998:431454.
36.Post, RM, Leverich, GS, Rosoff, AS, Altshuler, LL. Carbamazepine prophylaxis in refractory affective disorders: a focus on long-term follow-up. J Clin Psychopharmacol. 1990;10:318327.
37.Denicoff, KD, Smith-Jackson, EE, Disney, ER, Ali, SO, Leverich, GS, Post, RM. Comparative efficacy of lithium, carbamazepine, and the combination in bipolar disorder. J Clin Psychiatry. 1997;58:470478.
38.Frye, M, Ketter, TA, Kimbrell, TA, et al.A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. J Clin Psychopharmacol. 2000;20:607614.
39.Bowden, C, Calabrese, JR, Asher, J. Spectrum of efficacy of lamotrigine in bipolar disorder: overview of double-blind, placebo-controlled studies. Paper presented at: 39th Annual Meeting of American College of Neuropsychopharmacology; December 2000; San Juan, Puerto Rico.
40.Anand, A, Oren, DA, Berman, A, et al. Lamotrigine treatment of lithium failure outpatient—a double-blind, placebo-controlled study. Paper presented at: Third International Conference on Bipolar Disorder; June 1999; Pittsburgh, Pa.
41.Berk, M. Lamotrigine and the treatment of mania in bipolar disorder. Eur Neuropsychopharmacol. 1999;9:S119S123.
42.Calabrese, JR, Bowden, CL, McElroy, SL, et al.Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder. Am J Psychiatry. 1999;156:10191023.
43.Calabrese, JR, Bowden, CL, DeVeaugh-Geiss, J, et al. Lamotrigine demonstrates long-term mood stabilization in manic patients. Paper presented at: Annual Meeting of the American Psychiatric Association; May 2001; New Orleans, La.
44.Calabrese, JR, Suppes, T, Bowden, CL, et al.A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Lamictal 614 Study Group. J Clin Psychiatry. 2000;61:841850.
45.Suppes, P, Ascher, J, Bowden, CL. Lamotrigine in rapid-cycling bipolar disorder: predictors of response. Paper presented at: Annual Meeting of the American Psychiatric Association; May 2001; New Orleans, La.
46.Altshuler, LL, Keck, PE Jr, McElroy, SL. Gabapentin in the acute treatment of refractory bipolar disorder. Bipolar Disord. 1999;1:6165.
47.Ghaemi, SN, Goodwin, FK. Gabapentin treatment of the non-refractory bipolar spectrum: an open case series. J Affect Disord. 2001;65:167171.
48.Pande, AC, Crockatt, JG, Janney, CA, et al.Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy. Gabapentin bipolar disorder study group. Bipolar Disord. 2000;2:249255.
49.The Editors. Our readers answer [letter]. Psychiatry Drug Alerts. 2001;7:56.
50.Chengappa, R, Rathore, D, Levine, D, et al.Topiramate as add-on treatment of patients with bipolar mania. Bipolar Disord. 1999;1:4253.
51.McElroy, SL, Suppes, T, Keck, PE, et al.Open-label adjunctive topiramate in the treatment of bipolar disorders. Biol Psychiatry. 2000;47:10251033.
52.Grunze, HCR, Normann, C, Langosch, J, et al.Antimanic efficacy of topiramate in an open trial with an on-off-on design. J Clin Psychiatry. 2001;62:464468.
53.Calabrese, JR, Keck, PE Jr, McElroy, SL, Shelton, MD. A pilot study of topiramate as monotherapy in the treatment of acute mania. J Clin Psychopharmacol. 2001;21:340342.
54.Hussain, MX, Chaudry, ZA, Hussain, S. Topiramate in treatment of refractory bipolar depression. Paper presented at: Fourth International Conference on Bipolar Disorder; June 2001; Pittsburgh, Pa.
55.McIntyre, RS, Mancini, DA, McCann, SM, et al. Randomized, single-blind comparison of topiramate and bupropion SR as add-on therapy in bipolar depression. Paper presented at: 39th Annual Meeting of American College of Neuropsychopharmacology; December 2000; San Juan, Puerto Rico.
56.Marcotte, D. Use of topiramate, a new anti-epileptic, as a mood stabilizer. J Affective Disord. 1998;50:245251.
57.Schlatter, FJ, Soutullo, CA, Cervera-Enguix, S. J Clin Psychopharmacol. 2001;21:464466.
58.Emrich, HM. Studies with oxcarbazepine (Trileptal) in acute mania. Int Clin Psychopharmacol. 1990;5(suppl):8388.
59.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.
60.Reinstein, MJ, Sonenberg, JG, Chasanov, MA, et al. Oxcarbazepine and divalproex sodium: a comparison of efficacy and side effects for mania [poster]. Presented at: Annual Meeting of the American Psychiatric Association; May 2001; New Orleans, La.
61.Hummel, B, Stampfer, R, Grunze, H, et al. Acute antimanic efficacy and safety of oxcarbazepine in an open trial with an on-of-on design. Paper presented at: Fourth International Conference on Bipolar Disorder; June 2001; Pittsburgh, Pa.
62.Kaufman, KR. Adjunctive tiagabine treatment of psychiatric disorders: three cases. Ann Clin Psychiatry. 1998;10:181184.
63.Grunze, H, Erfurth, A, Marcuse, A, et al.Tiagabine appears not to be efficacious in the treatment of acute mania. J Clin Psychiatry. 1999;60:759762.
64.Schaffer, LC, Schaffer, CB, How, J. The use of tiagabine in the treatment of patients with refractory bipolar disorder. Paper presented at: Fourth International Conference on Bipolar Disorder; June 2001; Pittsburgh, Pa.
65.Kanba, S, Yagi, G, Kamijma, K, et al.The first open study of zonisamide, a novel anticonvulsant, shows efficacy in mania. Prog Neuropsychopharmacol Biol Psychiatry. 1994;18:707715.
66.Tohen, M, Sanger, TM, McElroy, SL, et al.Olanzapine versus placebo in the treatment of acute mania. Am J Psychiatry. 1999;156:702709.
67.Ghaemi, SN, Cherry, EL, Katzow, JA, Goodwin, FK. Does olanzapine have antidepressant properties? A retrospective, preliminary study. Bipolar Disord. 2000;2:196199.
68.Sanger, TM, Grundy, SL, Gibson, J, et al.Long-term olanzapine therapy in the treatment of bipolar I disorder: an open-label continuation phase study. J Clin Psychiatry. 2001;62:273281.
69.Aubry, JM, Simon, AE, Bertschy, G. Possible induction of mania and hypomania by olanzapine or risperidone. A critical review of reported cases. J Clin Psychiatry. 2000;61:649655.
70.Segal, J, Berk, M, Brook, S. Risperidone compared with both lithium and haloperidol in mania: a double-blind, randomized, controlled trial. Clin Neuropharmacol. 1998;23:176–80.
71.Grossman, F, Bowden, CL, Okamato, A. Risperidone plus mood stabilizer versus placebo plus mood stabilizer in patients with bipolar disorder: a combined efficacy analysis. Paper presented at: Annual Meeting of the American Psychiatric Association; May 2001; New Orleans, La.
72.Yatham, LN. Risperidone and mood stabilizer combination in acute and continuation treatment of mania. Paper presented at: Fourth International Conference on Bipolar Disorder; June 2001; Pittsburgh, Pa.
73.Benabarre, A, Vieta, E, Martinez-Aran, A, et al. Risperidone as adjunctive treatment in mixed mania. Paper presented at: Fourth International Conference on Bipolar Disorder; June 2001; Pittsburgh, Pa.
74.Shelton, RC, Addington, S, Augenstein, EJ, et al. Risperidone in bipolar depression. Paper presented at: Annual Meeting of the American Psychiatric Association; May 2001; New Orleans, La.
75.Aubry, JM, Simon, AE, Bertschy, G. Possible induction of mania and hypomania by olanzapine or risperidone. A critical review of reported cases. J Clin Psychiatry. 2000;61:649655.
76.McConville, BJ, Arvanitis, LA, Thyrum, PT, et al.Pharmacokinetics, tolerability and clinical effectiveness of quetiapine fumarate: an open-label trial in adolescents with psychotic disorders. J Clin Psychiatry. 2000;61:252260.
77.DelBello, MP, Rosenberg, HL, Hudopohl, AM, et al. Quetiapine as adjunctive treatment for adolescent mania. Paper presented at: Fourth International Conference on Bipolar Disorder; June 2001; Pittsburgh, Pa.
78.Ghaemi, SN, Goldberg, JF, Ko, JY, et al. Seroquel treatment of rapid-cycling bipolar disorder: an open prospective study. Paper presented at: Fourth International Conference on Bipolar Disorder; June 2001; Pittsburgh, Pa.
79.Chisolm, K, Suppes, T. Clinical response to quetiapine add-on for treatment of refractory bipolar disorder. Paper presented at: Fourth International Conference on Bipolar Disorder; June 2001; Pittsburgh, Pa.
80.Keck, PE Jr, Ice, KN, and the Ziprasidone Study Group. Controlled treatment of acute mania with ziprasidone. Paper presented at: Annual Meeting of the American Psychiatric Association; May 2000; Chicago, Ill.
81.Prien, RF, Kupfer, DJ, Mansky, PA, et al.Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders. Arch Gen Psychiatry. 1984;41:10961104.
82.Guille, C, Sachs, GS, Ghaemi, SN. A naturalistic comparison of clozapine, risperidone, and olanzapine in the treatment of bipolar disorder. J Clin Psychiatry. 2000;61:638642.
83.Frye, MA, Ketter, TA, Leverich, GS, et al.The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study. J Clin Psychiatry. 2000;61:915.

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The “Good Enough” Mood Stabilizer: A Review of the Clinical Evidence

  • David Kahn and Rebecca Chaplan

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