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The Contemporary Face of Bipolar Illness: Complex Diagnostic and Therapeutic Challenges

Published online by Cambridge University Press:  07 November 2014

Konstantinos N. Fountoulakis
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Abstract

Manic depression, or bipolar disorder, is a multifaceted illness with an inevitably complex treatment. The current article summarizes the current status of our knowledge and practice concerning its diagnosis and treatment. While the prototypic clinical picture concerns the “classic” bipolar disorder, today mixed episodes with incomplete recovery and significant psychosocial impairment are more frequent. The clinical picture of these mixed episodes is variable, eludes contemporary classification systems, and possibly includes a constellation of mental syndromes currently classified elsewhere. Treatment includes the careful combination of lithium, antiepileptics, atypical antipsychotics, and antidepressants, but not all of the agents in these broad categories are effective for the treatment of bipolar disorder.

Type
Review Articles
Information
CNS Spectrums , Volume 13 , Issue 9 , September 2008 , pp. 763 - 779
Copyright
Copyright © Cambridge University Press 2008

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References

REFERENCES

1.Kraepelin, E. Manic-Depressive Insanity and Paranoia. Manchester, NH: Ayer Company Publishers; 1921.CrossRefGoogle Scholar
2.Angst, J. The emerging epidemiology of hypomania and bipolar II disorder. J Affect Disord. 1998;50:143–151.Google Scholar
3.Judd, LL, Akiskal, HS. The prevalence and disability of bipolar spectrum disorders in the US population: re-analysis of the ECA database taking into account subthresh-old cases. J Affect Disord. 2003;73:123–131.Google Scholar
4.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.Google Scholar
5.Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.Google Scholar
6.Kennedy, N, Boydell, J, Kalidindi, S, et al.Gender differences in incidence and age at onset of mania and bipolar disorder over a 35-year period in Camberwell, England. Am J Psychiatry. 2005;162:257–262.CrossRefGoogle Scholar
7.Akiskal, H. Mood disorders. In: Sadock, B, Sadock, V, eds. Comprehensive Textbook of Psychiatry, vol 1. Philadelphia, Penn: Lippincott Williams & Wilkins; 2000:1338–1377.Google Scholar
8.Akiskal, HS, Pinto, O. The evolving bipolar spectrum. Prototypes I, II, III, and IV. Psychiatr Clin North Am. 1999;22:517–34, vii.Google Scholar
9.Hantouche, EG, Akiskal, HS, Lancrenon, S, et al.Systematic clinical methodology for validating bipolaMI disorder: data in mid-stream from a French national multi-site study (EPIDEP). J Affect Disord. 1998;50:163–173.Google Scholar
10.Manning, JS, Haykal, RF, Connor, PD, Akiskal, HS. On the nature of depressive and anxious states in a family practice setting: the high prevalence of bipolar II and related disorders in a cohort followed longitudinally. Compr Psychiatry. 1997;38:102–108.CrossRefGoogle Scholar
11.Angst, J, Sellaro, R, Stassen, HH, Gamma, A. Diagnostic conversion from depression to bipolar disorders: results of a long-term prospective study of hospital admissions. J Affect Disord. 2005;84:149–157.Google Scholar
12.Mitchell, PB, Malhi, GS. Bipolar depression: phenomenological overview and clinical characteristics. Bipolar Disord. 2004;6:530–539.Google Scholar
13.Judd, LL, Akiskal, HS, Schettler, PJ. et al.The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59:530–537.Google Scholar
14.Perugi, G, Akiskal, HS, Lattanzi, L, et al.The high prevalence of “soft” bipolar (II) features in atypical depression. Compr Psychiatry. 1998;39:63–71.CrossRefGoogle ScholarPubMed
15.Mitchell, PB, Goodwin, GM, Johnson, GF, Hirschfeld, RM. Diagnostic guidelines for bipolar depression: a probabilistic approach. Bipolar Disord. 2008;10(pt 2):144–152.Google Scholar
16.Akiskal, HS, Benazzi, F. Continuous distribution of atypical depressive symptoms between major depressive and bipolar II disorders: dose-response relationship with bipolar family history. Psychopathology. 2008;41:39–42.Google Scholar
17.Geller, B, Fox, LW, Clark, KA. Rate and predictors of prepubertal bipolarity during follow-up of 6- to 12-year-old depressed children. J Am Acad Child Adolesc Psychiatry. 1994;33:461–468.Google Scholar
18.Thase, ME. Recognition and diagnosis of atypical depression. J Clin Psychiatry. 2007;68(suppl 8):11–16.Google Scholar
19.Fountoulakis, KN, Iacovides, A, Nimatoudis, I, Kaprinis, G, Ierodiakonou, C. Comparison diagnosis of melancholic and atypical features according to DSM-IV and somatic syndrome according to ICD-10 in patients suffering from major depression. Eur Psychiatry. 1999;14:426–433.Google Scholar
20.Akiskal, HS, Benazzi, F. Atypical depression: a variant of bipolar II or a bridge between unipolar and bipolar II? J Affect Disorders. 2005;84:209–217.CrossRefGoogle ScholarPubMed
21.Parker, G, Parker, K, Mitchell, P, Wilhelm, K. Atypical depression: Australian and US studies in accord. Curr Opin Psychiatry. 2005;18:1–5.Google Scholar
22.Akiskal, HS, Benazzi, F. Validating Kraepelin's two types of depressive mixed states: “depression with flight of ideas” and “excited depression.” World J Biol Psychiatry. 2004;5:107–113.CrossRefGoogle ScholarPubMed
23.McGlashan, TH. The Chestnut Lodge follow-up study III. Long-term outcome of borderline personalities. Arch Gen Psychiatry. 1986;43:20–30.Google Scholar
24.Akiskal, HS, Hantouche, EG, Bourgeois, ML, et al.Gender, temperament, and the clinical picture in dysphoric mixed mania: findings from a French national study (EPIMAN). J Affect Disord. 1998;50:175–186.CrossRefGoogle ScholarPubMed
25.Akiskal, HS. The prevalent clinical spectrum of bipolar disorders: beyond DSM-IV. J Clin Psychopharmacol. 1996;16(suppl 1):4S–14S.Google Scholar
26.Ng, B, Camacho, A, Lara, DR, Brunstein, MG, Pinto, OC, Akiskal, HS. A case series on the hypothesized connection between dementia and bipolar spectrum disorders: bipolar type VI? J Affect Disord. 2008;107:307–315.Google Scholar
27.Maj, M, Pirozzi, R, Magliano, L, Bartoli, L. Agitated depression in bipolar I disorder: prevalence, phenomenology, and outcome. Am J Psychiatry. 2003;160:2134–2140.Google Scholar
28.Sato, T, Bottlender, R, Kleindienst, N, Moller, HJ. Irritable psychomotor elation in depressed inpatients: a factor validation of mixed depression. J Affect Disord. 2005;84:187–196.Google Scholar
29.Altshuler, LL, Suppes, T, Black, DO, et al.Lower switch rate in depressed patients with bipolar II than bipolar I disorder treated adjunctively with second-generation antidepressants. Am J Psychiatry. 2006;163:313–315.Google Scholar
30.Serretti, A, Artioli, P, Zanardi, R, et al.Genetic features of antidepressant induced mania and hypomania in bipolar disorder. Psychopharmacology (Berl). 2004;174:504–511.CrossRefGoogle ScholarPubMed
31.Wada, K, Sasaki, T, Jitsuiki, H, et al.Manic/hypomanic switch during acute antidepressant treatment for uniplolar depression. J Clin Psychopharmacol. 2006;26:512–515Google Scholar
32.Tyrer, P, Mitchard, S, Methuen, C, Ranger, M. Treatment rejecting and treatment seeking personality disorders: Type R and Type S. J Personal Disord. 2003;17:263–268.Google Scholar
33.Fountoulakis, KN, Kaprinis, GS. Personality disorders: new data versus old concepts. Curr Opin Psychiatry. 2006;19:90–94.CrossRefGoogle ScholarPubMed
34.Akiskal, H, Akiskal, K. Epilogue. The renaissance of the ancient concept of temperament (with a focus on affective temperaments). In: Maj, M, Akiskal, HS, Mezzich, JE, Okasha, A, eds. Personality Disorders. Hoboken, NJ: John Wiley & Sons, Inc.; 2005:479–500.Google Scholar
35.Cloninger, C, Svrakic, D, Bayon, C, Przybeck, T. Measurement of psychopathology as variants of personality. In: Cloninger, CR, ed. Personality and Psychopathology (American Psychopathological Association Series). 1st ed. Washington, DC: American Psychiatric Publishing, Inc.; 1999:33–65.Google Scholar
36.Costa, PT Jr.McCrae, RR. Personality disorders and the five-factor model of personality. J Personal Disord. 1990;4:362–371.Google Scholar
37.Tellegen, A, Grove, W, Waller, N. Inventory of Personality Characteristics #7 (IPC7). Minneapolis, Minn: University of Minnesota Department of Psychology; 1991.Google Scholar
38.Cattel, RB. Handbook for the Sixteen Personality Factor Ouestionnaire. Champaign, Ill: Institute for Personality and Ability Testing; 1970.Google Scholar
39.Akiskal, HS, Akiskal, KK, Haykal, RF, Manning, JS, Connor, PD. TEMPS-A: progress towards validation of a self-rated clinical version of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire. J Affect Disord. 2005;85:3–16.CrossRefGoogle ScholarPubMed
40.Cohen, P. Personality development in childhood: old and new findings. In: Cloninger, CR, ed. Personality and Psychopathology (American Psychopathological Association Series) 1st ed. Washington, DC: American Psychiatric Publishing, Inc.; 1999:101–127.Google Scholar
41.Maremmani, I, Akiskal, HS, Signoretta, S, Liguori, A, Perugi, G, Cloninger, CR. The relationship of Kraepelian affective temperaments (as measured by TEMPS-I) to the tridimensional personality questionnaire (TPQ). J Affect Disord. 2005;85:17–27.Google Scholar
42.Bolton, S, Gunderson, J. Distinguishing borderline personality disorder from bipolar disorder: differential diagnosis and implications. Am J Psychiatry. 1996;153:1202–1207.Google Scholar
43.Parnas, J, Licht, D, Bovet, P. Cluster A personality disorders: a review. In: Maj, M, Akiskal, HS, Mezzich, JE, Okasha, A, eds. Personality Disorders. Hoboken, NJ: John Wiley & Sons, Inc.; 2005:1–74.Google Scholar
44.Zanarini, M, Frankenburg, F, Vujanovic, A, Hennen, J, Reich, D, Silk, K. Axis II comorbidity of borderline personality disorder: description of 6-year course and prediction to time-to-remission. Acta Psychiatr Scand. 2004;110:416–420.Google Scholar
45.Stone, M. Long-term outcome in personality disorders. Br J Psychiatry. 1993;162:299–313.Google Scholar
46.Grilo, CM, Skodol, AE, Gunderson, JG, et al.Longitudinal diagnostic efficiency of DSM-IV criteria for obsessive-compulsive personality disorder: a 2-year prospective study. Acta Psychiatr Scand. 2005;110:64–68.Google Scholar
47.McGlashan, T, Grilo, C, Sanislow, C, et al.Two-year prevalence and stability of individual DSM-IV criteria for schizotypal, borderline, avoidant, and obsessive-compulsive personality disorders: toward a hybrid model of axis II disorders. Am J Psychiatry. 2005;162:883–889.CrossRefGoogle Scholar
48.Akiskal, HS, Djenderedjian, AM, Rosenthal, RH, Khani, MK. Cyclothymic disorder: validating criteria for inclusion in the bipolar affective group. Am J Psychiatry. 1977;134:1227–1233.Google Scholar
49.Judd, LL, Schettler, PJ, Akiskal, HS, et al.Residual symptom recovery from major affective episodes in bipolar disorders and rapid episode relapse/recurrence. Arch Gen Psychiatry. 2008;65:386–394.Google Scholar
50.Bauer, MS, Calabrese, J, Dunner, DL, et al.Multisite data reanalysis of the validity of rapid cycling as a course modifier for bipolar disorder in DSM-IV. Am J Psychiatry 1994;151:506–515.Google Scholar
51.Winokur, G, Turvey, C, Akiskal, H, et al.Alcoholism and drug abuse in three groups-bipolar I, unipolars and their acquaintances. J Affect Disord. 1998;50:81–89.Google Scholar
52.Akiskal, HS, Benazzi, F. Family history validation of the bipolar nature of depressive mixed states. J Affect Disord. 2003;73:113–122.CrossRefGoogle ScholarPubMed
53.Brieger, P, Roettig, S, Ehrt, U, Wenzel, A, Bloink, R, Marneros, A. TEMPS-a scale in ‘mixed’ and ‘pure’ manic episodes: new data and methodological considerations on the relevance of joint anxious-depressive temperament traits. J Affect Disord. 2003;73:99–104.Google Scholar
54.Oedegaard, KJ, Neckeimann, D, Fasmer, OB. Type A behaviour differentiates bipolar II from unipolar depressed patients. J Affect Disord. 2006;90:7–13.Google Scholar
55.Engstrom, C, Brandstrom, S, Sigvardsson, S, Cloninger, CR, Nylander, PO. Bipolar disorder. III: harm avoidance a risk factor for suicide attempts. Bipolar Disord. 2004;6:130–138.Google Scholar
56.Engstrom, C, Brandstrom, S, Sigvardsson, S, Cloninger, R, Nylander, PO. Bipolar disorder: I. Temperament and character. J Affect Disord. 2004;82:131–134.Google Scholar
57.Perugi, G, Toni, C, Passino, MC, Akiskal, KK, Kaprinis, S, Akiskal, HS. Bulimia nervosa in atypical depression: the mediating role of cyclothymic temperament. J Affect Disord. 2006;92:91–97.Google Scholar
58.Goldberg, JF, Harrow, M, Grossman, LS. Course and outcome in bipolar affective disorder: a longitudinal follow-up study. Am J Psychiatry. 1995;152:379–384.Google Scholar
59.Goldberg, JF, Harrow, M, Grossman, LS. Recurrent affective syndromes in bipolar and unipolar mood disorders at follow-up. Br J Psychiatry. 1995;166:382–385.Google Scholar
60.Keck, PE Jr, McElroy, SL, Strakowski, SM, et al.Twelve-month outcome of patients with bipolar disorder following hospitalization for a manic or mixed episode. Am J Psychiatry. 1998;155:646–652.Google Scholar
61.Strakowski, SM, Keck, PE Jr, McElroy, SL, et al.Twelve-month outcome after a first hospitalization for affective psychosis. Arch Gen Psychiatry. 1998;55:49–55.Google Scholar
62.Dean, BB, Gerner, D, Gerner, RH. A systematic review evaluating health-related quality of life, work impairment, and healthcare costs and utilization in bipolar disorder. Curr Med Res Opin. 2004;20:139–154.CrossRefGoogle ScholarPubMed
63.Martinez-Aran, A, Vieta, E, Torrent, C, et al.Functional outcome in bipolar disorder: the role of clinical and cognitive factors. Bipolar Disord. 2007;9:103–113.Google Scholar
64.Mur, M, Portella, MJ, Martinez-Aran, A, Pifarre, J, Vieta, E. Persistent neuropsychological deficit in euthymic bipolar patients: executive function as a core deficit. J Clin Psychiatry. 2007;68:1078–1086.Google Scholar
65.Daban, C, Martinez-Aran, A, Torrent, C, et al.Specificity of cognitive deficits in bipolar disorder versus schizophrenia. A systematic review. Psychother Psychosom. 2006;75:72–84.Google Scholar
66.Altshuler, LL, Ventura, J, van Gorp, WG, Green, MF, Theberge, DC, Mintz, J. Neurocognitive function in clinically stable men with bipolar I disorder or schizophrenia and normal control subjects. Biol Psychiatry. 2004;56:560–569.Google Scholar
67.Dixon, T, Kravariti, E, Frith, C, Murray, RM, McGuire, PK. Effect of symptoms on executive function in bipolar illness. Psychol Med. 2004;34:811–821.Google Scholar
68.Malhi, GS, Ivanovski, B, Szekeres, V, Olley, A. Bipolar disorder: it's all in your mind? The neuropsychological profile of a biological disorder. Can J Psychiatry. 2004;49:813–819.Google Scholar
69.Torrent, C, Martinez-Aran, A, Daban, C, et al.Cognitive impairment in bipolar II disorder. Br J Psychiatry. 2006;189:254–259.Google Scholar
70.Tabares-Seisdedos, R, Balanza-Martinez, V, Sanchez-Moreno, J, et al.Neurocognitive and clinical predictors of functional outcome in patients with schizophrenia and bipolar I disorder at one-year follow-up. J Affect Disord. 2008;109:286–299.Google Scholar
71.Torrent, C, Martinez-Aran, A, Amann, B, et al.Cognitive impairment in schizoaffective disorder: a comparison with non-psychotic bipolar and healthy subjects. Acta Psychiatr Scand. 2007;116:453–460.Google Scholar
72.Selva, G, Salazar, J, Balanza-Martinez, Vet al.Bipolar I patients with and without a history of psychotic symptoms: do they differ in their cognitive functioning? J Psychiatr Res. 2007;41:265–272.Google Scholar
73.Martinez-Aran, A, Torrent, C, Tabares-Seisdedos, R, et al.Neurocognitive impairment in bipolar patients with and without history of psychosis. J Clin Psychiatry. 2008;69:233–239.Google Scholar
74.Jamison, KR. Suicide and bipolar disorder. J Clin Psychiatry. 2000;61(suppl 9):47–51.Google Scholar
75.Valtonen, HM, Suominen, K, Mantere, O, Leppamaki, S, Arvilommi, P, Isometsa, ET. Prospective study of risk factors for attempted suicide among patients with bipolar disorder. Bipolar Disord. 2006;8(pt 2):576–585.Google Scholar
76.Baldessarini, RJ, Pompili, M, Tondo, L. Suicide in bipolar disorder: risks and management. CNS Spectr. 2006;11:465–471.Google Scholar
77.Balazs, J, Benazzi, F, Rihmer, Z, Rihmer, A, Akiskal, KK, Akiskal, HS. The close link between suicide attempts and mixed (bipolar) depression: implications for suicide prevention. J Affect Disord. 2006;91:133–138.Google Scholar
78.Isometsa, ET, Henriksson, MM, Aro, HM, Heikkinen, ME, Kuoppasalmi, KI, Lonnqvist, JK. Suicide in major depression. Am J Psychiatry. 1994;151(4):530–536.Google Scholar
79.Rihmer, Z, Akiskal, H. Do antidepressants t(h)reat(en) depressives? Toward a clinically judicious formulation of the antidepressant-suicidality FDA advisory in light of declining national suicide statistics from many countries. J Affect Disord. 2006;94:3–13.Google Scholar
80.Akiskal, HS, Benazzi, F, Perugi, G, Rihmer, Z. Agitated “unipolar” depression re-conceptualized as a depressive mixed state: implications for the antidepressant-suicide controversy. J Affect Disord. 2005;85:245–258.CrossRefGoogle ScholarPubMed
81.Rihmer, Z. Suicide risk in mood disorders. Curr Opin Psychiatry. 2007;20:17–22.Google Scholar
82.Maser, JD, Akiskal, HS, Schettler, P. et al.Can temperament identify affectively ill patients who engage in lethal or near-lethal suicidal behavior? A 14-year prospective study. Suicide Life Threat Behav. 2002;32:10–32.Google Scholar
83.Oquendo, MA, Currier, D, Mann, JJ. Prospective studies of suicidal behavior in major depressive and bipolar disorders: what is the evidence for predictive risk factors? Acta Psychiatr Scand. 2006;114:151–158.Google Scholar
84.Simon, NM, Pollack, MH, Ostacher, MJ, et al.Understanding the link between anxiety symptoms and suicidal ideation and behaviors in outpatients with bipolar disorder. J Affect Disord. 2007;97:91–99.Google Scholar
85.Frank, E, Cyranowski, JM, Rucci, P, et al.Clinical significance of lifetime panic spectrum symptoms in the treatment of patients with bipolar I disorder. Arch Gen Psychiatry. 2002;59:905–911.Google Scholar
86.Oquendo, MA, Bongiovi-Garcia, ME, Galfalvy, H, et al.Sex differences in clinical predictors of suicidal acts after major depression: a prospective study. Am J Psychiatry. 2007;164:134–141.Google Scholar
87.Comtois, KA, Russo, JE, Roy-Byrne, P, Ries, RK. Clinicians' assessments of bipolar disorder and substance abuse as predictors of suicidal behavior in acutely hospitalized psychiatric inpatients. Biol Psychiatry. 2004;56:757–763.Google Scholar
88.Cavazzoni, P, Grof, P, Duffy, A, et al.Heterogeneity of the risk of suicidal behavior in bipolar-spectrum disorders. Bipolar Disord. 2007;9:377–385.Google Scholar
89.Hawton, K, Sutton, L, Haw, C, Sinclair, J, Harriss, L. Suicide and attempted suicide in bipolar disorder: a systematic review of risk factors. J Clin Psychiatry. 2005;66:693–704.Google Scholar
90.Williams, JM, Crane, C, Barnhofer, T, Van der Does, AJ, Segal, ZV. Recurrence of suicidal ideation across depressive episodes. J Affect Disord. 2006;91:189–194.Google Scholar
91.Valtonen, H, Suominen, K, Mantere, O, Leppamaki, S, Arvilommi, P, Isometsa, ET. Suicidal ideation and attempts in bipolar I and II disorders. J Clin Psychiatry. 2005;66:1456–1462.Google Scholar
92.Rihmer, Z, Belso, N, Kiss, K. Strategies for suicide prevention. Curr Opin Psychiatry. 2002;15:83–87.Google Scholar
93.Isometsa, E, Henriksson, M, Aro, H, Heikkinen, M, Kuoppasalmi, K, Lonnqvist, J. Suicide in psychotic major depression. J Affect Disord. 1994;31:187–191.Google Scholar
94.Leverich, GS, Altshuler LL, Frye, MA, et al.Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar Network. J Clin Psychiatry. 2003;64:506–515.Google Scholar
95.Leverich, GS, McElroy, SL, Suppes, T, et al.Early physical and sexual abuse associated with an adverse course of bipolar illness. Biol Psychiatry. 2002;51:288–297.Google Scholar
96.Luoma, JB, Martin, CE, Pearson, JL. Contact with mental health and primary care providers before suicide: a review of the evidence. Am J Psychiatry. 2002;159:909–916.Google Scholar
97.Cipriani, A, Pretty, H, Hawton, K, Geddes, JR. Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. Am J Psychiatry. 2005;162:1805–1819.Google Scholar
98.Sachs, GS, Thase, ME, Otto, MW, et al.Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry. 2003;53:1028–1042.Google Scholar
99.Bauer, MS, Wisniewski, SR, Marangell, LB, et al.Are antidepressants associated with new-onset suicidality in bipolar disorder? A prospective study of participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). J Clin Psychiatry. 2006;67:48–55.CrossRefGoogle ScholarPubMed
100.Fountoulakis, KN, Grunze, H, Panagiotidis, P, Kaprinis, G. Treatment of bipolar depression: an update. J Affect Disord. 2007;109:21–34.Google Scholar
101.Fountoulakis, KN, Magiria, S, Siamouli, M, et al.A seven-year follow-up of an extremely refractory bipolar I patient. CNS Spectr. 2007;12:733–734.Google Scholar
102.Fountoulakis, KN, Vieta, E, Sanchez-Moreno, J, Kaprinis, SG, Goikolea, JM, Kaprinis, GS. Treatment guidelines for bipolar disorder: a critical review. J Affect Disord. 2005;86:1–10.Google Scholar
103.Fountoulakis, KN, Vieta, E, Siamouli, M, et al.Treatment of bipolar disorder: a complex treatment for a multi-faceted disorder. Ann Gen Psychiatry. 2007;6:27.Google Scholar
104.Vieta, E, Carne, X. The use of placebo in clinical trials on bipolar disorder: a new approach for an old debate. Psychother Psychosom. 2005;74:10–16.Google Scholar
105.Post, R, Leverich, G, Altshuler, L, Mikalauskas, K. Lithium-discontinuation-induced refractoriness: preliminary observations. Am J Psychiatry. 1992;149:1727.Google Scholar
106. Expert consensus guidelines are released for the treatment of bipolar disorder. Consensus Development Conferences. Am Fam Physician. 1997;55:1447–1449.Google Scholar
107.AACAP: AACAP official action. Practice parameters for the assessment and treatment of children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 1997;36:138–157.Google Scholar
108.Allen, MH, Currier, GW, Hughes, DH, Reyes-Harde, M, Docherty, JP. The Expert Consensus Guideline Series. Treatment of behavioral emergencies. Postgrad Med. 2001;(spec no):1–88.Google Scholar
109.Practice guideline for the treatment of patients with bipolar disorder. Am J Psychiatry. 1994;151:1–36.Google Scholar
110.American Psychiatric Association releases treatment guideline for bipolar disease. Am Fam Physician. 1995;51:1605–1606.Google Scholar
111.American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder [revision]. Am J Psychiatry. 2002;159:1–50.Google Scholar
112.Barreira, P, Duckworth, K, Goff, D, Flannery, RB Jr.Clinical practice guidelines: the Massachusetts experience in psychiatry. Harv Rev Psychiatry. 1999;7:230–232.Google Scholar
113.Dennehy, EB. Guidelines for treatment of bipolar disorder. Curr Psychiatry Rep. 2000;2:316–321.Google Scholar
114.Gilbert, DA, Altshuler, KZ, Rago, WV, et al.Texas Medication Algorithm Project: definitions, rationale, and methods to develop medication algorithms. J Clin Psychiatry. 1998;59:345–351.Google Scholar
115.Goldberg, JF. Treatment guidelines: current and future management of bipolar disorder. J Clin Psychiatry. 2000;61(suppl 13):12–18.Google Scholar
116.Goodwin, G, Bourgeois, M, Conti, L. Treatment of bipolar depressive mood disorders: algorithms for pharmacotherapy. Int J Psychiatry Clin Pract. 1997;1:S9–S12.Google Scholar
117.Goodwin, GM. Evidence-based guidelines for treating bipolar disorder: recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2003;17:149–173.Google Scholar
118.Grunze, H, Kasper, S, Goodwin, G, et al.World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of bipolar disorders. Part I: Treatment of bipolar depression. World J Biol Psychiatry. 2002;3:115–124.CrossRefGoogle ScholarPubMed
119.Grunze, H, Kasper, S, Goodwin, G, et al.The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders, Part II: Treatment of Mania. World J Biol Psychiatry. 2003;4:5–13.Google Scholar
120.Jobson, K. International Psychopharmacology Algorithm Project: algorithms in psychopharmacology. Int J Psychiatry Clin Pract. 1997;1:S3–S8.CrossRefGoogle ScholarPubMed
121.Kusumakar, V, Yatham, L, Parikh, S. Bipolar disorder: a summary of clinical issues and treatment options. Halifax, Canada: CANMAT Monograph; 1997.Google Scholar
122.Licht, RW, Vestergaard, P, Kessing, LV, Larsen, JK, Thomsen, PH. Psychopharmacological treatment with lithium and antiepileptic drugs: suggested guidelines from the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark. Acta Psychiatr Scand Suppl. 2003;108:1–22.Google Scholar
123.McClellan, J, Werry, J. Practice parameters for the assessment and treatment of children and adolescents with bipolar disorder. American Academy of Child and Adolescent Psychiatry. J Am Acad Child Adolesc Psychiatry. 1997;36:157S–176S.Google Scholar
124.Montgomery, DB. ECIMP Consensus Meeting March 2000 Nice: guidelines for investigating efficacy in bipolar disorder. European College of Neuropsychopharmacology. Fur Neuropsychopharmacol. 2001;11:79–88.Google Scholar
125.Rush, AJ, Crismon, ML, Kashner, TM, et al.Texas Medication Algorithm Project, phase 3 (TMAP-3): rationale and study design. J Clin Psychiatry. 2003;64:357–369.Google Scholar
126.Rush, AJ, Rago, WV, Crismon, ML, et al.Medication treatment for the severely and persistently mentally ill: the Texas Medication Algorithm Project. J Clin Psychiatry. 1999;60:284–291.Google Scholar
127.Sachs, GS, Printz, DJ, Kahn, DA, Carpenter, D, Docherty, JP. The Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder 2000. Postgrad Med. 2000;spec no:1–104.Google Scholar
128.Suppes, T, Calabrese, J, Mitchell, P, Pazzaglia, P, Potter, W, Zarin, D. Algorithms for the treatment of bipolar manic-depressive illness. Psychopharmacol Bull. 1995;31:469–474.Google Scholar
129.Suppes, T, Dennehy, EB, Swann, AC, et al.Report of the Texas Consensus Conference Panel on medication treatment of bipolar disorder 2000. J Clin Psychiatry. 2002;63:288–299.Google Scholar
130.Suppes, T, Rush, AJ, Dennehy, EB, et al.Texas Medication Algorithm Project, phase 3 (TMAP-3): clinical results for patients with a history of mania. J Clin Psychiatry. 2003;64:370–382.Google Scholar
131.Suppes, T, Swann, AC, Dennehy, EB, et al.Texas Medication Algorithm Project: development and feasibility testing of a treatment algorithm for patients with bipolar disorder. J Clin Psychiatry. 2001;62:439–447.Google Scholar
132.O'Dowd, A. NICE issues new guidance to improve the treatment of bipolar disorder. BMJ. 2006;333:220.Google Scholar
133.Yatham, LN, Kennedy, SH, O'Donovan, C, et al.Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: consensus and controversies. Bipolar Disord. 2005;7:5–69.Google Scholar
134.Yatham, LN, Kennedy, SH, O'Donovan, C, et al.Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: update 2007. Bipolar Disord. 2006;8:721–739.Google Scholar
135.Grunze, H, Kasper, S, Goodwin, G, Bowden, C, Moller, HJ. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders, part III: maintenance treatment. World J Biol Psychiatry. 2004;5:120–135.Google Scholar
136.Frances, A, Docherty, J, Kahn, D. The Expert Consensus Guideline Series: treatment of bipolar disorder. J Clin Psychiatry. 1996;57:1–88.Google Scholar
137.Bauer, MS, Callahan, AM, Jampala, C, et al.Clinical practice guidelines for bipolar disorder from the Department of Veterans Affairs. J Clin Psychiatry. 1999;60:9–21.Google Scholar
138.Hirschfeld, RMA. Guideline Watch for the Practice Guideline for the Treatment of Patients With Bipolar Disorder. 2nd ed. Arlington, Va: American Psychiatric Association; 2005.Google Scholar
139.Bowden, CL, Brugger, AM, Swann, AC, et al.Efficacy of divalproex vs lithium and placebo in the treatment of mania. The Depakote Mania Study Group. JAMA. 1994;271:918–924.Google Scholar
140.Bowden, CL, Grunze, H, Mullen, J, et al.A randomized, double-blind, placebo-controlled efficacy and safety study of quetiapine or lithium as monotherapy for mania in bipolar disorder. J Clin Psychiatry. 2005;66:111–121.Google Scholar
141.Kushner, SF, Khan, A, Lane, R, Olson, WH. Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trials. Bipolar Disord. 2006;8:15–27.Google Scholar
142.Keck, PE Jr, Sanchez, R, Torbeyns, A, Marcus, R, McQuade, R, Forbes, A. Aripiprazole monotherapy in the treatment of acute bipolar I mania: a randomized placebo- and lithium-controlled study (Study CN138-135). Paper presented at: Annual Meeting of the American Psychiatric Association; May 19-24, 2007. San Diego, Calif.Google Scholar
143.Young, AH, McElroy, H, Chang, W, Olausson, B, Paulsson, B, Brecher, M. A double-blind, placebo-controlled study with acute and continuation phase of quetiapine in adults with bipolar depression (EMBOLDEN i). Paper presented at: Biennial Conference of the International Society for Bipolar Disorders; January 27-28, 2008. Delhi, India.Google Scholar
144.Kane, JM, Quitkin, FM, Rifkin, A, Ramos-Lorenzi, JR, Nayak, DD, Howard, A. Lithium carbonate and imipramine in the prophylaxis of unipolar and bipolar II illness: a prospective, placebo-controlled comparison. Arch Gen Psychiatry. 1982;39:1065–1069.Google Scholar
145.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;57:481–489.Google Scholar
146.Bowden, CL, Calabrese, JR, Sachs, G, et al.A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Arch Gen Psychiatry. 2003;60:392–400.Google Scholar
147.Calabrese, JR, Bowden, CL, Sachs, G, et al.A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. J Clin Psychiatry. 2003;64:1013–1024.Google Scholar
148.Calabrese, JR, Goldberg, JF, Ketter, TA, et al.Recurrence in bipolar I disorder: a post hoc analysis excluding relapses in two double-blind maintenance studies. Biol Psychiatry. 2006;59:1061–1064.Google Scholar
149.Goodwin, GM, Bowden, CL, Calabrese, JR, et al.A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder. J Clin Psychiatry. 2004;65:432–441.Google Scholar
150.Goodwin, GM. Recurrence of mania after lithium withdrawal. Implications for the use of lithium in the treatment of bipolar affective disorder. Br J Psychiatry. 1994;64:149–152.CrossRefGoogle Scholar
151.Baldessarini, RJ, Tondo, L, Davis, P, Pompili, M, Goodwin, FK, Hennen, J. Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review. Bipolar Disord. 2006;8:625–639.Google Scholar
152.Gonzalez-Pinto, A, Mosquera, F, Alonso, M, et al.Suicidal risk in bipolar I disorder patients and adherence to long-term lithium treatment. Bipolar Disord. 2006;8:618–624.Google Scholar
153.Keck, PE Jr, Marcus, R, Tourkodimitris, S, et al.A placebo-controlled, double-blind study of the efficacy and safety of aripiprazole in patients with acute bipolar mania. Am J Psychiatry. 2003;160:1651–1658.Google Scholar
154.Sachs, G, Sanchez, R, Marcus, R, et al.Aripiprazole in the treatment of acute manic or mixed episodes in patients with bipolar I disorder: a 3-week placebo-controlled study. J Psychopharmacol. 2006;20:536–546.Google Scholar
155.Tohen, M, Sanger, TM, McElroy, SL, et al.Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group. Am J Psychiatry. 1999;156:702–709.CrossRefGoogle ScholarPubMed
156.Tohen, M, Jacobs, TG, Grundy, SL, et al.Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group. Arch Gen Psychiatry. 2000;57:841–849.Google Scholar
157.Tohen, M, Kryzhanovskaya, L, Carlson, G, et al.Olanzapine versus placebo in the treatment of adolescents with bipolar mania. Am J Psychiatry. 2007;164:1547–1556.Google Scholar
158.McIntyre, RS, Brecher, M, Paulsson, B, Huizar, K, Mullen, J. Quetiapine or haloperidol as monotherapy for bipolar mania–a 12-week, double-blind, randomised, parallel-group, placebo-controlled trial. Eur Neuropsychopharmacol. 2005;15:573–585.Google Scholar
159.Gopal, S, Steffens, DC, Kramer, ML, Olsen, MK. Symptomatic remission in patients with bipolar mania: results from a double-blind, placebo-controlled trial of risperidone monotherapy. J Clin Psychiatry. 2005;66:1016–1020.Google Scholar
160.Hirschfeld, RM, Keck, PE Jr, Kramer, M, et al.Rapid antimanic effect of risperidone monotherapy: a 3-week multicenter, double-blind, placebo-controlled trial. Am J Psychiatry. 2004;161:1057–1065.Google Scholar
161.Khanna, S, Vieta, E, Lyons, B, Grossman, F, Eerdekerts, M, Kramer, M. Risperidone in the treatment of acute mania: double-blind, placebo-controlled study. Br J Psychiatry. 2005;187:229–234.Google Scholar
162.Smulevich, AB, Khanna, S, Eerdekens, M, Karcher, K, Kramer, M, Grossman, F. Acute and continuation risperidone monotherapy in bipolar mania: a 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and halo-peridol. Eur Neuropsychopharmacol. 2005;15:75–84.Google Scholar
163.Keck, PE Jr.Versiani, M, Potkin, S, West, SA, Giller, E, Ice, K. Ziprasidone in the treatment of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized trial. Am J Psychiatry. 2003;160:741–748.Google Scholar
164.Potkin, SG, Keck, PE Jr, Segal, S, Ice, K, English, P. Ziprasidone in acute bipolar mania: a 21-day randomized, double-blind, placebo-controlled replication trial. J Clin Psychopharmacol. 2005;25:301–310.Google Scholar
165.Tohen, M, Vieta, E, Calabrese, J. et al.Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry. 2003;60:1079–1088.Google Scholar
166.Calabrese, JR, Keck, PE Jr, Macfadden, W, et al.A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry. 2005;162:1351–1360.Google Scholar
167.Thase, ME, Macfadden, W, Weisler, RH, et al.Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study). J Clin Psychopharmacol. 2006;26:600–609.Google Scholar
168.McQuade, RD, Sanchez, R, Marcus, R, et al.Aripiprazole for relapse prevention in bipolar disorder: a 26-week placebo-controlled study. Int J Neuropsychopharmacol. 2004;7:s161.Google Scholar
169.Keck, PE Jr, Calabrese, JR, McIntyre, RS, et al.Aripiprazole monotherapy for maintenance therapy in bipolar I disorder: a 100-week, double-blind study versus placebo. J Clin Psychiatry. 2007;68:1480–1491.Google Scholar
170.Tohen, M, Calabrese, JR, Sachs, GS, et al.Randomized, placebo-controlled trial of olanzapine as maintenance therapy in patients with bipolar I disorder responding to acute treatment with olanzapine. Am J Psychiatry. 2006;163:247–256.Google Scholar
171.Altamura, AC, Mundo, E, Dell'Osso, B, Tacchini, G, Buoli, M, Calabrese, JR. Quetiapine and classical mood stabilizers in the long-term treatment of Bipolar Disorder: a 4-year follow-up naturalistic study. J Affect Disord. 2008;110:135–141.Google Scholar
172.Altamura, AC, Salvadori, D, Madaro, D, Santini, A, Mundo, E. Efficacy and tolerability of quetiapine in the treatment of bipolar disorder: preliminary evidence from a 12-month open-label study. J Affect Disord. 2003;76:267–271.Google Scholar
173.Shopsin, B, Gershon, S, Thompson, H, Collins, P. Psychoactive drugs in mania. A controlled comparison of lithium carbonate, chlorpromazine, and haloperidol. Arch Gen Psychiatry. 1975;32:34–42.Google Scholar
174.Tohen, M, Goldberg, JF, Gonzalez-Pinto Arrillaga, AM, et al.A 12-week, double-blind comparison of olanzapine vs haloperidol in the treatment of acute mania. Arch Gen Psychiatry. 2003;60:1218–1226.Google Scholar
175.Zarate, CA Jr, Tohen, M. Double-blind comparison of the continued use of anti-psychotic treatment versus its discontinuation in remitted manic patients. Am J Psychiatry. 2003;60:1218–1226.Google Scholar
176.Pope, HG Jr, McElroy, SL, Keck, PE Jr, Hudson, JI. Valproate in the treatment of acute mania. A placebo-controlled study. Arch Gen Psychiatry. 1991;48:62–68.Google Scholar
177.Bowden, CL, Swann, AC, Calabrese, JR, et al.A randomized, placebo-controlled, multicenter study of divalproex sodium extended release in the treatment of acute mania. J Clin Psychiatry. 2006;67:1501–1510.Google Scholar
178.Weisler, RH, Kalali, AH, Ketter, TA. A multicenter, randomized, double-blind, place-bo-controlled trial of extended-release carbamazepine capsules as monotherapy for bipolar disorder patients with manic or mixed episodes. J Clin Psychiatry. 2004;65:478–484.Google Scholar
179.Weisler, RH, Hirschfeld, R, Cutler, AJ, et al.Extended-release carbamazepine capsules as monotherapy in bipolar disorder: pooled results from two randomised, double-blind, placebo-controlled trials. CNS Drugs. 2006;20:219–231.Google Scholar
180.Weisler, RH, Keck, PE Jr, Swann, AC, Cutler, AJ, Ketter, TA, Kalali, AH. Extended-release carbamazepine capsules as monotherapy for acute mania in bipolar disorder: a multicenter, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2005;66:323–330.Google Scholar
181.Davis, LL, Bartolucci, A, Petty, F. Divalproex in the treatment of bipolar depression: a placebo-controlled study. J Affect Disord. 2005;85:259–266.Google Scholar
182.Ghaemi, SN, Gilmer, WS, Goldberg, JF, et al.Divalproex in the treatment of acute bipolar depression: a preliminary dquble-blind, randomized, placebo-controlled pilot study. J Clin Psychiatry. 2007;68:1840–1844.Google Scholar
183.Ballenger, JC, Post, RM. Carbamazepine in manic-depressive illness: a new treatment. Am J Psychiatry. 1980;137:782–790.Google Scholar
184.Goldsmith, DR, Wagstaff, AJ, Ibbotson, T, Perry, CM. Lamotrigine: a review of its use in bipolar disorder. Drugs. 2003;63:2029–2050.Google Scholar
185.Okuma, T, Inanaga, K, Otsuki, S, et al.A preliminary double-blind study on the efficacy of carbamazepine in prophylaxis of manic-depressive illness. Psychopharmacology (Berl). 1981;73:95–96.Google Scholar
186.Calabrese, JR, Suppes, T, Bowden, CL, et al.A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Larnictal 614 Study Group. J Clin Psychiatry. 2000;61:841–850.Google Scholar
187.Oulis, P, Karapoulios, E, Kouzoupis, AV, et al.Oxcarbazepine as monotherapy of acute mania in insufficiently controlled type-1 diabetes mellitus: a case-report. Ann Gen Psychiatry. 2007;6:25.Google Scholar
188.Post, RM, Altshuler, LL, Frye, MA, et al.Rate of switch in bipolar patients prospectively treated with second-generation antidepressants as augmentation to mood stabilizers. Bipolar Disord. 2001;3:259–265.Google Scholar
189.Post, RM, Altshuler, LL, Leverich, GS, et al.Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline. Br J Psychiatry. 2006;189:124–131.Google Scholar
190.Leverich, GS, Altshuler, LL, Frye, MA, et al.Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry. 2006;163:232–239.Google Scholar
191.Bottlender, R, Rudolf, D, Strauss, A, Moller, HJ. Mood-stabilisers reduce the risk of developing antidepressant-induced maniform states in acute treatment of bipolar I depressed patients. J Affect Disord. 2001;63:79–83.Google Scholar
192.Cohn, JB, Collins, G, Ashbrook, E, Wernicke, JF. A comparison of fluoxetine imipramine and placebo in patients with bipolar depressive disorder. Int Clin Psychopharmacol. 1989;4:313–322.Google Scholar
193.Amsterdam, JD, Garcia-Espana, F, Fawcett, J, et al.Efficacy and safety of fluoxetine in treating bipolar II major depressive episode. J Clin Psychopharmacol. 1998;18:435–440.Google Scholar
194.Amsterdam, JD, Shults, J. Comparison of fluoxetine, olanzapine, and combined fluoxetine plus olanzapine initial therapy of bipolar type I and type II major depression-lack of manic induction. J Affect Disord. 2005;87:121–130.Google Scholar
195.Amsterdam, JD, Shults, J. Fluoxetine monotherapy of bipolar type II and bipolar NOS major depression: a double-blind, placebo-substitution, continuation study. Int Clin Psychopharmacol. 2005;20:257–264.Google Scholar
196.Brown, EB, McElroy, SL, Keck, PE Jr, et al.A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression. J Clin Psychiatry. 2006;67:1025–1033.Google Scholar
197.Keck, PE Jr, Corya, SA, Altshuler, LL, et al.Analyses of treatment-emergent mania with olanzapine/fluoxetine combination in the treatment of bipolar depression. J Clin Psychiatry. 2005;66:611–616.Google Scholar
198.Sachs, GS, Nierenberg, AA, Calabrese, JR, et al.Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356:1711–1722.Google Scholar
199.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;158:906–912.Google Scholar
200.Zarate, CA Jr, Singh, JB, Carlson, PJ, et al.Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study. Bipolar Disord. 2007;9:561–570.Google Scholar
201.Kulkarni, J, Garland, KA, Scaffidi, A, et al.A pilot study of hormone modulation as a new treatment for mania in women with bipolar affective disorder. Psychoneuroe ndocrinology. 2006;31:543–547.Google Scholar
202.Sachs, GS, Grossman, F, Ghaemi, SN, Okamoto, A, Bowden, CL. Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety. Am J Psychiatry. 2002;159:1146–1154.Google Scholar
203.Garfinkel, PE, Stancer, HC, Persad, E. A comparison of haloperidol, lithium carbonate and their combination in the treatment of mania. J Affect Disord. 1980;2:279–288.Google Scholar
204.Yatham, LN, Grossman, F, Augustyns, I, Vieta, E, Ravindran, A. Mood stabilisers plus risperidone or placebo in the treatment of acute mania. International, double-blind, randomised controlled trial. Br J Psychiatry. 2003;182:141–147.Google Scholar
205.Tohen, M, Chengappa, KN, Suppes, T, et al.Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy. Arch Gen Psychiatry. 2002;59:62–69.Google Scholar
206.Sachs, G, Chengappa, KN, Suppes, T, et al.Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study. Bipolar Disord. 2004;6:213–223.Google Scholar
207.Yatham, LN, Paulsson, B, Mullen, J, Vagero, AM. Quetiapine versus placebo in combination with lithium or divalproex for the treatment of bipolar mania. J Clin Psychopharmacol. 2004;24:599–606.Google Scholar
208.Klein, E, Bental, E, Lerer, B, Belmaker, RH. Carbamazepine and haloperidol v placebo and haloperidol in excited psychoses. A controlled study. Arch Gen Psychiatry. 1984;4:165–170.Google Scholar
209.Tohen, M, Chengappa, KN, Suppes, T, et al.Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone. Br J Psychiatry. 2004;184:337–345.Google Scholar
210.Small, JG, Klapper, MH, Marhenke, JD, Milstein, V, Woodham, GC, Kellams, JJ. Lithium combined with carbamazepine or haloperidol in the treatment of mania. Psychopharmacol Bull. 1995;31:265–272.Google Scholar
211.Lenox, RH, Newhouse, PA, Creelman, WL, Whitaker, TM. Adjunctive treatment of manic agitation with lorazepam versus haloperidol: a double-blind study. J Clin Psychiatry. 1992;53:47–52.Google Scholar
212.Vieta, E, Eggens, I, Persson, I, Paulsson, B, Brecher, M. Efficacy and safety of quetiapine in combination with lithium or divalproex as maintenance treatment for patients with bipolar I disorder: results from an international, multicenter, randomized, double-blind, parallel-group trial (Trial 126). Paper presented at: 20th Annual Congress of the European College of Neuropsychopharmocology; October 13-17, 2007; Vienna, Austria.Google Scholar
213.Weisler, R, Dunn, J, English, P. Adjunctive ziprasidone for acute bipolar mania: randomized, placebo-controlled trial. Paper presented at: Annual International Forum on Mood and Anxiety Disorders; November 19-21, 2003. Monte Carlo, Monaco.Google Scholar
214.Schaffer, A, Zuker, P, Levitt, A. Randomized, double-blind pilot trial comparing lamotrigine versus citalopram for the treatment of bipolar depression. J Affect Disord. 2006;96:95–99.Google Scholar
215.Chou, JC, Czobor, P, Charles, O, et al.Acute mania: haloperidol dose and augmentation with lithium or lorazepam. J Clin Psychopharmacol. 1999;19:500–505.Google Scholar
216.Muller-Oerlinghausen, B, Retzow, A, Henn, FA, Giedke, H, Walden, J. Valproate as an adjunct to neuroleptic medication for the treatment of acute episodes of mania: a prospective, randomized, double-blind, placebo-controlled, multicenter study. European Valproate Mania Study Group. J Clin Psychopharmacol. 2000;20:195–203.Google Scholar
217.Del Bello, MP, Schwiers, ML, Rosenberg, HL, Strakowski, SM. A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania. J Am Acad Child Adolesc Psychiatry. 2002;41:1216–1223.Google Scholar
218.Gyulai, L, Bowden, CL, McElroy, SL, et al.Maintenance efficacy of divalproex in the prevention of bipolar depression. Neuropsychopharmacol. 2003;28:1374–1382.Google Scholar
219.Denicoff, KD, Smith-Jackson, EE, Disney, ER, Ali, SO, Leverich, GS, Post, RM. Comparative prophylactic efficacy of lithium, carbamazepine, and the combination in bipolar disorder. J Clin Psychiatry. 1997;58:470–478.Google Scholar
220.Ball, JR, Mitchell, PB, Corry, JC, Skillecorn, A, Smith, M, Malhi, GS. A randomized controlled trial of cognitive therapy for bipolar disorder: focus on long-term change. J Clin Psychiatry. 2006;67:277–286.Google Scholar
221.Miklowitz, DJ, Otto, MW, Frank, E, et al.Psychosocial treatments for bipolar depression: a 1-year randomized trial from the Systematic Treatment Enhancement Program. Arch Gen Psychiatry. 2007;64:419–426.Google Scholar
222.Colom, F, Vieta, E, Sanchez-Moreno, J, et al.Stabilizing the stabilizer: group psychoeducation enhances the stability of serum lithium levels. Bipolar Disord. 2005;7:32–36.Google Scholar
223.Scott, J, Colom, F, Vieta, E. A meta-analysis of relapse rates with adjunctive psychological therapies compared to usual psychiatric treatment for bipolar disorders. Int J Neuropsychopharmacol. 2007;10:123–129.Google Scholar
224.Reinares, M, Vieta, E, Colom, F, et al.Impact of a psychoeducational family intervention on caregivers of stabilized bipolar patients. Psychother Psychosom. 2004;73:312–319.Google Scholar
225.Colom, F, Vieta, E, Sanchez-Moreno, J, et al.Psychoeducation in bipolar patients with comorbid personality disorders. Bipolar Disord. 2004;6:294–298.Google Scholar
226.Colom, F, Vieta, E, Reinares, M, et al.Psychoeducation efficacy in bipolar disorders: beyond compliance enhancement. J Clin Psychiatry. 2003;64:1101–1105.Google Scholar
227.Colom, F, Vieta, E, Martinez-Aran, A, et al.A randomized trial on the efficacy of group psychoeducation in the prophylaxis of recurrences in bipolar patients whose disease is in remission. Arch Gen Psychiatry. 2003;60:402–407.CrossRefGoogle ScholarPubMed
228.Daly, JJ, Prudic, J, Devanand, DP, et al.ECT in bipolar and unipolar depression: differences in speed of response. Bipolar Disord. 2001;3:95–104.Google Scholar
229.Small, JG, Klapper, MH, Kellams, JJ, et al.Electroconvulsive treatment compared with lithium in the management of manic states. Arch Gen Psychiatry. 1988;45:727–732.Google Scholar
230.Sikdar, S, Kulhara, P, Avasthi, A, Singh, H. Combined chlorpromazine and electroconvulsive therapy in mania. Br J Psychiatry. 1994;164:806–810.Google Scholar
231.Dolberg, OT, Dannon, PN, Schreiber, S, Grunhaus, L. Transcranial magnetic stimulation in patients with bipolar depression: a double blind, controlled study. Bipolar Disord. 2002;4:94–95.Google Scholar
232.Nahas, Z, Kozel, FA, Li, X, Anderson, B, George, MS. Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy. Bipolar Disord. 2003;5:40–47.Google Scholar
233.Saba, G, Rocamora, JF, Kalalou, K, et al.Repetitive transcranial magnetic stimulation as an add-on therapy in the treatment of mania: a case series of eight patients. Psychiatry Res. 2004;128:199–202.Google Scholar
234.Goldberg, JF, Allen, MH, Miklowitz, DA, et al.Suicidal ideation and pharmacotherapy among STEP-BD patients. Psychiatr Serv. 2005;56:1534–1540.Google Scholar
235.Goldberg, JF, Perlis, RH, Ghaemi, SN, et al.Adjunctive antidepressant use and symptomatic recovery among bipolar depressed patients with concomitant manic symptoms: findings from the STEP-BD. Am J Psychiatry. 2007;164:1348–1355.Google Scholar
236.Schneck, CD, Miklowitz, DJ, Miyahara, S, et al.The prospective course of rapid-cycling bipolar disorder: findings from the STEP-BD. Am J Psychiatry. 2008.Google Scholar
237.Truman, CJ, Goldberg, JF, Ghaemi, SN, et al.Self-reported history of manic/hypomanic switch associated with antidepressant use: data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). J Clin Psychiatry. 2007;68:1472–1479.Google Scholar
238.Ghaemi, SN, Hsu, DJ, Thase, ME, Wisniewski, SR, Nierenberg, AA, Miyahara, S, Sachs, G. Pharmacological Treatment Patterns at Study Entry for the First 500 STEP-BD Participants. Psychiatr Serv. 2006;57:660–665.Google Scholar
239.Miklowitz, DJ, Otto, MW, Frank, E, et al.Intensive psychosocial intervention enhances functioning in patients with bipolar depression: results from a 9-month randomized controlled trial. Am J Psychiatry. 2007;164:1340–1347.Google Scholar
240.Nierenberg, AA, Ostacher, MJ, Calabrese, JR, et al.Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone. Am J Psychiatry. 2006;163:210–216.Google Scholar