Bipolar Disorders: Mixed States, Rapid-Cycling, and Atypical Forms

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358 R. W. Baker et al.50% reduction in YMRS, were 43% on risperidone and 24% on placebo (P
359 Use of atypical antipsychotic agentsZajecka et al., 2002; Tohen et al., 2003a). Olanzapine has proven relatively free ofthe depressive symptom worsening and extrapyramidal side-effects that limit theusefulness of conventional antipsychotic agents.Two placebo-controlled studies of olanzapine monotherapy for acute maniahave been published (Tohen et al., 1999, 2000) and one for addition to treatmentwith valproate or lithium (Tohen et al., 2002b).A 3-week study compared olanzapine 5–20 mg/day (n ¼ 70) to placebo (n ¼ 66)for inpatients in acute manic or mixed episodes (Tohen et al., 1999). Olanzapinetreatedpatients had 36% mean reduction in YMRS, superior to 18% meanimprovement on placebo. Response rates, defined as 50% or greater YMRSimprovement, were 48.6% for olanzapine-treated patients and 24.2% for placebotreatedpatients. Efficacy was consistent across psychotic and non-psychoticsubgroups: interaction P ¼ 0.880. Interaction was also non-significant (P ¼ 0.998)for manic versus mixed subgroups. In this case, the advantage of olanzapine overplacebo was evident for the manic group (37% versus 16% YMRS improvement),but in the mixed group YMRS reduction on olanzapine averaged 28% versus 25%on placebo. Interaction was likely non-significant because so few mixed patientswere enrolled in this study: there were only 12 per treatment group. MeanHamilton Depression ratings improved similarly in olanzapine (23%) and placebo(21%) groups. The 39% discontinuation rate in the olanzapine group was significantlylower than the 65% discontinuation rate on placebo. Change in extrapyramidalsymptom ratings (Simpson-Angus and Barnes Akathisia scales) did notdiffer between treatment groups.A second trial (Tohen et al., 2000), this time of 4 weeks’ duration, comparedolanzapine 5–20 mg/day (n ¼ 55) to placebo (n ¼ 60) for inpatients in acute manicor mixed episodes. The 51% mean reduction in YMRS during olanzapine treatmentwas superior to the 28% mean improvement on placebo. Response rates,defined as an individual’s mania rating improvement of 50% or more, were 65%on olanzapine versus 43% on placebo (P ¼ 0.02). In this study, olanzapine’sadvantage was particularly evident in psychotic patients (mean YMRS reductionof 52% versus 13% on placebo; in non-psychotic patients, mean improvementswere 51% and 44%). The test of interaction was nearing significance (P ¼ 0.110);this finding is discrepant from other available studies, which point to olanzapineefficacy as great or greater among non-psychotic than psychotic patients; it mayreflect the particularly large improvement on placebo for non-psychotic individualsin this particular trial. In this study, the efficacy of olanzapine was consistentacross mixed and manic episodes (interaction P ¼ 0.706). Mean HamiltonDepression ratings trended to superior improvement on olanzapine (45%) comparedto placebo (28%). The 32% discontinuation rate in the olanzapine groupwas significantly lower than the 58% discontinuation rate on placebo. Change in
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Bipolar DisordersMixed States, Rapi
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ContentsList of contributorsPreface
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ContributorsValadeta Ajdacic PhDPsy
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ixList of contributorsAlexia E. Kou
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PrefaceBipolar disorders have a lon
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2 A. Marneros and F. K. Goodwinold
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4 A. Marneros and F. K. GoodwinFig.
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6 A. Marneros and F. K. GoodwinThe
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8 A. Marneros and F. K. GoodwinFig.
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10 A. Marneros and F. K. GoodwinFig
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12 A. Marneros and F. K. Goodwinit
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16 A. Marneros and F. K. Goodwin(19
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18 A. Marneros and F. K. GoodwinBip
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20 A. Marneros and F. K. GoodwinFre
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22 A. Marneros and F. K. Goodwinons
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26 A. Marneros and F. K. Goodwinbou
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28 A. Marneros and F. K. GoodwinAno
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30 A. Marneros and F. K. GoodwinTab
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32 A. Marneros and F. K. GoodwinBip
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38 A. Marneros and F. K. GoodwinAki
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40 A. Marneros and F. K. GoodwinDil
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42 A. Marneros and F. K. GoodwinMar
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44 A. Marneros and F. K. GoodwinPri
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46 G. Perugi and H. S. AkiskalTable
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50 G. Perugi and H. S. AkiskalDepre
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52 G. Perugi and H. S. Akiskalwith
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54 G. Perugi and H. S. Akiskal3020.
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59 Longitudinal perspective of mixe
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3Rapid-cycling bipolar disorder1 2O
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63 Rapid-cycling bipolar disorderPs
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65 Rapid-cycling bipolar disorderOn
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67 Rapid-cycling bipolar disorderBr
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69 Rapid-cycling bipolar disorderin
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71 Rapid-cycling bipolar disorderLa
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73 Rapid-cycling bipolar disorderre
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75 Rapid-cycling bipolar disorderCo
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77 Rapid-cycling bipolar disorderDe
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79 Rapid-cycling bipolar disorderan
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81 Rapid-cycling bipolar disorderTa
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83 Rapid-cycling bipolar disorderRE
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85 Rapid-cycling bipolar disorderJo
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87 Rapid-cycling bipolar disorderde
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89 Bipolar I and bipolar II: a dich
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101 Bipolar I and bipolar II: a dic
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5Recurrent brief depression as an i
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111 Recurrent brief depressionRecur
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113 Recurrent brief depressionbeen
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115 Recurrent brief depressioncorre
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117 Recurrent brief depressionThere
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Chronic 4.8 18.2 9.1 10 NCRapid-cyc
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121 Recurrent brief depressionTable
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123 Recurrent brief depressionPreva
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125 Recurrent brief depressionWe fo
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127 Recurrent brief depressionREFER
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129 Recurrent brief depressionMarne
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6Atypical depression and its relati
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133 Atypical depression and bipolar
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7Agitated depression: spontaneous a
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159 Agitated depression: spontaneou
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8Schizoaffective mixed statesAndrea
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189 Schizoaffective mixed statescon
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191 Schizoaffective mixed stateswas
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193 Schizoaffective mixed statesUni
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195 Schizoaffective mixed statesTab
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197 Schizoaffective mixed statesday
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199 Schizoaffective mixed statesTot
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201 Schizoaffective mixed statesBip
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203 Schizoaffective mixed statesThe
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205 Schizoaffective mixed statesMar
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9Acute and transient psychotic diso
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209 Acute and transient psychotic d
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Table 9.10 (cont.)ATPD(n ¼ 39)Bipo
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Table 9.11 (cont.)Bipolar affective
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Table 9.14b Significant differences
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10Bipolar disorder in children and
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239 Bipolar disorder in children an
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Pellegrini et al. (1986) 16 23 (7-1
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253 Atypical features of bipolarity
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12Comorbidity in mixed states and r
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265 Comorbidity in mixed states and
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13Challenges in the genetics of bip
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279 Challenges in the genetics of b
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Table 13.1 Proportion of first-degr
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Table 13.3 Summary of recent bipola
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13q32 = 3.321q22 = 3.6Liu, C.et al.
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Page 321 and 322: 307 Challenges in the genetics of b
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Page 325 and 326: 14Biological aspects of rapid cycli
Page 327 and 328: 313 Rapid cycling and mixed statesa
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Page 331 and 332: 317 Rapid cycling and mixed statesi
Page 333 and 334: 319 Rapid cycling and mixed statesC
Page 335 and 336: 321 Rapid cycling and mixed statesJ
Page 337 and 338: 323 Rapid cycling and mixed statesW
Page 339 and 340: 325 The treatment of bipolar mixed
Page 367 and 368: 16The use of atypical antipsychotic
Page 369 and 370: 355 Use of atypical antipsychotic a
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Page 383 and 384: 17Investigational strategies: treat
Page 385 and 386: 371 Investigational strategiesBIPOL
Page 387 and 388: 373 Investigational strategiesinsta
Page 389 and 390: 375 Investigational strategiesWhat
Page 391 and 392: 377 Investigational strategiesTable
Page 393 and 394: 379 Investigational strategiescateg
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Page 397 and 398: 383 Investigational strategies2. Th
Page 399 and 400: 385 Investigational strategiesSachs
Page 401 and 402: 387 Indexclinical course and outcom
Page 403 and 404: 389 Indexdepressive mixed states 51
Page 405 and 406: 391 IndexLange, J. 163learning disa
Page 407 and 408: 393 Indexpsychopharmacological revo
Page 409: 395 Indexmania, acute 334mixed stat
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Bipolar Disorders: Mixed States, Rapid-Cycling, and Atypical Forms

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