Page 24 - e-book CPG - Bipolar Disorder (full 92 pg) (1)
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     CLINICAL PRACTICE GUIDELINES              MANAGEMENT OF BIPOLAR DISORDER (2ND ED.)
             Phases of BD         Mania/hypomania with   Depression with mixed
                                  mixed features      features
             Acute episode
                First-line
                    Monotherapy   Olanzapine, aripiprazole,   Lurasidone, olanzapine,
                                  asenapine, paliperidone,    quetiapine, valproate
                    Combination therapy   Olanzapine + valproate   Lurasidone + valproate
                                  Olanzapine + lithium   Lurasidone + lithium
                                  Quetiapine + lithium   Olanzapine + valproate
                                  Quetiapine + valproate   Olanzapine + lithium
                                  Asenapine + valproate   Olanzapine/fluoxetine
                                  Aripiprazole + valproate   combination (OFC)
                                                      Ziprasidone + treatment as
                                                      usual
                Second-line       Cariprazine, ziprasidone,   Aripiprazole, asenapine,
                                  risperidone, clozapine,   carbamazepine
                                  valproate, lamotrigine,
                                  carbamazepine
             Maintenance
                First-line
                    Monotherapy   Lithium, valproate, olanzapine, quetiapine
                    Combination therapy   Quetiapine + valproate
                                  Quetiapine + lithium
                                  Aripiprazole + valproate
                                  Aripiprazole + lithium
                Second-line       Ziprasidone
                                  Risperidone + lithium
                                  Risperidone + valproate
                                  Aripiprazole + lamotrigine
            The same review recommended that antidepressants should be avoided in mixed episodes.
            Clozapine was an effective option in treatment-resistant patients.
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            A systematic review on adults with BD showed that in those with mixed episodes: 30, level I
                combination of olanzapine plus lithium or valproate was effective in acute episodes but
                combination of haloperidol or risperidone plus lithium or valproate was not
                combination of quetiapine plus lithium or valproate was effective in preventing relapse
                but the addition of aripiprazole on lithium or valproate was not
                lithium monotherapy was not effective in preventing relapse
            Quality assessment of primary papers however was not mentioned.
            A  post-hoc  analysis  of  three  RCTs  on  acute  bipolar  depression  with  concurrent  manic
            symptoms compared the effectiveness of cariprazine (1.5 mg and 3 mg) vs placebo at six
            weeks and showed that the former had: 44, level I
                significantly more improvement of MADRS total score, CGI-S and HAM-D scores
                significantly higher response and remission rates
                NS improvement of YMRS total score
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