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Treating mixed mania/hypomania: a review and synthesis of the evidence

Published online by Cambridge University Press:  22 December 2016

Minoru Takeshima
Minoru Takeshima*
Affiliation:
J Clinic, Kanazawa City, Japan
*
*Address for correspondence: Minoru Takeshima, J Clinic, 3-30-10 Sainen, Kanazawa City 920-0024, Japan. (Email: min-take@p2.tcnet.ne.jp)
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Abstract

The DSM–5 incorporates a broad concept of mixed states and captured ≥3 nonoverlapping symptoms of the opposite polarity using a “with mixed features” specifier to be applied to manic/hypomanic and major depressive episodes. Pharmacotherapy of mixed states is challenging because of the necessity to treat both manic/hypomanic and depressive symptoms concurrently. High-potency antipsychotics used to treat manic symptoms and antidepressants can potentially deteriorate symptoms of the opposite polarity. This review aimed to provide a synthesis of the current evidence for pharmacotherapy of mixed states with an emphasis on mixed mania/hypomania. A PubMed search was conducted for randomized controlled trials (RCTs) that were at least moderately sized, included a placebo arm, and contained information on acute-phase and maintenance treatments of adult patients with mixed episodes or mania/hypomania with significant depressive symptoms. Most studies were post-hoc subgroup and pooled analyses of the data from RCTs for acute manic and mixed episodes of bipolar I disorder; only two prospectively examined efficacy for mixed mania/hypomania specifically. Aripiprazole, asenapine, carbamazepine, olanzapine, and ziprasidone showed the strongest evidence of efficacy in acute-phase treatment. Quetiapine and divalproex/valproate were also efficacious. Combination therapies with these atypical antipsychotics and mood stabilizers can be considered in severe cases. Olanzapine and quetiapine (alone or in combination with lithium/divalproex) showed the strongest evidence of efficacy in maintenance treatment. Lithium and lamotrigine may be beneficial given their preventive effects on suicide and depressive relapse. Further prospective studies primarily focusing on mixed states are needed.

Keywords

Maniamixed episodesmixed maniamixed hypomaniamixed specifiermixed featuresmixed statesdysphoric maniabipolar disorderpharmacotherapy
Type
Review Articles
Information
CNS Spectrums , Volume 22 , Issue 2: Theme: Mixed features in major depressive episodes , April 2017 , pp. 177 - 185
Copyright
© Cambridge University Press 2016 

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Footnotes

The author would like to thank Editage (www.editage.jp) for the English-language editing. However, the author is solely responsible for the scientific content of the paper.

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