title: Treating mixed mania/hypomania: a review and synthesis of the evidence.
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.
authors.affiliation: J Clinic,Kanazawa City,Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Takeshima
mesh_terms: D000208:Acute Disease; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003951:Diagnostic Errors; D039721:Diagnostic and Statistical Manual of Mental Disorders; D006801:Humans; D008134:Long-Term Care; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D018692:Antimanic Agents; D014150:Antipsychotic Agents
keywords: Mania; bipolar disorder; dysphoric mania; mixed episodes; mixed features; mixed hypomania; mixed mania; mixed specifier; mixed states; pharmacotherapy