What are approaches to treatment-resistant depression in patients with bipolar disorder?

The first step to revisit the diagnostic assessment, considering alternatives. For example, patients who have a history of two weeks of psychotic symptoms in the absence of a major mood syndrome can meet criteria for schizoaffective disorder. The second step is to objectively assess medication adherence and substance abuse. With regard to treatment of bipolar depression, lithium is believed to work, and valproate has multiple positive research studies. The effectiveness of antidepressant medications is inconsistent in research, though there is research indicating that it can augment the effectiveness of mood stabilizers. Patients who have breakthrough symptoms on lithium alone often respond to addition of valproate. An olanzapine fluoxetine combination, and quetiapine and lurasidone are approved for treatment of bipolar depression. Lurasidone was approved for adjunctive use with lithium or valproate in bipolar depression. Multiple other second-generation antipsychotics have been studied in combination with a mood stabilizer, often lithium or valproate, and found to be more effective than a mood stabilizer alone. Patients with treatment-resistant bipolar disorder have responded to clozapine. Clozapine is an important option with other mood stabilizers and antipsychotics have failed. For more information on use of clozapine, visit the SMI Adviser Clozapine Center of Excellence. ECT has research supporting its efficacy. TMS is an option. Esketamine is approved for use in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression in adults.

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