Pharmacological options for treating bipolar disorder have increased over the past 20 years, with several second-generation antipsychotics receiving regulatory approval in the 1990s. The authors describe trends in use of pharmacological agents in the outpatient management of bipolar disorder.Using nationally representative data from the 1997-2016 National Ambulatory Medical Care Surveys, the authors examined trends in the use of mood stabilizers, first- and second-generation antipsychotics, and antidepressants among psychiatrist visits for which bipolar disorder was listed among the primary diagnoses. A logistic regression model was used to identify statistically significant trends, with covariates including age, gender, race/ethnicity, and primary insurance.Antipsychotics were increasingly more commonly prescribed, increasing from 12.4% of outpatient visits for bipolar disorder in the 1997-2000 period to 51.4% in the 2013-2016 period (adjusted odds ratio=5.05, 95% CI=3.65-7.01). Use of mood stabilizers decreased from 62.3% of visits for bipolar disorder in the 1997-2000 period to 26.4% in the 2013-2016 period (adjusted odds ratio=0.18, 95% CI=0.13-0.27). Prescription of antidepressants occurred in 47.0% of visits for bipolar disorder in the 1997-2000 period and 57.5% in the 2013-2016 period. Prescription of an antidepressant without a mood stabilizer increased substantially, from 17.9% in the 1997-2000 period to 40.9% in the 2013-2016 period (adjusted odds ratio=2.88, 95% CI=2.06-4.03).Substantial changes have occurred in the treatment of bipolar disorder over the past 20 years, with second-generation antipsychotics in large measure supplanting traditional mood stabilizers. Antidepressant prescriptions persisted despite a lack of evidence for their efficacy in bipolar disorder and concerns about increasing the risk of mania. Research is needed to compare the real-world effectiveness and tolerability of newer antipsychotics with those of traditional mood stabilizers.