Over Past 20 Years, Second Generation Antipsychotics Supplant Mood Stabilizers

Over the course of the study period, a smaller percentage of patients received psychotherapy, and significantly fewer visits exceeded 30 minutes compared with visits of 16 to 30 minutes.

A study published in the American Journal of Psychiatry indicated striking changes in the treatment of bipolar disorder over the past 20 years, with second generation antipsychotics largely replacing traditional mood stabilizers. The study also found that antidepressant prescriptions remained common, despite a lack of evidence of efficacy, and psychotherapy use diminished markedly.

Researchers investigated trends in the outpatient management of bipolar disorder with pharmacological agents based on nationally representative data from a sample of 4419 visits from the 1997–2016 National Ambulatory Medical Care Surveys. Annual visit observations were combined into 4-year blocks: 1997–2000, 2001–2004, 2005–2008, 2009–2012, and 2013–2016, for evaluation of changes over time. The researchers analyzed demographic variables, diagnostic subtypes, and the psychopharmacological management over time, comparing approaches between medication classes, namely mood stabilizers, first- and second-generation antipsychotics, and antidepressants.

During the study period, the total number of visits relating to bipolar disorder increased from 467,000 to 1.06 million, indicating a considerable increase in diagnoses. Over this time, a smaller percentage of patients received psychotherapy (P =.009), and significantly fewer visits exceeded 30 minutes compared with visits of 16 to 30 minutes (P =.014). Psychotherapy use decreased from 50.9% to 35.7%.

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Between the 1997–2000 and 2013–2016 periods, the percentage of bipolar disorder related visits involving antipsychotic prescriptions rose from 19.1% to 52.7%, mainly driven by second-generation antipsychotics, whereas the prescription of first-generation antipsychotics decreased. When further comparing the 1997-2000 and 2013-2016 periods, visits involving prescriptions for any mood stabilizer decreased from 62.3% to 26.4%. For antidepressants with or without mood stabilizers or antipsychotics, prescriptions increased nonsignificantly from 47% to 57.5% between the 2 periods. However, antidepressant use without mood stabilizers increased from 17.9% to 40.9%. Prescriptions for stimulants increased from 5.3% to 9.8%, but prescription rates for benzodiazepines were unchanged (range, 24%–31%).

Study limitations included reliance on inexact clinical diagnoses and lack of data on individual patients. Nonetheless, the researchers concluded that the findings point to some worrying trends, with second-generation antipsychotics supplanting lithium and other mood stabilizers regardless of “comparative effectiveness data” and “a persistence of the prescribing of antidepressants despite a consistent lack of evidence.” They noted that many new drugs had been approved in the study period, and “intensive marketing campaigns” promoted the medications to providers and patients.

The researchers wrote, “These findings could have important implications for public health and demonstrate a need for comparative analyses between second-generation antipsychotics and older mood stabilizers…with respect to efficacy, tolerability, and side effects.”


Rhee TG, Olfson M, Nierenberg AA, Wilkinson ST. 20-year trends in the pharmacologic treatment of bipolar disorder by psychiatrists in outpatient care settings (published online April 21, 2020). Am J Psychiatry. doi.org/10.1176/appi.ajp.2020.19091000