Upward Trends With Antipsychotics and Polypharmacy in Bipolar Disorder

More antipsychotics and polypharmacy are being prescribed for patients with bipolar disorder.

Primary clinical treatment for bipolar disorder (BD) is still mood stabilizers and antipsychotic drugs with a recent upward trend in antipsychotics and polypharmacy, according to study findings published in Frontiers in Psychiatry.

Investigators sought to characterize psychotropic drugs used to treat patients with BD and assess changes in medication treatments in acute and maintenance episodes, and overall adherence.

They conducted a retrospective study assessing inpatient medical records from the Ningbo Kangning Hospital, Ningbo, China that included 204 deidentified patients with BD ascertained with ICD-10 codes from January 2019 to December 2019. Diagnosis of all patients was made in-hospital by a psychiatrist, and all patients were treated with psychotropic drugs. Patients with a history of alcohol and psychoactive substance dependence, epilepsy, or schizophrenia were excluded as were those who were pregnant or nursing, or had history of serious physical disease, endocrine disease, or organic brain disease.

At baseline, participants were predominantly women who were single, predominately aged between 18 and 59 years, (13% were aged less than 18 years; 11% were aged more than 59 years) with a disease course of 13 to 60 months. Most common BD cases included major depression (54%), mania (27%), and mixed state (16%). There were 40% of patients who did not reach beyond a junior high school education. Patients were hospitalized less than 15 days (30%), 15 to 28 days (35%), 29 to 56 days (31%). An acute episode took place during the baseline period, and patients were reassessed during the maintenance period at 3 (n=173), 6 (n=153), 9 (n=147), and 12 (n=149) months.

Our study found that the average number of medications used by BD patients was 2.5, with more medication used during acute episodes than during maintenance periods.

Across acute and maintenance periods, investigators found the most common drugs used in patients with BD were antipsychotics (77%-95%) and mood stabilizers (72%-90%), and after 12 months of treatment, 73% of patients still took medications. The 3- and 6-month postdischarge periods were the most significant times of medication discontinuation. Additionally, investigators noted antidepressants were taken by 34% to 40% of patients and benzodiazepines by 20% to 34%.

Among antipsychotic drugs, quetiapine was more frequently prescribed (54%-65%) followed by olanzapine (12%-20%). Among mood stabilizers, lithium was more frequently prescribed (40%-56%) followed by valproate (33%-52%). The most commonly used antidepressants were sertraline (6%-9%) and fluoxetine (5%-9%) with no significant difference in use. The most frequently prescribed benzodiazepine was lorazepam (10%-18%).

Investigators found no changes across the 12-month study period in the prescription rate of the most common drugs. However, across the same period, prescription rates for oxazepam, valproate, and lithium decreased. They noted no significant changes for patients with BD in daily mean dosage across the 12-month study period.

Investigators noted that 36% to 44% of patients were prescribed psychotropic polypharmacy (use of 2 or more concomitant psychotropic drugs) of an antipsychotic plus a mood stabilizer drug. There were 35% to 48% of all patients co-treated by 2 psychotropic drugs and 24% to 36% who received co-treatment with 3 psychotropic drugs. At baseline, less than 3% of patients received 1 drug. At the 12-month study period, 23% received 1 drug. The average number of drugs used overall per patient was about 2.5 with more medication used during acute episodes than during maintenance periods.

Study limitations include an underpowered sample size, the single-center design, unaccounted-for different types of BD may have different treatment drugs, relatively short follow-up duration, and unaccounted-for factors influencing drug choice.

Investigators concluded that the use of psychotropic drugs is still the main clinical treatment for BD. It is common for clinicians to use polypharmacy for patients with BD. They said, “Our study found that the average number of medications used by BD patients was 2.5, with more medication used during acute episodes than during maintenance periods.” There were one-quarter to one-third of patients treated with 3 drugs and one-third to almost half of all patients treated with 2 drugs, expressing the recent, significant increase in polypharmacy. Investigators wrote, “While some of these combinations have been supported by clinical trials, the efficacy of many combinations has not been proven.” Drug-drug interactions with uncertain benefits in clinical outcomes reflects increased risk for patients.

This article originally appeared on Psychiatry Advisor


Jing P, Su J, Zheng C, Mei X, Zhang X. A retrospective study of psychotropic drug treatments in bipolar disorder at acute and maintenance episodes. Front Psychiatry. Published online February 7, 2023. doi:10.3389/fpsyt.2023.1057780