Comparing Pharmacologic Treatments for Prevention of Rehospitalization in Bipolar Disorder

empty hospital bed
empty hospital bed
Investigators sought to determine the most effective treatment modalities to prevent rehospitalization in patients with bipolar disorder.

In patients with bipolar disorder, lithium is the most effective mood stabilizer and long-action injections are the most effective antipsychotic medications to prevent hospitalization from mental or physical illness, according to results published online in JAMA Psychiatry.

These results suggest that lithium should remain the first line of treatment for bipolar disorder. If lithium is unsuitable for a patient, long-acting injections may be a safe, effective option.

The study included all patients who had been hospitalized for bipolar disorder in Finland from January 1, 1987, to December 31, 2012 (n=18,018). The main outcome was the risk for psychiatric, cardiovascular, and all-cause hospitalization. Mean follow-up time was 7.2 years.

Of all participants, 54.0% (n=9721) had at least 1 psychiatric rehospitalization.

The researchers found that risperidone long-acting injection (hazard ratio [HR] 0.58; 95% CI, 0.34-1.00), gabapentin (HR 0.58; 95% CI, 0.44-0.77), perphenazine long-acting injection (HR 0.60; 95% CI, 0.41-0.88), and lithium carbonate (HR 0.67; 95% CI, 0.60-0.73) were associated with the lowest risk for psychiatric rehospitalization.

Lithium (HR 0.71; 95% CI, 0.66-0.76) was associated with the lowest risk for all-cause hospitalization.

The most frequently used antipsychotic treatment, quetiapine fumarate, showed only modest effectiveness (risk for psychiatric rehospitalization: HR 0.92; 95% CI; 0.85-0.98]; risk for all-cause hospitalization: HR 0.93; 95% CI, 0.88-0.98). Benzodiazepines were associated with an increased risk for any-cause hospitalization (HR 1.15; 95% CI, 1.11-1.20).

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Overall, mood stabilizer therapies were associated with an increased risk for cardiovascular hospitalizations (HR 1.32; 95% CI, 1.10-1.58). Of the mood stabilizer medications, valproic acid and carbamazepine had the highest risk for associated cardiovascular events.

The results indicated that long-acting injections were associated with substantially better outcomes compared with identical oral antipsychotic medications (risk for psychiatric rehospitalization: HR 0.70; 95% CI, 0.55-0.90; risk for all-cause hospitalization: HR 0.70; 95% CI, 0.57-0.86).


Lähteenvuo M, Tanskanen A, Taipale H, et al. Real-world effectiveness of pharmacologic treatments for the prevention of rehospitalization in a Finnish nationwide cohort of patients with bipolar disorder [published online February 28, 2018]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.4711