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Lithium, injectable antipsychotics most effective at preventing rehospitalization for bipolar disorder in Finland

Study findings showed that lithium and long-acting antipsychotic injections were the most effective treatments to prevent rehospitalization among patients with bipolar disorder.

“The most efficient way to obtain a good estimate on the overall real-world effectiveness of therapies for bipolar disorder may be through observational studies,” Markku Lähteenvuo, MD, PhD, department of forensic psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland, and colleagues wrote. “To our knowledge, no studies have investigated the comparative effectiveness of long-acting antipsychotic injections vs. identical oral agents.”

Researchers compared the effectiveness of pharmacologic treatments in preventing rehospitalization among 18,018 Finnish patients with bipolar disorder enrolled in a cohort study that spanned from January 1987 to December 2012 using nationwide databases for hospitalization and dispensed medications. They conducted statistical analyses from the beginning of 1996 to the end of 2012 to assess rehospitalization due to any mental disorder, cardiovascular disease and all-cause hospitalization. Adjustments were made to account for the effect of related psychotropic medications, illness duration and the temporal orders of exposure and nonexposure periods. Additional analysis for rehospitalization was performed for lithium, valproic acid and quetiapine.

In total, 9,721 patients (54%) experienced at least one psychiatric rehospitalization. The pharmacologic treatments associated with the smallest risk for psychiatric rehospitalization were risperidone long-acting injection (HR = 0.58; 95% CI, 0.34-1), gabapentin (HR = 0.58; 95% CI, 0.44-0.77), perphenazine long-acting injection (HR = 0.6; 95% CI, 0.41-0.88) and lithium carbonate (HR = 0.67; 95% CI, 0.6-0.73).

Statistical analysis of the risk for all-cause hospitalization revealed that lithium was linked to the lowest risk for rehospitalization (HR = 0.71; 95% CI, 0.66-0.76), whereas benzodiazepines were linked to an increased risk for psychiatric rehospitalization (HR = 1.19; 95% CI, 1.12-1.26) and for any-cause hospitalization (HR = 1.15; 95% CI, 1.11-1.2).The researchers found that although quetiapine fumarate was the most commonly used antipsychotic therapy, it only showed modest effectiveness on the risk for psychiatric rehospitalization (HR = 0.92; 95% CI, 0.85-0.98) and all-cause hospitalization (HR = 0.93; 95% CI, 0.88-0.98).

People treated with long-acting injectable formulations of antipsychotic medications were more likely to experience better outcomes regarding the risk for psychiatric rehospitalization (HR = 0.7; 95% CI, 0.55-0.9) and the risk for all-cause hospitalization (HR = 0.7; 95% CI, 0.57-0.86) compared with those treated with identical oral formulations of the same medication. After performing sensitivity analyses, researchers observed consistent beneficial effects for lithium and long-acting injections only compared with their oral counterparts.

“Lithium is associated with substantially reduced risks of psychiatric and all-cause hospitalization and should remain as the first line of treatment for bipolar disorder, after decades of underprescription,” Lähteenvuo and colleagues wrote. “Although more research is needed to support the notion, [long-acting injections] might offer a safe and effective option for relapse prevention in bipolar disorder for patients for whom lithium is not suitable.”

Although analyses of national registers offer good information, it’s important to clarify certain issues in future study to strengthen findings on psychotropic drug effectiveness, according to a related editorial written by Stefan Leucht, MD, department of psychiatry and psychotherapy, Technische Universität München, Germany, and John M. Davis, MD, Psychiatric Institute, University of Illinois, and the Maryland Psychiatric Research Center.

“A major limitation is that analyses of national registers can never fully control for confounders. We would also caution against interpretation of findings without considering the events and years at risk,” Leucht and Davis wrote. “We want to reinforce the authors’ cautioning that the results from one country cannot necessarily be generalized to other settings.” – by Savannah Demko

Disclosures: Lähteenvuo reports research grants/awards from Boehringer-Ingelheim, being a shareholder and board member at Genomi Solutions Ltd, working as a coordinator for a research project funded by the Stanley Foundation and travel grants from Sunovion Ltd. Please see the full study for all other authors’ relevant financial disclosures. Leucht reports honoraria from Boehringer Ingelheim, Gedeon Richter, H Lundbeck A/S, LB Pharma International, LTS Lohmann Therapy Systems, Otsuka Pharmaceutical, Recordati SpA and Teva Pharmaceutical Industries Ltd, and for lectures from Eli Lilly & Company, H Lundbeck A/S, Janssen Pharmaceuticals, Otsuka Pharmaceutical, SanofiAventis and Servier Laboratories.