Individuals with bipolar disorder have the lowest risk of re-hospitalisation if treated with lithium, according to a study from Karolinska Institutet in Sweden. Long-acting injections of anti-psychotics were also effective, reducing the risk of re-hospitalisation by 30% compared with their oral counterparts.
Bipolar disorder is characterised by alternating periods of depression and elevated mood (mania) and is usually treated either with mood stabilising or antipsychotic drugs. Lithium is considered to be the most effective mood stabiliser, but only a few studies have been conducted comparing the long-term effects of different drugs in bipolar disorder.
In order to determine which treatment is most effective, researchers at Karolinska Institutet compared the risk of re-admission to hospital in more than 18,000 patients in Finland who had previously been hospitalised for bipolar disorder. Each patient was used as their own control and compared during periods with and without treatment.
During an average follow-up time of more than seven years, lithium treatment was associated with the lowest risk of re-hospitalisation in mental or physical disease, with a risk reduction of about 30% compared with no treatment at all. Long-acting injections of anti-psychotic drugs were also effective. The risk of re-admission was around 30% lower if patients were treated with long-acting injections compared to their receiving the same anti-psychotic medication but orally. The most commonly prescribed anti-psychotic drug for bipolar disorder, quetiapine (Seroquel), which is given in tablet form, reduced the risk by only 7%.
“The prescription of lithium has decreased steadily in recent years, but our results show that lithium should remain the first line of treatment for patients with bipolar disorder. Long-acting injections might offer a safe, effective option for patients for whom lithium is not suitable,” says Jari Tiihonen, specialist doctor and professor at Karolinska Institutet’s department of clinical neuroscience.
The research was funded by the Finnish Ministry of Social Affairs and Health. No company has financed this particular study, but several of the authors are associated with and have previously received funding/fees from pharmaceutical companies in different contexts. Two of the authors are employed by the contract research organisation EPID Research. The scientific article provides more detailed information about potential conflicts of interest.
Importance: Mood stabilizers and antipsychotics are the main maintenance treatments for bipolar disorder. Lithium is considered to be the most effective mood stabilizer, but very little is known about overall health outcomes associated with specific treatments and the comparative long-term effectiveness of specific psychotropics or routes of administration in the prevention of rehospitalizations.
Objective: To study the comparative effectiveness of pharmacologic treatments in the prevention of rehospitalization in a nationwide cohort of patients with bipolar disorder.
Design, Setting, and Participants: This cohort study examined the risk of psychiatric, cardiovascular, and all-cause hospitalization from January 1, 1987, to December 31, 2012, among all patients in Finland who had been hospitalized for bipolar disorder (N = 18 018; mean follow-up time, 7.2 years) using prospectively gathered nationwide databases for hospitalization and dispensed medications. The primary analysis was within-individual analysis, in which each individual was used as his or her own control to eliminate selection bias. The study adjusted for the effect of concomitant psychotropic medications, duration of illness, and the temporal orders of exposure and nonexposure periods. Statistical analysis was conducted from January 1, 1996, to December 31, 2012.
Main Outcomes and Measures: Adjusted hazard ratios (HRs) for rehospitalization were calculated.
Results: Among the cohort (9558 women and 8460 men; mean [SD] age, 46.6 [17.0] years), 9721 patients (54.0%) had at least 1 psychiatric rehospitalization. In comparison between use and no use among specific agents reaching nominal statistical significance, risperidone long-acting injection (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 of psychiatric rehospitalization. Concerning all-cause hospitalization, lithium (HR, 0.71 [95% CI, 0.66-0.76]) was associated with the lowest risk. The most frequently used antipsychotic treatment, quetiapine fumarate, showed only modest effectiveness (risk of psychiatric rehospitalization: HR, 0.92 [95% CI, 0.85-0.98]; risk of all-cause hospitalization: HR, 0.93 [95% CI, 0.88-0.98]). Long-acting injections were associated with substantially better outcomes compared with identical oral antipsychotics (risk of psychiatric rehospitalization: HR, 0.70 [95% CI, 0.55-0.90]; risk of all-cause hospitalization: HR, 0.70 [95% CI, 0.57-0.86]). Results from sensitivity analyses showed consistent beneficial effects only for lithium and for long-acting injections compared with their oral counterparts.
Conclusions and Relevance: Lithium was the most effective mood stabilizer, and long-acting injections the most effective antipsychotics, in preventing hospitalization due to mental or physical illness.
Markku Lähteenvuo, Antti Tanskanen, Heidi Taipale, Fabian Hoti, Pia Vattulainen, Eduard Vieta, Jari Tiihonen