When you live with bipolar disorder, treatment is most often based on a small tablet supposed to prevent relapses. For decades, this role fell to
lithiumstandard treatment to stabilize mood and reduce hospitalizations. Yet about one in five patients relapse despite having adequate blood levels, and up to half eventually stop this medication because of kidney or thyroid side effects. A gigantic North European study has just focused on what works when this pillar no longer works, alone or not at all.
Lithium, the standard treatment for bipolar disorders
Behind this work is the team of psychiatrist Johannes Lieslehto, who leveraged national registries in Sweden and Finland to track more than 160,000 people with
bipolar disorder. “Lithium is widely considered the gold standard treatment for bipolar disorder, but in real life many patients do not respond sufficiently or do not tolerate it. At the same time, clinicians often need to combine medications or modify treatment strategies, yet there is surprisingly little high-quality evidence on which combinations are most effective over the long term.“, explained Johannes Lieslehto to Medical Xpress.
When lithium is not enough, this analysis comes for the first time to systematically compare the combinations of drugs used long-term and their impact on rehospitalizations.
When lithium is no longer enough in bipolar disorder
In this cohort, lithium remains one of the most protective monotherapies against hospitalization, according to Johannes Lieslehto and colleagues. But some associations do even better. The duo Clozapine plus aripiprazole is linked to an approximately 58% reduction in risk compared to lithium alone, clozapine monotherapy to an approximately 39% reduction, and the addition of a long-acting injectable antipsychotic to lithium to an approximately 30% reduction.
These results place clozapine in the forefront, while in France this antipsychotic remains reserved for resistant forms, and also promote depot injections which secure compliance. Clozapine can cause rare but serious hematological disorders and therefore requires weekly then monthly blood monitoring. Furthermore, it does not have Marketing Authorization for this indication in France. The major international recommendations still classify it in third or fourth line, but these data suggest that it could, for certain profiles, provide better protection than lithium.
What alternatives to lithium after a complete shutdown
When lithium must be stopped, for example because of kidney damage, a thyroid problem or pregnancy, the need foralternatives to lithium becomes urgent. In the subgroup of 20,645 patients who discontinued this treatment, the study found that the combinations of quetiapine plus lamotrigine and olanzapine plus valproate reduced the risk of rehospitalization by approximately 35 to 36%, while none of these molecules achieved this alone. An encouraging signal also exists for regimens combining valproate with an injectable antipsychotic or risperidone, even if in France this medication is already very regulated, especially among women of childbearing age.
“Clinically, the key message is that viable alternatives exist when lithium is not sufficient or cannot be used“, summarized Johannes Lieslehto in Medical
Towards more personalized treatments for bipolar disorder
To limit bias, the team compared each patient to themselves according to their treatment periods. “So, instead of comparing different people taking different medications, we looked at how the same person did over periods of time on different treatments. This approach helps reduce bias because factors like genetics, disease severity, or lifestyle are naturally controlled (i.e., they do not vary within the same individual).” specifies Dr. Lieslehto.
The team plans to analyze functional recovery and quality of life to get a more complete picture of the treatment’s effectiveness. They also plan to combine this clinical data with genetic information and biomarkers to personalize therapeutic choices, and thus predict which treatment will be most effective for each patient.