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Widespread use of antidepressants in bipolar depression is linked to increased risk of both depression-related and mania-related hospitalisations, but mood stabilisers appear effective in preventing them, study results have suggested.
The findings, published in The Lancet on 5 February 2025, support lithium as the mainstay of treatment in bipolar disorder.
The study looked at the association between psychopharmacological treatments and hospital admission for bipolar depression, using a registry-based national Swedish cohort.
It used data from more than 105,000 participants, comprising 65,607 women (62%) and 39,888 men (38%).
Participants were on registers of inpatient and specialised outpatient care, sickness absence and disability pension between January 2006 and December 2021.
In medication class-based analyses, a higher risk of depression-related hospitalisation was associated with the use of antidepressant-only treatments (hazard ratio [HR] 1.25, 95% confidence interval [CI] = 1.16–1.34), antipsychotic-only treatments (HR 1.39, CI 1.24–1.55), antidepressant–antipsychotic combination treatments (HR 1.28, CI 1.18–1.39) and antipsychotic–mood stabiliser combination treatments (HR 1.13, CI 1.03–1.24).
In contrast, the use of mood stabilisers-only treatments was associated with a lower risk of depression-related hospitalisation (HR 0.89, CI 0.81–0.98). For specific monotherapies, only lithium was associated with lower depression-related hospitalisation risk (HR 0.75, CI 0.67–0.85).
The study authors concluded: “Lithium was the only specific monotherapy with significantly reduced risk of depression-related hospitalisations when compared with non-use of antidepressants, antipsychotics and mood stabilisers, and with more than 30% lower risk than any antidepressant, any antipsychotic, quetiapine, or lamotrigine monotherapy in the head-to-head analysis.
“Lithium was also associated with the lowest risk of somatic hospitalisation. Our findings supported the use of lithium as the mainstay of treatment in bipolar disorder.”
Commenting on the study, Orla Macdonald, lead research pharmacist at Oxford Health NHS Foundation Trust, said: “These real-world observational studies are really useful to see the long-term impacts of using medicines in chronic conditions, like bipolar disorder. Lithium is the most effective treatment for preventing relapse in bipolar disorder.
“It’s the gold standard, and we need to encourage prescribers and patients to consider it early in treatment, so patients can achieve the best outcomes in the longer term. We also know that antidepressants can induce a manic switch and, therefore, shouldn’t be used alone in bipolar disorder.”
However, Macdonald cautioned against making the “broad statement” that mood stabilisers appear more effective in treatment.
“The beneficial finding is most conclusive for lithium, and this drug is likely to be the reason this class of medicines does well. I’m unsure how robust the evidence is for other mood stabilisers, like valproate or lamotrigine, in preventing relapse, but suspect it isn’t that strong,” she added.
Simon Kitchen, chief executive of Bipolar UK, said: “Antidepressants should only ever be prescribed to people with bipolar alongside a mood stabiliser because of the risk that they can trigger high mood.
“However, when the Bipolar Commission surveyed 2,458 people living with bipolar, 55% reported that taking an antidepressant triggered an initial episode or relapse.
“This reflects what our bipolar community tells us is a common pathway to diagnosis, where someone sees a GP about symptoms of depression, get prescribed an antidepressant, then end up experiencing a first mania, which can often lead to hospitalisation.”
