Stopping depressive relapse is a serious objective within the administration of bipolar dysfunction. It has been proven that despair makes up round 72% of total time spent ailing in individuals with bipolar (Forte et al., 2015), and that bipolar despair particularly is related to vital bodily and psychological morbidity, in addition to elevated mortality (Baldessarini et al., 2020).
Lithium is the first-line beneficial remedy for stopping bipolar despair (NICE, 2014). Nonetheless, as a earlier Elf weblog has highlighted, prescription of lithium is declining, each within the UK and different nations (Edward, 2019). Antipsychotics, different temper stabilisers and – though not beneficial by NICE – antidepressants are additionally usually prescribed long-term for individuals with bipolar dysfunction. As just lately blogged right here and right here, using antidepressants within the long-term administration of bipolar dysfunction is controversial, with the danger of temper destabilisation related to antidepressant monotherapy, and it is suggested that they need to be prescribed for sufferers with bipolar dysfunction solely in particular medical eventualities (McIntyre et al., 2020; Pacchiarotti et al., 2013).
In a paper just lately printed in The Lancet Psychiatry, Ermis et al (2025) aimed to check whether or not the prescription of medicines utilized in bipolar despair have an effect on the probabilities of sufferers with bipolar dysfunction being admitted to hospital because of a depressive temper episode.
Stopping depressive relapse is a serious objective within the administration of bipolar dysfunction.
Strategies
Ermis et al used a cohort examine design to determine whether or not prescription of temper stabilisers, antidepressants and antipsychotics (prescribed and disbursed) had been related to admission to hospital as a result of depressive sickness (major end result), and admission to hospital as a result of mania or a somatic situation (secondary outcomes). Topics and end result knowledge had been recognized from ICD-10 codes (WHO, 2019) in Swedish nationwide registers from 2006-2021, while knowledge on topics’ medicines had been gathered from the Prescribed Medicine Register.
A within-subjects Cox regression evaluation (adjusted for time-variant covariates equivalent to time since cohort entry and use of different psychopharmacological medicines) was used to check durations of time during which the topic was prescribed a particular remedy towards instances during which no antidepressant, antipsychotic, or temper stabiliser had been prescribed. Various sensitivity analyses had been additionally carried out, to make sure the robustness of the findings.
Outcomes
105,495 individuals with bipolar dysfunction had been included. The imply age of the pattern was 44.2 years (normal deviation, SD 18.8), and 62.2% of the pattern recognized as ladies. Comorbidities had been current in a big minority (anxiousness issues 40.5%, substance use dysfunction 18.8%, persona issues 10.4% and former suicide try 10.6%).
Comply with-up was commenced from the date of bipolar analysis and the imply follow-up time was 9.1 years (SD 5.1). At follow-up, antidepressant monotherapy was the commonest publicity (utilized by 59,963 topics, 56.8% of the cohort, in some unspecified time in the future throughout the follow-up interval), adopted by temper stabiliser monotherapy (47,931, 45.4%) and antidepressant-mood stabiliser mixture (46,318, 43.9%).
General, 16,190 topics (15.3%) had been hospitalised with a depressive episode at the least as soon as throughout the follow-up interval; 8,066 topics (7.7%) had been hospitalised as a result of mania.
Decreased likelihood of depression-related hospitalisation
Temper stabiliser monotherapy was the one remedy group discovered to be related to a decreased likelihood of depression-related hospitalisation in contrast with the prescription of no medicines in any respect (adjusted hazards ration, aHR 0.89, 95% confidence interval, CI 0.81 to 0.98).
Temper stabilisers mixed with antipsychotics had been related to a touch decreased likelihood of depression-related hospitalisation, however this was not statistically vital (aHR 0.92, 95% CI 0.85 to 1.00).
In particular person remedy evaluation, solely lithium was related to a decreased likelihood of admission as a result of despair on this cohort of individuals with bipolar dysfunction (aHR 0.75, 95% CI 0.67 to 0.85).
Elevated likelihood of depression-related hospitalisation
Aside from temper stabiliser monotherapy and temper stabilisers mixed with antipsychotics, all different remedy teams, both alone or together, had been discovered to be related to an elevated likelihood of depression-related hospitalisation.
Notably, a number of medicines had been related to an elevated likelihood depression-related hospitalisation, specifically quetiapine, duloxetine, citalopram, olanzapine, mirtazapine, vortioxetine and aripiprazole.
Decreased likelihood of hospitalisation as a result of a somatic situation
By way of secondary outcomes, lithium was the one remedy related to a decreased likelihood of hospitalisation as a result of a somatic situation (aHR 0.86, 95% CI 0.80 to 0.93), with no statistically vital associations being discovered between the opposite medicines and somatic hospitalisation.
Elevated likelihood of mania-related hospitalisation
Antidepressants-only had been the one group that had been related to elevated probabilities of hospitalisation as a result of mania (aHR 1.22, 95% CI 1.03 to 1.44); all different medicines teams, alone or together, had been related to decreased probabilities of mania-related hospitalisation.
In particular person remedy evaluation, solely lithium confirmed a decreased likelihood of depression-related hospitalisation; all different medicines had been both equivocal or related to elevated likelihood of depression-related hospitalisation. [View full sized graphic]
Conclusions
The outcomes of this examine spotlight that lithium is the one monotherapy that decreases the probabilities of depression-related hospitalisation in individuals with bipolar dysfunction. Further advantages had been additionally seen within the probabilities of mania-related and somatic hospitalisations, emphasising lithium’s multimodal advantages.
In distinction, sure antidepressants and antipsychotics had been related to elevated likelihood of depression-related hospitalisation.
“Present findings supported the notion that lithium ought to stay the mainstay of remedy in bipolar dysfunction” – Ermis et al, 2025
Strengths and limitations
A cohort examine design was the fitting methodology to reply this query. Cohort research, of their observational nature, enable researchers to determine the impact of exposures in pure environments, making the outcomes extra generalisable to real-life conditions. It additionally allowed the authors to check a number of medicines on the similar time, which might not have been attainable to the identical extent in, for instance, an RCT design.
The examine inhabitants was taken from Swedish nationwide registers and ICD-10 codes had been used to establish these with bipolar dysfunction and the outcomes of curiosity. The outcomes are due to this fact reliant on appropriate software of the ICD-10 standards at time of analysis and proper coding of analysis into the well being registers. Inside these limitations, the authors had been capable of pattern a lot of the inhabitants with a bipolar analysis and supply follow-up over a number of years.
By way of the pattern demographics, charges of psychiatric comorbidity and suicide try historical past had been excessive, however this echoes the broader bipolar inhabitants (as highlighted by a earlier Elf weblog) and improves the generalisability of the outcomes from this pattern to real-world medical settings. It’s notable, nevertheless, that there have been twice as many ladies than males, which isn’t reflective of bipolar dysfunction’s 1:1 male-to-female distribution and that knowledge on ethnicity weren’t accessible, each of which restrict the generalisability of the examine outcomes to explicit teams.
The authors famous that by specializing in hospitalisation, the outcomes of this examine are solely related for probably the most extreme instances of bipolar despair and don’t think about the advantages or harms that these medicines could also be exerting in sufferers who’re managed totally as outpatients. Hospitalisation is an goal, binary measure that has vital real-world implications for sufferers, and so it may be argued that it’s nonetheless a great measure of the efficacy of those medicines.
A closing vital consideration is that use of registry knowledge doesn’t at all times correspond precisely to behavior. In different phrases, simply because a prescription was written, doesn’t imply the remedy was taken. Typically talking, nevertheless, it’s possible that almost all of these prescribed a drugs do take it, and the massive numbers included on this pattern are prone to minimise the impact that remedy non-compliance in small minority might have on total outcomes.
Regardless of limitations, the massive pattern dimension and lengthy follow-up make the outcomes pretty generalisable to the bipolar inhabitants and vital medical eventualities.
Implications for apply
This paper reaffirms the standing of lithium as “the simplest long-term remedy for bipolar dysfunction” (NICE, 2014). As such, it’s regarding that the charges of lithium prescription seem like declining (Lyall et al., 2019). The explanations for this are unclear, however, as a earlier Elf weblog highlights, it might be as a result of anxiousness amongst sufferers and clinicians concerning the elevated monitoring that’s required for lithium or as a result of its particular hostile impact profile. It might even be associated to the low value of lithium, which can be driving the pharmaceutical trade to promote using different, dearer choices, doubtlessly swaying affected person desire. Regardless of the motive, a transfer away from prescribing lithium poses the danger of many sufferers lacking out on its potential advantages.
After lithium, the second- and third-line NICE-recommended preventative medicines for bipolar dysfunction are antipsychotic monotherapy and augmentation with valproate. This paper confirmed that these medicines had been related to reductions in mania-related hospitalisation, however no such profit was seen with depression-related hospitalisation. Some antipsychotics had been in reality related to elevated likelihood hospitalisation as a result of a depressive episode. This may occasionally make clinicians suppose twice about prescribing antipsychotics or valproate long-term in bipolar dysfunction if the first goal of remedy is to stop additional depressive moderately than manic relapses. In lots of sufferers this would be the goal, significantly as despair makes up nearly all of sickness time in these with bipolar dysfunction (Forte et al., 2015).
So, on the very least, Ermis et al have demonstrated the necessity for additional analysis on this space in order that we are able to make clear whether or not present medical pointers for prevention of bipolar relapse are match for objective for every type of temper episodes, particularly in these for whom lithium is just not an choice.
A transfer away from prescribing lithium poses the danger of many sufferers lacking out on its potential advantages.
Assertion of pursuits
No conflicts of curiosity to declare.
I’m presently in receipt of PhD fellowship funding via a Wellcome Belief-funded examine in bipolar dysfunction, sleep and circadian rhythm (www.ambientbd.com).
Hyperlinks
Main paper
Ermis, C., Taipale, H., Tanskanen, A., Vieta, E., Correll, C. U., Mittendorfer-Rutz, E., & Tiihonen, J. (2025). Actual-world effectiveness of pharmacological upkeep remedy of bipolar despair: a within-subject evaluation in a Swedish nationwide cohort. The Lancet Psychiatry.
Different references
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Baldessarini, R. J., Vázquez, G. H., & Tondo, L. (2020). Bipolar despair: a serious unsolved problem. Worldwide journal of bipolar issues, 8(1), 1. https://doi.org/10.1186/s40345-019-0160-1
Edward, D., & Ahmed, S. (2019, 14 June 2019). Prescribing lithium for bipolar dysfunction: are we too scared? The Psychological Elf. https://www.nationalelfservice.internet/mental-health/bipolar-disorder/prescribing-lithium-bipolar-disorder/
Forte, A., Baldessarini, R. J., Tondo, L., Vázquez, G. H., Pompili, M., & Girardi, P. (2015). Lengthy-term morbidity in bipolar-I, bipolar-II, and unipolar main depressive issues. J Have an effect on Disord, 178, 71-78. https://doi.org/10.1016/j.jad.2015.02.011
Kalfas, M. & Leeks, P. (2024). Jury stays out on antidepressant-induced mania. Nationwide Elf Service. https://www.nationalelfservice.internet/mental-health/bipolar-disorder/antidepressant-induced-mania/
Lyall, L. M., Penades, N., & Smith, D. J. (2019). Modifications in prescribing for bipolar dysfunction between 2009 and 2016: national-level knowledge linkage examine in Scotland. The British Journal of Psychiatry, 215(1), 415-421. https://doi.org/10.1192/bjp.2019.16
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