Stopping depressive relapse is a significant purpose within the administration of bipolar dysfunction. It has been proven that melancholy makes up round 72% of total time spent unwell in individuals with bipolar (Forte et al., 2015), and that bipolar melancholy particularly is related to important bodily and psychological morbidity, in addition to elevated mortality (Baldessarini et al., 2020).
Lithium is the first-line advisable medicine for stopping bipolar melancholy (NICE, 2014). Nevertheless, as a earlier Elf weblog has highlighted, prescription of lithium is declining, each within the UK and different international locations (Edward, 2019). Antipsychotics, different temper stabilisers and – though not advisable by NICE – antidepressants are additionally usually prescribed long-term for individuals with bipolar dysfunction. As not too long ago blogged right here and right here, the usage of antidepressants within the long-term administration of bipolar dysfunction is controversial, with the danger of temper destabilisation related to antidepressant monotherapy, and it’s endorsed that they need to be prescribed for sufferers with bipolar dysfunction solely in particular scientific situations (McIntyre et al., 2020; Pacchiarotti et al., 2013).
In a paper not too long ago printed in The Lancet Psychiatry, Ermis et al (2025) aimed to review whether or not the prescription of medicines utilized in bipolar melancholy have an effect on the possibilities of sufferers with bipolar dysfunction being admitted to hospital on account of a depressive temper episode.
Stopping depressive relapse is a significant purpose within the administration of bipolar dysfunction.
Strategies
Ermis et al used a cohort research design to establish whether or not prescription of temper stabilisers, antidepressants and antipsychotics 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 information had been recognized from ICD-10 codes (WHO, 2019) in Swedish nationwide registers from 2006-2021, while information on topics’ medicines had been gathered from the Prescribed Medicine Register.
A within-subjects Cox regression evaluation (adjusted for time-variant covariates corresponding to time since cohort entry and use of different psychopharmacological medicines) was used to check durations of time wherein the topic was prescribed a particular medicine towards occasions wherein no antidepressant, antipsychotic, or temper stabiliser had been prescribed. Numerous 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 (customary deviation, SD 18.8), and 62.2% of the pattern recognized as ladies. Comorbidities had been current in a big minority (nervousness problems 40.5%, substance use dysfunction 18.8%, persona problems 10.4% and former suicide try 10.6%).
Observe-up was commenced from the date of bipolar prognosis 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 in the course of the follow-up interval), adopted by temper stabiliser monotherapy (47,931, 45.4%) and antidepressant-mood stabiliser mixture (46,318, 43.9%).
Total, 16,190 topics (15.3%) had been hospitalised with a depressive episode no less than as soon as in the course of 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 medicine 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 slightly decreased likelihood of depression-related hospitalisation, however this was not statistically important (aHR 0.92, 95% CI 0.85 to 1.00).
- In particular person medicine evaluation, solely lithium was related to a decreased likelihood of admission as a result of melancholy on this cohort of individuals with bipolar dysfunction (aHR 0.75, 95% CI 0.67 to 0.85).
Elevated likelihood of depression-related hospitalisation
- Other than temper stabiliser monotherapy and temper stabilisers mixed with antipsychotics, all different medicine 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, particularly quetiapine, duloxetine, citalopram, olanzapine, mirtazapine, vortioxetine and aripiprazole.
Decreased likelihood of hospitalisation as a result of a somatic situation
- When it comes to secondary outcomes, lithium was the one medicine 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 important 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 possibilities 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 possibilities of mania-related hospitalisation.
In particular person medicine 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 research spotlight that lithium is the one monotherapy that decreases the possibilities of depression-related hospitalisation in individuals with bipolar dysfunction. Extra advantages had been additionally seen within the possibilities 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 research design was the suitable technique to reply this query. Cohort research, of their observational nature, enable researchers to establish 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 identical time, which might not have been attainable to the identical extent in, for instance, an RCT design.
The research inhabitants was taken from Swedish nationwide registers and ICD-10 codes had been used to determine these with bipolar dysfunction and the outcomes of curiosity. The outcomes are subsequently reliant on right utility of the ICD-10 standards at time of prognosis and proper coding of prognosis into the well being registers. Inside these limitations, the authors had been capable of pattern numerous the inhabitants with a bipolar prognosis and supply follow-up over a number of years.
When it comes to 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 scientific settings. It’s notable, nonetheless, 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 information on ethnicity weren’t out there, each of which restrict the generalisability of the research outcomes to specific teams.
The authors famous that by specializing in hospitalisation, the outcomes of this research are solely related for essentially the most extreme instances of bipolar melancholy and don’t take into account the advantages or harms that these medicines could also be exerting in sufferers who’re managed solely as outpatients. Hospitalisation is an goal, binary measure that has important real-world implications for sufferers, and so it may be argued that it’s nonetheless measure of the efficacy of those medicines.
A ultimate vital consideration is that use of registry information doesn’t at all times correspond precisely to behavior. In different phrases, simply because a prescription was written, doesn’t imply the medicine was taken. Typically talking, nonetheless, it’s possible that almost all of these prescribed a drugs do take it, and the massive numbers included on this pattern are more likely to minimise the impact that medicine non-compliance in small minority could have on total outcomes.
Regardless of limitations, the massive pattern measurement and lengthy follow-up make the outcomes pretty generalisable to the bipolar inhabitants and vital scientific situations.
Implications for apply
This paper reaffirms the standing of lithium as “the best 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 nervousness amongst sufferers and clinicians concerning the elevated monitoring that’s required for lithium or as a result of its particular hostile impact profile. It could even be associated to the low price of lithium, which can be driving the pharmaceutical trade to promote the usage of different, dearer choices, probably 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 actually related to elevated likelihood hospitalisation as a result of a depressive episode. This may increasingly make clinicians assume twice about prescribing antipsychotics or valproate long-term in bipolar dysfunction if the first purpose of remedy is to stop additional depressive fairly than manic relapses. In lots of sufferers this would be the purpose, significantly as melancholy makes up the vast majority 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 will make clear whether or not present scientific pointers for prevention of bipolar relapse are match for function for all sorts of temper episodes, particularly in these for whom lithium will not be 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 by a Wellcome Belief-funded research 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 melancholy: a within-subject evaluation in a Swedish nationwide cohort. The Lancet Psychiatry.
Different references
Alsaif, M. (2017). Antidepressants for bipolar melancholy. Nationwide Elf Service. https://www.nationalelfservice.web/mental-health/bipolar-disorder/antidepressants-for-bipolar-depression/
Baldessarini, R. J., Vázquez, G. H., & Tondo, L. (2020). Bipolar melancholy: a significant unsolved problem. Worldwide journal of bipolar problems, 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.web/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 problems. 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.web/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 information linkage research in Scotland. The British Journal of Psychiatry, 215(1), 415-421. https://doi.org/10.1192/bjp.2019.16
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