Stopping depressive relapse is a serious purpose within the administration of bipolar dysfunction. It has been proven that despair makes up round 72% of general time spent sick in individuals with bipolar (Forte et al., 2015), and that bipolar despair particularly is related to important bodily and psychological morbidity, in addition to elevated mortality (Baldessarini et al., 2020).
Lithium is the first-line really helpful medicine 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 international locations (Edward, 2019). Antipsychotics, different temper stabilisers and – though not really helpful by NICE – antidepressants are additionally usually prescribed long-term for individuals with bipolar dysfunction. As just lately blogged right here and right here, the usage of antidepressants within the long-term administration of bipolar dysfunction is controversial, with the chance 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 medical eventualities (McIntyre et al., 2020; Pacchiarotti et al., 2013).
In a paper just lately revealed 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 on account of a depressive temper episode.
Stopping depressive relapse is a serious purpose within the administration of bipolar dysfunction.
Strategies
Ermis et al used a cohort research design to determine whether or not prescription of temper stabilisers, antidepressants and antipsychotics had been related to admission to hospital resulting from depressive sickness (major end result), and admission to hospital resulting from 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’ drugs had been gathered from the Prescribed Medication Register.
A within-subjects Cox regression evaluation (adjusted for time-variant covariates corresponding to time since cohort entry and use of different psychopharmacological drugs) was used to match intervals of time through which the topic was prescribed a selected medicine towards instances through which no antidepressant, antipsychotic, or temper stabiliser had been prescribed. Numerous sensitivity analyses had been additionally performed, 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 (nervousness 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 prognosis and the imply follow-up time was 9.1 years (SD 5.1). At follow-up, antidepressant monotherapy was the most typical 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%).
General, 16,190 topics (15.3%) had been hospitalised with a depressive episode a minimum of as soon as in the course of the follow-up interval; 8,066 topics (7.7%) had been hospitalised resulting from mania.
Decreased probability of depression-related hospitalisation
- Temper stabiliser monotherapy was the one medicine group discovered to be related to a decreased probability of depression-related hospitalisation in contrast with the prescription of no drugs 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 probability 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 probability of admission resulting from despair on this cohort of individuals with bipolar dysfunction (aHR 0.75, 95% CI 0.67 to 0.85).
Elevated probability of depression-related hospitalisation
- Aside from 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 probability of depression-related hospitalisation.
- Notably, a number of drugs had been related to an elevated probability depression-related hospitalisation, specifically quetiapine, duloxetine, citalopram, olanzapine, mirtazapine, vortioxetine and aripiprazole.
Decreased probability of hospitalisation resulting from a somatic situation
- By way of secondary outcomes, lithium was the one medicine related to a decreased probability of hospitalisation resulting from a somatic situation (aHR 0.86, 95% CI 0.80 to 0.93), with no statistically important associations being discovered between the opposite drugs and somatic hospitalisation.
Elevated probability of mania-related hospitalisation
- Antidepressants-only had been the one group that had been related to elevated probabilities of hospitalisation resulting from mania (aHR 1.22, 95% CI 1.03 to 1.44); all different drugs teams, alone or together, had been related to decreased probabilities of mania-related hospitalisation.
In particular person medicine evaluation, solely lithium confirmed a decreased probability of depression-related hospitalisation; all different drugs had been both equivocal or related to elevated probability of depression-related hospitalisation. [View full sized graphic]
Conclusions
The outcomes of this research spotlight that lithium is the one monotherapy that decreases the probabilities of depression-related hospitalisation in individuals with bipolar dysfunction. Extra 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 probability 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 correct 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 match a number of drugs on the similar 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 in a position to pattern numerous the inhabitants with a bipolar prognosis 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, 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 knowledge on ethnicity weren’t accessible, each of which restrict the generalisability of the research outcomes to explicit teams.
The authors famous that by specializing in hospitalisation, the outcomes of this research are solely related for probably the most extreme circumstances of bipolar despair and don’t think about the advantages or harms that these drugs could also be exerting in sufferers who’re managed fully 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 an excellent measure of the efficacy of those drugs.
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 medicine was taken. Usually talking, nonetheless, it’s possible that almost all of these prescribed a medicine do take it, and the big numbers included on this pattern are more likely to minimise the impact that medicine non-compliance in small minority could have on general outcomes.
Regardless of limitations, the big pattern measurement and lengthy follow-up make the outcomes pretty generalisable to the bipolar inhabitants and vital medical eventualities.
Implications for follow
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 resulting from nervousness amongst sufferers and clinicians in regards to the elevated monitoring that’s required for lithium or resulting from its particular adversarial impact profile. It could even be associated to the low value of lithium, which can be driving the pharmaceutical business to promote the usage of different, costlier choices, probably swaying affected person desire. Regardless of the motive, a transfer away from prescribing lithium poses the chance of many sufferers lacking out on its potential advantages.
After lithium, the second- and third-line NICE-recommended preventative drugs for bipolar dysfunction are antipsychotic monotherapy and augmentation with valproate. This paper confirmed that these drugs 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 probability hospitalisation resulting from a depressive episode. This will make clinicians assume twice about prescribing antipsychotics or valproate long-term in bipolar dysfunction if the first purpose of remedy is to forestall additional depressive quite than manic relapses. In lots of sufferers this would be the purpose, notably 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 tips for prevention of bipolar relapse are match for function for all sorts of temper episodes, particularly in these for whom lithium just isn’t an choice.
A transfer away from prescribing lithium poses the chance of many sufferers lacking out on its potential advantages.
Assertion of pursuits
No conflicts of curiosity to declare.
I’m at the moment 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 despair: a within-subject evaluation in a Swedish nationwide cohort. The Lancet Psychiatry.
Different references
Alsaif, M. (2017). Antidepressants for bipolar despair. Nationwide Elf Service. https://www.nationalelfservice.internet/mental-health/bipolar-disorder/antidepressants-for-bipolar-depression/
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
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