Frequent psychological well being issues like despair and anxiousness influence about 20% of the grownup inhabitants (NHS Digital, 2025). These situations could cause excessive emotional ache and might make it tough to perform in on a regular basis life.
Antidepressant medicine will be efficient in decreasing each despair (Cipriani et al, 2018) and anxiousness signs (Slee et al, 2019), however one of many largest considerations folks might have about beginning remedy is the potential danger of unwanted effects (An et al, 2025). That is significantly related for individuals who have already got, or are susceptible to, long-term bodily well being situations, as unwanted effects in these people may very well be extra harmful. Clinicians could also be reluctant to prescribe antidepressants in such eventualities.
We all know that completely different antidepressant medicines can have completely different unwanted effects (British Nationwide Formulary, 2025), however there’s restricted proof concerning the extent to which these unwanted effects may happen. Because of this the selection of antidepressant medicine can usually be primarily based on prescriber preferences or habits, reasonably than proof.
A brand new systematic assessment by Toby Pillinger et al. (2025), out right now in The Lancet, gathered data from antidepressant drug trials the place bodily well being unwanted effects had been reported. Their purpose was to evaluate and rank antidepressants primarily based on their bodily well being results.
Antidepressants are an efficient remedy for despair and anxiousness, however unwanted effects can range, and the selection of antidepressant medicine can usually be primarily based on prescriber habits, reasonably than person-centred proof.
Strategies
Pillinger et al. searched on-line databases to determine all related randomised managed trials (RCTs). They included trials that met the next standards:
- In contrast any single antidepressant both to a placebo or to a different antidepressant.
- Included adults with a psychiatric dysfunction or fibromyalgia (as antidepressants will be prescribed to deal with psychological well being signs in these people).
- Included not less than one of many following bodily well being measurements: weight, blood strain, coronary heart fee, qt interval (time taken for coronary heart to contract and reset), ldl cholesterol, blood sugar, blood electrolytes, kidney and liver perform assessments.
The authors mixed trial outcomes utilizing a community meta-analysis to match the consequences of various antidepressant medicines. A community meta-analysis is a solution to evaluate many remedies without delay, even when a few of them have by no means been immediately examined towards one another, by connecting the outcomes of research that share a typical remedy for comparability. They then checked out whether or not the consequences had been completely different primarily based on folks’s intercourse, age and weight at first of the examine.
Outcomes
Pillinger et al. recognized 168 RCTs that measured bodily well being results of antidepressants. These included a complete of 58,534 contributors and in contrast 30 completely different antidepressant medicines. Nonetheless, not all antidepressant medicines had been coated by numerous trials: the medicine with probably the most trials was fluoxetine (32 trials) and the medicines with the least variety of trials had been desipramine, phenelzine and selegeline (1 trial every). The period of the trials lasted from 3-12 weeks, with the common being 8 weeks. The common age of contributors was 45 years, 62% had been feminine and 75% had been white.
Clinically related results
The impact on bodily well being after 8 weeks diverse significantly between completely different antidepressant medicines. Of all of the unwanted effects measured, clinically related results (which means the consequences had been doubtlessly sufficiently big to make a distinction to somebody’s well being) had been present in these associated to long-term coronary heart well being. The clinically related results had been as follows:
- Amitriptyline elevated weight, coronary heart fee and blood strain.
- Duloxetine elevated whole ldl cholesterol, blood glucose, coronary heart fee, and blood strain.
- Desvenlafaxine and venlafaxine elevated whole ldl cholesterol, coronary heart fee and blood strain.
- Imipramine, levomilnacipran, and maprotiline elevated coronary heart fee and blood strain.
- Clomipramine, doxepin, nortriptyline and reboxetine elevated coronary heart fee.
- Fluvoxamine, mianserin, milnacipran, and mirtazapine elevated weight acquire
- Paroxetine elevated whole ldl cholesterol.
- Fluoxetine elevated blood strain.
The writer’s discovered that will increase in blood strain had been worse if folks had a better weight at first of antidepressant remedy. Will increase in glucose had been worse as folks elevated in age.
When folks have hypertension, coronary heart fee, whole ldl cholesterol, weight and/or blood sugar, this will enhance the danger of coronary heart illness, stroke and kind 2 diabetes. Nonetheless, it is very important notice that the will increase attributable to antidepressants is probably not sufficiently big to be dangerous for everybody. Their influence is dependent upon an individual’s well being at first of remedy and whether or not these modifications are sustained. For instance, if a person was below weight, or was sufficiently under the brink for being thought-about chubby, including an additional 1kg might not make a distinction. Nonetheless, if this enhance in 1kg continues over a number of months, the person might change into chubby and so would have an elevated danger of great long-term well being issues.
Antidepressants have various results on bodily well being, with some inflicting clinically related modifications in heart-related measures which will pose dangers relying on baseline well being and persistence.
Conclusions
The authors concluded that antidepressants differed significantly of their bodily well being unwanted effects, significantly for unwanted effects that elevated the danger of situations similar to coronary heart illness, stroke and kind 2 diabetes.
They steered that remedy tips needs to be up to date to replicate these variations. Nonetheless, additionally they careworn how the selection of antidepressant needs to be made on a person foundation, contemplating scientific want and particular person preferences.
Antidepressants differ in bodily well being unwanted effects, so remedy tips ought to replicate these dangers whereas supporting individualised prescribing.
Strengths and limitations
The authors carried out a radical search of all the suitable databases containing details about scientific drug trials. Their use of the community meta-analysis methodology allowed them to match a number of antidepressant medicines, no matter whether or not they had been immediately in contrast within the unique analysis research.
One limitation of this assessment is that not each antidepressant had data accessible for each bodily well being measurement. For instance, whereas citalopram and escitalopram didn’t present proof of dangerous unwanted effects, there have been no trials for citalopram measuring the liver and kidney perform markers – ALP and urea – and no trials for escitalopram measuring the blood electrolytes potassium or sodium.
The authors restricted their search to solely embrace RCTs. These are the gold customary solution to consider the consequences of medicines. Nonetheless, RCTs are usually brief in period, partly as a result of excessive value of working a trial. Due to this fact, a second limitation of this assessment was the short-term nature of the unwanted effects measured. Some modifications in bodily well being might take longer to happen and should enhance additional over time. This might imply the danger of great long-term penalties, similar to coronary heart illness, are underestimated on this assessment.
Lastly, RCTs might not all the time be consultant of the real-world inhabitants, or relevant to all teams of individuals. For instance, a lot of the trials excluded individuals who have already got bodily well being situations. These people could also be at larger danger of unwanted effects resulting from already impaired well being or interactions with different medicines they’re taking. Trials additionally usually exclude older folks, who’re at elevated danger of unwanted effects, or pregnant ladies; the place the danger of hurt is unethical.
The assessment used sturdy strategies to match unwanted effects of antidepressants, however limitations embrace lacking information for some medicine, brief period of included trials, and underrepresentation of higher-risk teams.
Implications for follow
This was the first systematic assessment to match the bodily well being unwanted effects of various antidepressant medicines. This can be a actually essential contribution to the proof base for antidepressants, as remedy tips advocate consideration of unwanted effects when selecting remedy (Nationwide Institute for Well being and Care Excellence, 2022).
The selection of antidepressant ought to all the time be mentioned with a medical practitioner. You will need to keep in mind that everybody reacts in another way to antidepressant medicine, and we nonetheless don’t totally perceive the explanations for this. Nonetheless, this assessment gives essential data that may assist information remedy selections, significantly in individuals who might already be at elevated danger of bodily well being issues.
The antidepressant medicines that confirmed the best danger of bodily well being unwanted effects should not usually prescribed as the primary alternative of antidepressant. Pointers advocate beginning remedy with a sort of antidepressant known as an “SSRI”. This consists of citalopram and escitalopram, which had the least unwanted effects on this assessment. Medicines similar to amitriptyline, duloxetine, desvenlafaxine and venlafaxine are often solely advisable when different antidepressants have didn’t work. At this level, a dialogue between affected person and physician ought to deal with the professionals and cons of enhancing psychological well being signs (which may additionally negatively influence bodily well being) versus the danger of unwanted effects.
Antidepressants with larger danger of bodily well being unwanted effects can generally have a big effect on enhancing folks’s psychological well being. In these conditions, scientific groups can monitor bodily well being measurements (similar to these on this assessment) extra carefully. Extra assist may very well be supplied to assist people keep a wholesome way of life, which may counterbalance the danger of unwanted effects similar to weight acquire or elevated blood strain.
Additional analysis is required to know the long-term bodily well being results of antidepressant medicines. The place this isn’t potential in drug trials, it may very well be potential by analysing real-world antidepressant use from medical information. This may additionally enable researchers to incorporate folks with bodily long-term situations, older folks and pregnant ladies with out risking hurt to those extra susceptible teams. Nonetheless, it may be tough to separate the impact of the antidepressant medicine on bodily well being from the detrimental influence of poor psychological well being itself.
Future RCTs ought to guarantee they embrace a full vary of bodily well being unwanted effects of their analysis of antidepressant medicines. This may be helpful for folks with widespread psychological problems, scientific groups, and even pharmaceutical corporations, to spotlight the most secure antidepressant medicines accessible.
This assessment gives the primary systematic comparability of bodily well being unwanted effects throughout antidepressants, providing proof to information personalised remedy selections, assist updates to prescribing tips, and encourage additional analysis into long-term dangers and susceptible populations.
Assertion of pursuits
Nothing to declare.
Hyperlinks
Main paper
Pillinger T, Arumuhan A, McCutcheon RA,… Cipriani A. et al. The results of antidepressants on cardiometabolic and different physiological parameters: a scientific assessment and community meta-analysis. The Lancet. 2025. https://doi.org/10.1016/S0140-6736(25)01293-0
Different references
NHS Digital (2025). Grownup Psychiatric Morbidity Survey: Survey of Psychological Well being and Wellbeing, England, 2023/4. https://digital.nhs.uk/data-and-information/publications/statistical/adult-psychiatric-morbidity-survey/survey-of-mental-health-and-wellbeing-england-2023-24
Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JPT, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara Ok, Tajika A, Ioannidis JPA, Geddes JR. Comparative efficacy and acceptability of 21 antidepressant medicine for the acute remedy of adults with main depressive dysfunction: a scientific assessment and community meta-analysis. Lancet. 2018 Apr 7;391(10128):1357-1366. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32802-7/fulltext
Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N. Pharmacological remedies for generalised anxiousness dysfunction: a scientific assessment and community meta-analysis. Lancet. 2019 Feb 23;393(10173):768-777. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31793-8/fulltext
An MH, Kim MG, Kim J, Chang S, Lee DY, Park RW. Public notion and altering attitudes towards antidepressants over a decade in social media: Classes discovered from on-line dialogue utilizing synthetic intelligence. PLoS One. 2025 Sep 4;20(9):e0318464. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0318464
British Nationwide Formulary (2025). Antidepressant medicine. https://bnf.good.org.uk/treatment-summaries/antidepressant-drugs/
Nationwide Institute for Well being and Care Excellence (2022). Despair in adults: remedy and administration. https://www.good.org.uk/steering/ng222
Discussion about this post