Frequent psychological well being issues like melancholy and nervousness impression about 20% of the grownup inhabitants (NHS Digital, 2025). These situations may cause excessive emotional ache and may make it tough to perform in on a regular basis life.
Antidepressant treatment may be efficient in lowering each melancholy (Cipriani et al, 2018) and nervousness signs (Slee et al, 2019), however one of many largest issues folks might have about beginning remedy is the potential danger of unwanted side effects (An et al, 2025). That is significantly related for individuals who have already got, or are vulnerable to, long-term bodily well being situations, as unwanted side effects in these people may very well be extra harmful. Clinicians could also be reluctant to prescribe antidepressants in such situations.
We all know that completely different antidepressant drugs can have completely different unwanted side effects (British Nationwide Formulary, 2025), however there’s restricted proof relating to the extent to which these unwanted side effects may happen. Which means the selection of antidepressant treatment can typically be primarily based on prescriber preferences or habits, somewhat than proof.
A brand new systematic overview by Toby Pillinger et al. (2025), out at the moment in The Lancet, gathered data from antidepressant drug trials the place bodily well being unwanted side effects have been reported. Their intention was to examine and rank antidepressants primarily based on their bodily well being results.
Antidepressants are an efficient remedy for melancholy and nervousness, however unwanted side effects can differ, and the selection of antidepressant treatment can typically be primarily based on prescriber habits, somewhat than person-centred proof.
Strategies
Pillinger et al. searched on-line databases to establish 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 may 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 price, qt interval (time taken for coronary heart to contract and reset), ldl cholesterol, blood sugar, blood electrolytes, kidney and liver perform checks.
The authors mixed trial outcomes utilizing a community meta-analysis to check the results of various antidepressant drugs. A community meta-analysis is a method to examine many therapies directly, 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 results have been completely different primarily based on folks’s intercourse, age and weight in the beginning 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 members and in contrast 30 completely different antidepressant drugs. Nonetheless, not all antidepressant drugs have been coated by numerous trials: the treatment with probably the most trials was fluoxetine (32 trials) and the drugs with the least variety of trials have 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 members was 45 years, 62% have been feminine and 75% have been white.
Clinically related results
The impact on bodily well being after 8 weeks diversified significantly between completely different antidepressant drugs. Of all of the unwanted side effects measured, clinically related results (that means the results have been probably sufficiently big to make a distinction to somebody’s well being) have been present in these associated to long-term coronary heart well being. The clinically related results have been as follows:
- Amitriptyline elevated weight, coronary heart price and blood strain.
- Duloxetine elevated whole ldl cholesterol, blood glucose, coronary heart price, and blood strain.
- Desvenlafaxine and venlafaxine elevated whole ldl cholesterol, coronary heart price and blood strain.
- Imipramine, levomilnacipran, and maprotiline elevated coronary heart price and blood strain.
- Clomipramine, doxepin, nortriptyline and reboxetine elevated coronary heart price.
- 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 have been worse if folks had the next weight in the beginning of antidepressant remedy. Will increase in glucose have been worse as folks elevated in age.
When folks have hypertension, coronary heart price, whole ldl cholesterol, weight and/or blood sugar, this may improve the danger of coronary heart illness, stroke and sort 2 diabetes. Nonetheless, it is very important be aware that the will increase attributable to antidepressants will not be sufficiently big to be dangerous for everybody. Their impression will depend on an individual’s well being in the beginning of remedy and whether or not these modifications are sustained. For instance, if a person was below weight, or was sufficiently under the edge for being thought-about chubby, including an additional 1kg might not make a distinction. Nonetheless, if this improve in 1kg continues over a number of months, the person might turn out to be 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 that will pose dangers relying on baseline well being and persistence.
Conclusions
The authors concluded that antidepressants differed significantly of their bodily well being unwanted side effects, significantly for unwanted side effects that elevated the danger of situations equivalent to coronary heart illness, stroke and sort 2 diabetes.
They instructed that remedy pointers needs to be up to date to replicate these variations. Nonetheless, in addition they burdened how the selection of antidepressant needs to be made on a person foundation, contemplating medical want and particular person preferences.
Antidepressants differ in bodily well being unwanted side effects, so remedy pointers ought to replicate these dangers whereas supporting individualised prescribing.
Strengths and limitations
The authors performed an intensive search of all the suitable databases containing details about medical drug trials. Their use of the community meta-analysis technique allowed them to check a number of antidepressant drugs, no matter whether or not they have been immediately in contrast within the unique analysis research.
One limitation of this overview is that not each antidepressant had data out there for each bodily well being measurement. For instance, whereas citalopram and escitalopram didn’t present proof of dangerous unwanted side 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 method to consider the results of medicines. Nonetheless, RCTs are sometimes brief in period, partly because of the excessive value of working a trial. Due to this fact, a second limitation of this overview was the short-term nature of the unwanted side effects measured. Some modifications in bodily well being might take longer to happen and should improve additional over time. This might imply the danger of great long-term penalties, equivalent to coronary heart illness, are underestimated on this overview.
Lastly, RCTs might not at all times 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 increased danger of unwanted side effects attributable to already impaired well being or interactions with different drugs they’re taking. Trials additionally typically exclude older folks, who’re at elevated danger of unwanted side effects, or pregnant ladies; the place the danger of hurt is unethical.
The overview used strong strategies to check unwanted side effects of antidepressants, however limitations embrace lacking information for some medication, brief period of included trials, and underrepresentation of higher-risk teams.
Implications for apply
This was the first systematic overview to check the bodily well being unwanted side effects of various antidepressant drugs. It is a actually necessary contribution to the proof base for antidepressants, as remedy pointers suggest consideration of unwanted side effects when selecting remedy (Nationwide Institute for Well being and Care Excellence, 2022).
The selection of antidepressant ought to at all times be mentioned with a medical practitioner. You will need to keep in mind that everybody reacts in a different way to antidepressant treatment, and we nonetheless don’t totally perceive the explanations for this. Nonetheless, this overview supplies necessary data that may assist information remedy choices, significantly in individuals who might already be at elevated danger of bodily well being issues.
The antidepressant drugs that confirmed the best danger of bodily well being unwanted side effects will not be sometimes prescribed as the primary alternative of antidepressant. Pointers suggest beginning remedy with a kind of antidepressant referred to as an “SSRI”. This contains citalopram and escitalopram, which had the least unwanted side effects on this overview. Drugs equivalent to amitriptyline, duloxetine, desvenlafaxine and venlafaxine are normally solely really helpful when different antidepressants have did not work. At this level, a dialogue between affected person and physician ought to concentrate on the professionals and cons of bettering psychological well being signs (which might additionally negatively impression bodily well being) versus the danger of unwanted side effects.
Antidepressants with increased danger of bodily well being unwanted side effects can typically have a huge impact on bettering folks’s psychological well being. In these conditions, medical groups can monitor bodily well being measurements (equivalent to these on this overview) extra carefully. Extra assist may very well be supplied to assist people keep a wholesome way of life, which might counterbalance the danger of unwanted side effects equivalent to weight acquire or elevated blood strain.
Additional analysis is required to know the long-term bodily well being results of antidepressant drugs. 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 is able to additionally permit 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 treatment on bodily well being from the detrimental impression of poor psychological well being itself.
Future RCTs ought to guarantee they embrace a full vary of bodily well being unwanted side effects of their analysis of antidepressant drugs. This is able to be useful for folks with widespread psychological problems, medical groups, and even pharmaceutical firms, to spotlight the most secure antidepressant drugs out there.
This overview supplies the primary systematic comparability of bodily well being unwanted side effects throughout antidepressants, providing proof to information personalised remedy choices, assist updates to prescribing pointers, and encourage additional analysis into long-term dangers and susceptible populations.
Assertion of pursuits
Nothing to declare.
Hyperlinks
Major paper
Pillinger T, Arumuhan A, McCutcheon RA,… Cipriani A. et al. The results of antidepressants on cardiometabolic and different physiological parameters: a scientific overview 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 Okay, Tajika A, Ioannidis JPA, Geddes JR. Comparative efficacy and acceptability of 21 antidepressant medication for the acute remedy of adults with main depressive dysfunction: a scientific overview 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 therapies for generalised nervousness dysfunction: a scientific overview 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 realized 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 medication. 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
