New Lancet findings underscore distinct antidepressant side effects, guiding personalized treatment for older patients

A landmark synthesis published in The Lancet Psychiatry shows antidepressants are not one-size-fits-all. Researchers from King’s College London and the University of Oxford analyzed more than 150 studies involving over 58,000 patients and found meaningful differences in side-effects during the first eight weeks of treatment. Weight changes, blood pressure, heart rate and cholesterol levels varied significantly across medications in this early period, a time when side-effects typically emerge and when people are most likely to discontinue treatment. The findings underscore the importance of tailoring antidepressant choices to the individual, balancing potential benefits against tolerability.

While the eight-week window may seem brief, it is precisely when patients decide whether to stay on therapy. Clinicians consider factors such as how sedating a drug is, whether it helps with pain or sleep, and how easy it is to taper off later. The Lancet analysis aligns with updated guidance from NICE, which recommends starting treatment with a selective serotonin reuptake inhibitor (SSRI) for many patients because these drugs are generally well tolerated and effective. If the initial SSRI does not work or causes troublesome side-effects, a different SSRI or another class may be tried. Dr Max Pemberton, a consultant psychiatrist, has drawn on decades of clinical experience and the Lancet findings to assemble a guide to the most commonly prescribed antidepressants in the UK. |

Sertraline (Lustral) is the most frequently prescribed SSRI in the UK and is often a first-line choice because it tends to be weight-neutral and has relatively neutral effects on blood pressure and cholesterol. Initial side-effects such as nausea can occur but typically improve after a few weeks. For those concerned about sexual function, all SSRIs can affect libido and arousal, with up to a majority experiencing some difficulty in this area during treatment. Sertraline’s broad tolerability profile makes it a common starting point, though individual responses vary.

Citalopram (Cipramil) is widely prescribed and regarded as a gentler option with fewer drug interactions and a relatively favorable side-effect profile. It is often recommended for new users and older adults due to tolerability, and it tends to have minimal effects on weight and cholesterol. Caution exists for those with heart rhythm problems at higher doses or who are taking multiple medications that affect the heart. Sexual side-effects are possible, as with other SSRIs.

Escitalopram (Cipralex) resembles citalopram but is a more purified form, allowing a lower dose to achieve the same effect and potentially reducing side-effects. It shares the general SSRI profile—good for anxiety and depression, minimal impact on weight, blood pressure and cholesterol—but sexual difficulties can occur, including reduced desire and delayed orgasm.

Paroxetine (Seroxat) is another SSRI with a notably sedating effect for many people, which can be beneficial for sleep problems but may contribute to daytime grogginess. It is also linked to withdrawal challenges if stopped abruptly and can be associated with weight gain. If future stopping is anticipated, clinicians often plan a careful tapering schedule.

Venlafaxine (Effexor) is an SNRI that can be effective when SSRIs do not fully address more severe depression or coexisting fatigue. It may raise blood pressure, heart rate and cholesterol levels at higher doses and can cause withdrawal symptoms if stopped suddenly. Sexual dysfunction can occur, though some patients experience it less than with certain SSRIs.

Duloxetine (Cymbalta) is another SNRI used for depressive symptoms and for pain conditions such as back pain or arthritis. It may influence cholesterol and liver function in some patients and requires caution in those with high blood pressure or liver problems. As with other antidepressants, sexual side-effects are possible, though the pattern varies individually.

Mirtazapine (Zispin) is a tetracyclic antidepressant often selected for sleep and appetite issues. It can be very sedating, which helps with insomnia but can leave people feeling fatigued the next day. Weight gain and increased appetite are common, yet it tends to have fewer sexual side-effects than SSRIs. It is particularly considered when sleep and appetite are major concerns, and when SSRIs have caused troublesome side-effects.

Amitriptyline is a older tricyclic antidepressant that remains useful for certain conditions such as chronic pain or insomnia when modern antidepressants have not worked. It is more sedating and has anticholinergic effects, which can lead to dry mouth, constipation and cognitive effects, and it carries a higher risk if misused or overdosed. It can raise heart rate and blood pressure and requires careful consideration in aging patients with heart or glaucoma issues.

Nortriptyline is another tricyclic option that is often better tolerated than amitriptyline, particularly in older adults. It can still raise heart rate and blood pressure and has anticholinergic effects, but it tends to cause fewer sexual side-effects. It is usually considered when a tricyclic is necessary but amitriptyline is not well tolerated.

Agomelatine (Valdoxan) acts on melatonin receptors to help regulate sleep-wake cycles. It has been associated with weight loss in some studies and generally causes fewer sexual side-effects than SSRIs. Liver function monitoring is essential, and certain drug interactions can raise blood levels of agomelatine, increasing the risk of adverse effects.

Vortioxetine (Brintellix) is a newer antidepressant that modulates multiple serotonin receptors and is often chosen for cognitive symptoms, including difficulties with concentration. It is typically well tolerated, with fewer sexual side-effects than SSRIs, though nausea can occur and usually improves with time. It is sometimes reserved for use after trying other options.

Fluoxetine (Prozac) has a long history dating back to the 1980s and is a well-known SSRI. It is less associated with withdrawal symptoms due to its long half-life and can be helpful for motivation and energy, though it can increase blood pressure in some individuals and may heighten anxiety or jitteriness early in treatment. Sexual side-effects are possible, and drug interactions can be a consideration due to its longer half-life. Some patients experience weight loss rather than gain.

The newest findings reinforce a core message: every antidepressant carries its own profile of benefits and risks, and a patient’s age, weight, blood pressure, coexisting conditions and personal priorities—such as sexual function or the ability to sleep through the night—shape the best-fit choice. A doctor will discuss these factors openly, weighing the likelihood of response against potential side-effects to arrive at a personalized plan. In some cases, psychotherapy remains an effective option, particularly for milder depression, while in others medication is essential for symptom relief.

Stopping antidepressants abruptly can cause withdrawal symptoms and increase the risk of depression returning. The Lancet Psychiatry major review published recently suggests that a slow taper, combined with psychological support, is the most effective strategy for stopping. Healthcare providers emphasize that patients should not alter dosing or discontinue medication without medical guidance and should engage in shared decision-making when adjusting treatment. Given the complexity of antidepressant effects, clinicians often monitor heart rate, blood pressure, weight, mood, sleep, appetite and sexual function closely during the early weeks and again after any change.

Ultimately, the key takeaway from these datasets and guidelines is personalization. The same drug that helps one patient may cause problematic side-effects in another. The ongoing challenge for clinicians is to balance efficacy with tolerability, adjust promptly when concerns arise, and support patients through the crucial early weeks of treatment to maximize the chances of sustained improvement.