Choosing antidepressants for older adults: Dr. Max Pemberton's guide to efficacy and side effects

A landmark Lancet analysis of more than 150 studies involving over 58,000 patients found meaningful differences in side effects among commonly prescribed antidepressants during the first eight weeks of treatment. Researchers from King’s College London and the University of Oxford reported notable variations in weight changes, blood pressure, heart rate and cholesterol, a critical period when adverse effects can drive patients to abandon therapy. While antidepressants can be life-changing for people with moderate to severe depression, there is no one-size-fits-all solution. Talking therapies can help some with milder symptoms, but medication remains essential for many with more significant illness. Drawing on years of clinical experience, Dr. Max Pemberton, a consultant psychiatrist, emphasizes the need to tailor the choice of medication to the individual, weighing age, weight, blood pressure, comorbidities and personal priorities.

Guidelines from NICE typically recommend starting with a selective serotonin reuptake inhibitor, or SSRI, given its tolerability and effectiveness for many patients. If an SSRI does not provide adequate relief or is poorly tolerated, clinicians may switch within the class or move to another antidepressant. The Lancet analysis helps explain why that first few weeks matter: side effects such as nausea, sleep disturbance or sexual dysfunction often appear early and can lead to discontinuation if not anticipated. For Dr. Pemberton, that underscores the importance of an informed, shared decision-making process that aligns a drug’s pharmacology with a patient’s health profile and life goals. He notes that nearly every antidepressant carries some risk of sexual side-effects, weight change or sedation, but the balance of benefits and drawbacks will differ from person to person. For example, mirtazapine may increase appetite and weight, which can be therapeutic in an older adult who has lost weight due to depression.

The guide to the UK’s most commonly prescribed antidepressants presented here reflects Dr. Pemberton’s clinical experience and the Lancet findings. It is written with older adults in mind, recognizing that age, weight, cardiovascular risk and comorbidities influence which medication is most appropriate. No single drug dominates every case, and doctors will weigh effectiveness against potential interactions and tolerability. Sexual side-effects, for instance, are a common concern across the class of SSRIs, which can affect libido, arousal and, in some cases, the ability to reach orgasm. In rare cases, post-SSRI sexual dysfunction can persist after stopping the medication, highlighting the need for careful tapering and follow-up. Patients should never stop an antidepressant abruptly, as withdrawal symptoms can include dizziness and electric-shock sensations and may increase the risk of relapse. Tapering should be gradual and supervised, a point reinforced by major reviews in Lancet Psychiatry.

SERTRALINE (Lustral) is the most commonly prescribed SSRI in the UK and is often used as a first-line option for both depression and anxiety. It tends to be weight-neutral and has a relatively neutral effect on blood pressure and heart rate, making it a practical choice for many older adults. Healthcare providers will warn about nausea or stomach upset in the early weeks, and all SSRIs carry a risk of sexual side-effects that can affect libido and arousal for some patients. New study findings indicate that sertraline is generally well tolerated, with initial side-effects such as nausea and sleep disturbances typically improving within a few weeks.

CITALOPRAM (Cipramil) is a widely prescribed SSRI regarded as a gentler antidepressant with fewer drug interactions and fewer side-effects than some peers. It is often recommended as a good starting point for older adults. It is best for first-time users, people with high blood pressure, and those concerned about cholesterol, though higher doses can affect heart rhythm and interactions with other medications can complicate management. Sexual side-effects are possible, as with other SSRIs. New study findings suggest citalopram remains among the better tolerated SSRIs overall, with minimal impact on weight, blood pressure and cholesterol, though sexual side-effects remain a consideration.

ESCITALOPRAM (Cipralex) is a refined SSRI that is not stronger than its parent compound but can be used at a lower dose for the same effect, potentially reducing side-effects. It is effective for anxiety disorders as well as depression and is generally well tolerated, with minimal effects on weight, blood pressure and cholesterol. Think twice if you have heart rhythm issues or are taking medications that affect heart rhythm, and sexual function concerns are common with this drug, as with other SSRIs. New study findings show a profile similar to citalopram, with generally good tolerability but some sexual difficulties, including decreased desire and delayed or absent orgasm.

PAROXETINE (Seroxat) is an SSRI particularly effective for anxiety disorders, including social anxiety and panic, and it can be sedating, which may help with sleep. It is associated with concerns about cholesterol and withdrawal difficulty if discontinued abruptly. Sexual function can be affected, and it is often noted for more pronounced withdrawal symptoms than some other SSRIs. New study findings indicate effects on cholesterol and blood pressure, with higher risk of sedation and weight gain, and a higher likelihood of withdrawal-related symptoms if stopped suddenly. Paroxetine is frequently cited as causing more sexual dysfunction than other SSRIs, though most patients see their sexual function return to baseline after stopping, a process that can take weeks in some.

VENLAFAXINE (Effexor) is an SNRI that targets both serotonin and norepinephrine, and it is commonly used for more severe depression or when SSRIs have failed to provide relief. It can help with fatigue and energy but carries risks: higher blood pressure at higher doses, potential cholesterol changes, faster heart rate and weight gain. It can also produce pronounced withdrawal symptoms if discontinued suddenly and may have sexual side-effects, though some patients report these less frequently than with SSRIs. New study findings show that venlafaxine can raise blood pressure and heart rate in a dose-related fashion and may influence cholesterol, underscoring the need for monitoring in older patients.

DULOXETINE (Cymbalta) is another SNRI frequently chosen when SSRIs are not effective, with licensed uses for pain—such as back pain or arthritis—and for diabetic nerve pain or stress incontinence in women. It can raise cholesterol levels and impair liver function in some people, so liver monitoring is advised, especially in those with preexisting liver concerns. It can also raise blood pressure and may cause daytime sedation in some patients. Sexual function can be affected, but reports often indicate fewer sexual side-effects than SSRIs. New study findings note cholesterol elevation and early gastrointestinal symptoms; like venlafaxine, careful blood pressure monitoring is recommended in older patients.

MIRTAZAPINE (Zispin) is a tetracyclic antidepressant with a different action: it blocks alpha-2 receptors to boost serotonin and norepinephrine release. It can be very sedating and tends to increase appetite and weight, which may be advantageous for depressed patients who have lost weight but problematic for those who are overweight. It generally causes fewer sexual side-effects than SSRIs, a notable advantage. However, daytime grogginess can limit its usefulness for some older adults. It is particularly helpful for depression with insomnia and for patients who need help with sleep and appetite when SSRIs have caused intolerable side-effects. New study findings show significant weight gain and appetite increases as common early effects, while also confirming its strong sedative profile and relatively favorable sexual side-effect profile.

AMITRIPTYLINE is a classic tricyclic antidepressant and an older option still used for certain cases. It increases serotonin and norepinephrine like newer antidepressants but also has antihistamine and anticholinergic effects, which can lead to dry mouth, constipation and blurred vision. It is more sedating and carries a higher overdose risk, so it is generally avoided in patients with active suicidality. It remains valuable for depression with chronic pain or nerve pain, severe insomnia and migraine prevention, particularly when newer drugs have failed. Think twice if you are concerned about weight gain or if you have heart problems or glaucoma or an enlarged prostate, because this drug can raise heart rate and blood pressure and worsen eye pressure. New study findings highlight weight gain and cardiovascular effects, along with multiple anticholinergic symptoms, though it often causes fewer sexual side-effects than SSRIs.

NORTRIPTYLINE is another tricyclic antidepressant, often better tolerated than amitriptyline and used when a tricyclic is needed but amitriptyline is not suitable. It is useful for depression in older adults and for chronic or nerve pain, with a lower overall burden of dry mouth, constipation and confusion than amitriptyline. Yet it can significantly raise blood pressure and heart rate and carries risks for those with glaucoma or falls history. New study findings indicate major effects on blood pressure and heart rate, though nortriptyline tends to cause fewer sexual problems than SSRIs, making it a viable option in selected patients.

AGOMELATINE (Valdoxan) is a newer antidepressant that engages melatonin receptors to help reset the sleep-wake cycle. It is associated with weight loss in early findings and has minimal sexual side-effects, appealing to patients who prioritize sleep and sexual function. Liver monitoring is essential, as agomelatine can, in rare cases, cause liver inflammation, and interactions with certain antibiotics or other antidepressants can raise blood levels. New study findings associate weight loss with this drug and note generally favorable tolerability, though long-term data remain more limited than for older agents.

VORTIOXETINE (Brintellix) is a newer antidepressant that acts on multiple serotonin receptors and may offer cognitive benefits such as improved concentration. It is less likely to cause sexual side-effects and is considered well tolerated in older adults, though it remains less familiar to many GPs than the best-known SSRIs. It requires caution with other serotonergic medications and certain painkillers that can raise serotonin levels, and there is some concern about bleeding risk with some patient profiles. New study findings describe generally good tolerability without significant weight, blood pressure or heart-rate changes, with nausea as the most common early complaint that typically eases over time.

FLUOXETINE (Prozac) is one of the best-known SSRIs and is often chosen for patients who want to avoid weight gain or who have had withdrawal difficulties with other antidepressants due to its long half-life. It can raise blood pressure and may initially increase anxiety or jitteriness in some patients. Sexual side-effects are common with fluoxetine, as with other SSRIs, though some patients report relatively lower rates than with others. New study findings note a tendency toward weight loss and higher energy, but also potential increases in blood pressure and jitters for some users, with withdrawal less abrupt because of the prolonged half-life.

In sum, the guidance for older adults is to balance mood improvement with the maintenance of physical health and cognitive function. Dr. Pemberton stresses that tapering off any antidepressant should be gradual and supervised to minimize withdrawal and relapse. The Lancet study reinforces the value of ongoing monitoring and shared decision-making, including regular checks of weight, blood pressure and cholesterol in patients with aging bodies and multiple health concerns. Patients are encouraged to discuss side-effects openly with their prescriber, who can adjust therapy or switch to another option to optimize outcomes. The goal is to align the chosen antidepressant’s benefits with a patient’s overall health goals, ensuring the best possible quality of life during treatment.