Choosing the best antidepressants for teenagers and seniors

Depression can affect people at any age. It is most common in teenagers and young adults, but antidepressant use rises with age. An analysis of Medavie Blue Cross drug claims found that older plan members fill antidepressant prescriptions more often than younger ones. Antidepressants, together with counselling, can help manage depression, but the safest choice and dose depend on age. Young people and older adults respond differently and face different risks. In other words, the best antidepressant for a young person may not be the best choice for a senior.

How is depression treated in teenagers?

For mild to moderate depression in teenagers, psychotherapy, such as cognitive behavioural therapy, is usually tried first. When medication is needed, the evidence points to a few options:

• Fluoxetine has the strongest evidence. In a large analysis of 34 trials in children and teenagers, it was the only antidepressant that worked clearly better than a placebo.
• Escitalopram and sertraline are alternatives that are generally avoided in youth due to the higher risk of suicide due to treatment failure in ultrarapid metabolizers.
• Paroxetine, venlafaxine, duloxetine and tricyclic antidepressants are generally not recommended for depression in young people because of weaker evidence or more side effects.

Treatment works best when medication and therapy are combined and the young person and family are closely involved.

Do antidepressants increase suicidal thoughts in young people?

Health Canada and the US Food and Drug Administration require a warning on all antidepressants: in children, teenagers and young adults under 25, they can increase suicidal thoughts and behaviours in a small number of people, especially in the first weeks of treatment or after a dose change. This does not mean antidepressants should be avoided. Untreated depression is itself a major risk for suicide. It means young people should be checked closely, especially in the first one to two months.

Genes can affect this risk. Escitalopram, citalopram and sertraline are broken down by the CYP2C19 enzyme. In a large Danish study of more than 17,000 people treated with antidepressants, young people who were CYP2C19 ultrarapid or poor metabolizers and took escitalopram or citalopram had a higher risk of suicide attempts and self-harm and were more likely to need a switch to another medication. In ultrarapid metabolizers, the medication is cleared too quickly to work at the usual dose, so depression may not improve. In poor metabolizers, levels build up and cause side effects. Testing CYP2C19 before starting treatment can help choose a medication and dose that suit the young person.

Families should watch for new or worsening agitation, restlessness, anger, trouble sleeping, or talk of self-harm, and contact the doctor right away if they appear. In Canada, anyone can call or text 9-8-8 at any time for support.

What should older adults know about antidepressants?

As we age, the liver and kidneys clear medications more slowly, and the body becomes more sensitive to side effects. Many older adults also take several medications, which raises the risk of interactions. The American Geriatrics Society Beers Criteria, a widely used guide for safer prescribing in older adults, highlights these points:

• Avoid tricyclic antidepressants and paroxetine when possible. They have strong anticholinergic effects that can cause confusion, constipation, dry mouth, urinary problems and dizziness.
• Watch for low sodium (hyponatremia). SSRIs, SNRIs and mirtazapine can lower sodium levels in older adults, which can cause confusion, unsteadiness and falls. Your doctor may check your sodium, especially in the first weeks.
• Watch for falls. Antidepressants can cause dizziness and unsteadiness. The risk is higher in people who have already fallen.
• Watch for bleeding. SSRIs and SNRIs raise the risk of stomach bleeding, especially with NSAIDs such as ibuprofen or naproxen, aspirin or blood thinners.
• Use lower doses of citalopram and escitalopram. Higher doses can affect the heart rhythm (QT prolongation). For adults over 60, the maximum recommended dose of citalopram is 20 mg a day.
• Watch blood pressure and eye pressure with SNRIs. SNRIs such as venlafaxine, desvenlafaxine and duloxetine can raise blood pressure, especially at higher doses, so it should be checked regularly. They can also widen the pupils and trigger a sudden type of glaucoma (angle-closure glaucoma) in people with narrow eye angles, a risk that increases with age. Seek urgent care for sudden eye pain, redness, blurred vision or seeing halos around lights, and tell your eye doctor which antidepressant you take.

Common choices for older adults include sertraline, escitalopram at a lower dose and mirtazapine, which can help when sleep and appetite are poor.

Which medication combinations are risky at any age?

Some medications often used alongside antidepressants add to the risks, especially in older adults:

• Benzodiazepines, such as lorazepam or diazepam, cause drowsiness, memory problems, falls and car accidents. Older adults should avoid them when possible.
• Pregabalin and gabapentin, used for pain and anxiety, can cause dizziness and falls. Combined with opioids or benzodiazepines, they can slow breathing.
• Antipsychotics, such as aripiprazole or quetiapine, are sometimes added to antidepressants. In older adults with dementia, they increase the risk of stroke and death.
• Other medications that affect the heart rhythm can add to the effect of citalopram or escitalopram.

How do genes affect antidepressants at different ages?

The CYP2C19 and CYP2D6 genes control how quickly the body breaks down many antidepressants. The Clinical Pharmacogenetics Implementation Consortium (CPIC) gives gene-based recommendations:

• CYP2C19 affects citalopram, escitalopram and sertraline. Poor metabolizers may need a lower dose. Ultrarapid metabolizers may not respond to citalopram or escitalopram and may need a different medication.
• CYP2D6 affects paroxetine, fluvoxamine, venlafaxine, vortioxetine and tricyclic antidepressants. Poor metabolizers can build up high levels and have more side effects.
• CYP2B6 affects sertraline and bupropion.

Your genes do not change with age, but their effect can add to age-related changes. For example, an older adult who is a CYP2C19 poor metabolizer may have much higher citalopram levels than expected, which increases the risk of heart rhythm problems. In young people, knowing these results early can help avoid side effects that lead to stopping treatment.

How can a pharmacogenetic test help?

A Pillcheck test shows how your genes affect antidepressants, pain medications and many other medications. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. A Pillcheck pharmacist reviews your results together with all your medications, takes your age into account, checks for interactions and gives recommendations to discuss with your doctor. Your results last a lifetime and can guide future prescriptions as needs change with age.

Summary

• Depression is most common in young people, but antidepressant use rises with age.
• For teenagers, psychotherapy comes first for mild to moderate depression, and fluoxetine has the strongest evidence when medication is needed.
• All antidepressants carry a warning about suicidal thoughts in people under 25, which means close monitoring, not avoiding treatment.
• Older adults should avoid tricyclic antidepressants and paroxetine when possible, and should be watched for low sodium, falls, bleeding, heart rhythm effects and, with SNRIs, high blood pressure and glaucoma.
• CYP2C19 and CYP2D6 testing, with a pharmacist review, helps choose a safer antidepressant and dose at any age.

Frequently asked questions

Which antidepressant is safest for teenagers?

Fluoxetine has the best evidence for teenagers with depression. Escitalopram and sertraline are generally avoided in youth because of the higher risk of suicide due to treatment failure in CYP2C19 ultrarapid metabolizers. The right choice depends on the young person's symptoms, health and other medications.

Should my teenager avoid antidepressants because of the suicide warning?

No. The warning means close monitoring, especially in the first weeks. Untreated depression carries its own serious risks. Talk to your child's doctor about how to monitor and when to call.

Which antidepressants should older adults avoid?

Tricyclic antidepressants, such as amitriptyline, and paroxetine are generally avoided in older adults because they can cause confusion, falls and other side effects. Your doctor will consider your other health conditions and medications.

Do my genes matter more as I get older?

Your genes do not change, but their effects can add to the slower drug clearance that comes with age. This is why knowing your results can be especially helpful for older adults who take several medications.

References

Cipriani A, Zhou X, Del Giovane C, et al. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Lancet. 2016;388(10047):881-890.

By the 2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081.

Steinman MA, et al. Alternative Treatments to Selected Medications in the 2023 American Geriatrics Society Beers Criteria. J Am Geriatr Soc. 2025;73(9):2657-2677.

Bousman CA, Stevenson JM, Ramsey LB, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants. Clin Pharmacol Ther. 2023;114(1):51-68.

Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update. Clin Pharmacol Ther. 2017;102(1):37-44.

US Food and Drug Administration. Drug Safety Communication: Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses. March 2012.