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Medication or therapy: what’s the best way to treat depression?

Ruslan Dorfman, PhD, MBA4 Nov 2026

Untreated depression can affect every part of life. It can strain relationships at work and at home, disrupt sleep, increase the risk of alcohol and drug use, and make physical illnesses harder to manage. The good news is that treatment helps most people. The two main treatments are psychotherapy (talk therapy) and antidepressant medication, and many people do best with both. So which should you try first, and how can you find a medication that suits you? Here is what the research and Canadian guidelines show.

What are the main treatments for depression?

Psychotherapy involves working with a trained therapist to understand thoughts, feelings and behaviours and to learn practical skills to cope with them. Cognitive behavioural therapy (CBT), interpersonal therapy (IPT) and behavioural activation (BA) have the strongest evidence. Guided internet-based CBT, with support from a therapist or coach, is also effective.
Antidepressants, such as SSRIs, SNRIs, bupropion, mirtazapine and vortioxetine, are first-line medications for depression.
Lifestyle changes, such as regular exercise and healthy sleep, help as well. Read more about exercise, diet and other options when depression is hard to treat.

Is therapy or medication better for depression?

Neither is better for everyone. In a large review of 101 studies with nearly 12,000 adults, psychotherapy alone and medication alone were equally effective. Combining the two was the most effective option: about 25% more people responded to combined treatment than to either treatment alone. People were also more likely to stay in treatment with psychotherapy or combined treatment than with medication alone.

The choice depends on how severe the depression is, what you have tried before, what is available to you and what you prefer. The Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 guidelines recommend making this decision together with your health care provider:

Mild depression: psychotherapy, guided internet CBT or supervised exercise can be used on their own.
Moderate depression: psychotherapy, an antidepressant or both are good options.
Severe depression: an antidepressant, usually combined with psychotherapy, is recommended, and in the most severe cases other treatments may be needed.

Why add therapy after medication starts to work?

Many people start with an antidepressant because it is easier to access than therapy, or because their symptoms make it hard to engage in therapy at first. Once the medication has started to work, adding psychotherapy has an important benefit. In a review of 17 clinical trials with 2,283 people, those who received psychotherapy after responding to an antidepressant had a lower risk of relapse than those who did not. CANMAT notes that the strongest evidence supports CBT, including mindfulness-based cognitive therapy, started after antidepressant treatment is established. Psychotherapy can also help with symptoms that remain after medication.

Some experts have called for new research on the best order of treatments. In a 2022 opinion article, psychiatrists Roy Perlis and Maurizio Fava proposed repeating the landmark STAR*D study with modern options, starting with an SSRI plus app-based CBT, and using pharmacogenetic testing to guide the next step when the first does not work.

How can I find the right antidepressant for me?

Only about one in three people reaches remission with their first antidepressant, and many try several medications before finding one that works. Some people also hesitate to start antidepressants because of fears about side effects.

Genes are one reason people respond differently. The liver enzymes CYP2C19 and CYP2D6 break down many antidepressants, and genetic differences in these enzymes change drug levels. A large analysis found, for example, that escitalopram levels were about 2.6 times higher in CYP2C19 poor metabolizers than in normal metabolizers. High levels can cause side effects, while very low levels in ultrarapid metabolizers can mean the medication does not work at the usual dose.

Pharmacogenetic testing shows how your body breaks down medications. The Clinical Pharmacogenetics Implementation Consortium (CPIC) gives prescribing advice for many antidepressants based on CYP2C19, CYP2D6 and CYP2B6. Testing can be useful before your first antidepressant or after a medication has not worked or caused side effects. Read more about how DNA testing can help find the best anxiety and depression medication and how personalized medicine improves mental health treatment.

If the first medication does not help enough, your doctor may increase the dose, switch to another antidepressant or add a second medication, such as aripiprazole, brexpiprazole, quetiapine or lithium. A psychiatrist can help if several treatments have not worked. Read more about what to do when antidepressants are not working and alternatives if you cannot tolerate an SSRI.

How long should I take an antidepressant, and how do I stop?

CANMAT recommends continuing an antidepressant for 6 to 12 months after your symptoms are gone, and longer for people with repeated or severe episodes. Psychotherapy can also help prevent relapse during and after this time.

When it is time to stop, do it gradually and with your prescriber. Up to half of people have discontinuation symptoms when they stop an antidepressant after long-term use, especially if they stop suddenly. These can include flu-like feelings, trouble sleeping, nausea, dizziness, brief electric-shock sensations and irritability. Antidepressants are usually tapered over several weeks or months, with longer gaps between dose reductions toward the end. Your therapist can support you through this time, while your prescriber guides the tapering plan. Read more about antidepressant withdrawal and when and how to taper antidepressants.

How can a Pillcheck test help?

A Pillcheck test reports CYP2D6, CYP2C19, CYP2B6 and other genes that affect antidepressants, add-on medications and many other drugs. A pharmacist reviews your results together with all your medications, and your report can be shared with your family doctor, psychiatrist and pharmacist. Your results can help guide the choice of the first antidepressant and its dose, or the next step if a medication has not worked.

Pillcheck testing is performed in CAP- and COLA-accredited clinical genetic laboratories located in Canada. 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. The Pillcheck test panel ensures high accuracy for people of non-European and admixed ancestries. Your results last a lifetime, and report updates are free of charge.

Summary

Psychotherapy and antidepressants are about equally effective for depression, and combining them works best.
The best first treatment depends on how severe the depression is and on your preferences. For mild depression, therapy or exercise alone can be enough.
Adding psychotherapy after an antidepressant starts to work lowers the risk of relapse.
Genes such as CYP2C19 and CYP2D6 change antidepressant levels, and pharmacogenetic testing helps choose the medication and dose.
Continue an antidepressant for 6 to 12 months after recovery, and stop gradually with your prescriber’s guidance.
See a psychiatrist if several treatments have not worked.

Frequently asked questions

Is therapy as effective as antidepressants?

Yes. On average, psychotherapy and antidepressants are equally effective for depression, and the combination is more effective than either alone.

Should I start therapy and medication at the same time?

Both approaches can work. Some people start both together, while others start with a medication and add therapy once their symptoms begin to improve. Talk with your health care provider about what suits you.

Can a genetic test tell me which antidepressant will work?

Not on its own. It shows which medications and doses your body is likely to handle well or poorly, which helps narrow the choices. Your symptoms, health and preferences also guide the decision.