Week 2 on an Antidepressant: The Hardest Week, and Why

Week two on an antidepressant is, according to Cochrane reviews of antidepressant adherence and population studies of discontinuation, the single highest-risk week for stopping treatment without prescriber knowledge. Early side effects are often still present, the mood benefit has not arrived, and the novelty of starting has worn off. Understanding why this is the hardest week makes it easier to get through it.

Why week two specifically

Side effects from the first week have not fully eased. Mood is typically unchanged — the four-to-six week onset window has not been reached. The initial commitment to trying something new has faded. The next prescriber appointment may still be weeks away. The combination — discomfort, uncertainty, and limited support — is what makes week two the trough.

What the evidence shows

Cochrane reviews of antidepressant adherence consistently identify the second and third weeks as the highest-risk window for premature discontinuation. Major guidelines including NICE NG222 and RANZCP recommend the first follow-up appointment within one to two weeks of starting precisely because the literature shows this is when patients are most likely to stop.

What helps in week two specifically

Know that this is normal and time-limited. Informed-consent reviews show that patients who know about the week-two trough are measurably less likely to stop treatment.

Keep the dose consistent. Don't adjust the dose or timing independently in response to how week two feels — stay the course and raise concerns with your prescriber.

Keep your daily record going. A short three-line daily note — how you felt, any side effects, anything significant — gives you and your prescriber something concrete to review.

Tell one person you trust. Having a single person who knows you are in week two of a new medication reduces the isolation that makes the trough harder to hold.

Bring your appointment forward if symptoms are difficult. Prescribers expect and welcome week-two contact — you do not have to wait for a scheduled appointment if you need support sooner.

What to flag to your prescriber

Raise these with your prescriber or seek urgent care

New or worsening suicidal thoughts.
Side effects severe enough to affect daily function.
Anxiety or agitation that is worsening rather than holding flat.
Any sense that you cannot get through another week — bring the appointment forward.

Frequently asked questions

Is week two really the worst?

For most patients yes, according to adherence research. Side effects often persist while mood benefits have not yet arrived. Most patients report meaningful improvement by week three as side effects ease, even before mood benefits fully emerge.

Should I stop if week two is unbearable?

Talk to your prescriber rather than stopping silently. Dose adjustments, additional support, or other strategies are often possible. Stopping abruptly without medical guidance can cause discontinuation effects and leaves the underlying condition untreated.

When will week two feel different?

Most patients report meaningful improvement by week three as side effects ease, even before mood benefits emerge. By weeks four to six, mood improvement begins for most patients who are on a suitable medication and dose.

Evidence and sources referenced

NICE Guideline NG222 — Depression in adults: treatment and management (United Kingdom).
Royal Australian and New Zealand College of Psychiatrists (RANZCP) — Clinical Practice Guidelines for Mood Disorders.
NPS MedicineWise — prescriber and patient resources on antidepressant treatment (Australia).
Royal College of Psychiatrists — patient information on antidepressants.
TGA and FDA — product information for SSRI and SNRI medication classes.
Maudsley Prescribing Guidelines in Psychiatry — prescribing patterns and side-effect timelines.