Antidepressants: what to expect in the first weeks

HICOA · Mental Health Clinic — Online sessions and in Matosinhos

Short answer: contrary to what is often said, improvement does not only begin after several weeks. Meta-analyses show the difference from placebo is already measurable in the first or second week — but it is small at first and continues to build until around week 6. Full response is typically assessed at 6 to 8 weeks. Side effects, when they occur, usually appear first and ease afterwards, and it is that order which leads many people to give up too early.

Why it takes so long

For decades it was taught that antidepressants had a "latency period" of two to four weeks before they began to act. More recent research has qualified that: a meta-analysis of 28 clinical trials with nearly 6,000 patients found drug-associated improvement already by the end of the first week, with gains continuing to accumulate for at least six weeks.

In practice this means two things. First: if after two weeks you feel absolutely nothing, it is worth telling your doctor rather than assuming you simply have to wait longer. Second: the early improvement is small and easy to miss — and that is precisely when side effects are at their peak. Knowing that window exists is half the work of getting through it.

What you may feel in the first weeks

This varies greatly between people and between drugs. The most commonly reported early on:

• Nausea or stomach discomfort — common in the first days, usually settling within one to two weeks. Taking it with food helps.
• Drowsiness or, conversely, trouble sleeping — depends on the drug. Sometimes resolved by changing the time you take it.
• Headache — frequent in the early days.
• Restlessness or increased anxiety — paradoxical but recognised, particularly early on and in people who already have anxiety. It should be reported to your doctor.
• Changes in appetite, up or down.
• Sexual side effects — among the most reported in the medium term, and the least talked about. There are alternatives; it is worth mentioning.

How to tell it is working

Improvement rarely arrives like a switch. It usually begins with indirect signs, and often others notice before the person does:

• Sleep settles, or appetite returns.
• You manage to do things that previously felt too heavy — even without yet wanting to.
• Rumination slows: the same thoughts come round less often.
• There are moments of normality, short at first, that gradually lengthen.

Pleasure in things — anhedonia lifting — tends to be among the last to return. That is not a sign it is not working.

Questions that always come up

Will I become dependent? Antidepressants do not produce the classic pattern of dependence — growing tolerance and compulsive craving — associated with benzodiazepines. What does exist are discontinuation symptoms on stopping: dizziness, strange sensations, irritability, disturbed sleep.

The scale of this was measured in a 2024 meta-analysis published in The Lancet Psychiatry, pooling 79 studies and more than 21,000 patients: around 31% of those stopping an antidepressant report at least one symptom — but 17% of those stopping placebo report the same, which places the true incidence attributable to the drug closer to 15%. Severe symptoms occurred in around 3% of cases. Venlafaxine, desvenlafaxine and imipramine are among those associated with the highest incidence.

This is why stopping is done gradually and with a plan — not because stopping is dangerous, but because doing it methodically greatly reduces the discomfort.

Will I be different? The aim is not to numb emotion or change personality. It is to restore the capacity to feel in proportion — including sadness, when there is cause. If you feel emotionally flattened, that is an effect to report, not something to tolerate in silence.

For how long? In a first episode, the usual recommendation is to continue for several months after feeling well — because stopping as soon as you improve greatly raises the risk of relapse. Duration is set case by case.

Can I drink alcohol? Not advisable, particularly early on. Alcohol is a depressant, interferes with sleep and can worsen side effects.

When to contact your doctor without waiting

Bring your review forward or make contact if: side effects are intense or have not eased after two to three weeks; marked agitation or anxiety appears; or if, after 6 to 8 weeks at the prescribed dose, there is no improvement at all — in which case the drug or dose likely needs revising, which is common and does not mean nothing will work.

Immediately, if thoughts of harming yourself or that life is not worth living appear. In Portugal, 112 or the SNS 24 line (808 24 24 24); elsewhere, the emergency services of the country where you live.

The essentials

Antidepressants are a treatment, not a quick fix. They work best combined with psychotherapy, taken consistently, and with someone supervising — to adjust, to answer questions, and to decide with you when and how to finish.