Antidepressant side effects in the first two weeks: what's normal and what isn't
Most start-up side effects peak in the first few days and ease within a couple of weeks. Here's what's expected, what can help, and what needs a call to your prescriber.
By Tanya Rybakova · Medically reviewed by Dr. Jason Tan , Consultant Psychiatrist · 2026-10-20 · 11 min read
Key takeaways Side effects usually show up before any benefit does. For most people they are strongest in the first days and ease within a couple of weeks, though sleep problems, restlessness and sexual side effects can last longer. Early side effects are not a sign that the medication has failed. They also don't predict whether it will work for you. The most common early complaints are increased anxiety, nausea, tiredness and disrupted sleep. Simple changes, agreed with your prescriber, often help: taking the dose with food, moving it to a different time of day, or increasing the dose more slowly. Some symptoms are not part of normal adjustment. Severe restlessness, thoughts of self-harm, signs of mania, or fever with confusion and muscle stiffness need prompt or urgent medical help. Don't stop suddenly because the first week is hard. Talk to your prescriber first: there are usually options between "push through" and "quit." On this page
Why antidepressant side effects start before benefits Antidepressant side effects: days 1–14 Common side effects and how to manage them How side effects differ by antidepressant When to call your doctor about side effects Should you stop antidepressants because of side effects? What to track when starting antidepressants It's day three on treatment. You took your first tablet on Monday. Tonight you're awake at 2 a.m. with your heart racing, a queasy stomach, and questions on repeat: is this my medication? Is this normal, or is this medication wrong for me?
For many people, those questions are a major part of starting antidepressants. People in their first weeks of treatment often ask less about how to cope with side effects and more about whether what they're feeling is expected.
This guide explains what the first 14 days can look like, which side effects are common, what tends to help, why antidepressants can feel different from one another, and when to contact your prescriber.
Why antidepressant side effects start before benefits
Antidepressants act on brain chemistry within hours, but improvement in mood usually takes weeks. That gap is the reason side effects tend to show up first.
Most antidepressants act on the serotonin or norepinephrine systems or both at once. Serotonin receptors are located throughout the body, particularly in the brain and intestines. During the first one to two weeks, many of these receptors adapt to the new serotonin level, and as this happens, many of the early side effects disappear. The reorganization of serotonin receptor activity in the digestive tract causes nausea and upset stomach, which are often the earliest side effects. The changes that alleviate depression and anxiety occur more slowly and require changes in the brain's neurotransmitter system. We cover that timeline in detail in how long antidepressants take to work .
Two things help from the start. First, having side effects does not mean the medication isn't working, and having none doesn't mean it is. Second, some of what people notice in the first weeks was there before the first tablet. In a large UK trial , many physical symptoms were reported more often before treatment started than as side effects afterward. Depression and anxiety cause headaches, poor sleep, stomach trouble and fatigue on their own. That's one reason a short note on how you feel before day one is so useful.
Antidepressant side effects: days 1–14
Everyone's start is different, but early side effects tend to follow a broad pattern. Treat what follows as a general guide, not a prediction for you.
Days 1–3
Side effects can begin soon after starting. Nausea, a mild headache, feeling wired or unusually tired, and changes in sleep are common in these first days. Some people notice nothing at all. Mood usually hasn't changed yet, and it isn't expected to.
Days 4–7
For many people this is the hardest stretch. Side effects are often at their most noticeable, and anxiety, restlessness or jitteriness may increase for a while before it settles. Because benefits may not be clear yet, this is when doubt peaks and when many people consider stopping.
Days 8–14
Nausea and headaches often start to ease during the second week as the body adjusts. Sleep may still be unsettled, and some people notice a little more energy or slightly better sleep before any clear change in mood. If your prescriber started you on a low dose, the first increase often comes around now, and some side effects can briefly return after a dose change.
Beyond two weeks. Not everything follows the two-week rule. The NHS notes that most side effects of sertraline ease after a couple of weeks, but some last longer. Sleep problems, restlessness, drowsiness, sweating and sexual side effects can persist for some people. If a side effect is still affecting your life after two to four weeks, that's worth raising rather than waiting out.
Common side effects and how to manage them
The table below summarizes the side effects people most often notice in the first weeks. The "what may help" column describes options to discuss with your prescriber or pharmacist. It isn't a list of changes to make on your own.
Common early side effects of antidepressants. General patterns only, not a prediction of your individual experience. Side effect How it usually goes What may help (agree with your prescriber) Contact your prescriber sooner if… Anxiety, restlessness, jitteriness Can rise soon after starting and often improves as treatment continues. A lower starting dose or slower increase; cutting back on caffeine; sometimes short-term extra support from your prescriber You can't sit still, feel driven to keep moving, have panic you can't manage, or have any thoughts of self-harm Nausea, upset stomach, loose stools Often strongest early on and usually improves with time. Taking the dose with food; smaller, more frequent meals; for some medicines, taking the dose in the evening You're vomiting, can't keep fluids down, or are losing weight Tiredness or drowsiness Common early, especially with some medicines; often improves Taking the dose in the evening if your prescriber agrees; not driving while drowsy It's severe or isn't improving after two to four weeks Trouble sleeping, vivid dreams Common early; may improve with time, but can persist for some people Taking the dose in the morning if your prescriber agrees; limiting caffeine later in the day Sleep loss is severe, or you feel unusually energetic and don't need sleep Headache Usually mild and short-lived Rest and fluids; ask a pharmacist which painkiller suits you, because some (such as ibuprofen) raise bleeding risk alongside SSRIs It's severe, unusual for you, or comes with confusion Sweating Can start early and may persist for some people Lighter layers; tell your prescriber if it bothers you It comes with fever, shivering or confusion Dizziness, mild tremor Often mild and early Standing up slowly; staying hydrated You faint, or the tremor comes with fever, sweating or muscle stiffness Sexual changes May appear early and can persist for some people Raising it at your review: there are options It's affecting your relationship or your willingness to keep taking the medicine Feeling flat or "numb" Can appear in the first weeks Noting it and raising it at your review It's making daily life feel empty or worrying you
Anxiety and restlessness
Anxiety that gets worse at first is one of the most common early worries. Clinicians sometimes call it jitteriness or activation: a rise in anxiety, restlessness or irritability after starting an antidepressant. Estimates of how often it happens range widely, from about 4% to 65% of people, but that range should not be read as a precise risk estimate because studies define and measure it differently. It can feel like proof the medication is wrong, especially if you started it for anxiety. It often improves as treatment continues, and it's one reason prescribers often start low and increase slowly, particularly for anxiety disorders.
One person described their first weeks in an online forum (shared anonymously):
"The first 2 weeks were horrific. I had every side effect going including exhaustion, increased anxiety, restlessness... From day 17, the side effects improved."
One kind of restlessness needs prompt attention: a strong inner urge to keep moving, pacing, or being unable to sit still. This is called akathisia. It isn't something to push through, so contact your prescriber.
Nausea and stomach upset
Nausea is one of the most common early effects of SSRIs and SNRIs, and one of the most likely to fade. It usually settles within one to two weeks. Taking the dose with a meal often helps. With some medicines, taking the dose in the evening means you sleep through the worst of it.
Tiredness or trouble sleeping
Some antidepressants make people drowsy, while others feel more activating. The same medicine can affect two people differently. If you feel sedated during the day, taking the dose in the evening may help. If you're lying awake, a morning dose may help. Check with your prescriber or pharmacist before changing the time, because the right timing depends on the medicine.
Sexual changes and feeling flat
These two are easy to leave unsaid, and they may not resolve as quickly as nausea or headache. Sexual side effects are well recognized with SSRIs and SNRIs and can persist for some people. Feeling emotionally flat, sometimes called emotional blunting , can also start early. Both are clinically relevant and can affect choices about dose or medication, so mention them even if everything else is going well. See feeling numb on antidepressants .
Download on the App Store WithClaro helps you track sleep, side effects, mood and daily functioning between visits, so you walk into your next appointment with a clear picture, not a blank mind.
How side effects differ by antidepressant
Different antidepressants work on different chemical messengers and are cleared from the body at different speeds. As a result, the first week can feel noticeably different from one medicine to the next. The notes below describe common patterns , not what will happen to you.
Lexapro (escitalopram) side effects in the first week
Escitalopram is an SSRI. Early side effects most often include nausea, headache, sleep changes in either direction, sweating and, for some, a temporary rise in anxiety. People taking it for anxiety are sometimes started on a lower dose for this reason. Most early effects ease within the first couple of weeks.
Zoloft (sertraline) side effects in the first week
Sertraline is an SSRI known for stomach side effects early on, especially nausea and loose stools. Headache, dizziness, sleep changes and a temporary increase in anxiety are also common. For panic and some anxiety disorders, it is often started at a lower dose and increased after about a week.
Prozac (fluoxetine) side effects in the first week
Fluoxetine tends to be more activating than other SSRIs, so trouble sleeping, restlessness and nervousness are common early complaints. It's often taken in the morning for that reason. Because it stays in the body for a long time, both its side effects and its benefits can build gradually over several weeks.
Paxil (paroxetine) side effects in the first week
Paroxetine is more likely than some SSRIs to cause drowsiness, dry mouth, constipation and sweating. These are often noticeable in the first weeks.
Effexor (venlafaxine) and Cymbalta (duloxetine) side effects
Both are SNRIs. Nausea is among the most common early effects, along with sweating, dizziness, dry mouth and either drowsiness or trouble sleeping. Some people taking duloxetine describe heavy tiredness in the first weeks. Venlafaxine can raise blood pressure, particularly at higher doses, so your prescriber may check it. With both, missed doses tend to be felt quickly.
Wellbutrin (bupropion) side effects in the first week
Bupropion works differently from SSRIs and SNRIs, and its first week feels different too. It is more likely to cause trouble sleeping, jitteriness, dry mouth, headache and reduced appetite. It's usually taken in the morning, and the second dose of twice-daily forms shouldn't be taken close to bedtime. It rarely causes sexual side effects or weight gain. It does carry a dose-related risk of seizures, and prescribing information says it should not be used in people with a seizure disorder or a current or previous diagnosis of bulimia or anorexia nervosa.
Mirtazapine side effects in the first week
Mirtazapine is the exception to the "wired" pattern. Drowsiness and increased appetite are its most common early effects, which is why it's taken at night.
When to call your doctor about side effects
Most early side effects are uncomfortable but not dangerous. A few are not part of normal adjustment. Before you start, make sure you know who to contact during working hours and where to go outside them.
Contact your prescriber promptly if:
You feel a strong inner restlessness, can't sit still, or feel driven to keep moving Side effects are getting worse rather than better after the first two weeks, or are stopping you from working, sleeping or eating Your mood or anxiety is clearly worse than before you started You notice unusual bruising or bleeding, especially if you also take aspirin, ibuprofen or a blood thinner You develop a new, severe headache, confusion, unusual weakness or unsteadiness. This matters most for older adults, in whom some antidepressants can lower sodium levels in the blood. Seek urgent help if:
You have thoughts of harming yourself or ending your life You feel unusually high, energetic or reckless, are barely sleeping, or your thoughts are racing (signs of mania) You have fever, heavy sweating, shivering, a racing heart, muscle stiffness or twitching together with agitation or confusion (possible serotonin syndrome) You have a seizure, or a rash with swelling of the face or throat, or difficulty breathing In the US: If there is immediate danger, call 911 or go to the nearest emergency department. The 988 Suicide and Crisis Lifeline is available free at any time by call, text or chat.
In the UK: If you or someone else is in immediate danger, call 999 or go to A&E. For urgent mental health support, use NHS 111 online or call 111. Samaritans are available free on 116 123 at any time.
Should you stop antidepressants because of side effects?
Not on your own, and not suddenly. Stopping in the first weeks is very common, but stopping abruptly can cause withdrawal symptoms that add to how bad you feel. If side effects are difficult, speak with your prescriber before changing or stopping the medicine.
"Push through" and "quit" usually aren't the only two choices. Which options make sense depends on you, your medication and your history, so that's a conversation to have with your prescriber. It helps to go in knowing what you want to ask:
Is what I'm feeling expected at this stage, and how long might it last? Is there anything that could make it easier in the meantime? When should we check in again to see how it's going? At what point would we consider changing the plan? If you're already wondering about a change, our guide to switching antidepressants explains how switching usually works.
People in this situation often tell each other to "wait it out." Whether that's right for you is something to decide with your prescriber, not alone.
What to track when starting antidepressants
Two weeks of side effects blur together quickly. By your first review, you may remember the worst night and little else. A few notes a day make that conversation much more useful.
Before your first dose: note how you've been sleeping, your anxiety level, your appetite and any physical symptoms you already have. This baseline is what everything afterward gets compared to.
Each day (it takes a minute or two):
The time you took your dose Your two or three main side effects, each rated 0–10 How you slept Anything new or unexpected For your first review: bring the trend rather than a single day. For example: "Nausea was bad on days 3 to 6 and gone by day 10. Anxiety rose in week one and is easing. Sleep is still broken." Add one question you want answered. For more on making a short appointment count, see how to prepare for a medication review .
WithClaro is built for exactly this: a short daily check-in that turns the first weeks into a clear summary you can bring to your prescriber.
Frequently asked questions Is it normal to feel worse in the first week on antidepressants? Yes, for many people. Side effects such as nausea, anxiety, restlessness and poor sleep often appear before mood improves, and they're usually strongest in the first days. Contact your prescriber if you feel much worse, can't cope, or have any thoughts of self-harm.
How long do antidepressant side effects last? Most early side effects, such as nausea and headache, ease within the first couple of weeks as the body adjusts. Others, including sleep problems, restlessness and drowsiness, can take longer to settle. Sexual side effects can persist for some people. Raise any side effect that is still bothering you after two to four weeks.
Do side effects mean the antidepressant is working? No. Side effects and benefits happen on different timelines and through partly different mechanisms. Having side effects doesn't show that the medication is working, and having none doesn't show that it isn't.
Can antidepressants make anxiety worse at first? Yes. A short-term rise in anxiety, restlessness or irritability is a recognized early effect, sometimes called jitteriness or activation. It often improves as treatment continues, but seek advice if it is severe, persistent, or feels unmanageable. Severe restlessness or an inability to sit still needs prompt attention.
Why am I so tired on antidepressants? Some antidepressants, such as paroxetine, mirtazapine and sometimes duloxetine, are sedating, and tiredness is common early on with many others. It often improves. Taking the dose in the evening may help, but check with your prescriber first. Avoid driving if you feel drowsy.
Should I take my antidepressant in the morning or at night? It depends on the medicine and on how it affects you. Activating medicines such as fluoxetine and bupropion are usually taken in the morning. Sedating ones such as mirtazapine are taken at night. For others, moving the dose to the time that causes the least trouble is a reasonable thing to ask your prescriber or pharmacist about.
Which side effects usually go away, and which may not? Nausea, headache, dizziness and early anxiety often improve within the first few weeks. Sweating, sexual side effects and emotional flatness can last longer for some people and are worth discussing rather than waiting out.
Should I stop taking my antidepressant if the side effects are bad? Talk to your prescriber before stopping. Stopping suddenly can cause withdrawal symptoms, and there are often other options to discuss. Which ones make sense depends on you and your medication. If you have thoughts of self-harm or signs of a serious reaction, seek urgent help.
Related articles
Taper guides
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