© Ann Tarazevich
June 1, 2026
Christine Bürg & Marianne Waldenfels
Many patients feel worse when starting antidepressants. Psychiatrist Prof. Andreas Menke explains why anxiety, restlessness, or nausea can increase at first — and why patients should not give up too quickly
With
Prof. Dr. med. Andreas Menke
Anyone seeking help for depression and being prescribed an antidepressant usually hopes for quick relief. It is all the more unsettling when suddenly the exact opposite happens: depression becomes stronger, inner restlessness increases, sleep worsens, or even nausea is added. Many affected individuals then wonder if the medication is working at all. In fact, many patients experience exactly this difficult initial phase. According to psychiatrist Prof. Dr. med. Andreas Menke, medical director of the Medical Park Chiemseeblick clinic, this is initially not an unusual sign but often part of the body's normal adjustment to the medication.
"Yes, it can initially make the affected person feel worse before it gets better," Menke explains.
If there is a moderate to severe depressive episode and there is an indication for an antidepressant, treatment should begin "slowly," according to Menke. This means: The therapy starts initially with a low dose. Only when the drug is well tolerated is the amount slowly increased.
This cautious approach is also recommended by medical guidelines for the treatment of depression. The reason for this: The brain and body are sensitive to changes in neurotransmitters. Antidepressants interfere with complex signaling processes, especially around serotonin and norepinephrine. The body therefore needs time to adjust.
“The body should first get used to the medication,” says Menke. Starting too quickly with a high dose risks significantly stronger side effects. The slow start, on the other hand, can help alleviate symptoms. "This way, there's even a possibility that there are hardly any side effects."
Problems particularly often occur in the first few days with so-called SSRIs – selective serotonin reuptake inhibitors. These drugs are among the most commonly used antidepressants worldwide.
“These can initially intensify restlessness, tension, or even anxiety,” explains Menke. For many patients, it is difficult to endure, especially since anxiety and inner tension are often already among the most distressing symptoms of depression.
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In addition, there are possible physical side effects such as:
According to experts, the severity of side effects depends heavily on the specific medication. While SSRIs can have a more activating effect, other medications have other typical effects. “Mirtazapine, for example, can cause increased appetite and weight gain,” explains Menke.
Depending on the class of active ingredient, different initial reactions occur:
Therefore, there is no "one" antidepressant for all patients. Doctors must decide individually which medication fits the symptoms, daily life, and possible pre-existing conditions. Also, age, Metabolism, other medications and personal sensitivity played a role.
According to experts, a common mistake is expecting antidepressants to work immediately. In fact, it often takes several weeks for the full effect to be reached.
"Usually after four to six weeks," says Menke. For those affected, this means: The initial period requires patience, even if the symptoms initially seem more burdensome than before. Many patients therefore discontinue treatment early, which can become problematic.
"Unless the side effects are dramatic, you should wait and see the antidepressant continue," emphasizes Menke. Mild complaints at the beginning are often temporary. Many symptoms improve significantly after a few days or weeks.
According to the psychiatrist, those who always stop the medication immediately when the first side effects appear quickly fall into a problematic cycle. "If you stop the medication again at the first signs of mild side effects, then at some point you've tried them all and have no options left."
Therefore, one thing is especially important: close medical supervision. Because even if initial reactions are often normal, it must always be individually checked whether a medication is well tolerated or if the dose and preparation should be adjusted.
Experts advise taking side effects seriously and speaking openly about changes. A differentiated assessment is especially important.
What is often temporary:
When immediate medical help is needed:
Antidepressants can help many people. However, especially the first weeks of treatment often require patience, medical supervision, and the knowledge that a temporary worsening does not automatically mean that the therapy is failing.
In most patients, mild side effects improve significantly or disappear completely within one to two weeks.
The full antidepressant effect usually occurs after four to six weeks.
Mild side effects at the beginning are often normal. If there is a severe worsening, massive restlessness, or suicidal thoughts, medical help should be sought immediately.
No. Antidepressants should never be stopped without medical consultation. Abrupt discontinuation can lead to relapses or withdrawal symptoms.
That cannot be answered in a general way. SSRIs are often considered the first choice, but tolerability varies greatly between individuals.
