What You Should Know About SSRIs

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed type of antidepressant. They include medications such as Zoloft (sertraline), Lexapro (escitalopram), Prozac (fluoxetine), Paxil (paroxetine), and Celexa (citalopram). They work by increasing the amount of serotonin—a neurotransmitter involved in regulating mood, sleep, appetite, energy, and cognitive function—between nerve cells in the brain (synapses). SSRIs do this by blocking the reabsorption (reuptake) of serotonin, allowing more to remain available in the brain.

In addition to increasing serotonin levels, SSRIs may also reduce neuroinflammation, enhance brain metabolism, and boost brain-derived neurotrophic factor (BDNF)—a protein often called “Miracle-Gro for the brain”—which supports neuroplasticity, or the brain’s ability to adapt and form new connections.

SSRIs have been used for decades and are considered safe, evidence-based treatments for conditions such as depression, anxiety, OCD, and panic disorder. About 13% of Americans take an antidepressant in any given month, and SSRIs make up the majority of these prescriptions.

When Will I Start to Feel Better?

One of the most common questions people have is: “When will it start working?”

While some people notice subtle improvements in sleep, energy, or appetite within the first 1–2 weeks, the full therapeutic benefits of SSRIs often take 4 to 6 weeks—and in some cases, even longer—to become fully noticeable. It’s important to continue taking the medication consistently, even if early improvements seem minimal.

If after 6–8 weeks you haven’t experienced noticeable improvement, your provider may discuss adjusting the dose or switching medications.

Common Side Effects (And What to Expect)

Most SSRI side effects are mild and temporary, especially during the first few weeks as your body adjusts. Not everyone experiences side effects, but common ones include:

• Nausea

• Headache

• Insomnia or drowsiness

• Mild anxiety or restlessness

• Sexual side effects (e.g., reduced libido or delayed orgasm)

• GI upset (e.g., diarrhea, constipation)

• Appetite or weight changes

These effects often subside within 2–4 weeks. If they persist or interfere with daily life, contact your provider. Side effects can often be managed by adjusting the timing or dose of the medication.

⚠️ Rare but Important Safety Concerns

1. Serotonin Syndrome

A rare but serious condition caused by too much serotonin in the brain. It can happen if SSRIs are combined with certain other medications, supplements, or substances.

Symptoms include:

• Muscle stiffness or twitching

• Fever or sweating

• Nausea/vomiting

• Agitation or confusion

• Rapid heart rate

• Seizures (in rare cases)

Seek immediate medical attention if these occur.

2. Low Sodium (Hyponatremia)

More common in older adults. Signs include:

• Dizziness

• Nausea

• Confusion

• Fatigue

Let your provider know if these symptoms occur.

3. Suicidality Warning

SSRIs carry a black box warning for increased suicidal thoughts or behaviors in young people under 25, particularly in the first few weeks of treatment. This is rare, and research shows that SSRIs reduce suicide risk overall by treating the underlying depression.

Still, it’s crucial to report any worsening mood or suicidal thoughts promptly.

4. Bleeding Risk

While SSRIs are generally safe, they can slightly increase the risk of bleeding, especially in the stomach and intestines. This is because SSRIs reduce the amount of serotonin in platelets, which is important for normal blood clotting.

The risk becomes higher when SSRIs are combined with NSAIDs (nonsteroidal anti-inflammatory drugs) such as:

• Ibuprofen (Advil, Motrin)

• Naproxen (Aleve)

• Aspirin

NSAIDs can irritate the stomach lining and also affect clotting. When taken together with SSRIs, the combined effect can increase your chances of stomach ulcers or gastrointestinal bleeding.

To stay safe:

• Try to avoid regular or high-dose use of NSAIDs while on an SSRI.

• If you need pain relief, consider acetaminophen (Tylenol) instead—unless your provider advises otherwise.

• Tell your provider if you have a history of ulcers, bleeding issues, or if you take blood thinners (like warfarin or aspirin).

• Seek medical attention if you notice symptoms such as black or tarry stools, vomiting blood, easy bruising, or prolonged bleeding.

To stay safe and reduce risk of interactions:

• Avoid combining SSRIs with other antidepressants unless directed by your provider.

• Tell your provider if you’re taking opioids or medications like Lyrica, tramadol, or migraine meds.

• Avoid herbal supplements that raise serotonin (e.g., St. John’s Wort, 5-HTP, SAMe).

• Do not take cold medicines with dextromethorphan (e.g., Robitussin, NyQuil) unless approved.

• Store your medication safely, away from children or others.

• Call your provider if you notice new or worsening depression, agitation, or suicidal thoughts.

• If you’re in crisis, call 911 or go to the nearest emergency room.

Final Thoughts

SSRIs can be a powerful tool for treating depression and anxiety, especially when combined with therapy, lifestyle changes, and support. While they don’t work overnight, patience and consistency are key. Keep an open line of communication with your provider and don’t hesitate to reach out with any questions or concerns.