Disclaimer: None of the information in this article constitutes medical advice, and is just the opinion of the writer(s) and published for informational purposes only. We recommend that patients follow their doctor’s guidance in regard to prescription medication.
Sertraline is an antidepressant drug taken by millions of Americans annually. It’s the generic version of a brand-name drug called Zoloft. We’ll use these terms interchangeably throughout the article because they refer to the same active drug ingredient.
Sertraline is a member of a class of drugs called Selective Serotonin Reuptake Inhibitors (SSRI), which is the most common class of medication used to treat depressive disorders.
In this article we’ll review published medical studies on sertraline to determine whether the medication is safe and effective. We’ll highlight side effects of the drug, explain whether the branded version is more effective, and share information about an over-the-counter (OTC) supplement that patients may want to speak to their doctor about which can treat depression with a very favorable side effect profile.
Does Sertraline Work?
Sertraline is well-studied for treating Major Depressive Disorder (MDD). The drug is approved by the Food and Drug Administration (FDA) in the U.S. for treating this condition, which requires a substantial amount of research backing.
Sertraline was approved decades ago, and a medical review published in 2001 found that the drug was one of the most effective pharmaceutical treatments for depression. The study authors documented how sertraline was as effective as the other leading antidepressants at the time, but caused fewer side effects on average.
In the above-linked medical review, sertraline performed better than Prozac in comparative medical studies, and was more effective than placebo pills for reducing the number and duration of panic attacks.
A 2019 clinical trial which analyzed the effects of sertraline on depressed patients had somewhat strange and surprising results. This trial was very well-designed to remove bias in our opinion, and it was funded by the National Institute for Health Research in the U.K. so there was no economic bias towards favorable results.
The study included 655 adult patients, and sertraline did not cause any reduction in depression compared with placebo throughout the six-week trial, although it did cause some reduction in anxiety and stress symptoms.
This is a very poor result for sertraline. It’s one thing to perform worse than another prescription antidepressant, but to perform worse than placebo, indicating no real benefit to the drug, is a bad sign.
Another recent clinical trial on sertraline had more favorable results. This trial, published in the Journal of Clinical Psychopharmacology, found 72% of patients to respond favorably to sertraline compared with only 32% of patients taking placebo pills. The researchers did note that sertraline took a relatively long time to start working.
We will conclude from the available research that sertraline is effective for treating depression, especially given that it’s approved by the FDA to do so, and that governmental body certainly reviewed more studies than we did.
That being said, we are not impressed by the clinical research backing sertraline. It appears to be an earlier-generation antidepressant medication that may not be as effective as newer-generation drugs.
How Does Sertraline Work?
As referenced previously, sertraline is an SSRI medication. This means that it delays processing and clearance of serotonin in the brain, leading to artificially increased levels of this neurotransmitter. Serotonin influences mood and emotions, so increasing its levels allows the drug to theoretically influence a more positive and relaxed mood.
Researchers still aren’t exactly sure how SSRI medications work, because it hasn’t been conclusively proven that depressed patients have lower serotonin levels than patients without depression.
Depression is likely multifactorial in most cases, so researchers don’t need to understand exactly how a drug works on an individual to conclude that it works on average. If a drug is proven to be safe and can reduce depression scores across a large population of depressed patients, it may be approved for use even if the exact biochemical mechanism of action isn’t fully understood.
Sertraline Side Effects
The most common side effects of sertraline are somewhat mild. StatPearls, which is one of the largest freely-accessible medical databases, describes the following side effects as the most commonly experienced by sertraline patients: fainting, lightheadedness, diarrhea and nausea. There is reference to the potential for sexual disorders for both men and women as well, which is unfortunately common for SSRI medications.
While these common side effects of the drug may be uncomfortable, they are not life-threatening which is a good sign.
A 2018 medical study reviewed relative side effect risk across a wide range of prescription antidepressants, and found that sertraline had the highest rates of seizure and sexual dysfunction as side effects.
The most concerning potential side effect of sertraline is the increased risk of suicidality. Like many SSRIs, sertraline’s FDA label has a “black box” warning detailing that the medication may increase suicidal throughts and actions.
We recommend that patients who are suffering from sexual dysfunction of any form or suicidal throughts speak with their doctor about potential alternative medications.
Should I Take The Brand Name Version of Sertraline?
Generally, we recommend that patients speak with their doctor about generic medications over branded ones, because they contain the same active chemical compound and the generic version is often cheaper.
However, in the case of sertraline, the branded version called Zoloft may be the more sensible choice. A medical review that we often cite on Illuminate Health found that patients taking sertraline had higher rates of psychiatric hospitalizations compared with patients taking Zoloft. This may be due to random variation, but considering a risk as severe as a psychiatric hospitalization, it seems logical to consider the branded verison of the drug.
Branded and generic medications are not always manufactured by the same company, so quality control issues could theoretically lead to discrepancies in effectiveness and safety even if the active ingredient is the same.
OTC Antidepressant - St. John’s Wort
A dietary supplement with a surprising amount of research backing for its antidepressant effect is St. John’s Wort.
This herb has been proven in medical research to be as effective as pharma drugs for mild-to-moderate depression, and has no reported side effects according to the linked trial if dosed appropriately.
For major depression, there isn’t enough research to conclusively say that St. John’s Wort is as effective as prescription antidepressants.
It’s also worth noting that the duration of studies on St. John’s Wort tends to be 12 weeks at the maximum, so the long-term safety of the herbal supplement is relatively unproven.
We would recommend that patients with mild or moderate depression speak with their doctor about trying St. John’s Wort, because the lack of harmful side effects definitely gives the treatment an advantage over pharmaceutical medication.
It’s important to not take this drug without notifying a physician, because it can interact with prescription medications.
Sertraline Vs. Lexapro
Lexapro is one of the most commonly-prescribed prescription antidepressants, so patients are often curious about whether sertraline or Lexapro is more effective. Thankfully, there have been medical studies directly comparing their efficacy.
A clinical trial reported the side effect rate of sertraline as 56%, while the side effect rate for Lexapro was only 45%. Both of these side effect rates are relatively high, but a 11% difference is notable.
We cannot find any studies suggesting that sertraline is more effective than Lexapro, so it may be logical to consider Lexapro if the two drugs have similar efficacy but Lexapro has a reduced risk of side effects.
Can Sertraline Make it Hard to Ejaculate?
Male patients often report that sertraline makes it more difficult to ejaculate, and at least one clinical trial provides an indirect research backing for this claim. The linked study, published in 1995, found that sertraline was an effective treatment for premature ejaculation. The drug caused a “significant prolongation of time to ejaculation.”
If sertraline is so effective at delaying ejaculation in patients with clinically-diagnosed premature ejaculation, it logically follows that the drug may unfavorably delay ejaculation in patients with typical ejaculation patterns.
This side effect appears common amongst SSRI drugs. A medical review of the ejaculatory effects of antidepressants, published in the Journal of Clinical Psychopharmacology, found that all four medications studied caused a delay in ejaculation.
Does Sertraline Cause Weight Gain?
Patients are often concerned about the risk of their medications causing weight gain, but often this risk is unproven in medical research. Since patients in developed nations tend to gain weight over the course of their adult life until middle age, it can be easy to blame this weight gain on external factors like medication.
We have not come across any medical research suggesting that sertraline causes weight gain in humans. One animal study found that sertraline inhibited appetite, food intake and body weight in both lean and obese animals.
A medical review using human trial data found that SSRIs do increase the risk of weight gain generally, but this risk only appears to be realized in the context of an unhealthy lifestyle. This suggests that patients taking sertraline that practice a healthy lifestyle including good sleep, nutritious whole foods and exercise are not likely to see any weight gain.
There doesn’t appear to be any convincing medical evidence that sertraline causes weight gain.
Does Sertraline Cause Withdrawals?
We can’t locate any medical studies suggesting that sertraline causes withdrawals. The drug’s FDA label mentions that newborns may experience withdrawals if their mother was using sertraline (which strongly suggests that pregnant women may want to consider discontinuing the drug), but no mention on the FDA label of adult patients being at risk of withdrawals.
A medical review on SSRI withdrawals found that this class of drugs does cause withdrawals in some cases, but just because the class confers this risk does not mean that sertraline specifically confers this risk.
In any case, the linked review found SSRI withdrawals to be mild and last no more than one week.
We do not believe that patients need to concern themselves with sertraline withdrawals, because there doesn’t appear to be any medical evidence of this side effect, and the FDA label doesn’t reference it.
Can I Use Alcohol While Taking Sertraline?
Since many medications interact negatively with alcohol, patients are often curious about whether sertraline does as well.
Sertraline’s FDA label notes that the drug does not cause any negative interactions like loss of psychomotor control or sleepiness that are common with other antidepressants. This means that patients should be able to intake moderate amounts of alcohol with no safety risk while using this drug, but as always it’s best to consult with a doctor first.
This data suggests that sertraline may be a safer antidepressant for patients with alcoholism than other drugs that interact negatively with alcohol and potentiate its effect (make it stronger).
StatPearls lists the effective dosage range for sertraline to be between 50 milligrams (mg) and 200 mg daily. There are certain patient populations such as breastfeeding women and patients with kidney disease which may require individualized dosage recommendations; this is just the general recommendation.
Doctors will typically prescribe sertraline at a starting dose of 50 mg, because lower doses will confer lower risk of side effects. If the patient responds positively to this low dose, they can remain at this dosage indefinitely. If the patient fails to respond, the doctor will titrate the dose up slowly over the course of weeks until the patient experiences relief.
Sertraline User Reviews
Sertraline has been reviewed over 1,000 times on Drugs.com, which is an online resource where patients can post reviews of their prescription medication. We can’t verify the authenticity or accuracy of any reviews from this site.
Sertraline has an average rating of 6.9/10 on Drugs.com for treating depression.
The top positive review is written by a user named “Saved_MyLife” who claims the drug caused a massive improvement in their quality of life:
“Two years ago I started [sertraline] and it literally saved my life, marriage, memories with my kids, saved me from me. I truly didn’t know what normal life was like until I started Zoloft. It hasn’t changed me, it helped me be the true, happy me that would show up periodically. All those ‘organic’ ways might help some people. Just don’t think ‘big pharma’ can’t help you, like I did before I tried meds. I never ever ever thought I would be saying that. For two years now I’ve been alive”
The top negative review comes from an anonymous user who claims that they experienced significant side effects including suicidal thoughts:
“The first few days my panic attacks got SEVERE. I had suicidal thoughts I never had before. I was constantly tense with fear, couldn’t eat or sleep. I almost went to the hospital. I was scared to be around family or out in public. It was AWFUL. I felt paralyzed. After 7 days I decided to stop taking it and have been in bed for the last two days. I’m already feeling SO much better”