Disclaimer: None of the information in this article constitutes medical advice, and is just the opinion of the writer(s). We recommend that patients follow their doctor’s guidance in regards to prescription medication.
Zoloft is a prescription antidepressant medication used by millions of Americans annually. Its generic name is sertraline. We will use these two terms interchangeably throughout the article. The drug is occasionally prescribed to treat panic disorder and social anxiety, but its typical use case is for depression.
Zoloft is a Selective Serotonin Reuptake Inhibitor (SSRI) drug, which is the most common class of antidepressant medications. Later in the article we’ll explain how SSRIs work.
In this article we’ll review the medical research on Zoloft to determine whether it’s likely to be safe and effective. We’ll highlight side effects to look out for, and mention a natural alternative supplement for depression that patients may want to speak to their doctor about.
Does Zoloft Work?
Like most prescription medication, Zoloft is proven to be effective in the aggregate, meaning it’s not guaranteed to work for every patient (no medication or supplement is), but it improves patient depression ratings on average. The Food and Drug Administration (FDA) wouldn’t approve a medication if it wasn’t effective based on the overall dataset of clinical trials.
Zoloft has been around for a long time, and a 2001 review of medical studies on the drug, published in the Expert Opinion on Pharmacotherapy journal, recommended it as a first-line treatment for depression. The researchers noted that Zoloft was just as effective as (at the time) popular antidepressant medications with a more favorable side effect profile.
The study authors noted that Zoloft performed better than Prozac in head-to-head clinical trials, and that the drug was more effective than placebo in reducing the number of panic attacks suffered weekly by patients with panic disorder.
A more recent clinical trial on Zoloft for depression was published in The Lancet journal and has 28 study authors which is more than we’ve ever seen for one medical study. The trial was extremely thorough and well-designed, and was funded by the National Institute for Health Research so it was unbiased.
The researchers tested Zoloft or placebo on 655 adult patients with depression and ended up with surprising results. Zoloft did not lead to a statistically significant reduction in depression over 6 weeks of treatment, although it did have a secondary benefit of reduced anxiety symptoms.
Since the patients enrolled in the trial were depressive and not anxious, this is a very poor result for Zoloft. It’s one thing to perform worse than another prescription medication in a trial, but for a medication with side effects to perform worse than placebo is a bad sign.
This was just one study surely, and there are many other studies suggesting Zoloft is effective, but we were surprised when reviewing this study.
How Does Zoloft Work?
As we referenced in the article intro, Zoloft is an SSRI. This means that it inhibits reuptake of serotonin in the brain. Serotonin is a neurotransmitter that influences mood (among other things), so by delaying its natural processing by the body and allowing its levels to remain artificially increased in the brain, the drug can positively influence mood and decrease depression.
It’s not conclusively proven in medical literature that low serotonin levels are the cause of most depression; it’s just a treatment that’s been shown to be relatively effective on average. It’s likely that there are many different causes of depression across various patients, and pharmaceutical medicine isn’t advanced enough yet to provide individual therapies to patients based on their unique physical condition.
Zoloft Side Effects
The most common side effects of Zoloft are relatively minor. StatPearls, which is a routinely-updated government medical database of research data, describes the primary side effects of Zoloft to be fainting, lightheadedness, diarrhea and nausea. There is reference of sexual disorders for both sexes as well, which is common for SSRI medications.
A medical review of side effect risk of various antidepressants, published in the Chonnam Medical Journal, found that Zoloft conferred the highest risk of seizure and sexual dysfunction.
The more rare and concerning side effect of Zoloft to consider is the increased risk of suicidal thoughts and behaviors. Like many SSRIs, Zoloft’s packaging lists a black box warning detailing how the medication can increase suicidality.
We strongly recommend that patients considering Zoloft speak with their doctor about any family history or previous suicidal ideation.
Should I Take Zoloft Generic?
We typically recommend generic drugs over name-brand drugs, because the chemical compound and dosage is exactly the same.
However, for Zoloft we recommend the name-brand drug over generic sertraline because an extensive medical review documented that users of the generic version had higher rates of psychiatric hospitalizations, suggesting the drug may be less effective.
We’re unsure of how a generic drug could lead to worse outcomes than the branded version. Perhaps the quality controls during manufacturing are less stringent, or potentially there is a placebo effect where users receiving the name-brand medication expect a better outcome.
In any case, out of an abundance of safety because psychiatric hospitalizations are a serious matter, we believe that trusting the medical research and sticking to Zoloft is the better option.
Zoloft Vs. Lexapro
As we highlighted in our Lexapro review, there have actually been medical studies directly comparing the effectiveness and safety of Zoloft and Lexapro.
Lexapro generally outperforms Zoloft because it tends to have fewer significant adverse effects.
A medical trial found that the side effect rate for Zoloft was 56%, while the side effect rate for Lexapro was only 45%. Both of these side effect rates seem high in our opinion.
Even though Lexapro may be superior on average, Zoloft may be better for some patients, so we recommend following the guidance of your medical professional when it comes to choosing between the two.
Natural Antidepressant Alternative - St. John’s Wort
One herbal supplement that is surprisingly effective at treating depression is St. John’s Wort.
Medical research has shown that this herb is as effective as prescription medication for mild-to-moderate depression, and has essentially zero side effects. The lack of serious side effects is one benefit of herbal medicine over pharmaceutical medicine generally in our opinion.
For major depression, it doesn’t appear that St. John’s Wort is as effective as drugs like Zoloft.
It’s also worth noting that the duration of studies on St. John’s Wort in the above-linked research only had a maximum of 12 weeks, so it’s unclear if the herb is safe to take for extended periods of time.
We believe it’s worthwhile for patients with mild or moderate depression to speak with their doctor about St. John’s Wort, because even if only taken for short periods of time, the potential for a natural compound that can be effective for depression with no side effects provides a great value to suffering patients.
It’s important to never take herbal antidepressants like St. John’s Wort at the same time as prescription antidepressants like Zoloft without a doctor’s approval, because the combination can significantly increase risk of serotonin syndrome which can be life-threatening.