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 regard to prescription medication.
Zoloft is an FDA-approved medication that's typically prescribed for its antidepressant effects. However, the drug is also approved to treat other mental health conditions including obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD).
The generic form of the drug is called sertraline. These two terms refer to the same active drug ingredient, so we'll use them interchangeably throughout this article.
But how much can Zoloft reduce depression symptoms? Is it more effective than other antidepressants? Does it cause side effects? And why is it a safer option than the generic version?
In this article we'll answer all of these questions and more, as we review research studies on Zoloft to determine if the drug relieves depression.
We'll also discuss potential side effects and interactions, compare the drug to other leading antidepressants, and explain why Zoloft may be a safer choice than its generic alternative (which is uncommon).
Key takeaways:
- Clinically proven to reduce depression scores
- Shown to be more effective than older-generation antidepressants
- Drug label has FDA "black box" warning due to risk of severe side effects
Does Zoloft Relieve Depression?
Zoloft has been tested in hundreds of clinical trials for its effects on depression.
A medical review published in the Expert Opinion on Pharmacotherapy journal found that Zoloft "offers several advantages over older antidepressants."
The drug is equally effective to older antidepressants, but has a more favorable side effect profile including a lower risk of addiction.
A 2019 clinical trial tested the efficacy of Zoloft on clinically depressed patients. The trial was funded by the National Institute for Health Research so it was unbiased.
After 12 weeks, 73% of patients on Zoloft experienced a partial or full reduction of depression symptoms.
This sounds impressive, but 65% of patients taking placebo pills experienced the same, which suggests a "true" effectiveness rate of 8%. The study authors concluded that there was not convincing evidence that Zoloft was more effective than placebo in this trial.
A clinical trial published in the Biological Psychiatry journal found Zoloft to be significantly more effective than placebo for reducing symptoms of depression.
Overall, we will conclude that Zoloft is effective for treating depression, which is unsurprising given that it's FDA-approved for this indication.
Does Zoloft Cause Side Effects?
As shown below, Zoloft's FDA label has a black box warning indicating an increased risk of suicidal thoughts or behaviors in children, adolescents and young adults:
A medical review on the side effect risk of various antidepressants, published in the Chonnam Medical Journal, found that Zoloft conferred the highest risk of seizure and sexual dysfunction of all medications surveyed.
The common side effects of Zoloft are more mild.
A 2023 medical review describes the primary side effects of Zoloft to be fainting, lightheadedness, diarrhea and nausea.
We strongly recommend that patients (especially younger patients) considering Zoloft speak with their doctor about any personal or family history of suicidal thoughts.
It may be worthwhile for young adult patients to ask their doctor about antidepressant medications that do not increase the risk of suicidal thoughts.
Does Zoloft Reduce Anxiety?
Zoloft is not FDA-approved for the treatment of generalized anxiety disorder (GAD), but patients are often curious if the drug is clinically shown to reduce anxiety symptoms, given that many depressed patients also suffer from anxiety.
A clinical trial published in The Journal of Clinical Psychiatry tested the effectiveness of Zoloft for treating anxiety symptoms.
The researchers found that Zoloft reduced anxiety in 59.2% of patients, while placebo pills reduced anxiety in 48.2% of patients, suggesting a "real" response rate of 11%.
Zoloft is more effective in patients with social anxiety disorder (SAD) than GAD, which is why it's FDA-approved for treating the former condition.
A 2003 clinical trial evaluated Zoloft in patients with severe social anxiety, and after 12 weeks, 55.6% of patients on Zoloft experienced reduced symptoms compared to only 29% of patients taking placebo pills.
Zoloft may offer improvements in anxiety symptoms, though the medication is not FDA-approved for generalized anxiety disorder. Patients with both depression and anxiety may experience relief from both conditions when taking Zoloft.
Zoloft appears particularly effective for treating social anxiety disorder.
Zoloft vs. Lexapro
Patients are often curious about whether Zoloft or Lexapro is more effective for depression, given that both drugs are commonly prescribed to treat this condition.
As we highlighted in our Lexapro review, there have been clinical trials directly comparing the effectiveness and safety of Zoloft and Lexapro.
Lexapro generally outperforms Zoloft because it tends to have fewer significant adverse effects.
A comparative study found that Lexapro and Zoloft were similarly effective, but the side effect rate for Zoloft was 56%, while the side effect rate for Lexapro was only 45%.
This suggests that Lexapro is a superior option.
We recommend that patients speak with their doctor about Lexapro rather than Zoloft in light of this information.
Is the Generic Version as Effective?
We typically recommend that patients speak with their provider about generic drugs instead of name-brand drugs, because the active 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 experienced higher rates of psychiatric hospitalizations, suggesting that Zoloft may be safer.
It's unclear 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, given this data it seems logical for patients who can afford it to use the branded Zoloft instead of the generic sertraline.
The generic version has a significantly lower retail price.
The retail price of Zoloft is around $400 at the time of updating this article, according to GoodRx.
The retail price of generic sertraline is currently under $7 on Cost Plus Drugs.
Can I Drink Alcohol on Zoloft?
Given that many prescription drugs have a negative interaction with alcohol, patients are often curious about whether or not it's safe to drink alcohol while taking Zoloft.
The medication's drug label explicitly states "Do not drink alcohol while you take Zoloft."
Because Zoloft may cause drowsiness, it appears that using alcohol at the same time may have dangerous effects, because alcohol is also a sedative.
It's especially important to avoid driving while using alcohol and Zoloft concurrently.
Given the potential health and safety risks of the use of Zoloft and alcohol, we recommend that patients be honest with their doctor about their alcohol intake.
If a patient is unable to refrain from using alcohol, their doctor may be able to prescribe them an antidepressant that does not interact negatively with alcohol.
How Does Zoloft Work?
Zoloft is a selective serotonin reuptake inhibitor (SSRI) medication.
This means that it delays the biological processing of serotonin.
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, Zoloft can positively influence mood and decrease depression.
It’s not conclusively proven in medical literature that low serotonin levels are the cause of depression; it’s just a treatment that’s been shown to be relatively effective on average in depressed patients.
It’s likely that there are many different causes of depression across different patients, and pharmaceutical medicine isn’t advanced enough yet to provide individual therapies to patients based on their unique biochemistry.
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