St. John's wort (Hypericum perforatum) is one of the most commonly used over the counter herbal supplements in the world for the treatment of depression. In fact, multiple studies have found positive results regarding its use, not only depression, but also for symptoms of anxiety and problems with insomnia. As is the case with herbal products, St. John's wort contains multiple constituents, all of which are thought to be as least partially responsible for its effects including:

  • Hypericin
  • Pseudohypericin
  • Naphthodianthrones
  • Various Flavonoids including quercetin 


The exact mechanism of action of St. John's wort isn't well understood but most studies indicate that it works in a similar way to prescription SSRI (selective serotonin re-uptake inhibitors) medications such as Zoloft (sertraline). More specifically, it is thought that St. John's wort can increase levels of the neurotransmitter serotonin in the brain. In addition to its effects of serotonin, it also appears to affect other neurotransmitters including dopamine and norepinephrine


While there is an overwhelming amount of evidence pointing to the efficacy of St. John's wort for the treatment of depression, it does appear to have significant interactions with many different prescription drugs, One of these interactions is with the SSRI class of medications, which includes Zoloft.


St. John's Wort - Zoloft (Sertraline) Interaction

As SSRI medications and St. John's wort share a similar mechanism of action (at least partially), there is the risk of possible additive effects on serotonin concentrations when using both together. Therefore, it is generally recommended to avoid combining St. John's wort with other serotonergic drugs.


The use of St. John's wort with Zoloft could potentially lead to a rare, but serious reaction known as serotonin syndrome. Serotonin syndrome is characterized by a variety of effects including:

  • Hyperthermia
  • High blood pressure
  • Muscle spasms
  • Rigidity
  • Mental status changes


The interaction between SSRI medications, such as Zoloft and St. John's wort, isn't simply theoretical and there have been documented cases of serotonin syndrome with concurrent use. Examples of these case reports and associated studies can be found here and here.


The combined use of St. John's wort and Zoloft is generally not recommended, but if they are used together, it should only be done under close supervision from your doctor.


Some medical guidelines, such as those from the American College of Physicians, consider St. John's wort as an option or alternative to conventional antidepressants for the treatment of mild depression for certain individuals. However, it's use isn't recommended for those taking many conventional prescription medications due to the high number of drug interactions associated with St. John's wort.


There unfortunately isn't a lot of data regarding how long into therapy potential drug interactions with St. John's wort are most likely to happen. While it would be unlikely to experience severe symptoms or reactions after one dose of St. John's wort, it is difficult to provide a definitive answer. In most cases, it would be considered more important to continue on your Zoloft to avoid symptoms of withdrawal. However, as everyone's medical situation is different, it is recommended to reach out your doctor as they have you complete medical profile and can provide you with a more specific and individualized answer.