St John's Wort (Hypericum Perforatum)- Induced Psychosis

A Case Report

Maria Ferrara; Francesco Mungai; Fabrizio Starace


J Med Case Reports. 2017;11(137) 

In This Article


Hypericum perforatum (St John's wort) has been known for its therapeutic properties, such as anti-inflammatory, antiseptic, and antidepressant, since the times of ancient Greece and interest in this plant has been documented throughout history.[1] Over the last two decades, St John's wort has gained significant relevance in the field of psychiatry for the treatment of mild-to-moderate depression. St John's wort has been investigated, providing evidence of its efficacy and tolerability profile,[2–7] and it has been included within internationally acknowledged guidelines.[8] At the same time, it has been increasingly advertised and commercialized across Europe and the United States of America as an over-the-counter medication. However, its rising popularity could also mean an increased risk for people self-medicating for potentially severe psychopathological conditions, for which there is no evidence of efficacy and tolerability, without receiving any professional supervision. In fact, even though a recent meta-analysis has provided further evidence supporting the comparability of St John's wort to standard selective serotonin reuptake inhibitors (SSRIs), with regards to mild and moderate depression,[7] to date, still too little is known about its safety, recommended dosage, and side effects in people at risk of psychiatric disorders.

St John's wort contains a combination of different components, which makes the interpretation of clinical trials rather complex.[9] However, among its active constituent fractions (for example, hypericin, hyperforin, and polyphenols) consensus has now been reached regarding the key role of the hyperforin component in antidepressant activity.[7] Furthermore, in many cases, the formulations available and advertised across countries as over-the-counter remedies for the treatment of mood disorder, anxiety, and jet lag syndrome, consist of a combination of Hypericum and other phytotherapeutics (for example, valerian) or melatonin.

St John's wort is a complex mixture containing a variety of constituents; some of these components are potent enzyme inducers and their pharmacokinetic interactions should be particularly cautioned with concomitant drug use.[10,11] In particular, hypericin and hyperforin are reported to be respectively CYP1A2 and CYP3A4 inducers.[7] Thus, attention should be paid when Hypericum is administered in combination with other medications in general[12,13] and more specifically with drugs such as antiretrovirals,[14] cyclosporine,[15] anticoagulants,[16] hormonal contraceptives,[17] and other psychotropic agents such as antidepressants[15] and antipsychotics.[18] The number of neurotransmitter systems potentially involved in the mechanism of action of Hypericum is remarkable, encompassing not only monoamines (serotonin, noradrenaline, and dopamine), for which the antidepressant effect is hypothesized, but also glutamate and ion channels.[19,20]

To the best of our knowledge, to date, the evidence available regarding the risk posed by Hypericum in terms of psychiatric adverse effects, with reference to its potential to precipitate psychosis, is limited;[21] the evidence is confined essentially to some case reports describing the onset of manic symptoms,[22–25] two cases of psychotic relapse,[26] and a case report regarding the onset of a first episode of psychosis in a 39-year-old Japanese woman who self-medicated with a high dosage of Hypericum during a spell of mild depressed mood.[27]