Clinical trials confirm that St John’s wort (Hypericum perforatum) effectively relieves symptoms associated with mild to moderate depression (1,2). The mechanism by which it exerts this effect is currently unknown. Although early studies noted monoamine oxidase (MAO) inhibition (3), this finding has not been confirmed by subsequent work (4,5). In vitro studies have found that St John’s wort may reduce the expression of serotonin receptors (6), increase the numbers of 5-HT_1A and 5-HT_2A receptors (7), and inhibit synapotosomal serotonin uptake (8,9). It has been questioned whether oral administration of St John’s wort extract produces in vivo concentrations comparable to those in vitro studies. The gamma-amino butyric acid (GABA) receptor activity of St John’s wort has also been investigated without conclusive results (10). Other putative targets of St John’s wort include melatonin and cytokine expression, although these reports are preliminary. The potential serotonergic action of St John’s wort has raised concerns that it could interact with other serotonergic medications and produce similar side effects.

Manuscript received December 1999, revised April 2000, and accepted May 2000.
¹ Staff Psychiatrist, Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario.
²Fellow, Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario.
³Assistant Professor, Department of Health Administration, Faculty of Medicine, University of Toronto, Toronto, Ontario.
⁴Professor Emeritus, Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario.
Address for Correspondence: Dr A Wong, Room 711, Centre for Addiction and Mental Health, Clarke Division, 250 College Street, Toronto, ON  M5T 1R8
e-mail: albert.wong@utoronto.ca

The first clinical cases of serotonin syndrome associated with the concurrent use of St John’s wort and prescription antidepressants (sertraline or nefazodone) have been recently reported (11,12). We report another case of serotonin syndrome in a patient with a history of reactions to serotonergic medications who took St John’s wort. In addition, we describe a case of hair loss, which has not previously been associated with ingestion of St John’s wort.

Serotonin Syndrome With St John's Work

Mr X is a 40-year-old man with a history of an anxiety disorder and depression who presented to the emergency room of a psychiatric hospital after taking 450 mg of St John’s wort. The brand and preparation of the product are unknown. He had been taking 450 mg daily for the past 10 days for depressed mood. Following dinner, he developed flushing, diaphoresis, agitation, weakness of the legs, dry mouth, tightness in the chest, and an inability to focus. These symptoms differed from his usual panic attacks and did not respond to his usual anti-anxiety coping strategies. He denied excessive use of alcohol. He was currently undergoing cognitive-behavioural therapy for social phobia with panic attacks precipitated by social situations. The panic attacks improved with clonazepam 0.5 mg twice daily, which he had been taking for some months. He was on no other medication.

When he presented to the emergency room, he was hypertensive (172/120 mm Hg) without a postural drop, his heart rate was 94/minute and regular, and his respiration rate was 22/minute. Mr X became progressively more confused over a period of 20 minutes and was disoriented regarding the month, the year, and the fact that it was the Christmas season.