6.2.09

Numerosos ensayos clínicos avalan el uso del extr seco de hypericum perforatum -hipérico o hierba de S. Juan- en el tratamiento de la depresión.

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La hierba de San Juan actúa, entre otros mecanismos, mediante la inhibición de la proteína MAO, que degrada la dopamina y la serotonina, lo que conduce a un aumento de los niveles de estos neurotransmisores.

Existen al menos ocho estudios clínicos realizados en humanos y publicados en la literatura científica, que indican la eficacia del extracto seco de Hypericum perforatum o "hierba de San Juan" en el tratamiento de la depresión. En este artículo vamos a mencionar tres estudios que fueron publicados en el año 2006.

El primer estudio listado aquí fue realizado por miembros del Departamento de Psiquiatría y Psicoterapia de la facultad de Medicina de Berlín, Alemania. El trabajo describe un estudio multicéntrico randomizado, en el que se compara un extracto de hierba de San Juan con el antidepresivo paroxetina, en pacientes que se han recuperado de un episodio de depresión moderada a grave. El antidepresivo paroxetina es un potente SSRI (fármaco inhibidor de la recaptación de serotonina). Este estudio demostró que el extracto seco de hierba de San Juan ensayado, en tratamiento continuado, tuvo una eficacia similar a la paroxetina, en la prevención de la recaida, tras la recuperación de un episodio de depresión -moderado a grave-. Por ello el hipérico o hierba de San Juan, según dicen los autores, contituiría un tratamiento alternativo importante para la prevención de la recaída en la depresión.

En el segundo estudio, llevado a cabo por el Departamento de Psiquiatría general de la Facultad de Medicina de Viena, Austria, se analiza el efecto del extracto seco de Hypericum perforatum en la depresión mayor. Se utilizaron dosis de 600 mg/día en una dosis o 1200 mg/día en dos dosis. El estudio fue doble-ciego, controlado con placebo, multicéntrico y randomizado. El tratamiento fue precedido de un periodo sin tratamiento farmacológico, y duró un total de seis semanas.
Los resultados del estudio fueron que ambas dosis fueron efectivas y mejor que el placebo en el tratamiento de la depresión de leve a grave.

El tercer estudio fue realizado en el Departamento de Psiquiatría y Psicoterapia del Hospital Psiquiátrico General en la Universidad de Essen, Alemania. Se centró en evaluar la eficacia y seguridad de una dosis diaria de extracto de hipérico (900 mg/día) y del fármaco antidepresivo citalopram (20 mg/día) , en pacientes con depresión moderada. Este estudio, como el anteriormente descrito, fue doble-ciego, randomizado, multicéntrico y controlado con placebo. El tratamiento se llevó a cabo también durante seis semanas. Los resultados del estudio demostraron que el extracto de hipérico no tenía un efecto inferior que citalopram. Ambos compuestos fueron más efectivos que el placebo. Además, se demostró que el extracto de hipérico era mejor tolerado y tenía un mejor perfil de seguridad que citalopram. Estos resultados revelan, según los autores de este estudio, que el extracto de hipérico ensayado es una buena alternativa a los antidepresivos químicos en el tratamiento de pacientes con depresión moderada.

Primer estudio:

Pharmacopsychiatry. 2006 Nov;39(6):213-9.

Comparison of Hypericum extract WS 5570 and paroxetine in ongoing treatment after recovery from an episode of moderate to severe depression: results from a randomized multicenter study.
Anghelescu IG, Kohnen R, Szegedi A, Klement S, Kieser M.

Department of Psychiatry and Psychotherapy, Charité- Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.

OBJECTIVE: To test and compare the efficacy and safety of Hypericum extract WS 5570 to paroxetine, a potent SSRI, in patients suffering from moderate or severe depression according to DSM-IV criteria. METHODS: In a multicenter, randomized, double-blind phase III study, the changes in moderate to severe major depression DSM-IV; 17-item Hamilton Depression Rating Scale (HAM-D total>or=22) after an acute treatment with Hypericum extract WS 5570 or paroxetine were analyzed in a 16-week continuation phase for relapse prevention. Patients with a HAM-D total score decrease of >or=50% during the 6 weeks of acute treatment were asked to continue the treatment for another 4 months. One-hundred and thirty-three adult out-patients who received maintenance doses of 900 (n=33) or 1800 mg/d (n=38) of WS 5570 and 20 (n=28) or 40 mg/d (n=34) of paroxetine, respectively, were included. The relevant dosage was already fixed during the acute treatment. RESULTS: Between baseline of the acute phase and end of continuation treatment the HAM-D total score decreased from 25.3+/-2.5 (mean+/-SD) to 4.3+/-6.2 points for WS 5570 and from 25.3+/-2.6 to 5.2+/-5.5 points for paroxetine (p=0.49, two-sided t-test; median relative decrease: 92.0 and 85.5%, respectively). During maintenance treatment alone (day 154-day 42), 61.6% of the patients randomized to WS 5570 and 54.6% treated with paroxetine showed an additional reduction (p=0.59) with respect to the HAM-D total score. Remission (HAM-D endpoint total score below 8) occurred in 81.6% (31 patients) of the patients for WS 5570 and in 71.4% (30 patients) for paroxetine (p=0.29). Three patients in the WS 5570 group and 2 patients in the paroxetine group showed a HAM-D increase>5 points during continuation treatment. In the continuation phase there were 0.006 adverse events per day of exposure for WS 5570 and 0.007 events for paroxetine. CONCLUSION: This study showed that WS 5570 and paroxetine were similarly effective in preventing relapse in a continuation treatment after recovery from an episode of moderate to severe depression and point therefore to an important alternative treatment option for long-term relapse-prevention.


Segundo estudio:

BMC Med. 2006 Jun 23;4:14.

Superior efficacy of St John's wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298].

Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser M.

Department of General Psychiatry, Vienna Medical University, Währinger Gürtel 18-20, A-1090 Wien, Austria. sci-genpsy@meduniwien.ac.at

ACKGROUND: The aim of the current study was to assess the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort) extract WS 5570 at doses of 600 mg/day in a single dose and 1200 mg/day in two doses. METHODS: The participants in this double-blind, randomized, placebo-controlled, multi-center clinical trial were male and female adult out-patients with an episode of mild or moderate major depressive episode (single or recurrent episode, DSM-IV criteria). As specified by the relevant guideline, the study was preceded by a medication-free run-in phase. For the 6-week treatment, 332 patients were randomized: 123 to WS 5570 600 mg/day, 127 to WS 5570 1200 mg/day, and 82 to placebo. The primary outcome measure was the change in total score on the Hamilton Rating Scale for Depression (HAM-D, 17-item version) between baseline and endpoint. Additional measures included the number of responders, the number of patients in remission, and several other standard rating scales. Efficacy and safety were assessed after 2 and 6 weeks. The design included an interim analysis performed after randomization with the option of early termination. RESULTS: After 6 weeks of treatment, mean +/- standard deviation decreases in HAM-D total scores of 11.6 +/- 6.4, 10.8 +/- 7.3, and 6.0 +/- 8.1 points were observed for the WS 5570 600 mg/day, 1200 mg/day and placebo groups, respectively (endpoint analysis). Secondary measures of treatment efficacy also showed that both WS 5570 groups were statistically superior to placebo. Significantly more patients in the WS 5570 treatment groups than in the placebo group showed treatment response and remission. WS 5570 was consistently more effective than placebo in patients with either less severe or more severe baseline impairment. The number of patients who experienced remission was higher in the WS 5570 1200 mg/day group than the WS 5570 600 mg/day group. The incidence of adverse events was low in all groups. The adverse event profile was consistent with the known profile for Hypericum extract preparations. CONCLUSION: Hypericum perforatum extract WS 5570 at doses of 600 mg/day (once daily) and 1200 mg/day (600 mg twice daily) were found to be safe and more effective than placebo, with comparable efficacy of the WS 5570 groups for the treatment of mild to moderate major depression.

Tercer estudio:

Pharmacopsychiatry. 2006 Mar;39(2):66-75.

Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study.

Gastpar M, Singer A, Zeller K.

General Psychiatric Hospital, Department of Psychiatry and Psychotherapy, University of Essen, Essen, Germany. m.gastpar@uni-essen.de

OBJECTIVE: The objective of this double-blind, randomised, placebo-controlled, multicentre clinical study was to demonstrate the non-inferiority and safety of the hypericum extract STW3-VI in a once-daily dosage regime in the treatment of moderate depression. During the 6-week treatment phase, the course of depression was documented by use of HAMD (items 1-17), the von Zerssen's Adjective Mood Scale (BfS) and the CGI scales. The primary objective of this 3-arm design study was to demonstrate the non-inferiority of hypericum extract STW3-VI (900 mg) to the SSRI citalopram (20 mg) and superiority of hypericum over placebo. METHODS: Outpatients (N = 388) suffering from moderate depression were enrolled. The safety and tolerability of hypericum extract in comparison to citalopram and placebo was investigated on the basis of CGI, the occurrence of adverse events and the investigation of laboratory parameters and vital signs. RESULTS: From almost identical baseline values of 21.9 +/- 1.2 points (hypericum extract), 21.8 +/- 1.2 points (citalopram) and 22.0 +/- 1.2 points (placebo), the HAMD score was reduced to 10.3 +/- 6.4 (hypericum extract), 10.3 +/- 6.4 (citalopram) and 13.0 +/- 6.9 (placebo), respectively. Based on this data, the statistical significant therapeutic equivalence of hypericum extract STW3-VI to citalopram (p < 0.0001) and the superiority of this hypericum extract over placebo (p < 0.0001) was demonstrated. At the end of treatment 54.2 % (hypericum extract), 55.9 % (citalopram) and 39.2 % (placebo) of the patients were assessed as therapy responders. The secondary efficacy parameters, change in BfS, CGI and amount of therapy responders showed that the hypericum group was not statistically different from the citalopram group, and significantly superior to the placebo group. Significantly more adverse events with "certain", "probable" or "possible" relation to study medication were documented in the citalopram group (hypericum: 17.2 %, citalopram: 53.2 %, placebo: 30 %). In most cases, the investigators assessed the tolerability of hypericum extract, citalopram and placebo as "good" or "very good". CONCLUSION: The non-inferiority of hypericum extract as compared to citalopram and the superiority of both active compounds to placebo were demonstrated, as well as a better safety and tolerability of hypericum extract in comparison to citalopram. These results revealed that hypericum extract STW3-VI is a good alternative to chemically defined antidepressants in the treatment of outpatients with moderate depression.