The antidepressant effect of combined extracts of Hypericum perforatum and Echium amoenum supplementation in patients with depression symptoms: A randomized clinical trial

Document Type : Short communication


1 Department of Psychiatry, Kashan University of Medical Sciences, Kashan, Iran

2 Barij Medicinal Plants Research Center, Kashan, Iran

3 Social Determinants of Health Research Center, Department of Biostatistics and Epidemiology, Kashan University of Medical Sciences, Kashan, Iran

4 Research Center for Biochemistry and Nutrition in Metabolic Disease, Kashan University of Medical Sciences, Kashan, Iran


Objective: Echium amoenum and Hypericum perforatum dried flowers have been used for therapy of mental disorders in Iranian traditional medicine. In this study, we assessed the efficacy of the E. amoenum and H. perforatum extracts in patients with mild to moderate depression.
Materials and Methods: In an 8-week double-blind, parallel-group trial, 51 patients randomly consumed 20 mg of fluoxetine or 350 mg of herbal medicine twice daily. The Hamilton Rating Scale for Depression (HAM-D) was used to assess depression severity in patients at weeks 0, 4, and 8.
Results: According to the Hamilton score, there were no significant differences between the fluoxetine- and herbal medicine-treated groups after 4 and 8 weeks (p>0.05). Dry mouth was the only reported side effect which was significantly lower in the herbal group (p<0.05) in weeks 2 and 4.
Conclusion: E. amoenum and H. perforatum have anti-depressant properties similar to fluoxetine and they can be used to treat depression as an alternative to fluoxetine.


Akhondzadeh S. Herbal medicines in the
treatment of psychiatric and neurological
disorders. In Low-Cost Approaches to
Promote Physical and Mental Health 2007
pp. 119-138.
Akhondzadeh S, Kashani L, Fotouhi A,
Jarvandi S, Mobaseri M, Moin M, Khani
M, Jamshidi AH, Baghalian K, Taghizadeh
M. 2002. Comparison of Lavandula
angustifolia Mill. Tincture and imipramine
in the treatment of mild to moderate
depression: a double blind, randomized
trial. Prog Neuropsychopharmacol Biol
Psychiatry, 27: 123-127.
Anjaneyulu M, Chopra K, Kaur I. 2003.
Antidepressant activity of quercetin, a
bioflavonoid, in streptozotocin-induced
diabetic mice. J Med Food, 6: 391-395.
Baker EJ, Miles EA, Burdge GC, Yaqoob P,
Calder PC. 2016. Metabolism and
functional effects of plant-derived omega3 fatty acids in humans. Prog Lipid Res,
64: 30-56.
Bech P, Cialdella P, Haugh MC, Birkett MA,
Hours A, Boissel JP, Tollefson GD. 2000.
Meta-analysis of randomised controlled
trials of fluoxetine v. placebo and tricyclic
antidepressants in the short-term
treatment of major depression. Br J
Psychiatry, 176: 421-428.
Bjerkenstedt L, Edman GV, Alken RG,
Mannel M. 2005. Hypericum extract LI
160 and fluoxetine in mild to moderate
depression: a randomized, placebocontrolled multi-center study in
outpatients. Eur Arch Psychiatry Clin
Neurosci, 255: 40-47.
Desai AK, Grossberg GT. 2003. Herbals and
botanicals in geriatric psychiatry. Am J
Geriatr Psychiatry, 11: 498-506.
Sadeghi et al.
AJP, Vol. 13, No. 4, Jul-Aug 2023 336
Fava M, Alpert J, Nierenberg AA, Mischoulon
D, Otto MW, Zajecka J, Murck H,
Rosenbaum JF. 2005. A double-blind,
randomized trial of St John's wort,
fluoxetine, and placebo in major
depressive disorder. J Clin
Psychopharmacol, 25: 441-447.
Gastpar M, Singer A, Zeller K. 2005. Efficacy
and tolerability of hypericum extract
STW3 in long-term treatment with a
once-daily dosage in comparison with
sertraline. Pharmacopsychiatry, 38: 78-
Godfrin KA, Van Heeringen C. 2010. The
effects of mindfulness-based cognitive
therapy on recurrence of depressive
episodes, mental health and quality of
life: A randomized controlled study.
Behav Res Ther, 48: 738-746.
Hamilton MC. 1960. The Hamilton depression
scale (HAM-D). J Neurol Neurosurg
Psychiatry, 23: 56-62.
Hamilton M. 1986. The hamilton rating scale
for depression. In: Sartorius N, Ban TA.
Assessment of Depression. Berlin:
Springer-Verlag, pp. 143-152.
Hevia F, Berti M, Wilckens R, Cifuentes P.
2002. Quality and yield in St. John's wort
(Hypericum perforatum L.) harvested in
different phenological stages. Acta Agron
Hung, 50: 349-358.
Davidson JR, Gadde KM, Fairbank JA,
Krishnan KRR, Califf RM, Binanay C,
Parker CB, Pugh N, Hartwell TD, Vitiello
B, Ritz L, Severe J, Cole JO, de Battista
C, Doraiswamy PM, Feighner JP, Keck P,
Kelsey J, Lin K-M, Londborg PD,
Nemeroff CB, Schatzberg AF, Sheehan
DV, Srivastava RK, Taylor L, Trivedi
MH, Weisler RH. 2002. Effect of
Hypericum perforatum (St John's wort) in
major depressive disorder: a randomized
controlled trial. JAMA, 287: 1807-1814.
Kirsch I. 2014. Antidepressants and the
placebo effect. Z Psychol, 222: 128-134
Klainin-Yobas P, Cho MAA, Creedy D. 2012.
Efficacy of mindfulness-based
interventions on depressive symptoms
among people with mental disorders: A
meta-analysis. Int J Nurs Stud, 49: 109-
LaFrance WC Jr, Lauterbach EC, Coffey CE,
Salloway SP, Kaufer DI, Reeve A, Royall
DR, Aylward E, Rummans TA, Lovell
MR. 2000. The use of herbal alternative
medicines in neuropsychiatry. A report of
the ANPA Committee on Research. J
Neuropsychiatry Clin Neurosci, 12: 177-
Marcus M, Yasamy M, van Ommeren M,
Chisholm D, Saxena S. 2012. Depression:
a global public health concern. WHO
Department of Mental Health and
Substance Abuse, 1: 6-8.
Moallem SA, Hosseinzadeh H, Ghoncheh F.
2007. Evaluation of antidepressant effects
of aerial parts of Echium vulgare on mice.
Iran J Basic Med Sci, 10: 189-196.
Mohammadi A, Zargar F, Akkasheh G. 2014.
Comparing the efficacy of combined
mindfulness based cognitive therapy with
cognitive behavioral therapy and
traditional cognitive behavior therapy in
reducing dysfunctional attitudes of
patients with major depressive disorder. J
Birjand Univ Med Sci, 20: 383-392.
Nouri M, Farajdokht F, Torbati M, Ranjbar F,
Hamedyazdan S, Araj-Khodaei M,
Sadigh-Eteghad S. 2019. A close look at
Echium amoenum processing,
neuroactive components, and effects on
neuropsychiatric disorders. Galen Med J,
8: e1559.
Rodriguez-Landa JF, Contreras CM. 2003. A
review of clinical and experimental
observations about antidepressant actions
and side effects produced by Hypericum
perforatum extracts. Phytomedicine, 10:
Saddiqe Z, Naeem I, Maimoona A. 2010. A
review of the antibacterial activity of
Hypericum perforatum L. J
Ethnopharmacol, 131: 511-521.
Sadeghi S, Sohrabi F, Delavar A, Borjaali A,
Ghassemi GR. 2010. Combined effect of
anti depressant and mindfulness-based
group cognitive therapy (MBCT) on
psychological well being of divorced
women. J Isfahan Med Sch, 28: 681-698.
Sayyah M, Sayyah M, Kamalinejad M. 2006.
A preliminary randomized double blind
clinical trial on the efficacy of aqueous
extract of Echium amoenum in the
treatment of mild to moderate major
depression. Prog Neuropsychopharmacol
Biol Psychiatry, 30: 166-169.
Schulz V. 2002. Clinical trials with hypericum
extracts in patients with depression–
Results, comparisons, conclusions for
therapy with antidepressant drugs.
The antidepressant effect of Hypericum perforatum and Echium amoenum
AJP, Vol. 13, No. 4, Jul-Aug 2023 337
Phytomedicine, 9: 468-474.
Shafaghi B, Naderi N, Tahmasb L,
Kamalinejad M. 2010. Anxiolytic effect
of Echium amoenum L. in mice. Iranian J
Pharm Res, 1: 37-41.
Shahidi S, Akbari H, Zargar F. 2017.
Effectiveness of mindfulness-based stress
reduction on emotion regulation and test
anxiety in female high school students. J
Educ Health Promot, 6: 87.
Sooky Z, Sharifi K, Tagharrobi Z, Akbari H,
Mesdaghinia A. 2010. Depression
prevalence and its correlation with the
psychosocial need satisfaction among
Kashan high-school female students. Feyz
J Kashan Univ Med Sci, 14: 256-263.
Stevinson C, Ernst E. 1999. Hypericum for
depression: An update of the clinical
evidence. Eur Neuropsychopharmacol, 9:
Szegedi A, Kohnen R, Dienel A, Kieser M.
2005. Acute treatment of moderate to
severe depression with hypericum extract
WS 5570 (St John's wort): randomised
controlled double blind non-inferiority
trial versus paroxetine. BMJ, 330: 503-
WHO, 2001. The World Health Report 2001:
Mental health: new understanding, new
hope, World Health Organization.
Yaghubi M, Zargar F, Akbari H. 2017.
Comparing effectiveness of mindfulnessbased relapse prevention with treatment
as usual on impulsivity and relapse for
methadone-treated patients: a randomized
clinical trial. Addict Health, 9: 156-165