1.
Abstract
Depression is a common mental illness that involves a
significant and persistent lowering of mood associated with
great sadness, and a loss of interest in life. When these
problems last two weeks or more, and are so bad that they get in
the way of daily living, this is depression. Other symptoms
include loss of ability to experience pleasure, anxiety,
panic, fearfulness, irritability or apathetic mood, changes in
appetite and weight, changes in sleep, fatigue or loss of
energy, guilty and pessimistic thoughts, hopelessness and
helplessness, Concentration may be affected and thoughts of
death and suicide may be present.
Depression
is common, serious and treatable.
Untreated, it can result in disability and even death.
It
affects 1 in 25 people in any 1 month. Some 43% of those with
depression suffer severe disability.
It
tends to be episodic and of
varying
severity. Most major depression begins in the late 20s. Symptoms
develop over days to weeks, though there may be symptoms over
the preceding months. Half respond to 6–8 weeks of active
treatment. The likelihood of recovery decreases with the
duration of symptoms. Remission is partial for 20–30% of people
with depression, who experience continuing symptoms and social
and occupational impairment. The more episodes of depression a
person experiences, the more likely they are to experience a
recurrence.
For the
treatment of depression, a variety of antidepressant medications
are available that have proven beneficial effects. Other
treatments including cognitive
behavioural
therapy and interpersonal psychotherapy are also used. Treatment
varies with type and severity of depressive symptoms.
Extracts of
the plant St. John’s Wort, have been used in folk medicine for a
long time for a range of indications, including depressive
disorders, anxiety and sleep disorders. St John’s Wort contains
at least seven constituents or groups of components that may
contribute to its effects. The exact mechanism of action is
still unclear.
There is
good evidence that St John’s Wort improves symptoms of mild to
moderate depression. For major depression the evidence is
inconclusive.
There is good evidence that St John’s Wort extracts caused fewer
side-effects than older antidepressant but a similar number to
selective serotonin reuptake inhibitors.
Many patients buy
St John’s
Wort products from health-food stores and might not disclose
this to their doctors. This can be problematic, because serious
interactions can occur with a number of frequently used drugs
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2.
Type of treatment
Herbal
Scientific name (genus and species):
Hypericum
perforatum
Synonyms and common names:
St. John’s Wort
Indication:
Depression, anxiety and sleep disorders
3.
Background
Depression is a mood state that involves a significant and
persistent lowering of mood associated with great sadness, and a
loss of interest in life. Many people feel sad, discouraged, or
"down" once in a while, but for some people, this mood does not
go away. When these problems last two weeks or more, and are so
bad that they get in the way of daily living, this is
depression.
http://www.infrapsych.com/root/1033/Depression/Depression_Symptoms.htm
Other
symptoms include loss of interest and ability to
experience pleasure, irritable rather than depressed or
apathetic mood. The following physical symptoms may also be
present: changes in appetite and weight, changes in sleep, and
fatigue or loss of energy. Thinking may be affected with an
increase in guilty and pessimistic thoughts, hopelessness and
helplessness, Concentration may be affected and the person may
become quite forgetful. Thoughts of death and suicide may be
present.
Depression
is common, serious and treatable.
In the Australian Mental Health Survey, 4% of adults had a
depressive disorder in the past month.
Untreated, it can result in significant disability and even
death.
Some 43% of those with depression suffer severe disability.
It
tends to be episodic and of
varying
severity. Moderate to severe depression is as disabling as heart
failure, and its relapsing nature accounts for one of the
highest levels of disease burden of any condition. Depression is
the most likely condition to co-exist with other physical and
psychiatric disorders, and is often unrecognized by healthcare
workers.
Depression
does occur in children but more often in teenagers. Most major
depression begins in the late 20s. Symptoms develop over days to
weeks, though there may be anxiety, panic, fearfulness and
lowered mood over preceding months. Sudden onset is usually
associated with major stress. Untreated moderate episodes last
up to 9 months. Half respond to 6–8 weeks of active treatment.
The likelihood of recovery decreases with the duration of
symptoms. Remission is partial for 20–30% of people with
depression, who experience continuing symptoms and social and
occupational impairment. The more episodes of depression a
person experiences, the more likely they are to experience a
recurrence.
If
untreated, depression increases risk of suicide and other
violent acts. Unemployment, isolation, impulsivity and misuse of
alcohol and drugs increase the risk. Depression, especially when
recurrent or chronic, distresses family and friends and it may
affect a person’s capacity to parent, and is often associated
with occupational problems.
Many factors
protect against, predispose to, or precipitate depression:
genes, childhood experience, previous trauma, social and
cultural supports, physical factors (including drugs) and
stress. Depression occurs more commonly in the young and in
women, at least in Western society. Depression affects about
5–14% of those with medical illness. Rates of 50% are associated
with some conditions, for example HIV-AIDS. It is commonly
associated with Parkinson’s disease, migraine and chronic pain.
Increased rates may be a direct effect of physical illness, a
side-effect of treatment or a reaction to illness. (RANZCP 2004)
For the
treatment of depression, a variety of antidepressant medications
are available that have proven beneficial effects. Other
treatments including cognitive
behavioural
therapy and interpersonal psychotherapy are also used. Treatment
varies with type and severity of depressive symptoms. (RANZCP
2004) All antidepressant medications have adverse effects, and
some are expensive. Additional treatments with little risk,
credible benefit, and moderate costs could be a useful addition
to depression management.
Extracts of
the plant Hypericum perforatum L. (popularly called St.
John’s Wort), have been used in folk medicine for a long time
for a range of indications, including depressive disorders.
Extracts of St. John’s Wort are licensed and widely used in
Germany for the treatment of anxiety, depressive and sleep
disorders. In recent years, St John’s Wort has also become very
popular in other countries. St John’s Wort contain at least
seven constituents or groups of components that may contribute
to its pharmacological effects While some isolated substances,
as for example hyperforin, have been shown to have
antidepressant activity, the total extract seems to be clearly
more effective. The exact mechanism of action is still
unclear.(Linde, Mulrow et al. 2005)
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4.
Objectives
To investigate whether extracts of hypericum are more effective
than placebo and as effective as standard antidepressants in the
treatment of depressive disorders in adults; and whether they
have less adverse effects than standard antidepressant drugs.
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5.
Criteria for including studies
Types of study: Published systematic reviews or
double-blind randomised controlled trials of
extracts of St John’s Wort versus standard antidepressant
treatment or placebo applied for at least 4 weeks;
limited to the English language.
Types of participants: Adults (≥18 years) with a depressive disorder.
Types of intervention:
Extracts of St John’s Wort versus standard antidepressant
treatment or placebo.
Types of outcome measure:
All clinical
outcome measures such as depression scales or symptoms.
Exclusions: Combined herbal treatments; treatment period of less
than 4 weeks; studies examining prevention of depression.
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6.
Search strategy
We
searched the following databases in May 2006: AMED, The Cochrane
Library, PSYCHINFO, MEDLINE, and CINAHL from 2004. We also
checked the reference lists of publications retrieved by the
search for further relevant studies. We also searched the World
Wide Web for any other relevant studies.
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7. Data Collection, Analysis and Development of
Recommendations
We used the above search strategy to obtain titles and abstracts
of studies that were potentially relevant to this review. Where
studies met the criteria for inclusion, they were assessed in
full text. The quality of each study was evaluated using the
GATE criteria (http://www.health.auckland.ac.nz/population-health/epidemiology-biostats/epiq/)
for the evaluation of RCTs and systematic reviews. Where
primary studies were included in a good quality systematic
review, the systematic review was included rather than the
individual primary studies. Where the systematic reviews
included the same primary studies, the Cochrane review was used.
The overall quality of the body of evidence (including all the
included studies) was graded according to the NZGG CAM levels of
evidence system.
Relevant data were extracted from the studies selected for
inclusion.
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8.
Description of studies
A
Cochrane systematic review, updated in February 2005, was
identified. In addition, three other systematic reviews and six
additional
randomised
controlled trials (not included in the systematic reviews) met
the criteria for inclusion. The Cochrane review included 37 RCTs,
published prior to April 2004. Another systematic review (Werneke,
Horn et al. 2004) included 18 RCTs, published prior to September
2003. All these studies were included in the Cochrane systematic
review. A systematic review (Knuppel, Geddes et al. 2004) that
looked at safety and adverse effects was included. A review (Trautmann-Sponsel
and Dienel 2004) of three RCTs was excluded as the studies were
included in the Cochrane review. One other RCT (Murck, Fava et
al. 2005) was a re-analysis of an RCT already included (Fava,
Alpert et al. 2005). The six additional RCTs were all published
between July 2004 and 2006.
Summary details of the included
studies are as follows:
Systematic Reviews
|
Study |
Participants |
Intervention & Comparison |
Outcomes measured |
Comment |
|
Linde K,
2005
Cochrane Database of Systematic reviews |
Included studies: 37 studies published prior to April
2004
N=4925
Adults with depressive disorders |
St John’s Wort for at least 4 weeks
vs
placebo
standard antidepressants |
Assessment of symptoms with a depression scale or
general assessment of clinical response |
The methodological quality of most of
the included studies was reasonable to good.
26 studies used placebo as the comparator; 14 used
standard antidepressants |
|
Knuppel, L.
2004
Germany |
Included studies: 35 RCTs and
17
observational studies |
St John’s Wort for at least 4 weeks
vs
placebo
standard antidepressants |
Drop outs due to adverse effects
Numbers reporting adverse effects |
Drop out rates and adverse effects are similar for St
John’s Wort, SSRIs and no treatment
St John’s Wort is better tolerated than older standard
antidepressants
Short follow up periods and small sample sizes may
increase the chance that adverse effects are overlooked |
|
Werneke, U.
2004
UK |
Included studies: 18 studies |
St John’s Wort
vs
placebo
|
Hamilton depression scale
|
All studies were included in the above Cochrane review
so this systematic review was not used |
Randomised
controlled trials
|
Study |
Participants |
Intervention & Comparison |
Outcomes measured |
Comment |
|
Gastpar, M
2005
Multicentre trial in Germany |
241 patients with moderate depression |
Hypericum extract 612mg once daily
vs
sertraline 50mg once daily
Duration 12 weeks
Follow-up 24 weeks |
Hamilton
depression scale
Von Zerssen’s Adjective Mood Scale
Clinical Global Impression
Adverse events |
Blinded
Drop out 17% at 12 weeks
|
|
Randlov, C.
2006
Denmark |
150 patients with mild or moderate depressive episode or
dysthymia
Mean age 50.9 years (range 23-74)
113 women; 37 men |
Hypericum extract either 0.12% hypericine (low-dose) or 0.18%
hypericine (high-dose) taken 3 times daily
vs
placebo
Duration 6 weeks |
Hamilton depression scale
Beck depression inventory
Visual analogue scale
D-2-test
Adverse events |
Blinded
Drop out rate 14%
Ad hoc statistical analysis
No power calculation |
|
Szegedi, A.
2005
Germany |
251 adult outpatients with acute major depression
|
Hypericum extract (WS 5570) 300mg three times a day
vs
Paroxetine 20mg once daily
Duration 6 weeks |
Hamilton depression scale
Montgomery-Åsberg
depression rating scale
Beck depression inventory
Clinical Global Impression
Adverse events |
Mean age and average duration of current episode were
higher in the St John’s Wort group
Blinded
Power calculation
Drop out rate 18% |
|
Bjerkenstedt, L
2005
Sweden |
163 adults from 15 GP practises with mild to moderate
major depression |
Hypericum extract (LI160) 300mg three times a day
vs
Fluoxetine 20mg daily
vs
Placebo
Duration 6 weeks |
Hamilton depression scale
Montgomery-Åsberg
depression rating scale
Clinical Global Impression
Adverse events |
Blinded
Drop out rate from ITT population 9%
Drop-outs after start of treatment but before first
follow-up were excluded from ITT analysis
No placebo group at week 6 since the placebo group was
switched to either active treatment groups after 4 weeks |
|
Fava,
M
2005
Germany |
135 adult outpatients with major depression
Mean age 37.3 |
Hypericum extract (LI160) 300mg three times a day
vs
Fluoxetine 20mg daily
vs
Placebo
Duration 12 weeks |
Hamilton depression scale
Beck depression inventory
Clinical Global Impression
Adverse events |
Blinding
Drop out rate 47%
ITT analysis |
|
Uebelhack, R.
2004
Germany |
140 outpatients with moderate depressive disorder
46 men; 94 women |
Hypericum extract (STW 3-VI) 900mg once daily
vs
Placebo
Duration 6 weeks |
Hamilton depression scale
Von Zerssen’s Adjective Mood Scale
Clinical Global Impression
Adverse events |
Blinding
Drop out rate 14%
ITT analysis |
