Identification
of genetic markers for antidepressant side
effects
Most
antidepressants are metabolised by various liver
cytochrome P450 isoenzymes, mainly 2D6 (CYP2D6).
A study was undertaken to examine the effects of
genetic variation at the CYP2D6 and 5-HT2A
receptors on undesirable side effects of two
antidepressants, paroxetine, and mirtazapine
..........Click
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Treating
depression can improve pain in elderly
patients
Arthritis
and depression are common and leading causes of
functional disability in elderly patients,
reducing their quality of life. A recent study
set out to determine the effects of treating
depression on pain and functional outcomes in
old patients with arthritis and concurrent
depression.................. Click
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Alteration
of 5-HT1A signal transduction
pathways in brain of suicide victims
A
recent study examined distinct activities of
second messengers stimulated by 5-HT-1A
receptors in postmortem brain samples from
depressed suicide victims. Psychological autopsy
procedure using DSM III-R criteria established
the postmortem diagnosis. The occipital cortex
samples from six suicide victims who suffered
from major depression and six matched controls
were dissected ..................
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Increased
poststroke survival with
antidepressants
Stroke
patients who are depressed have a greater
morbidity than stroke patients without
depression. A recent study assessed the effect
of antidepressant treatment on recovery and
mortality after a stroke over a 9 year follow up
period. Of the patients who received
antidepressant treatment, 67.9% were alive after
9 years, compared with only 35.7% of patients on
placebo. Surprisingly there was a significant
beneficial effect of antidepressants both in
patients who were depressed and those who were
not ................. Click
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Different
brain activity in treatment-resistant
depression
30-40%
of depressed patients fail to respond to
antidepressant treatment. Emotional responses to
the images were studied using functional
magnetic resonance imagery to track brain
activity and elucidate brain areas used in
specific tasks. There was a clear association
between hypo- and hyperactivity of some specific
brain regions and non-responsiveness to
antidepressant treatment......................
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Identification
of subgroups of fibromyalgia
Fibromyalgia
is very frequently co-morbid with depression.
Patients meeting the American College of
Rheumatology criteria for fibromyalgia completed
self-report questionnaires on mood, cognition
and hyperalgesia/tenderness. Cluster analysis
revealed three distinct subgroups of
fibromyalgia patients with different relations
between the key symptoms of teh
disorder................... Click
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New
rating system for depression based on fuzzy
logic
A
new scale based on fuzzy logic theory has been
recently proposed to evaluate depressive
symptoms. Based on a patient or clinician scored
visual analogue scale, the new system uses
categorical weighting and multivariate analysis
to determine the symptom severity. Validity of
this new evaluation tool was tested in
comparison with the Hamilton Depression Rating
Scale in 10 depressed patients.................
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Possible
faster onset of antidepressant action with
milnacipran in comparison to fluvoxamine and
paroxetine
A
retrospective cohort analysis was carried out in
outpatients diagnosed with major depressive
disorder or bipolar disorder according to the
DSM-IV criteria. The daily dose of fluvoxamine
was 50-150 mg, that of paroxetine was 20-40 mg,
and that of milnacipran was 50-100 mg. Patients
were evaluated as either responder or
non-responder before treatment and every week
during antidepressant treatment using the
21-item Hamilton depression rating
scale.................... Click
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Possible
association between severe obesity and
depression
A
group of investigators studied depression in
patients before and after undergoing
surgery-induced weight loss. A group of 487
consecutive patients entering the investigators
clinic completed the Beck Depression Inventory
(BDI) questionnaire before and at yearly
intervals after gastric restrictive weight loss
surgery. A total of 262 paired preoperative and
1-year postoperative scores were used to
identify predictors of BDI score
changes................... Click
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article
Hyperactivity
of HPA axis in response to interferon-alpha and
development of
depression
Rates
of depression are higher in patients
experiencing major medical illness than in the
general population. Interferon-alpha has been
shown to induce depression. A recent study
examined the response of the
hypothalamic-pituitary-adrenal (HPA) axis to
interferon-alpha and evaluated the possible
relationship between this reaction and the
development of major depression during
interferon-alpha treatment.................
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Antidepressants
protect against loss of hippocampal volume
Depression
is associated with a reduction in hippocampal
volume. The effect of antidepressant treatment
on hippocampal volumes has been studied in
patients with major depression. There was an
association between the longer episodes during
which depression was untreated and decreases in
hippocampal volume. The cumulative hippocampal
volume loss shown in this study strongly
dictates the necessity for early recognition and
treatment of depression...................
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Modulation
of stress-induced depression by a serotonin
transporter genotype
Stressful
events, such as losing a loved one or a job, are
well known precipitating factors of major
depression. The serotonin (5-hydroxytryptamine,
5-HT) transporter (5-HTT) gene codes for the
transport protein which is blocked by most
antidepressants and is thought to be central to
their mode of action. There are two forms
(alleles) of the 5-HTT gene, a long and a short
form. Animal studies and human functional
neuroimaging have suggested that the 5-HTT
genotype may be associated with responses to
stressful conditions. A recent study
investigated why some people adapt to stressful
events while others become depressed in relation
to the 5HTT genotype..................
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"Do
not prescribe paroxetine to children and
teenagers" warn British and American
regulators
Recently
the British Medicines and Healthcare Products
Regulatory Agency warned that patients younger
than 18 should not receive paroxetine because of
an enhanced risk of suicidal thoughts and
behaviour. The US FDA repeated the warning a few
days later. The warning is based on 9 studies
which show a 2-3 fold increase in suicidal
thoughts on paroxetine. The British Committee
for the Safety of Medicines has decided to
investigate the relevance of these findings for
the use of paroxetine in adults..............
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Possible
impairment of 1-carbon metabolism in
depression
It
has been suggested that low folate
concentrations may be associated with depression
and that folate supplementation might be useful.
In a recent study blood levels of folate and
other indicators of 1-carbon metabolism were
measured in nearly 6000 middle aged and elderly
depressed patients and the relationship between
affective disorders and elements of the 1-carbon
metabolism determined using logistic regression
models................ Click
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High
risk of relapse into depression by
antidepressant discontinuation in bipolar
patients
Following
successful treatment of patients with bipolar
disorder, antidepressant discontinuation is
currently recommended 6 months after remission
of depressive symptoms to prevent inducing
mania. The potential risk of relapse into
depression caused by this strategy has not,
however, been evaluated. A prospective study has
therefore been conducted on bipolar patients
successfully treated for an acute depressive
episode in whom antidepressant discontinuation
or continuation was carried out.................
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Differential
efficacy of nortriptyline and fluoxetine in
melancholic depression
Although
globally tricyclic antidepressants (TCA) and
selective serotonin reuptake inhibitors (SSRI)
are considered to be equally effective in major
depression, some studies suggest superior
efficacy for TCA in depressed patients with
melancholic symptoms. Over 100 patients who met
criteria for melancholia were randomised to
receive either nortriptyline or fluoxetine and
response measured after 6 weeks of
treatment................ Click
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article
Despite
the high prevalence of depression, treatment,
when given, is frequently inadequate
Over
9000 adults participated in a replication of the
US National Comorbidity Survey. The results show
6.6% had experienced an episode of major
depression during the 12 months preceeding the
survey. Although 51.6% of these patients took
antidepressant medication, less than half of the
treatments were considered "adequate". Thus in
spite of better diagnosis, almost 80% of
patients did not receive adequate antidepressive
treatment............... Click
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Association
between polymorphism in receptor kinase gene and
bipolar disorder
A
polymorphism of the G protein kinase 3 (GRK3)
gene has been found to be associated with
bipolar disorder in families of northern
European Caucasian ancestry. GRK3 is expressed
widely in the brain and plays a key role in the
desensitization of G protein-coupled receptor
signaling. The mutation could result in an
increased neural sensitivity to dopamine leading
to the mood extremes that characterize the
disorder............... Click
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article
Increased
serum levels of substance P in depressed
patients
To
investigate the possible link between SP and
depression, a recent study measured serum SP
levels in depressed patients before and after
antidepressant treatments. SP levels in
drug-free, depressed patients were significantly
higher than in controls. There was no change in
mean SP levels in depressed patients between
baseline and 4-week treatment with
antidepressants. When individual SP levels were
considered, however, 37% of them were decreased
by 15% to 50%, a change which correlated with
the reduction of depression severity.Although
preliminary, these findings may contribute to
better understand the role of neuropeptides in
depression and lead to the development of new
antidepressants............. Click
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Increased
body temperature in depressed patients
An
enhancement of extracellular levels of 5-HT has
been linked with an increase in temperature. A
recent study investigated the body temperature
of depressed patients and normal subjects in
relation to 5-HTTLPR deletion. In depressed
patients, body temperatures were higher than in
controls. Depressed or normal subjects with the
5-HTTLPR deletion (short SERT allele) had a
higher temperature than those without the short
allele on either chromosome.These results
suggest a link between body temperature,
depression and genetic differences in 5-HT
transport.............. Click
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Pain
relief in polyneuropathy by venlafaxine
In
a randomized, double-blind, placebo-controlled
study, with a three-way crossover, enrolled 40
patients which were assigned to one of the three
treatment sequences, (placebo, imipramine 125
mg/day or venlafaxine 225 mg/day) each of 4
weeks duration. Total pain scores during
the fourth week of treatment was lower in
patients receiving venlafaxine (80% of baseline
score) and imipramine (77%) than those taking
placebo (100%). The results suggest that
venlafaxine may be useful to relieve pain in
polyneuropathic patients with cannot tolerate
TCA. The newer antidepressant is not, however,
more effective.............. Click
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article
Link
between brain N-acetyl aspartate, depression and
pain
Although
the physiological mechanism is still unknown,
there is considerable evidence to suggest that
chronic pain and depression are associated. A
recent study examined the relationship between
N-acetyl aspartate levels in different brain
regions and the severity of depression and pain
in 10 patients suffering from chronic pain and
depression in comparison to 10 normal sex and
age matched subjects.............
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Preschool
children with depression exhibit typical
symptoms
Depression
in children has been thought to be characterised
by indirect symptoms such as stomach ache rather
than sadness or lack of enjoyment. A study
investigated the clinical features of depression
in 174 preschool children from 3 to 5 years old.
Three groups were studied; depressed children
who met criteria for major depressive disorder;
children with a non-affective psychiatric
disorder, attention-deficit/hyperactivity
disorder (ADHD) and/or oppositional defiant
disorder (ODD), and a third group with no
pychiatric disorder...............
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Reduction
of cortical 5-HT2A receptor binding
in drug-naive but not in paroxetine-responder
depressed
patients
5-HT2A
receptors may be involved in the pathophysiology
of depression. A positron emission tomography
(PET) study using the 5-HT2A and
dopamine D2 receptor antagonist,
[18F]fluoroethylspiperone
([18F]FESP), compared
5-HT2A receptor binding in patients
with major depressive disorder, either never
treated with antidepressants (drug-naive) or
responding to the selective serotonin reuptake
inhibitor, paroxetine and healthy
volunteers................. Click
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article
Enhanced
amygdala volume in first depressive episode
Changes
in amygdala volume have been observed in
patients with affective disorders. Increased
amygdala volume has been reported in
first-episode major depression patients compared
with age-matched healthy control subjects. The
recent study found increased amygdala volume in
patients in first-episode patients but not in
patients with recurrent major
depression.............. Click
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Potentiation
of basal 5-HT levels in rat hippocampus by
combination of chronic citalopram and subchronic
lithium
In
patients who fail to respond to antidepressant
monotherapy co-administration of lithium as an
augmentation strategy is considered as the
first-choice procedure. The effect of
chronic citalopram and subchronic lithium was
investigated on hippocampal 5-HT levels and
behaviour in animals and showed enhanced the
extracellular levels of 5-HT................
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Prediction
of response to paroxetine by PET
scanning
Patients
with major depressive disorder and
obsessive-compulsive disorder (OCD) respond to
treatment with selective serotonin reuptake
inhibitors (SSRI) , however the neurobiological
substrates implicated in the treatment response
for both disorders may not be the same. Cerebral
glucose metabolism was measured using
[18F]fluorodeoxyglucose
positron emission tomography (PET) in patients
with OCD and major depressive disorder before
and after treatment with
paroxetine................ Click
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Link
between chronic pain and depression
Physical
symptoms such as pain are among the principal
presenting compaints in depression. A random
sample of nearly 19 000 subjects representative
of the general populations of several European
countries took part in a telephone survey.
Subjects reporting at least one chronic painful
physical condition represented 17.1%............
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Increased
a2-adrenoceptor
binding in the locus coeruleus of subjects with
major
depression
The
locus coeruleus (LC) is the brain region where
the majority of noradrenergic neuron cell bodies
are found. A recent study investigated density
of a2-adrenoceptors
in the LC of subjects with major
depression.
Postmortem
brain tissues containing the LC and dorsal and
median raphe nuclei were obtained from 14
subjects diagnosed with major depression and 14
controls.............. Click
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Reduction
of relapse rate by antidepressants used for a
long duration
A
systematic review of 31 randomised trials
involving more than 4400 patients suffering from
acute depressive disorders, who had responded to
a 4 to 6-month standard treatment with
antidepressants, was recently undertaken. The
subjects were assigned to continue treatment or
to placebo. Continued antidepressant treatment
for 1 to 2 years decreased the odds of relapse
by about 66%. Patients who continued
therapy............... Click
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Efficacy
of collaborative care management of late-life
depression
The
elderly suffering from depression often do
receive the correct treatment in primary care.
The effectiveness of a new collaborative care
management program for late-life depression,
IMPACT (Improving Mood-Promoting Access to
Collaborative Treatment), has been studied in
comparison with usual care...........
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Link
between bulimia nervosa and seasonal depression
in Japan
Changes
in appetite are among the symptoms of depression
and there is a strong comorbidity of depression
and eating disorders. Seasonal variation in
eating disorders in Japan has been the subject
of a recent survey using the Jpanaese version of
the Seasonal Pattern Assessment Questionnaire
(SPAQ), ............ Click
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Similar
efficacy of S-adenosyl-L-methionine (SAMe) and
imipramine in major
depression
S-adenosyl-L-methionine
(SAMe) is the most important methyl donor in
transmethylation reactions in the central
nervous system and several clinical trials have
suggested that SAMe is efficacious in
depression. A recent study compared the efficacy
and safety of SAMe in the treatment of major
depression in comparison with
imipramine............... Click
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Comparison
between venlafaxine and selective serotonin
reuptake inhibitors in depression
A
recent meta-analysis compared the efficacy of
venlafaxine and SSRIs in 8 randomised,
double-blind, placebo-controlled trials. The
pooled analysis showed that the mean decrease in
the HAMD(21) was significantly greater in
patients on venlafaxine compared to those on
SSRIs. Both drug treatments were superior to
placebo. The mean MADRS scores were also
decreased to a greater extent by venlafaxine
than by SSRIs.......... Click
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Supersensitivity
of alpha2A-adrenoceptors in brains of
suicide victims
A
recent study determined receptor function in
postmortem suicide victim brain by measuring the
modulation of [35S]GTPgammaS
binding to G-proteins. Stimulation of
[35S]GTPgammaS binding by the
alpha2A-adrenoceptor agonist,
UK14304, showed a 4.6-fold higher sensitivity in
brains of suicide victims than in controls,
without changes in the maximal stimulation. No
differences were observed in any other
receptors............ Click
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Influence
of sunlight on serotonin production in the
brain
CSF
levels are imprecise indicators of serotonin
release by the brain, which has prompted the
measurement of serotonin concentrations from
blood vessels draining the brain as a more
accurate assessment of brain serotonin. Turnover
of serotonin by the brain was found to be lower
in winter than in summer or spring and the rate
of serotonin production was directly associated
with the prevailing duration of bright
sunlight.............. Click
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