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Depression: Beating the odds for
remission
Depression takes a huge toll on society in
lost productivity, family distress and
dysfunction, and suicide, explained John
H. Greist (Healthcare Technology
Systems, Inc, Madison, WI, USA).
Depression is a multidimensional illness,
reported more often in women than in
men, with a host of emotional, physical
and associated symptoms. “The cardinal
emotional symptoms are sadness, lack of
energy, lack of interest, feelings of guilt,
and suicidality,” Dr. Greist told the
audience.
Treatment phases of depression can
include response, remission, recovery,
relapse and recurrence. The Sequenced
Treatment Alternatives to Relieve
Depression (STAR*D) study provides
some real-world insights into outcomes in
patients with depression treated with
initial therapy, switching to a different
drug and augmentation strategies. This
study included 2,876 outpatients with
major depressive disorder (MDD) seen in
23 psychiatric and 18 primary care ‘real-
world’ settings who were initially treated
with flexible doses of citalopram for up to
14 weeks [1]. Approximately one third
achieved remission on monotherapy with
citalopram, switching from citalopram to
a different antidepressant achieved
remission in 20% to 25%, and
augmentation of citalopram with either
buspirone or sustained-release bupropion
achieved remission in 30% [2,3].
Remission may not be long-lasting due to
delayed onset of remission, unresolved
symptoms of depression, recurrent
episodes of depression and systemic issues,
Dr. Greist explained. Delayed onset of re-
mission is associated with poor outcome [4],
he continued. Also, some patients respond
but do not achieve remission. Residual
symptoms of depression predict worse
outcomes [5], he added.
Making an accurate diagnosis and getting
the patient on the right treatment increases
the chances of response, recovery and
remission. In clinical practice, many
patients are undertreated and do not have
NEWS FLASHES FROM APA
MAJOR DEPRESSIVE
DISORDER A HUGE BURDEN
TO SOCIETY
Julie C. Locklear. AstraZenecaPharmaceuticals, LP, Wilmington,DE, USA.
PREDICTORS OF SUICIDAL
IDEATION IN POST-PARTUM
WOMEN WITH NEURO-
PSYCHIATRIC ILLNESS
Tamara E. Weiss. Emory University,Atlanta, GA, USA.
DEEP BRAIN STIMULATION
FOR TREATMENT-RESISTANT
DEPRESSION
Sidney H. Kennedy. University HealthNetwork, Toronto, ON, Canada.
DEPRESSION AND ALCOHOL
ABUSE CLOSELY LINKED IN
WOMEN, NOT MEN
Nelli Boykoff. Mayo Clinic,Rochester, MN, USA.
STEREOTYPED RESPONDING
IN MAJOR DEPRESSION
Didier Schrijvers. University ofAntwerp, Antwerp, Belgium.
PREVALENCE OF SUBSTANCE
DEPENDENCE AND
PSYCHIATRIC/MEDICAL
CONDITIONS
William J. Meehan. AdCare Hospital,Boston, MA, USA.
MEDUNET CONGRESS NEWS
FROM DATA PRESENTED AT THE
2008 ANNUAL MEETING OF THE AMERICAN PSYCHIATRIC ASSOCIATION (APA)
MAY 3–8, 2008, WASHINGTON, DC, USA
TANGLED UP IN BLUE: OPTIMISING TREATMENT
OF DEPRESSION IN THE PRESENCE OF
COMORBIDITIES
Patients with depression commonly have physical and psychiatric
comorbidities. There are few definitive studies to guide treatment of
depression in the presence of comorbidities and treatment is often
empirical. Experts speaking at a satellite symposium explored the
magnitude of the problem of comorbidity in depression, as well as
treatment approaches for comorbid somatic symptoms and
psychiatric problems. Evidence suggests that antidepressants that
inhibit both serotonin and norepinephrine may improve associated
pain and other somatic symptoms as well as depressive symptoms.
Please visit www.medical-ip.com to discuss this report with your colleagues and leave your comments on other articles!
TANGLED UP IN BLUE
MAJOR DEPRESSIVE DISORDER A HUGE BURDENTO SOCIETY
MDD takes a huge toll on patients’
ability to work, function, and perform
daily activities, according to a large
survey from the U.S. and European
Union (EU). Julie C. Locklear
(AstraZeneca Pharmaceuticals, LP,
Wilmington, DE, USA) presented sur-
vey results on the burden of depressive
illness at a poster session.
Worldwide, the six-month prevalence of
MDD ranges from 3.8% to 9.9%. The
survey included 474 physicians from the
U.S. and five European countries
recording information on 1,582 patients
with MDD and 8,459 subjects classified
as “All Other Neuroses” (AON). Of
patients treated for MDD about 65% was
female and mean age was 47 years.
In both the EU and US, patients with
MDD had a higher mean number of
symptoms than those with AON (17.7
vs. 9.2 in the EU, respectively,
p < 0.001) and 15.9 vs. 7.7, respectively,
in the U.S., p < 0.001). Most patients
with MDD reported between 11 and 15
symptoms, whereas most patients with
AON reported between 6 and 10
symptoms. In the EU, 25% of the MDD
patients suffered more than 20
symptoms vs. 23% in the U.S., whereas
only 6% of EU patients and 3% of U.S.
patients with AON reported having more
than 20 symptoms.
When patients were asked how much
impact on their lifestyle these symptoms
had, (ranging from 1 [not affected] to 10
[not able to continue with normal
activities at all]), the average score for
patients with MDD was 6.3 compared
with 5.0 in the EU and 4.5 in the U.S for
those with AON.
Reference: Locklear JC, et al. Poster presented at the2008 Annual Meeting of APA. Washington,DC., USA, 2008 (Abstr. NR3-064).
2
an adequate trial of an antidepressant. “If
the diagnosis is correct, undertreatment is
the primary cause of recurrent, resistant
and refractory depression,” Dr. Greist
stated. Many studies have shown that
keeping patients on antidepressants will
maintain them in remission [6], he said.
Patients with a suboptimal response to
monotherapy can be switched to a
different drug and a proportion of them
will respond. As STAR*D showed,
remission was observed in a similar
proportion of patents switched from
citalopram to bupropion-SR, sertraline or
venlafaxine-XR [2].
If the first switch is not effective, then
switch again, Dr. Greist suggested. One
study found that 50% of patients
responded to the first drug; 63%% to a
second drug and 66% to a third drug [7]. In
that trial, 93% of patients who completed
therapy achieved remission.
Exercise can improve depressive
symptoms, Dr.Greist said. “Exercise is at
least as important as psychotherapy, as
several trials have shown.” Electro-
convulsive therapy (ECT) is reserved for
patients who fail to respond to several
adequate trials of antidepressants [8].
Augmentation of antidepressant therapy is
effective in a proportion of patients who
fail to respond to initial monotherapy.
Most of the drugs used for augmentation
of antidepressant effect are off label, he
said. Evidence supports use of T3 and
lithium, but there is no evidence to
support the most widely used drugs to
augment selective serotonin reuptake
inhibitors (SSRIs), such as bupropion,
methylphenidate, atypical neuroleptics,
mirtazapine, buspirone, tricyclic
antidepressants and valproic acid.
He urged audience members to validate the
correct diagnosis, administer an adequate
trial of antidepressants, use scientific data
when making decisions, and, most of all,
not to give up on patients with depression.
The goal of treatment is to restore
functioning and to relieve suffering;
hopefully this will achieve remission.
Depression with psychiatric comorbidity;
recognition and management
Psychiatric comorbidity commonly occurs
in patients with depression but is often not
recognised, said James W. Jefferson
(Department of Psychiatry, University of
Wisconsin School of Medicine and Public
Health, Madison, WI, USA). Common
psychiatric comorbidities include general
anxiety disorder as well as specific
phobias, panic disorder, post-traumatic
stress disorder, seasonal affective disorder,
obsessive-compulsive disorder,
personality disorder and substance use
disorder (drugs and/or alcohol).
It is easy to miss psychiatric comorbidity
in patients with MDD in clinical practice,
partly as a result of time constraints. “You
won’t find something unless you spend a
lot of time trying to find it,” Dr. Jefferson
said. “It takes about 1 hour and 43
minutes to administer the Structured
Clinical Interview for DSM-IV (SCID)
and another 45 minutes to check a
patient’s medical records. Most
psychiatrists in the U.S. don’t have the
time to do that.” Another problem with
the U.S. healthcare system is that many
patients with MDD never see a
psychiatrist or other doctor.
Tools for diagnosing comorbid psychiatric
conditions include SCID, the Mini-
International Neuropsychiatric Interview
(MINI), the Primary Care Evaluation of
Mental Disorders (PRIME-MD), the
Mental Health Screener and the
Psychiatric Diagnostic Screening
Questionnaire (PDSQ). Dr. Jefferson said
that the MINI and PDSQ are the ones
most commonly used.
The STAR*D study had findings that are
generalisable to the real world; it found a
substantial amount of comorbidity in
patients with depression who were
recruited from community practices [1]. At
baseline, the PDSQ was used to assess
comorbidity in this group of patients; only
one third of subjects had no psychiatric
comorbidity, 65.2% had one or more
comorbidities, and 12.9% had four
comorbidities (Figures 1, 2).
PREDICTORS OF SUICIDALIDEATION IN POST-PARTUMWOMEN WITH NEURO-PSYCHIATRIC ILLNESS
Post-partum suicide is a leading cause of
mortality. According to a prospective
observational study of perinatal
psychiatric illness, risk factors for post-
partum suicidal ideation were distinct
from those for suicidal ideation
unrelated to childbirth and the post-
partum period, although there is some
overlap. Strongest predictors of risk of
suicidal ideation were current major
depressive episode and history of
substance abuse. Histories of eating
disorder and of miscarriage were
also strong predictors. Lead author was
Tamara E. Weiss (Emory University,
Atlanta, GA, USA).
Four hundred women with psychiatric
illness were enrolled in the study either
during pregnancy or prior to conception;
mean age was 24 years; 91.5% were
Caucasian, and 86.8% were married.
Suicidal ideation was present in 9.75%
of the women as measured on the Beck
Depression Inventory and in 7.75% on
the Hamilton Rating Scale for
Depression (HRSD). About 60% had
both Mood and Anxiety Disorder and
36.5% had both Mood and Substance
Abuse Disorder.
Multivariate logistic regression analysis
showed that a current major depressive
episode had an odds ratio (OR) of 10.77,
and a 95% confidence interval (CI) of
2.64–44.01 for predicting suicide ide-
ation. For other significant predictors,
OR were as follows:
• History of opioid abuse or dependence,
OR 29.63, 95% CI 1.66–528.58;
• History of polydrug dependence,
OR 64.35, 95% CI 3.95 – >999;
• History of eating disorder,
OR 6.47, 95% CI 1.74–24.05;
• History of miscarriage,
OR 7.49, 95% CI 1.62–34.55.
Surprisingly, psychiatric disorders and
lifetime mood disorders were not strong
predictors of suicidal ideation in this
sample.
Reference: Weiss TE, et al. Poster presented at the 2008Annual Meeting of APA. Washington, DC,USA, 2008 (Abstr. NR2-094).
3
TANGLED UP IN BLUE
and duloxetine), “but just because an
antidepressant isn’t indicated for a
comorbid psychiatric indication doesn’t
mean it doesn’t work,” he said. Some
SSRIs have as many as seven indications
(e.g., paroxetine). There are no studies to
guide treatment selection for depression
with psychiatric comorbidity. The
approach is basically empirical, trying to
match the antidepressant of choice with
the existing comorbidity on the basis of
FDA approval, but this is not always
effective, he said.
Cognitive behavioural therapy (CBT) has
been found effective for MDD and
comorbid anxiety disorders and can be
combined with drug treatment, but CBT
is not widely available.
For the present, Dr. Jefferson advised
psychiatrists to get ready (evaluate), aim
(diagnose) and fire (treat). He
emphasised that more effectiveness
research on MDD and psychiatric
comorbidity is greatly needed.
A greater number of Axis I comorbid
disorders were found in patients with
younger onset of MDD, longer duration of
MDD, greater severity of MDD, poorer
quality of life, more impaired daily
function, more prior suicide attempts, and
in those treated in primary-care practices.
Dr. Jefferson noted that “the presence of
comorbid medical or psychiatric disorders
may be associated with or induce
biological changes that render otherwise
useful treatments ineffective.”
Although comorbid psychiatric illness is
best treated within an integrated mental-
health system that provides
comprehensive care and case
management, even when such programs
exist, patients with MDD and other
psychiatric disorders are not always
willing to participate in them.
The choice between available SSRIs is not
always clear, he continued. Some SSRIs
are only approved for one or two
indications (e.g., citalopram, fluvoxamine
Figure 1 STAR*D BASELINE COMORBID PSYCHIATRIC DISORDERS
Source: Trivedi MH, et al. Am J Psychiatry 2006;163:28–40.
Social GAD PTSD OCD Panic Bulimia
phobia disorder
31.3
23.620.6
14.3 13.1 13.0
50
40
30
20
10
0
Fre
quen
cy (
%)
GAD = generalised anxiety disorder; PTSD = post-traumatic stress disorder; OCD = obsessive-compulsive disorder
Figure 2 STAR*D BASELINE COMORBID PSYCHIATRIC DISORDERS (CONT’D)
Source: Trivedi MH, et al. Am J Psychiatry 2006;163:28–40.
Alcohol abuse/ Agoraphobia Drug abuse/ Hypochondriasis Somatoform
dependence dependence disorder
12.0 11.8
7.4
4.4
2.4
20
15
10
5
0
Fre
quen
cy (
%)
DEEP BRAIN STIMULATIONFOR TREATMENT-RESISTANTDEPRESSION
In 2005, Mayberg et al. reported
encouraging results with deep brain
stimulation (DBS) to the subgenual
cingulate cortex in a pilot study of a
small number of patients with treatment-
resistant MDD. These findings have
been replicated in a larger series of
patients in a multicentre trial reported at
a poster session by Sidney H. Kennedy
(University Health Network, Toronto,
ON, Canada).
The study included 20 patients with
MDD and a current depressive episode
at least 24 months long who were
treatment-resistant (i.e., failed at least
four depression treatments including
Cognitive Behavioural Therapy). All
patients had a Hamilton Depression
Rating Scale for Depression (HRSD-17)
of 20 or higher.
Five of the cases were treated in
Vancouver, six in Montreal, and nine in
Toronto. At the time the poster was
prepared, the six-month evaluation was
completed on 16 patients, nine (56%) of
whom had at least a 40% improvement
on HRSD. After the poster was prepared,
six additional patients reached the six-
month mark, and now 15 of 19 patients
have had at least a 40% improvement on
the HRSD, for a response rate of 79%.
There is tremendous interest in DBS, and
these are robust findings, said Prof.
Kennedy. The technique entails inserting
electrodes into the subgenual cingulate
cortex Brodmann Area 25, which is
thought to be disregulated in brains of
depressed patients. Only about 50 cases
of MDD worldwide have been treated
with DBS, all of them highly refractory
to other treatments. Prof. Kennedy said
that these results warrant a double-blind
randomised trial of the technique.
Reference: Kennedy SH, et al. Poster presented at the2008 Annual Meeting of APA. Washington,DC, USA, 2008 (Abstr. NR3-113).
4
TANGLED UP IN BLUE
second week. The ‘blues’ are
characterised by labile mood, tearfulness
and mild sleep disturbances. No treatment
is required, unless the episode is
prolonged and other symptoms develop,
such as suicidality.
Several user-friendly instruments can
screen women for perinatal depression:
Edinburgh Postnatal Depression Scale
(EPDS, 10 items); Beck Depression
Inventory (BDI-II, 21 items); and
Postpartum Depression Screening Scale
(PDSS, 35 items). The EPDS is the
oldest and most common one and
requires only a few minutes to score [12].
A score of 12 (range 0–30) has good
sensitivity/specificity for MDD, she said,
and a score of nine signals probable mild
depression.
“Screening alone is not enough. These
women require treatment,” she said. It is
important to let the obstetric provider
know when an EPDS score signals the
presence of depression, so that he/she can
discuss depression and treatment with the
patient. Often patients at risk for
depression fall through the gap and are not
treated or followed appropriately. A
collaborative-care model is needed to
standardise follow-up, provide support
and education, provide referrals for
treatment, and cooperate with specialty
care.
Untreated perinatal depression has
adverse physical and emotional
consequences for mother and child.
Maternal depression increases the risk of
ectopic pregnancy, miscarriage,
hyperemesis, preterm contractions and
pre-eclampsia [13,14]. After children of
mothers with depression are born, they are
at risk for poor follow-up and routine care
and the mother’s misuse of pediatric
emergency services, she said.
A cohort of children whose mothers were
depressed and anxious during pregnancy
had significantly greater psychiatric
problems at 81 months compared with the
general population (Figure 3) [15].
Furthermore, these effects were seen at
age 4 and persisted until 81 months.
More than the blues: medical
comorbidity in perinatal depression
The lifetime risk of depression is twice as
high for women as for men, explained
Maria Muzik (Department of Psychiatry,
University of Michigan, Ann Arbor, MI,
USA). Life transitions, such as
adolescence, premenstruation, peripartum
and perimenopause, make women more
vulnerable to depression and this
vulnerability appears to be related to
hormonal fluctuations during these
transitions. Dr. Muzik’s presentation
focused on depression during pregnancy
and the post-partum period.
“We used to think that pregnancy
prevented depression because of increases
in oestrogen, but now we know that is not
the case. The percentage of women who
experience depression during pregnancy is
14% [9] and about 10–15% of women
experience post-partum depression [10],”
she told listeners. “The percentages are
similar even in cultures where women
have lots of support from extended family
members,” she added.
Post-partum ‘blues’ are distinct from
depression and are much more common;
“the blues are almost the norm,” she said.
Anywhere from 50% to 85% of women
report feeling ‘blue’ or sad after giving
birth. Psychosis is rare, she said, occurring
in one or two women per 1,000 [11].
Perinatal depression, according to DSM-
IV-TR criteria for major depression, has
onset within the first four weeks of giving
birth. Dr. Muzik said that in her
experience, most post-partum depressions
have onset from 6 to 12 weeks [10]. Unique
features of post-partum depression include
prominent anxiety related to loss of
control, loneliness, and intrusive and
obsessive thoughts of harming the baby.
Post-partum psychosis has a more rapid
progression, within a week or two, and
requires immediate treatment. Sometimes
this represents new onset of bipolar
disorder. By contrast, post-partum ‘blues’
typically begins two to four days after
giving birth and usually resolves by the
DEPRESSION AND ALCOHOLABUSE CLOSELY LINKED INWOMEN, NOT MEN
Depressive symptoms correlated with
alcohol craving in women, but not in
men, according to a large retrospective
clinical data set of more than 300
patients voluntarily participating in a
28-day intensive addiction program at
the Mayo Clinic in Rochester, MN,
USA. Women appeared to be drinking
to relieve feelings of anxiety and
depression, whereas men may be
drinking just to feel good, speculated
lead author Nelli Boykoff (Mayo Clinic,
Rochester, MN, USA).
On admission to the program, women
had significantly higher scores for
depressive symptoms (p = 0.001) and
alcohol craving (p < 0.0001) compared
with men. The gender difference
persisted in those with a clinical
diagnosis of alcohol dependence only
(n = 92) or a dual diagnosis (n = 139;
alcohol dependence plus depression,
bipolar disorder or anxiety disorder).
The retrospective analysis included 364
patients (135 women and 229 men).
Mean age was about 48 years and
subjects began drinking at about age 20.
All were heavy drinkers; women
averaged 10.8 drinks per day and mean,
13.8 drinks per day. Fifty-three per cent
were daily drinkers; 75% fulfilled the
National Institute of Alcohol Abuse and
Alcoholism (NIAA) definition of
hazardous users (>5 drinks/day for men
and >4 drinks/day for women).
A correlation between depression and
alcohol craving scores in women (not
men) was seen in those with alcohol
dependence alone (r = 0.78, p < 0.0001)
and in women with dual diagnosis
(r = 0.36, p = 0.01).
This is one of the first studies to show
gender differences regarding clinical
correlates of alcoholism. Further study
may reveal gender-specific targets for
treatment of alcohol craving.
Reference: Boykoff N, et al. Poster presented at the 2008Annual Meeting of APA. Washington, DC,USA, 2008 (Abstr. NR1-013).
5
TANGLED UP IN BLUE
Subclinical hypothyroidism can
masquerade as perinatal depression, with
symptoms of fatigue, depression, weight
gain, impaired memory and concentration,
and muscle pains. It is important to
diagnose subclinical hypothyroidism in
pregnant women, because it can progress
to clinical hypothyroidism and adverse
health consequences for both mother and
child. Subclinical hypothyroidism is
defined as thyroid stimulating hormone
(TSH) > 4.12 mIU/L in the presence of
normal T3/T4 level. Women with a
history of thyroidism or difficulty
conceiving should be screened for
thyroidism before conception.
Treatment of maternal depression during
pregnancy is problematic, due to concerns
about teratogenicity of antidepressants.
Mild to moderate depression can be
treated with psychotherapy, but severe
depression will require pharmacotherapy,
Dr. Musik said. The FDA has classified
the following antidepressants as having no
evidence of human risk: buspirone,
zolpidem, bupropion and clozapine. Risk
of teratogenicity cannot be ruled out for
tricyclic antidepressants and SSRIs
(except paroxetine).
The rule for treating depression during
pregnancy is to balance the risk of a
recurrent episode with the risk of
medications. Avoid polypharmacy and use
the lowest effective dose of medications
with the lowest teratogenic effects, she
suggested. The risk of teratogenicity is
highest during the first trimester of
pregnancy; patients on an antidepressant
should take 3 to 5 mg folic acid daily.
Studies are inconsistent regarding
antidepressants and breast feeding. Most
medical associations encourage breast-
feeding for the first 6 to 12 months of life,
yet all medications are transferred to
breast milk, albeit at low concentrations.
Dr. Musik concluded that the use of
pharmacotherapy in peripartum asks for a
case-by-case decision. The risk of
untreated maternal depression has to be
balanced with the risks of foetal exposure.
Depression, physical symptoms and
pain: a roadmap for psychiatrists
Physical comorbidities are the norm for
patients with depression and contribute to
the huge burden and costs of MDD, said
John F. Greden (Department of
Psychiatry, University of Michigan, Ann
Arbor, MI, USA). Treatment of comorbid
pain and physical symptoms is based on
an understanding of pain mechanisms and
should be guided by a ‘road map,’ he said
(Figure 4).
Shared symptoms of depression and
physical illness can include headache,
dizziness, joint pains, back pain, fatigue,
weakness, abdominal pains and muscle
and chest pains. Pain is typically the chief
presenting complaint of patients who
consult physicians. The more physical
symptoms and the more sites for pain a
patient has, the more likely the diagnosis
Figure 3 MATERNAL DEPRESSION/ANXIETY IN PREGNANCY INCREASES
THE RISK OF CHILD PROBLEMS AT AGE 7
Significant differences: * p < 0.05; ** p < 0.01
Source: O’Connor TG, et al. J Child Psychol Psychiatry 2003;44:1025–1036.
ADHD Conduct problems Depression/ Total
anxiety problem behaviours
*
*
*
**
2.8
2.5
2.2
1.9
1.6
1.3
1
Odds
rati
o
STEREOTYPED RESPONDINGIN MAJOR DEPRESSION
A small, preliminary study suggests that
patients with MDD exhibit more stereo-
typed repetitive behaviour and
substantially slower performance on
psychomotor tasks than healthy
volunteers. These phenomena, which
have also been identified in patients with
schizophrenia, appear to be correlated in
MDD. Didier Schrijvers (University of
Antwerp, Antwerp, Belgium) was lead
author of this poster presentation at
APA.
The study included 20 patients with
MDD and 20 healthy volunteers. Mean
age of patients was 38.8 years; eight
were males. All had a unipolar Major
Depression episode and Hamilton
Depression Rating Scores of 18 or
above. Patients with comorbid
psychiatric disorders were excluded.
Nineteen patients were taking
antidepressants and four of them were
treated with augmentation strategies
(low-dose neuroleptic or benzo-
diazepine). Healthy controls had a mean
age of 37.4 years; six were males.
Subjects were tested with the Stereotypy
Test Apparatus (STA) and asked to copy
single lines, simple figures and complex
figures as fast as possible. STA scores
(redundancy of two consecutive presses
of computer buttons) were significantly
higher in patients versus controls
(p < 0.05). Psychomotor responses
(reaction time and movement time) were
significantly slower in patients versus
controls for all three tasks: single-line
reaction time and single-line motor time
(p = 0.01 for both); simple-figure reac-
tion time and motor time (p = 0.01 for
both); complex-figure motor time
(p < 0.001).
These results suggest that patients with
MDD may have impaired executive
function. Further studies in medication-
free depressed subjects are needed to
confirm these findings.
Reference: Schrijvers D, et al. Poster presented at the2008 Annual Meeting of APA. Washington,DC, USA, 2008 (Abstr. NR1-044).
6
TANGLED UP IN BLUE
and depression, and these include trauma,
war, abuse and psychological stressors
such as death and divorce.
Treatment of comorbid pain and
depression should incorporate education
and non-pharmacologic therapies (such
as exercise, healthy sleep, good nutrition,
relaxation exercises and CBT), he said.
CBT and aerobic exercise are
particularly helpful for pain conditions,
he added.
There is good evidence to support the
role of medications that inhibit both
serotonin and norephinephrine, two
neurotransmitters involved in pain
processing. These include duloxetine,
venlafaxine, milnacipran and tricyclic
antidepressants [17–19]. Anticonvulsants
such as pregabalin and gabapentin may
also be helpful. Other medications used
to treat comorbid pain have less
evidence, but people use them anyway,
he said.
“If a medication is effective for
controlling depression and comorbid
pain, then continuing the patient on that
medication is crucial. This is the take
home message,” Prof. Greden stated.
of depression is [16]. Physical complaints
often obscure the diagnosis of MDD.
Most of the time, patients with physical
complaints are referred to a psychiatrist
after failed attempts at getting adequate
treatment for their physical problems.
Prof. Greden described three types of
neuroscience pain profiles: peripheral
(nociceptive) pain, neuropathic pain and
central (non-nociceptive) pain. Central
pain is the most important for
psychiatrists, he said. Central pain is
primarily due to a brain disturbance in
pain processing; examples are
fibromyalgia, irritable bowel syndrome,
tension headache and idiopathic low back
pain. Depression is often linked. Drugs
most effective in the treatment of central-
pain conditions include selective
norepinephrine reuptake inhibitors
(SNRIs), tricyclic antidepressants and
other medications that act on the central
nervous system.
Patients with depression appear to have
‘sensory amplification,’ that is, their brains
register what is being processed to a
greater extent than normal brains and “the
sensory volume is turned up,” Prof. Greden
said. Stressors can trigger comorbid pain
Figure 4 RECOMMENDED APPROACH (‘PRE-TRIP ROADMAP’)
Source: Greden JF. Data presented at the 2008 Annual Meeting of the American Psychiatric Association (APA).Washington, DC, USA, 2008.
PHQ-9 = Patient Health Questionnaire; OTC = over the counter; SNRI = selective norepinephrine reuptake
inhibitor; CBT = cognitive behavioural therapy; BZD = benzodiazepine
1. Screen (PHQ-9 and Pain Scale) and tell patient you will monitor
1
2
3
4
5
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7
8
9
10
11
12
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15
2. Identify and refer for treatment of ‘peripheral’ pain 3. Educate BEFORE treatment starts about length of
treatment, healthy sleep, avoidance of alcohol andOTC medications, exercise, etc.
4. Start CBT5. Start SNRIs or tricyclics at low dose
and increase slowly6. Begin exercise programme after
1 week; start low, go slow
7. If inadequate improvement, consider pregabalin orgabapentin after 6–8 weeks if necessary (higher dose at night)
8. If necessary after 6–8 weeks, add tramadol in low doses
9. Zolpidem or trazodone for sleep;avoid overuse or routine use of BZDs
10. Begin discontinuation of somemedications before adding more medicines
11. Long treatment periods are indicated (several months); be persistent
12. Long-term maintenance treatment(�2 years) once improved
13. Consider cytochrome P450 genetic polymorphism ifpatient ‘unable to tolerate’ multiple medications
14. Passionately promotecontinuation of CBT, exercise,
healthy sleep, nutrition 15. Continue maintenance treatment once the person is improved
TANGLED UP IN BLUE
7
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References
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2. Rush AJ, et al. N Engl J Med 2006;354:1231–1242.
3. Trivedi MH, et al. N Engl J Med 2006;354:1243–1252.
4. Szádóczky E, et al. J Affect Disord 2004;83:49–57.
5. Judd LL, et al. J Affect Disord 1998;50:97–108.
6. Kupfer DJ, et al. Arch Gen Psychiatry 1992;49:769–773.
7. Quitkin FM, et al. J Clin Psychiatry 2005;66:670–676.
8. Prudic J, et al. Psychiatry Res 1990;31:287–296.
9. Evans J, et al. BMJ 2001;323:257–260.
10. O’Hara MW, Swain AM. Int Rev Psychiatry1996;8:37–54.
11. Gale S, Harlow BL. J Psychosom Obstet Gynecol2003;24:257–258.
12. Cox JL, et al. Br J Psychiatry 1987;150:782–786.
13. Seng JS, et al. Obstet Gynecol 2001;97:17–22.
14. Kurki T, et al. Obstet Gynecol 2000;95:487–490.
15. O’Connor TG, et al. J Child Psychol Psychiatry2003;44:1025–1036.
16. Kroenke K, et al. Arch Fam Med 1994;3:774–779.
17. Goldenberg DL, et al. JAMA 2004;292:2388–2395,
2005;293:796–797.
18. Jenkins AL. JAMA 2005;293:796.
19. Anonymous. J Fam Pract 2005;54:105.
PREVALENCE OF SUBSTANCEDEPENDENCE, PSYCHIATRICDISORDERS AND CHRONICMEDICAL CONDITIONS IN ADETOXIFICATION/REHABILITATION SETTING
Substance-related disorders and
psychiatric/medical conditions have a
high rate of co-occurrence, according to
analysis of a large database of electronic
medical records of 5,588 patients
discharged from inpatient detoxification
and rehabilitation programs from
October 1, 2005, though September 30,
2006. These findings confirm the high
rates of comorbidity of substance
dependence and psychiatric and medical
illness reported in large epidemiologic
studies. Lead author of the study,
presented at a poster session, was
William Meehan (AdCare Hospital,
Boston, MA, USA).
Median age was 43 years; 70% were
male and 85% were Caucasian. The
most prevalent substance abuse
diagnoses were for: opioids (47%),
alcohol (44%), cocaine (25%) and
sedative-hypnotic-anxiolytics (21%).
Overall, 4,655 patients (83%) had at
least one Axis I psychiatric disorder
(mood, anxiety, or psychosis), and 3,552
patients (64%) had at least one chronic
medical condition (hypertension,
hepatitis C, chronic pulmonary
condition, hypercholesterolaemia,
diabetes, alcohol-related liver condition,
pancreatitis, HIV or AIDS). The
majority of patients (54%) had both
psychiatric and medical disorders; 29%
had psychiatric disorders only and 9%
had medical conditions only. Only 8%
had no co-occurring disorders.
These findings underscore the
importance of designing integrated
collaborative treatments for patients with
substance-related and comorbid
psychiatric/medical disorders. A
collaborative model includes a team of
experts in internal medicine, addiction
medicine, nurses, counsellors and mental
health professionals.
Reference:Meehan WJ, et al. Poster presented at the2008 Annual Meeting of APA. Washington,DC, USA, 2008 (Abstr. NR1-005).
Support for symptom improvement
with dual SSRI and SNRI inhibition
Symptoms of depression, as well as
somatic symptoms (i.e., disturbances in
sleep, and appetite and gastrointestinal
problems), were improved in patients with
MDD treated with duloxetine, according to
a post-hoc analysis of a double-blind,
parallel design trial reported by Susan G.
Kornstein (Virginia Commonwealth
University Mood Disorders Institute,
Richmond, VA, USA).
The analysis was designed to assess
differences in symptom improvement and
tolerability between males and females
with MDD treated with duloxetine.
Patients (n = 652) were randomised to
receive one of three duloxetine doses: 30
mg per day, 30 mg twice a day or 60 mg
per day. After the first week of treatment,
all patients received 60 mg per day for an
additional five weeks. The analysis
presented at APA pooled all dose groups
and stratified patients according to gender.
Symptoms were evaluated using the
Association for Methodology and
Documentation in Psychiatry adverse event
scale (AMDP) and the 17-item Hamilton
Depression Rating Scale (HAMD-17).
Baseline HAMD-17 total scores were
almost similar between males (21.1) and
females (21.7). At baseline, no significant
differences were observed between genders
for HAMD-17 factors, except more
psychomotor retardation was seen in
females. AMDP symptom category scales
were also similar at baseline between
genders, except more appetite disturbance
was seen in females. Mild to moderate
sleep disturbances were reported in both
genders at baseline, according to mean
AMDP scores; other symptom categories
were mild at baseline.
At six weeks, duloxetine reduced HAMD-
17 scores by about 11 points in both
genders and no statistically significant
differences according to gender were found
for total HAMD-17 score, the Maier
subscale or other HAMD-17 factors.
From baseline to end point, duloxetine
improved sleep disturbances, appetite
disturbances and gastrointestinal
disturbances to a similar extent in both
genders. Other somatic disturbances
(headache, heaviness in legs, hot flashes,
chills and conversion symptoms) were
similarly improved from baseline in males
and females. A significant difference from
baseline to end point was seen for
decreased appetite for males (0.28 vs. 0.17
point improvement for males vs. females,
p = 0.05). Micturition difficulty worsened
in males and improved in females from
baseline to end point (p < 0.001) and
backache improved in males versus
females (p = 0.004).