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

6

7

8

9

10

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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.

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9. Evans J, et al. BMJ 2001;323:257–260.

10. O’Hara MW, Swain AM. Int Rev Psychiatry1996;8:37–54.

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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.

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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).