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Adding to all that ails people managing their multiple sclerosis is depression ― for which MS sufferers have a lifetime risk as high as 50 percent.

Yet despite its prevalence, the cause of this depression is not understood. It's not related to how severe one's MS is, and it can occur at any stage of the disease. That suggests it is not simply a psychological reaction that comes from dealing with the burden of a serious neurologic disorder.

Now, in the first such study in living humans, researchers at UCLA suggest a cause, and it's not psychological, but physical: atrophy of a specific region of the hippocampus, a critical part of the brain involved in mood and memory, among other functions.

Reporting in the early online edition of the journal Biological Psychiatry, senior study author Dr. Nancy Sicotte, a UCLA associate professor of neurology, Stefan Gold, lead author and a postdoctoral fellow in the UCLA Multiple Sclerosis Program, and colleagues used high-resolution magnetic resonance imaging to identify three key sub-regions of the hippocampus that were found to be smaller in people with MS when compared with the brains of healthy individuals.

The researchers also found a relationship between this atrophy and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, a complex set of interactions among three glands. The HPA axis is part of the neuroendocrine system that controls reactions to stress and regulates many physiological processes. It's thought that this dysregulation may play a role in the atrophy of the hippocampus and the development of depression.

"Depression is one of the most common symptoms in patients with multiple sclerosis," Gold said. "It impacts cognitive function, quality of life, work performance and treatment compliance. Worst of all, it's also one of the strongest predictors of suicide."

The researchers examined three sub-regions of the hippocampus region ― CA1, CA3 and the dentate gyrus area of the hippocampal region called CA23DG (CA stands for cornu ammonis). They imaged 29 patients with relapsing remitting multiple sclerosis and compared them with 20 healthy control subjects who did not have MS. They also measured participants' cortisol level three times a day; cortisol is a major stress hormone produced by the HPA axis that affects many tissues in the body, including the brain.

In addition to the difference between MS patients and healthy controls, the researchers found that the multiple sclerosis patients diagnosed with depression showed a smaller CA23DG sub-region of the hippocampus, along with excessive release of cortisol from the HPA axis.

"Interestingly, this idea of a link between excessive activity of the HPA axis and reduced brain volume in the hippocampus hasn't received a lot of attention, despite the fact that the most consistently reproduced findings in psychiatric patients with depression (but without MS) include hyperactivity of the HPA axis and smaller volumes of the hippocampus," Sicotte said.

"So the next step is to compare MS patients with depression to psychiatric patients with depression to see how the disease progresses in each," she said.

Other authors of the study included Kyle C. Kern, Mary-Frances O'Connor, Michael J. Montag, Aileen Kim, Ye S. Yoo and Barbara S. Giesser, all of UCLA.

Funding was provided by the National Multiple Sclerosis Society, the National Institutes of Health, the UCLA Cousins Center for Psychoneuroimmunology, and Claire and William Vaughn.

Source: Eureka Alert (02/07/10)

Treatment with escitalopram appears to be an effective therapy for patients who have multiple sclerosis (MS) and comorbid major depressive disorder (MDD), researchers suggested at the 2010 Annual Meeting of the American Psychiatric Association (APA).

"Despite studies highlighting the comorbidity of multiple sclerosis and depression, it continues to be underdetected, underdiagnosed, and undertreated," stated Suzanne Hardeman, MSN, PMHNP-BC, University of South Carolina School of Medicine, Columbia, South Carolina, speaking at her poster presentation here on May 24.

"There has not been much evidence that antidepressants are useful in treating depression in patients with multiple sclerosis. Results from this small sampled study demonstrate that escitalopram may be a viable treatment option for this population," Hardeman explained.

Hardeman and her colleagues considered escitalopram for these patients because of the low likelihood of drug-drug interactions. The researchers, working with consent of the Institution Review Board, recruited 14 adult patients (12 women) with both MS and MDD.

Participants were monitored for efficacy using the Hamilton Depression Rating 17-Item Scale (HAM-D17), Clinical Global Impression of Severity (CGI-S) and Improvement (CGI-I), Beck Anxiety and Depression Inventory (BAI;BDI), Expanded Disability Status Scale (EDSS), and McGill Quality of Life Scale (McQLS).

At baseline, patients' HAM-D17 scores were 14 or greater with no history of psychotic disorder or bipolar depression. Patients had no current risk of suicide or history of substance abuse in the previous 6 months. Patients also had no history of unstable medical disorders and were not pregnant or planning pregnancy.

Patients were administered a 10 to 20 mg flexible dose of escitalopram at bedtime in an open-label manner for 8 weeks. Patient visits occurred at baseline and at weeks 1, 2, 4, 6, and 8.

Nine of the 14 patients completed the study. Four patients discontinued because of nausea or diarrhoea that did not resolve within 2 weeks.

Patients responding to the treatment showed significant improvement in depressive symptoms on the HAM-D17, with scores declining from a mean of about 22 at baseline to 10 after 8 weeks (P = .000; Cognitions Questionnaire). On the BDI, mean scores declined from about 27 to about 12 after 8 weeks (P = .001). Scores from the CGI-S also were reduced greatly in patients (P = .003), and scores from the CGI-I were also significant (P = .002). McQLS scores significantly improved (P = .022), as did scaled quality of life (P = .003).

There were no significant changes in anxiety symptoms.

Funding for this study was provided by Forest Laboratories, Inc.

[Presentation title: An Open-Label, 8-Week, Flexible Dose Trial of Escitalopram (Lexapro) in Comorbid Major Depression With Multiple Sclerosis. Abstract NR3-49]

Source: Doctor's Guide Channels (c) 1995-2010 Doctor's Guide Publishing Limited (31/05/10)

Background: Multiple sclerosis (MS) is a chronic disease with unclear etiology, unpredictable clinical course, and no cure. Patients' ability to cope with MS moderates the adaptation to the disease.

Objectives: To compare coping in patients recently diagnosed with MS and healthy controls and to study the association between depressive symptoms and patients' coping styles.

Methods: A sample of 86 recently diagnosed patients with definite or probable MS and 93 healthy population controls completed questionnaires assessing coping styles and depressive symptoms.

Results: Compared with healthy controls, patients with MS used significantly less the problem focused strategies including planning, restraint coping, and seeking social support for instrumental reasons, and they used less the emotion-focused strategies seeking social support for emotional reasons, focusing on and venting of emotions, and positive reinterpretation and growth. The mean Beck Depressive symptoms Inventory scores were 10.8 and 4.7 in patients and controls, respectively. In stress situations connected to MS, depressive symptoms in these patients were related to the problem-focused strategies of restraint coping and planning, the emotion-focused strategy of focusing on and venting of emotions, and the avoidance strategies of behavioural- and mental disengagements, and denial.

Lode K, Bru E, Klevan G, Myhr K, Nyland H, Larsen J.
The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.

Source: Pubmed PMID: 19299438 (02/04/09)

A mental health nurse-led multidisciplinary team has set up a project to meet the emotional and mental health needs of patients who have multiple sclerosis

This project provides a unique service that aims to enhance the mental and emotional well-being of people who have multiple sclerosis (MS).

In collaboration with King's College Hospital MS service, South London and Maudsley NHS Foundation Trust, the Institute of Psychiatry and the MS Society, this service provides assessment and treatment using medication, cognitive behavioural therapy (CBT) and psychosocial interventions.

Patients also receive education that helps to empower them to take control over their lives.

Background

Research suggests that mental health issues are undertreated in people with MS because of overlapping physical symptoms and that there is a high incidence of mental health problems, which is exacerbated by the uncertainty of the condition.

However, the evidence also suggests that mental health problems in MS are treatable, with patients responding well to antidepressants/other neuroleptics and/or CBT and psychosocial interventions.

In light of this, we felt it was necessary to provide a service to meet this need, and evaluate it after three years to ascertain whether patients do benefit from mental health nurses' input.

As research in this area is limited, part of my work is to develop a research agenda, with a view to raising the profile of the issue within mental health and MS services.

Aims

People with MS can experience a variety of mental health problems, with up to 50% of them experiencing depression during their lifetime.

There are also high rates of anxiety and other mental health problems such as psychosis, mania, pathological laughter and crying.

Many people with MS have not received adequate care for mental health problems because of overlapping physical symptoms and difficulties in accessing services.

Our project aims to reduce psychological distress by offering patients assessment, treatment and follow-up. We also educate MS nurses so they feel more empowered to manage mental health issues.

The project

The project began in March 2006 and was completed at the end of 2008. It has received over 120 referrals, indicating the service is desperately needed in the area.

All patients complete initial assessment scales when they start treatment and rating scales at six months.

This means we can quantify whether the service is having an impact and what patients respond well to. This will hopefully provide opportunities to make important changes and enable us to be more responsive to patient needs.

Benefits for patients

Patients are provided with an initial assessment within 4–8 weeks of the referral. If a patient is in crisis, I assess them within one week of referral. This is quicker than assessment by local community mental health teams and, because the service is more specific to MS, patients feel I have an understanding of their experiences.

Care is tailored to individual patients' needs. A range of services is offered including: home visits for mental health assessment and treatment for people who are unable to attend clinic; an outpatient clinic co-managed with a neuropsychiatrist; and a CBT clinic.

Regular teaching sessions are provided to MS nurse specialists in the south east of England.

These nurse specialists have been asked to complete questionnaires at the beginning and end of the module to evaluate whether the teaching has changed their attitudes to mental health issues and whether they feel more confident in working with people with mental health difficulties.

Plans

I have developed guidelines on depression and anxiety for south-east London, and nurses in this area are using these to change their practice.

This has been done in conjunction with their mental health training, and has led to increased confidence and positive attitudes to mental health issues. The training will also be promoted nationally with the MS Society and this will lead to further dissemination of practice.

We plan to publish the results of the evaluation this year. We hope that publication of its benefits will lead to the project being established on a more permanent basis.

Further studies could establish whether this model could be used in other parts of the UK.

Find out more

If you would like to have additional information on this project, contact Sally.Jones@iop.kcl.ac.uk 

Principal Author
Sally Askey-Jones, BN, RN,is mental health nurse specialist in multiple sclerosis, Institute of Psychiatry, King's College London.

Other authors
Richard Gray, PhD, RN,is professor of mental health, University of East Anglia;Pauline Shaw, BSc, RN,is multiple sclerosis nurse specialist, Southwark PCT;Trudie Chalder, PhD, MSc, SRN, RN,is professor of cognitive behaviour psychotherapy;Anthony David, FRCP, FRCPsych, MSc, MD,is professor of neuropsychiatry;Kevin Gournay, CBE, PhD, FRCPsych, CPsychol, RN,is professor emeritus, all at the Institute of Psychiatry, King's College London;
Eli Silber, MD,is neurologist, King's College Hospital, London.

Source: Nursing Times Copyright Emap 2009 (27/02/09)

A poster presentation here at the 21st annual meeting of the Consortium of Multiple Sclerosis Centers reported the results of a University of Washington study involving 96 MS patients enrolled in a trial investigating the value of exercise as a treatment for depression. Inclusion criteria for the study were a diagnosis of MDD and/or dysthymia based on the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th ed (DSM-IV).

Investigators became aware that some subjects in the primary study were being treated with antidepressants and some were not. This offshoot study investigated the proportion of people with MS and MDD and/or dysthymia taking antidepressants and assessed behavioural variables associated with antidepressant use.

Celeste Hunter, from the Multiple Sclerosis Rehabilitation Research and Training Center, University of Washington, in Seattle, and an author of the poster, explained to Medscape that 1 of her colleagues noticed that although all patients in the study suffered from clinical depression, there appeared to be no discernible difference in terms of affect between patients who took antidepressants and those who did not.

"Depression is harder to pin down in patients with MS," Ms. Hunter said. "I see the MS patients as being more emotionally reactive in a given situation than if they didn't have MS. The unpredictability factor is so important — they don't know, if they have a really bad exacerbation, whether they'll get the same function back as before."

Almost half of the patients in this group (44%) were not taking antidepressants. Those on treatment were receiving various agents.

Patient-Reported Antidepressant Use Treatment (%)
None 44.0
Fluoxetine 5.0
Citalopram 6.0
Bupropion 14.0
Venlafaxine 11.0
Sertraline 6.0
Other 14.0

Subjects were 85% female, 42.7% employed, and 91.7% white. Their Expanded Disability Status Scale scores were 4 or less in 52.1%, 4.5 to 6.0 in 45.8%, and 6.5 or more in 2.1%.

The researchers compared patients taking antidepressants (n = 54) with those not taking antidepressants (n = 42) — using the Hamilton Rating Scale for Depression, the Hopkins Symptom Checklist, the Modified Fatigue Impact Scale, item 8 of the Brief Pain Inventory, and the Expanded Disability Status Scale — and found no significant difference between the outcome scores of the 2 groups on any of these scales.

The authors concluded, "Because the study did not include people who were on antidepressants and not suffering from current MDD, our results may have been biased against finding improved outcomes associated with antidepressant use." Further studies in this area of MS treatment are needed, they added.

Kurt Johnson, PhD, a professor in the department of rehabilitation medicine at the University of Washington, but not an author of this study, commented to Medscape that there has not been much evidence in the MS literature that antidepressants are useful in treating depression. "We found the same thing in another study with a larger group of people. A lot of people in our sample were taking antidepressants when they weren't depressed, and a lot were depressed but were not taking antidepressants."

Higher Incidence of Depression

Medscape also talked with Stephen Kirzinger, MD, from the Multiple Sclerosis Care Center Program, Department of Neurology, University of Louisville, in Kentucky, about this poster. "Certainly we feel that patients who have a chronic disease can develop a reactive depression, but in the MS population the incidence is much greater than what you would expect, comparing it with other chronic-disease processes," said Dr. Kirzinger. "So we feel it is a manifestation of the disease that our patients, because of their MS activity, actually have a chemical change that leads to depression."

The antidepressants listed by patients participating in this study are serotonin reuptake inhibitors. Dr. Kirzinger noted that some preliminary data have indicated that serotonin itself has a beneficial effect on the immune system. "I think the present study flies in the face of most of our clinical experience [in which] the patients who have depression seem to respond to antidepressants. The fact that they did not see a dramatic difference between those on antidepressants and those not taking antidepressants is a little surprising."

This study was funded by the National Rehabilitation Research and Training Center on Multiple Sclerosis from the US Department of Education, National Institute on Disability and Rehabilitation Research.

Consortium of Multiple Sclerosis Centers 21st annual meeting: Abstract S110. (08/06/07)

Source: MedScape Today Copyright © 1994-2007 by Medscape (06/06/07)

“I had seen him within the last week,” said Dr. Mary Hughes, a neurologist and director of the Augusta Multiple Sclerosis Center. “My nurse had seen him, and we had picked up on nothing. We were all just dumbfounded.”

“When someone is diagnosed, it is a major life change,” said Dr. Sarah Shelton, a postdoctoral psychology fellow in multiple sclerosis at the center. “Patients have to learn a lot of information about their disease and go through the process of acceptance that every facet of their life could be altered significantly. It’s a huge transition.”

Possible lifestyle changes include loss or change in job status, which can lead to a drastic financial adjustment and a loss of identity. Personal relationships are affected as the patient and family members adjust to the disease.

The suicide rate in patients with multiple sclerosis is seven times that of any other population. Fifty percent of patients are diagnosed with depression. At the time of her patient’s suicide attempt, reports of increasingly high rates of depression, mood disorders and suicidal ideation in the MS population were being published, and Dr. Hughes went looking for solutions.

She found Dr. Lara Stepleman, an assistant professor of psychiatry in the Department of Psychiatry and Health Behaviour, who had a strong interest in chronic medical illness care and was directing a program focused on the mental health needs of HIV patients. The two assessed needs of MS patients to determine how a psychology consult service could best help them, co-founding MS Psychology Consultation Services in 2003.

Key to the program is the on-site availability of psychology services. Traditional mental health settings are under-utilised by MS patients for several reasons.

Mobility plays an important role in multiple sclerosis. Multiple appointments in numerous locations can strain transportation budgets and energy levels, lessening the chance of patients receiving the service they need as symptoms of their disease fluctuate.

The potential stigma of seeing a mental health provider decreases when psychological services are accessible during regular appointments. “Sometimes people don’t understand the many stressors that come along naturally as part of having a chronic illness, or that some of the symptoms of MS can cause psychiatric issues,” explains Dr. Stepleman. “Having it integrated as part of normal medical appointments makes it much more acceptable.”

A patient’s emotional state has a vital connection to his physical health when treating a disease like multiple sclerosis that requires compliance and adherence to a strict medical regimen. “If they are so depressed that they are not motivated or invested enough to follow that regimen, their health is going to be directly affected,” said Dr. Shelton.

On-site psychological services also allow inclusion of people who typically bring patients to their appointments – spouses, parents, children and other caregivers who are themselves at high risk for mental-health problems.

Integrated medical and psychological services benefit providers as well. “Dr. Hughes helps me understand how the disease is medically affecting the patient’s emotions, cognitions or thoughts,” said Dr. Shelton, “and I help her understand some of the personality, situational and psychological factors that might be presenting. If you have separate services, the providers don’t get that complete picture, they only see half, which is a false dichotomy because the medical and psychological really work together.”

Dr. Hughes concurs: “By keeping a psychologist involved when physicians are doing screening evaluations, it increases our effectiveness because of our different training, our different skills.”

“This is really unique. In 95 percent of clinical services, you won’t find this level of integration,” said Dr. Stepleman. “Some programs have psychologists, but they’re not actively involved at the same time the medical treatments are being done.”

Beginning with one clinic a week in 2004, Dr. Hughes and Dr. Stepleman committed themselves to the psychology consultation service without funding. “It was one of those ‘If you build it, they will come’ things,” said Dr. Hughes. The project received Quality of Life grants from the Multiple Sclerosis Foundation and the Christopher Reeve Foundation and a research grant from MCG’s Combined Intramural Grants Program in 2005, allowing expansion.

The clinic’s escalating reputation for a full range of services with a high level of quality and responsiveness has fueled tremendous growth. “Patients come with an awareness of what we’re able to do,” said Dr. Hughes. The center now follows over 1,500 people with multiple sclerosis, with a psychology presence at five weekly clinics. Dr. Shelton came on board in August 2005 to manage day-to-day issues, treat patients and assist in training residents. Monthly interdisciplinary team meetings address clinical, educational and research aspects of the collaboration, and a monthly support group has begun, drawing patients and caregivers who may drive as long as two hours to attend.

“The question hasn’t been, ‘Do we recognise this need?’” said Dr. Hughes. “It’s been, ‘How do we meet this need?’ The challenge is with mental health coverage. It’s the classic issue of limited resources in health care.”

“That’s why getting these grants is so important,” added Dr. Shelton. “We’re able to provide psychological care at little or no charge without billing the insurance company. That allows us to provide quality comprehensive care in a way and a place the patient can receive it.”

Since January, funding has provided for 300 depression screenings, 146 psychological consults, 108 psychotherapy/counseling sessions and 34 specialised psychological and cognitive testings. In addition to the consultation services, a two-year study based on a five-session problem-solving model for MS patients also diagnosed with clinical depression began in February to learn how to better meet patients’ needs.

Other treatment providers are taking notice and visiting the Augusta Multiple Sclerosis Center. “People are fascinated with how we are trying to address this need,” said Dr. Hughes. “They have the same need in their clinic setting, but they’re all struggling with how to meet it. The leap from identifying the need to what’s the best way to provide those services is the gap that we’re trying to learn to fill.”

As leaders in developing the innovative programming model, Drs. Hughes, Shelton and Stepleman are presented last week at the 22nd European Committee on the Treatment and Research of Multiple Sclerosis in Madrid, Spain, on two topics: Predicting depression and anxiety in a multiple sclerosis clinic population: the contributions of illness severity, illness management and perceived cognitive impairment; and Overcoming mental health care barriers for individuals with multiple sclerosis: innovations in psychological consultation.

“We want to be able to spread this information so that other clinics learn from our experience,” said Dr. Hughes. “Unfortunately, we started with a crisis and worked backwards. Fortunately, the young man who had attempted suicide is now doing well. We’d have much rather been preventive. Part of what we were interested in when we developed this model was to make it applicable to various settings, and so while we were concentrating on multiple sclerosis, in the future, we’d be interested in implementing it in Parkinson’s disease or dementia or other chronic care clinics. You see enormous need and we really want to be able to pass on this information to people who can benefit from the work we’re doing here at MCG.”

Source: MCG Science/Medical News © Medical College of Georgia All rights reserved (05/10/06)

Her data contradicted the widespread belief that depression is the most common neuropsychiatric symptom in MS.

In her study, sleep disorders occurred in 82% of the patients, significant obsessive-compulsive symptoms in 75%, and some form of eating disorder in 67%. Depression was seen in 61%, which is higher than the estimated 40%.

Source: About ©2006 About, Inc. (19/07/06)