Wednesday, 3 October 2012

Research: depression and relapses

Moore et al. Multiple sclerosis relapses and depression. J Psychosom Res. 2012;73:272-6

OBJECTIVE: The expression of clinically significant depression symptoms during and post MS relapse was investigated. The point prevalence of possible depression during a confirmed MS relapse and at 2 and 6 months post-relapse was examined and the influence of disability on the time course of depression symptoms post-relapse determined.
METHODS: 132 sequential MSers were recruited from an open access relapse clinic. Clinical data including disability (Expanded Disability Status Scale: EDSS) and depression symptoms (Hospital Anxiety and Depression Scale depression subscale: HADS-D) were recorded at 0, 2 and 6 months post-relapse.

RESULTS: Prevalence of possible depression (HADS-D score of≥8) was 44.5% during relapse, reducing to 29.2% at 2 months and 34.4% at 6 months post-relapse. HADS-D scores were significantly lower at follow-up than during relapse. Possible depression at relapse was significantly related to a higher likelihood of possible depression at 2 month follow-up (OR 12.12) and improvement in EDSS was related to a lower likelihood (OR 0.51). EDSS at relapse (OR 1.47) and possible depression at relapse (OR 11.87) were significantly associated with possible depression 6 months post-relapse.

CONCLUSIONS: High rates of possible depression were observed during relapse. Although depression scores reduced significantly post-relapse, rates of possible depression at follow-ups remained high. The results suggest that although improvements in disability may influence depression symptoms over the short-term, once depression symptoms are elevated at relapse then depression symptoms become persistent.
 

"Not surprising that there is a link between clinical disease activity and depression. What is not clear is the mechanism. Does it relate to lesions in parts of the brain associated with cognitive problems? Do the inflammatory mediators released during a relapse cause depression? Is it a reactive depression in response to  having a relapse? Clinical attacks are a reminder that you have a disease and bring back anxiety about the future, both near and far. Will I recover from this attack? Will I need a walking aid? What will happen to my job? Will I be able to complete University? How will I pay for my daughter's wedding? What is happening to me? Etc.? Etc.? This is another good reason to prevent relapses; why should MSers have relapses if we can prevent them and possibly the associated depression that goes with  them? Any thoughts on this?"

Other posts of interest in relation to depression:

01 Sep 2012
Very interesting - I have suffered from depression for a very long time and always have felt that it must be 'organic' i.e. related to some brain changes. It would be interesting to know if depression in female MSers is among the ...
12 Aug 2012
INTRODUCTION: Studies have found that people with Multiple Sclerosis experience relatively high rates of anxiety and depression. Although methodologically robust, many of these studies had access to only modest sample ...
21 Jul 2012
Methods: In this cross-sectional study, the authors evaluated 49 children with demyelinating disorders (multiple sclerosis and acute disseminated encephalomyelitis) and 92 healthy controls for depression and/or fatigue using ...
27 Jun 2012
The Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety (cut-point >7) and depression (>7) and the Fatigue Severity Scale (FSS) to measure fatigue (≥5). Results: At cohort entry, prevalence of ...

22 Nov 2011
Results: MS'ers with depression had a 10 point lower MPR (P < 0.01) and were less likely to achieve a MPR of at least 80% (odds ratio (OR) = 0.55; 95% confidence interval (CI) 0.42-0.74) than those without depression.
19 Aug 2011
Fatigue and its relationships with cognitive functioning and depression in paediatric multiple sclerosis. Mult Scler. 2011 Aug 15. Background: There is limited information on fatigue and its clinical and psychosocial correlates in ...
12 May 2011
There is a high prevalence of depression in PwMS and other neurological disorders. A systematic review and meta-analysis of 20 randomised controlled trials showed that anti-depressant treatment was associated with a ...
18 Jun 2012
69 couples completed measures of mindfulness, acceptance and adjustment (depression, anxiety, life satisfaction, positive affect and relationship satisfaction). Results: As hypothesised there were actor effects of mindfulness ...

17 Dec 2011
BACKGROUND: MS'ers are at high risk of depression. This pilot study of computerised cognitive behavioural therapy (CCBT) for the treatment of depression in MS'ers was to test the feasibility of undertaking a full trial.

20 Jan 2011
Cognitive symptoms and depression are common in people with MS. A recent study shows an association between these symptoms; subjects with cognitive impairment were more likely to report low mood. Barwick FH, Arnett ...


17 comments:

  1. I saw this interesting article today that argues that depression triggers the immune system and is biologically adaptive. In some cases, doctors are using monoclonal antibodies to shut off that connection:

    http://www.theatlantic.com/health/archive/2012/10/the-evolutionary-advantage-of-depression/263124/#

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  2. This is another good reason to prevent relapses; why should MSers have relapses if we can prevent them and possibly the associated depression that goes with them? Any thoughts on this?

    I think you're preaching to the converted on that one! It is absurd that effective medication exists now to substantially prevent relapses and thus hugely reduce the significance of MS as a condition and yet (a) few people take them up, perhaps only 25% of MSers and (b) many neuros are conservative to the point of farce about prescribing them.

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  3. Will I recover from this attack? Will I need a walking aid? What will happen to my job? Will I be able to complete University? How will I pay for my daughter's wedding? What is happening to me? Etc.? Etc.?

    This anxiety related depression is where I think the MS societies and this blog have a responsibility to present a more balanced view of the condition than they currently do. By all means, present the facts and the worst case to ensure people make informed decisions about DMTs (which I think anyone who is not on is mad, personally). However, MS is a bad enough condition without the need to try and almost make is seem even worse by presenting all the worst case examples. There's a great site (this is not a plug!) called ActiveMsers which has a series of stories of people with MS who are doing really well - one guy, for example, who has just completed his first Iron Man almost 30 years post-diagnosis and one who has just climbed to Everest base camp with his family 15 years post. There are many others whose MS is so insignificant they do these things but don't consider them particular achievements and so don't make a big deal of them. That is why the post the other day about the politicians with MS etc are much more important than perhaps is realised. That is the kind of thing that can help drag MSers out of depression and realise they can have a normal life still. Then, moving from the anecdotes to the stats, we have the natural history studies on walking aids etc which were referenced on comments the other day on here which show it is more like 25-30 years before most MSers would statistically need one than the more commonly propogated 15 years. None of this is to say this condition isn't terrible for many, many people - and unwanted by everyone who has it - but the picture of life with MS frequently isn't as bleak as it sometimes looks.

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  4. In keeping with the above - see this from today:

    http://www.calgaryherald.com/sports/hockey/vancouver-canucks/Courtney+Taylor+battles+back+from+give/7334622/story.html

    This guy is on Tysabri (so one would assume fairly highly active disease) and is about to step out and play professional US football. He's only 4 years post-diagnosis but nevertheless this is the kind of thing that I think is really good to hear. Perhaps this blog isn't the place for it as it is obviously a research focused one (and a brilliant one at that) - maybe there's a place for a new blog/site focusing on the positive outcomes of those with MS?

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  5. Sorry - last one I promise (at least I'm not linking to dozens of CCSVI articles!) but here's another great, current example of someone living a full and highly productive life despite MS.

    http://www.theleafchronicle.com/article/20120930/NEWS01/309300017/Mayor-Multiple-Sclerosis-does-not-define-me?nclick_check=1

    It can be done. Many people do it. Get on a good DMT, get a great neuro, eat well, exercise and enjoy life to the maximum your current circumstances allow. I'm not meaning to be preaching - and those words are directed at myself as much as others - but MS really doesn't necessarily mean a life of disability and misery. One final link to an article I thought really balanced on this point is below:

    http://www.wishboneclover.com/2010/07/i-have-ms-and-its-really-not-a-big-deal.html

    (I'm sorry if we aren't supposed to post-links on here - I hope these aren't controversial ones though; I have no agenda save for hoping to provide a little hope to possibly depressed MSers asking themselves the questions posed by Prof G in his comment).

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  6. I'm all for keeping a positive mental attitude, but please keep it balanced. The life and care of someone with Primary Progressive MS is vastly different to that of someone with RRMS. Get on a good DMT isn't an option, I'm not sure everyone, even with MS is that clued up to the the other's plight. Yes keep the 'Good News' stories coming, but also appreciate the days of, C'mon pull yourself together, thankfully have long gone and people realise depression is a much more complex state.

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  7. Re: “MS really doesn't necessarily mean a life of disability and misery.”

    To whomever posted such a disparaging comment (and I know that you post here very frequently because I can detect the smugness of tone in your numerous anecdotes), shame on you for being so ignorant.

    I have PPMS , am physically disabled and not on any of the venerated DMTs you constantly pontificate over. However, even though I may have marked disabilities, I have achieved so much in spite of them. I am a trainee journalist for a major publication. I am an amateur bodybuilder. I am so many things that cannot be reduced to disabilities caused by MS leading to a life of misery.

    I’m glad that being on DMTs has given you the confidence to sleep easy at night and belittle others that choose not to embrace them. My particular course of MS has no treatment options but, to be honest, I wouldn’t take them even if they were offered to me. I believe that a healthy lifestyle and positive mindset beats all the toxic medication on offer to MSers.

    People that eschew DMTs are not “mad” as you so elegantly describe, they have just made a conscious choice, as have you for choosing to adopt them. For you to denigrate those that perhaps don’t believe in DMTs is callous and uncalled for. I have encountered more seasoned neurologists that don’t yet believe that early and aggressive treatments for MS is suitable than those that do. In fact, an esteemed neurologist at my hospital recently informed me that he doesn’t believe that they really do anything of significance.

    If you are on DMTs then good for you. If you’re not on DMTs through choice or because of circumstances, then good for you too. It’s not then of the world. But please stop accentuating your own insecurities into statements about how to not embrace medication is somehow an act of absolute stupidity. Your choices are half-chance, as is everyone else’s.

    Post all you want about MSers with no apparent disabilities scaling mountains or managing to make lots of money, but just because one is in a wheelchair doesn’t mean they have a miserable life and not capable of achieving comparable feats. If you actually saw me you may feel sorry for my situation and pray your disease doesn’t advance like mine has, but that will only be because you lack emotional intelligence. I don’t blame you for remaining anonymous all the time.

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  8. I think you entirely miss the point of my post above and I'm sorry to the extent it wasn't clear.

    Firstly, whilst I think the evidence for RRMSer and DMTs is overwhelming, it was not meant to disparage those not on DMTs and I accept my choice of language was loose in that respect (and I was specifically referring to RRMSers as I'm only too aware of the lack of DMT for PPMSers).

    Secondly, it was also not to focus on the achievements of those without apparent disabilities - it was to focus on the achievements of all with MS. I was not insinuating that disability = misery; quite the contrary. I was trying to suggest that MS doesn't necessarily equal misery. My ambigous statement should have said "doesn't mean a life of disability OR misery". Malu Dreyer is wheelchair bound and has achieved an incredible amount and I posted about how we need more examples like her on here. You too have achieved an awful lot and would be another great example of how MS does not need to lead to a life without purpose, as many people fear. The point of the post above was to stress that MS does not automatically equate to disability (because, being frank, people have a huge fear of that when newly diagnosed) and also that disability, in whatever form through MS, doesn't have to be the end of the world. You are actually proof positive of the very point I was trying to make. MS is a serious condition, requiring a lifetime commitment to its management - but it doesn't mean that MSers can't live a full, productive and happy life; whether disabled by their condition or not. There is a lack of that message online.

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  9. It seems that PwMS are entirely capable of constructing and presenting their points of view! Long may it continue - well at least until MS is dispensed with...

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  10. Is there a possibility Team G to have the statistics on how people who had been trialled for Alemtuzumab or BG12 have been doing disability-wise since first starting the treatment? I reckon it must have been ca. five years so some data should be available on those new DMTs. It would either reinforce or contradict the view that the new drugs are more effective. I believe that there are people like me who get depressed unless they are presented with bullet-proof facts.

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    Replies
    1. Just search on here - all the trial results are available. Alemtuzumab for 5 years and BG-12 for 2. Both show real promise - Alemtuzumab is the game-changer though in my opinion with BG12 still excellent and exciting but more suited to those managing mild disease.

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  11. MONDAY, 26 MARCH 2012

    Alemtuzumab 5 year follow up
    Coles AJ, et al. Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 Clinical Trial.Neurology. 2012 Mar 21. [Epub ahead of print]

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  12. Susan said...
    Studies have suggested that clinical depression, the severest form of depression, is more frequent among people with MS than it is in the general population or in persons with other chronic, disabling conditions. Depression does not indicate weak character and it should not be considered something shameful that needs to be hidden.

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  13. How about this for an achiever with MS:

    Scott Johnson, CEO of the Myelin Repair Foundation has had MS since 1976. He wears a leg brace and has no use of his right arm. He has taken his impressive business credentials to form the MRF which is dedicated to (a) accelerating the pace of drug development for MS (and more generally) through innovative working and (b) as the name suggests develop a myelin repair therapy which they aim to be available to patients by 2019. They are currently running ahead of schedule with some phase 1 trials already underway. They raised over $45m to get the project off the ground. Inspirational example of someone with MS not just achieving but working to achieve something for all with MS. They also sound very confident of successfully having myelin repair therapies available in this decade which would potentially transform MS treatment - combining immunomodulation with myelin protection/repair would really reduce the impact of MS beyond recognition.

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  14. To start with thank you for bringing to everyone’s attention the above paper. We all know that depression is a common feature in multiple sclerosis, but this is the first paper to look at it in terms of its prevalence in the various stages of relapse,recovery and remission in RRMS.

    Firstly I think it’s important to distinguish the difference between depression as an illness, and feelings of demoralization, discouragement, difficulty coping and worry that occur in all chronic illnesses, MS included.

    What I want to discuss is the relationship between recent research in depression and the immune system and MS, as I think this is highly relevant to this paper.

    Over the past 10-15 years all so a great deal of research has been undertaken looking at disturbances in the immune system and depression. I’ll put some links at the bottom of this reply. In summary, the research has focused at how pro inflammatory cytokines influence the metabolism of tryptophan. Tryptophan is a dietary amino acid, which undergoes two distinct metabolic pathways in the body. The first one which accounts for around 15% of all tryptophan metabolism is the one in which most people are familiar, namely the production of serotonin and subsequently melatonin in the brain. Serotonin has a key role in regulation of mood,anxiety, impulsivity and suicidality (amongst many others). Melatonin which is synthesized from serotonin in the brain has the key role in the maintenance of the sleep- wake cycle, and circadian rhythms.

    The second metabolic pathway which accounts for 85% of tryptophan metabolism occurs in the liver, the kynurenine pathway. The kynurenine pathway has a number of interesting metabolites (more of which you later). The enzyme indolamine di-oxygenase (IDO) is the rate limiting step within this pathway, and induction of this enzyme metabolises tryptophan down the kynurenine pathway.

    The depression research has indicated a number of pro inflammatory cytokines that appear to induce IDO, thereby shunting tryptophan metabolism away from the production of serotonin and towards the production of kynurenine, with subsequent development of depressive illness.We can see evidence of this in the treatment for hepatitis C with interferon alpha, in which high levels of depression are reported.

    The question is what evidence do we have had similar mechanisms might be occurring in MS ? If it were the case that cytokines were inducing IDO in MS, we might expect to see disturbances within the tryptophan-serotonin pathway as well as the tryptophan-kynurenine pathway. Research earlier this year indicated that nocturnal levels of melatonin were reduced in treatment naive patients with relapsing limiting MS, as might be expected if activity in the tryptophan-serotonin pathway was diminished. Interestingly levels returned to normal following treatment with interferon beta. Increases in the kynurenine metabolite KYNA , have also been reported in patients with active MS disease, again indicating shunt towards kynurenine production within the tryptophan kynurenine pathway.

    It’s not surprisingly therefore that high levels of depression are seen during high levels of cytokine production in MS, as experienced in a relapse, and reduce as the patient enters recovery and remission.

    For those patients undergoing treatment with interferon alpha for hepatitis C resilience to developing depression is seen in those patients who have a particular genetic polymorphism of the serotonin transporter gene. It would be interesting to see whether similar resilience to developing depression was seen within patients carrying this gene suffering from RRMS in the Cardiff study.

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  15. part 2

    With respect to treatment, we now know that antidepressants have an attenuating effect on an array of pro-inflammatory cytokines, as well as there effects on serotonin metabolism. Of interest maybe to patients suffering from MS is the use of minocycline augmentation of antidepressants, which seems to suggest some shared pathways between the two disease processes, with the current ongoing trials of minocycline in RRMS.

    There is another relapsing remitting illness, of a higher prevalence in MS in which during periods of remission debilitating deficiencies in the working memory and executive function are seen. That illness being bipolar affective disorder and it’s postulated that KYNA is implicated in these cognitive deficiencies.

    Finally I think it’s important for those patients experiencing significant mood disorder in MS to have an assessment undertaken by a psychiatrist with sufficient knowledge of mental illness in the context of physical health problems in order to provide an accurate diagnosis and indicate which treatments biological or psychological are going to be most effective.

    For me I think the evidence is developing that depression can as much a symptom of disease activity in MS as for example motor and sensory deficits, and not just a consequence of the psychosocial stress of living with the illness.

    I obviously have not been able to go into the above in any great depth (this is of course a reply to a blog rather than a formal academic paper for discussion!) But I hope people have found it of interest.

    Declaration of interest: Currently working as a Consultation-liaison Psychiatrist with a diagnosis of relapsing remitting multiple sclerosis. (Currently recovering from a recent relapse and using the new dictation feature in OSX, blame Apple for any grammar or spelling mistakes!)

    Will return to post to put in references and links.

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