The mixed state - the name alluding to a mix between depression and mania - has traditionally been viewed (more or less) as combining the dysphoria of depression with the energy of mania. Anger, agitation, restlessness and so forth.
I've been depressed and I know only too well the difference between that "active" depression and the "inactive" kind; if I had to choose, I'd always go for the latter, because at least you're in less danger of doing or saying something you later regret.
However, in the proposals for DSM-5, "mixed" episodes as such will be abolished. Instead, a depressive episode will have "mixed features" if it is associated with at least 3 of 7 symptoms normally seen in (hypo)mania. But - and here's the key novelty - those 7 are only the "good" symptoms of mania. Not things like anger, irritability, insomnia or 'aimless' hyperactivity. (Edit: There are also separate criteria for "mixed" manic and hypomanic episodes).
What will this mean? In a new paper, psychiatrists Perlis, Cusin, and Fava tried to find out. The large STAR*D antidepressant trial recruited people with depression, but it gave everyone the Psychiatric Diagnosis Screening Questionnaire (PDSQ), amongst many other measures. This helpfully included six items on "mania symptoms", which correspond pretty closely to the DSM-V proposed "mixed" features.
Perlis et al found that depressed patients who reported experiencing these "mixed" items had a better response to antidepressant treatment. The more mixed symptoms, the more likely they were to get better on the common SSRI citalopram, even adjusting for other variables.
That's the exact opposite of what you'd expect from a measure of "mixed states", as these are thought to be less responsive to antidepressants - maybe even caused by them. There was no placebo group, so it's unclear why they got better, but either way, it's unexpected; the authors declare themselves "surprised". Hmm. What a mystery...
Or maybe not. These manic symptoms are all things that you're not when you're depressed. The 6 items actually make a good summary of what depression, even agitated depression (except maybe #6) isn't.
So, one interpretation of these results is that people who endorsed these items just weren't depressed, at some point in the 6 months prior to doing the PDSQ. Assuming they were depressed at other points that means their mood was variable over time.
People whose depression is variable might well be more likely to recover than the ones whose depression was unrelenting.
Now Perlis et al do consider this -
further models were fit incorporating the IDS-C30 pleasure and reactivity items; results were essentially unchanged indicating that they are unlikely to be confounded by mood variability per se...But this assumes that the IDS-C30 questionnaire is a good measure of mood variability in this sample. Maybe it's not, and these data are telling us so. I'd have said that's more likely than the idea that these people were actually both cheerful and depressed at the same time, which seems like a contradiction in terms.
Maybe I'm wrong, and these people did feel that, but the problem is, we can't tell, because no-one actually sat down and asked these people what was going on, or heard their account of what they meant by ticking both the "depressed" and "manic" boxes.
Did they experience a strange mixed emotional state in which they simultaneously depressed and happy? Did their mood see-saw from one day to the next? Or weekly, monthly? Were they depressed in the day and happier in the evening? Were they depressed, then back to normal, leading them to see the normal as a 'high', by comparison with the lows? Were they depressed when sober and happy when drunk? Vice versa? Are they experiencing normal ups and downs and interpreting them as 'mood swings' because they've become convinced, for whatever reason, that they have a mood disorder? Did they just have a poor command of English and weren't really trying to say what the highly-educated investigators assume they were?
Who knows? No-one, because no-one asked. Rely on questionnaire 'measures' (as if emotions can be measured) as a replacement for understanding, and you'll end up where this paper does - with a 'result' that's impossible to understand.
Don't seek, and ye shan't find.
It's not great news for the DSM-5 proposals, either way, although defenders could hold out hope that the differences between those criteria and the PDSQ measure might mean the DSM-5 will perform better...
Perlis, R., Cusin, C., and Fava, M. (2012). Proposed DSM-5 mixed features are associated with greater likelihood of remission in out-patients with major depressive disorder Psychological Medicine, 1-7 DOI: 10.1017/S0033291712000281
18 comments:
I've experienced (probably) SSRI-induced mania and hypomania; two points:
1) During a period of extremely rapid cycling I was *petrified* that the impulsivity, energy bursts and agitaion of mania would merge with the despair of depression and result in a suicide attempt (a possible cause of possibly increased suicide rates in SSRI medicated patients?)
2) I've been dosed on various SSRIs at various levels at various times in my life. I've enough experience of them now to suspect that when they *do* work for me, they do so by inducing some 'good' hypomanic symptoms / behaviours; my mood brightens and my neuroticism falls away, but there's something more flighty and bold about my mind (I don't take them any more for this reason). The most recent example was the sudden interest in global financial markets which gripped me for a few weeks back in June (I still have shares in AstraZeneca from that little blip...)
I can easily imagine that those with 'mixed' depression under the proposed definition might be those more susceptible to experiencing this effect.
Actually psychiatry is not a medical field were Havard means excellence.
Psychiatrists there have been known to be heavily on the payroll of big Pharma on a great scale.
See the CARLAT PSYCHIATRY BLOG former posts on it. Nb: Dr calat is heading up to Whashington.
America great country! ofhttp://carlatpsychiatry.blogspot.fr/
I think that you hit the nail on the head. The PDSQ is a screening questionnaire and cannot be used to make diagnoses. Screening tests are good for excluding diagnoses but not good for confirming a diagnosis. For that, you need a clinical assessment and expert judgement.
That is one of the reasons why we spend 5 years doing a psychiatry residency...
The APA explicitly changed the name from DSM-V to DSM-5 a few years ago...
Unless I'm misreading this post, the claim that "But - and here's the key novelty - those 7 are only the "good" symptoms of mania. Not things like anger, irritability, insomnia or 'aimless' hyperactivity" is just straight-up wrong. In the current DSM-5 draft revision, there is this:
" If predominantly Manic or Hypomanic, full criteria are met for a Manic Episode (see Criteria for Manic Episode) or Hypomanic Episode (see Criteria for Hypomanic Episode), and at least 3 of the following symptoms are present nearly every day during the episode:
·Prominent dysphoria or depressed mood as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful).
·diminished interest or pleasure in all, or almost all, activities, (as indicated by either subjective account or observation made by others).
·psychomotor retardation nearly every day (observable by others, not merely subjective feelings of being slowed down).
·fatigue or loss of energy.
·Feelings of worthlessness or excessive or inappropriate guilt (not merely self-reproach or guilt about being sick).
·recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide."
Source: http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=483
Allen J. F. - Sorry, that was unclear. The post (and the paper) are about the "mixed" specifier for depressive episodes. As you point out DSM-5 also proposes to introduce "mixed" (hypo)manic episodes, in which some symptoms of depression are present.
These results (if they do hold true for the DSM-5 criteria and not just the PDSQ) would suggest that DSM-5 "mixed" depression is unlike the classical concept of the mixed state.
It could be a different story for "mixed" (hypo)mania.
Phil: That's an interesting idea. When I started on SSRIs I thought I might be hypomanic for a while. But in retrospect I wonder if it wasn't just a normal mood and it only seemed 'high' by comparison.
I guess it really depends what your personal 'normal mood' is. There are some people who just naturally behave in a way that would be evidence of hypomania in other people, and vice versa...
So if you only have 2 symptoms of mania or hypomania and you are depressed, you can't be diagnosed with a mixed state? And just when did Mother Nature decree that? DSM is a bunch of crap. There is no science behind it-- just a bunch of compromised psychiatrists voting behind closed doors about "diagnoses" and "disorders."
@Phil and @Neurocritic:
Though it is has been clinical lore for some time, there is some evidence from small case-control studies that people with bipolar depression are more likely to develop mixed symptoms including suicidal ideation when they are treated with antidepressants before they have an untriggered hypomanic or manic episode.
http://www.ncbi.nlm.nih.gov/pubmed/17850879
What I tend to see most often is people feeling "overly energized" and start cleaning or renovating their apartment out of nowhere, then just lose interest when the feeling wears off. People also describe the "racing thoughts" (IMHO the worst term in the world), which is often described as "I can't hold on to thoughts" or "It's like my thoughts are switching channels". This is distinctly different from ruminations and worry seen in depression.
It is very hard for people to differentiate between hypomania and normal mood. That is why a good assessment focuses on what OTHER PEOPLE notice as unusual. Other people will usually say things like "What are you on?" and ask the person if they took drugs. Others will often comment that the person is talking more quickly, that it is difficult to follow their train of thought or that they are acting out of character. If all else fails, the best thing to do is interview friends and family.
Again, making a retrospective diagnosis of hypomania is one of the most challenging aspects of interviewing in psychiatry and I would not put too much weight in results obtained from a patient self-report questionnaire.
Someone proposed a theory that depresson: mania is like stability: instability and I think that the experiment from Perlis supports this theory somewhat. People who are more unstable are more likely to improve since they are closer to what is considered euthymic.
In addition there was some research that optimist's have more of a placebo response. If individuals have more positive features than maybe they are more optimistic?
I remember reading in one book that diurnal variation wasn't a constant feature of depression and that it tended to disappear as depression became more severe. People, as you say, could be confusing diurnal variation with a mixed type of state. Personally when younger I used to experience a rather extreme diurnal variation that was hard to distinguish from rapid cycling.
The willingness of both psychology and psychiatry to settle for pretty low quality source data like self-reported questionaires and "experiments" involving college students in highly artificial conditions as an acceptable basis for reaching conclusions is really remarkable.
So much of the research program seems as if it was formulates by misanthropes who have no personal experience of real human beings in real life.
I'd have said that's more likely than the idea that these people were actually both cheerful and depressed at the same time, which seems like a contradiction in terms.
I thought it was long known that people can be depressed and happy. They can experience pleasure but it is not lasting, the anhedonia so prevalent in psycho pathology is not pervasive but there are other symptoms. They lack motivation, their goal orientation vanishes, but they keep happy by playing computers games for ever and finding clever ways to avoid their obligations because they know if they are pushed too far ... . Yep, currently there myself.
Regarding the anger issue, it was known with the first antidepressants that there was a suicide risk once treatment commenced. There may be a recovery of nore and 5HT levels prior to a reduction in pro-inflammatory cytokine expression. To use a broad brush: in the cat an injection of interleukin 1, a major inflammatory cytokine, into the hypothalamus will induce defensive rage. Heightened inflammatory cytokine expression is possibly the most common biomarker of depression.
Stuff the molecules. In my view we have created societal dynamics that simply drive too many towards depression. Additionally we are introducing shit into the environment which induces inflammatory cytokine production so that's another problem. Furthermore we treat depression as a chemical problem when it is really about the interface of the organism and the environment. So now I'm really depressed thinking about depression. Time to play Sid Meier's Pirates.
John,
Very interesting as usual but beware with cats:
I was taught for my general pharmacology master a bit of animal pharmacology.
I hated that subject :It was hell to learn by heart the difference of effect of drugs according to animal species. But some healthy skepticism about interspecies studies of drug remains.
Morphine will sedate humans and make most of them cool and peaceful when morphine administration will excite cat and horses to the point of helping race horses ‘owners make money in the distant past by increasing the doped horses speed.
Always nice to read from you.
An American lawyer 2 April 2012 01:05
///So much of the research program seems as if it was formulates by misanthropes who have no personal experience of real human beings in real life.///
What about greed for fame,career promotion and money?
Plus -as Alastair Campbell- put it publicly , psychiatrists being selected from the silliest of physicians and having an image problem -shared with psychologists- leaving them seeking to look "the real thing" as far as science is concerned.
Sorry Neuroskeptic, off topic but relevant to diagnostic issues at least!
Hey Ivana,
Only recently did I become aware of how different psychiatry is in France. Your previous comments cast some light on why that difference occurs. The below is tragic and the relevant professionals need to be called to account.
http://www.bbc.co.uk/news/magazine-17583123
France's autism treatment 'shame'
Does the DSM exist for the benefit of insurance companies and big pharma or is there any added value in disclosing anything proven beyond statistical doubt to truly diagnose and treat? A line in the sand is a start, but I keep recalling all the hype about "social anxiety" that came about almost as a result of the marketing of meds to treat that previously undocumented condition.
Dear John,
Thanks and remeber whatever you read , it is even worst in the reality.
Anonymous 04 04 12
Thanks for your useful comment but my take is that the worst people are the academics who take the DSM 5 proposals as already a done thing -and not only proposals under severe critics like the Yale professor of child psychiatry for the autism DSM5 proposals - and dare to use those proposals as an argument of autority against their own more informed and decent colleagues!
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