research

How to Research Bipolar Disorder or another Mental Illness

→ July 23, 2012 - 10 Comments

How to Research Bipolar Disorder or another Mental Illness

When you or someone you love is diagnosed with a mental illness like bipolar disorder, likely, you don’t know much about the mental illness outside of what the media and popular culture has told you. Unfortunately, these are not the best sources of information about bipolar disorder, depression, schizophrenia or other mental illnesses.

Mental Health Research

What is critical is that you take it upon yourself to research the mental illness so you can get the facts and not believe the fictions propagated about mental illness. If you’re here at the Bipolar Burble, and reading this, you’ve made an excellent start but I encourage you to continue with these other trusted research options.

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Breaking Bipolar Reading Round-Up

→ December 23, 2011 - Comments off

Best in Breaking Bipolar by Natasha TracyHappy holidays all.

I’m a pretty busy gal right now, so not a lot of time to write new material. I promise I’ll try to get to something new next week.

However, while you’re waiting, have you caught up on all your Breaking Bipolar articles? No? I didn’t think so. Here’s a run-down on some of what I’ve been doing over at HealthyPlace:

  1. Last Minute Holiday Tips for the Bipolar – just published today. Here are four things you should know before you get any deeper into the holidays.
  2. What 2011 Taught us About Mental Illness – a wrap-up of the top ten things research taught us about mental illness last year including: bipolar misdiagnosis, bipolar treatment success predictor, mania treatment comparison and antipsychotic information. Part one and part two.
  3. You’re Narcissistic! Getting Over Insults – How one reader got to me even though I knew they shouldn’t have.
  4. Celebrating Mental Health News – on why we should celebrate the good moments in mental illness.
  5. How to Choose a Good Psychiatrist – one I’ve touched on here but in more detail.
  6. Bipolar Disorder Thought Types – have you ever considered the odd types of thoughts you have a person with a mental illness? I have.
  7. The Importance of Self-Care in Bipolar Disorder – tips on self-care plus a video.
  8. Sexual Health and Bipolar Disorder – the sexual concerns of people with mental illness.

Drug Trials, Antidepressants and Placebo Effect – Is it Bad?

→ December 12, 2011 - 6 Comments

When drug trials are conducted, the gold standard (and requirement for FDA approval) is a double-blind placebo-controlled study. In this kind of drug study participants are randomly assigned to receive either the medication or an inert (does nothing) pill known as a placebo. Neither the doctor not the patient knows whether they are getting the placebo or the real drug.

The study then compares what happens to those who received the real drug versus those who received the placebo and determines the efficacy of the real drug.

The Placebo Effect

This is critical because of something known as the “placebo effect.” The placebo effect is this odd scenario where people get better just because you give them a pill, even if the pill does nothing. Doctors and scientists don’t understand the placebo effect but not only will people get better on a placebo, but they will even experience side effects – something that isn’t possible given that the placebo is inert. But the brain is a powerful thing and something we don’t fully understand.

Treatment vs. No Treatment OutcomesAnd one of the problems with antidepressants (and many medications) is that sometimes they aren’t better than the placebo. Additionally, sometimes when they are better than the placebo, it’s only by a small margin. Drug companies have to prove that their drug is statistically significantly better than a placebo in order to get FDA approval but even this statistically significant amount can be very small.

However, this isn’t a piece about how effective are when antidepressants are compared to placebos. This is a piece about how effective antidepressants are compared to no treatment.

Depression Treatment vs. No Treatment

Now, each disorder would have to be studied individually, but basically the question is, if you put treatment vs. placebo vs. no treatment, what would happen? ^

I can tell you what would happen – the people who received no treatment would do worse than those who received a placebo.

To the best of my knowledge there is no exact study like this, likely because it wouldn’t make it past an ethics board. If you determine a person is ill and needs treatment it is unethical to offer them none.

There is, however, a comparison of treatment vs. no treatment that I’m aware of. Here, they study people who have received treatment vs. those who have not. (They break down those who have not into three additional groups: those that don’t think they need treatment, those who think they need treatment but don’t get it, and those that don’t need treatment.) Note that “treatment” isn’t specified so it could be of any kind.

What they find for depression is that those who receive treatment go from around 30 to 24 on a depression scale in one year and those that need treatment but don’t get it go from about a 27 to 23 in one year (in both cases a higher number indicates greater depression).

So, treatment moves them 6 points and no treatment moves them 4 points. Approximately.*

No Big Deal?

Well, it depends if you’re the one depressed.

Firstly, it’s important to note that those in treatment were more depressed than those who weren’t. This should be noted as those people would likely have worse outcomes in one year. (The study wasn’t designed to take this into account but does note that symptom severity at outset is the biggest predictor of poor outcomes.)

Secondly, it’s worth noting that 2 points on a 35-point scale can lead to a significantly greater quality-of-life for the person in general. Many people with treatment-resistant depression I know would kill for that kind of improvement.

Thirdly, this improvement marker isn’t the only relevant one; it’s just the only one I have to go on.

Numbers on the kind of improvement seen in treatment versus no treatment vary, but everyone agrees that no treatment is worse. (The above estimate is rather conservative.)

What, No Placebo?

Unfortunately, no. There is no placebo in this study. Sorry.

But as we do know that people on a placebo do almost as well, and sometimes better, than those on the drug, we can guess (yes, guess; again, sorry) that people on a placebo would land somewhere in between the two above outcomes.

Question: How Do We Improve Outcomes without Giving a Placebo?

So the question is, if people on a placebo do better than no treatment (but not as well as those treated) then is there a way to preserve that gain? Doctors can’t prescribe placebos, it’s unethical.

Or is the placebo effect when being given an antidepressant such a bad thing? If, really, you respond to a real medication because of the placebo effect (and you wouldn’t know the difference, no one would) is that really all that bad? Does that not have a value?

People decry the placebo effect saying it proves that antidepressants are worthless. But I say how would all those people benefiting from them, even from the placebo effect, get better without them?

^ See the comment Placebo Effect in Depression as well. 

 * In case you were wondering, people who were depressed but didn’t think they had a problem were less depressed than those that perceived a need for treatment; however, they only moved down the scale from about 18 to 16 in one year.


No Evidence of the Effectiveness of Psychotherapy? – 3 New Things

→ September 15, 2011 - 20 Comments

This week I learned three new things about psychotherapy and depression.

I’m a fan of psychotherapy for everyone. In fact, if we could get the mid-East folks to sit down for some good counselling, I think it would be more effective in bringing peace than anything you can do with a gun.

With that said, there are limitations to therapy and sometimes therapy is not all it’s cracked up to be. So this week, a look at three perspectives on psychotherapy:

  • Psychotherapy is no better than placebo in treating depression?
  • Which type of psychotherapy is better for depression?
  • How does psychotherapy change the brain?

1. Is Psychotherapy Better Than a Placebo in Treating Depression?

When the study came out  a couple of years ago alleging that antidepressants were no better at treating mild-to-moderate depression than a placebo, the antipsychiatry world went crazy (if you will). All their dire claims, it seems, had been proven true.

Well, the sky hasn’t fallen yet, but interestingly the same kind of analysis, when applied to psychotherapy, can also allege that psychotherapy is no better than a placebo too.

Can Psychotherapy Treat Depression?Placebo for Therapy

Of course, there is no such thing as a placebo in therapy. There is no “inert” counselling session. Scientific literature attempts to compare cognitive behavioural therapy (CBT), interpersonal therapy (IP) and others against wait-listed participants and those who have received therapy not containing the specific therapeutic technique being tested. Basically, they tell a therapist not to therapy. Which is a pretty tough thing to ask a human to do. And naturally, humans aren’t going to do it well.

Does Psychotherapy Work to Treat Depression?

I would say yes, therapy, various types, including cognitive behavioural, interpersonal and supportive therapy, all help treat depression. However, some suggest the jury is still out on how effective therapy really is in treating depression.

2. What Therapy is Best for Depression?

[push]Psychologist Gary Greenberg states CBT is more of an ideology and a “method of indoctrination into the pieties of American optimism.”[/push]

When selecting a therapy for depression one has many choices but the prevailing one in the scientific community right now is cognitive behavioural therapy (CBT). Everybody loves it. It’s the golden child. CBT is a highly intellectual and analytical therapy that is short-term and action-oriented so it’s no wonder that people like it.

In the same article as the one talking about therapy effectiveness in the treatment of depression, they also discuss which therapy is best for depression, and it kind of seems like none of the therapies are best. (This could be because, statistically, some people respond better to one treatment while others respond to other treatments and when you lump them all together, a similar percentage responds to each.)

3. What Does Psychotherapy Do to the Brain?

As I have mentioned several times, depression decreases brain volumes over time – ie, depression shrinks your brain. It does this through decreasing neurogenesis (the creation of new neurons); however, electroconvulsive therapy (ECT) and antidepressants have both been shown to increase neurogenesis and brain volume.

Interestingly, so does psychotherapy.

More on brain changes as a result of psychotherapy here.

Until next week all. I’ll learn more and do better.

New Antipsychiatry Discussion, L-Theanine, Rapid Cycling Markets – 3 New Things

→ September 1, 2011 - 2 Comments

This week’s three new things include:

  • A new supplement that may help brain health and mental illness: l-theanine
  • A poor comparison between rapid cycling bipolar disorder and the financial markets
  • A new discussion of antipsychiatry

1. New to Me: L-Theanine as an Antidepressant

Maurya, a commenter, asked if I knew anything about l-theanine. Well, I didn’t. Every once in a while even I run across something of which I haven’t heard.

So, for those of you in my boat, here’s a bit about l-theanine:

As always, as this is a supplement it is not FDA-controlled and there is no guarantee as to what you will get in the bottle and you should never take any supplement without first checking with your doctor.

More studies on l-theanine can be found here.

Rapid Cycling Brings Out Stigma Comments2. What I Don’t Like – A Half-Assed Comparison Between Bipolar Disorder and the Financial Markets

I’m a writer so questionable metaphors irk me. And rapid cycling bipolar disorder as a metaphor for the financial marketplace? Really? That’s a whole new level of irk.

If you really want to make that comparison then the bulk of the article should be on the markets and not mental illness, and not the other way around like Lloyd I. Sederer M. D. did in Rapid Cycling Bipolar Disorder: In the Office and On ‘The Street.’

Comments of Mental Illness Stigma

All this poorly-written article did was confuse people and elicit a bunch of anti-bipolar comments like:

“The foundation of the Bi-Polar epidemic is based in suppressed biochemist­ry, outdated understand­ing of genetics and a complete misunderst­anding of our true spiritual nature.”

And,

“So how exactly is this different from saying some people dramatical­ly over-react to external circumstan­ces?

Sorry folks, but this one goes into the notebook for the next philosophi­cal discussion of “medicaliz­ation” as a way of discussing deviance.”

Seems to me he just wanted to use mental illness as an eyeball-grabber, tricking readers onto a topic they would never otherwise read – with the extra bonus of eliciting remarks of stigma.

Gee, thanks.

3. What I Find Interesting – New Discussion of Antipsychiatry

As you might know, I’m not a fan of antipsychiatry folks. I have written a lot on this topic and I’m sure I will write much more in times to come. But I can across this article, Getting It From Both Sides: Foundational and Antifoundational Critiques of Psychiatry which has an interesting discussion of antipsychiatry viewpoints.

Two Sides to Antipsychiatry

It astutely notes there are two sides of antipsychiatry – those who feel that nothing can be defined and thus no mental illness can be defined; and those who feel illness is rigidly defined and mental illness doesn’t meet that definition.

Both sides, as the author says,

“. . . have had the effect of discrediting and marginalizing psychiatry and of delegitimizing psychiatric diagnosis and nosology.”

It’s a very intelligent view of antipsychiatry criticism that is elevated far beyond what we normally see online. Check it out.

Until next week: Smarter and Better.

Linky-Madness, Drugging Children and Anxious Hat Makers – 3 New Things

→ August 25, 2011 - 4 Comments

In my line of work I come across the most obscure information, which is why I love sharing it with you. This week’s three new things about mental illness include:

  • A weekly mental health link-party
  • How scientists want to drug children who might get a mental illness
  • How hat makers used to experience social phobia

How could you not want to know the details about that?

1. What I Like – Madness Mental Health Linky

I’ve been participating for a few weeks in the Monday Madness Mental Health Linky over at the WordsinSynch blog by Shah Wharton. As the name implies, there are fresh links every Monday.

[push]Anyone can contribute a useful mental health link. Shah features her own work or the work of others and then lists useful links.[/push]

(No offence to Shah, but the layout is awful and kind of hard to understand.  Here’s how it works: Simply read the Monday Linky article and at the bottom there are featured links. Below that is the “blog hop” where the reader-submitted useful mental health links are posted and below that you can enter your own link.)

Click. Read. Enjoy.

2. What I Don’t Like – Drugging Children (or anyone unnecessarily)

Drugging Children with AntipsychoticsI could just leave it there but what I especially don’t like is the drugging of children who might get a mental illness. This is one of the troubles with that fad diagnosis I mentioned last weekpsychosis risk syndrome. While we do, honestly, know what puts a person at risk for psychosis, that’s a far cry from actually being able to accurately predict who is going to get a psychotic disorder.

For example, I know smoking puts you at risk for lung cancer, but you still might not get it. (Although smoking’s a lot more clear cut than psychosis. Don’t smoke. Seriously.)

In this study, people age 15-40 were to be given an antipsychotic (quetiapine) to see if it would delay or prevent the onset of a psychotic disorder like schizophrenia. And – here’s the kicker – up to 80% may never get the disorder anyway.

So I ask you, is it worth exposing a 15-year-old to a powerful antipsychotic associated with an increased mortality rate on a guess? I think not. (More next week.)

3. What is Just Bizarre – Hat Makers, Mercury  and Anxiety

Think you have social phobia? Do you make hats?

Excessive shyness, embarrassment, self-consciousness, timidity, social-phobia and lack of self-confidence are components of erethism, which is a symptom complex that appears in cases of mercury poisoning. Mercury poisoning was common among hat makers in England in the 18th and 19th centuries, as they used mercury to stabilize wool into felt fabric.

(From Wikipedia, where else?)

See you all next week for an attempt at a smarter and better me.

PS: Have you entered to win yet?

Five New Bipolar Depression Treatments You Don’t Know About – Part 2/2

→ June 22, 2011 - 6 Comments

As I mentioned, people with bipolar type II spend 35X more time depressed than hypomanic, and yet there are very few treatments available.

As we discussed last time, the neurotransmitter glutamate and the inflammatory complex are two new, badly-needed areas of bipolar depression treatment research. Here are three additional bipolar depression treatment areas you probably don’t know about: diet, antioxidants and modafinil.

Diet, Insulin and Bipolar Disorder

There are quite a few people talking about diet and bipolar disorder, and diet and depression. And for all the words they say, the one thing we actually know through study is: no diet is known to treat bipolar disorder. Period. We know an unhealthy diet will possibly make you worse, but the only thing science can recommend is to eat a healthy, balanced diet.

Diet and Insulin

[push]The only thing science can currently recommend is to eat a healthy, balanced diet.[/push]

That being said, insulin interacts with many parts of the body responsible for much of the brain functioning. For example, insulin regulates the concentration of neurotransmitters and monoamines in the central nervous system; and these chemicals are thought to impact mood disorders, Alzheimer’s and schizophrenia. It appears a lack of insulin can produce mental illness symptoms.

This area is in extremely early development but there is currently testing of insulin increasing drugs in treatment of bipolar disorder and depression. And yes, other dietary issues are being studied (more carbohydrates and less carbohydrates are being studied) but as of yet, there is nothing concrete.

Antioxidants and Bipolar Depression (N-acetylcysteine (NAC))

We know something unfortunate about the brain and mental illness: mental illness shrinks the brain. (Mental illness decreases neuroplasticity, technically.) And we know that some drugs protect or reverse this effect (SSRI antidepressants, lithium, electroconvulsive therapy (ECT)). [pull]We know something unfortunate about the brain and mental illness: mental illness shrinks the brain.[/pull]

And one of the possible causes of brain shrinkage currently being considered is oxidative stress. Oxidative stress represents an imbalance that prevents detoxification and repair within tissues. (It’s complicated. See Wikipedia.) Some amount of oxidative stress is normal (and important) but this stress combined with cell abnormalities is implicated in bipolar disorder. Evidence suggests lithium and valproic acid protect neurons against oxidative stress.

(Still with me? Good. It’s going to get easier. Just hang on a bit longer.)

This oxidative stress can be caused due to decreased levels of antioxidants. One in particular, glutathione, is known to have abnormal levels in bipolar disorder. And in order to make enough glutathione, a body must have enough of an amino acid, cysteine.

Increasing cysteine levels using N-acetylcysteine (NAC) has been reported to be neuroprotective and impact glutamate (which we think is good, see here). NAC has been able to alleviate depressive symptoms in people with bipolar disorder in a double-blind placebo-controlled study as an add-on medication.

New Bipolar Depression Research AreasN-Acetylcysteine for Bipolar Disorder Depression – The Good and The Bad

The good? NAC is cheap, over-the-counter, and from what we know, safe.* The bad news? NAC can take up to five months to work and study on it is limited. (See bipolar disorder type 2 depression and NAC notes by Dr. Jim Phelps.)

In a completely non-medical, Natasha-only-based opinion, NAC seems like something you could talk to your doctor about adding. There doesn’t seem to be a downside other than waiting for five months to see if it works. This doesn’t mean try it on your own. It means talk to your doctor.^

Modafinil and Bipolar Depression

Last, but not least, is the research into modafinil treatment of bipolar depression. Modafinil is a “wakefulness promoting agent” prescribed to people “with excessive sleepiness.” This is not an amphetamine but is a stimulant. Basically, we don’t understand this medication but it increases monoamines like norepinephrine and dopamine, which we generally like.

Modafinil has been shown effective in treating bipolar depression (without inducing mania or hypomania) by week two of treatment. In the study, modafinil decreased depressive symptoms and increased remission rates.

This medication is one some doctors are already using off label for the treatment of bipolar depression.

Summary of Bipolar Depression Treatments You Didn’t Know About

Basically, under all of this, the message is: we’re working on it. It’s long and slow and frustrating for us crazies but the doctors have their lab coats out and they’re thinking up stuff all the time. Will any of these help you? I don’t know. But what I do know is these five areas should be a reason to hold onto hope, even if what you’re doing right now isn’t working.

Information Reference

The information in this article is primarily from: Novel Treatment Avenues for Bipolar Depression By Roger S. McIntyre, MD and Danielle S. Cha. Clinical Psychopharmacology. April 19, 2011.

See the article for all the nitty gritty details about the above.

Notes

* Safe in this case means no known drug interactions (to the best of my knowledge and according to a doctor). In the drug database used by doctors up here in Canada it reports no side effects. In the study they note it as “safe” but report change in energy, headaches, heartburn and joint pain as possible side effects – these being basically the same in the placebo and NAC group. Keep in mind though, so little study has been done on this there may be all sorts of gotchas we haven’t seen.

^ Remember: your doctor should know about all medications, vitamins and supplements you take. Just because it’s over-the counter doesn’t mean it’s harmless.

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Depressed People Who Take Antidepressants Do Better Long-Term – Part 2

→ May 16, 2011 - 5 Comments

As I mentioned last week, it’s very difficult to measure long-term outcomes of depression treatment due to the confounding depression variables like severity of depression, duration of depression, number of depressions and so on.

In short, the sicker you are, the more depressed you are, the more likely it is you’ll get treatment.

Antidepressant Treatment Outcomes Long-Term, A Study

I discussed the basic outcomes of this study: The association between antidepressant use and depression eight years later: A national cohort study by Colman et al. (you may have to select Science Direct to see the study, you don’t need a subscription) which tries to take these variables into account.

Colman et al. showed those who took antidepressants had better depression treatment outcomes than those who didn’t, eight years later, once confounding variables were taken into consideration.

I’ll now point out the strengths and weaknesses of this study as well as some other interesting tidbits shown or cited in the study. Oh, and I’ll give my opinion on what it all means.

Strengths of this Depression Treatment Outcome Study

No study, of course is perfect, but each has its strengths. In the case of this study on depression treatment outcomes, some of the strengths include:

  • An attempt to quantify and account for factors we know will affect treatment outcomes
  • Study uses a large, heterogeneous, real-life, population base
  • Quality, fairly comprehensive data available
  • Replicated findings of a British study involving anxiolytics (anti-anxiety medication) and antidepressants

Weaknesses of this Depression Treatment Outcomes Study

Weaknesses mostly bias the outcome towards the conservative. In other words, the relationship between antidepressant use and a positive long-term outcome may be stronger than reported.

  • Does not have 100% data over eight years (Those who dropped out had worse depressions. This biases the data likely indicating a stronger relationship than shown.)
  • Not a randomized controlled trial (not likely possible)
  • Does not capture comorbid (co-occurring) disorders (likely indicating a stronger relationship than shown)
  • Does not specifically capturing other treatments*
  • Didn’t control for perception of need for treatment. In other words, those who were able to identify the need for, and seek, treatment took antidepressants and had better outcomes. So a factor then would be the person’s treatment-seeking behavior.

For all the nitty gritty on the strengths and weaknesses of this depression treatment outcome study, see here.

Outcomes of Antidepressant Treatment of Depression, Facts

In addition to their main findings, here are some other interesting depression treatment outcome facts either shown or referenced in the study:

  • Antidepressants are particularly useful for those with severe symptoms
  • Of 285 depressed patients, those using higher levels of antidepressants were significantly more likely to recover from symptoms in the short term (from a 20-year study)
  • British study found that of 204 depressed patients, those using antidepressants or anxiolytics (anti-anxiety medication) were significantly less likely to be suffering from symptoms of depression ten years later
  • Maintenance use of antidepressants has been shown to reduce future depressions
  • Those with partial remission (still having some depression symptoms) are far more likely to experience future depressions
  • The longer depressive symptoms persist before treatment the worse the long-term prognosis
  • The most strongly correlated value to better outcome was recent antidepressant use

Depression Long-Term TreatmentFunding of Depression Treatment Outcome Study

Because I knew you’d want to know (I did too):

Funding for this longitudinal depression treatment outcome study was provided by government, grant and award money. Study was cleared through the Health Research Ethics Board of the University of Alberta.

So Long-Term Antidepressant Use is Good?

Well, I can’t say that. What I can say is this study is suggestive^ of the fact that people who are depressed and take antidepressants do better over the long-term than those who don’t. But remember:

  1. People weren’t necessarily on antidepressants the whole eight years.
  2. The key (shown in studies and in my opinion) is to treat the depression as soon as possible and get all symptoms into remission.

So, that doesn’t mean get and stay on antidepressants forever, nor does it mean go on and off antidepressants. Those are individual choices depending on the person’s situation. If you can achieve #2 then your prognosis (in my opinion) is very good. And generally this is done with antidepressants, but depending on your personal situation, you may be able to achieve it through other means.

This also shows people taking antidepressants don’t do worse. This matters because there is a meme out there that taking antidepressants will somehow eat your brain and create mental illness.** This study suggests not.

A Little Bit More

* Study also talks about the role of therapy in depression treatment but no relationship was found between those who got therapy and those that had more positive outcome, suggesting there was no benefit to therapy. However, this is likely due to the broad definition of the word “therapy.” This is why I chose to omit information therapy findings.

^ This is not a causational relationship (where we know one thing causes another) as causation is hard to ascertain without real double-blind placebo controlled randomized study. And we don’t have that.

** Antidepressants actually increase the creation of neurons (neurogenesis) and increase brain volume.

Depressed People Who Take Antidepressants Do Better Long-Term

→ May 12, 2011 - 17 Comments

Recently the controversy over long-term outcomes of those who use psychotropic medication has flared up again. Some people argue depression/bipolar/mental illness patients do the same, or better, when they don’t take psychiatric medications long-term. However, the statistics they use to assert this claim are often faulty.

A study from Calgary, Alberta, Canada (yes, we do research up here too, select Science Direct to see the study) has attempted to fix some of the bias seen in other long-term depression treatment outcome statistics. I’ll cut to the chase for you:

Over the course of eight years people with depression who took antidepressants had better outcomes.

Depressed People Do Not Do Better by Taking Antidepressants

The reason people say those with depression who take antidepressants do not do better, or do worse, goes something like this:

We looked at 100 people with depression and over five years those who didn’t take antidepressants were less depressed.

Put that in the middle of some persuasive text and the villagers gather with pitchforks at the doors of psychiatrists everywhere.

Why are they Wrong? What’s the Problem with This Data?

Treatment Outcomes in Depression

Um, OK. Anyone see the problem here? Anyone?

It should be obvious. Those who don’t take antidepressants (or who go off antidepressants) are typically less sick than those who do take antidepressants. If you’re sicker, you’re more likely to get treatment. It’s not rocket science.

For some reason everyone wants to gloss over that bit.

This is what you call sampling bias.

Measuring Depression Treatment Outcomes Long-Term

Trouble is, you can’t randomly assign people people with a mental illness to treatment/no treatment over the course of a year or more. Sure, the depression treatment outcome data would be better, but the people might not fair so well.

We have to think smarter. If you can’t assign people at random, can you account for variables like duration of mental illness and severity of depression symptoms?

The association between antidepressant use and depression eight years later: A national cohort study by Colman et al. tried to take these variables into account.

Confounding Depression Variables

As I’ve mentioned in the past, depression is not one thing, depression is a spectrum disorder. You may have a variety of symptoms with a variety of severities and still be “depressed” (bipolar is the same). Somehow, we have to quantify that.

We do know some variables that correlate to depression treatment outcomes. Colman et al. measured:

  • Severity of depression
  • History of depression
  • Duration of past depression
  • Suicidal behavior
  • Physical health
  • Demographics (gender, education, etc.)

Depression variables were measured based on scientific scales derived from various methods including personal interviews. You can read all about it here.

Population of People with Depression

For this study, patient population data used was collected by a Canadian agency in the National Population Health Survey in 1998/99 through 2006/2007 every two years. 486 people (of 17,276) were identified as having depression in 98/99 and were followed, 66% of which provided complete data in 06/07 (321 people). Population was all ages, treatments and representative of general population.

Colman et al. analyzed the above variables for all 486 so they could ascertain who was most likely to drop out of the study (or give incomplete information) based on their variables; however, obviously only 321 were used to determine treatment outcome measures.

Depression Treatment Outcomes and Adjusting for Variables

As I said above, if you do not adjust for variables that lead to treatment likelihood, you get statistics that aren’t valid (they’re too biased). Sicker people get treatment.

So, the numbers when you do not account for bias look like this in the depressed population over eight years:

  • Those who took antidepressants were as likely to be depressed as those who didn’t take antidepressants.

But when you adjust for the mentioned variables, that changes to:

  • Those who took antidepressants in 98/99 were less likely to be depressed eight years later (OR = 0.36, 95% CI: 0.15–0.88)

(There are other findings and statistics (not overly significant and in scientist-eze) here.)

Long-Term Depression Outcomes Better with Antidepressants

All that is a fancy way of proving the people who took antidepressants were less likely to be depressed eight years later.

In part two, discussion about the strength and limitations of this study and other interesting findings and citations.

Is There a Blood Test for Schizophrenia? – VeriPsych Tests for Schizophrenia

→ April 18, 2011 - 7 Comments

Hot on the heels of the Bipolar Burble’s post about the neurobiological evidence for major depressive disorder comes this: the first blood-based diagnostic aid for schizophrenia.

Um, what’s that again?

[At this time I’m forced to remind you that I am not a doctor or researcher and everything stated is my opinion or interpretation. Thanks.]

A Blood Test for Schizophrenia

A company VeriPsych, affiliated with Rules-Based Medicine Inc., is offering a blood test for schizophrenia. Or, more specifically, they are offering to test your blood and supply a likelihood that you have recent-onset schizophrenia.

A sample VeriPsych Conditional Probability of Schizophrenia report can be found here.

VeriPsych and a Blood Test for Schizophrenia

The VeriPsych folks, through Rules-Based Medicine, apparently in conjunction with the US Military, ran a study to look for biomarkers of schizophrenia and then develop a test for them. (I should mention here the only thing VeriPsych appears to do, according to their web site, is offer this “diagnostic aid for schizophrenia.”)

Now, admittedly I am not a doctor or a researcher, but here’s what I make of the VeriPsych schizophrenia biomarkers study.

[FYI: Biomarker: a protein measured in blood whose concentration reflects the severity or presence of some disease state.]

Blood Test for Schizophrenia Research

Specifically: Validation of a Blood-Based Laboratory Test to Aid in the Confirmation of a Diagnosis of Schizophrenia by Emanuel Schwarz et al. Biomarker Insights 2010:5 39–47

The study was in two phases, in the first phase researchers looked for reproducible schizophrenia biomarkers and in the second phase, a test was developed to use these biomarkers to test for schizophrenia.

Phase One: Schizophrenia Biomarker Selection

  • Assed 181 biomarkers
  • Used 806 clinical samples
  • Participants were in multiple countries, some from the US military

Initial assessment resulted in the finding of 22 biomarkers. These were retested in 63 subjects 3 months later and showed a correlation of 0.83 (83%).

Nine addition biomarkers were added for phase two due to known association with schizophrenia.

VeriPsych then did something odd: they included 20 biomarkers they felt indicated bipolar disorder, “to facilitate the future development of a test with differential diagnosis capability,” and to “enhance[d] the accuracy of VeriPsych.” (The former is from the research paper, the latter is from the website.)

Notes on Schizophrenia Biomarker Selection

This says to me they are really testing 31 biomarkers of schizophrenia, and 20 for “other reasons.” So when they claim to use a 51 biomarker test, that stretches the truth a little.

Also, the numbers on these seem to vary from the paper to the website making it difficult to deduce exactly how many biomarkers are used for each purpose. A spot on the website says: 36 identified and 15 added. Sorry, it’s just not clear.

Phase Two: Validation of Schizophrenia Biomarkers

  • Phase two used 480 samples for biological test validation
  • Biomarkers appear consistent for paranoid and nonparanoid schizophrenia
  • Biomarkers test seems to work even after 4-6 weeks of antipsychotic treatment (85% accurate)
  • Accuracy increases with chronic schizophrenia
  • Appears (to me) to have more false-positives than false-negatives
  • “Overall sensitivity of 83% and specificity of 83%”

Accuracy of Schizophrenia Blood Test?

There are some super-math algorithms and statistics going on here, but from what I can tell:

  • You get a “score” from the blood test
  • Depending on the score, you get a percent chance of having schizophrenia
  • Some tests are inconclusive

Who Tested the Validity of These Results?

Good question. No one except the lab (Rules-Based Medicine) from what I can tell. This is not an FDA-approved test as it is a “laboratory-developed test.”

Laboratory-developed tests are:

  • The activity of a single laboratory, not a traditional device manufacturer
  • Not commercially marketed to other labs
  • Wikipedia says: assays developed in the laboratory for internal use, or research use only, and not intended for diagnostic or medical use, and therefore treated differently by regulatory agencies; describes most current genetic testing.

Blood Test for SchizophreniaSo, Is This a Blood Test to Diagnose Schizophrenia?

No. It isn’t. This isn’t a blood test to diagnose schizophrenia. They mention this on their home page. This test is to, “aid a psychiatrist in the diagnosis of recent-onset schizophrenia.”

In other words, it’s a freaking guess with a number attached.

This test can’t tell you whether you have schizophrenia, it can provide a somewhat-accurate statistical likelihood. So how useful is that? You have an x% chance of schizophrenia plus-or-minus some variable. Based on one study by one company Does that sound useful? Actionable?

It doesn’t to me.

In Natasha Tracy’s Opinion:

This is a money-grab taking advantage of desperate mentally ill people.

I actually find this “diagnostic aid” blood test for schizophrenia to be bordering on unethical. VeriPsych can cover their ass with math and statistics and probabilities and legal-eze and I’m sure that makes it “OK,” but if you ask me, they are a hair’s breath away from lying. It feels irresponsible to me to hand out these kinds of results about a very serious illness based on one study. One. And there is so much math needed to make this model work that I would fall down dead if there wasn’t a mistake in there somewhere. Nobody gets it right the first time.

This test should be in a lab, used for further research and study, and not be used on the paying public.

(I have other reasons why I don’t like this test too, but as this has gone on long enough, I’ll save them for another day.)

The Neurobiology of Depression – Depression and the Brain

→ April 15, 2011 - 14 Comments

Major Depressive Disorder: it isn’t just “all in your head.”

I have spent quite a bit of time in the last week looking at a paper: Pathophysiology of Depression: Do We Have Any Solid Evidence of Interest to Clinicians? By Gregor Hasler.

This paper discusses seven research areas relating to the neurobiology of major depressive disorder (MDD). In other words, it talks about the biological evidence of depression, mental illness. It discusses the strengths and weaknesses of biological theories of depression via evidence and aims to point out some of the reasons our current treatment isn’t as successful as it should be. Hasler’s article talks about the neurobiology of mental illness and how depression treatment effects that neurobiology.

The paper cites 88 other studies and was published in the Journal of World Psychiatry in 2010. It’s pretty educational.

Neurobiology of Depression – Depression Is In the Brain

The neurobiology (biology of the brain) of major depression research areas discussed include:

  • Psychosocial stress and stress hormones
  • Neurotransmitters such as serotonin, norepinephrine, dopamine, glutamate and gamma-aminobutyric acid (GABA)
  • Neurocircuitry (neuroimaging)
  • Neurotrophic factors
  • Circadian rhythms

(That brain scan for mental illness stuff I mentioned a little while ago is covered in more detail in the article.)

Biological Evidence for Depression Layperson’s Articles Available

I wrote a layperson’s version of the article on Breaking Bipolar at HealthyPlace: Biological Evidence for Depression – Mental Illness exists, part 1 and part 2. I take out the big words and try to explain the crux of central ideas in English rather than scientist. (And if you’re super lazy, there is a table in the article that summarizes the neurobiological theories of depression along with their strengths and weaknesses.)

Here are a couple of notes that didn’t make the Breaking Bipolar article.

Aspirin May Make Antidepressants Work Faster

This very small cited study suggests acetylsalicylic acid (ASA) (also known as aspirin) taken with a selective serotonin reuptake inhibitor (SSRI antidepressant) can make antidepressants work more quickly. This is pre-clinical data so it may end up meaning nothing, but it is interesting. It’s discussed in Stress Hormones and Cytokines section of Hasler’s article.

Protein Involved in Stress Response, Neurogenesis and Depression

(How do Antidepressants Encourage Brain Cell Growth?)

Neurobiological Theories of DepressionConsistently, studies show parts of untreated depressed brains shrink, but we don’t really know why. We also know antidepressants (and electroconvulsive therapy) increase neurogenesis (making of new brain cells) but again, we aren’t sure why.

Hasler’s article discusses glucocorticoid receptors. It mentions their possible role in depression, specifically, in The Neurotrophic Hypotheses of Depression section it mentions glucocorticoid neurotoxicity as a possible mechanism of brain volume loss seen in depression.

Interestingly enough, scientists have just figured out the glucocorticoid receptors are essential for neurogenesis and they “turn immature stem cells into adult brain cells.” And what’s more, antidepressants activate these glucocorticoid receptors.

Why Care About Biological Evidence of Depression?

The answer to this one is pretty obvious if you read the comments here: people think mental illness, depression, bipolar don’t exist as diseases. People think mental illness isn’t biological. People think there is no evidence of physical mental illness. People say there is no science behind mental illness. People say there is no science behind mental illness treatment.

Well, they’re just wrong.

I recommend you read the whole paper, or read my layperson’s translation. Reading about the real studies, the real people, the real images and the real research behind the biology of mental illness brought me back to reality.

Mental illness exists. Depression exists. It’s not just you. It’s just your brain.

Will ECT Work for Me? – Predictors of ECT Efficacy

→ May 12, 2010 - 2 Comments

It would be nice to know ahead of time if a treatment would work. Unfortunately, no one cal tell the future: not for cancer treatment and not for mental illness treatment like electroconvulsive therapy (ECT) either.

Will Electroconvulsive Therapy Work for Me?

But very smart people try to figure out what might predict the outcome of treatments. Especially treatments like ECT, a hotly debated, and much maligned treatment. That’s the good news. And the bad news.

In a retrospective chart review of depressive and bipolar patients in a Netherlands hospital, of those who received  ECT, 65.8% met the standards for remission. The only predictor of response found was duration of index series.

The good part here is that medication failure did not predict response; so theoretically, no matter how many medications you have failed you have an equal chance of response to ECT.

The bad part is that the more times you get ECT in your initial series, the more likely you are to respond. I say this is bad because the more times you do ECT the more chances are you’re going to suffer more and worsening cognitive side effects too.

It’s something to consider when thinking about starting or stopping ECT treatment.

Image by rolffimages / 123RF Stock Photo.

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