Wednesday, September 29, 2010

Atomoxetine for ADHD

 Atomoxetine (Strattera) is one of the pharmacological options for treating ADHD symptoms (attention or concentration problems, hyperactivity, impulsivity) in children and adults.  I think it is a good drug, quite safe, quite effective.  It is not likely to help with mood or anxiety symptoms.  Its effect is probably not quite as robust, for most people, compared to stimulants, but it has the compelling advantage of working continuously throughout the day, instead of wearing off (as the stimulants do) after a few hours.  It takes at least 2 weeks of daily dosing for it to work, which differs from the immediate effect of stimulants. 

While it has only a 5-hour half-life in the body, it probably works just as well if dosed once-daily compared to twice-daily.  Side-effects are usually quite mild, including possible dry mouth and reduced appetite.  

It is quite expensive, and is not covered well by medication funding plans in BC.

Here is a brief survey of some of the research literature about atomoxetine that I found interesting:

http://www.ncbi.nlm.nih.gov/pubmed/20665133
This 2010 article demonstrates that once-daily atomoxetine is superior to placebo for treating adult ADHD symptoms, over a 6-month follow-up period.   Treated patients typically had about a 30% reduction in their symptom scores.  Doses were about 80 mg/day.

http://www.ncbi.nlm.nih.gov/pubmed/18448861
This is an important study, with 4 years of follow-up, treating adult ADHD patients on an open-label basis.  The medication was tolerated well, again with ADHD symptom reductions of about 30%.  Depression and anxiety symptoms were not affected.  I tried unsuccessfully to find a clear statement about average doses used in the study; the dosing regime was similar to other studies, with a maximum of 160 mg/day.   From the authors' previous paper on the interim results of this study, the mean dose was about 100 mg/day, the median about 120 mg/day.  So these are higher doses than in some of the other studies, which typically had 80 mg/day dosing.  

http://www.ncbi.nlm.nih.gov/pubmed/20070786
This was a 6-week open study, showing that adults with "atypical ADHD" showed improvement with atomoxetine treatment, doses averaging about 80 mg/day.


http://www.ncbi.nlm.nih.gov/pubmed/20051220
This is an important 2008 meta-analysis, comparing effect sizes of different therapies for adult ADHD.  Short-acting stimulants were best; long-acting stimulants similar (no advantage--if anything, not quite as high an effect size compared to short-acting stimulants); non-stimulants such as atomoxetine significantly helpful, but not quite as large an effect size as stimulants.


http://www.ncbi.nlm.nih.gov/pubmed/17110824This study shows modest but significant improvement in quality-of-life ratings for adult ADHD patients treated with atomoxetine 80 mg/day for 6 weeks.  

http://www.ncbi.nlm.nih.gov/pubmed/20642391
This study shows reduction in high-risk behaviours in adolescents treated with atomoxetine over a 40-week period.  Looking quickly at the results, I see significant differences between atomoxetine and placebo, but the absolute differences were quite modest in size (typically about a 10% change).  Also the study design has a variety of weaknesses. 


http://www.ncbi.nlm.nih.gov/pubmed/17474814
This is one of many studies showing that atomoxetine does not help with depressive symptoms.  In this case, it was used as an adjunct to an SSRI.

http://www.ncbi.nlm.nih.gov/pubmed/19358788
This study showed no improvement in cognitive function in patients with schizophrenia treated with atomoxetine over 8 weeks.  There were no adverse psychiatric effects, however.   This is an important area to study, to determine if ADHD treatments such as atomoxetine are psychiatrically safe for those with other major mental illnesses, such as schizophrenia or bipolar disorder. 

http://www.ncbi.nlm.nih.gov/pubmed/20679638
This 2010 article from Neurology shows that atomoxetine is not useful for treating depression in Parkinson Disease patients.  I find this type of study useful, to look at psychiatric symptoms in medical illnesses.  In such situations, the biological impact of the treatment often seems more clear to me, perhaps with fewer confounding psychological factors.    The study did find that patients treated with atomoxetine (target dose 80 mg/day) had significantly less daytime sleepiness, and significant improvement in "global cognitive function."

http://www.ncbi.nlm.nih.gov/pubmed/19025777
This similar study shows a possible improvement due to atomoxetine treatment--averaging about 90 mg/day--of executive dysfunction in Parkinson Disease patients.  I note also that there was a reduction in other symptom domains, such as apathy and emotional lability; these problems can be difficult to address in those with mood disorders. 


http://www.ncbi.nlm.nih.gov/pubmed/17900980
Here's another interesting study, using atomoxetine to treat sleep apnea patients, averaging about 80 mg/day over 4 weeks.  The atomoxetine did not help reduce apnea, but it did significantly reduce subjective sleepiness.   There are only a couple of fragmentary mentionings of atomoxetine in treating narcolepsy, another disorder of excessive sleepiness; here is one case report: http://www.ncbi.nlm.nih.gov/pubmed/16268387 Excessive sleepiness is another challenging symptom I see a lot of in young adult depression; antidepressants often don't help with the sleepiness, and tolerance tends to develop for stimulants.  So atomoxetine may be another useful option. 

Thursday, September 16, 2010

"Vitamin Water" and "Energy Drinks"

Here's another exploitative marketing scheme going on, in the middle of university campuses:

A sugary drink, consisting of water with 23 grams (about 5 teaspoons) of sugar per 500 mL, sold in large, colourful bottles of 300 - 500 mL each  -- is being aggressively marketed to young people, with many implied claims about healthfulness.  There are funny, witty, ironic statements printed on the bottles, which I think would appeal to young adults, and consolidate the notion that these are actually healthy. 

A similar drink, which also contains caffeine and a bizarre mixture of added chemicals,  is also being aggressively marketed, with free samples being given out by smiling, athletic young people in decorated sports cars.  Today I noticed the energy drink people occupying one of the university's athletic fields with three large garishly decorated vehicles, hip musical accompaniment blaring out as they handed out samples.  It was a bothersome irony that an athletic field (another health-associated prop) had to be the setting for this.   


It is not a healthy practice to consume sugary drinks.  Aside from the risk of tooth decay, and the exposure to metabolically harmful simple carbohydrates, the habit of consuming these drinks conditions people to expect sweetness while they hydrate themselves.  Ordinary, pure, free drinking water becomes bland and undesirable.  Though the direct health effects of having a glass of sweetened water are not catastrophic, there are a variety of indirect harmful effects:

-because you are quenching your thirst, and hunger, with a solution containing glucose or fructose, you will have a smaller appetite, and less money,  to obtain or consume a healthy meal.

-because of the advertising involved, you will become conditioned to believe that you are engaging in a healthy behaviour.

-you will be financially supporting one of the largest junk food manufacturers in the world; the magnitude of harm done to the world's population (directly and indirectly) by such companies would be staggering to calculate.

-by purchasing these products, you are contributing to the phenomenon of  retailers stocking their shelves with "vitamin water" instead of with healthier choices.  In one of my favourite local cafes, my favourite healthy, locally-made fruit juice is gone, replaced by rows of multi-coloured "vitamin water."  The reason was economic -- the bright colours and the sugar make for a rapidly-selling product.


The presence of vitamins, minerals, amino acids, etc. in these products is, in my opinion, irrelevant.  It is pure marketing.  If you need extra vitamins in your day, you can take a daily supplement, or have a piece of fresh fruit.   The other ingredients are largely placebo as well, just like the colouring.

The case is made by some that there is less sugar in these drinks, compared to other familiar soft drinks.  The difference is actually not very substantial, it reminds me of cigarette companies manufacturing "light" cigarettes, to try to sell people on the idea that this is "healthier."  

I consider this type of marketing to have little ethical difference from a hypothetical example of cigarette companies hiring athletic, charming young people to hand out free samples from a flashy new car.

What bothers me most about this issue is the use of healthy-sounding nutrition talk ("vitamins," etc.) to persuade people to buy an unhealthy product.

I do not support a puritanical view of food & eating though.  I think there are many sweet, wonderful, decadent foods to be savoured (in moderation of course!)   Generally, dessert vendors do not market their tastiest pastries by emphasizing their vitamin content!  In any case, such foods can be enjoyed more richly, in smaller, healthier portions, if one is less conditioned to expect sweetness frequently through the day, such as in drinking water.  


Here are a few references to some pertinent review articles:
http://www.ncbi.nlm.nih.gov/pubmed/20631477
http://www.ncbi.nlm.nih.gov/pubmed/20682226
http://www.ncbi.nlm.nih.gov/pubmed/18809264

One exception, in which a case could be made to supplement drinks with vitamins, could be in the management of chronic, severe alcoholism.  There is a syndrome called "Wernicke-Korsakoff encephalopathy", in which severely malnourished alcoholics develop irreversible, catastrophic brain damage due to metabolism of carbohydrates without adequate vitamin B1.  Adding vitamin B1 (thiamine) to hard liquor, could conceivably prevent some cases of irreversible brain damage in malnourished alcoholics who keep drinking.  I'm not sure if thiamine would be chemically stable in an ethanol solution though--if anyone knows the answer to this one, please let me know.   Anyway, I don't believe this consideration is relevant to health management on university campuses (!)

Conclusion:  if you're thirsty, drink water!

Wednesday, September 15, 2010

Personality Tests

Here's a site which has a good selection of  free personality questionnaires:

http://similarminds.com/personality_tests.html

I find that questionnaires of this type rarely give any novel information that you wouldn't know about yourself already, and be able to describe in a short self-descriptive paragraph.  Many such questionnaires are actually copyrighted, and one needs to pay a fee just to have a copy. I've always had a bit of a problem with this, as I think it exaggerates the importance of what is usually a simple set of questions, which in my opinion should usually be in the public domain.  It is annoying to read a journal article about questionnaires (which are often referred to, in a somewhat aggrandizing way, as "instruments," as though we are talking about some kind of highly sophisticated engineering technology), where the copyrighted questionnaire is referred to in the article, but you can't actually see the questions! 

But spending some time with these things can have a few positives:


1) a framework for reflection -- sometimes questionnaires can deal with questions or phenomena which are relevant, but rarely thought about or discussed.  The questions can be a cue or a framework to contemplate issues.  Some of these issues could be addressed in a therapeutic discussion. 

2) entertainment  -- it can be an interesting or possibly enjoyable activity to fill out questionnaires, and compare your results with others in the population.

It would be important to resist any tendency to be self-critical about your results; everyone will have a unique set of responses,  some of which may change over time, or be mood-dependent, as well.  Questionnaires are an imperfect way to measure any sort of characteristic anyway.  But in any case, a questionnaire is a bit like a lens or a camera--it  produces data which can be informative.  Sometimes the information can be unique or interesting, like a clever snapshot of yourself from a camera; but other times the information may not be very unique or interesting at all (like a poorly-lit or blurry snapshot of yourself).  Even if you may have issues with the way a particular questionnaire is constructed, it can be interesting to see how your responses compare on a percentile basis with others.  You may find certain phenomena about yourself that you previously thought were quite extreme, are in fact really quite close to the population average.  Or you might discover there are other phenomena which are farther from the mean.  Any of these findings might be a subject of future therapeutic dialog. 

Wednesday, September 8, 2010

Health Tips for the new school year

Here are some suggestions for maintaining your health during the new school year:

1) Have a healthy study schedule.  You will learn much more efficiently and enjoyably if you study regularly, in a disciplined schedule.  I don't believe it is possible to master any subject, much less build up an enjoyment of it, by procrastinating or cramming.  Each full-year course probably deserves about 200 hours of study, to be spread out as evenly as possible.   Mastery of a specific field of study probably requires about 10 000 hours of work, which would be full-time for 5 years.   Even if you can get good grades without working hard, I would emphasize to you that doing the bare minimum is an extremely harmful habit--the consequence is that your potential will remain unrealized, also your enjoyment and respect for your subject will never be fully developed.   
2) Have a healthy leisure schedule.  Time must be reserved for pleasure (outside of the hoped-for intrinsic pleasure of studying or working).  A type of "meta-subject" at university is learning to have a pleasurable and healthy lifestyle, with a sense of friendship and community, in the midst of working hard.
3) Be physically active.  Exercise & sports will help you maintain your strength, sharpen your mind, relieve stress, and offer potential sources of community & friendship.  A common problem, however, is excessive exercise, which drains time and energy away from other activities, and which can cause an addictive pattern leading to a psychological dependence on fitness activities alongside a diminished capacity to manage stress in other ways.
4) Don't binge drink.  There is an illusion that binge drinking is an essential part of university social culture.  While it may be a common phenomenon, I think many people minimize its extremely negative health impact.  Anything more than 2 drinks per 24 hours is, from an epidemiologic point of view, harmful to health.    For those dealing with anxiety, depression, trouble fitting in, etc., alcohol can lead to an illusory sense of relief or social belonging while insidiously deepening and entrenching the problems.
5) Eat well.  It's easy to neglect this one, particularly if you're living on your own for the first time.  Basic nutritional advice is not hard to find.  Unfortunately, I think that unhealthy food choices are too easy to find on university campuses.  I think that university cafeterias should not sell junk food, soft drinks, etc. (I also think such items should be taxed heavily, in the same way that cigarettes are).   It's always disappointing to see soft drink companies or fast food restaurants as major food sponsors, with vending machines all over the place, including in hospitals and gyms, etc.   Two simple changes for most people would be to increase vegetables in the diet, and to eliminate junk food.   Allowing oneself to go hungry, or to be carbohydrate-deprived, is likely to substantially impair academic performance, attention, and mood.
6) Make cultural choices with care.  Developing personal culture is very important, and deserves time and energy.   I don't think it is healthy to make a particular cultural choice (e.g. "let's go clubbing!") just because everyone else seems to be doing it. I see a lack of personal culture, with an ensuing lack of a sense of meaningful community, to be one of the leading problems driving loneliness and perpetuating depression on university campuses.
7) Seek medical help if you have symptoms.  There are treatments and supports to be connected with, which can help address anxiety, mood problems, physical symptoms, etc.  It can be better to connect with resources early, rather than wait for things to get worse.
8) Be wary of viral contagion.  A single banal respiratory infection could substantially reduce your enjoyment and learning for a week or more at a time.  The best preventative strategy is to wash your hands frequently, especially if handling objects which thousands of other people have handled or coughed on.  It's important not to go overboard with this--which could be an obsessive-compulsive symptom-- but basic infection control techniques could save you a lot of headache.
9) If you tend to get tired or depressed in the winter months, consider trying a light box.  This is an easy, safe physical treatment which can help with seasonal depression.  Daylight is diminishing rapidly in September, so this is probably a good time to get out your light box.
10) Nutritional supplements.  Women should have ferritin levels checked, and in general should take iron supplements if ferritin is below 50 ug/L.  A daily multivitamin/mineral supplement is a good idea, especially if having abundant fruits and vegetables in the daily diet is not happening consistently.   Harmless at worst.  Extra vitamin D is indicated, I'd suggest 2000 IU extra per day.  DHA/EPA supplements could be useful (omega-3 fatty acids, typically from fish oils). I have some references about this in other entries.  
11) Addiction inventory.  I'd encourage everyone to take an inventory of all addictive or compulsive behaviours, and take steps to stop or moderate them all.  Alcohol or drug use are obvious examples, but other activities could include internet use, gambling, exercise, self-injury, phoning or texting, etc.  Many habits consume so much time and attention, that there is much less time, energy, or enthusiasm left for other things that may be more deeply important to you.

Friday, July 16, 2010

Dopamine Agonists in Psychiatry

The dopamine agonists pramipexole and ropinirole are drugs used in the treatment of Parkinson Disease.

These drugs are now well-established in treating restless legs syndrome (RLS) and periodic limb movement disorder of sleep (PLMS), which are frequent problems afflicting about 10% of the population, and which can negatively impact quality of life & mood symptoms.

There is a small body of evidence showing possible benefits of dopamine agonists in the treatment of depression.

Unfortunately, dopamine agonists can exacerbate addictive/compulsive behaviour: http://www.ncbi.nlm.nih.gov/pubmed/20484726 

Here are some references about the role of dopamine agonists in RLS and PLMS:

http://www.ncbi.nlm.nih.gov/pubmed/20120624

Here's a good review article on the use of ropinirole to treat these conditions: http://www.ncbi.nlm.nih.gov/pubmed/20421915
Here's a recent review of dopamine agonists in general to treat RLS: http://www.ncbi.nlm.nih.gov/pubmed/20206780
Here's a 2008 meta-analysis comparing ropinirole with pramipexole for treating RLS.  Pramipexole is shown to be slightly superior:
http://www.ncbi.nlm.nih.gov/pubmed/18226947

In this 2010 study, gabapentin was compared to ropinirole for treating RLS.  While ropinirole was superior in reducing objective measures of periodic limb movements, subjects taking gabapentin had a higher subjective benefit:
http://www.ncbi.nlm.nih.gov/pubmed/20049491


Here's a case study showing remission of depressive symptoms with ropinirole used as an augmenting agent:
http://www.ncbi.nlm.nih.gov/pubmed/20188777 

Here's a 2005 study looking at ropinirole augmentation in treating depression:
http://www.ncbi.nlm.nih.gov/pubmed/15999953
This 2010 review in Lancet showed a direct antidepressant effect of pramipexole in Parkinson Disease patients:  http://www.ncbi.nlm.nih.gov/pubmed/20452823
Here's a rather weak but positive 2010 paper describing a group of patients with bipolar depression who appeared to benefit from longer-term pramipexole treatment; doses averaged about 1 mg/d:  http://www.ncbi.nlm.nih.gov/pubmed/20425143


The side effects from these drugs include frequent nausea and dizziness, possibly some daytime sleepiness.  Psychiatric adverse effects can include hallucinations, and increased compulsive or impulse-control problems.

In summary, I think dopamine agonists have a role in selected psychiatric conditions, particularly if there are restless-legs symptoms contributing to insomnia or nocturnal discomfort.  They may help treat refractory depression, but there is a risk of causing impulse control problems or hallucinations in predisposed individuals.