Melatonin: benefits and risks

Melatonin is a hormone synthesized in the pineal gland, and is thought to be important in the regulation of circadian (day-night) rhythms.

It has been used to treat insomnia and sleep-phase abnormalities.

The most interesting study I found regarding long-term use of melatonin was published in JAMA in 2008: http://www.ncbi.nlm.nih.gov/pubmed/18544724
In this prospective, blinded study, elderly patients with dementia were given 2.5 mg melatonin near bedtime, over an average of 15 months of follow-up. Patients in another group were exposed to bright light during the day (approximately 1000 Lux indoors, from 10:00 AM to 6:00 PM). A third group received both melatonin at night and bright light in the day. Placebo groups received no melatonin, or were exposed to typical indoor office lighting, of about 300 Lux.* Interestingly, caregivers were not able to tell whether their site had the ordinary lighting or the bright light (the increased light intensity was measurable with a meter, but was not noticeable subjectively).

The results showed that melatonin consistently improved sleep, particularly helping reduce the time required to fall asleep, and increasing total sleep time.

However, the group receiving melatonin alone showed worsening mood (less positive affect & more negative affect).

The group exposed to bright light in the day, plus melatonin at night, did not show worsened mood.

The authors conclude that bright light in the day helps with mood, cognition, and function in elderly dementia patients. Melatonin alone helps with sleep but has a negative impact on mood. Bright light plus melatonin had a positive impact on all the symptoms studied.

Based on this study, I would encourage anyone using melatonin at night to ensure that they get plenty of bright light during the daytime. It also suggests that any study looking at melatonin treatments should also consider daytime bright light exposure as an important variable which could affect response to melatonin.


Here's a reference to a study showing that 2 mg of sustained-release melatonin improves sleep:
http://www.ncbi.nlm.nih.gov/pubmed/18036082

In this study, children with intellectual disabilities experienced relief of their insomnia (including reduced time to fall asleep, reduced time awake, and increased total sleep time) with 5 mg melatonin supplementation over a 4-week period:
http://www.ncbi.nlm.nih.gov/pubmed/18261024

Here's a study showing improved sleep, with no adverse effects, due to melatonin administration to autistic children:
http://www.ncbi.nlm.nih.gov/pubmed/18182647

Here's a study showing improved sleep in children with epilepsy who were treated with adjunctive melatonin (6-9 mg). There were no significant side-effects:
http://www.ncbi.nlm.nih.gov/pubmed/15794175

High-dose melatonin (1 mg/kg body weight) has been used experimentally to treat intractable epilepsy, but more research is needed to evaluate effectiveness & safety. Here is one reference:

http://www.neurology-asia.org/articles/20043_114.pdf

This study showed improved sleep in adolescents with ADHD, when they were given 5 mg melatonin over a 30-day trial. However there was no improvement in ADHD symptoms:
http://www.ncbi.nlm.nih.gov/pubmed/16670647

Melatonin has been associated with autoimmune conditions. Here is a case report associating melatonin use with autoimmune liver disease:
http://www.ncbi.nlm.nih.gov/pubmed/9412927

Here is an article about melatonin possibly exacerbating rheumatoid arthritis (various reports show increased melatonin levels in rheumatoid arthritis patients):
http://www.ncbi.nlm.nih.gov/pubmed/19069959

Yet, in various other reports, melatonin has been shown in animals to protect the liver from various forms of artificially-induced toxicity. (e.g. http://www.ncbi.nlm.nih.gov/pubmed/15386534)


In conclusion, melatonin appears to be have a reasonable safety profile, and is a potentially effective treatment for insomnia, particularly "initial insomnia" in which there is difficulty falling asleep at the beginning of the night. Typical doses of melatonin range from about 2 mg - 6 mg.

The one main concern about adverse effects concerns possible exacerbation of autoimmune diseases such as rheumatoid arthritis, although the evidence is not clear on this point. Other types of toxicity, while possible, appear to be rare. Melatonin may even protect cells from a variety of different types of harm. But it is important to recognize the possibility that there could be other unknown adverse effects over long periods of time.

As with any treatment, we have to balance risks against benefits: insomnia itself clearly has a variety of negative long-term health effects (ranging from increased risk of physical and psychiatric illness, to increased risk of accidents). Other treatments for insomnia have their own risk/benefit profiles.

Cognitive-behavioural therapies for insomnia are clearly the safest and most beneficial, and should be optimized before any other medical therapy. But it appears to me that melatonin ought to have a place in the medical treatment of insomnia, alongside other established therapies.

*here are some measures of light intensity in different settings, to help give you some reference points to compare:

50 Lux -- family living room

100 Lux -- very dark overcast day

300-500 Lux -- recommended office lighting

400 Lux -- sunrise or sunset on a clear day

1000 Lux -- overcast day

10 000 Lux -- clear day (not direct sun)

100 000 Lux -- direct sun

Increasing Anxiety in Recent Decades

Another question from a visitor:

Shifts towards higher anxiety and neuroticism: Twenge** has noted an increase in anxiety and neuroticism in recent decades. Is this the failure of psychiatry/psychology?

Here's the reference:
http://www.ncbi.nlm.nih.gov/pubmed/11138751

This is a good and important article by Twenge, showing that anxiety and neuroticism (the tendency to experience negative emotion) have increased substantially in the past 5 decades, such that, for example, normal children in the 90's had similar scores on anxiety tests as child psychiatric patients from the 50's. The author finds that economic factors are not associated with this change, but that decreased social connectedness, and an increased sense of environmental danger or threat, are associated.

Here's a related comment:

Baumeister* suggests that purpose, values, sense of efficacy, and self-worth are needed for a meaningful life. Religions and spiritual belief-systems have long provided meaning and more. Nietzsche has supposedly said: "He who has a why to live for can bear almost any how". How do you think one can live a meaningful life? *Baumeister, R. F., & Vohs, K. D. (2002). The pursuit of meaningfulness in life. In C. R. Snyder& S. J. Lopez (Eds.), Handbook of positive psychology (pp. 608-618). Oxford: OxfordUniversity Press.

I have always felt that a strong sense of belonging, safety, meaningfulness, and community is necessary for mental health. Modern culture supports independence. Perhaps modernity also encourages the solitary pursuit of wealth, educational success, etc., in an increasingly competitive and busy culture. People are less likely to join community organizations or visit friends. People are more likely to remain single or live alone for longer periods of their lifetime (in their 20's and beyond). There are more activities that can absorb time and attention while alone (e.g. video games, recreational drugs). Even music--an aspect of life that was previously associated strongly with social connection--has become a medium in which a person can disappear alone, disconnected from the social milieu, thanks to portable music players. A cost of sexual or relationship freedom, particularly in the internet age, can be a tendency for people to have brief, less committed relationships, in the quest for variety, or in the quest for an "ideal mate." Intellectual freedom and advanced knowledge, while possibly allowing for heightened meaningfulness and enlightenment, may also shatter previous bastions of meaningfulness (such as religious dogmas), and may finally cause one to confront the absurdity and seeming empty arbitrariness of the universe. Owen Barfield, in his book Saving the Appearances, described modernity as a "shattering of idols", leaving a spiritual emptiness which science cannot fill.

I guess this is a failure of psychiatry/psychology. Not because the therapies don't work, but because the issue is one of public health and culture. I think this type of evidence emphasizes the importance of encouraging social connectedness and community involvement--to whatever degree is possible--as essentials in a therapeutic prescription for treating anxiety or depression.

In this regard, I encourage involvement in volunteering, community organizations, churches, sports teams, activity clubs, etc. It may be necessary to change one's personal culture in order to change anxiety or depression. You must be wary about being swept up in the prevailing culture, and must instead make active choices about what is healthy and meaningful for you.

*As an addendum here, I have to say that research data of this type may be biased by a variety of factors which differ between one time period and another, including use of language, cultural acceptance of symptoms, etc. Therefore, the children in the 50's may have had lower anxiety scores because they were less familiar with the language associated with anxiety symptoms, were less likely to admit such symptoms on a questionnaire, were more likely to deal with the underlying cause of such symptoms in a different way, etc. We now realize many terrible problems which were going on in the 50's (such as abuse), but which people did not talk about as openly back then. A questionnaire on these issues done at that time might have underestimated the degree of such problems.

**Here's another article, showing increasing life satisfaction over the past decades:
http://www.ncbi.nlm.nih.gov/pubmed/19227700

Intuition in Psychiatric Practice

Another question from a visitor:

Evidence-Based Medicine: Do you find that intuition has its place in practice of clinical psychiatry? Despite years of positive experience with a certain technique or medicine, would you decide against it if the only study done on it finds it harmful or useless? If not, how do you go about qualifying your sense of intuition and personal experience?

Good question. I think the crucial point here is "what constitutes evidence?"

Years of positive personal experience with something is itself a strong type of evidence. A negative study is another type of evidence. In all logical assessments of treatments, we must weigh the positive evidence against the negative.

If there was such a strong negative study, particularly if it was done with scientific and statistical rigour, it should lead to a critical re-appraisal of one's own practice, to examine reasons why one's own experience was so different from what another study shows. We should always be prepared to change our ways if strong evidence challenges the status quo.

I don't think "intuition" need be placed in opposition to "logic" or "evidence." I like to think that healthy intuition is a way to incorporate logic and evidence in a way which is flexible and open-minded, and which allows room for creativity.

In clinical practice, a manifestation of "intuition" may at times be a product of a great deal of experience or mastery in something (with the acquisition of "formal operations" in one's area of specialty, in a Piagetian sense), such that pattern recognition and responses can happen very quickly. We can see this in chess players, musicians, auto mechanics...any type of acquired expertise. Things appear to happen effortlessly, seemingly without a thought--certainly without the laborious calculations or stilted rumination which a beginner might apply to the task. These "formal operations" though, represent a great efficiency of weighing evidence and decision-making, not an absence of reason. Those who reject formal evidence in favour of their supposed "intuition" are in a different camp. This would be like the chess player or musician who does not pay attention to his or her weaknesses of technique, or like the auto mechanic who doesn't bother to check the oil. I consider this practice to be inefficient and potentially quite dangerous. There are studies which show that "intuitive" diagnostic impressions in psychiatry are often inaccurate (I'll have to find some references); yet I return to my claim that intuition can be a manifestation of our ability to process information quickly, efficiently, even subconsciously, and often with a natural grace and ease which can be a joy of life to practice or witness.

But intuition cannot be used recklessly or with disregard for other types of evidence.

Conversely, over-reliance on non-intuitive evidence can also be stilted and inefficient. The musician who has note-perfect technique, without grace, is uninteresting. A physician who goes through a symptom checklist meticulously, but fails to attend to alarming non-verbal cues, may entirely miss the underlying problem--a problem which is not detectable by a checklist, because checklist data may not be valid or relevant in cases where process is not attended to.

Metaphors

Here's another question from a visitor:

You note that you like using metaphors in psychotherapy. Can you elaborate more on the use of metaphor. I personally find that using metaphors can have its downside. Some metaphors, once useful--or helpful to those who never heard of them--can become quite trite and cliché. They may even take on negative connotations if associated with unpleasant memory or a disagreeable person from the client's past.

To some degree it is a personal indulgence on my part to attempt to use metaphors. I think you're quite right that this could be unhelpful or annoying to others, and at the very least trite or cliché. I would need to keep this tendency of mine healthily reigned in when necessary. It is, however, very characteristic of me, and a pleasure of mine, to seek out a new metaphor, and therefore an aspect of genuineness that I would attempt to share with patients at times.

Theoretically, it has been part of a larger world-view of mine, that a great deal of wisdom is couched in metaphorical language, yet this language is often taken literally by dogmatic adherents. The dogmatism intensely suppresses the wisdom. This happens frequently in religion, politics, and even in science and medicine. Joseph Campbell was one of my influences: I think he had a great balance of wisdom, humour, and story-telling ability--these are qualities of a good physician, thinker, or healer. Campbell himself was influenced by psychoanalytic thinkers such as Freud, and particularly Jung, but in my opinion his writing never had the annoyingly dogmatic and preachy tone characteristic of these psychoanalysts. Yet, Campbell's ideas are intellectually limited, and I think one should be wary of going too far with them (I find many styles of therapy which are overtly about "exploring myths", etc. to be tiresome, ignorant of modern scientific evidence, and overburdened with jargon). But I liked Joseph Campbell's style, and maybe this is one of the reasons I like "indulging in metaphor" at times as part of my work.

Psychologists Prescribing Antidepressants?

Here's another question from a visitor:

Your views on psychologists' obtaining the right to administer antidepressant.

I don't have any problem with this. If psychologists, or anyone else, were to have prescribing privileges, I do think there should be an educational program with a licensing exam, with continuing education requirements for maintaining licensure, etc., to ensure that the prescribers are up-to-date and knowledgable about the medications and risks, etc. At that point, it could be up to an informed patient to decide whether to trust and accept a prescription from a psychologist. As far as I'm concerned, this is a fair balance between regulation and individual rights in a freedom-oriented society.

I think some psychiatrists' opposition to psychologist prescribing has a lot to do with wanting to hold on to more influence, authority, power, or perhaps a greater sense of importance or exclusivity. There may be elements of narcissism and insecurity which underlie this position. It reminds me of the history of modern medical opposition to midwifery.

While many patients need complicated regimes of medication, may have complex comorbid medical problems, and may therefore require a highly specialized expert in psychopharmacology to prescribe for them (actually, the level of expertise in this area among psychiatrists is very inconsistent), the majority of patients who might benefit from antidepressants require a very simple regimen. Such a regimen does not require many years of advanced education to competently administer. It seems a waste of time and health-care expense for those individuals to have to seek out an MD for their prescriptions.

Furthermore, many antidepressant prescriptions are currently written by a gp who may have only seen the patient for a few minutes--if psychologists were prescribing, this would most likely be in the context of knowing the patient very well, with hour-long appointments, and offering very good follow-up care.

There are risks associated with prescription antidepressants, and there are bound to be patients who run into problems after being prescribed antidepressants from a psychologist. But I am doubtful that these risks would be higher than if antidepressants were only available from an MD, particularly if prescribing privileges required passing a licensing exam, etc.

Future of personalized antidepressants

Another question from a visitor:

Advances in psychiatrist medications: Holsboer has recently elaborated on the future of personalized antidepressants designed using genotype and biomarkers. Where do you think psychiatry is headed, in terms of ideology, but also medications and treatments?

Here's the reference:
http://www.ncbi.nlm.nih.gov/pubmed/18628772

It's an interesting and important subject. In current practice, it can be hard to find medications or other types of therapy which are helpful. It would relieve a great deal of suffering much more quickly to have some way of determining, in advance, which particular treatment for psychiatric illnesses might help best.

Also, the article emphasizes the need to search for treatments outside of the current pharmacological paradigms; we probably have enough medication choices affecting serotonin uptake, etc. It will probably be important to search for pharmacological treatments which affect other systems in the brain.

I don't feel very well-informed about the cutting edge of this science (translating genetic research into pharmacological treatments), but I can see this being a huge advance in the coming decades.

Are Psychiatrists Professionals, Friends, or Healers?

Another question from a visitor:

Are psychiatrists professionals, friends, or healers? I personally believe that healing occurs in a time and place beyond professional rules and regulations. Even friendships can be healing. I wonder if professionalization of medicine is antithetical to a healing process that is dependent on...deep human connection.

This is a good question, one I've often thought about.

The standard of practice in psychiatry, and in other areas of medicine, is for the therapeutic relationship to be "well-boundaried." Mind you, this seems like an obvious truth; furthermore, any healthy friendship also needs to be "well-boundaried." Many unhealthy friendships or family dynamics are problematic due to unhealthy or absent boundaries. But in psychiatry, there are formal legal and professionally-mandated restrictions around the type of relationships permitted between therapist and patient, or between therapists and former patients. In general, I would say the rule is that any interaction between psychiatrist and patient (or between psychiatrist and former patient) needs to be considered a "therapeutic action," or at least an attempt to be a "therapeutic action," and if this interaction cannot be justified as such, it would be considered outside a healthy boundary. These rules protect patients from unethical practioners.

But I do consider any type of healthy human interaction to be a manifestation of a type of friendship. And I consider it a healthy way to live, to consider that all of one's interactions in the world are "friendship-building" activities. To experience the very personal relationship of psychotherapy as strictly bereft of "friendship" seems wrong to me.

Different individuals will have different needs or wishes in this regard. For many people, they prefer to interact with a psychiatrist or other professional in a polite but formal and distant way. Many people would not want to have a friendship with their psychiatrist or physician.

For many others, closeness and trust in a therapy relationship is extremely important to nurture.

One thing I strongly feel to be true is that the therapy relationship needs to be a setting in which growth of healthy relationships outside of the therapy relationship can be encouraged.

I am reminded of some of the psychiatric theory from the previous century about "object relations." This theory generally considers that relationships become "internalized" as abstract mental models, during the course of development. Relationships with parents during early childhood become the first internalized models. Recent evidence establishes that early peer relationships are extremely important in psychological development, perhaps having an equal or larger effect than parental relationships in many cases. Included in these internalized relationships are a sense of "other," a sense of "self," and a sense of expected dynamics between "self" and "other." Future relationships then develop which tend to be in synchrony, or in a type of resonance, with the internalized models. If these internalized models are disturbed by unhealthy relationships, absent or neglectful caregivers, abuse, environmental adversity, or inherent neuropsychiatric symptoms (such as innate tendencies to be anxious, irritable, depressed, etc.), then future relationships are likely also to be disturbed. This leads to a vicious cycle of unhealthy relationships and escalating symptoms.

In a therapeutic relationship, I think this "object relations" idea is important. The therapeutic relationship should aim to be one in which previous vicious cycles are not allowed to repeat. Over time, if the therapeutic relationship is healthy, it could perhaps become "internalized" as well, hopefully as a model of comfort, stability, nurturance, respect, trust, and healthy boundaries. In this way, I think the role of therapist is a bit more like the role of a parent, in that there is an element of friendship, a strong expectation of nurturance, a benevolent "paternalism" to some degree (some desire this element more or less than others), but also the observation that the "parent" becomes less and less necessary for meeting personal needs as the relationship develops over time.

There can sometimes be experiences of very great personal need. The experience of therapy can partially meet this need. The boundaries of the therapy can feel tremendously frustrating for a patient if this need is only partially met. Yet I feel that part of the growth experience in therapy can be to come to terms with this frustration, i.e. that the therapist is a positive, caring figure, but also that the therapist is limited and unable to meet any need completely or perfectly. If the therapy is to be truly effective or "healing," then the more complete or "perfect" satisfaction of needs eventually could occur outside of the therapy, during daily life.

Here's a light-hearted poem about this theme. It's by Hal Sirowitz, from the collection My Therapist Said.

BETTER THAN A FRIEND
You shouldn't tell everyone that you're
in therapy, my therapist said. Some people
might think you're crazy. If
someone asks why you go to the city
at the same time each week, you should
just tell him that you have an appointment
with a friend, which is not really a lie,
because I'm your friend. But I'm also
so much more. You can insult me, & I'll
never get mad. I'll just say that you're
transferring again. I'll never leave you,
but you can leave me. One day you'll
tell me that you don't need to see me anymore,
& instead of being mad, I'll be happy,
because that'll mean you're cured. But
I wouldn't advise you to do that
in the near future. You still have problems.

* I like this poem but it's okay with me if you tell people you're in therapy!
**Thank you to the reader who found the author's name & info for me.

Political Involvement of Psychiatrists

Here's another excellent question from a visitor to the site:

Political involvement of psychiatrists: We live in a "therapeutic culture". [There] are changing sociocultural norms for what is considered normal and acceptable. Are--and should--psychiatrists be aware of the sociological and political changes occurring as a result of the millions taking antidepressants or receiving psychotherapy? Should psychiatrists take a more active role in managing forces that influence communities, given the positive therapeutic effects of unconditional positive regard, hope, trust, interpersonal connection, and belonging (some of the common factors)?

Psychiatrists as a group are extremely heterogeneous, in terms of personality style, intellectual background, and political beliefs. Those who involve themselves in administration or politics may do so in a loving attempt to help their community, but may also do so due to a need to have more influence, control, money, or self-aggrandizement (to be fair, I suppose most people would be motivated by all of these factors, to some degree). There are a lot of big egos in psychiatry, just like everywhere else.

I've often thought of the ideal role of psychiatrist (politically) as some kind of monastic figure ("Jedi-like", if I could indulge in a popular culture metaphor): serenely outside the political machine, possessing wisdom but healthily setting aside the need to exert power or control at all. This type of paradigm is in conflict with the competitive and ambitious world of politics or administration.

I do agree that we all need to be more active in informing ourselves about political concerns, and attempting to help not only individuals, but also groups, communities, or nations. And psychiatry as an organized group most definitely needs to be aware of large-scale social effects of treatments such as psychotherapy and medications.

In very dark and troubled times, or in dark and troubled parts of the world, very bad things can happen politically. The institution of psychiatry has sometimes been involved in these events. At other times, psychiatrists or therapists are themselves persecuted. It is a luxury to live in a peaceful and free nation, and we need to be vigilant to maintain social and political freedom.
Here are a few articles about this:
http://www.atypon-link.com/GPI/doi/pdf/10.1521/prev.88.2.295.17677 (an essay about psychiatry in Nazi Germany)
http://www.nybooks.com/articles/16082 (an 2003 excerpt published in the New York Review of Books about psychiatry in China)

Neurology & Psychiatry

Here's another question from a visitor to the site:

"Neurology and Psychiatry: ...I continue to read the scientific literature and I find it somewhat arbitrary how different fields are divided up. What do you think of joining psychiatry and neurology?"

The field of "neuropsychiatry" is extremely interesting. At UBC there is a specialized ward devoted to helping patients who suffer from a combination of neurological diseases (such as epilepsy, head injuries, etc.) and psychiatric illnesses. Some "neuropsychiatrists" have completed specialty training in both neurology and psychiatry. At UBC a particular focus in neuropsychiatry has been the treatment of severe somatization and conversion disorders: these are psychiatric illnesses which present with severe physical or neurological symptoms (such as paralysis, blindness, or seizures). In conversion disorders, symptoms such as paralysis, blindness, or seizures, are not caused by neurologic problems such as stroke or epilepsy, but by severe, complicated depression in most cases. Treatment of the underlying psychiatric illness causes the neurological symptoms to disappear.

So, neurology and psychiatry do have an intersection in current practice. However, many neurologists may not be predisposed to dealing with psychiatric problems, or may not be willing to offer the type of regular follow-up which I believe is a healthy standard of care in psychiatry (unfortunately, the same could be said of some psychiatrists). Conversely, most psychiatrists would be uncomfortable dealing with acute or esoteric neurological problems.

So, in practice, while neurology and psychiatry have an overlap, the areas outside of the overlap are sufficiently large for the specialties to exist separately.

Passion Flower

There's not a lot of research information about passion flower's medical effects.

It's a beautiful flower though! I would encourage having some in your garden if possible.

Here's a reference to a 2007 Cochrane review:
http://www.ncbi.nlm.nih.gov/pubmed/17253512

Passion flower is mentioned in a good 2006 review article on complementary medicines in psychiatry, from The British Journal of Psychiatry:
http://www.ncbi.nlm.nih.gov/pubmed/16449696

Here's a reference to a 2001 study from Iran, showing that passionflower relieved anxiety to a similar degree as oxazepam (a benzodiazepine), over a 4 week trial.
http://www.ncbi.nlm.nih.gov/pubmed/11679026

The same author published a study suggesting that passionflower could help with opiate withdrawal symptoms:
http://www.ncbi.nlm.nih.gov/pubmed/11679027

In conclusion, not a lot of evidence. The existing studies are only of short duration. But passionflower extract does look like an interesting substance to research further.

"Micronutrient Treatment"

There are examples of "micronutrient treatments" being marketed to help various mental health problems.

These treatments may be marketed aggressively: there may be slick internet sites, perhaps with an enthusiastic following of people who believe strongly in the product.

If the manufacturer of such a product is quoting "research studies," I encourage you to look carefully at the studies referred to. If you are seriously considering products of this type, I would suggest looking at the articles in their entirety at a library.

I encourage anyone interested in pursuing treatments of this sort to ask the following questions:

1) What type of evidence exists regarding effectiveness & safety? Is the evidence from large, double-blinded, randomized, controlled studies conducted by researchers who do not have financial connections with the manufacturer?

2) Is the research pertaining to the product published in a journal with high scientific standards? (In order to answer this question for yourself, I would invite you to leaf through numerous issues of the journal, and compare this with an independent, peer-reviewed journal such as Lancet or The New England Journal of Medicine).

2) Is the evidence mainly from enthusiastic testimonial accounts or case studies? Is this type of evidence reliable enough for you?

3) How much money is required to purchase the treatment? Does the manufacturer encourage you to involve yourself in a long-term financial commitment?

4) After acquainting yourself with common sales and marketing tactics (for a primer on this subject, see Robert Cialdini's book, The Psychology of Persuasion), do you see evidence of highly persuasive or biased sales tactics being used in the marketing of the product? Are vulnerable people being taken advantage of in the marketing of the product?

Have a look at this link, which gives a brief history and overview of charlatanism--being familiar with this history may allow you to make more informed choices about your own medical care:
http://en.wikipedia.org/wiki/Quackery

I do not mean to single out alternative remedies in this post--I encourage the same critical standards to be applied regarding all types of therapy. Mainstream pharmaceutical manufacturers and other providers of mainstream therapies may often be guilty of devious marketing behaviours. In my opinion, though, mainstream pharmaceutical manufacturers have a much harder time getting away with overt charlatanism at this point, compared to many manufacturers of alternative remedies.

Also, I wholeheartedly acknowledge that there can be alternative remedies which are helpful, and which are marketed ethically.

Here in Canada, we live in a free society, with a strong emphasis on freedom of speech. Imposing more strict legal restrictions or regulations upon health choices would limit freedom. I support maintaining a free society, but the presence of charlatanism is one of the costs of this freedom.

Inositol

Inositol is chemically similar to glucose (the type of sugar required by the brain for energy). It is a precursor in a so-called "second messenger system," which cells require to communicate with each other. In the brain, these second messenger systems are activated by various neurotransmitters including serotonin. There is some evidence that brain levels of inositol are reduced in depression and anxiety disorders. Inositol is present in a typical diet, in amounts of about 1 gram per day. Doses of supplemental inositol are typically 10-20 grams per day.

A Cochrane review from 2004 concluded that there was no clear evidence of supplemental inositol being beneficial in the treatment of depression:
http://www.ncbi.nlm.nih.gov/pubmed/15106232

Here's a 2006 reference from Bipolar Disorders showing that supplemental inositol could help treat bipolar depression in some patients already taking lithium or valproate. In 4 out of 9 patients taking 6-20 grams per day of inositol, their depression substantially improved over 6 weeks, with continuing improvement over an additional 8 weeks. However, the other 5 out of 9 patients either did not improve, or actually had worse symptoms. The patients who got worse had more manic or irritable symptoms at the beginning of the trial. When the results were averaged, the inositol did not appear to help significantly--however, it is notable that a subgroup of patients appeared to benefit significantly.
http://www.ncbi.nlm.nih.gov/pubmed/16542187

This 2001 study from the Journal of Clinical Psychopharmacology compared 1 month of inositol (up to 18 grams per day) with fluvoxamine (up to 150 mg per day) in the treatment of panic disorder. Both groups improved similarly. The fluvoxamine group had more side effects of tiredness and nausea. The study is limited by its short duration.
http://www.ncbi.nlm.nih.gov/pubmed/11386498

This 1995 study from the American Journal of Psychiatry compared 12 grams per day of inositol with placebo, for one month, in the treatment of panic disorder. The authors conclude that inositol was effective with no significant side effects. Mind you, when eyeballing the chart of data from individual patients, the results did not look very impressive.
http://www.ncbi.nlm.nih.gov/pubmed/7793450

Here's a negative study, showing no difference between inositol and placebo, when added to antidepressant therapy for OCD:
http://www.ncbi.nlm.nih.gov/pubmed/11281989

The same author as above published a study in 1996 showing that inositol on its own was superior to placebo for OCD treatment. However, despite "statistical significance" being found, eyeballing the data from each patient (presented in the body of the paper) reveals doubtful clinical significance (that is, the amount of benefit looked quite unimpressive to me):
http://www.ncbi.nlm.nih.gov/pubmed/8780431

Here's a reference to a 2001 study showing that inositol was superior to placebo in treating binge eating and bulimic symptoms. In this case, I found the data to be clinically significant. However, the study was limited by its small size.
http://www.ncbi.nlm.nih.gov/pubmed/11262515

Here's a small 1995 study showing that 4weeks of inositol (12 grams per day) was superior to placebo in treating depressive symptoms. The data appeared clinically significant, though modest.
http://www.ncbi.nlm.nih.gov/pubmed/7726322

Here's a 2004 reference from a dermatology journal showing that inositol supplementation led to improvement of psoriasis in patients taking lithium:
http://www.ncbi.nlm.nih.gov/pubmed/15149510

In conclusion, inositol may be modestly effective for treating anxiety, eating disorder, and depressive symptoms. It may perhaps be quite variable in its effectiveness, i.e. some individuals might have much more benefit than others. It appears to be well-tolerated with few side-effects. I could not find good data on long-term safety though. The quality of the evidence is not very robust-- the studies have involved only small numbers of patients, for short periods of time. More research is needed.

Kava

Kava is a perennial shrub native to islands of the South Pacific. It has been ingested there as part of local culture. It has a relaxing effect.

Kava has been associated with liver toxicity: there have been cases of liver failure necessitating liver transplant, and there have been fatalities. As a result, the sale of kava is restricted in Canada.

Here is a reference about the liver toxicity issue:

http://www.ncbi.nlm.nih.gov/pubmed/15068826

In this 2008 article from a liver disease journal, cases of kava toxicity are reviewed. It is concluded that liver damage is a rare side effect of kava. It also found that many of those experiencing liver toxicity had used higher doses of kava, for longer periods of time, than recommended.

http://www.ncbi.nlm.nih.gov/pubmed/18989142

Effectiveness:

Here is a 2009 prospective, randomized, controlled study from Australia, in which 3 weeks of kava treatment (250 mg kava lactones per day) had minimal side-effects and led to substantial, clinically significant improvements compared to placebo in generalized anxiety symptoms and depressive symptoms:

http://www.ncbi.nlm.nih.gov/pubmed/19430766
As a critical commentary here, I think that 3 weeks is a VERY short study period, and therefore has limited clinical relevance. A great many approaches can relieve anxiety over a brief period of time (e.g. benzodiazepines); it's of much greater interest to see what happens after 3 months, or after 3 years!

Here is a 2003 Cochrane review, showing significant benefits in anxiety symptoms from kava treatment:

http://www.ncbi.nlm.nih.gov/pubmed/12535473

Here is a negative study from 2005, which showed that neither valerian nor kava differed from placebo in relieving anxiety or insomnia. The study participants were recruited on the internet, and were sent the blinded medication or placebo through the mail (another example of an interesting new study design):

http://www.ncbi.nlm.nih.gov/pubmed/16010204

In conclusion, kava seems promising as a treatment for anxiety. But there appears to be a small risk of very dangerous liver toxicity. It will require ongoing study to clarify risks vs. benefits, or to discover ways to minimize the risk of liver damage.

Valerian

Valerian is a perennial flowering plant native to Europe. Its sweetly-smelling flowers have been used to make perfume. Extracts from valerian root have been used as natural remedies in the treatment of insomnia and anxiety since ancient times.

Here is a review of the evidence:


This is a reasonably-done randomized 2009 study showing no effect of valerian vs. placebo in arthritis patients with insomnia:
http://www.ncbi.nlm.nih.gov/pubmed/19114414

This interesting 2007 study--in which subjects were recruited via a TV health program, randomly mailed placebo or valerian, with results collected on-line--showed a very slight improvement in symptoms with valerian, with no differences in side effects, compared to placebo. Subjects in the valerian group took 3600 mg of Valeriana officinalis one hour before bedtime, for 14 days. Perhaps the most significant bottom-line result from the study to report here is that 9.1% of the valerian subjects reported feeling "better or much better", compared to 3.7% of the placebo subjects, after the end of the study period.
http://www.ncbi.nlm.nih.gov/pubmed/17940604


Here is a 2007 review from a sleep medicine journal, concluding that valerian is safe but not effective in the treatment of insomnia:
http://www.ncbi.nlm.nih.gov/pubmed/17517355


Here's a 2006 Cochrane review, showing no evidence of valerian helping with anxiety disorders (mind you, the amount of data is very small):
http://www.ncbi.nlm.nih.gov/pubmed/17054208

Here's one positive 2005 study from Sleep, showing a modest benefit in sleep parameters and quality of life, from 28 days of a valerian-hops combination, compared to placebo, in the treatment of mild insomnia:
http://www.ncbi.nlm.nih.gov/pubmed/17054208

Here's an interesting reference suggesting that valerian could have been the first treatment for epilepsy: but its potential benefit would have been extremely inconsistent, and at this point it is certainly not a practical treatment for epilepsy.
http://www.ncbi.nlm.nih.gov/pubmed/15509234

There are some other articles of dubious quality, which I found in some of the herbal medicine journals.

There could be dangerous interactions between valerian and other medications:
This is a case report of side effects with valerian + lorazepam:
http://www.ncbi.nlm.nih.gov/pubmed/19441067


In conclusion, I am not impressed with the evidence about valerian. It does appear to be quite safe. Mind you, there does not appear to be a good evidence base about possible dangerous interactions with other compounds. I recommend avoiding it, or using it with extreme caution, if you are taking other psychotropic medications. It may have modest benefits for some people, but for the vast majority the evidence suggests that it does not differ from placebo.

Valerian-based perfumes or scented oils might be pleasant and safe to use as aromatherapy for insomnia or anxiety, in conjunction with other relaxing activities.

Herbal Supplements & Vitamins

I'm starting a series of posts based on some questions that were sent in by a visitor (A.E.).

Here's the first question:
1. Herbal supplements and vitamins: What are your views on therapeutic value of multivitamins, Valerian, Kava, Inositol, Passion Flower, and so on?

-I think the risk:benefit ratio of multivitamins is quite favorable. I've written a few other posts about vitamins. With respect to mood or brain function in general, there may be particular benefit from folic acid, thiamine, and higher doses of vitamin D. Standard dose vitamin-mineral supplements are probably harmless at worst (as long as you get a good-quality brand--there's some evidence of dangerous impurities such as lead, in some ). Many people have poor diets, and a supplement could at least help prevent deficiencies in vitamins and iron which may further obstruct recovery from mental health problems. Supplements should not be a substitute for improving the healthiness of one's overall diet (you still need to eat your vegetables even if you're taking vitamins!)

Selling supplements is a huge business: the world market has about $180 billion of annual sales, and is rapidly growing (reference: http://www.nutraceuticalsworld.com/articles/2008/04/dietary-supplements-the-latest-trends-issues).
This is comparable in size to the $440 billion annual market size of the pharmaceutical industry (reference: http://www.valuenotes.com/Prabhudas/pl_pharma_31Mar09.asp?ArtCd=143465&Cat=I&Id=12).

I think we need to be wary of the sales tactics that go on in the dietary supplement business, especially since the quality of research in this area is, for the most part, quite primitive. If you walk into the nutritional supplement area of a health food store or pharmacy, you may be bombarded with advertising, possibly a sales person offering you attention, concern, and apparent expertise--and all of this is in the context of all sorts of other obviously healthy things, perhaps organic vegetables, right next to you. It is a biased environment. Proximity to healthy food and healthy people does not constitute evidence of effectiveness! Yet, there are some supplements that could be helpful. Just be wary of the hype, pseudo-scientific claims, and sales jargon, etc.

I'll write separate posts about valerian, kava, passion flower, and inositol.

In the meantime, here's a reference to a 2006 review in The British Journal of Psychiatry about complementary medicines in psychiatry. I recommend having a look at the whole article at a library:
http://www.ncbi.nlm.nih.gov/pubmed/16449696

Sleep & Napping Improve Memory & Learning

Sleeping after learning improves consolidation of memory. Slow-wave sleep, which tends to occur in the first few hours after you fall asleep, is particularly important for memory consolidation. In one clever 2007 study published in the presitigious journal Science, subjects were exposed to an odor when learning a task. If they were exposed to that same odor during subsequent slow-wave sleep, their retention of the learning task was significantly improved. Here's the reference:
http://www.ncbi.nlm.nih.gov/pubmed/17347444

This suggests a simple aromatherapy technique to enhance your studying: infuse your study environment with a distinct, pleasant fragrance (for example, try an aromatherapy oil) -- then infuse your pillow with the same fragrance afterwards. During an exam or test, try infusing the same fragrance on your skin or clothes (just don't overdo it, or you might irritate the people writing their exams next to you!)

Furthermore, there is evidence that brief naps (60-90 minutes) in the middle of the day can help with memory consolidation, motor learning, and can also prevent the deterioration of mental and physical performance which tends to happen in a long day. Here is one reference about this:
http://www.ncbi.nlm.nih.gov/pubmed/12819785

There's a lot more research on sleep & learning. All of it supports the practice of healthy sleep habits in the life of a successful student. Many students have a very unhealthy, disrupted, perhaps heavily-caffeinated sleep schedule, particularly while "cramming" during the week of exams or other tests. This is hard on the body, physically and emotionally; it also leads to inefficient learning.

So, consider good sleep to be a component of your studying. And a nap after a bout of hard academic work can help you learn better.

Antidepressant Combinations for Resistant Depression

In many cases, a single form of therapy does not relieve symptoms of depression or anxiety. For every person, I recommend a range of healthy lifestyle changes, and I usually would encourage psychotherapy. For many, I encourage trials of antidepressant medication as well. For a significant number of people, a single medication does not relieve symptoms. In these cases of treatment-resistance, it can help to search for an effective combination of several medications. In this post, I will discuss the evidence-based foundation for combining antidepressants.

I find that several different antidepressant combos are worth trying, including an SSRI + mirtazapine, venlafaxine + mirtazapine, or an SSRI + bupropion. Adding trazodone to another antidepressant can be helpful for sleep, although I am less convinced of this combination substantially improving depressive symptoms. Combining newer antidepressants with older tricyclics is another area of interest, which I think we should be open-minded about, but I don't tend to prescribe tricyclics very often, mainly due to concerns about safety and side-effects. There are far fewer careful studies of antidepressant combinations compared to studies looking at single medication treatments, so the level of evidence in this area is not very strong yet. But here are a few references to existing articles from the research literature (I will try to expand my list over time):

http://www.ncbi.nlm.nih.gov/pubmed/19345072
This is a 2009 article from a Montreal group (Blier et al.) showing that a combination of mirtazapine + SSRI (paroxetine) led to significantly more improvement in depressive symptoms over 6 weeks, compared to groups taking either medication alone. The combination was well-tolerated for the most part-- in particular there was little difference in side effects experienced by the combination group compared to the group taking mirtazapine alone. Unfortunately, there are conflict-of-interest problems here: the study was funded by Organon, the mirtazapine manufacturer. And several authors of the study were "consultants" paid by the drug manufacturers for speaking engagements. The continued behaviour of psychiatrists accepting corporate money to give "educational lectures" is unfortunate. Usually large sums of money are involved. Please see my posts on industry-sponsored research: http://garthkroeker.blogspot.com/2008/11/biases-associated-with-industry-funded.html and http://garthkroeker.blogspot.com/2009/05/my-experiences-with-industry.html

Here's another recent article (2010) by Blier et al, again making a strong case for using combination antidepressants right from treatment initiation: http://www.ncbi.nlm.nih.gov/pubmed/20008946

http://www.ncbi.nlm.nih.gov/pubmed/18832958
This is an open study looking at combining escitalopram (Cipralex) with bupropion in chronic depression. There was no placebo or comparison group, so the study has a weak design. But it shows the combination was quite well-tolerated, and led to 50-60% of patients experiencing a remission of symptoms after 12 weeks, which in general is a better result than most single-agent trials, especially in chronic depression. The study was funded by NIMH, which reduces the likelihood of bias.

http://www.ncbi.nlm.nih.gov/pubmed/16165100
This is a 2006 review from Biological Psychiatry looking at combinations of bupropion with SSRIs. It is a good paper, but really most of the evidence presented is of mediocre quality. It does support the idea of using bupropion-SSRI combos, to improve treatment response in depression, and also to reduce SSRI-induced sexual side-effects such as delayed or inhibited orgasm.

http://www.ncbi.nlm.nih.gov/pubmed/15539864
This interesting 2004 paper is looking at the treatment of patients with depression plus chronic headache, using citalopram alone, or amitriptyline (a tricyclic antidepressant) alone, for 16 weeks. Then, a combination of the two medications was given to non-responders, for a further 16 weeks. The combination group showed substantial improvement in both headache and depression.

http://www.ncbi.nlm.nih.gov/pubmed/14744472
This is an important 2004 study from Biological Psychiatry showing that 6 weeks of a fluoxetine (SSRI) + desipramine (tricyclic) combination was more effective than either drug alone, in treating depressed patients admitted to hospital. While similar proportions (about 35-50%) of patients failed to respond to any of the three treatments, those patients who did respond improved much more with the combination. That is, the combination treatment led to a significantly higher chance of total remission compared to either single antidepressant treatment. The study was funded by NIMH.

http://www.ncbi.nlm.nih.gov/pubmed/12172337
This 2002 study looked at several options to treat non-responding depressed patients taking fluoxetine: the first group took a higher dose of fluoxetine (40-60 mg/d), the second group took a combination of regular-dose fluoxetine + desipramine, and the third group took fluoxetine + lithium. The results favoured the first strategy, of maximizing the dose of fluoxetine, instead of combining with something else. However, this result is not very useful, since normally we would maximize the dose of a single agent first anyway, before resorting to a combination. Yet the study does show that combining is not necessarily the best first step in addressing treatment-resistance. It was funded by NIMH.

http://www.ncbi.nlm.nih.gov/pubmed/8988452
This is one of the few studies looking at trazodone combinations: in this case, trazodone+fluoxetine showed some promise in treating resistant depression.

http://www.ncbi.nlm.nih.gov/pubmed/1548249
A weak old study from 1992 showing that trazodone can sometimes help as a combination with an SSRI (in this case, fluoxetine). 3 out of 8 depressed patients in this study improved with the combination (of course, this means that 5 out of 8 did not improve).

http://www.ncbi.nlm.nih.gov/pubmed/19415584
This is a 2009 review article on combining antidepressants. It is in German, which makes it hard for me to read!

MDMA (ecstasy): risks and benefits

"Ecstasy" is a common recreational drug. Chemically, it is known as MDMA, or 3,4-methylenedioxymethamphetamine. It is a type of chemically modified amphetamine compound which causes a release of serotonin and other transmitters from brain cells. It probably has a variety of other pharmacological effects.

MDMA has been shown in many studies to be neurotoxic, particularly causing harm to the cells in the brain which produce serotonin. There is evidence that MDMA can cause permanent harm or cell death. These studies have been done using rodents, monkeys, and using laboratory cell cultures. The neurotoxicity seems to be associated with, or magnified by, the increase in body temperature caused by ecstasy ingestion. Here are a few of the many references about this:
http://www.ncbi.nlm.nih.gov/pubmed/1379014
http://www.ncbi.nlm.nih.gov/pubmed/18991870
http://www.ncbi.nlm.nih.gov/pubmed/16884865
http://www.ncbi.nlm.nih.gov/pubmed/12464456

But here is a paper describing long-term MDMA exposure in monkeys, which did not lead to chemical evidence of neurotoxicity:
http://www.ncbi.nlm.nih.gov/pubmed/15039771

An important body of research is the Netherlands XTC Toxicity (NeXT) study. This 2008 paper from the NeXT study describes a prospective follow-up of new low-dose ecstasy users, and found evidence through functional brain imaging of neurotoxicity in the ecstasy-using group:
http://www.ncbi.nlm.nih.gov/pubmed/18842607

Here is another similar 2007 paper published in Archives of General Psychiatry describing a slight reduction in verbal memory performance in individuals who had used even just a few doses of ecstasy, compared to individuals who had not used any:
http://www.ncbi.nlm.nih.gov/pubmed/17548754

However, this paper gave rise to a good debate in subsequent issues of this journal. Basically, neither group in the study declined in memory performance, it's just that the non-ecstasy group improved more than the ecstasy group on re-testing. The ecstasy group included some people who had used much more than others. Also, the ecstasy-using group may have been more anxious about negative memory effects, since they had been warned about this possibility in advance. Such anxiety can impare test performance. The ecstasy-using group may have taken drugs tainted with impurities. A very important point I would add is that most people who use ecstasy recreationally do so in a chaotic, loud environment such as a rave--the drug may act as an emotional or interpersonal "amplifier", which in the case of a rave, could give rise to an amplification of social chaos. Also such an environment might lead to a higher degree of hyperthermia, which is associated with worse neurotoxicity. Use of ecstasy in a controlled, gentle, intimate environment might be much safer.


Here's a reference to a 2009 British Journal of Psychiatry study showing no difference in serotonin transporter binding between groups of former MDMA users, other drug users, and controls with no history of street drug use:
http://www.ncbi.nlm.nih.gov/pubmed/19336788?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum


This is a randomized, double-blind study looking at physical and emotional effects of acute MDMA ingestion, at low (1 mg/kg) and high (1.6 mg/kg) doses. It did not demonstrate hyperthermia as an effect of the drug, rather it implies that hyperthermia is caused by the environmental situation in conjunction with the drug (e.g. vigorous activity dancing indoors in a crowd).
http://www.ncbi.nlm.nih.gov/pubmed/18626271

There may be therapeutic applications for MDMA. The subjective effects of the drug can be to dramatically increase a feeling of openness, empathy or connectedness with other people, both on an emotional level and also sensually or physically.

Here are some references about this:
http://www.ncbi.nlm.nih.gov/pubmed/19273493
{this is a brief 2009 review of the subject of possible psychotherapeutic uses of MDMA, such as in anxiety disorders and PTSD}

http://www.ncbi.nlm.nih.gov/pubmed/19004414
{this 2008 study from Madrid showed that 50-75 mg doses of MDMA used in conjunction with psychotherapy for PTSD appeared to be physiologically and emotionally safe for 6 subjects. The study apparently had to be ended due to political pressures, before more subjects could be treated. Clearly, this is a controversial issue}

A psychiatrist by the name of Michael Mithoefer is trying to do research about using MDMA for treating PTSD. Here are some related sites:
http://scienceblogs.com/neurophilosophy/2007/11/mdma_for_ptsd.php
http://www.maps.org/mdma/protocol/
http://www.maps.org/mdma/

I think it is important to be open-minded about things outside the mainstream, and to recognize that mainstream research may sometimes dismiss ideas considered too controversial. Yet I recognize that the above sites have a biased agenda of their own which may undervalue important risk analyses published in the mainstream literature.

Answering questions relating to controversial issues, such as the potential use of MDMA as a therapeutic agent, requires a very neutral, unbiased research environment.

Aside from therapeutic possibilities in PTSD, it seems to me that MDMA might be worth investigating as an adjunct for couples' therapy, particularly for couples who feel inhibited or disconnected with each other. MDMA can foster a sense of connectedness, sensuality, and empathy. These three domains are often major weaknesses in troubled relationships. Apparently MDMA has been used in relationship therapy in the past, but the results have been poorly documented.

I have seen patients for whom MDMA use appears to have been part of a destructive long-term drug abuse pattern, which has most likely exacerbated mood, anxiety, and interpersonal problems. I have also seen a few patients for whom isolated experiences with MDMA have led to strong, memorable experiences of openness and intimacy with friends or partners.

In conclusion, I emphasize that MDMA is clearly a dangerous drug. It is most definitely neurotoxic. The risk of neurotoxicity is most likely higher with frequent, regular, or long-term use. Most "ecstasy" obtained on the street is tainted with numerous impurities--both deliberately, to reduce production costs, and as by-products of crude synthetic techniques; the impurities are likely to add to potential toxicity. I think that the setting in which MDMA is used most frequently (e.g. as a "dance drug") is likely to magnify its toxicity, in that hyperthermia is more likely, and any intimate emotional benefit is less likely. Many MDMA users are taking this drug frequently, over a period of years--I think this pattern has a very high risk of causing permanent neuropsychiatric harm.

We do not know yet if MDMA could have a positive therapeutic role for some people, but if it did, it would most likely have to be used only a very small number of times, in a carefully controlled, socially supported, comfortable, quiet, cool setting, by individuals who are already in a state of relative emotional calm. I suspect that a history of psychotic or bipolar illness, or a history of other street drug use or dependence, would greatly magnify the psychiatric risks of MDMA use. In the meantime, the existing research shows that any possible benefits would have to be weighed against very substantial risks. It remains an illegal drug in most jurisdictions.

Eating Disorders

Disordered eating is a complex problem which takes a variety of forms.

Anorexia nervosa is characterized by restrictive eating behaviours and excessive exercise which lead to medically dangerous weight loss.

Bulimia nervosa is characterized by binge-eating, and by purging (most commonly, self-induced vomiting). During binges, people often feel out of control, unable to stop.

In many cases, individuals have a mixture of anorexic and bulimic symptoms, without having a full syndrome of anorexia or bulimia.

In most cases of any eating disorder, there is a prominent disturbance of body image. Individuals may feel disgusted with their physical appearance. There may be an extremely strong preoccupation with fat. Fat (the word itself, as well as everything it represents) becomes something to be feared, avoided, and reviled. Any perception of normal subcutaneous fat is met with self-criticism or loathing. A perception of becoming thinner can be met with a feeling of satisfaction or addictive euphoria. Dietary fat, and dietary calories, often become subjects of intense preoccupation. Planning meals, or thinking about past meals, can lead to a great deal of anxiety. Eating socially with others can be extremely difficult. Situations in which people are more physically exposed (e.g. swimming pools, or the outdoors on a hot summer day) can cause increased self-consciousness and consequent self-loathing. Therefore, these situations are often avoided. Physical comparisons with other people can intensify symptoms. Many eating disorder behaviours (such as binges and purges) occur in secret.


Eating disorders can be medically dangerous: severe anorexia nervosa can be fatal. Other metabolic abnormalities from starvation or purging can cause weakness, cognitive impairments, bone demineralization, and abnormal heart rhythms. Repeated vomiting can cause damage to the esophagus. Overall poor nutrition makes it hard to treat other mental health problems, such as anxiety or depression.

In the treatment of eating disorders, sometimes a hospital stay is needed if weight is dangerously low.

Effective long-term resolution of severe symptoms can begin with an intensive multi-disciplinary day program, and may require lifelong treatment.

But here are a few basic ideas that I think can help in a less intensive outpatient setting:

1) It is important to be well-educated about basic nutrition -- to know what your body needs in a day, in terms of calories, fat, protein, vitamins, etc -- and to have a good sense of what foods might contain this balance of nutrients in a typical day. A consult with a dietician can be helpful.

2) Regular meals are important. Having regular meals can reduce the tendency to binge, since hunger will not build up as intensely. Experiencing meals is a component of behavioural therapy: planning the meal, obtaining & preparing the food, consuming the food, and then allowing the food to stay inside and be digested without purging. Each of these aspects may carry a lot of anxiety and stress. Having interpersonal support during these times can be powerfully helpful. Cognitive-behavioural techniques could also be helpful to manage the anxiety.

3)It can be important to recognize familiar patterns of thinking (e.g. having to do with fat or caloric calculations, dieting, weight loss plans, etc.) and practicing ways of directing attention away from these themes. It is also unhelpful to be bombarded with these themes in your social or cultural life, so I encourage a practice of redirecting social, cultural, or conversational energy away from subjects such as dieting, weight loss, etc.

4) Antidepressants such as SSRIs can help with bulimia (reference: http://www.ncbi.nlm.nih.gov/pubmed/14583971). The anticonvulsant topiramate can help reduce binge eating (references: http://www.ncbi.nlm.nih.gov/pubmed/18774432; http://www.ncbi.nlm.nih.gov/pubmed/14728106). Pharmacologic treatments for anorexia have not yet been very successful.

5) I think a very important element to work on is the confrontation and challenge of negative body image, its associated language, and its associated impairment in sensuality. Steps may need to be taken to stop or challenge "negative self-talk" and criticism about your body--about the way your body looks in a mirror, or the way your body feels to touch. This negative self-talk, and the ensuing negative emotions, need to be replaced by affirmations and by enjoyment. I think this type of work needs to be done every day. It can sometimes require work to gain pleasure from something, or to learn how to experience pleasure: this is a theme strongly present in the treatment of depression as well. Actually, I think it is a theme present in life generally -- we need to learn and practice something, to be with it consistently, in order for love or enjoyment to grow.

6) Similarly, I think it is important to reclaim the sensuality of food: the process of planning, preparing, consuming, and digesting food needs to be transformed from a source of dread or anxiety to a set of simple life pleasures. I think this type of sensuality should be emphasized in behavioural therapeutic techniques. Mindfulness meditation techniques can be helpful along these lines.

Antidepressants and Bone

There is some evidence that antidepressants, particularly the serotonin reuptake inhibitors, can reduce bone density, and increase the risk of fractures. This risk would be most pertinent in an elderly population.

Serotonin is a relevant factor in bone metabolism, so it is important to consider the potential impact of serotonergic antidepressants on bone health.

Here's a study showing an association between depression and reduced bone mineral density. Depression itself is an understandable cause for bone mineral loss, since it is associated with fatigue, therefore less exercise, worse nutrition, and increased stress hormones such as corticosteroids. In this study, antidepressant use was independently associated with bone mineral density loss in women. It is a retrospective analysis from a large catchment area study involving over 1000 people, who were followed since 1981.
http://www.ncbi.nlm.nih.gov/pubmed/19126857

There are some other studies showing an association between antidepressant use (especially SSRIs) and fractures due to fragile bone. One of the better such studies was published in 2008, looking at the incidence of fractures in a large population-based cohort involving 7983 people aged 55 and over. Importantly, the authors attempted to control for the impact of depression itself on fracture incidence, and basically showed that current SSRI use approximately doubles the risk of fractures:
http://www.ncbi.nlm.nih.gov/pubmed/18626268

There is one important prospective animal study, which shows a small effect of SSRI treatment on bone quality over a 6-month period:
http://www.ncbi.nlm.nih.gov/pubmed/17163489

In conclusion, it is important to know that antidepressants could possibly reduce bone density, and therefore contribute to an increased risk of fractures in the elderly. If antidepressant therapy is needed, it is especially important to encourage activities which protect bone health, such as regular exercise, and good nutrition (including ample calcium and vitamin D in the diet). Non-SSRI antidepressants such as tricyclics may have a smaller effect than the SSRIs. Bone density testing could be indicated, as could medication treatments to protect bone mineralization. These issues should be discussed with your family physician and your psychiatrist.

Long-term stimulants & ADHD

The long-term use of stimulants such as methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and mixed amphetamine salts (Adderall), in the treatment of attention or behaviour problems in children and adults, has been a controversial issue.

Symptoms of so-called ADHD include inability to sustain attention while doing academic, social, domestic, or work activities; restlessness, and inability to sit quietly or wait patiently. Of course, everyone has difficulties in these domains at times. The diagnosis of ADHD is intended to apply to individuals whose symptoms are so severe in these areas that it causes serious, ongoing problems functioning socially, academically, and with other life tasks. Those with an ADHD diagnosis are much more likely to drop out of school, to be unable to maintain jobs, to have difficulty maintaining friendships, and to have conduct problems ultimately leading to problems with the law, etc.

It is abundantly clear, from careful research, that stimulants improve symptoms of ADHD, and associated problems with social behaviour and disordered conduct.

I do not see good evidence that stimulants adversely affect personality traits or sense of self. Rather, in many cases, the experience of having severe untreated ADHD symptoms adversely affects personality traits and sense of self.

I will add to this post later, to discuss potential adverse effects from stimulant therapy. But stimulants are generally well-tolerated, with a low risk of serious adverse effects for most people.

Existing psychosocial treatments can help ADHD symptoms as well, but they do not work as well as stimulants, and--surprisingly--combining psychosocial treatments with stimulant therapy does not work much better than stimulants alone, except possibly for some individual cases. Here is some evidence, from a 2008 meta-analysis, for this finding:
http://www.ncbi.nlm.nih.gov/pubmed/18068284
Here are a few other important studies pertaining to long-term stimulant use:

This 5 year prospective study shows that stimulant therapy substantially reduces the rate of smoking and substance use disorders in adolescents with ADHD:
http://www.ncbi.nlm.nih.gov/pubmed/18838643

About 20% of ADHD adolescents treated with stimulants over 5 years developed a substance use disorder, compared to 55% of ADHD adolescents not treated with stimulants.

Stimulant-treated adolescents also had much lower rates of smoking. This is a very strong and compelling study, showing profound reductions in addictive disorders as a result of long-term stimulant treatment.


This 2008 study looked at a group of 169 children with ADHD, and followed up on them 9 years later:
http://www.ncbi.nlm.nih.gov/pubmed/18928410

The children who had taken stimulant treatment for their ADHD fared better than those with ADHD who had not taken stimulants, in terms of academic performance (as measured in several different ways). Neither ADHD group performed as well as a comparison group without ADHD.


This 2007 study from the Journal of Developmental and Behavioral Pediatrics is particularly strong, in that it looks at an entire birth cohort (all 5718 children born in Rochester between 1976-1982, of whom 370 with ADHD were identified):
http://www.ncbi.nlm.nih.gov/pubmed/17700079

It looked at long-term outcomes, over an average of 18 years. The study shows reduced absenteeism, reduced likelihood of being held back a grade, and slightly higher reading test scores, for ADHD children receiving long-term stimulant therapy.

Reading scores were particularly higher in the children who had received high doses of stimulants for longer periods of time.

The stimulant group did not differ from the non-stimulant group with respect to sociodemographic variables or duration of follow-up. The study was retrospective and was not randomized, yet it remains a very strong piece of evidence about long-term effects of stimulant treatment for ADHD.


I think these findings emphasize a number of things:
1) stimulants work very well for ADHD symptoms
2) stimulants unfortunately only have a slight effect on long-term academic outcomes
3) existing psychosocial treatments work modestly well on their own, but for most people do not add to the benefits of stimulants. The psychosocial treatments did not improve long-term academic outcomes. The duration of psychosocial treatment did not correlate with better improvement in symptoms, so the weakness of existing psychosocial treatments is not likely due to inadequate length of treatment.
4) long-term stimulant therapy may substantially reduce the risk of ADHD kids getting into alcohol use, substance use, or smoking problems. This finding is strong evidence against the idea that stimulant use increases the risk for subsequent addictive disorders.

I do think we need to keep working on better psychosocial treatments. I suspect that intensive, long-term, individualized treatment, with a style which suits the personality and strengths of each person, will be most effective. And I suspect that such treatments would need to be combined with positive, supportive milieux at home, school, work, and in peer relationships.

I will add to this post, or write a sequel post, to discuss other treatments for ADHD, such as atomoxetine, antidepressants, EEG biofeedback, dietary modification, and some newer psychosocial treatment ideas.

Direct personal requests for help

I encourage all of you who might be searching for help, waiting for help, or struggling with existing help, to be patient, to be brave, to hold onto hope.

At times I have had some direct personal requests for help from individuals who are not currently my patients. I feel that I have to stick to a policy of not being able to respond directly to such requests, as I feel that a direct response would, for me, cause me to feel a professional duty to maintain ongoing care.

But, once again, I do encourage all those who are struggling to hold on, to be patient, to be brave, to be open-minded about your options for new things to try, to hold onto hope.

For those in the Vancouver area, I remind you of some of the local resources:
http://garthkroeker.blogspot.com/2008/12/finding-help.html
If local resources are failing to keep you afloat, please keep an open mind about using emergency services, such as the local hospital emergency rooms.

My Experiences with Industry Sponsorship

Around 2001, when I was a mood disorders fellow, I was asked to do an educational lecture by Organon, the manufacturer of the antidepressant mirtazapine. The company clearly wanted one of the more prominent mood disorders research psychiatrists to do the lecture--but since no one else was available, they settled for me. It was common practice for research psychiatrists or other perceived "leaders in the field" to be paid by drug companies for "educational lectures" attended by family physicians or other psychiatrists, usually at expensive restaurants or lavishly-catered hotel conference rooms (the drug company footing the bill, of course); I think this common practice remains. To be fair, I think everyone assumed that this was all fine, even a useful educational service. Probably many of those involved in this practice still believe that. And perhaps many of these lectures are useful educational services to some degree, it's just that both the lecturers and the recipients may be unaware of the biases involved. Anyway, my lecture was supposed to be about treating resistant depression. I was provided by the company rep with numerous powerpoint slides about mirtazapine to include in my lecture. I did the lecture, and was paid generously for it. I included a few of the slides about mirtazapine, but I truly tried to give a lecture broadly about treating resistant depression, and discussed mirtazapine for only about 20% of the talk. Clearly the company rep was not impressed with my performance, and I was never again asked to do a lecture for them. I'm glad of that, since the more one does these things, the more one can be convinced that it is professionally appropriate, despite the obvious biases involved.

Around 2000-2001 I was involved in a clinical study of a new drug. The drug company sponsored the study, flew everyone business-class to Monaco (on the French Riviera), and put us up in a lavish 5-star hotel, to attend an introductory meeting regarding the study. Such meetings, in my opinion, are utterly needless expenses. Introductions and instructions about a study can be done without transcontinental travel. Training for rating scales, etc., could be done in some other simple, standardized way, without any need for travel. I did enjoy the trip, and I wouldn't doubt that it contributed to my having a more favourable view of that company's products in the following years.

Also around 2000-2001 I was involved in another clinical study. The drug company, also sponsoring the study, flew everyone business-class to Miami, Florida, and put us up in a famous 5-star hotel. By this time I was starting to have more questions about the neutrality of the research, under these circumstances. Something that struck me during that trip was my observations of the company reps meticulously preparing their video presentation for us -- they were preparing a show; it was basically a slick info-mercial, sound-effects and all. I was also struck by the fact that no one around me seemed to notice this or have a critical view of it. I felt like, on the one hand, we were being treated like royalty, but on the other hand we were simply being bought. I realize that it is good for companies to make participation in research projects attractive to everyone involved. It can be frustrating work to recruit patients for clinical studies, and many psychiatrists would rather not take time away from other aspects of work to participate in research. Research is important, and maybe travel & adventure could be fair aspects to enjoying the life of a researcher. BUT -- the travel is really not necessary at all. It is an extravagance. Information and training about a research protocol can happen locally. Other communication can happen over the phone, over the net, or over a video link. The other expensive extravagances just reduce the neutrality of the study, and also bias all participants (many of whom are "leaders in the field" who often influence other practitioners) to have and convey a more favourable view of the company's products, irrespective of the results of the particular study.

I think it would be interesting to have disclosures in research papers not only about the authors' affiliations with, or income received from, the drug companies, but also about the travel expenses paid by the companies for meetings pertaining to the study in question.

A more mundane aspect of industry sponsorship, during my residency between 1995-2000, was the weekly phenomenon of the "drug lunch." Basically, during almost every group meeting or rounds, food would be provided by a drug rep--usually quite a tasty lunch.

A continuing aspect of industry sponsorship is the distribution of free samples. At times I find this quite useful, to help someone get started on something right away, without the time or expense of a pharmacy visit. At other times, people have not been able to afford medication (the most common psychiatric medications are available for free in BC, through a government plan, but many more exotic medications are not covered by this plan): in some cases, the drug companies have provided a free "compassionate release" supply of medication for extended periods of time. Yet, I recognize that these phenomena lead to bias. The presence of a particular sample can influence the choice of which particular medication to recommend, particularly when the different choices are all similarly effective.

I realize this post may come off sounding like some kind of anti-corporate rant. I don't want to slam corporations too much though -- thanks to large companies, we have many more treatments which can profoundly improve quality of life, and which can save many lives. Profit-oriented motivations can drive productivity, competition, and better research. It's just that we can't be swept into the current of advertising and other biased persuasive tactics which companies use to sell more of their products. We can sympathize with the reality that companies behave this way, but as health care professionals, or as individuals contemplating whether or not to take a particular medication or other treatment, we need to have information which is clear, unbiased, as objective as possible.

Dietary Fat and Mood

Dietary fat is necessary for mental and physical health. Excessively lean diets may be mentally and physically unhealthy. A balanced diet, with abundant fruits and vegetables, at least 30% of calories coming from fat, and with carbohydrates coming from foods with a lower glycemic index (e.g. reducing amounts of simple sugars), is probably a sound recommendation for good physical and mental health.

The type of fat is important, though: trans-fats are particularly harmful (these are from hydrogenated oils including hydrogenated margarines). It is probably true that omega-6 fatty acids (present in vegetable or soybean oils), while necessary in moderation, are over-abundant in western diets. Saturated fats (such as from red meat and dairy) have been associated with worse health outcomes.

Yet, as I review the literature, I see that this assumption about saturated fat may not be as clear as what most people assume. I intend to review this literature more thoroughly, and add to this post later. It may be that saturated fats from plant foods such as coconut are more benign. And it may be that health problems associated with eating a lot of red meat are due to factors aside from the saturated fat content.

*As I look into the coconut oil issue, I see there is a tremendous amount of hype and salesmanship going on--it seems to be touted as some kind of miracle food, also with a variety of scientific claims (e.g. about medium-chain triglyceride content) intended to strengthen the persuasion. When I look into what the research literature has to say, there really isn't a lot out there. What is out there at this point is not very consistent. It is true that there are groups of people, such as in Polynesia, who consume a lot of coconut oils, apparently without developing high rates of heart disease. In any case, I think it is fair to say that coconut or coconut oil in small quantities could be reasonably included in a healthy diet.

Clearly healthy sources of fat include fish, olive oil, nuts, avocados, and canola oil.

There are several types of cholesterol in the blood, the main subtypes being LDL and HDL. High LDL is a risk factor for cardiovascular disease (e.g. heart attacks and strokes). HDL is considered "the good cholesterol", and it is quite clear that higher HDL levels reduce the risk of developing cardiovascular disease. It is possible to increase HDL by exercising regularly, maintaining a healthy weight, stopping smoking, increasing dietary intake of monounsaturated fat (e.g. olive oil & canola oils), and increasing soluble fiber in the diet (e.g. oats, fruits, vegetables, legumes). 1-2 drinks per day (but no more) of alcohol may favourably impact HDL levels and overall health. It is important to note that the actual cholesterol present in certain foods, such as eggs, has an inconsistent relationship with serum cholesterol levels (perhaps a stronger relationship in some people than others), and an even less consistent effect on health variables--so cholesterol content of foods need not be a particularly important variable to assess.
(reference:http://www.ncbi.nlm.nih.gov/pubmed/18726564

In this 1998 study from the British Journal of Nutrition, subjects initially consumed a diet with 41% of calories coming from fat, then half of these subjects switched to a low-fat diet with only 25% of calories from fat. The group with the lower-fat diet developed higher levels of anger, hostility, and anxiety compared to the group continuing the higher-fat diet:
http://www.ncbi.nlm.nih.gov/pubmed/9505799

In this 2008 meta-analysis from Annals of Behavioural Medicine, an inverse association is found between serum cholesterol levels and depression. It is an interesting and surprising finding, given that we recognize lower cholesterol levels as beneficial for your heart:
http://www.ncbi.nlm.nih.gov/pubmed/18787911


In this 2008 study, a group with chronic depression was compared with a group with normal mood, and it was found that depression was associated with lower HDL levels (i.e. lower "good cholesterol"), even after controlling for several confounding factors. This type of study is unfortunately a bit weak. Here's a link to the abstract:
http://www.ncbi.nlm.nih.gov/pubmed/18583011

Here's a reference to a 2003 article from Encephale reviewing some of the evidence about low cholesterol being associated with depression and suicide. The authors also suggest that inadequate omega-3 fatty acids compared to omega-6 fatty acids in the diet may be a contributing factor to higher rates of depression.
http://www.ncbi.nlm.nih.gov/pubmed/12640327

This is a small but convincing 2008 study which showed significantly lower cholesterol levels in suicidal patients with schizoaffective disorder, compared to non-suicidal patients with schizoaffective disorder, and compared to healthy controls. HDL (the "good cholesterol") was higher in the non-suicidal patients and in the control group. The groups did not differ significantly with respect to BMI, so the association between cholesterol and symptoms would not have been due to weight.
http://www.ncbi.nlm.nih.gov/pubmed/17850945

Here's another 2007 study showing low cholesterol levels in an elderly group with cognitive impairment, and in an elderly group with depression, compared to a healthy elderly group.
http://www.ncbi.nlm.nih.gov/pubmed/17712096

Here's a 2007 study showing strong association between higher HDL cholesterol and better physical functioning among the oldest elderly (over 80 years old):
http://www.ncbi.nlm.nih.gov/pubmed/17913756

Here's a 2004 review describing the many findings about higher HDL being associated with better physical and mental functioning in the elderly, and in particular that people who live over 100 years have higher HDL levels:
http://www.ncbi.nlm.nih.gov/pubmed/15557706

In this strong, prospective 2009 study following 1,468 nurses with type II diabetes, higher dietary saturated and trans fat intake, and a lower ratio of polyunsaturated fat to saturated fat in the diet, was associated with worse cognitive decline (those in the highest third of saturated+trans fat intake effectively aged an extra 7 years with respect to cognitive decline, compared to those in the lowest third):
http://www.ncbi.nlm.nih.gov/pubmed/19336640

Here's a similar 2004 article from Neurology showing worse cognitive decline associated with higher saturated fat intake, lower monounsaturated fat intake, and a lower ratio of polyunsaturated to saturated fat intake:
http://www.ncbi.nlm.nih.gov/pubmed/15136684

In this strong, prospective, randomized 2007 study from JAMA, a diet with a low glycemic load (e.g. reducing simple sugars and increasing complex, slowly-digested carbs) and 35% of energy coming from fat, was compared with a low-fat diet (20% of energy from fat), with follow-up over 18 months. The higher-fat, low-glycemic load diet led to better improvement (increase) of HDL levels, and considerably better weight control:
http://www.ncbi.nlm.nih.gov/pubmed/17507345