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.