Friday, February 13, 2009

Brainstem Stimulation - cranial nerves

There are some novel therapies such as vagal nerve stimulation or deep brain stimulation, which can improve symptoms of depression. These treatments may be increasingly important sources of relief for chronically suffering depressed patients-- particularly as the technology advances, becomes safer and more refined.

Here are a few links to references about these treatments:

http://www.ncbi.nlm.nih.gov/pubmed/16641939

http://www.ncbi.nlm.nih.gov/pubmed/19137233

Of greater interest to me in an outpatient office psychiatry practice, is an idea based on looking at trivially available techniques to accomplish "deep brain stimulation" or "vagal nerve stimulation", etc. All parts of the brain -- even the "deep brain", and even the vagal nerve -- are connected to all other parts of the body! Specific life events can obviously affect deep brain or vagal nerve stimulation, without requiring an implanted electrical device or neurosurgery! Some of these life events could be deliberately sought out as therapeutic strategies.

Something I've noted about some of these new, radical techniques, is that they involve stimulation of brainstem structures, often involving the cranial nerves. It seems to me that the cranial nerves are an extremely visceral set of portals through which stimuli are exchanged between the environment and the deep structures of the brain which regulate mood and consciousness. Here's a summary of all the cranial nerves, with speculations about techniques to "stimulate" them in a way that might be therapeutic:

Cranial Nerve I (olfactory): Stimulation of this nerve requires exposure to different scents. Aromatherapy is a familiar component of alternative health strategies. Here is some evidence from the mainstream medical literature, showing that aromatherapy can be helpful:
http://www.ncbi.nlm.nih.gov/pubmed/19125379
(a review article)
http://www.ncbi.nlm.nih.gov/pubmed/18178322
(a randomized study showing that the scent from lemon oil improves mood, compared to water or lavender, and regardless of expectancies or past experience with aromatherapy)
http://www.ncbi.nlm.nih.gov/pubmed/18713168
(a study showing improvement with lavender oil aromatherapy vs. controls in neuropsychiatric symptoms of elderly dementia patients)
http://www.ncbi.nlm.nih.gov/pubmed/17342790
(another study showing improvements in dementia patients with lavender)

Given the fact that there is virtually no risk to aromatherapy treatments, why not give it a try? It could help with sleep, relaxation, studying, or as a conditioning device (e.g. associating a particular odor with sleep, or with studying a particular subject, etc.)

Cranial Nerve II (Optic): Bright light therapy has a considerable evidence base. Probably looking at beautiful things in nature is good for your mood (I'll need to find a reference to prove this!). These images would have to pass through Cranial Nerve II, on their way to your brain.

Cranial Nerves III, IV, and VI: these innervate the muscles which move the eyes. There is a type of therapy called "EMDR" which calls upon patients to move their eyes back and forth as an essential part of the therapeutic technique. I suspect this acts as a conditioning phenomenon, which at once distracts the person, while perhaps permitting exposure therapy regarding uncomfortable thoughts or PTSD symptoms to take place in a more relaxed state, or in a state associated with therapeutic benefit. But maybe the "brainstem stimulation" from eye movements is an integral part of EMDR's therapeutic effect.

Here are some links to review papers or meta-analyses looking at EMDR:
http://www.ncbi.nlm.nih.gov/pubmed/16740177
(here, EMDR and CBT are both shown to be substantially and similarly effective in the treatment of post-traumatic stress disorder)

http://www.ncbi.nlm.nih.gov/pubmed/17636720

(a Cochrane review also showing EMDR and CBT to be the psychological treatments of choice in post-traumatic stress disorder)


Cranial Nerve V (trigeminal): this nerve transmits tactile sensations from the face into the brainstem. I do not know of any deliberate psychiatric therapy involving this nerve. But there is acupuncture. Also, there is massage, and in particular "facial treatments" (involving massage, aromatherapy, moisturizing creams, etc.) available in health spas--these seem to have a positive effect on overall well-being. I'd be curious to see a controlled study on this: in the meantime, though, it seems another risk-free thing to try.
http://www.ncbi.nlm.nih.gov/pubmed/19129675
(well, this is a pretty weak study -- but it's a start, and it involves a totally harmless treatment -- it shows reduction of anxiety in women receiving facial massage)

Cranial Nerve VII (facial): this nerve innervates the muscles of the face. As noted in a previous post, actions which affect facial musculature can affect emotion, just as emotion changes facial muscle tone (it's always interesting how these phenomena can work both ways). A branch of Nerve VII also conducts information about taste (gustatory sensation) from the tongue to the brain. I have no doubt that enriching one's culinary sensations in life has a positive impact on mood. But I'll have to look for a study to prove it.

Cranial Nerve VIII: the cochlear branch of this nerve transmits information about sounds from the ears to the brain. Hearing music, soothing sounds, and speech clearly affect mood and cognition. Noise, as I claimed in an earlier post, has a negative impact on mental health. Silence itself "rests" the cochlear nerve, which could itself be therapeutic (in moderation).
The vestibular branch of nerve VIII seems interesting to me as a prospective therapeutic target. This nerve transmits signals about balance, head position, and head movement to the brain. Sometimes individuals in an autistic or highly agitated psychotic state will stimulate their vestibular nerve by rocking repetitively. The action of a parent rocking a baby to sleep, or calming an agitated, crying baby, involves stimulating the baby's nerve VIII. It would be interesting to see if various stimulations of the vestibular nerve could be useful in adults, to treat anxiety, agitation, insomnia, or mood disorder. Balance exercises could be a start (perhaps some of yoga's therapeutic effects come from this). Maybe something like sleeping in a hammock, which would rock slowly, could be more soothing on this level, compared to a regular bed. Some people might find a boat to be very soothing (for others it would just cause nausea). If there are any engineers out there, reading this, it would be an interesting project to design a device which could be programmed to gently rock an adult back and forth (with different waveforms and frequencies).

Cranial Nerve IX: Glossopharyngeal. This nerve innervates your throat. The action of swallowing involves this nerve. People with anxiety states often have uncomfortable throat sensations, or problems with swallowing. It's hard to come up with therapeutic ideas directly relating to this one. Except perhaps the idea of eating really spicy food -- which stimulates not only taste buds but also sensory nerves (partly from Cranial Nerve V) in the mouth and throat. Strong culinary sensations can be a source of pleasure, and perhaps can also teach one to be more open about new things (I remember taking a long time getting used to wasabi on sushi after being introduced to Japanese food upon moving to Vancouver in 1995).

Cranial Nerve X: This is the vagus nerve that is stimulated electronically in an advanced surgical treatment for depression. The vagus nerve innervates the parasympathetic system of the body's viscera (e.g. it slows the heart, speeds up the bowel, etc.). One can train the vagus nerve through activities such as yoga, meditation, biofeedback, and through physical exercise.

Cranial Nerve XI: this nerve allows you to turn your head back and forth. Perhaps this could be an element not to forget in your exercise regime -- do some stretching and gentle exercises involving rotation of your head.

Cranial Nerve XII: this nerve allows you to move your tongue. Speech, singing, eating, and a variety of other pleasurable activities -- all involve your tongue. In anxiety states, people can have an exaggerated awareness of their tongue movements. Taking voice lessons or attending a voice coach can help build confidence, reduce social anxiety, literally help you "strengthen your voice"--a strong and clear voice, both metaphorically and literally, can be part of a healthy emotional life.

In conclusion, perhaps there are a variety of readily available techniques that can accomplish "deep brain stimulation" in ways that benefit your mental health, without actually requiring a neurosurgical procedure!

Singing

There are a number of reasons why singing (out loud!) can be beneficial for mood:

1) the parts of the brain, as well as the facial and pharyngeal muscles, involved in singing, are similar to those most active in positive mood states. This may seem a trite or ridiculous association, but it is supported by evidence, namely that voluntary actions associated with happiness, even if unconsciously initiated, lead to more positive mood. Here's a link to the abstract of a classic, amusing, 1988 paper by Fritz Strack, published in The Journal of Personality and Social Psychology (another great journal that I recommend following), demonstrating that changing the position of facial muscles leads to a change in emotional response:
http://psycnet.apa.org/journals/psp/54/5/768/

2) singing is active, yet relaxing; potentially social, yet individual; creative, yet structured

3) Fellow singers--if singing is done in a group--are likely themselves to be emotionally positive and encouraging, leading to a positive social environment.

Here's a link to an abstract demonstrating that choir singing leads to improved mood and reduced stress hormone levels:
http://www.ncbi.nlm.nih.gov/pubmed/15669447

Of note, actively singing music -- not merely listening to music -- was required to produce a beneficial effect.

Tuesday, February 10, 2009

Bipolar Depression

The depression which occurs in the context of bipolar disorder may have a variety of unique features (sometimes such a depression may occur BEFORE a clear manic episode has ever happened, so a depression with these features can sometimes be a warning sign of latent bipolarity, or a risk sign that bipolar disorder may develop in the future):

1) excessive sleep (rather than insomnia), along with marked physical lethargy
2) depression beginning early in life (during teenage or young adult years)
3) depressive episodes of short duration
4) depressive episodes having psychotic features (e.g. delusions)
5) other "atypical" depressive features, such as increased eating
6) Sometimes a very rapid response to antidepressants (e.g. within one or two doses)

Nevertheless, these features are not invariably present in bipolar depression; and many people may have depressive episodes with these features, who do not have bipolar disorder.

Conversely, in my opinion, there is one significant element from a person's history which points strongly away from a diagnosis of bipolar depression:

If a person has taken an antidepressant, especially at a high dose, and especially for a long period of time (over 3 months), and especially a tricyclic antidepressant or venlafaxine -- if a person has taken such an antidepressant on its own, without a mood stabilizer, and WITHOUT developing overt symptoms of mania, this is fairly strong evidence against underlying bipolarity.

Some of the recent evidence about treating bipolar depression leads us to question the role, value, or safety of antidepressants in the bipolar population.

http://www.ncbi.nlm.nih.gov/pubmed/18727689
(a 2008 review, showing little effect of antidepressants when added to mood stabilizers in treating bipolar disorder over at least 6 months of follow-up)

http://www.ncbi.nlm.nih.gov/pubmed/17392295

(this is from the New England Journal of Medicine--one of the world's leading medical journals--in 2007, and it showed, over 26 weeks of follow-up, that adding antidepressants to a mood stabilizer regime did not improve outcome, in fact the antidepressant group did not do quite as well)

Which treatments have an evidence base in bipolar depression?

1) Lamotrigine. It has the advantage of helping modestly with depressive symptoms with a low risk of causing mania. It may be true that some of the studies over the past few years have exaggerated the benefit of lamotrigine, however. In any case, it appears quite safe, and can be helpful for some people. There is a small risk of a very serious skin rash with this drug, otherwise it is quite safe and well-tolerated.

http://www.ncbi.nlm.nih.gov/pubmed/19200421
(a recent study looking at Lithium + Lamotrigine vs. Lithium + Placebo over 8 weeks of follow-up; the benefits of lamotrigine are significant but modest)

http://www.ncbi.nlm.nih.gov/pubmed/15003074

(this study also showed a benefit from lamotrigine, over a whole year, but there was no placebo group, so the results carry much less weight)

2) Other mood stabilizers, e.g. lithium, valproate, and carbamazepine. Unfortunately these drugs are probably more effective for preventing manic episodes than for preventing or treating depression. Yet, the combination of a standard mood stabilizer with another agent such as lamotrigine could be a valid step.

3) Atypical antipsychotics, e.g. olanzapine, quetiapine, and risperidone. These drugs undoubtedly are beneficial as mood stabilizers, possibly more so than the standard mood stabilizers such as lithium or valproate. There is evidence that antipsychotics + other mood stabilizers are additively effective in combination. They can be worth a try for treating bipolar depression. Unfortunately, if the bipolar depression is already characterized by excessive sleep, tiredness, and appetite, antipsychotics can sometimes make these symptoms worse. But if there are psychotic features with the depression, an antipsychotic can be an essential part of the treatment.

4) Omega-3 supplements : see my previous post

5) Light therapy: I have seen this be helpful at times. The light exposure may need to be carefully titrated (e.g. just a few minutes at a time), to prevent overstimulation or agitation. Light therapy requires the purchase of a 10 000 Lux light box, which could cost about $200-300.
http://www.ncbi.nlm.nih.gov/pubmed/18076544

6) Cognitive-behavioural therapy. Elements of CBT help with most anything, it seems to me (from learning to play the violin, to doing mathematics, to treating anxiety or depression from any cause). CBT can be adapted so as to be more tolerable and interesting (some of the workbooks can be hard to get through). I think its core features require daily written work, journaling, conducting a dialog with oneself about thoughts and emotions (hopefully to work at identifying forms of depressive thinking, and being willing to challenge such thoughts if they occur), and deliberately challenging oneself behaviourally to face fears, a little at a time. In bipolar disorder CBT may work best in conjunction with ideas that help to stabilize or structure daily behavioural rhythms (e.g. getting up regularly in the morning, having a routine, eating regularly, exercising, doing some intellectually challenging work, doing some creative work, going to bed around the same time, etc.). Of course, in depression of any sort, it can be extremely hard to initiate or maintain such lifestyle habits--if there is too much fatigue or lack of motivation to get started with very much, I encourage getting started with the very smallest of tasks or daily structures, and building from there; consistency is more important than amount.

http://www.ncbi.nlm.nih.gov/pubmed/18324665

7) Other psychotherapy: basic supportive care can be very important, provided there is a resilient, trusting therapeutic relationship

8) Antidepressants: despite the negative results of late, there are selected individuals for whom antidepressants may be very helpful. Over the past decade, bupropion has perhaps been the first antidepressant to consider, due to its lower rate of causing a manic switch, and possibly its higher likelihood of helping with the low energy states characteristic of bipolar depression. SSRI antidepressants have been the second-choice agents. MAOI's are probably lower risk with respect to causing manic switch, and the reversible MAOI moclobemide could be a good option. Venlafaxine and tricyclic antidepressants have been agents to avoid, due to their high risk of causing a manic switch.

References:
http://www.ncbi.nlm.nih.gov/pubmed/16449476

http://www.ncbi.nlm.nih.gov/pubmed/16880481

9) Stimulants: I have found that stimulants can be quite useful in bipolar depression, provided that they are not increasing psychotic symptoms or agitation. They have the advantage of working quickly, helping immediately with energy and attention, and often helping with mood. Furthermore, they can be withdrawn quickly if manic symptoms or agitation arises; if stimulants are withdrawn quickly, it causes a relative state of sedation. (Note that there is some evidence from a few older studies that stimulant treatment can actually reduce symptoms of mania) There are several older stimulants, such as methylphenidate (Ritalin), and dextroamphetamine (Dexedrine), and several newer formulations of these older drugs (e.g. Adderall). A newer, atypical stimulant called modafinil can be an option as well. However, modafinil is quite expensive and often not covered by medication plans in Canada.

References:
http://www.ncbi.nlm.nih.gov/pubmed/15383134
http://www.ncbi.nlm.nih.gov/pubmed/18980736

http://www.ncbi.nlm.nih.gov/pubmed/16974196

http://www.ncbi.nlm.nih.gov/pubmed/367183

http://www.ncbi.nlm.nih.gov/pubmed/3312177

(the above two references are to older, interesting studies showing that stimulant treatments actually helped REDUCE manic symptoms acutely--I cite this as evidence that stimulants are reasonable to use in bipolar patients, however I would not go so far as to recommend stimulants in the treatment of mania, as other anti-manic treatments are much more effective and accepted as a standard of care)


10) ECT:electroconvulsive therapy is unequivocally effective for treating both depression and mania. However, there may be a higher risk of mild but persistent cognitive side-effects in the bipolar population:
http://www.ncbi.nlm.nih.gov/pubmed/17653292

If there are "borderline" phenomena occuring in the context of bipolar depression, once again some of Dawson's ideas may be helpful (see my previous postings about borderline personality); these involve emphasizing the role and competence of the individual patient in choosing treatment options, and avoiding an authoritarian stance on the part of the therapist.

Other references:

http://www.ncbi.nlm.nih.gov/pubmed/18992784
(A recent study correlating early age of onset for depression with bipolarity, severity, recurrence, etc.)

http://www.ncbi.nlm.nih.gov/pubmed/18199233

(A review of diagnostic issues regarding bipolar depression)

Probabilistic Model of Psychotropic Medication Effects

This is an idea I have considered for many years. It fits with my overall view of a lot of evidence from treatment studies.

For many actions in life, an event either happens, or it doesn't. This seems obvious, I guess. You either throw a ball, or you don't. You either show up for work, or you don't. (Mind you, in my own case, I would say that my own modest level of athletic skill causes me quite often to "sort of" throw a ball, or "sort of" swim.)

In medicine, many actions are similarly unambiguous. The surgical removal of an appendix either happens, or it doesn't. An infection either responds to an antibiotic, or it doesn't. Clear.

Yet, I find that many treatments in medicine are much less clear.

In the case of psychiatric treatments, it has been a theory of mine that the drug (or therapy) may reduce the probability of a symptom occurring, in addition to, or instead of, directly reducing the symptom (or not). This phenomenon may be apparent not only in studies of populations, but in an individual.

Many disease processes are driven by multiple variables, which, together, alter probabilities of symptom recurrence. The variables may include genetic factors, environmental stress, etc. There may be a core phenomenon in nature, as manifest on a chemical, or even quantum-mechanical, level, of minute, truly random events, influencing a cascade of effects. The presence of a medication in the body may be just one more variable, influencing the likelihood of a symptom occuring, or developing, or advancing.

Some medications may appear not to be working, if a short-term view is taken. But in a longer-term view, it may be seen that symptom frequency and intensity is diminished. This is consistent with the theory that the medication affects probabilities.

This theory supports the idea that medications, and other psychiatric treatments, could have an important preventative role, beyond their role in an acute situation. And it encourages giving treatments a long period of time to work--at least months, if not years-- in order to most accurately assess effectiveness.

There have been some long-term studies which support this idea, but unfortunately most of the treatment studies in psychiatry have been relatively short-term (only a few months of follow-up, rarely more than a year).

Omega-3 Supplementation

Omega-3 fatty acids are present in a variety of foods.

The fatty acids EPA and DHA are present mainly in fish such as salmon, herring, mackerel, anchovies, and sardines. These fatty acids, especially DHA, are probably important for brain function, and are also found in the retina of the eye.

Another omega-3 fatty acid, ALA, is present from plant sources such as canola oil, flax, and walnuts. ALA may be converted in the body to DHA.

There is some evidence that there are health benefits from diets higher in omega-3 fatty acids, or diets supplemented with extra omega-3.

Of interest for psychiatry, omega-3 supplementation may be a safe adjunct in the treatment of depression. Fish oil is probably the simplest source of extra EPA and DHA.

The only problem with increasing fish consumption is the exposure to environmental contaminants such as mercury and PCBs. Fish oil capsules may actually have less of these contaminants than pure fish, especially if the oil has been refined to remove contaminants. In any case, I think the benefit-risk ratio is very favourable, and that 1-3 capsules per day of fish oil is quite safe. And I feel confident to recommend increased fish intake in the diet. For vegetarians, increased intake of walnuts, canola, and flax could be recommended.

http://www.ncbi.nlm.nih.gov/pubmed/18183532
(a review of the studies over the past decade looking at omega-3 supplements in mood disorders)

http://www.ncbi.nlm.nih.gov/pubmed/16741195

(a nice review from The American Journal of Psychiatry in 2006, summarizing epidemiological data associating low fish consumption with higher rates of mood disorder, and summarizing some of the treatment studies showing antidepressant effects of omega-3 supplements in depression, bipolar disorder, and borderline personality)

http://www.ncbi.nlm.nih.gov/pubmed/19156158

(this is a recent study showing beneficial effects of omega-3 supplements in children with bipolar symptoms;but it was not a randomized or controlled study)

http://www.ncbi.nlm.nih.gov/pubmed/19200125

(this is a recent local study analyzing fish oil supplements for environmental pollutant levels, such as PCBs. Based on this study, one should avoid supplements of products such as seal or shark oils, which have much higher contaminant levels.)

http://www.ncbi.nlm.nih.gov/pubmed/19139352
(one of the articles summarizing evidence that omega-3 intake reduces the incidence or progression of macular degeneration, which is a common cause of visual loss in those over 65 years of age).

http://www.ncbi.nlm.nih.gov/pubmed/19064523
(a huge study, published in 2006, involving data from over
40 000 people over 18 years of follow-up--it shows a slight reduction in cardiac disease associated with higher fish consumption, but no change in overall "major chronic disease risk". But, incredibly, and unfortunately, they did not include mood or other psychiatric disorders in their assessment of "chronic disease" outcomes. Yet, studies of this type exemplify that The American Journal of Clinical Nutrition is an excellent journal, a valuable and practical source of evidence-based health information which could guide nutritional choices).