Anti-Depressive Procedures
     by Richard Brown, M.D. 

Ed.- Dr. Richard Brown is one of the leading psychiatrists in New York and an advocate of cutting-edge international pharmaceutical technology.  He is also a  regular author of innovative medical books both for the public and professional alike.  His writings include Stop Depression Now and Alternative Treatments in Psychiatry published by John Wiley & Sons, Ltd, London, UK.  A forthcoming publication is Alternative Treatments in Brain Injury, published by the American Psychiatric Press, Inc., Washington, D.C.

In this article, Dr. Brown introduces to us some of his therapies and the success they have had with his patients. 

I first began to use International Anti-Aging Systems products from around the world nearly ten years ago. IAS was in fact brought to my attention by a patient who, having failed multiple antidepressants, had read scientific articles on the Internet which described the use of SAM-e in the treatment of depression. Since the patient had a resistant depression after multiple trials of conventional antidepressants and had difficulty with side effects, she was desperate to find an alternative.  Fortunately, she responded well to SAM-e with no side effects.  

Stop Depression Now with SAM-e 

Success with SAM-e in that patient led to my using it in hundreds more and eventually writing the book Stop Depression Now which has helped thousands of people who could never have come to see me in my office.

Let me give you some examples of a few of those patients.  

A middle-aged physician who had originally trained in the United States, but who has been practicing in a European country for some years now had experienced chronic depression.  He did not tolerate the side effects of conventional antidepressants well.  He was not able to respond to the antidepressants at a dose which was comfortable, because of side effects.  He read my book Stop Depression Now, followed the directions and treated himself with SAM-e and B vitamins.  

He contacted me after he had been well consistently for six months to thank me and also to discuss the use of SAM-e in his own practice.  He recommended SAM-e to several colleagues all of which rapidly improved after having failed conventional treatments.  

I have had numerous people contact me from England, France, Sweden, Australia and from all over the United States, including Hawaii, who had severe depressions that were unresponsive to all classes of conventional antidepressants and electroconvulsive therapy.  These individuals had been very ill, some with severe suicidal attempts, others bed ridden for years.  They were able to obtain SAM-e and responded completely with a return to normal life within several months and have maintained their recovery since then.   

SAM-e is not a panacea, but it clearly has many significant advantages.  It often works rapidly, although not always. Sometimes, as with conventional antidepressants, there may be a protracted course before response occurs. Secondly, it has far fewer side effects for most patients compared to conventional antidepressants. The most important side effect is the possible stimulation of a manic state, in the vulnerable person with bipolar or manic-depressive disorder.  Also, in the higher doses sometimes needed to treat serious depressions, it may cause loose bowels and other gastrointestinal upset.  Other side effects such as headache, jitteriness, or palpitations are rare. Its profile of action on the electroencephalogram of the brain is similar to tricyclic antidepressants.  However, SAM-e is more tolerable and often works more rapidly than tricyclics. 

In addition, SAM-e acts on the dopamine system (tricyclic antidepressants do not) and this may be important for a subgroup of depressed patients.  Tricyclic antidepressants may be especially helpful for more severe depressions, especially in the geriatric population. SAM-e may also be beneficial for physical illnesses including arthritis, liver disease, Parkinson's, and other medical conditions. Some patients have quite a dramatic response to SAM-e.  A subset of these may have a problem in their B vitamin dependent methylation pathways in the brain based on genetic variants.  Hopefully, further genetic research will enable us to identify these patients so that they can be started quickly on SAM-e, a highly effective treatment in this subgroup, rather than wasting time on other approaches.  Some patients have a good but modest response to SAM-e.  

In many of these cases SAM-e is best combined as an augmenting agent with other conventional antidepressants.  There are at least three studies using SAM-e in combination with conventional tricyclic antidepressants.  In my own practice, I find it also boosts venlafaxine (brand name Effexor®), so that I may use a much lower dose of the conventional antidepressant with good results.   

Tianeptine: A New French Anti-Depressant 

Another exciting product which most of my patients have been very happy with is tianeptine (Stablon®).  This French antidepressant improves the activity of the serotonin system by accelerating serotonin reuptake, but does not cause sexual dysfunction or weight gain.  It is helpful for anxiety as well as serious depression.  Of the last twenty patients I have treated with tianeptine, fifteen out of twenty have had very good responses with virtually no side effects.  The five who did not respond have had extremely refractory depressions, that have failed multiple medications and their chance of responding to any agent was extremely low.  The following cases are illustrative examples of patients who have responded to tianeptine.  

One woman is a 50-year-old married mother of three children who has had life long depression and anxiety.  The anxiety becomes extreme when she has to fly on an airplane. She frequently worries about having cancer.  These symptoms responded reasonably well to treatment with any SSRI (selective serotonin reuptake inhibitor) including fluoxetine, paroxetine, fluvoxamine, sertraline, and citalopram.  Unfortunately all of the SSRIs cause complete absence of sexual functioning and on average a thirty to fifty pound weight gain.  The patient found these side effects to be intolerable. The weight gain occurred despite dieting and exercising extremely vigorously for at least two hours a day, using both aerobic exercise and weight training.  The patient has had a very good response to the tianeptine with a concomitant weight loss back down to her normal body weight.  She is far happier being on this medication.  

Another patient is a single woman in her forties who has had mood instability and dysthymic disorder, with recurrent major depressions all her life.  She has failed all available classes of antidepressants and mood stabilizers, including lithium, three anticonvulsants and a smattering of other augmenting medications.  She had the first good treatment response in her life to tianeptine and has been consistently much better. For years I had become accustomed to frequent phone calls at night and over the weekends from this patient. I now rarely hear from her because she is doing so well. I must congratulate the French on finding an antidepressant that would help the serotonin system while allowing patients to enjoy both sex and food freely. 

Reboxetine: The Noradrenaline Reuptake Inhibitor

I have also found that reboxetine (Edronax®) has been extremely helpful for difficult to treat depressions. This selective norepinephrine reuptake inhibitor in some ways is like the tricyclic desipramine.  There is data suggesting that it improves social interaction more quickly than Prozac® in controlled trials. It does have somewhat less anticholinergic side effects than tricyclic antidepressants, but more than SSRI's.  However, it does not appear to cause difficulty with orgasm or delayed ejaculation.  It rarely will cause painful ejaculation in men. I found that in my practice of predominantly treatment resistant depressed patients, that reboxetine worked well as a combination agent with another drug that acts on the serotonin system.  It can however work well on its own and it tends to be reasonably activating.  

A patient I have seen for over five years now is a single mother who is working on rebuilding a career. She had very resistant depressions in the past, failing multiple trials of SSRI's, Bupropion (Wellbutrin®), tricyclic antidepressants, lithium, and anticonvulsants.  She has had several hypomanic periods on monoamine oxidase inhibitors (MAOIs), which could not be managed by mood stabilizing agents or antipsychotics. However, she has been doing well now for over two years on reboxetine at 6 mg a day, combined with a little bit of an herbal treatment which I use for depression called Rhodiola rosea.   

Picamilon: The Russian Development    www.picamilon.net

I have also found picamilon to be a helpful medication.  This Russian medication is a combination of GABA and niacin in the same molecule.  It is helpful for anxiety and depression, especially with cerebral vascular disorder with mood symptoms and/or confusion.  For example, a middle-aged divorced university professor who I have now been seeing for nine years came for treatment of a resistant depression.  She failed multiple trials of all available classes of antidepressants.  She had transient response to a course of electroconvulsive therapy.  As I tried to puzzle over why a patient with a relatively classical depression was so unresponsive to multiple trials of conventional antidepressants, I commenced a work up of her cardiovascular system that indicated she had not only abnormalities in her lipid profile and glucose metabolism (although not diabetic), but also had problems with elevated homocysteine, (a major risk factor for vascular disease) and highly sensitive C-reactive protein. These findings, combined with subtle cognitive deficits (which were not characteristic of her previous outstanding academic performance), led me to believe that she had developed a slowly progressive cerebral vascular disease which was interfering with her response to medications.  She was perhaps twenty percent better on extended release Effexor® 600 mg per day, reboxetine 4 mg a day (more made her feel uncomfortably anxious), quetiapine 100 mg at night for agitation and insomnia, and S-adenosyl methionine 400 mg per day.  The addition of picamilon ultimately at 100 mg three times a day cleared up the kind of brain fog under which she has labored for some time.  The picamilon enabled her to have more energy, more enthusiasm, and a greater sense of involvement in her daily activities.  I believe she falls into an often-ignored category now recognized by geriatric psychiatrists as being vascular depression.  

However, picamilon is more versatile than this. It can be useful in patients post-stroke. I also commonly see patients with Parkinson's disease, depression, and evidence of cerebral vascular disease from a history of strokes or abnormal findings on magnetic resonance imaging.  Picamilon can be extremely helpful in giving these patients a decrease in anxiety and depression, without sedation and with a mild pleasant stimulation.  It may be used in a variety of other organic brain syndromes.  For example, one patient in his mid-fifties had developed a treatment resistant depression during the course of which he also suffered several strokes and cognitive impairment. This was ultimately found to be due to an antiphospholipid antibody syndrome. Although his depression was at least partially responsive to Effexor®, his cognitive functioning and energy were poor.  His daily activity was quite limited, particularly because of apathy and fatigue. In this case the patient was greatly helped by the addition of acetyl L-carnitine, picamilon, and SAM-e.  For all three medications the doses had to be given aggressively.  If any one medication were decreased he would basically become non-functional. 

Racetams: The European Alternatives 

Another group of medications which are relatively unfamiliar to most American physicians are the pyrolidones or racetams.  I most commonly use pramiracetam or piracetam from this class.

These medications have a positive effect on nerve cell energy metabolism and seem to boost the function of cholinergic and NMDA-glutamate receptor systems.  Pyrollidones facilitate the transfer of information between the cerebral hemispheres across the corpus callosum.  They improve the function of the verbal areas of the left cerebral cortex. They can be used to lessen the cognitive side effects of anticonvulsants, as well boost the anticonvulsant efficacy of these medications.  Even less well known is that there are several studies showing that the racetams can boost the efficacy of antidepressants.  Yet they are extremely benign in terms of side effects, rarely causing stimulation and over activation. 

For example, a 55-year-old lawyer who had been extremely highly functioning came to see me several years ago, after approximately a ten-year course of deterioration following the development of an ovarian hyperstimulation syndrome, secondary to taking fertility medication.  She developed physical symptoms of this disorder, as well as depression and cognitive problems that became so pronounced that she became unable to work.  Her deficits were documented on neuropsychological tests which were consistent with blood flow abnormalities, seen on SPECT (Single Proton Emission Computed Tomography) scans of her brain.  Her depression responded well to a combination of Zoloft® and SAM-e. However, her cognitive functioning remained poor. She was also extremely hypersensitive to light, sound, and touch.  (It should be noted that ovarian hyperstimulation syndrome causes marked changes in the vasculature of animals, as well as overproduction of stress hormones through the stress response system).  The patient had great difficulty tolerating conventional psychotropic medications and experienced extremely severe side effects.  Fortunately, her brain function improved dramatically when she was given pramiracetam 600 mg twice a day.  For the first time in ten years, the patient felt that her brain had been returned to her.  She was able to read and do other mental work without collapsing in a short time. 

Another less dramatic example is a 23-year-old patient who was tested in childhood and found to possess a genius level IQ.  He went to a prestigious college.  At about that time he developed an idiopathic autoimmune disease which caused diabetes mellitus requiring insulin and an idiopathic alopecia.  He developed severe cognitive problems which were well documented, not only on neuropsychological testing but also on brain scans. Conventional treatments by neurologists and psychiatrists were to no avail.  The patient had some response to donepezil, a cholinesterase inhibitor, over a nine-month period.  However, the response was not satisfactory and with help from IAS, I began to treat him with galantamine up to 24 mg a day with a partial positive response.  Picamilon 50 mg a day further improved his cognitive functioning and energy.  Adding pramiracetam 600 mg per day has enabled him to recover his previous cognitive function level as documented by repeat neuropsychological testing.  If he takes more of any of these medications he is over stimulated and has trouble sleeping.  However, if any of the medications are lowered, his ability to function comes to a screeching halt.  As noted in IAS Bulletins, pramiracetam goes very well with drugs which act on the cholinergic system  (Galantamine being, of course, a weak cholinesterase inhibitor, but a powerful allosteric nicotinic receptor agonist).   

In summary, the antidepressants offered by IAS have allowed me to give great relief to many patients who would not otherwise have been helped due to intolerance, side effects, or non-response to standard medications.  In patients with neurological degenerative disorders or brain injury, the cognitive enhancing agents supplied by IAS, which are extremely benign in side effects, have greatly enhanced the quality of life for many patients and their families. 

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