Do nutritional supplements, vitamins and minerals, actually help psychiatric disorders, like bipolar disorder, and improve mental function? Some doctors and researchers say they do.

Leave your drugs in the chemist's pot if you can heal the patient with food." Hippocrates.

In a study published in the July 2002 British Journal of Psychiatry, 172 young adult prisoners in maximum security were given supplements of vitamins and minerals roughly equating to the US recommended daily allowance (RDA), plus fatty acids. The average time for those staying in the study was 146 days. While there was no change in the placebo group, there was a 35.1 percent drop in antisocial behavior for those taking supplements for at least two weeks and a 37 percent drop in violent offenses.

Speaking at a symposium, "Mineral/Vitamin Modification of Mental Disorders and Brain Function" at the 2003 American Psychiatric Association's annual meeting, the study's lead author, Bernard Gesch CQSW of Oxford, noted that crime has increased seven-fold in the last 50 years. Over the same period of time, he reported, the trace element content in fruits and vegetables appears to have fallen significantly. According to the Centers for Disease Control, 79 percent of high school students eat less than five fruits or vegetables a day, and it is estimated that the ratio of omega-6 to omega-3 intake has increased six-fold since Paleolithic times.

The RDA was never meant to be regarded as optimal, more than one speaker reminded those at the same symposium. Instead, it is the minimum considered to prevent diseases such as scurvy or beriberi. According to a review article by Fairfield and Fletcher published in the June 19, 2002 JAMA, "most people do not consume an optimal amount of all vitamins by diet alone."

At the same session, David Benton PhD of the University of Wales, Swansea, cited his 1991 study where those who took 50 mg of thiamin (Vitamin B1) - nearly 50 times the RDA - reported improved moods and exhibited faster reaction times, with no change in the placebo group. The study population (female undergrads) were all well-nourished with no mood disorders. In another study, those on 100 mcg of the trace mineral selenium - twice the RDA - reported less depression, anxiety, and tiredness following five weeks than the control group. Finally, a 1995 study on young healthy adults found that 10 times the recommended doses of nine vitamins after 12 months resulted in improved performance on a range of cognitive functions in the females but not the males.

Dr. Benton related that the brain is arguably the most nutritionally sensitive organ in the body, playing a key role in controlling bodily functions. It is the most metabolically active organ, with two percent of the body's mass accounting for 20 percent of basal metabolic rate. With millions of chemical processes taking place, he went on to say, if each of these is only a few percent below par, it is easy to imagine some sort of cumulative effect resulting in less than optimal functioning.

Added Bonnie Kaplan, PhD of the University of Calgary: "We know that dietary minerals and vitamins are necessary in virtually every metabolic action that occurs in the mammalian brain."

According to William Walsh PhD, Senior Scientist at the Health Research Institute and Pfeiffer Treatment Center in Illinois, writing on Safe Harbor's Alternative Mental Health On-Line website:

"The brain is a chemical factory that produces serotonin, dopamine, norepinephrine, and other brain chemicals 24 hours a day. The only raw materials for their syntheses are nutrients, namely, amino acids, vitamins, minerals, etc. If the brain receives improper amounts of these nutrient building blocks, we can expect serious problems with our neurotransmitters."

For instance, some depression patients have a genetic pyrrole disorder which renders them grossly deficient in vitamin B6. Pyrroles bind with B6 and then with zinc, thus depleting these nutrients. According to Dr Walsh, these individuals cannot efficiently create serotonin since B6 is an important factor in the last step of its synthesis.

An outcome study of 200 depressed patients treated at the Pfeiffer Center found 60 percent reported major improvement and 25 percent minor improvement. Treatment complements medications, but as the patient begins improving meds may be lowered or gradually dropped. Stopping treatment will result in relapses.

Another article on Safe Harbor's website notes that depression can stem from any number of other conditions in the body, including hypothyroidism, heart problems, lack of exercise, diabetes, and the side effects of other drugs. Nutrient deficiencies include: Vitamin B2, Vitamin B6 (which can be low in those taking birth control or estrogen), and Vitamin B9 (folic acid). According to the article, 31 to 35 percent of depressed patients have folic acid deficiencies.

Other deficiencies affecting depression include Vitamin B12, Vitamin C (to a lesser extent), magnesium, SAM-e, tryptophan, and omega-3.

A 2003 Finnish study of 115 depressed outpatients being treated with antidepressants found that those who responded fully to treatment had higher levels of vitamin B12 in their blood at the beginning of treatment and six months later. The comparison was between patients with normal B12 levels and higher than normal ones rather than between deficient and normal. The study's lead author, Jukka Hintikka MD, told BBC News that one possible explanation could be that B12 is needed to manufacture certain neurotransmitters. Another theory is that vitamin B12 deficiency leads to the accumulation of the amino acid homocysteine, which has been linked to depression. A 1999 study found that both higher levels of B12 (compared to patients with deficient levels) and folate (vitamin B9 found in leafy green vegetables)corresponded with a better outcome.

A 1997 Harvard study supports earlier findings that show: 1) a link can be made between folate deficiency and depressive symptoms, and 2) that low folate levels can interfere with the antidepressant activity of the SSRIs. A 2002 Oxford review of three studies involving 247 patients found that folate when added to other treatment reduced Hamilton Depression scores by 2.65 points in two studies while a third found no added benefit, leading the authors to conclude "folate may have a potential role as a supplement to other treatment for depression."

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Psychology Today reports that several small studies have found that the mineral chromium - either by itself or with antidepressants - has proved effective for treating mild to severe depression. A recent Duke University study found 600 mcg of chromium picolinate resulted in a reduction of symptoms associated with atypical depression, including a tendency to overeat. Chromium may act on insulin, which controls blood sugar (researchers have linked depression and diabetes). The mineral is found in whole grains, mushrooms, liver, and brewer's yeast.

It isn't just about mood. According to Mattson and Shea of the NIH in a 2002 study: "Dietary folate is required for normal development of the nervous system, playing important roles regulating neurogenesis and programmed cell death."

An article in Psychology Today reports that antioxidants scavenge and fight off free radicals, those rogue oxygen molecules that damage cell membranes and DNA. The brain, being the most metabolically active organ in the body, is especially susceptible to free radical damage. Free radical damage is  implicated in cognitive decline and memory loss, and may be a leading cause of Alzheimer's. Studies suggest that vitamins C and E may work synergistically to prevent Alzheimer's and to slow memory loss. The RDA for vitamin E is 22 international units (IU) and 75 to 90 mg for vitamin C, but supplements may contain up to 1,000 IU of vitamin E and more than 1,000 mg of vitamin C. In the Alzheimer's study, involving 5,000 individuals, the greatest impact occurred among those who took the two vitamins in combination. Taking either of the vitamins alone or taking multivitamins provided no protection.

A 2003 USDA Human Nutrition Research Center on Aging/Welch Foods study of rats nearing the end of their expected life spans found that feeding them Concord grape juice "appeared to reduce or reverse the loss of sensitivity of muscarinic receptors, thus enhancing cognitive and some motor skills." Juice-fed rats negotiated a water maze in 20 percent less time than the controls, among other tasks. Similar effects have been found in blueberries. Concord grape juice has the highest antioxidants of any fruits, vegetables, or juices.

Julia Ross, author of The Mood Cure, advises taking amino acids to counter some of the brain's deficiencies, including:

• Tyrosine, a precursor of both norepinephrine and dopamine, can act as an energizer, and is available over the counter. Phenylalanine, a precursor, to tyrosine, is also an option.
• Tryptophan, the precursor to serotonin, was removed from the US market in 1989 after a manufacturer produced a highly toxic contaminate, but is still available by prescription. Less is more, with lower doses (one to three gm) more effective than higher doses. Taking the amino acid with carbohydrates helps in its absorption.
• The intermediary between tryptophan and serotonin, 5HTP, is available without prescription. An Eli Lilly study found that combining 5HTP with Prozac significantly increased 5HTP in rats' brains compared to Prozac alone.
• Julia Ross refers to GABA as "our natural ," and recommends it to her clients for calming down. However, as this neurotransmitter does not easily cross the blood-brain barrier, you may wind up instead with very expensive urine.

Psychology Today reports that Andrew Stoll MD, the Harvard psychiatrist who put omega-3 on the map with his 1999 pilot study, is exploring the amino acid taurine for treating bipolar disorder. Taurine acts as an inhibitory neurotransmitter. According to Psychology Today: "The results of the study have not yet been published, but Stoll did say that 'it works really well for bipolar disorder.'"

Rita Elkins in her book, "Solving the Depression Puzzle," notes that soil depletion may account for the deficiencies of certain vitamins and minerals in our diet. In making the case for nutritional supplements, she notes:

• Average calcium consumption in the US and Canada is two thirds of the RDA level of 800 mg.
• Fifty-nine percent of our calories come from nutrient-poor sources such as soft drinks, white bread, and snack foods.
• The average American achieves only half the recommended levels of folic acid.
• Nine of 10 diets contain only marginal amounts of vitamins A, C, B1, B2, B6, chromium, iron, copper, and zinc.
• Only one person in five consumes adequate levels of vitamin B6.
• Seventy-two percent of adult Americans fall short of the RDA recommendation for magnesium.
• The Journal of Clinical Nutrition reported less than 10 percent of those surveyed ate a balanced diet.
• Up to 80 percent of exercising women have iron-deficient blood.

In 1969 the Nobel scientist Linus Pauling coined the term "orthomolecular" to describe the use of naturally occurring substances, particularly nutrients, in maintaining health and treating disease. According to Dr Pauling: "Orthomolecular psychiatry is the achievement and preservation of mental health by varying the concentrations in the human body of substances that are normally present, such as the vitamins."

Orthomolecular medicine was pioneered by Abram Hoffer MD, PhD, who said in a 1998 interview, "I made a prediction in 1957 that by 1997 our practices would be accepted. I assumed it would take 40 years, since in medicine it typically takes two generations before new ideas are accepted. We're more or less on schedule."

Back at the midpoint in the schedule, a 1973 American Psychiatric Association task force report used the word "deplorable" to describe the lack of hard research evidence to back the claims of proponents of high-dose vitamins and orthomolecular treatment" In light of the fact that funding for these kind of studies is virtually nonexistent, however, the criticism is rather disingenuous. In fact, there is an institutional bias against studying more than one ingredient at a time, which dooms proposals for large-scale randomized control trials for multi-vitamins and minerals to death by red tape.

To turn the critical spotlight around, the evidence for the three meds combinations most of us find ourselves on is totally lacking, with no studies whatsoever, which would make any polypharmacy claims by the psychiatric profession equally deplorable (not that we would ever think of using such a term).

Thirty years later, the profession is still a long way from embracing nutritional supplements, but it has probably advanced from employing excessive rhetoric to attack its practitioners. Having said that, in today's largely unregulated market, quacks with fantastic claims abound, along with suppliers of shoddy goods. Buyer beware is the rule.

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Speaking of fantastic claims:

In 2000, this writer happened to come across an item in a Canadian newspaper about an Alberta Company, Synergy of Canada Ltd, that was test marketing a mix of 36 supplements, called EMPower, based on a formula to calm aggressive hogs. I ran a short item in my newsletter, McMan's Depression and Bipolar Weekly, and next thing the company was bombarded with enquiries about its product.

Founder Anthony Stephan's story is compelling, how after his bipolar wife Deborah committed suicide in 1994, and how after exhausting all medical routes, he turned to friend David Hardy for help for two of his bipolar children. David came up with a variation on his formula he used for calming down hogs, and Anthony administered the supplement to his kids. As he describes it:

"Joseph was treated with lithium. When he would take the lithium he complained of severe side effects ... when he refused it, he would lapse into severe mania and panic within a couple of days.

"On January 20, 1996, Joseph started using the nutritional supplementation program. He weaned off the lithium within four days. Within two weeks, his mood and emotional control improved drastically. He has maintained total wellness, and essentially no symptoms of bipolar since that time."

As for daughter Autumn, who first exhibited symptoms when she was 20 and became increasingly difficult to control with her rapid-cycling moods and suicidal states:

"On February 18, 1996, Autumn started the supplement program. Within four days she was forced to eliminate Haldol and Rivotril [Klonopin] because of the drastically increasing side effects. Ativan was no longer required as the mania became more manageable in the absence of hallucinations. After one week on the program, she returned home to her husband. After one month, she began the reduction and elimination of the Epival [Depakote] (used as a mood stabilizer). March 28, 1996 marks the last day that Autumn took medication for bipolar affective disorder.

"Autumn has remained stable and healthy beyond her wildest dreams and the expectations of her psychiatrist, doctor and family for over four years now. In her final visit with her psychiatrist, he indicated that there was never an expectation for remission, given her diagnosis and severe and unrelenting cycles."

The downside of the Synergy program is it initially costs in the neighborhood of $130 a month to go on the eight capsules four times a day regimen. This eventually comes down to about 16 capsules a day, but the expense is likely to come out of your pocket rather than your health plan's.

EMPower has not suffered from lack of controversy. Health Canada has attempted to shut down its operations, its nonprofit arm, Truehope, Synergy's nonprofit arm which works with patients, has been accused of being hostile to psychiatrists and medications, a number of patients have complained of getting worse rather than better, a quack watch group has made Synergy its great white whale, and its founders have been taken to task for making allegedly exaggerated claims.

In December 2001, however, Synergy received a significant boost to its credibility with a pilot study and accompanying commentary published in the Journal of Clinical Psychiatry. In a University of Calgary open trial, 14 bipolar patients were placed on EMPower, concurrent with their meds. Thirty-three of the 36 ingredients in the supplement are vitamins and minerals, most about 10 times the RDA. After 44 weeks, depression scores dropped by 55 percent and mania scores by 66 percent. Most patients were able to lower their meds doses by 50 percent. Two were able to replace their meds with the supplement. Three dropped out after three weeks. The only side effect was nausea, which went away at a lower dose.

In her article, the study's author, Dr Kaplan, noted that deficient levels of some nutrients (eg B vitamins) are related to brain and behavior disorders as well as poor response to antidepressant medication. Less is known about trace elements, but zinc, magnesium, and copper all appear to play important roles in modulating the brain's NMDA receptor (which is being targeted by at least 20 medications presently in the development pipeline). Bipolar disorder, she speculates, may be an error of metabolism, or those with bipolar may be vulnerable to nutrient deficiencies in the food supply. "There is very good work," she said in an interview, "going back to the 1950s on something called biochemical individuality. For example, your requirements for zinc or B12 may be different from another person's. We're not clones. We're really very different biochemically."

In the November 2002 Journal of Child and Adolescent Psychopharmacology, Dr Kaplan reviewed earlier findings into minerals and vitamins and mood, including:

• Low intracellular calcium levels in bipolar patients.
• Serum zinc levels significantly lower in depressed patients, with the severity of the deficiency corresponding with the severity of the illness.
• A double-blind trail finding resulted in improved cognition.
• Dr Benton's study linking thiamin at a high dose to improved cognition and selenium to improved mood.
• A year-long double-blind trial finding high-dose multivitamins improved mood.

In an accompanying commentary to Dr Kaplan's EMPower study, Charles Popper MD of Harvard observed: "In view of the 50 years of experience with lithium, the notion that minerals can treat bipolar disorder is unsurprising ... Depending on how this line of research develops, [we] may need to rethink the traditional bias against nutritional supplementation as a potential treatment for major psychiatric disorders."

Dr Popper notes other promising developments, including omega-3, calcium, chromium, inositol, amino acids, and high-dose multi-vitamins.

Dr Popper in his commentary mentioned using the supplement to treat 22 bipolar patients, 19 who showed a positive response, 11 who have been stable for nine months without drugs.

Dr Popper, who co-chaired the APA symposium mentioned at the beginning of this article, observed that while nutrient supplements are probably safer than psychiatric drugs, one should be mindful of toxic levels and special circumstances. For example, high doses of vitamin A need to be avoided in pregnant women owing to risk of fetal harm.

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The issue of interactions with meds was raised, but Dr Kaplan expressed her dissatisfaction with the term, interaction. Her theory is that nutritional supplements may improve the performance of metabolic pathways, thus amplifying the positive and negative effects of meds. As a result, therapeutic doses of meds can become overdoses. Truehope advises that new users will experience initial side effects from their meds thanks to the amplification factor, and urges patients to work with their doctor in lowering their meds dose. Overenthusiastic Truehope people may say you need to eventually go off all your meds, but just two patients in Dr Kaplan's small study and only half of Dr Popper's patients achieved this result..

If you are considering therapy with vitamins or other nutrients, do so with your psychiatrist in the loop. Since "integrative psychiatrists" are a rarity, it is wise to seek nutritional expertise from another source. It also pays to ensure that your psychiatrist is open-minded about nutritional supplements and would consider adjusting your meds if you responded well to your new regimen. Keep in mind that the final decision regarding lowering meds is one to be made between you and your psychiatrist, not with the person who is advising you on nutrition.

MDs with holistic expertise exist, some who conduct special lab tests to look for nutritional deficiencies or metabolic quirks. The American Holistic Medical Association provides a directory of its members, searchable by location and specialty.

You may wish to seek out a nutritionist, who has two to four years of specialized training, far more than the one class medical students get, though some MDs take additional courses to qualify as nutritionists. Clinical nutritionists have completed at least 900 hours of on-the-job experience. The National Association of Nutritional Professionals provides a directory of its members, searchable by location.

Naturopaths are another option, with training in nutrition, herbology, Chinese medicine, and other fields, but not medicine. Those who are NDs - naturopathic doctors - have four years of graduate training from a handful of schools in the US. The American Association of Naturopathic Physicians provides a directory of its members, searchable by location.

Safe Harbor also has a directory ranging from MDs to unlettered alternative practitioners.

And once more: Buyer beware. Nutritional supplements may turn out to be a life-saver for you, but you may have to negotiate a Wild West marketplace first. If you are highly skeptical of drug industry claims, maintain that same skepticism for natural products. Live well ...

Buy Elkins' Solving the Depression Puzzle from Amazon.com.

Buy Julia Ross' The Mood Cure from Amazon.com.

About the author: John McManamy is diagnosed with bipolar disorder. He is a professional writer and author of "Living Well With Depression and Bipolar" and runs McMan's Depression and Bipolar website.

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When it comes to bipolar disorder in children, there's an amazing lack of research and professional agreement about diagnosis and treatment of pediatric bipolar disorder.

Focus on diagnosis, but what about treatment?

What's an episode? Does irritability include everything from mere whining all the way to ferocious rage? How many types of bipolar disorder in children are there, anyway?

It may surprise CABF (Child and Adolescent Bipolar Foundation) parents to learn that such basic diagnostic questions are still undecided among experts on the front lines of research. Many of them gathered in Boston on April 3rd to seek a common language and explore opportunities for collaboration. The NIMH-funded conference, organized by Dr. Joseph Biederman, drew about a hundred researchers from the U.S. and abroad, and included five CABF parent representatives.

Our impression, as parents, was that the field is moving forward in research on diagnosis - but treatment studies, so badly needed, were disappointingly few. Researchers are developing standardized screening tools, coming closer to agreeing on some common types of bipolar disorder in children, and working on "operationalizing" (agreeing upon standard rating measures for) behavioral symptoms that vary widely in frequency, intensity and duration, such as irritability. These things will help identify children who fall between the cracks in the DSM-IV. However, once a diagnosis is made, the first question parents ask is "what do we do now" and the answers remain elusive, with little data from research about the efficacy, dosing, and side effects of the medications prescribed for our children.

Parents are often astonished to hear their child's doctor ask them, "what would you like to do?" It is painful for parents to learn just how little is known about how to treat pediatric bipolar disorder. Every day parents report on our message boards various combinations of treatments being used - including off-label combinations of medications, herbs, craniosacral massage, nutritional supplements, neurofeedback, the Feingold diet, for which there is little or no research. Parents want to know if they should consider the promising mood stabilizers being used in an increasing number of very young, very ill children, with much success reported on our Web site but with great concerns about side-effects. Preliminary results are showing that the sickest adults in the STEP-BP study subjects age 14 and above are those who had the earliest onset. The majority of children with bipolar disorder in CABF's nearly 20,000 families are 13 and under. The prospect of watching our young children suffer with inadequate treatments while research in adults and older adolescents plods slowly on, hoping that results will "trickle-down" to children, is unacceptable. Recent neuroimaging studies show that more episodes are associated with more structural differences in the brain. With the huge wave of children being identified and presenting for treatment, now that the blinders are off, Congress, the National Institute of Mental Health and the FDA must seize this opportunity to vastly expand treatment research. I can't think of a better investment in our youth, with such an enormous potential payoff in cost savings and reduction of human suffering.

Who will help our Bipolar kids

The house is on fire, and parents are desperate for help to save our beloved children. Yet the fire department, the child psychiatrists, the pediatricians, the psychotherapists, the social workers, those who claim expertise in helping children lack decent tools to quench the flames. What tools they do have, they often don't know how to use. For now, it's up to the bucket brigade, resourceful parents and a few professionals passing information hand to hand, through the Internet, using whatever means are available to save our kids. Meanwhile, the death toll is rising in my neighborhood, an 8th grader with bipolar disorder hung herself a couple of weeks ago, and in Virginia last week a father and model citizen received a light sentence for killing his sleeping bipolar son, age 19, with six bullets to the head. If it feels like we are living on the frontier, it's because we are.

At the Boston meeting, some exciting projects in the areas of genetics research and neuroimaging were conceived, and the spirit of collaboration was definitely in the air. It remains to be seen what new projects will evolve from this meeting. Collaboration is needed not only within this group, but also with researchers in endocrinology, in schizophrenia, in cognitive rehabilitation, in autism, in genetics, in the neurobiology of addiction, and more. Being in the same room with some of the smartest people in science who are working on the illness that devastates our kids' lives was encouraging indeed. We wish the researchers great success. In the meantime, we parents hug our despondent and suicidal kids and reassure them that the fire department is surely on its way.

The scientific conference was organized by Joseph Biederman, M.D., Professor of Psychopharmacology at Harvard Medical School, and funded by the National Institute of Mental Health. CABF board members Rachel Adler, Dorie Geraci, Marcie Lipsitt, Sheila McDonald, and myself participated as parent representatives.

About the author: Martha Hellander, J.D., is the executive director of the Child & Adolescent Bipolar Foundation (CABF).

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What are the similarities and the differences between ADHD and Bipolar Disorder in children? Find out how it's easy to misdiagnose one for the other.

Similarities Between ADHD and Bipolar Disorder

Both disorders share many characteristics: impulsivity, inattention, hyperactivity, physical energy, behavioral and emotional lability (behavior and emotions change frequently), frequent coexistence of conduct disorder and oppositional-defiant disorder, and learning problems. Motor restlessness during sleep may be seen in both (children who are bipolar are physically restless at night when "high or manic",though they may have little physical motion during sleep when "low or depressed"). Family histories in both conditions often include mood disorder. Psychostimulants or antidepressants can help in both disorders (that is, depending on the phase of the bipolar disorder). In view of the similarities, it is not surprising that the disorders are hard to tell apart.

Differences Between ADHD and Bipolar

So what features can help in distinguishing these two disorders? Some distinctions are obvious.

1. Destructiveness may be seen in both disorders but differs in origin. Children who are ADHD often break things carelessly while playing ("non-angry destructiveness"), whereas the major destructiveness of children who are bipolar is not a result of carelessness, but tends to occur in anger. Children who are bipolar may exhibit severe temper tantrums, during which they release manic quantities of physical and emotional energy, sometimes with violence and property destruction.

2. The duration and intensity of angry outbursts and temper tantrums in the two disorders differs. Children who are ADHD usually calm down within 20-30 minutes, whereas children who are bipolar may continue to feel and act angry for over 30 minutes and even for 2-4 hours. The physical energy that a child with ADHD "puts out" during an outburst of anger could be mimicked by an adult who tries to "enact" the tantrum, whereas the energy generated by angry children who are bipolar could not be imitated by most adults without reaching exhaustion within a few minutes.

3. The degree of "regression" during angry episodes is typically more severe for children who are bipolar. It is rare to see an angry child who is ADHD display disorganized thinking, language, and body position, all of which may be seen in angry bipolar children during a tantrum. Children who are bipolar may also lose memory of the tantrum.

4. The "trigger" for temper tantrums is also different in these disorders. Children who are ADHD are typically triggered by sensory and affective overstimulation (transitions, insults), whereas children who are bipolar typically react to limit-setting (i.e., a parental "NO") and conflict with authority figures. A child who is bipolar will often actively seek this conflict with authority.

5. The moods of children who have ADHD or bipolar disorder may change quickly, but children with ADHD do not generally show dysphoria (depression) as a predominant symptom. Irritability is particularly prominent in children who are bipolar, especially in the morning on arousal. Children with ADHD tend to arouse quickly and attain alertness within minutes, but children with mood disorders may show overly slow arousal (including several hours of irritability or dysphoria, fuzzy thinking or "cobwebs", and somatic complaints such as stomach aches and headaches) upon awakening in the morning.

6. Sleep symptoms in children who are bipolar include severe nightmares (explicit gore, bodily mutilation). Additional information on the specific content of these dreams and why children do not freely reveal these dreams is available in another article by Charles Popper (Diagnostic Gore in Children's Nightmares). Children who are ADHD mainly show difficulty going to sleep, whereas children who are bipolar are more apt to have multiple awakenings each night or have fears of going to sleep (both of which may be related to the dream content described above).

7. The ability to learn in children who are ADHD is often compromised by the coexistence of specific learning disabilities, whereas learning in children who are bipolar is more likely compromised by motivational problems. On the other hand, children who are bipolar are more able to use motivation to overcome inattention; they can stay tuned to an awesome TV show for long periods of time, but children who are ADHD (even if interested) may not stay involved, follow the plot or even stay in the room (especially during commercials).

8. Children who are bipolar often show giftedness in certain cognitive functions, especially verbal and artistic skills (perhaps with verbal precocity and punning evident by age 2 to 3 years).

9. In an interview room, children who are bipolar often demonstrate dysphoric, rejecting, or hostile responses during the first few seconds of meeting. Children who are ADHD, on the other hand, are more likely to be pleasant or at least non-hostile at first meeting, and if they are in a noisy location, they may immediately show symptoms of hyperactivity or impulsively. Children who are bipolar are also often "interview intolerant". They try to disrupt or get out of the interview, ask repeatedly when the interview will end, or even insult the interviewer. The child who is ADHD, on the other hand, may get frustrated, bored, or more impulsive, but usually without direct challenging the interview or the interviewer.

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10. The misbehavior of children who are ADHD is often accidental. If they crash into a wall (or a limit or an authority figure), it is often due to oblivious inattentiveness. The child who is bipolar, in the other hand, is more likely to crash into a wall with intent, for the sake of challenging its presence, Children who are bipolar are highly aware of "the wall" and are sensitive to ways of creating the biggest feeling of impact or challenge to it.

11. The child who is ADHD may stumble into a fight, whereas the child who is bipolar will look for a fight and enjoy the power struggle. While a child who is ADHD may engage in self-endangering behavior without noticing the danger, the child who is bipolar enjoys the danger and seeks it out. The child who is bipolar is intentionally dare-devilish (yet needle phobia is quite prevalent). In general, the danger-seeking is grandiosity ("I'm invincible") in the child who is bipolar and inattentiveness in the child who is ADHD.

12. In the child who is bipolar, danger-seeking grandiosity, energized giggling, and sexual hyperawareness may be seen early in the preschool years, and persist into adolescence and adulthood.

13. The natural course of ADHD is chronic and continuous, but tends toward improvement. There may be periods of worsening, however, during situational or developmental stress, or if a coexisting conduct disorder worsens. Children with bipolar disorder may or may not show clear behavioral episodes or cycles, but they do tend to exhibit increasingly more severe or dramatic symptoms over the course of years, particularly as the child becomes larger and the impulsivity becomes more difficult to contain.

14. Children with ADHD do not exhibit psychotic (thoughts and behavior reveal a loss of contact with reality) symptoms unless thy have coexisting psychotic depression, preschizophrenia, a drug-induced psychosis, a psychotic grief reaction. Children with bipolar disorder may, on the other hand, exhibit gross distortions in perceiving reality or in interpreting affective (emotional) events. They may even exhibit paranoid-like thinking or openly sadistic impulses.

15. Lithium treatment generally improves bipolar disorder but has no or little effect on ADHD.

The Coexistence of ADHD and Bipolar Disorder

Children may have ADHD, bipolar disorder, or unipolar disorder (depression), and some children have a combination of ADHD and bipolar disorder or ADHD and unipolar disorder (depression). A child who has either bipolar disorder or unipolar disorder, but not ADHD, may be misdiagnosed ADHD, however, because both the bipolar and unipolar disorders may include symptoms of inattention, impulsivity, and even hyperactivity. There is concern that ADHD is being overdiagnosed and bipolar disorder underdiagnosed in the population of children.

About the author: Dr. Charles Popper, MD is a psychopharmacologist from Harvard University

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Neurofeedback has been used successfully to improve brain function after brain injury, stroke, and in ADHD and depression for more than 15 years.

Neurofeedback is a scientific technique for measuring and modifying brain performance that has moved into the clinical setting to provide fast and lasting relief.

Neurofeedback is a special kind of biofeedback using an electro-encephalograph (EEG) to display the brain's functioning. This information is presented to the patient graphically in real time to allow the person to learn to control the brain more effectively. In the case of ADHD, the person has limited ability to concentrate. On an EEG, the brain waves are similar to those of a normal person who is daydreaming. To train such a person, a variation of a computer game is created, where the motion of an object, such as an airplane, is controlled by brain waves. The patient sits in front a monitor, "flying" the plane to avoid obstacles and the ground. The patient is learning to control the brain waves that provide concentration while having fun. The result is that the patient learns to concentrate the attention where it will do the most good.

In the case of depression, there are characteristic brain wave patterns. With neurofeedback, those patterns can be replaced by ones characteristic of normal mental behavior without drugs and without talk therapy.

About the author: Cory Hammond is the immediate Past President of the International Society for Neuronal Regulation (ISNR), the Past President and a Fellow of the American Society of Clinical Hypnosis, and the past Chair of the Board of Trustees of the ASCH Education and Research Foundation. He is a full Professor of Physical Medicine & Rehabilitation and a Psychologist at the University of Utah School of Medicine. Dr. Hammond has published 57 journal articles or reviews, 40 chapters, numerous sections in books, and 8 books, including a leading textbook, Handbook of Hypnotic Suggestions & Metaphors.

For the most comprehensive information about Depression, visit our Depression Community Center here, at HealthyPlace.com.

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Is spirituality a depression cure? At a Krishna center in India, students chat hymns, meditate and discuss their problems with monks to relieve depression.

The global Hare Krishna sect has floated a new wing to counsel students who are depressed, demoralized and even addicted to drugs.

The International Society for Krishna Consciousness (ISKCON) sect, headquartered in West Bengal's Mayapur town, says distressed students are getting back their zest for life by chanting "Hare Krishna" and listening to regular religious discourses.

The sect's counseling centre, called the Youth Forum, is run at its premises in the city. "We started the forum a couple of months ago and the response has been tremendous," said ISKCON official Ananga Mohan Das.

The forum is now visited by about 176 students "and the number is growing by the day".

At these sessions, held every Sunday, students listen to discourses by ISKCON monks, chant hymns, meditate and discuss their problems with the monks.

"The students come from the best of colleges and universities and also from very reputed families," Das said.

Besides its endeavour with students, ISKCON is planning programmes for reformation in the state's jails.

The sect wants to conduct regular religious sessions in jails in the hope that it would awaken spirituality in convicts and make them better human beings.

The proposal, already submitted to the state government, is that ISKCON volunteers would introduce convicts to meditation and religious discourses.

ISKCON monks want to distribute Hindu religious texts such as the Bhagwad Gita and hold its readings regularly. They also want convicts to chant "Hare Krishna".

ISKCON philosophy says a convict is not to be blamed for his crime, but it is society that is responsible because it could not impart the right lessons to the sinner.

Source: Times of India

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A fuller understanding of signaling in the brain of people with schizophrenia offers new hope for improved therapy

Today the word "schizophrenia" brings to mind such names as John Nash and Andrea Yates. Nash, the subject of the Oscar-winning film A Beautiful Mind, emerged as a mathematical prodigy and eventually won a Nobel Prize for his early work, but he became so profoundly disturbed by the brain disorder in young adulthood that he lost his academic career and floundered for years before recovering. Yates, a mother of five who suffers from both depression and schizophrenia, infamously drowned her young children in a bathtub to "save them from the devil" and is now in prison.

The experiences of Nash and Yates are typical in some ways but atypical in others. Of the roughly 1 percent of the world's population stricken with schizophrenia, most remain largely disabled throughout adulthood. Rather than being geniuses like Nash, many show below- average intelligence even before they become symptomatic and then undergo a further decline in IQ when the illness sets in, typically during young adulthood. Unfortunately, only a minority ever achieve gainful employment. In contrast to Yates, fewer than half marry or raise families. Some 15 percent reside for long periods in state or county mental health facilities, and another 15 percent end up incarcerated for petty crimes and vagrancy. Roughly 60 percent live in poverty, with one in 20 ending up homeless. Because of poor social support, more individuals with schizophrenia become victims than perpetrators of violent crime.

Medications exist but are problematic. The major options today, called antipsychotics, stop all symptoms in only about 20 percent of patients. (Those lucky enough to respond in this way tend to function well as long as they continue treatment; too many, however, abandon their antipsychotic medicines over time, usually because of side effects of schizophrenia medications, a desire to be "normal" or a loss of access to mental health care). Two-thirds gain some relief from antipsychotics yet remain symptomatic throughout life, and the remainder show no significant response.

An inadequate arsenal of medications is only one of the obstacles to treating this tragic disorder effectively. Another is the theories guiding drug therapy. Brain cells (neurons) communicate by releasing chemicals called neurotransmitters that either excite or inhibit other neurons. For decades, theories of schizophrenia have focused on a single neurotransmitter: dopamine. In the past few years, though, it has become clear that a disturbance in dopamine levels is just a part of the story and that, for many, the main abnormalities lie elsewhere. In particular, suspicion has fallen on deficiencies in the neurotransmitter glutamate. Scientists now realize that schizophrenia affects virtually all parts of the brain and that, unlike dopamine, which plays an important role only in isolated regions, glutamate is critical virtually everywhere. As a result, investigators are searching for treatments that can reverse the underlying glutamate deficit.

Multiple Symptoms

To develop better treatments, investigators need to understand how schizophrenia arises--which means they need to account for all its myriad symptoms. Most of these fall into categories termed symptom "positive," "negative" and "cognitive." Positive symptoms generally imply occurrences beyond normal experience; negative symptoms generally connote diminished experience. Cognitive, or "disorganized," symptoms refer to difficulty maintaining a logical, coherent flow of conversation, maintaining attention, and thinking on an abstract level.

The public is most familiar with the positive symptoms, particularly agitation, paranoid delusions (in which people feel conspired against) and hallucinations, commonly in the form of spoken voices. Command hallucinations, where voices tell people to hurt themselves or others, are an especially ominous sign: they can be difficult to resist and may precipitate violent actions.

Picture: PERCEIVING FRAGMENTS as parts of a whole can be difficult for people with schizophrenia. When normal subjects view fractured images like those above in sequence, they identify the object quickly, but schizophrenic patients often cannot make that leap swiftly.

The negative and cognitive symptoms are less dramatic but more pernicious. These can include a cluster called the 4 A's: autism (loss of interest in other people or the surroundings), ambivalence (emotional withdrawal), blunted affect (manifested by a bland and unchanging facial expression), and the cognitive problem of loose association (in which people join thoughts without clear logic, frequently jumbling words together into a meaningless word salad). Other common symptoms include a lack of spontaneity, impoverished speech, difficulty establishing rapport and a slowing of movement. Apathy and disinterest especially can cause friction between patients and their families, who may view these attributes as signs of laziness rather than manifestations of the illness.

When individuals with schizophrenia are evaluated with pencil-and-paper tests designed to detect brain injury, they show a pattern suggestive of widespread dysfunction. Virtually all aspects of brain operation, from the most basic sensory processes to the most complex aspects of thought are affected to some extent. Certain functions, such as the ability to form new memories either temporarily or permanently or to solve complex problems, may be particularly impaired. Patients also display difficulty solving the types of problems encountered in daily living, such as describing what friends are for or what to do if all the lights in the house go out at once. The inability to handle these common problems, more than anything else, accounts for the difficulty such individuals have in living independently. Overall, then, schizophrenia conspires to rob people of the very qualities they need to thrive in society: personality, social skills and wit.

Beyond Dopamine

THE BRAIN IN SCHIZOPHRENIA Click for full-size image: Part 1Part 2

The emphasis on dopamine-related abnormalities as a cause of schizophrenia emerged in the 1950s, as a result of the fortuitous discovery that a class of medication called the phenothiazines was able to control the positive symptoms of the disorder. Subsequent studies demonstrated that these substances work by blocking the functioning of a specific group of chemical-sensing molecules called dopamine D2 receptors, which sit on the surface of certain nerve cells and convey dopamine's signals to the cells' interior. At the same time, research led by the recent Nobel laureate Arvid Carlsson revealed that amphetamine, which was known to induce hallucinations and delusions in habitual abusers, stimulated dopamine release in the brain. Together these two findings led to the "dopamine theory," which proposes that most symptoms of schizophrenia stem from excess dopamine release in important brain regions, such as the limbic system (thought to regulate emotion) and the frontal lobes (thought to regulate abstract reasoning).

Over the past 40 years, both the strengths and limitations of the theory have become apparent. For some patients, especially those with prominent positive symptoms, the theory has proved robust, fitting symptoms and guiding treatment well. The minority of those who display only positive manifestations frequently function quite well--holding jobs, having families and suffering relatively little cognitive decline over time--if they stick with their medicines.

Yet for many, the hypothesis fits poorly. These are the people whose symptoms come on gradually, not dramatically, and in whom negative symptoms overshadow the positive. The sufferers grow withdrawn, often isolating themselves for years. Cognitive functioning is poor, and patients improve slowly, if at all, when treated with even the best existing medications on the market.

Picture: Objects often have hidden meanings to people with schizophrenia, who may hoard news items, pictures or other things that would seem useless to others. This wall is a re-creation.

Such observations have prompted some researchers to modify the dopamine hypothesis. One revision suggests, for example, that the negative and cognitive symptoms may stem from reduced dopamine levels in certain parts of the brain, such as the frontal lobes, and increased dopamine in other parts of the brain, such as the limbic system. Because dopamine receptors in the frontal lobe are primarily of the D1 (rather than D2) variety, investigators have begun to search, so far unsuccessfully, for medications that stimulate D1 receptors while inhibiting D2s.

In the late 1980s researchers began to recognize that some pharmaceuticals, such as clozapine (Clozaril), were less likely to cause stiffness and other neurologic side effects than older treatments, such as chlorpromazine (Thorazine) or haloperidol (Haldol), and were more effective in treating persistent positive and negative symptoms. Clozapine, known as an atypical antipsychotic, inhibits dopamine receptors less than the older medications and affects the activity of various other neurotransmitters more strongly. Such discoveries led to the development and wide adoption of several newer atypical antipsychotics based on the actions of clozapine (certain of which, unfortunately, now turn out to be capable of causing diabetes and other unexpected side effects). The discoveries also led to the proposal that dopamine was not the only neurotransmitter disturbed in schizophrenia; others were involved as well.

Theories focusing largely on dopamine are problematic on additional grounds. Improper dopamine balance cannot account for why one individual with schizophrenia responds almost completely to treatment, whereas someone else shows no apparent response. Nor can it explain why positive symptoms respond so much better than negative or cognitive ones do. Finally, despite decades of research, investigations of dopamine have yet to uncover a smoking gun. Neither the enzymes that produce this neurotransmitter nor the receptors to which it binds appear sufficiently altered to account for the panoply of observed symptoms.

The Angel Dust Connection

If dopamine cannot account well for schizophrenia, what is the missing link? A critical clue came from the effects of another abused drug: PCP (phencyclidine), also known as angel dust. In contrast to amphetamine, which mimics only the positive symptoms of the disease, PCP induces symptoms that resemble the full range of schizophrenia's manifestations: negative and cognitive and, at times, positive. These effects are seen not just in abusers of PCP but also in individuals given brief, low doses of PCP or ketamine (an anesthetic with similar effects) in controlled drug-challenge trials.

Such studies first drew parallels between the effects of PCP and the symptoms of schizophrenia in the 1960s. They showed, for example, that individuals receiving PCP exhibited the same type of disturbances in interpreting proverbs as those with schizophrenia. More recent studies with ketamine have produced even more compelling similarities. Notably, during ketamine challenge, normal individuals develop difficulty thinking abstractly, learning new information, shifting strategies or placing information in temporary storage. They show a general motor slowing and reduction in speech output just like that seen in schizophrenia. Individuals given PCP or ketamine also grow withdrawn, sometimes even mute; when they talk, they speak tangentially and concretely. PCP and ketamine rarely induce schizophrenia-like hallucinations in normal volunteers, but they exacerbate these disturbances in those who already have schizophrenia.

One example of the research implicating NMDA receptors in schizophrenia relates to the way the brain normally processes information. Beyond strengthening connections between neurons, NMDA receptors amplify neural signals, much as transistors in old-style radios boosted weak radio signals into strong sounds. By selectively amplifying key neural signals, these receptors help the brain respond to some messages and ignore others, thereby facilitating mental focus and attention. Ordinarily, people respond more intensely to sounds presented infrequently than to those presented frequently and to sounds heard while listening than to sounds they make themselves while speaking. But people with schizophrenia do not respond this way, which implies that their brain circuits reliant on NMDA receptors are out of kilter.

If reduced NMDA receptor activity prompts schizophrenia's symptoms, what then causes this reduction? The answer remains unclear. Some reports show that people with schizophrenia have fewer NMDA receptors, although the genes that give rise to the receptors appear unaffected. If NMDA receptors are intact and present in proper amounts, perhaps the problem lies with a flaw in glutamate release or with a buildup of compounds that disrupt NMDA activity.

Some evidence supports each of these ideas. For instance, postmortem studies of schizophrenic patients reveal not only lower levels of glutamate but also higher levels of two compounds (NAAG and kynurenic acid) that impair the activity of NMDA receptors. Moreover, blood levels of the amino acid homocysteine are elevated; homocysteine, like kynurenic acid, blocks NMDA receptors in the brain. Overall, schizophrenia's pattern of onset and symptoms suggests that chemicals disrupting NMDA receptors may accumulate in sufferers' brains, although the research verdict is not yet in. Entirely different mechanisms may end up explaining why NMDA receptor transmission becomes attenuated.

New Schizophrenia Treatment Possibilities

Regardless of what causes NMDA signaling to go awry in schizophrenia, the new understanding--and preliminary studies in patients--offers hope that drug therapy can correct the problem. Support for this idea comes from studies showing that clozapine (Clozaril), one of the most effective medications for schizophrenia identified to date, can reverse the behavioral effects of PCP in animals, something that older antipsychotics cannot do. Further, short-term trials with agents known to stimulate NMDA receptors have produced encouraging results. Beyond adding support to the glutamate hypothesis, these results have enabled long-term clinical trials to begin. If proved effective in large-scale tests, agents that activate NMDA receptors will become the first entirely new class of medicines developed specifically to target the negative and cognitive symptoms of schizophrenia.

The two of us have conducted some of those studies. When we and our colleagues administered the amino acids glycine and D-serine to patients with their standard medications, the subjects showed a 30 to 40 percent decline in cognitive and negative symptoms and some improvement in positive symptoms. Delivery of a medication, D-cycloserine, that is primarily used for treating tuberculosis but happens to cross-react with the NMDA receptor, produced similar results. Based on such findings, the National Institute of Mental Health has organized multicenter clinical trials at four hospitals to determine the effectiveness of D-cycloserine and glycine as therapies for schizophrenia; results should be available this year. Trials of D-serine, which is not yet approved for use in the U.S., are ongoing elsewhere with encouraging preliminary results as well. These agents have also been helpful when taken with the newest generation of atypical antipsychotics, which raises the hope that therapy can be developed to control all three major classes of symptoms at once.

None of the agents tested to date may have the properties needed for commercialization; for instance, the doses required may be too high. We and others are therefore exploring alternative avenues. Molecules that slow glycine's removal from brain synapses--known as glycine transport inhibitors--might enable glycine to stick around longer than usual, thereby increasing stimulation of NMDA receptors. Agents that directly activate "AMPA-type" glutamate receptors, which work in concert with NMDA receptors, are also under active investigation. And agents that prevent the breakdown of glycine or D-serine in the brain have been proposed.

Many Avenues of Attack

Scientists interested in easing schizophrenia are also looking beyond signaling systems in the brain to other factors that might contribute to, or protect against, the disorder. For example, investigators have applied so-called gene chips to study brain tissue from people who have died, simultaneously comparing the activity of tens of thousands of genes in individuals with and without schizophrenia. So far they have determined that many genes important to signal transmission across synapses are less active in those with schizophrenia--but exactly what this information says about how the disorder develops or how to treat it is unclear.

Genetic studies in schizophrenia have nonetheless yielded intriguing findings recently. The contribution of heredity to schizophrenia has long been controversial. If the illness were dictated solely by genetic inheritance, the identical twin of a schizophrenic person would always be schizophrenic as well, because the two have the same genetic makeup. In reality, however, when one twin has schizophrenia, the identical twin has about a 50 percent chance of also being afflicted. Moreover, only about 10 percent of first-degree family members (parents, children or siblings) share the illness even though they have on average 50 percent of genes in common with the affected individual. This disparity suggests that genetic inheritance can strongly predispose people to schizophrenia but that environmental factors can nudge susceptible individuals into illness or perhaps shield them from it. Prenatal infections, malnutrition, birth complications and brain injuries are all among the influences suspected of promoting the disorder in genetically predisposed individuals.

Over the past few years, several genes have been identified that appear to increase susceptibility to schizophrenia. Interestingly, one of these genes codes for an enzyme (catechol-O-methyltransferase) involved in the metabolism of dopamine, particularly in the prefrontal cortex. Genes coding for proteins called dysbindin and neuregulin seem to affect the number of NMDA receptors in brain. The gene for an enzyme involved in the breakdown of D-serine (D-amino acid oxidase) may exist in multiple forms, with the most active form producing an approximately fivefold increase in risk for schizophrenia. Other genes may give rise to traits associated with schizophrenia but not the disease itself. Because each gene involved in schizophrenia produces only a small increase in risk, genetic studies must include large numbers of subjects to detect an effect and often generate conflicting results. On the other hand, the existence of multiple genes predisposing for schizophrenia may help explain the variability of symptoms across individuals, with some people perhaps showing the greatest effect in dopamine pathways and others evincing significant involvement of other neurotransmitter pathways.

Finally, scientists are looking for clues by imaging living brains and by comparing the brains of people who have died. In general, individuals with schizophrenia have smaller brains than unaffected individuals of similar age and sex. Whereas the deficits were once thought to be restricted to areas such as the brain's frontal lobe, more recent studies have revealed similar abnormalities in many brain regions: those with schizophrenia have abnormal levels of brain response while performing tasks that activate not only the frontal lobes but also other areas of the brain, such as those that control auditory and visual processing. Perhaps the most important finding to come out of recent research is that no one area of the brain is "responsible" for schizophrenia. Just as normal behavior requires the concerted action of the entire brain, the disruption of function in schizophrenia must be seen as a breakdown in the sometimes subtle interactions both within and between different brain regions.

Because schizophrenia's symptoms vary so greatly, many investigators believe that multiple factors probably cause the syndrome. What physicians diagnose as schizophrenia today may prove to be a cluster of different illnesses, with similar and overlapping symptoms. Nevertheless, as researchers more accurately discern the syndrome's neurological bases, they should become increasingly skilled at developing treatments that adjust brain signaling in the specific ways needed by each individual. 

Report indicating Lamictal is an effective maintenance therapy for bipolar I disorder.

Lamotrigine (Lamictal) has been shown to be an effective maintenance therapy for patients with bipolar I disorder, and is approved in the United States for the treatment of adults to delay the time to occurrence of mood episodes in patients treated by standard therapy for acute mood episodes.

In a recent publication, David R. Goldsmith and colleagues of Adis International Limited in Auckland, New Zealand, performed an overview of lamotrigine (Lamictal®), a well-established anticonvulsant agent, and its application in cases of bipolar disorder.

Early studies in patients with epilepsy who were treated with lamotrigine indicated a propensity for improved mood, leading to clinical trials in patients with bipolar disorder. Although lamotrigine's mechanism of action in bipolar patients is undetermined, it may be related to the inhibition of sodium and calcium channels in presynaptic neurons and subsequent neuronal membrane stabilisation.

Compared to placebo, lamotrigine monotherapy has been demonstrated to significantly delay time to intervention with additional pharmacotherapy or electroconvulsive therapy for any new mood episode, as well as prolong time to intervention for depression.

Furthermore, lamotrigine appears superior to lithium at prolonging time to intervention for a depressive mood episode. While lamotrigine has also been found to significantly delayed time to intervention for a manic/hypomanic episode, it does not appear effective in the treatment of acute mania.

In 2 maintenance trials, lamotrigine monotherapy was generally well tolerated, with common adverse events being headache (19%), nausea (14%), infection (13%), and insomnia (10%). After 52-weeks of treatment, lamotrigine did not appear to cause an increase in body weight.

Approximately 0.1% of study participants receiving lamotrigine developed a serious rash, including 1 case of mild Stevens-Johnson syndrome. Subsequently, the dosage of lamotrigine is titrated over a 6-week period to 200 mg/day to minimise the incidence of serious rash.

Dosages over 200 mg/day are not recommended, and no formal recommendations exist for lamotrigine (Lamictal) maintenance therapy duration in bipolar I disorder.

Source: CNS Drugs 2004;18:1:63-67. "Spotlight on lamotrigine in bipolar disorder"

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Thousands of young, impotence-free guys are popping erection pills to become wayward weekend warriors. But at what cost?

"A few years ago, I got offered a at a party" says Mike Rodriguez, 26, recalling the first time he took the blue pill. "I was with this girl I met the week before and I was pretty sure I could take her home. I popped the pill a half-hour before we left the party. We had sex until she literally made me stop."

Rodriguez, a network engineer from New York City, had never suffered from impotence or performance anxiety. Yet he was using Viagra anyway, in this case as an insurance policy against the effects of alcohol.

Xavier Motley, a 27-year-old soldier from Pennsylvania, buys Viagra from an online pharmacy in Mexico. "I take it to enhance my endurance," says Motley, who has never had performance issues, either.

Viagra (sildenafil citrate) and its newer rivals, and Cialis (tadalafil), are erectile-dysfunction drugs, which were developed and intended for old salts who had trouble hoisting their sails. But in the last few years, these pharmaceuticals have caught on as recreational drugs with the under-30 crowd.

A new study published in the International Journal of Impotence Research (yes, it's a real publication) found that, while the largest group of Viagra users are still in the 56-and-older age group, there's been a 300% increase in prescriptions for men under 45 since the drug was launched in 1998. Add to that the untold thousands who buy it online, and it's clear that the country is in for some hard times.

But there's a dark side to this invisible helping hand. The consequences of large numbers of men taking potency pills they don't need are raising eyebrows in the medical community. For one thing, Viagra works for four to six hours, which, when combined with alcohol, can open the door wider to making unwise late-night choices. "Alcohol promotes uninhibited behavior," notes Andrew McCullough, M.D., a Manhattan urologist. "All of a sudden, an inebriated guy might decide, 'I'm not gonna wear a condom tonight.'"

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The same goes for men who get all revved up and have no place to go. Desperately searching for release with any matter of partner can also lead to less-than-smart lifestyle decisions. "If I'm out and I pop a pill and I can't get sex," admits Rodriguez, "I usually call an escort service."

These pharmaceuticals are creating another potential set of dilemmas. Scientists have found that, while men don't develop physical dependencies on the medications or loss of normal function if they stop taking them after extended use, psychological dependence on erectile-dysfunction drugs is a different matter altogether. The recreational user might take Viagra to help sell himself as a sexual superman early in a relationship. But once things get serious, he has to perform without the support of his little diamond-shaped friend.

Says Motley, "I worry that not taking it will cause my girlfriends to notice a drop-off in my performance."

All work in the same way. Each blocks an enzyme called phosphodiesterase-5, relaxing smooth-muscle cells to allow increased blood flow to the penis. (All three also have similar possible side effects, the must common being headaches and facial flushing.)

Each of the three drugs has also targeted the same demographic: younger men. Though Viagra is still far and away the industry leader, Cialis and Levitra have made serious inroads in market share, especially in Europe. So tar, Viagra has been prescribed 170 million times to 23 million men worldwide. Since Cialis and Levitra were launched last year, they have claimed 24% and 12%, respectively, of the European marketplace, compared with Viagra's 64%. In France, Cialis has been dubbed "Le Weekender,' as it stays potent for up to 36 hours. Cool. But imagine the problems posed by an almost two-day stiffy.

"I saw a 22-year-old with a prolonged erection," says McCullough. "I saw another with a penile fracture. He had had rodeo sex. She came down on him and it broke" Ouch.

Buckin' broncos aside, there are many young males who have legitimate erectile dysfunction. For them, Viagra and the other drugs may mean the difference between knocking down three pointers from the top of the key and warming the bench. But other than for reproductive sex, what is Viagra for if not recreational use?

"The problem in our society is, if good is good, why not be better than good?" says McCullough. "We haven't studied the effect in men without erectile dysfunction--there may be consequences. Enhancing sex for the sake of enhancing sex should not be condoned."

by Jonathan Yevin, a Brooklyn-based writer and photographer

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Frequently asked questions about Topiramate, used for treatment of mood disorders -mania and depression- and PTSD.

NOTE: Topiramate (Topamax) is only approved for the treatment of people with seizures. There are few systematic studies that establish the safety or efficacy of topiramate as a treatment for people with mood disorders or PTSD. While such studies are underway, what is currently known about the use of topiramate for the control of mood disorders and PTSD comes mostly from uncontrolled case reports.

1. What is topiramate (Topamax)?

Topiramate is an anticonvulsant that is chemically unrelated to any other anticonvulsant or mood regulating medication. The mechanism of action is unknown.

2. When was topiramate approved for marketing in the USA and for what indications may it be promoted?

Topiramate received final approval for marketing in the USDA on 24 December 1996 and is labeled for use as an anticonvulsant.

3. Is a generic version of topiramate available?

There is no generic topiramate as the manufacturer has patent protection.

4. How does topiramate differ from other mood stabilizing drugs?

Topiramate differs from other mood stabilizing drugs in two major ways:

1. topiramate's frequent effectiveness for patients who have failed to respond to antidepressants or mood stabilizers;
2. topiramate's unique side-effect profile.

5. What, if anything, uniquely distinguishes topiramate from carbamazepine and valproate?

Topiramate has been successful in controlling rapid cycling and mixed bipolar states in people who have not received adequate relief from carbamazepine and/or valproate.

6. People with what sorts of disorders are candidates for treatment with topiramate?

It is too early to be very specific about which mood disorders are most likely to respond to treatment with topiramate. There are just about no published reports on topiramate's use in psychiatry. Patients with hard-to-treat bipolar syndromes have been treated more often than patients with "treatment-resistant" unipolar disorders.

Topiramate seems especially useful when it comes to treating people who have become manic as the result treatment with lamotrigine.

There has recently been a report regarding the control of the symptoms of PTSD by topiramate.

7. Is topiramate useful for the treatment of acute depressed, manic and mixed states, and can it also be used to prevent future episodes of mania and/or depression?

The initial use of topiramate was to treat people with depressed, manic rapid-cycling, and mixed states that did not respond to existing medications. Some patients are now being maintained on topiramate on a long term basis in an attempt to prevent future episodes. The effectiveness of topiramate as a long-term prophylactic agent is currently being established.

8. Are there any laboratory tests that should precede the start of topiramate therapy?

Before topiramate is prescribed the patient should have a thorough medical evaluation, including blood and urine tests, to rule out any medical condition, such as thyroid disorders, that may cause or exacerbate a mood disorder.

9. How is treatment with topiramate initiated?

Topiramate is usually initially prescribed at an initial dose of 12.5 -25 mg once or twice a day and the total daily dose is increased by 12.5 - 25 mg every week. When prescribed in addition to other anticonvulsants being used as mood stabilizers, the final dose is often between 100 and 200 mg per day. Some patient with Bipolar Disorder do well on as little as a total daily dose of 50 mg/day. When used for the control of the symptoms of PTSD the average final dose is about 175 mg/day (with a range of 25 - 500 mg/day).

10. Are there any special problems prescribing topiramate for people taking lithium, carbamazepine (Tegretol), or valproate (Depakene, Depakote)?

An interaction between lithium and topiramate has not been reported.

Carbamazepine and valproate both have the ability to lower plasma levels of topiramate . . . carbamazepine by about 50% and valproate by about 15%. Topiramate has no effect on the plasma level of carbamazepine but can reduce the plasma level of valproate by about 10%. Pharmacokinetic interactions between topiramate and either lamotrigine (Lamictal) or gabapentin (Neurotin) have not been reported.

11. What is the usual final dose of topiramate?

When used as a mood-stabilizing agent the final dose of topiramate is most often between 50 and 200 mg/day. Some people require doses as high as 400 mg/day to achieve a good mood stabilizing effect . . . especially when topiramate is being used as a monotherapy . . . while others do fine on 25 mg/day.

12. How long does it take for topiramate to 'kick-in?'

While some people notice the antimanic and antidepressant effects early in treatment, others have to take a therapeutic amount of topiramate for up to a month before being aware of a significant amount of improvement.

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13. What are the side-effects of topiramate?

Here is a listing of topiramate's side effects that affected 10% or more of the 711 people taking the drug during clinical trials and the frequency of those side effects in the 419 people treated with placebo in those trials:

Common Adverse Reactions (%)
(Topiramate = 200 mg/day)

Side-effects are most noticeable the few days after an increase in dose and then often fade.

14. Which side-effects are severe enough to force people to discontinue topiramate?

The side-effects that most frequently caused people to discontinue therapy with topiramate were: psychomotor slowing (4.1%), memory problems ( (3.3%), fatigue (3.3%), confusion (3.2%), and somnolence (3.2%).

Much less frequently happening but more serious side-effects that force people to stop topiramate therapy include kidney stones, which affect about 1% of people taking the drug, and acute glaucoma, which to date had been reported in about one person in 35,000 taking topiramate. The sudden onset of back pain may indicate the presence of a kidney stone, while eye pain, changes in vision or the the develpment of redness in the eye may indicate glaucoma. Most cases of glaucoma have devdeloped within the first two months of therapy with topiramate.

Information from the FDA on topiramate and glaucoma.

15. Does topiramate have any psychiatric side effects?

Among the reported side effects of topiramate are sedation, psychomotor slowing, agitation, anxiety, concentration problems, forgetfulness, confusion, depression, and depersonalization. As with other anticonvulsants, psychosis has rarely been reported as a side-effect.

16. How does topiramate interact with prescription and over-the-counter medications?

Only a few interactions between topiramate and other drugs have been identified. Topiramate may increase the plasma level of phenytoin (Dilantin). Phenytoin lowers the concentration of topiramate in the blood by about 50%. While topiramate has little effect on the plasma level of carbamazepine, the latter may decrease the plasma level of topiramate by about 50%. Valproate lowers the plasma level of topiramate by about 15%. Topiramate may lead to decreased effectiveness of some oral anticontraceptives.

Interactions with other prescription and over-the-counter drugs are not known at this time.

17. Is there an interaction between topiramate and alcohol?

Alcohol may increase the severity of the side-effects of topiramate.

18. Is topiramate safe for a woman who is about to become pregnant, pregnant or nursing an infant?

Topiramate is has been placed in the FDA pregnancy Category C:

"Animal studies have shown an adverse effect on the fetus but there are no adequate studies in humans; The benefits from the use of the drug in pregnant women may be acceptable despite its potential risks . . . ."

19. Is topiramate safe for children and adolescents?

The FDA has recently approved the use of topiramate in children.

20. Can topiramate be used in elderly people?

Older people seem to handle topiramate similarly to younger ones. There is little experience using topiramate for the treatment of psychiatric disorders in the elderly.

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21. Do symptoms develop if topiramate is suddenly discontinued?

There are no specific symptoms that have been described following the abrupt discontinuation of topiramate, other than the seizures that sometimes follow the rapid discontinuation of any anticonvulsant. Only when necessary because of a serious side effect, should topiramate be suddenly discontinued.

22. Is topiramate toxic if taken in overdose?

There is only limited data on the effects of overdoses of topiramate. There have been no reports of deaths following an overdose.

23. Can topiramate be taken along with MAO inhibitors?

Yes, the combination has been used without any special problems.

24. What does topiramate cost?

As of 21 March 04, an on-line pharmacy (Drugstore.com) was selling topiramate for the following amounts per tablet (when bought in lots of 100 tablets):

25 mg - $1.45
100 mg - $2.06
200 mg - $2.6725. Might topiramate be effective in people who have failed to receive benefit from other psychopharmacologic agents?

The major use of topiramate in psychiatry is with people who have mood disorders that have not been adequately controlled by other medications at times including lamotrigine and gabapentin. A developing use is for people with PTSD.

Topiramate has also been shown to decrease craving for alcohol in people with alcoholism, and to prevent migraine headaches.

26. What are the advantages of topiramate?

Topiramate seems to be effective in some people with bipolar mood disorders that have not responded to lithium and/or other mood-stabilizers. Some people who have not been able to tolerate any antidepressant because of switches to mania or increased speed or intensity of cycling, or because of the development of mixed states, have been able to tolerate therapeutic doses of anti- depressants when taking topiramate.

For most people, topiramate has tolerable side effects and it can be taken twice a day.

The weight loss that accompanies topiramate therapy in some instances is useful for those individuals who have gained weight while taking other mood stabilizing drugs. In some studies 20-50% of people taking topiramate lost weight.

27. What are the disadvantages of topiramate?

As topiramate has only been available for a relatively short time, it was first marketed in 1996, there is no information about long term side-effects. As its use with people with mood disorders started even more recently, it is not known if people who initially do well on topiramate continue to do so after many years of treatment.

Topiramate increases the probability of kidney stones. the development of kidney stones may be prevented by increasing one's intake of water.

28. Why should physicians prescribe, and patients take, topiramate, when there are mood regulating medications that have been available for many years and which have been shown to be effective in double-blind placebo- controlled studies?

There are two major reasons why physicians prescribe and patients take topiramate rather than conventional, better established drugs. They are that not everyone benefits from treatment with the older, better known drugs, and that some patients find the side effects of the established drugs to be unacceptable.

As there has not been a good psychopharmacologic treatment for people with PTSD, topiramate offers such people the possibility of medically -induced relief.

29. Is topiramate available in countries other than the USA?

Topiramate is available in many countries throughout the world.

30. Has anything been published on the use of topiramate as a therapeutic agent for people with mood disorders and/or PTSD?

While reports on the use of topiramate as a treatment for people with mood disorders and PTSD have been presented at various psychiatric meetings, little is in print about the psychiatric uses of this medication.

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The following publications are relevant to the psychiatric uses of topiramate:

Alao AO, Dewan MJ.
J Nerv Ment Dis. 2001 Jan;189(1):60-3.
Evaluating the tolerability of the newer mood stabilizers.
[No MEDLINE abstract available]

American Journal of Ophthalmology 2001, 132, 112-114
Presumed topiramate-induced bilateral acute angle-closure glaucoma.
[MEDLINE abstract]

Andrade C.
Bipolar Disord. 2001 Aug;3(4):211-212.
Confusion and dysphoria with low-dose topiramate in a patient with bipolar disorder.
[MEDLINE abstract]

Barbee JG.
Intwenational Journal of Eating Disorders, 2003, 33, 468-472. Topiramate in the treatment of severe bulimia nervosa with comorbid mood disorders: A case series. [MEDLINE abstract]

Berlant JL.
Journal of Clinical Psychiatry 2001, 62 (Suppl 17), 60-63.
Topiramate in posttraumatic stress disorder: preliminary clinical observations.
[MEDLINE abstract]

Berlant J.
Poster, presented at 39th Annual Meeting New Clinical Drug Evaluation Program (NIMH) Boca Raton, Florida, June 1-4, 1999.
Open-lable topiramate treatment of post-traumatic stress disorder.

Berlant J.
Journal of Clinica Psychiatry 2002, 63, 15-20.
Open-label topiramate as primary or adjunctive therapy in chronic civilian posttraumatic stress disorder: a preliminary report.
[MEDLINE abstract]

Besag FM.
Drug Safety 2001, 24, 513-536.
Behavioral effects of the new anticonvulsants.
[MEDLINE abstract]

Bowden CL.
Expert Opin Investig Drugs. 2001, 10, 661-671.
Novel treatments for bipolar disorder.
[MEDLINE abstract]

Brandes JL, Saper JR, Diamond M, et al.
Journal of the Americcan Medical Associagtion, 2004, 291,965-973.
Topiramate for migraine prevention: A randomized controlled trial.
[MEDLINE abstract]

Calabrese JR, Keck PE Jr, McElroy SL, Shelton MD.
Journal of Clinical Psychopharmacology 2001, 21, 340-342.
A pilot study of topiramate as monotherapy in the treatment of acute mania.
[MEDLINE abstract]

Calabrese JR, van Kammen DP, Shelton MD, et al
American Psychiatric Association Annual Meeting 1, New Research Abstracts NR680
Topiramate in severe treatment-refractory mania.
[No MEDLINE abstract available]
[MEDLINE abstract]

Calabrese JR, Shelton MD, Rapport DJ, Kimmel SE.
Journal of Clinical Psychiatry 2002, 63 (Suppl 3),5-9.
Bipolar disorders and the effectiveness of novel anticonvulsants.

Carpenter LL, Leon Z, Yasmin S, Price LH
Journal of Affective Disorders 2002 May; 69, 251-255.
Do obese depressed patients respond to topiramate? a retrospective chart review.
[MEDLINE abstract]

Cassano P, Lattanzi L, Pini S, et al.
Bipolar Disorders 2001, 3, 161.
Topiramate for self-mutilation in a patient with borderline personality disorder.
[No MEDLINE abstract available]

Chengappa K N, Gershon S, Levine J. Bipolar Disorders 2001, 3,215-232
The evolving role of topiramate among other mood stabilizers in the management of bipolar disorder.
[MEDLINE abstract

Chengappa KN, Rathore D, Levine J, et al.
Bipolar Disorder. 1999 Sep;1(1):42-53.
Topiramate as add-on treatment for patients with bipolar mania.
[MEDLINE Abstract]

Chengappa KN, Levine J, Rathore D, Parepally H, Atzert R.
European Psychiatry 2001, 16, 186-190.
Long-term effects of topiramate on bipolar mood instability, weight change and glycemic control: a case-series.
[MEDLINE abstract]

Colom F, Vieta E, Benaberra A, et al
Journal of Clinical Psychiatry 2001, 62, 475-476.
Topiramate abuse in a bipolar patient with an eating disorder.
[MEDLINE abstract]

Davanzo P, Cantwell E, Kleiner J, et al.
Journal of the American Academy of Child and Adolescent Psychiatry 2001, 40, 262-263.
Cognitive changes during topiramate therapy.
[No MEDLINE abstract available]

De Leon OA. Harvard Review of Psychiatry. 2001, 9, 209-222.
Antiepileptic drugs for the acute and maintenance treatment of bipolar disorder.
[MEDLINE abstract]

DelBello MP, Kowatch RA, Warner J, et al.
Journal of Child and Adolescent Psychopharmacology, 2002, 12, 323-330.
Adjunctive topiramate treatment for pediatric bipolar disorder: a retrospective chart review.
[MEDLINE abstract]

Deutsch SI, Schwartz BL, Rosse RB, et al.
Clinical Neuropharmacology, 2003, 26, 199-206.
Adjuvant topiramate administration: a pharmacologic strategy for addressing NMDA receptor hypofunction in schizophrenia.
[MEDLINE abstract]

Doan RJ, Clendenning M.
Canadian Journal of Psychiatry 2000, 45, 937-938.
Topiramate and hepatotoxicity.
[No MEDLINE abstract available]

Drapalski AL, Rosse RB, Peebles RR, Schwartz BL, Marvel CL, Deutsch SI.
Clinical Neuropharmacology 2001, 24, 290-294.
Topiramate improves deficit symptoms in a patient with schizophrenia when added to a stable regimen of antipsychotic medication.
[MEDLINE abstract]

Dursun SM, Deakin JF.
J Psychopharmacol 2001 Dec;15(4):297-301.
Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: A naturalistic case-series outcome study.
[MEDLINE Abstract]

Dursun SM, Devarajan S.
Canadian Journal of Psychiatry 2001, 46, 287-288.
Accelerated weight loss after treating refractory depression with fluoxetine plus topiramate: possible mechanisms of action?
[No MEDLINE abstract available]

Erfurth A, Kuhn G.
Neuropsychobiology 2000, 42 (Suppl 1), 50-51.
Topiramate monotherapy in the maintenance treatment of bipolar I disorder: Effects on mood, weight and serum lipids.
[MEDLINE abstract]

Felstrom A, Blackshaw S.
American Journal of Psychiatry, 2002, 159, 1246-1247 .
Topiramate for bulimia nervosa with bipolar II disorder. [No MEDLINE abstract available]

Gareri P, Falconi U, de Fazio P et al.
Progress in Neurobiology 2000, 61, 353-396.
Conventional and new antidepressants drugs in the elderly.
[MEDLINE abstract]

Ghaemi S N, Manwani S G, Katzow J J, Ko J Y, Goodwin F K.
Annals of Clinical Psychiatry 2001, 13, :185-189.
Topiramate treatment of bipolar spectrum disorders: A retrospective chart review.
[MEDLINE abstract]

Gitlin MJ.
Bulliten of the Menninger Clinic 2001 65, 26-40.
Treatment-resistant bipolar disorder.
[MEDLINE abstract]

Goldberg JF, Burdick KE.
Journal of Clinical Psychiatry 2001, 62 Suppl 14, 27-33.
Cognitive side effects of anticonvulsants.
[MEDLINE abstract]

Gordon A, Price LH
American Journal of Psychiatry 1, 156, 968-969.
Mood stabilization and weight loss with topiramate.
[No MEDLINE abstract available]

Grunze HC, Normann C, Langosh J et al.
Journal of Clinical Psychiatry 2001,62, 464-468.
Antimanic effacacy of topiramate in 11 patients in an open trial with an on-off-on design.
[MEDLINE abstract]

Jochum T, Bar KJ, Sauer H. J Neurology Neurosurgery and Psychiatry, 2002, 73, 208-209
Topiramate induced manic episode.
[No MEDLINE abstract available]

Khan A, Faught E, Gelliam F. et al.
Seizure 1, 8, 235-237.
Acute psychotic symptoms induced by topiramate.
[MEDLINE abstract]

Ketter TA et al.
Neurology 1, 53, (5, Suppl 2), S53-S67.
Positive and negative psychiatric effects of antiepileptic drugs in patients with seizure disorders.
[MEDLINE abstract]

Ketter TA et al.
Cell Mol Neurobiology 1, 19, 511-532.
Metabolism and excretion of mood stabilizers and new anticonvulsants.
[MEDLINE abstract]

Klufas A, Thompson D.
American Journal of Psychiatry. 2001, 158, 1736.
Topiramate-induced depression.
[No MEDLINE abstract available]

Komanduri R.
Journal of Clinical Psychiatry, 2003, 64, 612.
Two cases of alcohol craving curbed by topiramate.
[No MEDLINE abstract available]

Kupka RW, Nolen WA, Altshuler LL et al.
British Journal of Psychiatry, Suppliment 2001, 41, s177-s183.
The Stabley Foundation Bipolar Network. 2. Preliminary ssummary of demographics, ccourse of illness and response to novel treatments.
[MEDLINE abstract]

Kusumakar V, Yatham LN, O'Donovan CA, et al
American Psychiatric Association Annual Meeting 1, New Research Abstracts NR477
Topiramate in rapid-cycling bipolar women.
[No MEDLINE abstract available]

Letmaier M, Schreinzer D, Wolf R, Kasper S.
International Clinical Psychopharmacology. 2001, 16, 295-298.
Topiramate as a mood stabilizer.
[MEDLINE abstract]

Li X, Ketter TA, Frye MA
Journal of Affective Disorders 2002, May;69, 1-14.
Synaptic, intracellular, and neuroprotective mechanisms of anticonvulsants: are they relevant for the treatment and course of bipolar disorders?
[MEDLINE abstract]

McElroy SL, Suppes T, Keck PE, et al
Biological Psychiatry, 2000, 47, 1025-1033.
Open-label adjunctive topiramate in the treatment of bipolar disorders.
[MEDLINE abstract]

McIntyre RS, Mancini DA, McCann S, Srinivasan J, Sagman D, Kennedy SH.
Bipolar Disorders. 2002, 4, 207-213.
Topiramate versus bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single-blind study.
[MEDLINE abstract]

Maidment ID
Annals of Pharmacotherapy, 2002, 36(7):1277-1281 .
The use of topiramate in mood stabilization.
[MEDLINE abstract]

Marcotte D
Journal of Affective Disorders 1998, 50, 245-251.
Use of topiramate, a new anti-epileptic as a mood stabilizer.
[MEDLINE abstract]

Martin R, Kuzniecky R, Ho S, et al.
Neurology, 1, 15, 321-327.
Cognitive side effects of topiramate, gabapentin, and lamotrigine in healthy young adults.
[MEDLINE abstract]

Millson RC, Owen JA, Lorberg GW, Tackaberry L.
American Journal of Psychiatry 2002, 159, 675.
Topiramate for refractory schizophrenia.
[No MEDLINE abstract available]

Normann C, Langosch J, Schaerer LO et al.
American Journal of Psychiatry, 1, 156, 2014.
Treatment of acute mania with topiramate.
[No MEDLINE abstract available]

Pavuluri MN, Janicak PG, Carbray J.
Journal of Child and Adolesc Psychopharmacology, 2002, 12, 271-273.
Topiramate plus risperidone for controlling weight gain and symptoms in preschool mania.
[No MEDLINE abstract available]

Pecuch PW, Erfurth A.
Journal of Clinical Psychopharmacology 2001 21, 243-244.
Topiramate in the treatment of acute mania.
[ No MEDLINE abstract available]

Pinninti NR, Zelinski G.
Journal of Clinicsl Psychopharmacology, 2002, 22, 340 .
Does topiramate elevate serum lithium levels?
[No MEDLINE abstract available]

Post RM
Schizophrenia Research 1, 39, 153-158.
Comparative pharmacology or bipolar disorder and schizophrenia.
[MEDLINE abstract]

Post RM, Frye MA, Denicoff KD, et al.
Neuropsychopharmacology 1998 Sep;19(3):206-219
Beyond lithium in the treatment of bipolar illness.
[MEDLINE abstract]

Post RM, Frye MA, Denicoff KD et al.
Bipolar Disorders 2000, 2, 305-315. Emerging trends in the treatment of rapid cycling bipolar disorder: a selected review.
[MEDLINE abstract]

Schlatter FJ, Soutullo CA, Cervera-Enguix S.
Journal of Clinical Psychopharmacology 2001 21, 464-466.
First break of mania associated with topiramate treatment.
[No MEDLINE abstract available]

Tondo L, Hennen J, Baldessarini RJ.
Acta Psychiatr Scand. 2003 Jul;108(1):4-14.
Rapid-cycling bipolar disorder: effects of long-term treatments.
[MEDLINE abstract]

Vieta E, Gilabert A, Rodriguez A, et al.
Actas Esp Psiquiatr 2001, 29, 148-152.
Effectiveness and safety of topiramate in treatment-resistant bipolar disorder
[MEDLINE abstract]

Vieta E, Goikolea JM, OLivares JM, et al.
Journal of Clinical Psychiatry, 2003, 64, 834-839.
1-year follow-up of patients treated with risperidone and topiramate for a manic episode.

Vieta E, Sanchez-Moreno J, Goikolea JM, et al.
World Journal of Biological Psychiatry, 2003, 4, :172-176.>/I>
Adjunctive Topiramate in Bipolar II Disorder.
[MEDLINE abstract]

Vieta E, Torrent C, Garcia-Ribas G, Gilabert A, et al.
Journal of Clinical Psychopharmacolpgy, 2002, 22, 431-435
Use of topiramate in treatment-resistant bipolar spectrum disorders.
[MEDLINE abstract]

 

Winkelman JW.
Sleep Medicine, 2003, 4, 243-266.

Treatment of nocturnal eating syndrome and sleep-related eating disorder with topiramate.
[MEDLINE abstract]

Source: Ivan K. Goldberg, M.D.

 

 

next: Lithium for Maintenance Treatment of Mood Disorders
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Lithium, Carbamazepine (Tegretol), and Valproic Acid (Depakote) have been used when mood disorders co-exist with ADHD. One frequently sees bipolar patients with supposed comorbid ADHD or diagnosed solely with ADHD. This is becoming increasingly common in adults as well as kids thanks to the popularity of the ADHD diagnosis. The problem is that just about all bipolar patients have a disorder of attention. To differentiate between the two, it is sometimes helpful to look for symptoms that are seen in bipolar disorders but not usually in ADHD, for example:

• racing thoughts
• not needing to sleep or hypersomnia
• changes in energy parallel to the above
• tangential thinking
• overspending, overcommitting
• grandiosity
• grandiose thrill seeking (eg, jumping off of high places)
• psychosis.

When ADHD and Bipolar Disorder are comorbid, starting treatment with a stimulant in these patients will often exacerbate the hyperactivity, flatten affect, and greatly decrease appetite. Some doctors start instead with either clonidine or guanfacine plus one of the following mood stabilizers: lithium, carbamazepine, valproic acid, or lamotrigine.

Once the patient is stable on therapeutic doses, a stimulant can be added if ADHD symptoms remain; if necessary, an antidepressant is sometimes added as well.

The boundary between persistent hypomania and ADHD is unclear. The usual practice is to treat such cases with stimulants before puberty and with mood-stabilizing agents in adulthood.

Drug Monographs -
Selected Medications Mentioned in this Section:

• Lithium Carbonate (Eskalith, Lithobisd, Lithonate, etc.)
• Divalproex Sodium / Sodium Valproate + Valproic Acid (Depakote )
• Carbamazepine (Tegretol)
• Lamotrigine (Lamictal)
• Guanfacine HCL (Tenex)
• Clonidine (Catapres)

 

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