Qnexa--The next frontier in weight management drugs--or is it?

Below my pontificating you will see a press release for a new weight loss medication, Qnexa.

My initial impressions:

1. This looks like the new twist on the old "phen-fen," phentermine being the common ingredient in both, with the problem compound, fenfluramine, being replaced with topiramate (Topamax). Topiramate is a mood stabilizing drug that has been found to have weight loss effects in some people and has been used in an off-label fashion for this purpose.

2. For the record, I've collected a bunch of references on potential side effects reported with topiramate, including: kidney stones, reduced testosterone in males, dry mouth, nausea, reduced sweating, body temperature regulation (which could become an issue if you're following directions and exercising more), cerebellar cognitive affective syndrome, and delusional parasitosis. (That's when you have the creepy feeling that bugs are crawling all over you when none are there.) References are provided below.

3. People aren't overweight because they have phentermine or topiramate deficiencies. Obesity is a huge target for drug research because there's such a huge market--it's a gold mine for anyone who can create and patent a medication that can stay on the market without its negative side effects forcing it to be yanked. My concern is once this med is used in large numbers some of these side effects are going to become huge problems.

4. Just beware if you decide to try this medication when it becomes available. It's not 100% foolproof. Anyone who prescribes you this medication without advising you of these potential problems may not fully understand how this medication works. And that's your red flag of a potential problem. Be informed!

Otoom S, Batieneh H, Hassan Z, Daoud A. Effects of long-term use Topiramate on fertility and growth parameter in adult male rats. Neuro Endocrinol Lett. 2004 Oct;25(5):351-5.

Sharief M, Viteri C, Ben-Menachem E, Weber M, Reife R, Pledger G, Karim R. Double-blind, placebo-controlled study of topiramate in patients with refractory partial epilepsy. Epilepsy Res 1996 Nov;25(3): 217-24.

Incecik F, Herguner MO, Altunbasak S. Topiramate associated hypohidrosis and hyperthermia. Indian Pediatr. 2008 Mar;45(3):238-40.

Cerminara C, Seri S, Bombardieri R, Pinci M, Curatolo P. Hypohidrosis during topiramate treatment: a rare and reversible side effect. Pediatr Neurol 2006 May;34(5):392-4.

Baillieux H, Verslegers W, Paquier P, De Deyn PP, Mariën P. Cerebellar cognitive affective syndrome associated with topiramate. Clin Neurol Neurosurg. 2008 May;110(5):496-9.


Fleury V, Wayte J, Kiley M. Topiramate-induced delusional parasitosis. J Clin Neurosci. 2008 May;15(5):597-9.

Vega D, Maalouf NM, Sakhaee K. Increased propensity for calcium phosphate kidney stones with topiramate use. Expert Opin Drug Saf 2007 Sep;6(5):547-57.

Koçer A, Dikici S, Atakay S, Okuyucu E. Serum Uric Acid and Lipid Levels While Taking Topiramate for Migraine. Headache. 2007 Dec 27.

Qnexa Meets Primary Endpoint by Demonstrating Superior Weight Loss over
Components and Placebo in the 28-Week Equate Study (OB-301)

Subjects on Full-Dose Qnexa Attained an Average Weight Loss of 9.2% with
66% Achieving 5% or Greater Weight Loss

MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--Dec 11, 2008 - VIVUS, Inc.
(NASDAQ: VVUS), a pharmaceutical company dedicated to the development
and commercialization of novel therapeutic products, today announced
positive results from the EQUATE study (OB-301), a 28-week, phase 3
obesity trial conducted at 32 sites with QnexaTM, an investigational
drug. The EQUATE study met the primary endpoint by demonstrating
superior weight loss with both the full-dose and mid-dose of Qnexa, as
compared to the individual components and placebo. Subjects treated with
full-dose and mid-dose Qnexa had an average weight loss of 9.2% and 8.5%
respectively, as compared to weight loss of 1.7% reported in the placebo
group (ITT LOCF p<0.0001). Average weight loss was 19.8 pounds and 18.2
pounds in the treatment arms as compared to 3.3 pounds in the placebo
group. Qnexa was well-tolerated, with no drug-related serious adverse
events in the study.

"The results from the EQUATE trial once again confirmed our belief in
Qnexa. In addition to hitting the primary endpoints of the study with
the full-dose, we were also able to show excellent results with the
mid-dose of Qnexa," commented Leland Wilson, president and chief
executive officer of VIVUS. "The EQUATE study is the first of three
studies in the Qnexa phase 3 obesity program. Data from the EQUIP and
CONQUER studies, which combined enrolled over 3,750 subjects, is
expected in mid-2009."

The EQUATE study included 756 obese subjects (599 females and 157 males)
across 32 centers in the United States. The average baseline BMI of the
study population was 36.3 kg/ m2 and baseline weight was 223 pounds. The
proportion of patients losing 5% or more of their initial body weight
was 66% for full-dose, 62% for mid-dose and 15% for placebo (p<0.0001).
The proportion of patients losing 10% or more of their initial body
weight was 41% for full-dose, 39% for mid-dose and 7% for the placebo
group (p<0.0001).

The most common drug-related adverse events reported for the full-dose,
mid-dose and placebo group were paresthesia (20%, 15%, 3%), dry mouth
(18%, 12%, 0%), altered taste (15%, 8%, 0%) and constipation (11%, 6%,
6%). Reported drug related adverse events for depression and altered
mood were minimal (1.9%, 0.9% and 1.8% respectively) . Moreover,
individual depression assessments for each subject, as measured by
PHQ-9, demonstrated statistically significant improvements (p<0.05) from
baseline for both Qnexa treatment groups. Overall average completion
rate for the Qnexa treatment group was 71%.

Subjects in the EQUATE study had a 4-week dose titration period followed
by 24 weeks of treatment. The study was a randomized, double-blind,
placebo-controlled, 7-arm, prospective trial with subjects randomized to
receive once-a-day treatment with mid-dose Qnexa (7.5 mg phentermine/ 46
mg topiramate CR), full-dose Qnexa (15 mg phentermine/ 92 mg topiramate
CR), the respective phentermine and topiramate constituents, or placebo.
Subjects were asked to follow a hypocaloric diet representing a
500-calorie/ day deficit and advised to implement a simple lifestyle
modification program.

About the Qnexa Phase 3 Obesity Program

In addition to the EQUATE study, the phase 3 Qnexa program includes two
pivotal, double-blind, placebo-controlled, multi-center studies that
will compare the efficacy and safety of Qnexa to placebo during a
56-week treatment period. The first year long study, known as EQUIP
(OB-302), has enrolled approximately 1,250 morbidly obese adult subjects
with a Body Mass Index (BMI) of 35 or greater with or without controlled
co-morbidities. The second trial, known as CONQUER (OB-303), has
enrolled overweight and obese adult subjects with BMIs from 27 to 45 and
at least two co-morbid conditions, such as hypertension, dyslipidemia
and type 2 diabetes. The co-primary endpoints for these studies are the
mean percent weight loss and the percentage of subjects achieving a
weight loss of five percent or more. Results from these studies are
expected mid-2009. In total the phase 3 program has enrolled
approximately 4,500 subjects.

VIVUS R&D Day December 12, 2008

As previously announced, VIVUS will host a Research and Development Day
Event on Friday, December 12, 2008 at 8:00 a.m. ET in New York City.
Additional details on the data released today will be presented.

To access the webcast of this event, please visit:
http://phx.corporat e-ir.net/ phoenix.zhtml? p=irol-eventDeta ils&c=79161& ev
entID=2046581 or VIVUS' Investors site at http://www.vivus. com. Replay
will also be available on demand from the website at the conclusion of
the program and will run through December 31, 2008.

If you are interested in attending, please contact Brian Korb at The
Trout Group at 646 378 2923 or bkorb@troutgroup. com.

About VIVUS

VIVUS, Inc. is a pharmaceutical company dedicated to the development and
commercialization of novel therapeutic products. The current portfolio
includes investigational product candidates addressing obesity, diabetes
and sexual health. The investigational pipeline includes: QnexaTM, which
is in phase 3, for the treatment of obesity and has completed a phase 2
study for the treatment of type 2 diabetes; avanafil, for which a phase
2 study has been completed for the treatment of erectile dysfunction
("ED") and LuramistTM (Testosterone MDTS(r)), for which a phase 2 study
has been completed for the treatment of Hypoactive Sexual Desire
Disorder ("HSDD"). MUSE(r) is approved and currently on the market for
the treatment of ED. For more information on clinical trials and
products, please visit the company's web site at http://www.vivus. com/.

Certain statements in this press release are forward-looking within the
meaning of the Private Securities Litigation Reform Act of 1995. These
statements may be identified by the use of forward-looking words such as
"anticipate, " "believe," "forecast," "estimated" and "intend," among
others. These forward-looking statements are based on VIVUS' current
expectations and actual results could differ materially. There are a
number of factors that could cause actual events to differ materially
from those indicated by such forward-looking statements. These factors
include, but are not limited to, substantial competition; uncertainties
of patent protection and litigation; uncertainties of government or
third party payer reimbursement; reliance on sole source suppliers;
limited sales and marketing efforts and dependence upon third parties;
risks related to the development of innovative products; and risks
related to failure to obtain FDA clearances or approvals and
noncompliance with FDA regulations. As with any pharmaceutical under
development, there are significant risks in the development, regulatory
approval and commercialization of new products. There are no guarantees
that future clinical studies discussed in this press release will be
completed or successful or that any product will receive regulatory
approval for any indication or prove to be commercially successful.
VIVUS does not undertake an obligation to update or revise any
forward-looking statement. Investors should read the risk factors set
forth in VIVUS' Form 10-K for the year ended December 31, 2007 and
periodic reports filed with the Securities and Exchange Commission.

Topamax and kidneys...these two will probably never be BFF's

I've noticed in looking at my blog statistics that a previous entry on kidney stones resulting from topiramate (Topamax) use continues to be one of my most visited pages on this blog. So when I found more information about this medication and its effect on kidneys I wanted to be sure to share it.

Within 5 days of starting topiramate, the six subjects in this study experienced an average drop of calcium in their urine of about 31% and of citrate by about 40%. When calcium and citrate are not showing up in the urine, it's likely because it's accumulating elsewhere. Like in kidney stones.

Interestingly, increasing the topiramate dose seemed to improve calcium readings and to worsen citrate readings. Meaning you might get less of one kind of kidney stone and more of another.

The authors of this study said that the degree of reduction of urinary citrate was profound enough to be compared to the clinical presentation of renal tubular acidosis. This is a condition in which the body's pH is shifted to an unhealthy level, promoting important changes such as bone demineralization. And THIS will cause rickets in children and osteomalacia in adults. These are not things you will see or feel in those first few days. You need to measure them clinically.

I would strongly recommend, if you and your physician have concluded that the absolute only way to manage your bipolar disorder, your migraine, or your epilepsy, is with topiramate, that you closely monitor your urinary metabolites to be sure you're not doing more harm than good.

And if you're one of those souls who's been convinced that it might be nice to try topiramate to see if it helps you lose weight, consider that you might not just be
losing fat, you might also be losing bone. What's the point of being thin if you have to be sick when you get there?

The only way to know is to monitor. Please don't stick your head in the sand and hope it's not happening to you.

Warner BW, LaGrange CA, Tucker T, Bensalem-Owen M, Pais VM Jr. Induction of progressive profound hypocitraturia with increasing doses of topiramate. Urology. 2008 Jul;72(1):29-32; discussion 32-3.



I found a photo of a kidney stone on the 'net. Imagine trying how it feels to pass something this big through an opening about as big as a piece of cooked pasta. Now you know why I'm trying to get your attention!

What to do about essential tremor

I recently gave a presentation at UCLA, after which a very nice woman asked me if I knew anything about diet and essential tremor. I did not, and I promised to get back to her. What I learned took a little while to get through! For her benefit and the rest of you reading this, here is a short synopsis.

Essential tremor is very strongly genetic. Interestingly, at the same time I was reading research on the topic, I was reading a biography of our second President, John Adams. I learned that he, his son, and his famous cousin Samuel all experienced the affliction, as evidenced in handwriting samples available for analysis. Samuel's tremor was so bad that toward the end of his life he had to dictate all of his correspondence. There was some alcoholism in the family, to which some of this may be attributed, but even so, a genetic link seems to be apparent.

As far as dietary considerations, some of the more common considerations have been whether or not caffeine and ethanol (alcohol) consumption are correlated with tremor severity. While caffeine intake is lower in people who have tremors, tremor severity is not clearly correlated with total caffeine intake. So the reason for this association is not completely understood. Ethanol appears to have a more consistent influence on tremors.

Reduced body mass is a common problem with essential tremor, likely because of the energy spent in nonproductive muscle activity. One research group recommended that physicians pay attention to this and encourage adequate nutritional intake in persons with essential tremor. There may be an interesting conflict in this observation, in that individuals who are trying to gain weight tend to eat more protein...and red meat intake was recently associated with a greater degree of tremor severity in men (not women). This finding underlies the importance of not giving out dietary advice unless it is specifically evidence-based with regard to the problem at hand, not just general advice that might work on the average person.

My friend asked me specifically about the potential for using omega-3 fatty acids to help with tremors. To date, no research is in Pub Med regarding this possibility. However, it was only in April 2008 that the potential connection between omega-3 intake and Parkinson's disease showed up in the literature, so I would venture to guess it won't be long before this research is available.

Supporting my assumption is the fact that a correlation has been shown between a Mediterranean diet pattern and a lower incidence of essential tremor. Even though there is research suggesting that the blood components associated with essential tremor and red meat consumption don't consistently explain the origin of tremors, you have to admit, it certainly never hurts, for many reasons, to eat more fish and less red meat, more fruits and vegetables and healthy fats!

In going through my medication fact sheets, I find that three of the psychotropic medications I regularly research have been reported as being used in an off-label fashion for essential tremor. These medications are olanzapine (Zyprexa), pregabalin (Lyrica), and topiramate (Topamax). Olanzapine and pregabalin are associated with weight gain, and topiramate with weight loss. Given the fact that weight change even in the absence of medications is a problem, it would seem that minimizing the dosages of medications that might interfere with overall health would be an important consideration. Medications can also change one's appetite for certain kinds of food. My experience is that, especially with olanzapine, appetites for carbohydrates and the wrong kind of fats can intensify, which can make adherence to a Mediterranean diet challenging.

The dietary emphases I describe above, to start with the Mediterranean diet in hopes of decreasing the necessary dose of medication for tremor management, would be the most ideal combination of approaches.

I also found some interesting effective non-pharmaceutical therapies that might be worthwhile to try. Who knows, maybe they can help put all that good nutrition into muscle and nerve tissue where it's needed, and prevent unnecessary loss of important tissues. Weight training, for example, improved their steadiness and decreased the magnitude of their tremors. Behavioral relaxation training was also found to reduce tremor severity.

Quite an interesting--albeit unexpected research project! Thank you for stimulating my interest in compiling information with potential to help others.

Lundervold DA, Belwood MF, Craney JL, Poppen R. Reduction of tremor severity and disability following behavioral relaxation training. J Behav Ther Exp Psychiatry. 1999 Jun;30(2):119-35.

Paulson G. Illnesses of the brain in John Quincy Adams. J Hist Neurosci. 2004 Dec;13(4):336-44.

Louis ED, Kavanagh P, Gertrude H. John Adams' essential tremor. Mov Disord. 2005 Dec;20(12):1537-42.

Louis ED, Jurewicz EC, Applegate L, Luchsinger JA, Factor-Litvak P, Parides M.Semiquantitative study of current coffee, caffeine, and ethanol intake in essential tremor cases and controls. Mov Disord. 2004 May;19(5):499-504.

Dogu O, Sevim S, Louis ED, Kaleagasi H, Aral M. Reduced body mass index in patients with essential tremor: a population-based study in the province of Mersin, Turkey. Arch Neurol. 2004 Mar;61(3):386-9.

Louis ED, Keating GA, Bogen KT, Rios E, Pellegrino KM, Factor-Litvak P. Dietary epidemiology of essential tremor: meat consumption and meat cooking practices. Neuroepidemiology. 2008;30(3):161-6.

Scarmeas N, Louis ED. Mediterranean diet and essential tremor. A case-control study. Neuroepidemiology. 2007;29(3-4):170-7.

Louis ED, Zheng W, Applegate L, Shi L, Factor-Litvak P. Blood harmane concentrations and dietary protein consumption in essential tremor. Neurology. 2005 Aug 9;65(3):391-6.

Yetimalar Y, Irtman G, Gurgor N, Basoglu M. Olanzapine efficacy in the treatment of essential tremor. Eur J Neurol 2003 Jan;10(1): 79-82.

Zesiewicz TA, Ward CL, Hauser RA, Pease Campbell JA, Sullivan KL. Pregabalin (Lyrica) in the treatment of essential tremor. Mov Disord 2007 Jan;22(1):139-41.

Zesiewicz TA, Ward CL, Hauser RA, Salemi JL, Siraj S, Wilson MC, Sullivan KL. A pilot, double-blind, placebo-controlled trial of pregabalin (Lyrica) in the treatment of essential tremor. Mov Disord 2007 Jun 19.

Lyons K, Pahwa R, Comella CL, Eisa MS, Elble RJ, Fahn S, Jankovic J, Juncos JL, Koller WC, Ondo WG, Sethi KD, Stern MB, Tanner CM, Tintner R, Watts RL. Benefits and risks of pharmacological treatments for essential tremor. Drug Saf 2003; 26(7): 461-81.

Ondo WG, Jankovic J, Connor GS, Pahwa R, Elble R, Stacy MA, Koller WC, Schwarzman L, Wu SC, Hulihan JF; Topiramate Essential Tremor Study Investigators. Topiramate in essential tremor: a double-blind, placebo-controlled trial. Neurology 2006 Mar 14;66(5):672-7.

Connor GS, Edwards K, Tarsy D. Topiramate in essential tremor: findings from double-blind, placebo-controlled, crossover trials. Clin Neuropharmacol. 2008 Mar-Apr;31(2):97-103.

Bilodeau M, Keen DA, Sweeney PJ, Shields RW, Enoka RM. Strength training can improve steadiness in persons with essential tremor. Muscle Nerve. 2000 May;23(5):771-8.

Topamax and kidney stones

I just ran across an abstract reporting increased uric acid and risk of uric acid stones in users of Topamax. This adds to my list--I'd already found an abstract on the increased risk of calcium phosphate stones. The uric acid research group recommends increasing fluid intake if on Topamax. I would think if you have a history of kidney stones it might be a good idea to discuss with your physician the possibility that another medication may be more appropriate.

Vega D, Maalouf NM, Sakhaee K. Increased propensity for calcium phosphate kidney stones with topiramate use. Expert Opin Drug Saf 2007 Sep;6(5):547-57.
Koçer A, Dikici S, Atakay S, Okuyucu E.Serum Uric Acid and Lipid Levels While Taking Topiramate for Migraine. Headache. 2007 Dec 27.

Epileptic medications and suicidal risk

This just in from the FDA....

...in placebo-controlled trials of 11 different medications used to treat epilepsy (and other disorders as detailed in previous posts), individuals using these medications experienced twice the risk of suicidal thoughts and/or behaviors. It didn't take long for some, only a week, to experience this very significant side effect. The risk WAS higher for those given these medications for epilepsy than those given the medications for other reasons.

This is the FDA's list of medications evaluated in this study:

Carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol XR)
Felbamate (Felbatol)
Gabapentin (Neurontin)
Lamotrigine (Lamictal)
Levetiracetam (Keppra)
Oxcarbazepine (Trileptal)
Pregabalin (Lyrica)
Tiagabine (Gabitril)
Topiramate (Topamax)
Valproate (Depakote, Depakote ER, Depakene, Depacon)
Zonisamide ()

Here is the FDA reference for more information:

http://www.fda.gov/medwatch/safety/2008/safety08.htm#Antiepileptic


MY SOURCE: http://www.docguide.com/news/content.nsf/news/852571020057CCF6852573E1007057A9

Just a note from a nutritionist...fish oil can help reduce seizure activity. I AM NOT, I repeat AM NOT, advising anyone reading this post to discontinue their medications and replace them with a nutritional supplement. However, I AM encouraging you to discuss the possibility of a blend of nutrition therapy AND medication for a potentially gentler approach to safely managing a very serious medical issue.

The multi-talented Topamax?

I just finished adding new references to my Topamax page. I was surprised at how many off-label uses needed to be added to the list!

As I mentioned in an earlier post, off-label uses aren't a bad thing, provided the prescribing physician understands the rationale for the use and the patient understands the nature of off-label uses.

Here is my list, with references posted below.

Alcohol dependence, aggression, alternating hemiplegia, binge eating disorder, bipolar disorder, borderline personality disorder, catatonia, cerebellar tremors, chronic low back pain, chronic paroxysmal hemicrania, cocaine dependence, cyclic vomiting, depression, ejaculation pain, essential tremor, hemiballism, hemicrania continua, hemifacial spasm, idiopathic intracranial hypertension, impulsive behavioral disorders, infantile spasms, kleptomania, neuropathic pain, nicotine dependence, nocturnal eating, obesity, obsessive-compulsive disorder, paraphilic sexual disorders, paroxysmal kinesigenic choreoathetosis, pathologic gambling, pervasive developmental disorders, phrenic nerve palsy, post-traumatic stress disorder, Prader-Willi Syndrome, pseudotumor cerebri, restless legs syndrome, sexual compulsions, sleep-related eating disorder, smoking cessation, spinal myoclonus, trichotillomania.

Rubio G, Ponce G, Jimenez-Arriero MA, Palomo T, Manzanares J, Ferre F. Effects of topiramate in the treatment of alcohol dependence. Pharmacopsychiatry. 2004 Jan;37(1):37-40.

Heilig M, Egli M. Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther 2006 Sep;111(3):855-76.

Collins GB, McAllister MS, Adury K. Drug adjuncts for treating alcohol dependence. Cleve Clin J Med 2006 Jul;73(7):641-4, 647-8, 650-1, passim.

Ma JZ, Ait Daoud N, Johnson BA. Topiramate reduces the harm of excessive drinking: implications for public health and primary care. Addiction 2006;Nov;101(11):1561-8.

Fernandez Miranda JJ, Marina Gonzalez PA, Montes Perez M, Diaz Gonzalez T, Gutierrez Cienfuegos E, Antuna Diaz MJ, Bobes Garcis J. Topiramate as add-on therapy in non-respondent alcohol dependant patients: a 12 month follow-up study. Actas Esp Psiquiatr 2007 Jul-Aug;35(4):236-42.

Hargreaves GA, McGregor IS. Topiramate moderately reduces the motivation to consume alcohol and has a marked antidepressant effect in rats. Alcohol Clin Exp Res 2007 Nov;31(11):1900-7.

Johnson BA. Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings. Biochem Pharmacol 2008 Jan 1;75(1):34-56.

Johnson BA, Rosenthal N, Capece JA, Wiegand F, Mao L, Beyers K, McKay A, Ait Daoud N, Anton RF, Ciraulo DA, Kranzler HR, Mann K, O’Malley SS, Swift RM; Topiramate for Alcoholism Advisory Board; Topiramate for Alcoholism Study Group. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA 2007 Oct 10;298(14):1641-51.

Johnson BA. Topiramate-induced neuromodulation of cortico-mesolimbic dopamine function: a new vista for the treatment of comorbid alcohol and nicotine dependence? Addict Behav. 2004 Sep;29(7):1465-79.

Gobbi G, Gaudreau PO, Leblanc N. Efficacy of topiramate, valproate, and their combination on aggression/agitation behavior in patients with psychosis. J Clin Psychopharmacol 2006 Oct;26(5):467-73.

Navarro JF, Buron E, Martin Lopez M. Antiaggressive effects of topiramate in agonistic encounters between male mice. Methods Find Exp Clin Pharmacol 2007 Apr;29(3):195-8.

Nickel MK, Loew TH. Treatment of aggression with topiramate in male borderline patients, part II: 18-month follow-up. Eur Psychiatry 2007 Nov 14.

Jiang W, Chi Z, Ma L, Du B, Shang W, Guo H, Wu W. Topiramate: a new agent for patients with alternating hemiplegia of childhood. Neuropediatrics 2006 Aug;37(4):229-33.

Appolinario JC, McElroy SL. Pharmacological approaches in the treatment of binge eating disorder. Curr Drug Targets. 2004 Apr;5(3):301-7.

Zilberstein B, Pajecki D, Garcia de Brito AC, Gallafrio ST, Eshkenazy R, Andrade CG. Topiramate after adjustable gastric banding in patients with binge eating and difficulty losing weight. Obes Surg. 2004 Jun-Jul;14(6):802-5.

De Bernardi C, Ferraris S, D'Innella P, Do F, Torre E. Topiramate for binge eating disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Feb;29(2):339-41. Epub 2004 Dec 28.

Kotwal R, Guerdjikova A, McElroy SL, Keck PE Jr. Lithium augmentation of topiramate for bipolar disorder with comorbid binge eating disorder and obesity. Hum Psychopharmacol 2006 Oct;21(7):425-31.

Tata AL, Kockler DR. Topiramate for binge-eating disorder associated with obesity. Ann Pharmacother 2006 Nov;40(11):1993-7.

McElroy SL, Hudson JI, Capece JA, Beyers K, Fisher AC, Rosenthal NR; Topiramate Binge Eating Disorder Research Group. Topiramate for the treatment of binge eating disorder associated with obesity: a placebo-controlled study. Biol Psychiatry 2007 May 1;61(9):1039-48.

Claudino AM, de Oliveira IR, Appolinario JC, Cordas TA, Duchesne M, Sichieri R, Bacaltchuk J. Double-blind, randomized, placebo-controlled trial of topiramate plus cognitive-behavior therapy in binge-eating disorder. J Clin Psychiatry 2007 Sep;68(9):1324-32.

Lykouras L, Hatzimanolis J. Adjunctive topiramate in the maintenance treatment of bipolar disorders: an open-label study. Curr Med Res Opin. 2004 Jun;20(6):843-7.

McDaniel WW, Spegel DR, Sahota AK. Topiramate effect in catatonia: a case series. J Neuropsychiatry Clin Neurosci 2006 Spring;18(2):234-8.

Sechi G, Agnetti V, Sulas FM, Sau G, Corda D, Pitzolu MG, Rosati G. Effects of topiramate in patients with cerebellar tremor. Prog Neuropsychopharmacol Biol Psychiatry 2003 Sep; 27(6): 1023-7.
M

uehlbacher M, Nickel MK, Kettler C, Tritt K, Lahmann C, Leiberich PK, Nickel C, Krawczyk J, Mitterlehner FO, Rother WK, Loew TH, Laplan P. Topiramate in treatment of patients with chronic low back pain: a randomized, double-blind, placebo-controlled study. Clin J Pain 2006 Jul-Aug;22(6):526-31.

Cohen AS, Goadsby PJ. Paroxysmal hemicrania responding to topiramate. J Neurol Neurosurg Psychiatry 2007 Jan;78(1):96-7.

Camarda C, Camarda R, Monastero R. Chronic paroxysmal hemicrania and hemicrania continua responding to topiramate: Two case reports. Clin Neurol Neurosurg 2008 Jan;110(1):88-91.

Kampman KM, Pettinati H, Lynch KG, Dackis C, Sparkman T, Weigley C, O'Brien CP. A pilot trial of topiramate for the treatment of cocaine dependence. Drug Alcohol Depend. 2004 Sep 6;75(3):233-40.

Sofuoglu M, Kosten TR. Novel approaches to the treatment of cocaine addiction. CNS Drugs. 2005;19(1):13-25.

Sofuoglu M, Kosten TR. Emerging pharmacological strategies in the fight against cocaine addiction. Expert Opin Emerg Drugs 2006 Mar;11(1):91-8.

Ohnez A, Kose G, Turanli G. Cyclic vomiting with generalized epileptiform discharges responsive to topiramate therapy. Pediatr Neurol 2006 Nov;35(5):348-51.

Jordi P, Maria-Jose A, Luis-Alfonso M, Mauro S. Management of ejaculation pain with topiramate: a case report. Clin J Pain. 2004 Sep-Oct;20(5):368-9.

Lyons K, Pahwa R, Comella CL, Eisa MS, Elble RJ, Fahn S, Jankovic J, Juncos JL, Koller WC, Ondo WG, Sethi KD, Stern MB, Tanner CM, Tintner R, Watts RL. Benefits and risks of pharmacological treatments for essential tremor. Drug Saf 2003; 26(7): 461-81.

Ondo WG, Jankovic J, Connor GS, Pahwa R, Elble R, Stacy MA, Koller WC, Schwarzman L, Wu SC, Hulihan JF; Topiramate Essential Tremor Study Investigators. Topiramate in essential tremor: a double-blind, placebo-controlled trial. Neurology 2006 Mar 14;66(5):672-7.

Gatto EM, Uribe Roca C, Raina G, Gorja M, Folgar S, Micheli FE. Vascular hemichorea/hemiballism and topiramate. Mov Disord. 2004 Jul;19(7):836-8.

Brighina F, Palermo A, Cosentino G, Fierro B. Prophylaxis of hemicrania continua: two new cases effectively treated with topiramate. Headache 2007 Mar;47(3):441-3.

Alonso Navarro H, Rubio L, Jimenez Jimenez FJ. Topiramate as treatment for hemifacial spasm. Clin Neuropharmacol 2007 Sep-Oct;30(5):308-9.

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