Side effects are variable like many drugs (AAS comes to mind). Suffice it to say topiramate is also known as the California drug....it makes you thin and dumb. However precomp dietingmakes me dumb anyway, so it might not be such a big deal. Here's an indepth article from Loki over at Anavtlabs.com:
Topiramate for Weight Loss
When the FDA finally granted Ortho-McNeil Pharmaceuticals the go-ahead to market their new anti-epilepsy ?wonder-drug? topiramate (under the brand name Topamax ®) in 1996, everything seemed golden for the Raritan, New Jersey pharmaceutical giant. After all, what they had on their hands was a wholly singular and truly versatile drug that had passed well-tolerated through numerous clinical trials, and displayed a sterling safety profile. ?Bub was popped, speed boats were bought? hell, life was good over at Ortho-McNeil. But then, as Topamax started to circulate commercially, a curious effect started being reported over and over in connection with treatments that incorporated it. It caused weight loss. Serious weight-loss, weight loss so marked and widespread that several researchers speculated that it might even be the drug?s downfall; at full therapeutic dosages, patients lost weight so fast it was starting to worry them.
Furthermore, even Ortho-McNeil?s own research staff admitted they didn?t really understand how their drug managed to do this. Were its mechanisms anorectic? Directly lipolytic? Strangely enough, nobody seemed to know. But? in looking back at the data of their clinical trials with topiramate? I saw the phenomenon had been there from the very start; subjects who used topiramate consistently for as little as a month noticed statistically significant weight loss. This was not some form of 'wasting' either? we're talking documented, large-scale fat loss. It seems as if the FDA had just kind of ?overlooked? this little quixotic facet to topiramate during the approval proceedings. Fast-forward a few years, and the exact weight-loss-inducing mechanisms of topiramate are still inconclusive. However, my own personal research on the compound? combined with a plethora of information from other tests and trials on topiramate (not to mention a fair bit of good ol? fashioned speculation)? is starting to lead me to think that I may have topiramate at least partially ?figured out.? So follow along for a little look at the myriad marvels of this novel and potentially rather nifty ?gray-area? weight-loss aide.
Topiramate, a sulphamate fructopyranose derivative, is a broad-spectrum, highly orally bioavailable anti-epileptic drug (AED) or ?anticonvulsant? that is used to treat partial onset and generalized seizures (1). Its precise chemical designation is 2,3:4,5- bis-O-(1-methylethylidene) -ßß-D-fructopyranose sulfamate, and ?raw? topiramate exists as a white, chyrstalline powder with a slightly bitter, ?Leptigen-beta-?esque? taste [but I jest. Please don?t edit me]. As a drug, topiramate boasts a myriad of uses, many of which? albeit fascinating? I could care less about, as well as several others that are quite intriguing to say the least. It is primarily marketed as an AED drug, and has become extremely popular based on its performance in several head-to-head clinical trials against several of the other prominent AED drugs currently available (1,2). In addition, it is also well-regarded in the medical community for its low incidence of side effects (1,2) Furthermore, topiramate demonstrates a remarkable clinical efficacy when it comes to treating individuals who suffer from post-traumatic stress and/or bipolar disorders (2,3,4,5,6). Finally, topiramate has also been used in some recent preliminary research as an alternate method for treating migraines, alcoholism, substance abuse, and binge eating (1,7,8,9). Yes, that?s right: topiramate treatment seems to have a direct and pronounced effect on the body?s neurochemical ?reward-signaling? system, a process we all know has far-reaching consequences when it comes to regulating our eating, activity, and behavioral patterns (10). ?Houston, we may have a good drug here....?
So how exactly does topiramate work? Actually, it exerts its pharmacological effects through a number of mechanisms [author?s note: there are at least five, although I?m only going to address the three I feel are relevant given the scope of this article] (1,2,11). Unlike other AED drugs, topiramate does not raise an individual?s neuro-seizure threshold, but rather works directly in the brain to block its ability to spread (12). One of its primary mechanisms for achieving this is through its potent potentiation of y-aminobutyric acid (GABA) neuroinhibition (1,13). It should be noted that topiramate does not inhibit synaptosomal GABA uptake or interact directly with gamma-aminobutyrate acid-A (GABA-A), nor is it antagonistic towards any other neurotransmitter receptor binding sites. Instead, it increases the frequency at which GABA is able to activate the ?A? receptors (14).
If you couple this with the findings of one study on topiramate which found that a single dose was able to acutely increase cerebral GABA concentrations by 70% for several hours in healthy human subjects, it?s clear that this compound is able to exert a truly powerful effect in this regard (15). It also means that we?ve stumbled upon the first of topiramate?s beneficial effects. Namely, topiramate has the propensity to elevate the release and subsequent circulation of norepinephrine/noradrenaline (through GABA-A activation), a neurotransmitter in the catecholamine family that most are familiar with for its ability to increase lipolysis through inter-signaling with the sympathetic nervous system or SNS (16,17,18).
Another active property of topiramate certainly worth mentioning is its effects on satiety and ?reward signaling.? As a drug, topiramate acts as an antagonist of the kainate/AMPA glutamate receptors (2). More specifically, it antagonizes glutamates? effects at non-N-methyl-D-aspartate (non-NMDA) receptors, inhibiting the ability of glutamate to essentially ?do its job,? particularly in places like the nucleus accumbens, where it acts as a neurotransmitter that is intimately involved in sending the ?ahhhh...that?s-good-shit?-signal, and also the expectant ?ahhhh...that-will-be-good-shit? signal in ?stimulatory? situations (2). Now, coupled with topiramate?s ability to facilitate GABA activity, topiramate likely does an exceedingly good job of ?numbing? the mind to the oft-intoxicating effects of good food, alcohol, and/or some forms of narcotics by inhibiting mesocorticolimbic dopamine (DA) release (19,20,21). So now, not only is topiramate facilitating an increase in lipolysis, it?s also exerting an intense pro-anorectic effect. After all, if both the prospect of eating a twinkie and the actual act of eating it turn out to be one massive, unsatisfying let down, the chances of ?Twinkie acrasia? suddenly become nil-to-none, making that oatmeal, tuna, and greens regimen far easier to stick to.
Stat-Tracker-Score-Update: Topiramate: 2, adipocytes: 0.
Oh, but there?s also one more little interesting, weight-loss-potentiating property that I?m willing to guess topiramate possesses, although I should mention that it is one facet to topiramate supplementation that I would contend does pose a possible health risk in humans. You see, it appears that topiramate treatment is also somehow able to inhibit natural homeostatic thermoregulation of the human body, which is a rather rare effect, and one that certainly warrants further examination. So just how might topiramate accomplish this? Well, one of topiramate?s other pharmacological properties is its ability to inhibit certain isoenzymes of carbonic anhydrase (1,2,22). Another is its ability to actually block certain sodium channels, especially those that are voltage-sensitive (23,24). Together, these two modes of action have actually been demonstrated to induce mild hyperthermia and/or hypohyrdosis, a state where? with the body?s sweat-response impaired? core temperature becomes elevated above normal for a period of time without any internal regulating mechanism to bring it back down (23). If this assessment is accurate, then it?s possible topiramate may exert an effect on body temperature similar to a mild uncoupler or a low dose of T3 by inducing an actual?albeit slight? long-term increase in heart-rate and basal resting energy expenditure (REE; i.e. whole-body thermogenesis). [author?s note: I would care to caution readers though that this is only my initial hypothesis, and I truly feel more work needs to be done in regards to this understanding and accurately evaluating this proposed effect.]
However (and moreover), I would also like to point out that veritable hyperthermia does not appear to be a serious? or even common? result of topiramate use. There are only three documented instances (all occurring in epileptic pediatric patients ages 17-months, 9 years, and 16 years, respectively) of topiramate-induced hyperthermia since the drugs inception, none of which were fatal, and all of which were resolved by the subjects taking a cold bath, probably with bubbles and a rubber ducky (25,26). Upon discontinuation of topiramate, normal sweat function and thermoregulation returned in all three subjects (25,26). Honestly, I almost wish I could say this drug was really dangerous and hardcore, but the simple fact is that anything that?s most potentially dangerous direct side-effect can be mitigated by a friggin? shower just isn?t all that ?riskeé? in my opinion.
So now that I?ve addressed the potential and proposed mechanisms through which topiramate works in the body, I?d like to move on briefly to discuss the actual documented effects of the drug on body composition, because, ?they ain?t too shabby.? According to Ortho-McNeil?s own data on the efficacy of topiramate at promoting weight loss, the company estimates that approximately 90% of all users have experienced some form of weight loss when administered the drug for a given period of time, with higher doses generally being associated with greater weight loss (24).
Recently, these predictions have been validated by several clinical studies (13,27,28,29). In one study, a group of adults who suffered from onset-seizures had their weight, BMI, and bodyfat percentage tracked over one year of topiramate treatment while no changes were implemented in regards to diet or exercise. In non-obese subjects, one year of topiramate treatment resulted in a 7.3% mean reduction in bodyweight. In obese subjects, the weight loss was even more pronounced; mean bodyweight reduction in that group was 11%. In both cases, the research team was clear to note that ?weight loss was primarily caused by a reduction in body-fat mass? (27). Furthermore, even after a full year, not a single subject displayed any sign of weight rebound, every one having settled in at their new, leaner ?setpoint.?
A second, smaller study, this time conducted with bipolar patients, also makes a strong case for topiramate?s ability to induce weight loss without any set changes in diet or activity levels (13). For example, one specific female in the trial, designated ?Mrs. A,? entered the trial at a bodyweight that the researchers classified ?detrimentally obese.? For the next three months, Mrs. A received 375mg (125mg in the morning and a further 150mg in the evening) of topiramate a day. There were no changes made to her existing medication regimen, nor was she asked to make any changes in regards to her food intake or lifestyle choices. After one month, and then again at three months of treatment, her weight was checked and evaluated. The changes, needless to say, were profound. With topiramate therapy, Mrs. A lost forty-two pounds in the first month of treatment alone, and then went on to lose another fourteen over the course of the next two months, ultimately decreasing her total body mass by nearly 25%. Even the study?s lone, non-obese subject (another female who was actually fairly lean to begin with), also experienced noticeable weight-loss with topiramate. During her three months on topiramate, she managed to lose eighteen pounds, once again, with no changes in diet or activity level (13).
In sum, what we have with topiramate is a drug that works through several different pathways to promote weight loss and inhibit weight gain. It?s ability to regulate neurotransmitter release and function, inhibit food cravings and improve self-control through the negation of ?fed state? related reward mechanisms, as well as its ability to also potentially elevate REE makes it a drug with serious potential for the resourceful and experimental dieter. From the studies testing for weight loss with topiramate, the ?ideal? weight-loss dose appears to be roughly 400mg/day, with returns diminishing noticeably in this regard at higher doses. And, while I myself have obtained a quantity of topiramate, I have as of yet been unable to test it for myself, nor am I aware of any other individual in the bodybuilding community who has experimented with it to date. Thus, I will leave it up to you the reader to decide if you feel topiramate might be a beneficial and/or worthwhile investment in lieu of your current goals and priorities for phenotype-augmentation.
Lastly, I would like to point out that? as topiramate is a categorically unique drug that has only recently emerged on the pharmaceutical landscape? there is simply no information about the long term side-effects of its use. Also, while side-effects with short-term topiramate usage (i.e. one year or less) are rare (and also dose-dependent with a high correlation to heavy, long-term dosage schemes), topiramate has been associated with sensations of drowsiness, nervousness, tingling or numbness in various parts of the body, and in rare cases exerts a detrimental effect on motor skills and cognitive faculties (1,2). Also, the formation of kidney stones has been observed in roughly 1% of regular topiramate users (1,2). There is no known toxicity level for topiramate, although dosages as high as 1.6g/day have been tolerated in adult human studies without adverse effect (28).
In general, there has been little research conducted on topiramate and its possible interactions with other medications, although no egregious incidents of detrimental interactions have been reported thus far (25,30). For obvious reasons, it would probably be a poor idea to stack or use topiramate concomitantly with any other carbonic anyhydrase inhibitors, as the risk of developing either hyperthermia, nephrolithiasis, or hyperhidrosis would likely be quite high. If you are using oral contraceptive drugs, you should also avoid topiramate, as it has been found to decrease their efficacy markedly (1,2,25). Also, I do not at all advocate the use of topiramate in conjunction with alcohol or CNS depressant drugs, as the use of both simultaneously could potentially lead to the onset of depression, pronounced cognitive impairment, or adverse neuropsychiatric episodes.
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) but if you don't need an A-D, should u be taking one? (Just in case it becomes a diet-aid...). 
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