• Topamax (topiramate) is ineffective as an antimanic medication: Repeated placebo-controlled, double-blind, randomized clinical trials have shown that Topamax (topiramate) is no more effective than a placebo in the treatment of the manic or mixed episodes of Bipolar I Disorder. (See references at the end of this post.)



• Topamax (topiramate) is relatively ineffective as a weight-loss medication: The few pounds of weight loss that results from Topamax therapy can easily be matched by the weight loss on any standard diet. Topamax is a very expensive way to lose 10 lbs.



• Topamax (topiramate) causes significant intellectual impairment: Topamax is called "Dopamax" by many physicians because it significantly "dumbs-down" our patients. (See references at the end of this post.)

• Repeated studies have shown that Topomax is no more effective than placebo in the treatment of Bipolar I Disorder.
  
  Bipolar Disord. 2007 Sep;9(6):609-17.
  
  A placebo-controlled, random-assignment, parallel-group pilot study of adjunctive topiramate for patients with schizoaffective disorder, bipolar type.
  
  Roy Chengappa K, Kupfer DJ, Parepally H, John V, Basu R, Buttenfield J, Schlicht P, Houck P, Brar JS, Gershon S.
  
  OBJECTIVES: This pilot study evaluated the efficacy and safety of adjunctive topiramate compared with placebo in the treatment of patients with a diagnosis of schizoaffective disorder, bipolar type (SAD-BT).
  
  METHODS: A sample of 48 adult patients with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) diagnosis of SAD-BT (supported by the Structured Clinical Interview for DSM-IV Axis I Disorder, Patient Edition) were randomly assigned in a 2:1 ratio (favoring topiramate) to 8 weeks of double-blind treatment with topiramate (100-400 mg/day) or placebo. Patients who had achieved a > or =20% decrease from baseline in their Positive and Negative Syndrome Scale (PANSS) total scores were given the opportunity to continue for an additional 8 weeks of double-blind treatment. The dosage of the study medicine was continued unchanged from the earlier 8-week study period. At the end of the study period, the study medicine was tapered and discontinued over a 2-week period. Primary efficacy was assessed at 8 weeks using the mean change between treatment groups of the PANSS total scores in the intent-to-treat population of randomized patients. Several secondary measures were also assessed. Safety analyses included monitoring of adverse events, vital signs, electrocardiogram (ECG) and laboratory values.
  
  RESULTS: Even though both treatments reduced scores on various psychopathology rating scales, adjunctive topiramate treatment (nearly 275 mg/day) did not show increased efficacy relative to placebo on the primary outcome measure (PANSS scale) or any of the secondary outcome measures. Topiramate-treated patients lost significantly more body weight than placebo-treated patients, which led to a significant reduction in body mass index (BMI). Relative to adjunctive placebo, topiramate-treated patients experienced higher rates of paresthesia, sedation, word-finding difficulty, sleepiness, and forgetfulness, but these differences were not statistically significant. There were no clinically significant abnormalities in either the ECG or laboratory results. There were no serious adverse events in the study. Further, there was no worsening of the PANSS total scores (to > or =10% from baseline), and no significant differences between the treatments on worsening of total Montgomery-Asberg Depression Rating Scale (MADRS) scores [1/13 (7.7%) for placebo; 1/25 (4.0%) for topiramate].
  
  CONCLUSIONS: This pilot study did not support clinical efficacy for adjunctive topiramate treatment in patients with SAD-BT. There were no major safety or tolerability issues in this study. Confirming the results of other studies, topiramate-treated patients did experience greater body weight loss and reduction in BMI.
  PMID: 17845276
  
  
  J Clin Psychiatry. 2006 Nov;67(11):1698-706.
  
  Adjunctive topiramate therapy in patients receiving a mood stabilizer for bipolar I disorder: a randomized, placebo-controlled trial.
  
  Roy Chengappa KN, Schwarzman LK, Hulihan JF, Xiang J, Rosenthal NR; Clinical Affairs Product Support Study-168 Investigators.
  
  OBJECTIVE: To investigate the efficacy and safety of topiramate versus placebo as adjunctive therapy for the outpatient management of bipolar I disorder.
  
  METHOD: In this 12-week, randomized, double-blind, placebo-controlled trial, adults with bipolar I disorder (DSM-IV criteria) experiencing a manic or mixed episode with a Young Mania Rating Scale (YMRS) score of >or= 18 while taking therapeutic levels of valproate or lithium received adjunctive topiramate or placebo. Topiramate was titrated from 25 to 400 mg/day over 8 weeks and was continued for 4 additional weeks. The study was conducted from October 2001 through October 2003. The primary outcome measure was the change in YMRS score from baseline to last study visit during the double-blind phase.
  
  RESULTS: The mean +/- SD change in YMRS score from baseline was -10.1 +/- 8.7 (-40.1%) in the topiramate group (N = 143) and -9.6 +/- 8.2 (-40.2%) in the placebo group (N = 144, p = .797). Greater than 50% reduction in YMRS was achieved by 39% of the topiramate group and 38% of the placebo group (p = .914). No significant treatment differences were observed for secondary efficacy measures. Compared with adjunctive placebo, adjunctive topiramate did not worsen mania or induce depression. Paresthesia, diarrhea, and anorexia were more common in the topiramate group. The topiramate group achieved greater reductions than the placebo group in body weight (-2.5 vs. 0.2 kg, p < .001) and body mass index (-0.84 vs. 0.07 kg/m(2), p < .001).
  
  CONCLUSION: In patients treated with lithium or valproate, there was no difference in the reduction of YMRS score in the topiramate and placebo groups. Both groups showed declines of 40%. Topiramate reduced body weight significantly relative to placebo without worsening depressive or manic symptoms.
  PMID: 17196048
  
  
  Bipolar Disord. 2006 Feb;8(1):15-27.
  
  Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trials.
  
  Kushner SF, Khan A, Lane R, Olson WH.
  
  OBJECTIVE: To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder.
  
  METHODS: In four trials, adults hospitalized with acute mania, a diagnosis of bipolar I disorder, history of > or =1 previous manic or mixed episodes, and > or =20 Young Mania Rating Scale (YMRS) score were randomized to double-blind treatment with topiramate (target doses: 200, 400, or 600 mg/day) or placebo; two trials included an active comparator (lithium, 1500 mg/day). The core study duration in all trials was 3 weeks; three trials also had 9-week double-blind extensions. The primary efficacy variable was mean change from baseline in YMRS in the core 3-week study.
  
  RESULTS: Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo (mean YMRS reductions, -5.1 to -8.4). Mean YMRS reductions in lithium-treated groups were significantly greater (p < or = 0.001 versus placebo and topiramate). A similar pattern was observed after 12 weeks of double-blind treatment in studies with double-blind extensions. Paresthesia, appetite decrease, dry mouth, and weight loss were more frequently associated with topiramate than with placebo.
  
  CONCLUSIONS: These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder. Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment-emergent depression. Lithium was confirmed as an effective therapy in this population.
  PMID: 16411977
  



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• Topomax causes very significant intellectual impairment:
  
  
  Neurology. 2005 Mar 8;64(5):792-8.
  
  Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers.
  
  Salinsky MC, Storzbach D, Spencer DC, Oken BS, Landry T, Dodrill CB.
  
  OBJECTIVE: To evaluate the cognitive effects of topiramate (TPM) and gabapentin (GBP).
  
  METHODS: Forty healthy volunteers were randomized to a 12-week course of TPM, GBP, or placebo. Doses were gradually escalated over 10 weeks to a maximum of 400 mg/day of TPM or 3,600 mg/day of GBP or to the highest tolerated dose. Subjects were interviewed and examined biweekly. Cognitive testing was performed prior to initiating the drug and again 12 weeks later, at least 2 weeks after achieving plateau dosing. For each subject and cognitive measure, test-retest Z scores were calculated based on regression equations derived from 73 healthy volunteers. Group comparisons utilized the Wilcoxon test.
  
  RESULTS: There were significant TPM vs GBP and TPM vs placebo differences in test-retest Z scores for four of six target cognitive measures (Digit Symbol, Story Recall, Selective Reminding, Controlled Oral Word Association), always indicating worse retest performance for subjects receiving TPM. Overall, 12 of 24 cognitive measures were similarly affected. TPM effects were large, and several target measures averaged >2 SD of negative change. One measure was significantly affected by GBP.
  
  CONCLUSIONS: Topiramate (TPM) impaired cognitive test performance, whereas gabapentin had minimal effects. The effects of TPM were of sufficient magnitude potentially to affect daily and occupational function.PMID: 15753411
  
  Epilepsy Behav. 2006 Jun;8(4):736-41. Epub 2006 May 2.
  
  Cognitive effects of low-dose topiramate monotherapy in epilepsy patients: A 1-year follow-up.
  
  Lee HW, Jung DK, Suh CK, Kwon SH, Park SP.
  
  The present study was conducted to evaluate the long-term effects of low-dose topiramate (TPM) monotherapy on the cognitive function of epilepsy patients. Forty-seven epilepsy patients received TPM, with target doses of 50, 75, and 100 mg/day. Cognitive tests were performed twice, at baseline and 1 year after starting medication. Thirty-six patients completed the follow-up neuropsychological tests. After a year of treatment, 16 patients (44%) complained of cognitive problems. Although it improved seizure frequency and EEG abnormalities, TPM had significantly negative effects on the digit span and verbal fluency tests. These cognitive effects were dose-related and significantly improved after withdrawal from TPM and substitution with older antiepileptic drugs. In conclusion, even at a low dose, TPM has long-term, negative effects on working memory and verbal fluency.
  PMID: 16647301




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• Equally disturbing, 23-67% for patients treated with Topomax (topiramate) develop metabolic acidosis. This is a potentially serious adverse effect.
  
  
  (Letter to Physicians from Janssen-Ortho, the manufacturer of Topamax)
  
  January 12, 2004
  
  IMPORTANT DRUG SAFETY INFORMATION
  TOPAMAX* (topiramate) use is associated with Metabolic Acidosis
  
  Dear Healthcare Professional:
  
  Janssen-Ortho Inc., following discussions with Health Canada, would like to inform you of emerging important safety information which indicates that TOPAMAX* (topiramate) tablets and sprinkle capsules cause hyperchloremic, non-anion gap metabolic acidosis (decreased serum bicarbonate). TOPAMAX* is approved and marketed as adjunctive therapy for the management of patients (adults and children two years and older) with epilepsy who are not satisfactorily controlled with conventional therapy.
  Data on hyperchloremic, non-anion gap metabolic acidosis are derived from placebo-controlled trials and post-marketing experience in over 2.5 million patients. In clinical trials, the rate of occurrence of a persistently decreased serum bicarbonate ranges from 23-67% for patients treated with topiramate and 1-10% for placebo. The incidence of markedly low serum bicarbonate in clinical trials ranges from 3-11% for topiramate and 0 to <1% for placebo.




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• An individual on topiramate can expect only to lose between 2-6% of their body weight.
  
  Am J Cardiol. 2005 Jul 15;96(2):243-51.
  
  Efficacy and safety of topiramate in the treatment of obese subjects with essential hypertension.
  
  Tonstad S, Tykarski A, Weissgarten J, Ivleva A, Levy B, Kumar A, Fitchet M.
  
  The effect of topiramate on weight and blood pressure (BP) was examined in a randomized, placebo-controlled trial in obese subjects who had hypertension. After a 4-week, placebo, run-in period, 531 obese subjects (body mass index 27 to 50 kg/m(2)) who had established hypertension were randomly assigned to placebo or 96 or 192 mg/day of topiramate. All subjects received a standardized diet, exercise advice, and behavioral modification from run-in through study end. Initially scheduled for 60 weeks on medication, the sponsor ended the study early to develop a new controlled-release formulation. As a consequence, efficacy was assessed within a predefined modified intent-to-treat population (subjects who enrolled early enough to potentially complete 28 weeks on medication). The placebo and 96- and 192-mg groups had respective weight losses of 1.9%, 5.9%, and 6.5% from baseline (p <0.001 for each comparison with placebo) and decreases in diastolic BP of 2.1, 5.5, and 6.3 mm Hg (p <0.015 vs placebo). Systolic BP was decreased by 8.6 and 9.7 mm Hg in the 96- and 192-mg groups and 4.9 mm Hg in the placebo group (p = NS). Compared with placebo, the topiramate groups had larger proportions of subjects whose weight decreased by > or =5% and 10%, whose diastolic BP decreased by > or =5 and 10 mm Hg, and who achieved normalization of BP (BP <130/85 mm Hg). Adverse events included paresthesia, fatigue, taste perversion, loss of appetite, and difficulty with concentration and attention. In conclusion, topiramate produced clinically relevant effects in reducing body weight and BP, with generally mild to moderate adverse effects.
  PMID: 16018851
  
  There are many cheaper, more effective ways to lose weight that topiramate. These other weight loss methods don't significantly lower a person's intellectual functioning (whereas topiramate does). A much more effective way to lose weight is the "3-S Diet" (no seconds, no sugars, no starches).

• Lithium: for non-rapid-cycling Bipolar I Disorder



• Certain anticonvulsants (divalproex sodium/valproic acid and carbamazepine) for the treatment and prevention of rapid-cycling Bipolar I Disorder, and lamotrigine for the prevention of depressive relapses (and to a lesser degree manic relapses).



• Antipsychotic medication: half of all individuals with Bipolar I Disorder need antipsychotic medication to augment the effectiveness of their lithium or anticonvulsant therapies.

Phil Long M.D.
Administrator

quote:

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Originally posted by EmergingArtist

S,
What kind of neg. thoughts do you have?

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