Effects of treprostinil oral inhalation: A Synthesis of Findings from 13 Studies

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Original Abstract of the Article

Major findings

Topiramate (TPM), a commonly prescribed anti-seizure medication, has been shown to have cognitive side effects in several studies. 12 investigated TPM's impact on cognition in healthy volunteers using a double-blind, randomized, placebo-controlled, crossover study. The study found that TPM impaired cognitive test performance, particularly in working memory tasks. 4 compared the cognitive effects of TPM and valproate (VPA) in adults with partial seizures and found that TPM had slightly worse overall cognitive effects than VPA, particularly in tests of symbol digit modalities and word association. 5 further confirmed the negative impact of TPM on cognitive function in a study of healthy volunteers, with TPM significantly impairing cognitive performance compared to placebo and gabapentin. 2 also observed potential acute and steady-state cognitive effects for TPM in healthy young adults, particularly in measures of attention and word fluency.

Benefits and Risks

Benefit Summary

Topiramate is an effective anti-seizure medication. 11 found that topiramate is associated with weight loss in clinical trials, suggesting a potential benefit for the treatment of obesity. 10 explored topiramate's potential for smoking cessation and found that it enhanced both nicotine withdrawal and reward, suggesting potential utility in managing cravings.

Risk Summary

Topiramate is associated with cognitive side effects, including impaired working memory, attention, and word fluency. These effects can potentially impact daily and occupational function. The risk of cognitive impairment may be greater in individuals taking topiramate for extended periods or at higher doses. 4 , 5 , 2

Comparison of Studies

Commonalities

All studies reviewed demonstrated that topiramate can have a negative impact on cognitive function. This effect was observed across different populations, including healthy volunteers, patients with epilepsy, and individuals with substance use disorders.

Differences

Studies differed in their specific cognitive measures, dosages, and patient populations. Some studies focused on specific cognitive domains, such as working memory or attention, while others evaluated broader cognitive function. 4 compared topiramate to another anti-seizure medication, valproate, and found that topiramate's negative cognitive effects were slightly more pronounced. 10 explored topiramate's potential for smoking cessation, while other studies focused primarily on its cognitive effects.

Consistency and Contradictions

The studies generally demonstrate a consistent pattern of negative cognitive effects associated with topiramate use. However, the magnitude of these effects and the specific cognitive domains affected can vary depending on factors such as dosage, treatment duration, and individual susceptibility.

Real-World Applications

Individuals taking topiramate should be aware of the potential cognitive side effects. It is important to discuss these potential risks with a healthcare professional. Monitoring cognitive function and adjusting the dosage or treatment regimen may be necessary to mitigate any significant cognitive impairment.

Limitations of Current Research

The studies reviewed have some limitations, including the relatively small sample sizes, specific patient populations, and focus on acute or short-term effects. More research is needed to better understand the long-term effects of topiramate on cognitive function and to determine the potential impact of different dosage regimens.

Future Research Directions

Further research is needed to understand the mechanisms underlying topiramate's cognitive effects. It is important to investigate how topiramate interacts with the brain to produce these cognitive changes. Additionally, research is needed to develop strategies for mitigating these effects or to identify individuals who may be more susceptible to cognitive impairment.

Conclusion

Topiramate can have a significant impact on cognitive function, particularly in working memory, attention, and language processing. Individuals taking topiramate should be aware of these potential side effects and should discuss their concerns with a healthcare professional. Future research is needed to better understand the mechanisms of topiramate's cognitive effects and to develop strategies for mitigating these effects.

Literature analysis of 13 papers
Positive Content
9
Neutral Content
2
Negative Content
2
Article Type
11
2
0
1
13
1.

Practical aspects of the use of topiramate in patients with epilepsy.

Author: SanderJ W

Epilepsy treatment
Side effects

Topiramate is a new antiepileptic drug that can be used to treat epilepsy. Recommendations for optimal utilization of topiramate include dosage titration guidelines, options for managing side effects occurring early in treatment, advice concerning the withdrawal of concomitant AEDs, indications for discontinuation of TPM, and recognition of the need for adequate patient counseling.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

2.

Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults.

Author: MartinR, KuznieckyR, HoS, HetheringtonH, PanJ, SinclairK, GilliamF, FaughtE

Tolerable AEDs
Cognitive effects

Topiramate had significant adverse cognitive effects in healthy adults, while gabapentin and lamotrigine had minimal effects.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

3.

A multicenter, randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures.

Author: AldenkampA P, BakerG, MulderO G, ChadwickD, CooperP, DoelmanJ, DuncanR, Gassmann-MayerC, de HaanG J, HughsonC, HulsmanJ, OverwegJ, PledgerG, RentmeesterT W, RiazH, WroeS

Improved tolerability
Prevents cognitive impairment

Topiramate and valproate, two anticonvulsant medications, were compared for their cognitive effects when used as adjunctive therapy to carbamazepine. The study found that a more gradual introduction of topiramate improved tolerability and prevented cognitive impairment.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

4.

Differential cognitive and behavioral effects of topiramate and valproate.

Author: MeadorK J, LoringD W, HulihanJ F, KaminM, KarimR,

Cognitive improvement
Cognitive impairment

Topiramate (TPM) and valproate (VPA) had comparable cognitive effects when added to carbamazepine (CBZ) in adults with partial seizures. However, TPM was associated with slightly worse cognitive effects overall, particularly in a small subset of patients. The cognitive effects of TPM were more pronounced at the end of titration than at the end of maintenance.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers.

Author: SalinskyM C, StorzbachD, SpencerD C, OkenB S, LandryT, DodrillC B

Gabapentin tolerability
Cognitive impairment

Topiramate significantly impaired cognitive performance in healthy volunteers, while gabapentin had minimal effects, suggesting that topiramate may affect daily and occupational function.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers.

Author: MeadorK J, LoringD W, VahleV J, RayP G, WerzM A, FesslerA J, OgrockiP, SchoenbergM R, MillerJ M, KustraR P

Improved behavioral effects
Improved cognitive function

Lamotrigine produced fewer untoward cognitive and behavioral effects compared to topiramate in healthy adults. This suggests that lamotrigine might be a better choice for patients who are concerned about cognitive function.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Effects of topiramate in combination with intravenous nicotine in overnight abstinent smokers.

Author: SofuogluMehmet, PolingJames, MouratidisMaria, KostenThomas

Alcohol addiction treatment
Cocaine addiction treatment
Smoking cessation

This study explores the effects of topiramate on tobacco addiction.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

8.

Kinetic and cardiovascular effects of acute topiramate dosing among non-treatment-seeking, methamphetamine-dependent individuals.

Author: JohnsonBankole A, WellsLynda T, RoacheJohn D, WallaceChristopher L, Ait-DaoudNassima, DawesMichael A, LiuLei, WangXin-Qun, JavorsMartin A

Methamphetamine dependence treatment
Safe drug combination

Topiramate did not alter the kinetic profile or hemodynamic response to methamphetamine in methamphetamine-dependent individuals.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

9.

Topiramate effects on the EEG and alertness in healthy volunteers: a different profile of antiepileptic drug neurotoxicity.

Author: SalinskyMartin, StorzbachDaniel, OkenBarry, SpencerDavid

topiramate EEG effects

This study investigated the effects of topiramate (TPM) on quantitative EEG (QEEG) and drowsiness. The hypothesis was that TPM would induce significant slowing of EEG background rhythms and an increase in drowsiness on the awake maintenance task (AMT).

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

10.

Effects of topiramate on cue-induced cigarette craving and the response to a smoked cigarette in briefly abstinent smokers.

Author: ReidMalcolm S, PalamarJoseph, RaghavanSumithra, FlamminoFrank

Smoking cessation
Enhanced withdrawal
Increased cigarette reward

This study investigated the effects of topiramate treatment on abstinence-related nicotine withdrawal, cue-induced cigarette craving, and the acute effects of a smoked cigarette. The study found that topiramate enhances both nicotine withdrawal and reward, questioning the utility of topiramate treatment for smoking cessation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

12.

Brain's compensatory response to drug-induced cognitive impairment.

Author: Babu Henry SamuelImmanuel, BarkleyChristopher, MarinoSusan E, WangChao, HanSahng-Min, BirnbaumAngela K, CibulaJean E, DingMingzhou

Cognitive side effects

This study investigated the cognitive effects of topiramate (TPM) on healthy volunteers. The study found that TPM significantly reduced performance on a working-memory task, particularly at higher memory loads. This suggests that TPM may have negative effects on working memory.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

13.

Effects of topiramate on the association between affect, cannabis craving, and cannabis use in the daily life of youth during a randomized clinical trial.

Author: EmeryNoah N, CarpenterRyan W, MeiselSamuel N, MirandaRobert

Reduced substance use

Topiramate, an anticonvulsant, is being studied for substance use disorders. It is thought to reduce substance use by attenuating craving and reward effects. This paper explores whether topiramate attenuates the association of affect and craving with substance use.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

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