Truly &amp;#x201C;Rational&amp;#x201D; Polytherapy: Maximizing Efficacy and Minimizing Drug Interactions, Drug Load, and Adverse Effects

Louis, Erik K. St.

doi:10.2174/157015909788848929

Cited by 117 publications

(75 citation statements)

References 68 publications

(89 reference statements)

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“…The combination was also well tolerated, as shown by the low discontinuation rate due to AEs (6.7% in the overall population and 3.6% among those who discontinued their SCB). Based on the proposed tenets of combination therapy 2 and the results of this trial, the addition of LCM to LEV could present an acceptable therapeutic approach. Furthermore, for patients who still experience seizures despite combination therapy with a SCB, the cross‐titration schedule described here, as well as by others,10, 20 could offer a practical approach to initiating LCM while minimizing potential pharmacodynamic interactions.…”

Section: Discussionmentioning

confidence: 98%

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Lacosamide and sodium channel-blocking antiepileptic drug cross-titration against levetiracetam background therapy

et al. 2016

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ObjectiveTo assess prospectively the effectiveness of lacosamide (LCM) added to levetiracetam (LEV) after down‐titration of a concomitant sodium channel blocker (SCB) among patients with focal epilepsy not adequately controlled on LEV and SCB.MethodsIn this open‐label trial, LCM was initiated at 100 mg/day and up‐titrated to 200‐600 mg/day over 9 weeks; SCB down‐titration started when LCM dose reached 200 mg/day. Patients remained on stable LCM/LEV doses for 12 weeks’ maintenance (21‐week treatment period). The primary outcome was retention rate on LCM.ResultsDue to recruitment challenges, fewer than the planned 300 patients participated in the trial, resulting in the trial being underpowered. Overall, 120 patients (mean age 39.7 years) started and 93 completed the trial. The most frequently used SCBs were lamotrigine (39.2%), carbamazepine (30.8%) and oxcarbazepine (27.5%). Eighty‐four patients adhered to protocol and discontinued their SCB after cross‐titration, but there was insufficient evidence for 36 patients. Retention rate was 73.3% (88/120) for all patients and 83.3% (70/84) for those with evidence of SCB discontinuation. Seizure freedom for patients completing maintenance was 14.0% (13/93). Discontinuation due to adverse events (6.7%) and lack of efficacy (3.3%) occurred primarily during cross‐titration. Most frequently reported adverse events during treatment were dizziness (23.3%), headache (15.0%) and fatigue (8.3%).ConclusionsIn patients with uncontrolled seizures on LEV/SCB, the LCM/LEV combination appeared to be effective and well tolerated. A cross‐titration schedule—flexible LCM up‐titration, concomitant SCB down‐titration and stable background LEV—could present a feasible and practical approach to initiating LCM while minimizing pharmacodynamic interactions with a SCB.

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Section: Discussionmentioning

confidence: 98%

“…It has been proposed that combination therapy should include selection of drugs with low potential for drug‐drug interactions (DDIs) and for amplification of adverse effects, while minimizing total drug load 2. Combining AEDs based on their mechanism of action can also provide a rational approach to the challenge 1, 3.…”

Section: Introductionmentioning

confidence: 99%

Lacosamide and sodium channel-blocking antiepileptic drug cross-titration against levetiracetam background therapy

et al. 2016

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“…2,4 Treatment options for the 30% to 40% of refractory patients include other AED monotherapies or combination therapy using an additional AED as adjunctive therapy. Data from AED combination therapy trials in patients with POS have shown elimination of seizures in 15% to 35% of patients and reduction of seizure frequency by more than half in 12% to 29% of patients.…”

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confidence: 99%

Effectiveness of Antiepileptic Drug Combination Therapy for Partial-Onset Seizures Based on Mechanisms of Action

et al. 2014

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IMPORTANCE To our knowledge, the current study is the first to describe antiepileptic drug (AED) combination therapy patterns according to their mechanism of action (MOA) in a real-world setting and to evaluate the differences in outcomes comparing different-MOA combination therapy with same-MOA combination therapy for patients with partial-onset seizure.OBJECTIVE To compare treatment persistence and health care use with AED combinations categorized by MOA in patients with partial-onset seizures. DESIGN, SETTING, AND PARTICIPANTS Using the Truven Health MarketScan Commercial Claims Database containing 96 million covered lives from July 1, 2004, through March 31, 2011, adults with concomitant use of 2 different AEDs and a recent partial-onset seizure diagnosis were selected. Antiepileptic drugs were categorized by MOA: sodium channel blockers (SC), gamma-aminobutyric acid analogs (G), synaptic vesicle protein 2A binding (SV2), and multiple mechanisms (M). Patients were assigned a combination category based on their concomitant AED use. MAIN OUTCOMES AND MEASURES Treatment persistence was measured from the start of AED combination therapy until the end of the combination. Health care resource use was measured during the combination treatment duration. Multivariate analyses evaluated AED discontinuation risk and health care use according to MOA combinations.RESULTS Distribution of 8615 selected patients by combination was 3.3% for G+G, 7.5% for G+SV2, 8.6% for G+M, 13.9% for SC+SC, 19.0% for G+SC, 21.5% for SC+M, and 26.3% for SC+SV2. The same-MOA (G+G and SC+SC) combinations had the shortest persistence (mean [SD], 344 [345] days and 513 [530] days, respectively) and greater hazard of discontinuation compared with different-MOA combinations. Patients with different-MOA G combinations had a significantly lower risk for inpatient admission (odds ratio, 0.716; 95% CI, 0.539-0.952; P = .02) compared with G+G combinations. Patients with different-MOA SC combinations had significantly lower risks for emergency department visits (odds ratio, 0.853; 95% CI, 0.742-0.980; P = .03) compared with SC+SC combinations. CONCLUSIONS AND RELEVANCEThe findings suggest that AED combinations with different MOAs have greater effectiveness as measured by treatment persistence and lower risks for hospitalization and emergency department visits. Further research is needed to more fully understand the role of the MOA in achieving optimal outcomes.

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“…It does, however, lead to problems of chronic toxicity, drug interactions, failure to evaluate individual drugs, and sometimes exacerbation of seizures. Also Erik and St. Louis in 2009 [27] reported that Monotherapy is usually preferred over polytherapy whenever possible in epilepsy care. However, a substantial number of patients with intractable epilepsy may respond to AED polytherapy.…”

Section: Discussionmentioning

confidence: 99%

Monotherapy versus Polytherapy in Epileptic Adolescents

et al. 2013

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Objective: Comparison between the effect of monotherapy and polytherapy on cognitive functions and growth measurements among epileptic adolescents. Methods:This study was carried on 57 adolescents from those with antiepileptics either monotherapy or polytherapy, in comparison with 20 controls. All were exposed to full neurological examination, Psychometric studies using Revised Behavior Problem Checklist "RBPC", anthropometric measurements including height, weight, estimation of blood haemoglobin "Hb", serum levels of copper and zinc. Results:We found that 29 cases were with monotherapy and 28 cases were with polytherapy. Scores of RBPC revealed that conduct disorders, socialized aggression and social anxiety withdrawn scales, showed significant increase in epileptic adolescents in comparison with controls which is more in cases with polytherapy, with higher frequency in distractability and restlessness in those with monotherapy. Those with polytherapy showed high frequency in depression and psychomotor retardation. Levels of heamoglobin, copper, and zinc was statistically decreased among epileptics, more with Polytherapy. There was increase in weight and BMI with monotherapy while there was decrease in weight and BMI with polytherpy as compared with controls. Conclusion:Epileptic patients with monotherapy scored better cognitive functions, than those with polytherapy. So we recommend monotherapy in treatment of epilepsy for better cognitive functions.

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Truly “Rational” Polytherapy: Maximizing Efficacy and Minimizing Drug Interactions, Drug Load, and Adverse Effects

Cited by 117 publications

References 68 publications

Lacosamide and sodium channel-blocking antiepileptic drug cross-titration against levetiracetam background therapy

Lacosamide and sodium channel-blocking antiepileptic drug cross-titration against levetiracetam background therapy

Effectiveness of Antiepileptic Drug Combination Therapy for Partial-Onset Seizures Based on Mechanisms of Action

Monotherapy versus Polytherapy in Epileptic Adolescents

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