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Antiseizure Medications for Adults With Epilepsy: A Review

Author/s: 
Kanner, A. M., Bicchi, M. M.

Importance: Epilepsy affects approximately 65 million people worldwide. Persistent seizures are associated with a 20% to 40% risk of bodily injuries (eg, fractures, burns, concussions) over 12-month follow-up. The primary goal of epilepsy treatment is to eliminate seizures while minimizing adverse effects of antiseizure drugs (ASDs).

Observations: An epileptic seizure is defined as a sudden occurrence of transient signs and symptoms caused by abnormal and excessive or synchronous neuronal activity in the brain. Focal and generalized epilepsy are the 2 most frequent types of epilepsy; diagnosis is based on the type of seizures. There are 26 US Food and Drug Administration-approved medications for epilepsy, of which 24 have similar antiseizure efficacy for focal epilepsy and 9 have similar efficacy for generalized epilepsy. The decision to initiate an ASD should be individualized, but should be strongly considered after 2 unprovoked seizures or after 1 unprovoked seizure that occurred during sleep and/or in the presence of epileptiform activity on an electroencephalogram and/or in the presence of a structural lesion on the brain magnetic resonance imaging. The ASDs must be selected based on the seizure and epilepsy types, the epilepsy syndrome, and the adverse effects associated with the drug. For focal epilepsy, oxcarbazepine and lamotrigine are first-line therapy, while levetiracetam can be also considered if there is no history of psychiatric disorder. For generalized epilepsy, the selection of the ASD is based on the type of epilepsy syndrome and the patient's sex, age, and psychiatric history. Seizure freedom is achieved in approximately 60% to 70% of all patients. A total of 25% to 50% of patients also experience neurologic, psychiatric, cognitive, or medical disorders, such as mood, anxiety, and attention deficit disorders and migraines. For these patients, selecting an ASD should consider the presence of these disorders and concomitant use of medications to treat them. ASDs with cytochrome P450 enzyme-inducing properties (eg, carbamazepine, phenytoin) may worsen comorbid coronary and cerebrovascular disease by causing hyperlipidemia and accelerating the metabolism of concomitant drugs used for their treatment. They can also facilitate the development of osteopenia and osteoporosis.

Conclusions and relevance: Epilepsy affects approximately 65 million people worldwide and is associated with increased rates of bodily injuries and mortality when not optimally treated. For focal and generalized epilepsy, selection of ASDs should consider the seizure and epilepsy types and epilepsy syndrome, as well as the patient's age and sex, comorbidities, and potential drug interactions.

Keywords 
Epilepsy Antiseizure Medication Seizures treatment

Midodrine for the Prevention of Vasovagal Syncope : A Randomized Clinical Trial

Author/s: 
Sheldon, R., Faris, P., Tang, A., Ayala-Paredes, F., Guzman, J., Marquez, M., Morillo, C. A., Krahn, A. D., Kus, T., Ritchie, D., Safdar, S., Maxey, C., Raj, S. R.

Background: Recurrent vasovagal syncope is common, responds poorly to treatment, and causes physical trauma and poor quality of life. Midodrine prevents hypotension and syncope during tilt tests in patients with vasovagal syncope.

Objective: To determine whether midodrine can prevent vasovagal syncope in usual clinical conditions.

Design: Randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT01456481).

Setting: 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom.

Patients: Patients with recurrent vasovagal syncope and no serious comorbid conditions.

Intervention: Patients were randomly assigned 1:1 to placebo or midodrine and followed for 12 months.

Measurements: The primary outcome measure was the proportion of patients with at least 1 syncope episode during follow-up.

Results: The study included 133 patients who had had a median of 6 syncope episodes in the prior year (median age, 32 years; 73% female). Compared with patients receiving placebo, fewer patients receiving midodrine had at least 1 syncope episode (28 of 66 [42%] vs. 41 of 67 [61%]). The relative risk was 0.69 (95% CI, 0.49 to 0.97; P = 0.035). The absolute risk reduction was 19 percentage points (CI, 2 to 36 percentage points), and the number needed to treat to prevent 1 patient from having syncope was 5.3 (CI, 2.8 to 47.6). The time to first syncope was longer with midodrine (hazard ratio, 0.59 [CI, 0.37 to 0.96]; P = 0.035; log-rank P = 0.031). Adverse effects were similar in both groups.

Limitation: Small study size, young and healthy patients, relatively short observation period, and high proportion of patients from 1 center.

Conclusion: Midodrine can reduce the recurrence of syncope in healthy, younger patients with a high syncope burden."

Keywords 
Midodrine Vasovagal Syncope clinical trial prevention treatment

Sexually Transmitted Infections Treatment Guidelines, 2021

Author/s: 
Workowski, K. A., Bachmann, L. H., Chan, P. A., Johnston, C. M., Muzny, C. A., Park, I., Reno, H., Zenilman, J. M., Bolan, G. A.

The term “sexually transmitted infection” (STI) refers to a pathogen that causes infection through sexual contact, whereas the term “sexually transmitted disease” (STD) refers to a recognizable disease state that has developed from an infection. Physicians and other health care providers have a crucial role in preventing and treating STIs. These guidelines are intended to assist with that effort. Although the guidelines emphasize treatment, prevention strategies and diagnostic recommendations also are discussed.

This report updates Sexually Transmitted Diseases Treatment Guidelines, 2015 (1) and should be regarded as a source of clinical guidance rather than prescriptive standards. Health care providers should always consider the clinical circumstances of each person in the context of local disease prevalence. These guidelines are applicable to any patient care setting that serves persons at risk for STIs, including family planning clinics, HIV care clinics, correctional health care settings, private physicians’ offices, Federally Qualified Health Centers, clinics for adolescent care, and other primary care facilities. These guidelines are focused on treatment and counseling and do not address other community services and interventions that are essential to STI and HIV prevention efforts.

These STI treatment guidelines complement Recommendations for Providing Quality Sexually Transmitted Diseases Clinical Services, 2020 (2) regarding quality clinical services for STIs in primary care and STD specialty care settings. This guidance specifies operational determinants of quality services in various clinical settings, describes on-site treatment and partner services, and indicates when STI-related conditions should be managed through consultation with or referral to a specialist.

Keywords 
Sexually Transmitted Infection treatment STI HIV clinics

Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication

Author/s: 
Schaefer, J. K., Errickson, J., Li, Y., Kong, X., Alexandris-Souphis, T., Ali, M. A., Decamillo, D., Haymart, B., Kaatz, S., Kline-Rogers, E., Kozlowski, J. H., Krol, G. D., Shankar, S, R., Sood, S. L., Froehlich, J. B., Barnes, G. D.

Importance: It is unclear how many patients treated with a direct oral anticoagulant (DOAC) are using concomitant acetylsalicylic acid (ASA, or aspirin) and how this affects clinical outcomes.

Objective: To evaluate the frequency and outcomes of prescription of concomitant ASA and DOAC therapy for patients with atrial fibrillation (AF) or venous thromboembolic disease (VTE).

Design, setting, and participants: This registry-based cohort study took place at 4 anticoagulation clinics in Michigan from January 2015 to December 2019. Eligible participants were adults undergoing treatment with a DOAC for AF or VTE, without a recent myocardial infarction (MI) or history of heart valve replacement, with at least 3 months of follow-up.

Exposures: Use of ASA concomitant with DOAC therapy.

Main outcomes and measures: Rates of bleeding (any, nonmajor, major), rates of thrombosis (stroke, VTE, MI), emergency department visits, hospitalizations, and death.

Results: Of the study cohort of 3280 patients (1673 [51.0%] men; mean [SD] age 68.2 [13.3] years), 1107 (33.8%) patients without a clear indication for ASA were being treated with DOACs and ASA. Two propensity score-matched cohorts, each with 1047 patients, were analyzed (DOAC plus ASA and DOAC only). Patients were followed up for a mean (SD) of 20.9 (19.0) months. Patients taking DOAC and ASA experienced more bleeding events compared with DOAC monotherapy (26.0 bleeds vs 31.6 bleeds per 100 patient years, P = .01). Specifically, patients undergoing combination therapy had significantly higher rates of nonmajor bleeding (26.1 bleeds vs 21.7 bleeds per 100 patient years, P = .02) compared with DOAC monotherapy. Major bleeding rates were similar between the 2 cohorts. Thrombotic event rates were also similar between the cohorts (2.5 events vs 2.3 events per 100 patient years for patients treated with DOAC and ASA compared with DOAC monotherapy, P = .80). Patients were more often hospitalized while undergoing combination therapy (9.1 vs 6.5 admissions per 100 patient years, P = .02).

Conclusion and relevance: Nearly one-third of patients with AF and/or VTE who were treated with a DOAC received ASA without a clear indication. Compared with DOAC monotherapy, concurrent DOAC and ASA use was associated with increased bleeding and hospitalizations but similar observed thrombosis rate. Future research should identify and deprescribe ASA for patients when the risk exceeds the anticipated benefit.

Keywords 
aspirin anticoagulant therapy treatment heart-valve replacement thrombosis

Bupropion and Naltrexone in Methamphetamine Use Disorder

Author/s: 
Madhukar H., Walker, Robrina, Ling, Walter, Cruz, Adriane, Sharma, Guarav, Carmody, Thomas, Ghitza, Udi, Wahle, Aimee, Kim, Mora, Shores-Wilson, Kathy, Sparenborg, Steven, Coffin, Phillip

BACKGROUND

The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied.

METHODS

We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone–bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone–bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses.

RESULTS

A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone–bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone–bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone–bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone–bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone–bupropion during the trial.

CONCLUSIONS

Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo

Keywords 
methamphetamine addiction treatment

Acupuncture for Recurrent Urinary Tract Infection in Women: A Systematic Review and Meta-Analysis

Author/s: 
Qin, X., Corle, M.E., Yang, L., Liang, J., Wang, K., Guo, X., Zhang, A.L., Mao, L., Lu, C., Xue, C.C., Liu, X.

Abstract

Background: Increasing antibiotic resistance has motivated interest in non-antibiotic prophylaxis of recurrent urinary tract infections (rUTI).

Objectives: To conduct a systematic review of the current state of evidence of acupuncture for uncomplicated rUTI in women.

Search strategy: Nine databases (PubMed, Embase, CENTRAL, CINAHL, AMED, CBM, CNKI, CQVIP, Wanfang) were searched from inception to February 2019.

Selection criteria: Randomised controlled trials (RCTs) evaluating the effects of acupuncture and related therapies for prophylaxis or treatment of uncomplicated rUTI in women were included.

Data collection and analysis: Risk of bias was assessed, and the quality and strength of evidence evaluated using the GRADE framework. Results were reported as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI).

Main results: Five RCTs involving 341 participants were included. Methodological quality of studies and strength of the evidence were low to moderate. The chance of achieving a composite cure with acupuncture therapies was greater than that with antibiotics (three studies, 170 participants, RR 1.92, 95% CI 1.31-2.81, I2 = 38%). The risk of UTI recurrence was lower with acupuncture than with no treatment (two studies, 135 participants, RR 0.39, 95% CI 0.26-0.58, I2= 0%) and sham acupuncture (one study, 53 participants, RR 0.45, 95% CI 0.22-0.92).

Conclusions: Acupuncture appeared to be beneficial for treatment and prophylaxis of rUTIs, noting the limitations of the current evidence. Given the growing challenge of antibiotic resistance, there is a need for high-quality RCTs of non-pharmacological interventions such as acupuncture.

Tweetable abstract: This review found that acupuncture may improve treatment and prevent recurrence of urinary tract infection in women.

Keywords: Acupuncture; prophylaxis; recurrent urinary tract infection; systematic review; treatment.

Keywords 
treatment Acupuncture prophylaxis systematic review recurrent urinary tract infection

Combined Pharmacotherapy and Cognitive Behavioral Therapy for Adults With Alcohol or Substance Use Disorders: A Systematic Review and Meta-analysis

Author/s: 
Ray, L.A., Meredith, L.R., Kiluk, B.D., Walthers, J., Carroll, K.M., Magill, M.

Abstract

Importance: Substance use disorders (SUDs) represent a pressing public health concern. Combined behavioral and pharmacological interventions are considered best practices for addiction. Cognitive behavioral therapy (CBT) is a first-line intervention, yet the superiority of CBT compared with other behavioral treatments when combined with pharmacotherapy remains unclear. An understanding of the effects of combined CBT and pharmacotherapy will inform best-practice guidelines for treatment of SUD.

Objective: To conduct a meta-analysis of the published literature on combined CBT and pharmacotherapy for adult alcohol use disorder (AUD) or other SUDs.

Data sources: PubMed, Cochrane Register, MEDLINE, PsychINFO, and Embase databases from January 1, 1990, through July 31, 2019, were searched. Keywords were specified in 3 categories: treatment type, outcome type, and study design. Collected data were analyzed through September 30, 2019.

Study selection: Two independent raters reviewed abstracts and full-text articles. English language articles describing randomized clinical trials examining CBT in combination with pharmacotherapy for AUD and SUD were included.

Data extraction and synthesis: Inverse-variance weighted, random-effects estimates of effect size were pooled into 3 clinically informative subgroups: (1) CBT plus pharmacotherapy compared with usual care plus pharmacotherapy, (2) CBT plus pharmacotherapy compared with another specific therapy plus pharmacotherapy, and (3) CBT added to usual care and pharmacotherapy compared with usual care and pharmacotherapy alone. Sensitivity analyses included assessment of study quality, pooled effect size heterogeneity, publication bias, and primary substance moderator effects.

Main outcomes and measures: Substance use frequency and quantity outcomes after treatment and during follow-up were examined.

Results: The sample included 62 effect sizes from 30 unique randomized clinical trials that examined CBT in combination with some form of pharmacotherapy for AUD and SUD. The primary substances targeted in the clinical trial sample were alcohol (15 [50%]), followed by cocaine (7 [23%]) and opioids (6 [20%]). The mean (SD) age of the patient sample was 39 (6) years, with a mean (SD) of 28% (12%) female participants per study. The following pharmacotherapies were used: naltrexone hydrochloride and/or acamprosate calcium (26 of 62 effect sizes [42%]), methadone hydrochloride or combined buprenorphine hydrochloride and naltrexone (11 of 62 [18%]), disulfiram (5 of 62 [8%]), and another pharmacotherapy or mixture of pharmacotherapies (20 of 62 [32%]). Random-effects pooled estimates showed a benefit associated with combined CBT and pharmacotherapy over usual care (g range, 0.18-0.28; k = 9). However, CBT did not perform better than another specific therapy, and evidence for the addition of CBT as an add-on to combined usual care and pharmacotherapy was mixed. Moderator analysis showed variability in effect direction and magnitude by primary drug target.

Conclusions and relevance: The present study supports the efficacy of combined CBT and pharmacotherapy compared with usual care and pharmacotherapy. Cognitive behavioral therapy did not perform better than another evidence-based modality (eg, motivational enhancement therapy, contingency management) in this context or as an add-on to combined usual care and pharmacotherapy. These findings suggest that best practices in addiction treatment should include pharmacotherapy plus CBT or another evidence-based therapy, rather than usual clinical management or nonspecific counseling services.

Keywords 
substance abuse treatment

Diagnosis and Treatment of Clinical Alzheimer’s-Type Dementia

Author/s: 
Hemmy, L.S, Fink, H.A., Linskens, E.J., Silverman, P.G., MacDonald, R., McCarten, J.R., Talley, K.M.C., Desai, P.J., Forte, M.L., Miller, M.A., Brasure, M., Nelson, V.A., Taylor, B.C., Ng, W., Ouellette, J.M., Greer, N.L., Sheets, K.M., Wilt, T.J., Butler, M.

Objective. To summarize evidence on: (1) the accuracy of brief cognitive tests for identifying clinical Alzheimer’s-type dementia (CATD) in individuals with suspected cognitive impairment; (2) the accuracy of biomarkers for identifying Alzheimer’s disease (AD) in individuals with dementia; and (3) the benefits and harms of prescription drugs and supplements for cognition, function, and behavioral and psychological symptoms of dementia (BPSD) in patients with CATD.

Data sources. Electronic bibliographic databases to March 2019, ClinicalTrials.gov, systematic review bibliographies.

Review methods. Cognitive test accuracy studies must have used explicit CATD diagnostic criteria and a non-CATD control group. Biomarker accuracy studies must have used neuropathologic criteria to define AD cases and non-AD controls. All treatment trials must have enrolled participants with CATD; those evaluating BPSD enrolled individuals with CATD and BPSD. Minimum trial duration was 2 weeks for agitation, aggression, psychosis, and disinhibited sexual behavior, and 24 weeks for other outcomes. Two reviewers rated risk of bias (ROB) and strength of evidence. One reviewer extracted data; a second checked accuracy. We analyzed English-language studies with low or medium ROB.

Results. We analyzed 56 unique studies on the accuracy of brief cognitive tests for CATD, 24 on accuracy of biomarkers for AD (15 brain imaging, nine cerebrospinal fluid [CSF] testing), and 67 trials of CATD treatment (54 reporting cognition or function, 13 reporting BPSD). Multiple brief cognitive tests were highly sensitive and specific (>0.8) for distinguishing CATD from normal cognition, but less so for distinguishing mild CATD from normal cognition or CATD from mild cognitive impairment (MCI). Based on few studies, compared with clinical evaluation alone, amyloid positron emission tomography (PET), fluorodeoxyglucose (FDG)-PET, and combinations of CSF tests added to clinical evaluation may improve accuracy for distinguishing AD from non-AD dementia. Regardless of CATD severity, cholinesterase-inhibitors produced small improvements in cognition and function compared with placebo but may increase serious adverse events and withdrawals due to adverse events. For moderate to severe CATD, memantine plus a cholinesterase inhibitor slightly improved global change and inconsistently improved cognition, but not function, compared with a cholinesterase inhibitor alone. Evidence was mostly insufficient about the effects of prescription drugs and supplements on agitation, aggression, psychosis, or disinhibited sexual behavior.

Conclusion. Brief cognitive tests accurately distinguished CATD from normal cognition, but were less accurate distinguishing smaller clinical differences. Whether biomarkers improve diagnostic accuracy when added to clinical evaluation needs further verification, but potential benefits of testing are limited by lack of effective treatments for AD and non-AD dementias. Cholinesterase-inhibitors slightly outperformed placebo for cognition and function, but evidence of whether any drug treatments improved BPSD was largely insufficient.

Keywords 
cognitive screening tests alzheimer's disease treatment
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