Dana G. Carroll

Use of Antidepressants for Management of Hot Flashes

A growing body of evidence suggests that antidepressant therapies, particularly selective serotonin reuptake inhibitors and venlafaxine, are effective in the management of hot flash symptoms. Several of these agents have the support of the American College of Obstetricians and Gynecologists and the North American Menopause Society. To review the literature on antidepressants for the treatment of hot flashes in women, we searched the PubMed, International Pharmaceutical Abstracts, and MEDLINE databases from inception through May 2009. All publication types that included human participants and that were published in English were eligible for review. These articles, relevant abstracts, and additional references were used to collect pertinent data. Although initial small pilot trials were conducted solely in breast cancer survivors, additional studies have been conducted both in breast cancer survivors and in relatively healthy menopausal women. Data on the benefits with many of these agents are conflicting. Venlafaxine and paroxetine have been studied more extensively than any of the other antidepressants and are more consistent in effectively reducing the frequency and severity of hot flashes, based on these study results. Desvenlafaxine, sertraline, fluoxetine, and citalopram should be considered second‐ or third‐line options if patients fail therapy with or cannot tolerate venlafaxine or paroxetine, based on the current published data. Duloxetine, escitalopram, fluvoxamine, and mirtazapine should be reserved as last‐line therapy until more rigorous studies are conducted assessing their use in the management of hot flashes.

Interactions Between Warfarin and Three Commonly Prescribed Fluoroquinolones

Objective: To critically evaluate a possible increased anticoagulant response during concomitant warfarin and fluoroquinolone therapy. Data Sources: A literature search was conducted using PubMed, International Pharmaceutical Abstracts, and MEDLINE, from inception to January 2008, combining the term warfarin individually with ciprofloxacin, levofloxacin, and moxifloxacin. These 3 quinolones were selected based on their commercial availability and use in the US. Study Selection and Data Extraction: All publication types including human participants and published in English were eligible for review. Reports were selected based on the use of typical treatment courses of fluoroquinolones during concomitant warfarin therapy and the reporting of prothrombin time (PT) or international normalized ratio (INR). Data Synthesis: Twenty-two publications were evaluated including 16 case reports or case series, 2 retrospective cohort studies, and 4 prospective studies, which included 2 placebo-controlled investigations, identified reports covered a wide range of patient ages with multiple comorbidities. Changes in PT and INR values were considerably variable and inconsistent during concomitant warfarin and fluoroquinolone therapy. Results from the 6 structured reports demonstrated mean increases in PT and INR values that were clinically insignificant. However, some patients experienced significant increases above the desired therapeutic range. Increased anticoagulation was typically observed within the first week of concomitant fluoroquinolone therapy. Bleeding complications during times of increased anticoagulation were not always observed, but did result in death for 2 patients. Conclusions: Published data show no consistent increase in anticoagulant effects during concomitant warfarin and 3 commonly prescribed fluoroquinolones. Therefore, more frequent monitoring during concomitant therapy would be prudent.

Use of Gabapentin for the Management of Natural or Surgical Menopausal Hot Flashes

Objective: To review the literature examining the use of gabapentin for treatment of hot flashes during natural or surgically Induced menopause. Data Sources: A literature search was conducted via PubMed, MEDLINE, and International Pharmaceutical Abstracts (1948-November 2010) using the search terms gabapentin, hot flashes, and menopause. Literature was limited to English-language, human studies. Additional material was identified by reviewing reference citations of the articles retrieved. Study Selection and Data Extraction: Studies with data describing gabapentin for hot flash management during natural or surgically induced menopause were included. Any studies including women with a history of breast cancer were excluded. Four studies met the inclusion criteria. Data Synthesis: Gabapentin significantly decreased hot flash frequency and hot flash composite scores by 45-71% from baseline in the 4 trials included in this review. In 2 of the trials, gabapentin was comparable to hormone replacement therapy (71 % vs 72%, respectively, p = 0.63) in decreasing hot flash composite scores at the end of 12 weeks and in decreasing hot flash frequency at the end of 8 weeks (58.9% vs 70.1 %, p > 0.05). In all trials, the most common adverse effects with gabapentin were somnolence/drowsiness, unsteadiness, and dizziness. These adverse effects were most pronounced during the first 1-2 weeks of therapy, but resolved and were similar to those reported with placebo by week 4. These trials were short (<12 weeks) and had small sample sizes; however, their results appear to show that gabapentin is safe and effective for short-term treatment of hot flashes in women who have entered menopause either naturally or surgically. Conclusions: Gabapentin 600-2400 mg/day in divided doses may be a viable option for treating hot flashes in menopausal women who do not want to use hormone replacement therapy.

A review of current treatment strategies for gestational diabetes mellitus.

Approximately 90% of diabetes cases in pregnant women are considered gestational diabetes mellitus (GDM). It is well known that uncontrolled glucose results in poor pregnancy outcomes in both the mother and fetus. Worldwide there are many guidelines with recommendations for appropriate management strategies for GDM once lifestyle modifications have been instituted and failed to achieve control. The efficacy and particularly the safety of other treatment modalities for GDM has been the source of much debate in recent years. Studies that have demonstrated the safety and efficacy of both glyburide and metformin in the management of patients with GDM will be reviewed. There is a lack of evidence with other oral and injectable non-insulin agents to control blood glucose in GDM. The role of insulin will be discussed, with emphasis on insulin analogs. Ideal patient characteristics for each treatment modality will be reviewed. In addition, recommendations for postpartum screening of patients will be described as well as recommendations for use of agents to manage subsequent type 2 diabetes in patients who are breastfeeding.

Implementation of a school-wide clinical intervention documentation system.

Objective. To evaluate the effectiveness and impact of a customized Web-based software program implemented in 2006 for school-wide documentation of clinical interventions by pharmacy practice faculty members, pharmacy residents, and student pharmacists. Methods. The implementation process, directed by a committee of faculty members and school administrators, included preparation and refinement of the software, user training, development of forms and reports, and integration of the documentation process within the curriculum. Results. Use of the documentation tool consistently increased from May 2007 to December 2010. Over 187,000 interventions were documented with over

Critical appraisal of paroxetine for the treatment of vasomotor symptoms

6.2 million in associated cost avoidance. Conclusions. Successful implementation of a school-wide documentation tool required considerable time from the oversight committee and a comprehensive training program for all users, with ongoing monitoring of data collection practices. Data collected proved to be useful to show the impact of faculty members, residents, and student pharmacists at affiliated training sites.

Drug-Induced Lupus Associated with Synthetic Conjugated Estrogens:

Background Vasomotor symptoms (VMS), characterized by hot flashes and night sweats, are the most commonly reported symptoms associated with estrogen deficiency during menopause and occur in up to 70% of women. The goal of treatment is to reduce the frequency and severity of symptoms. Although hormone therapy (HT) is generally recommended as first-line treatment, it is not appropriate for all patients. Antidepressants, specifically selective serotonin reuptake inhibitors, have been evaluated and utilized internationally for alternative treatment for VMS. In 2013, paroxetine mesylate (Brisdelle®) received a US Food and Drug Administration-labeled indication for moderate-to-severe hot flashes, making it the first nonhormonal treatment for VMS associated with menopause. The objective of this review is to critically evaluate available clinical data regarding the efficacy and safety of paroxetine for the treatment of VMS in menopausal women. Methods MEDLINE, PubMed, and Google Scholar were searched using the keywords paroxetine, vasomotor symptoms, hot flashes, and menopause. Searches were limited to humans, English language, and clinical trial design with a primary outcome of hot flash/vasomotor changes. Results Paroxetine (hydrochloride and mesylate) has been associated with a 33%–67% reduction in hot flash frequency with 6–12 weeks of treatment compared to 13.7%–37.8% reductions with placebo in patients both with and without a history of breast cancer. It was also associated with significant reductions in hot flash severity. Benefits of treatment persisted through 24 weeks in the study of the longest duration. Most adverse effects reported were of mild-to-moderate severity, with improved tolerability associated with lower doses (7.5–12.5 mg/day). Conclusion Paroxetine is a safe and effective therapy for the treatment of VMS during menopause. Paroxetine (7.5–12.5 mg/day) should be considered a first-line therapy option for VMS in patients when HT is either inappropriate or intolerable.

Review of metformin and glyburide in the management of gestational diabetes

Objective: To report a case of drug-induced lupus (DIL) in a patient taking Cenestin, a combination product of synthetic conjugated estrogens. Case Summary: A 54-year-old white female presented with a 4 month history of bilateral arm pain that developed and progressively worsened after initiating Cenestin 0.625 mg daily. The patients symptoms, findings on physical examination (eg, degenerative changes of the acromioclavicular joint), and laboratory test results (eg, antinuclear antibody titer 1–640 [normal <1–40]) were suggestive of DIL. Her symptoms rapidly resolved with discontinuation of Cenestin and promptly resumed with reinitiation of the drug. Laboratory test values also improved significantly with discontinuation of Cenestin. Based on these findings and the Naranjo probability scale score, this reaction was probably associated with Cenestin. Discussion: DIL differs from systemic lupus erythematosus in that it is caused by prolonged exposure at adequate doses to a drug rather than being an autoimmune reaction. The most commonly reported and studied medications are hydralazine, quinidine, and procainamide. Other medications have been associated with DIL; however, data are limited in these reports, especially with estrogen. There have been no previous reports in the literature of synthetic estrogen products associated with DIL. Conclusions: A diagnosis of DIL can be very challenging to make, especially since there are no clear criteria on which to base it. While estrogen has rarely been reported to be associated with DIL, it may be considered as a possible cause.

Venlafaxine and desvenlafaxine in the management of menopausal hot flashes

Background: Worldwide, gestational diabetes affects 15% of pregnancies. It is recommended in patients with gestational diabetes to initiate diet therapy and if this is not adequate, insulin is the next treatment modality. While insulin is the preferred drug therapy to manage gestational diabetes in the majority of women, it may not always be the best option for all women. Objective: The purpose of this review is to assess the efficacy and safety of oral agents for treatment of gestational diabetes. Methods: A literature search of the MEDLINE, Ovid databases and Google Scholar was performed using the search term “gestational diabetes” combined with each “metformin” and “glyburide”. The time frame for the search was inception through August 2014. Randomized controlled trials and cohort (both prospective and retrospective) trials, published in English, with human participants were included. Studies included only pregnant women diagnosed with gestational diabetes. Results: There were no significant differences in preterm deliveries, delivery modes, macrosomia, and birth weights and large for gestational age when utilizing glyburide vs insulin for gestational diabetes management. There were significantly higher neonatal intensive care unit admissions as well as longer lengths of stay for hypoglycemia and respiratory distress in babies whose mothers were treated with glyburide versus insulin. For the studies comparing metformin to insulin, there are no significant differences reported for birth weight, gestational age, delivery mode, prematurity and perinatal deaths. Women taking metformin may require supplemental insulin more frequently than those taking glyburide. Conclusion: Glyburide and metformin appear to be safe and effective to manage blood glucose in patients with gestational diabetes who prefer to not utilize insulin or who cannot afford insulin therapy. All other oral therapies to manage blood glucose levels during gestational diabetes should be reserved until additional evidence is available regarding safety and efficacy to both mother and fetus.

In women with gestational diabetes requiring drug treatment, glibenclamide may be inferior to insulin and metformin: metformin (plus insulin when required) performs better than insulin

Vasomotor flushes are common complaints of women during and after menopause, affecting about 75 percent of this population. Estrogen therapy is the most effective treatment for hot flashes. However, there are a significant number of women who have contraindications or choose not to use estrogen due to potential risks such as breast cancer and thromboembolic disorders. These women need alternative options. The selective norepinephrine reuptake inhibitors, venlafaxine and desvenlafaxine, have shown efficacy in alleviating hot flashes. Objective The purpose of this review is to assess the efficacy and tolerability of these two agents for treatment of hot flashes in healthy postmenopausal women. Methods A literature search of the MEDLINE and Ovid databases from inception to June 2011 was conducted. Randomized controlled trials, published in English, with human participants were included. Studies included postmenopausal women, and trials with breast cancer only populations were excluded. Results Venlafaxine reduced hot flashes by 37 to 61 percent and desvenlafaxine by 55 to 69 percent. Both agents were well tolerated. The most common adverse effects were headache, dry mouth, nausea, insomnia, somnolence, and dizziness. Conclusions Based on the evidence, venlafaxine and desvenlafaxine are both viable options for reducing the frequency and severity of hot flashes.