"N-Acetylcysteine for Obsessive-Compulsive and Related Disorders in Children and Adolescents: A Review".

OBJECTIVE: To evaluate clinical data using oral n-acetylcysteine (NAC) in obsessive-compulsive and related disorders (OCDRD) treatment. DATA SOURCES: PubMed, Ovid MEDLINE (1946-July 2022), and the Cochrane Library database were searched using the terms NAC, children, adolescent, obsessive-compulsive disorder (OCD), trichotillomania (TTM), excoriation, hoarding disorder, and body dysmorphic disorder. Bibliographies were reviewed for relevant trials and case studies. STUDY SELECTION AND DATA EXTRACTION: English language, clinical trials, or case studies analyzing NAC use in patients aged 3 to 21 years old with OCDRD as determined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. DATA SYNTHESIS: Three randomized double-blind placebo-controlled trials of NAC in children and adolescents studied 121 patients with OCDRD. Trials assessed symptom severity from baseline to 10 to 12 weeks of NAC therapy. Two OCD trials identified statistically significant improvements, with only 1 trial demonstrating a clear clinically relevant difference from placebo. One trial in TTM found no difference between the NAC and placebo. Adverse effects were mild and included nausea, blurred vision, fatigue, tremor, and sweats. N-acetylcysteine titrated to 2400 or 2700 mg/day in divided doses was the most studied regimen. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Many OCDRD patients fail to completely respond to first-line treatment with cognitive behavioral therapy (CBT) and/or selective serotonin reuptake inhibitors (SSRIs) leaving practitioners with few additional treatment options. Preliminary efficacy and safety data are presented in this review. CONCLUSIONS: Limited evidence suggests children and adolescents with OCD refractory to SSRIs or CBT may benefit from NAC augmentation.

Inhaled Amphotericin B as Aspergillosis Prophylaxis in Hematologic Disease: An Update.

This review summarizes the literature on inhaled amphotericin B for invasive aspergillosis prophylaxis in patients with neutropenia secondary to hematologic malignancy treatment or stem cell transplant. Six trials, 2 randomized controlled and 4 with historical controls, were identified. Three inhaled amphotericin B deoxycholate trials found a reduced invasive aspergillosis incidence, 1 reaching statistical significance. Three inhaled liposomal amphotericin B trials demonstrated similar reductions with 2 finding statistical significance. Relative risk reductions for invasive aspergillosis were routinely 40-60%. Both formulations were without reported systemic or severe adverse effects. The most common adverse events were cough, bad taste, and nausea. Discontinuation rates ranged from 0-45%. The only randomized, placebo-controlled trial utilized inhaled liposomal amphotericin B reported a nearly 60% relative risk reduction. Inhaled liposomal amphotericin B 12.5 mg twice weekly is an alternative for invasive aspergillosis prophylaxis in high risk neutropenic patients with hematologic malignancies and stem cell transplant recipients when recommended azole agents are contraindicated or should not be used.

Bumetanide for Autism Spectrum Disorder in Children: A Review of Randomized Controlled Trials.

OBJECTIVE: To evaluate clinical trials using bumetanide in autism spectrum disorder (ASD) treatment. DATA SOURCES: PubMed and Ovid MEDLINE (1946 to October 2018) were searched using terms bumetanide and autism. Bibliographies were reviewed for other relevant trials. STUDY SELECTION AND DATA EXTRACTION: English language, randomized, controlled, clinical trials in humans were evaluated. Three trials met all inclusion criteria. DATA SYNTHESIS: Oral bumetanide was studied in 208 patients, 2 to 18 years old, with ASD. Trials evaluated bumetanide's impact on core behavioral features using several different autism assessment scales. All trials used the Childhood Autism Rating Scale to assess improvement at 90 days, with one trial finding statistical significance. The Clinical Global Impressions Scale identified statistically significant improvements in 2 of the 3 trials. The Autism Behavioral Checklist and Social Responsiveness Scales identified statistical benefit in the 2 trials utilizing those outcomes. Behaviors most improved by bumetanide included social communication, interactions, and restricted interest. No dose-effect correlation was identified in the dose-ranging trial. Adverse effects, including hypokalemia and polyuria, occurred more often with higher doses and resulted in withdrawal rates of 17% to 43%. Bumetanide 0.5 mg twice daily was the most studied and best tolerated dose. Limitations included unclear clinical success definitions and evaluation methodology variability. Relevance to Patient Care and Clinical Practice: No effective treatment options for core ASD symptoms have been approved. This review presents preliminary safety and efficacy data for bumetanide in ASD. CONCLUSIONS: Low-dose oral bumetanide may be useful in patients with moderate to severe ASD when behavioral therapies are not available.

Comparing the Impact of Prescription Omega-3 Fatty Acid Products on Low-Density Lipoprotein Cholesterol.

Elevated levels of triglycerides are associated with pancreatitis and an increased risk of coronary heart disease. Numerous pharmacologic therapies are available to treat hypertriglyceridemia, including prescription omega-3 fatty acids, which reduce triglyceride levels by 20-50%. Available data indicate the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be beneficial for secondary prevention of coronary heart disease. Products containing DHA may increase low-density lipoprotein cholesterol (LDL-C) and, subsequently, coronary heart disease risk. We reviewed prescription omega-3 fatty acid products, of which two-omega-3 acid ethyl esters (OM3EE) and omega-3 carboxylic acid (OM3CA)-contain both DHA and EPA, whereas the other-icosapent ethyl (IPE)-contains EPA only. We identified three retrospective chart reviews and three case reports comparing IPE with OM3EE, whereas two studies compared IPE with placebo. We also reviewed the major studies of OM3EE versus placebo used to gain US FDA approval. LDL-C levels decreased or did not increase significantly in all available studies and case reports in patients receiving the IPE product, with the best data supporting a dose of 4 g per day. The majority of studies only included patients taking IPE concomitantly with statins, but limited data from one study using IPE monotherapy showed a small reduction in LDL-C. Many questions remain regarding IPE, including whether the product reduces cardiovascular events and mortality.

Nebivolol versus other beta blockers in patients with hypertension and erectile dysfunction.

Erectile dysfunction (ED) impacts over 100 million men worldwide and occurs at a higher incidence in men with hypertension. Beta blockers are one of several antihypertensive drug classes associated with ED. Nebivolol is a beta blocker with vasodilating properties mediated through endothelial release of nitric oxide which facilitates penile erection. Thus, nebivolol may offer an advantage over other beta blockers in the patient with hypertension and ED. A literature search comparing nebivolol with other beta blockers identified four European studies of limited duration, with the longest study being 28 weeks. Survey scores for erectile function showed significant improvement in erectile function with nebivolol in two of the studies, while the other two studies showed erectile function did not significantly worsen with nebivolol as compared with other beta blocker agents. One study showed improved erectile function scores, possibly due to the presence of a Hawthorne effect. Based on this small sample of studies, nebivolol may be of use in the patient with or at risk of developing ED, when a practitioner specifically wants to use a beta blocker as add-on antihypertensive treatment.

Gabapentin in Alcohol Dependence.

Objective: To review the literature related to the use of gabapentin in alcohol dependence following acute alcohol withdrawal. Data Sources: Searches of MEDLINE (1946-January 2015) and Cochrane Database (2005-January 2015) were performed using gabapentin, alcohol, and alcoholism as MeSH terms and keywords. Results were limited to human trials in English-language journals. Study Selection and Data Extraction: Inclusion criteria included randomized controlled trials with a minimum 4 weeks of gabapentin therapy and at least one alcohol dependence related outcome measure (ie, cravings, abstinence, percent days abstinent, or heavy drinking days). Six randomized clinical trials were identified. Data Synthesis: Four trials identified beneficial effects of gabapentin on at least one alcohol-related outcome measure. Two smaller studies, which enrolled patients with minimal withdrawal symptoms, failed to demonstrate beneficial effects on primary outcomes related to heavy drinking or abstinence. Gabapentin at doses up to 1800 mg daily was well tolerated with no serious adverse drug reactions being reported. Conclusions: Clinical trials have shown gabapentin is a well-tolerated adjunctive therapy in the management of alcohol dependence. The strongest efficacy evidence occurred in patients experiencing moderate to severe withdrawal when gabapentin was administered early in or concurrently during acute withdrawal and continued for up to 12 weeks.

Acetaminophen for patent ductus arteriosus.

OBJECTIVE: To evaluate the literature describing acetaminophen use in treatment of patent ductus arteriosus (PDA). DATA SOURCES: Searches were conducted in MEDLINE with full text (EBSCOhost; 1946 to September 2014) using the search terms acetaminophen, paracetamol, and patent ductus arteriosus. The references of identified articles were reviewed to identify other relevant articles. STUDY SELECTION AND DATA EXTRACTION: Human clinical trials and case reports limited to the English language were reviewed. In all, 12 case reports and 2 randomized, controlled clinical trials explored the use of acetaminophen in treating PDA. DATA SYNTHESIS: The case reports described the use of oral or intravenous acetaminophen in patients with contraindications to or who had previously failed nonsteroidal anti-inflammatory drug therapy for PDA. More than 76% of patients achieved successful PDA closure in reported cases. The clinical trials compared the efficacy of oral acetaminophen versus oral ibuprofen in preterm infants. Acetaminophen was noninferior to ibuprofen, with closure rates from 72.5% to 81.2%. The acetaminophen dose used in most case series and trials was 15 mg/kg dose every 6 hours for 3 days. Acetaminophen therapy was well tolerated, with only a few incidents of elevated liver enzymes being reported. CONCLUSION: Oral acetaminophen is an alternative to PDA therapy in preterm infants when indomethacin/ibuprofen is not effective or is contraindicated, and it may be considered before surgical ligation.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for the prevention of migraines.

OBJECTIVE: To evaluate the literature examining the efficacy of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for migraine prophylaxis. DATA SOURCES: MEDLINE (1966-October 2009) and International Pharmaceutical Abstracts were searched using the terms migraine, headache, renin-angiotensin system, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, aldosterone antagonist, and the individual agents in these classes. STUDY SELECTION AND DATA EXTRACTION: English-language human clinical trials, case reports, and systematic reviews were evaluated for efficacy and safety data. The references of reviewed articles were examined to identify additional sources. DATA SYNTHESIS: Preventative trials evaluating ACE inhibitors consist of a case series, 2 open-label trials, and a placebo-controlled trial. Lisinopril reduced headache hours 20%, headache days 17%, and migraine days 21% versus placebo in the controlled trial (p < 0.05). Clinically significant (>50%) reductions in migraine measures were more common (52-66%) in open-label ACE inhibitor trials than in the controlled (32-36%) trial. Preventive trials evaluating ARBs consist of a meta-analysis, an open-label trial, and 2 placebo-controlled trials. Candesartan reduced headache hours 31%, headache days 26%, and migraine days 28% versus placebo in the first controlled trial (p < or = 0.001). Telmisartan did not reduce any prespecified primary or secondary outcome measures in the second controlled trial. Clinically significant reductions (>50%) in migraine measures were more common (54-88%) in open-label ARB trials than in the controlled (26-38%) trials. A prescription database review found that ACE inhibitor or ARB therapy halved the use of abortive migraine agents compared to diuretic therapy. CONCLUSIONS: ACE inhibitors and ARBs have migraine prophylaxis activity similar to that of some currently utilized agents. Low-dose lisinopril or candesartan may be reasonable second- or third-line agents, particularly in patients with other indications for ACE inhibitor or ARB therapy. Further controlled clinical trials are needed to delineate the role of these agents in migraine prevention.

Phosphodiesterase-5 inhibitors for lower urinary tract symptoms in men.

OBJECTIVE: To review the efficacy of phosphodiesterase-5 (PDE-5) inhibitors for the treatment of lower urinary tract symptoms in men. DATA SOURCES: MEDLINE and International Pharmaceutical Abstracts were searched (1970-August 2007) using the terms phosphodiesterase inhibitor, sildenafil, vardenafil, tadalafil, lower urinary tract symptoms, and benign prostatic hypertrophy. STUDY SELECTION AND DATA EXTRACTION: English-language clinical trials, case reports, and background material were evaluated for safety and efficacy data. References of reviewed articles were examined and used to identify additional sources. DATA SYNTHESIS: Erectile dysfunction (ED) and lower urinary tract symptoms have numerous shared risk factors and are common in aging men. PDE-5 inhibitors may relax urinary tract smooth muscle tissue, which has led to interest in their utility for lower urinary tract symptoms. Six 12 week clinical trials were identified. Three uncontrolled trials (N = 168) examined the effects of on-demand sildenafil ED dosing on lower urinary tract symptoms. The 2 largest trials found that, the greater the ED response, the larger the reduction in lower urinary tract symptoms. A single prospective placebo-controlled trial (N = 369) studied sildenafil 100 mg daily in men with ED and lower urinary tract symptoms. Lower urinary tract symptoms improved significantly in the sildenafil group; patients with the worst lower urinary tract symptoms experienced the greatest benefits. An open-label trial (N = 62) compared daily sildenafil 25 mg, alfuzosin 10 mg, or sildenafil 25 mg plus alfuzosin 10 mg on ED and lower urinary tract symptoms. Combination therapy resulted in greater improvements in ED and lower urinary tract symptoms and urinary flow than did either drug alone. The effects of daily tadalafil 20 mg were studied in 281 men with lower urinary tract symptoms independent of ED. Tadalafil produced statistically significant but clinically modest improvements in lower urinary tract symptoms when compared with placebo. CONCLUSIONS: PDE-5 inhibitors consistently produced modest reductions in lower urinary tract symptoms. Further studies are needed to fully elucidate the efficacy, cost effectiveness, safety, and appropriate place in therapy of PDE-5 inhibitors. At this time, data are insufficient to routinely recommend chronic use of PDE-5 inhibitors for lower urinary tract symptoms in men.

Pyridostigmine in the treatment of orthostatic intolerance.

OBJECTIVE: To review the efficacy of pyridostigmine bromide for the treatment of orthostatic intolerance. DATA SOURCES: MEDLINE and International Pharmaceutical Abstracts were searched (1966-December 2006) using the terms pyridostigmine, acetylcholinesterase inhibitor, orthostatic intolerance, orthostatic hypotension, neurogenic orthostatic hypotension, postural tachycardia syndrome, tachycardia, and orthostatic tachycardia. STUDY SELECTION AND DATA EXTRACTION: Pertinent English-language human clinical trials, case reports, and background material were evaluated for safety and efficacy data. The references of reviewed articles were reviewed and used to identify additional sources. DATA SYNTHESIS: Pyridostigmine bromide has been associated with improved baroreceptor sensitivity and presents a novel approach to treatment of orthostatic intolerance. Four single-dose trials and a follow-up survey encompassing a total of 106 patients were identified. One open-label and one placebo-controlled single-dose trial in patients with neurogenic orthostatic hypotension (NOH) found statistically significant improvement in standing diastolic blood pressures (DBP). Absolute improvements in standing DBP were 3.7 and 6.4 mm Hg in the open-label and controlled trials, respectively. Long-term data consist of a single survey of patients receiving open-label pyridostigmine bromide. Twenty-nine percent of patients who initiated maintenance pyridostigmine bromide discontinued therapy. Concomitant NOH medications were taken by 75% of patients, and 85% of patients reported receiving benefit from pyridostigmine bromide. When evaluated for postural tachycardia syndrome, pyridostigmine bromide significantly reduced standing heart rate (10%). Pyridostigmine bromide significantly reduced symptom scores when compared with baseline but not placebo. The majority of patients included in these trials did not have supine hypertension. CONCLUSIONS: Single doses of pyridostigmine bromide produced modest but statistically significant improvements in hemodynamic measurements. At this time, long-term data are insufficient to support recommending the routine use of pyridostigmine bromide for treatment of orthostatic intolerance.

Short-course oral antiviral treatment for recurrent genital herpes.

OBJECTIVE: To evaluate the literature regarding short-course oral therapy for recurrent genital herpes. DATA SOURCES: Literature was accessed through MEDLINE (1966-March 2003), IOWA Drug Information Service (1966-March 2003), and International Pharmaceutical Abstracts (1966-March 2003). DATA SYNTHESIS: Data are available describing short-course (2 or 3 d) therapy with acyclovir and valacyclovir. Short-course acyclovir therapy was superior to placebo. Three- and 5-day regimens of valacyclovir were equivalent. Early initiation of therapy may be more important than duration of therapy. CONCLUSIONS: More head-to-head studies are needed to determine the most efficacious and cost-effective short-course regimens for recurrent genital herpes.