Showing papers on "Tolerability published in 1996"
TL;DR: Ciprofloxacin has retained its excellent activity against most Gram-negative bacteria, and fulfilled its potential as an important antibacterial drug in the treatment of a wide range of infections.
Abstract: Ciprofloxacin is a broad spectrum fluoroquinolone antibacterial agent. Since its introduction in the 1980s, most Gram-negative bacteria have remained highly susceptible to this agent in vitro ; Gram-positive bacteria are generally susceptible or moderately susceptible. Ciprofloxacin attains therapeutic concentrations in most tissues and body fluids. The results of clinical trials with ciprofloxacin have confirmed its clinical efficacy and low potential for adverse effects. Ciprofloxacin is effective in the treatment of a wide variety of infections, particularly those caused by Gram-negative pathogens. These include complicated urinary tract infections, sexually transmitted diseases (gonorrhoea and chancroid), skin and bone infections, gastrointestinal infections caused by multiresistant organisms, lower respiratory tract injections (including those in patients with cystic fibrosis), febrile neutropenia (combined with an agent which possesses good activity against Gram-positive bacteria), intra-abdominal infections (combined with an antianaerobic agent) and malignant external otitis. Ciprofloxacin should not be considered a first-line empirical therapy, for respiratory tract infections if penicillin-susceptible Streptococcus pneumoniae is the primary pathogen; however, it is an appropriate treatment option in patients with mixed infections (where S. pneumoniae may or may not be present) or in patients with predisposing factors for Gram-negative infections. Clinically important drug interactions involving ciprofloxacin are well documented and avoidable with conscientious prescribing. Recommended dosage adjustments in patients with impaired renalfunction vary between countries ; major adjustments are not required until the estimated creatinine clearance is <30 ml/min/1.73m 2 (or when the serum creatinine level is ≥2 mg/dl). Ciprofloxacin is one of the few broad spectrum antibacterials available in both intravenous and oral formulations. In this respect, it offers the potential for cost savings with sequential intravenous and oral therapy in appropriately selected patients and may allow early discharge from hospital in some instances. In conclusion, ciprofloxacin has retained its excellent activity against most Gram-negative bacteria, and fulfilled its potential as an important antibacterial drug in the treatment of a wide range of infections. Rational prescribing will help to ensure the continued clinical usefulness of this valuable antimicrobial drug.
344 citations
TL;DR: Each drug was significantly better than placebo at preventing seizures, but none was significantly different from the others in terms of efficacy or tolerability, though the confidence intervals were wide Randomised trials comparing active treatments are needed to further evaluate these drugs.
Abstract: Objectives: To evaluate the efficacy and tolerability of the newly developed antiepileptic drugs gabapentin, lamotrigine, tiagabine, topiramate, vigabatrin, and zonisamide in patients with refractory partial epilepsy. Design: Systematic review of published and unpublished randomised controlled trials of add-on treatment with new antiepileptic drugs. Subjects: 20 published and eight unpublished trials representing 3883 patients with refractory partial epilepsy. Main outcome measures: Proportion of patients who (a) showed 50% or greater reduction in frequency of seizures (50% responders) and (b) withdrew from each study for any reason. Results: Odds ratios (95% confidence intervals) relative to placebo for 50% responders were 2.29 (1.53 to 3.43) for gabapentin, 2.32 (1.47 to 3.68) for lamotrigine, 3.03 (2.01 to 4.58) for tiagabine, 4.22 (2.80 to 6.35) for topiramate, 3.68 (2.45 to 5.51) for vigabatrin, and 2.47 (1.36 to 4.47) for zonisamide. Odds ratios for withdrawal were 1.36 (0.75 to 2.49) for gabapentin, 1.19 (0.79 to 1.79) for lamotrigine, 1.81 (1.21 to 2.70) for tiagabine, 2.42 (1.43 to 4.11) for topiramate, 2.58 (1.26 to 5.27) for vigabatrin, and 5.70 (1.76 to 18.49) for zonisamide. Comparing results for each drug showed that all of the 95% confidence intervals overlapped, indicating that they were not significantly different in terms of efficacy and tolerability. Conclusions: All six drugs were significantly better than placebo at reducing frequency of seizures. These results do not allow an evidence based choice between these drugs as we have no conclusive indication of differences in efficacy or tolerability. Key messages At present there is insufficient evidence to guide a choice between these new treatments We systematically reviewed randomised placebo controlled studies of supplementary gabapentin, lamotrigine, tiagabine, topiramate, vigabatrin, and zonisamide Each drug was significantly better than placebo at preventing seizures, but none was significantly different from the others in terms of efficacy or tolerability, though the confidence intervals were wide Randomised trials comparing active treatments are needed to further evaluate these drugs
335 citations
TL;DR: The safety profile of simvastatin, 20 to 40 mg daily, over 5 years was excellent, and the frequency of adverse events related to the central nervous system was similar in both groups.
Abstract: Background: Long-term safety is an important consideration in the selection and use of drugs, such as lipid-lowering agents, that are prescribed to reduce the risk of clinical events during long periods. Methods: The Scandinavian Simvastatin Survival Study was designed to evaluate the effects of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease. The 4444 patients aged 35 to 70 years (mean, 58.9 years) with angina pectoris or previous myocardial infarction and serum cholesterol levels of 5.5 to 8.0 mmol/L (213-310 mg/dL) receiving a lipid-lowering diet were randomly assigned to take double-blind treatment with simvastatin, 20 to 40 mg once daily, or placebo. In addition to previously reported end-point events, detailed clinical and laboratory safety data were collected during a median follow-up period of 5.4 years (range in survivors, 4.9-6.2 years). Results: The only clearly drug-related serious adverse event during the 5.4-year median follow-up period was a single reversible case of myopathy. The frequencies of persistent elevations of hepatic aminotransferase levels above 3 times the upper limit of normal and of nonviral hepatitis in the simvastatin and placebo treatment groups were not significantly different. Examination of the lens showed no between-group differences, and no previously unrecognized adverse effects of the drug were observed. There were no significant between-group differences in adverse events in any body system. In particular, the frequency of adverse events related to the central nervous system was similar in both groups. Conclusion: The safety profile of simvastatin, 20 to 40 mg daily, over 5 years was excellent. Arch Intern Med. 1996;156:2085-2092
280 citations
TL;DR: There were no statistically significant differences between either dose of anastrozole and megestrol acetate in terms of objective response rate, time to objective progression of disease or time to treatment failure, and the higher 10 mg dose did not result in additional clinical benefit, but was well tolerated reflecting the good therapeutic margin with anast rozole.
254 citations
TL;DR: Pending long term data, losartan potassium is likely to find initial use in patients with mild to severe hypertension who are unresponsive to, or intolerant of, their current therapy and, lastly, cost effectiveness and influence on quality of life.
Abstract: Losartan potassium is an orally active, nonpeptide angiotensin II (AII) receptor antagonist. It is the first of a new class of drugs to be introduced for clinical use in hypertension. This novel agent binds competitively and selectively to the AII subtype 1 (AT(1)) receptor, thereby blocking AII-induced physiological effects. An active metabolite, E3174, contributes substantially to its antihypertensive effect, which persists throughout 24 hours after once-daily administration. In patients with mild to moderate hypertension, losartan potassium 50 to 100mg once daily as monotherapy lowers blood pressure to a similar degree to enalapril, atenolol and felodipine extended release (ER). Losartan potassium combined with hydrochlorothiazide reduces blood pressure further than either drug given separately. About one-third of patients with severe hypertension have responded to the combination product. Losartan potassium appears to be effective in elderly patients. Losartan potassium is very well tolerated. In clinical trials, dizziness was the only drug-related event reported more frequently with losartan potassium monotherapy than with placebo. First-dose hypotension is uncommon. An aspect of the drug's tolerability profile which may prove to be particularly advantageous is that it is associated with a similar incidence of cough to placebo in patients with a history of ACE inhibitor-related cough. Additionally, clinically relevant adverse metabolic effects or laboratory abnormalities have not been documented during losartan potassium therapy and renal function is preserved in patients with or without renal insufficiency. The adverse effect profile of the losartan potassium-hydrochlorothiazide combination resembles those for losartan potassium monotherapy and placebo. Long term tolerability data are limited (<2 years) but support the very good tolerability profile in shorter studies. Elements of the drug's profile yet to be assessed or reported fully in the literature include long term efficacy; potential to favourably influence cardiovascular and renovascular systems (and ultimately mortality) in patients with hypertension and, lastly, cost effectiveness and influence on quality of life. In summary, losartan potassium is the first AT(1)+ receptor antagonist to become available for the management of hypertension and, as such, it is an important new antihypertensive agent. Pending long term data as outlined above, it is likely to find initial use in patients with mild to severe hypertension who are unresponsive to, or intolerant of their current therapy. However, with its novel mechanism of action, good efficacy and favourable tolerability profile, losartan potassium is well placed to claim a prominent position in the management of patients with essential hypertension in the future.
233 citations
TL;DR: Docetaxel has major activity against SCCHN and appears to be well tolerated in this group of patients and can be safely administered on an outpatient basis.
Abstract: Purpose We conducted a phase II study designed to evaluate the activity, safety, and tolerability of docetaxel (Taxotere: Rhone-Poulenc Rorer Pharmaceuticals Inc, Collegeville, PA) in patients with advanced, incurable, or recurrent squamous cell carcinoma of the head and neck (SCCHN) who had not received prior palliative chemotherapy. Patients and methods Thirty-one patients with measurable, locoregional, or metastatic SCCHN were treated with docetaxel, administered at a dose of 100 mg/m2 as a 1-hour intravenous (i.v.) infusion once every 21 days on an outpatient basis. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Prophylactic administration of growth factors or antiemetics was not permitted. Results Thirty-one patients were treated. Twenty-nine patients were assessable for response and 30 for toxicity. Four of 31 patients (13%) achieved complete response (CR), nine (29%) achieved partial response had stable disease (SD) and seven (23%) experienced progression of disease (PD). The major response rate was 42% (95% confidence interval [CI], 24% to 60%). The median duration of responses was 5 months (range, 2 to 14). The principal toxicity was leukopenia, which occurred with rapid onset and brief duration. Sixteen patients (53%) experienced nadir fever, and 13 required dose reduction. Hypersensitivity reactions occurred in four patients. Grade 3 peripheral neuropathy occurred in two patients; grade 2 or 3 fatigue occurred in six (20%) and 10 (33%), respectively. Minimal edema (grade 1) occurred in five patients (17%). Clinically significant mucositis, diarrhea, or dermatitis were not observed. Conclusion Docetaxel has major activity against SCCHN. It appears to be well tolerated in this group of patients and can be safely administered on an outpatient basis. Premedication with dexamethasone, cimetidine, and diphenhydramine is associated with a reduced incidence of significant edema, hypersensitivity reactions, and dermatologic toxicities.
230 citations
TL;DR: Paroxetine is as effective as clomipramine in the treatment of OCD and the comparable efficacy and better tolerability of parxetine suggest that it would be an appropriate treatment for OCD.
Abstract: BACKGROUND The aim was to assess the effect of a flexible dose of paroxetine, compared with clomipramine and placebo, in obsessive-compulsive disorder (OCD).
METHOD In a multinational randomised study, 406 subjects with OCD of at least six months duration received double-blind medication for up to 12 weeks. Doses were adjusted according to therapeutic effect and side-effects. Primary efficacy measures were the Yale-Brown Obsessive-Compulsive Scale and the National Institute of Mental Health Obsessive-Compulsive Scale. Secondary efficacy measures were the Montgomery-Asberg Depression Rating Scale, Symptom Check-List (90), Clinical Global Impression, and Patients Global Evaluation.
RESULTS Paroxetine was significantly more effective than placebo, and of comparable efficacy to clomipramine. Paroxetine had significantly superior tolerability to clomipramine on three measures: CGI efficacy index, anticholinergic adverse events, and adverse events leading to withdrawal.
CONCLUSION Paroxetine is as effective as clomipramine in the treatment of OCD. The comparable efficacy and better tolerability of paroxetine suggest that it would be an appropriate treatment for OCD.
225 citations
TL;DR: This study establishes a rational and generally well tolerated dosing regimen for administration of tirofiban as adjunctive therapy in high risk angioplasty patients and establishes a dose-dependent inhibition of ex vivo ADP-mediated platelet aggregation that was sustained during intravenous infusion and resolved rapidly after drug cessation.
218 citations
Journal Article•
TL;DR: Nefazodone and sertraline are well tolerated, and there was no statistically significant difference in their antidepressant activity.
Abstract: Background : The efficacy, tolerability, and effects on sexual function and satisfaction of nefazodone and sertraline were compared in a multicenter, randomized, double-blind, parallel-group study in outpatients with major depression. Method : One hundred sixty patients, 18 years of age or older, who met DSM-III-R criteria for single or recurrent nonpsychotic major depressive episodes were randomly assigned to 6 weeks of treatment with either nefazodone (100-600 mg/day) or sertraline (50-200 mg/day). Symptoms were assessed before and during treatment using the 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinical Global Impressions (CGI) Improvement scale, the CGI Severity of Illness scale, and a sexual function questionnaire. Results : Of 143 patients evaluable for efficacy, 72 received sertraline and 71 received nefazodone. The mean modal daily dose at endpoint was 148 mg for sertraline and 456 mg for nefazodone. Analysis of efficacy measures (HAM-D-17 and CGI) showed consistent and comparable improvement in symptoms of depression for both treatment groups. Sertraline had negative effects on sexual function and satisfaction in both men and women, and nefazodone had no adverse effect on sexual well-being. Safety assessments based on adverse events, vital sign measurements, electrocardiographs, physical examinations, and clinical laboratory tests revealed no serious adverse events or organ toxicity associated with nefazodone or sertraline administration. Conclusion : Nefazodone and sertraline are well tolerated, and there was no statistically significant difference in their antidepressant activity. Sertraline treatment has negative effects on sexual function and performance in both sexes, while nefazodone has none. These findings may have clinical implications when choosing antidepressant therapy.
197 citations
TL;DR: MeCsA appears to be a safe and effective therapy in stable renal transplant patients and provides superior and more consistent absorption of cyclosporine when compared with ConCsA, a prospective, randomized, concentration-controlled, pharmacoepidemiologic study.
Abstract: Background. The safety, tolerability, and pharmacokinetics of conventional cyclosporine (ConCsA) and cyclosporine microemulsion (MeCsA) were compared under conditions of normal clinical practice in a prospective, randomized, concentration-controlled, pharmacoepidemiologic study. Methods. Between September 1994 and March 1995, 1097 stable renal transplant recipients in 14 Canadian centers were randomized 2:1 to treatment with MeCsA or ConCsA Patients were commenced on each study drug at a dose equal to their previous therapy with ConCsA, and the dose was adjusted to maintain predose whole blood cyclosporine concentrations within the therapeutic range established for each center. Prednisone and azathioprine were continued unless dose adjustment was required for clinical reasons. Results. The mean cyclosporine concentration was comparable in both treatment groups at all time points throughout the 6 months of follow-up. The mean dose of cyclosporine was 3.6 mg/kg/day in both treatment groups at entry to the study, and declined by 0.3% and by 2.8% in patients receiving ConCsA and MeCsA, respectively. The nature and severity of adverse events were similar in both treatment groups, but there was a transient increase in neurological and gastrointestinal complications in the group receiving MeCsA within the first month after conversion (P<0.05). Serum creatinine and creatinine clearance did not change in either treatment group throughout the study. Biopsy-proven acute rejection occurred in three patients (0.8%) receiving ConCsA and in seven patients (0.9%) receiving MeCsA, with non-histologically proven acute rejection in an additional three patients (0.8%) receiving ConCsA and five patients (0.6%) receiving MeCsA (P=NS). Serum creatinine rose transiently in 35 patients (9.8%) receiving ConCsA and 138 patients (18.7%) receiving MeCsA (P<0.05) and resolved either spontaneously or after a reduction in the cyclosporine dose. One graft was lost in the MeCsA group due to irreversible rejection, and seven patients died, three in the group receiving ConCsA and four of those receiving MeCsA (P=NS). Absorption of cyclosporine was more rapid and complete from MeCsA than from ConCsA during the first 4 hr of the dosing interval, resulting in almost 40% greater exposure to the drug (P<0.001). There was close correlation between area under the time-concentration curve (AUC) over the first 4 hr of the 12-hr dosage interval and AUC over the entire 12-hr dosage interval for both formulations, making AUC over the first 4 hr a good predictor of total cyclosporine exposure. Using this parameter, patients with low absorption randomized to receive MeCsA showed a marked increase in drug exposure by months 3 and 6, whereas there was no change in those who continued on ConCsA A limited sampling strategy utilizing samples at the predose and postdose trough levels provided an excellent correlation with drug exposure, particularly for patients receiving MeCsA (r 2 =0.94 MeCsA vs. r 2 =0.89 ConCsA). Conclusions. MeCsA appears to be a safe and effective therapy in stable renal transplant patients and provides superior and more consistent absorption of cyclosporine when compared with ConCsA. Transient toxicity after conversion to MeCsA occurs in some patients, and may reflect the increased exposure to cyclosporine. Use of a limited sampling approach combining trough and 2-hr postdose concentrations may provide an effective way to monitor this exposure.
194 citations
TL;DR: The migraine prophylactic effect of 10 mmol magnesium twice-daily has been evaluated in a multicentre, prospective, randomized, double-blind, placebo-controlled study, with no benefit with magnesium compared to placebo.
Abstract: The migraine prophylactic effect of 10 mmol magnesium twice-daily has been evaluated in a multicentre, prospective, randomized, double-blind, placebo-controlled study. Patients with two to six migraine attacks per month without aura, and history of migraine of at least 2 years, were included. A 4-week baseline period without medication was followed by 12 weeks of treatment with magnesium or placebo. The primary efficacy end-point was a reduction of at least 50% in intensity or duration of migraine attacks in hours at the end of the 12 weeks of treatment compared to baseline. With a calculated total sample size of 150 patients, an interim analysis was planned after completing treatment of at least 60 patients, which in fact was performed with 69 patients (64F, 5M), aged 18-64 years. Of these, 35 had received magnesium and 34 placebo. The number of responders was 10 in each group (28.6% under magnesium and 29.4% under placebo). As determined in the study protocol, this was a major reason to discontinue the trial. With regard to the number of migraine days or migraine attacks there was no benefit with magnesium compared to placebo. There were no centre-specific differences, and the final assessments of treatment efficacy by the doctor and patient were largely equivocal. With respect to tolerability and safety, 45.7% of patients in the magnesium group reported primarily mild adverse events like soft stool and diarrhoea in contrast to 23.5% in the placebo group.
TL;DR: It is suggested that topically applied Aloe vera extract 0.5% in a hydrophilic cream is more effective than placebo, and has not shown toxic or any other objective side‐effects, and can be considered a safe and alternative treatment to cure patients suffering from psoriasis.
Abstract: The purpose of this double-blind, placebo-controlled study was to evaluate the clinical efficacy and tolerability of topical Aloe vera extract 0.5% in a hydrophilic cream to cure patients with psoriasis vulgaris. Sixty patients (36M/24F) aged 18-50 years (mean 25.6) with slight to moderate chronic plaque-type psoriasis and PASI (Psoriasis Area and Severity Index) scores between 4.8 and 16.7 (mean 9.3) were enrolled and randomized to two parallel groups. The mean duration of the disease prior to enrollment was 8.5 years (range 1-21). Patients were provided with a precoded 100g tube, placebo or active (with 0.5% Aloe vera extract), and they self-administered trial medication topically (without occlusion) at home 3 times daily for 5 consecutive days per week (maximum 4 weeks active treatment). Patients were examined on a weekly basis and those showing a progressive reduction of lesions, desquamation followed by decreased erythema, infiltration and lowered PASI score were considered healed. The study was scheduled for 16 weeks with 12 months of follow-up on a monthly basis. The treatment was well tolerated by all the patients, with no adverse drug-related symptoms and no dropouts. By the end of the study, the Aloe vera extract cream had cured 25/30 patients (83.3%) compared to the placebo cure rate of 2/30 (6.6%) (P < 0.001) resulting in significant clearing of the psoriatic plaques (328/396 (82.8%) vs placebo 28/366 (7.7%), P < 0.001) and a decreased PASI score to a mean of 2.2. The findings of this study suggest that topically applied Aloe vera extract 0.5% in a hydrophilic cream is more effective than placebo, and has not shown toxic or any other objective side-effects. Therefore, the regimen can be considered a safe and alternative treatment to cure patients suffering from psoriasis.
TL;DR: It is indicated that patients with advanced CTCL can achieve a high response rate for an extended period with photopheresis and that interferon alfa combined with photobheresis is a well-tolerated regimen that appears to produce higher response rates than photophersis alone.
Abstract: Background: Extracorporeal photopheresis is a pheresis-based therapy that permits the direct targeting of psoralen-mediated photochemotherapy to circulating pathogenic T cells. Although photopheresis is currently used to treat cutaneous T-cell lymphoma (CTCL), limited data are available regarding overall response rates and durability of responses among patients with advanced disease. Furthermore, little is known about the effectiveness and tolerability of combined regimens employing other biologic response modifiers including interferon alfa. Objective: Our purpose was to determine the efficacy of photopheresis among 41 patients with the clinical and laboratory diagnosis of CTCL; the majority of patients had stage III or IV disease with the presence of circulating malignant T cells. Methods: A retrospective chart review during a 10-year period at a single university hospital was performed for all patients receiving either photopheresis monotherapy on two consecutive days every 4 weeks (one cycle) and for an additional 12 patients who also received interferon alfa 1.5 to 5 million U subcutaneously three to five times weekly. Results: Thirty-one of 41 patients (76%) were treated for six or more cycles. The remaining 10 were treated with less than six cycles because of rapidly progressing disease ( n = 6), death unrelated to CTCL ( n = 2), or withdrawal from treatment ( n = 1); one of the 10 patients had only received five cycles of treatment but is still receiving therapy. Twenty-eight of the 31 patients treated for six or more cycles received photopheresis alone. Among the 28, seven patients (25%) had a complete remission, 13 (46%) had a partial remission defined as more than 50% clearing of skin disease, and eight (29%) did not respond to treatment. The presence of Sezary cells in the peripheral blood was associated with a favorable response. Median time to treatment failure was 18 months, whereas median survival from initiation of therapy was 77 months and from the time of diagnosis exceeded 100 months. Nine of these 28 patients went on to receive combination therapy with interferon alfa and, in some cases, other agents. Among these nine patients, five had an enhanced clinical response to the combination therapy compared with treatment with photopheresis monotherapy. The combined regimen was well tolerated. Conclusion: These results indicate that patients with advanced CTCL can achieve a high response rate for an extended period with photopheresis and that interferon alfa combined with photopheresis is a well-tolerated regimen that appears to produce higher response rates than photopheresis alone.
TL;DR: Preliminary clinical trials suggest that lornoxicam is as effective as the opioid analgesics morphine, pethidine (meperidine) and tramadol in relieving postoperative pain following gynaecological or orthopaedic surgery, and aseffective as other NSAIDs after oral surgery.
Abstract: Lornoxicam (chlortenoxicam), a new nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with analgesic, anti-inflammatory and antipyretic properties, is available in oral and parenteral formulations. It is distinguished from established oxicams by a relatively short elimination half-life (3 to 5 hours), which may be advantageous from a tolerability standpoint. Data from preliminary clinical trials suggest that lornoxicam is as effective as the opioid analgesics morphine, pethidine (meperidine) and tramadol in relieving postoperative pain following gynaecological or orthopaedic surgery, and as effective as other NSAIDs after oral surgery. Lornoxicam was also as effective as other NSAIDs in relieving symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute sciatica and low back pain. Lornoxicam has a tolerability profile characteristic of an NSAID, with gastrointestinal disturbances being the most common adverse events. Limited clinical experience to date suggests that, as with a number of other NSAIDs, lornoxicam may provide a better-tolerated alternative or adjuvant to opioid analgesics for the management of moderate to severe pain. It has also demonstrated potential as an alternative to other NSAIDs for the management of arthritis and other painful and inflammatory conditions. These preliminary findings require confirmation in further comparative and long term studies.
TL;DR: There is evidence that lamotrigine, zonisamide, felbamate and, possibly, topiramate may also be effective in generalized epilepsies, and further studies are required to characterize their activity spectrum as well as their potential value in monotherapy.
Abstract: 1. After a hiatus of over 20 years, several new antiepileptic drugs (vigabatrin, lamotrigine, gabapentin, oxcarbazepine, topiramate, felbamate, zonisamide and tiagabine) have reached or approached the registration phase. 2. Compared with older agents, many new drugs exhibit simpler pharmacokinetics. This is especially true for vigabatrin and gabapentin, which are renally eliminated and have a low interaction potential. 3. Unlike most of the older agents, vigabatrin, lamotrigine, gabapentin and tiagabine are devoid of significant enzyme inducing or inhibiting properties. Topiramate, oxcarbazepine and felbamate may induce the metabolism of steroid oral contraceptives. In addition, felbamate also acts as a metabolic inhibitor. 4. To date, the efficacy of new drugs has been evaluated extensively only under add-on conditions in patients with partial seizures (with or without secondary generalization) refractory to conventional treatment. However, there is evidence that lamotrigine, zonisamide, felbamate and, possibly, topiramate may also be effective in generalized epilepsies. 5. In placebo-controlled studies, typically between 15 and 40% of patients with difficult-to-treat partial epilepsy have shown an improvement (defined as a 50% or greater decrease in seizure frequency) after addition of a new drug. Only a small minority of these patients achieved complete seizure control. 6. Compared with older agents, some of the new drugs may have a better tolerability profile. Felbamate, however, has been associated with a high risk of aplastic anaemia and hepatotoxicity. 7. At present, the main use of the new agents is in patients refractory to first-line drugs such as carbamazepine or valproate, and further studies are required to characterize their activity spectrum as well as their potential value in monotherapy. In most patients, new drugs cannot be recommended for first-line use until evidence is obtained that potential advantages in tolerability or ease of use outweigh the drawback of their high cost.
TL;DR: Cyclosporine may offer an effective, safe, and well-tolerated short-term treatment option for children with severe AD.
Abstract: Background:Severeatopic dermatitis (AD) remains difficult to treat. Cyclosporine is effective in adults but has not previously been investigated in children with AD.
Objective: The aims were to investigate the efficacy, safety, and tolerability of cyclosporine in severe refractory childhood AD.
Methods: Subjects 2 to 16 years of age were treated for 6 weeks with cyclosporine, 5 mg/kg per day, in an open study. Disease activity was monitored every 2 weeks by means of sign scores, visual analogue scales for symptoms, and quality-of-life questionnaires. Adverse events were monitored. Efficacy and tolerability were assessed with five-point scales.
Results: Twenty-seven children were treated. Significant improvements were seen in all measures of disease activity. Twenty-two showed marked improvement or total clearing. Quality of life improved for both the children and their families. Tolerability was considered good or very good in 25 subjects.
Conclusion:Cyclosporine may offer an effective, safe, and well-tolerated short-term treatment option for children with severe AD.
TL;DR: Cabergoline, a long-acting dopamine agonist administered once or twice weekly, has been shown to be significantly more effective than bromocriptine in suppressing prolactin secretion in hyperprolactinaemic patients, and is better tolerated, particularly in terms of nausea and vomiting.
Abstract: Dopamine agonists are the treatment of choice for the majority of patients with hyperprolactinaemic disorders. Although characterised by a relatively high incidence of adverse effects, most commonly gastrointestinal, cardiovascular and neurological, these are usually mild and transient, and can be minimised by starting with a low dose and gradually increasing it, or taking the drug with food or while recumbent. Bromocriptine, introduced in 1971, is the reference preparation against which newer dopamine agonists are compared. It is effective in suppressing prolactin secretion, reducing prolactinoma size and restoring gonadal function. However, up to 12% of patients cannot tolerate the drug at therapeutic dosages. Cabergoline, a long-acting dopamine agonist administered once or twice weekly, has been shown to be significantly more effective than bromocriptine in suppressing prolactin secretion in hyperprolactinaemic patients, and is better tolerated, particularly in terms of nausea and vomiting. In suppressing physiological lactation, cabergoline is at least as effective as bromocriptine, and is associated with significantly fewer rebound symptoms and adverse effects. Quinagolide is a non-ergot dopamine agonist that is administered once daily. It has similar efficacy to bromocriptine, but is probably less effective than cabergoline in hyperprolactinaemic patients; it is not licensed for suppression of lactation. It is better tolerated than twice-daily bromocriptine, but is probably inferior to cabergoline in this regard. Neither bromocriptine, cabergoline nor quinagolide has been associated with any detrimental effect on pregnancy or fetal development. However, experience with bromocriptine is far more extensive; thus, for women requiring treatment for subfertility, this drug remains the treatment of choice in most centres, with cabergoline and quinagolide as acceptable second-line drugs in bromocriptine-intolerant patients. In hyperprolactinaemic men, hyperprolactinaemic women not wishing to become pregnant, and for suppression of physiological lactation, cabergoline is recommended as first-line treatment.
TL;DR: Both sumatriptan and dihydroergotamine were effective in aborting migraine headaches and headache recurrence was two and a half time as likely with sum atriptan as with dihydropriptan.
Abstract: Objective: To assess the efficacy and tolerability of subcutaneous dihydroergotamine mesylate (DHE-45) vs subcutaneous sumatriptan succinate (Imitrex) for the treatment of acute migraine with or without aura. Design: Double-blind, randomized trial with parallel treatment arms. Setting: Clinics and private neurology practices. Subjects: Patients of either sex, with migraine with or without aura, between the ages of 18 and 65 years. Interventions: Patients with moderate or severe head pain were randomized to receive either 1 mg of subcutaneous dihydroergotamine mesylate or 6 mg of subcutaneous sumatriptan succinate. Patients rated head pain, functional ability, nausea, and vomiting at baseline and at 0.5, 1, 2,4, and 24 hours after the injection. Presence or absence of headache at 3 hours was calculated from collected data. If pain persisted after 2 hours, a second injection of the same study medication was allowed, and self-ratings were repeated 30 and 60 minutes later. Follow-up data were collected at 24 hours. Main Outcome Measures: Relief of head pain and recurrence of successfully treated headache. Results: There were 295 evaluable patients. At 2 hours, 73.1% of the patients treated with dihydroergotamine and 85.3% of those treated with sumatriptan had relief ( P =.002). There was no statistical difference in headache relief between the groups at 3 or 4 hours. Headache relief was achieved by 85.5% of those treated with dihydroergotamine and by 83.3% of those treated with sumatriptan by 4 hours. By 24 hours 89.7% of dihydroergotamine-treated patients and 76.7% of sumatriptan-treated patients had relief ( P =.004). Headache recurred within 24 hours after treatment in 45% of the sumatriptan-treated patients and in 17.7% of the dihydroergotamine-treated patients ( P ≤.001). Conclusions: Both sumatriptan and dihydroergotamine were effective in aborting migraine headaches. Headache recurrence was two and a half times as likely with sumatriptan as with dihydroergotamine.
TL;DR: Paclitaxel demonstrates activity against metastatic breast cancer when administered over 96 hours to patients with disease that recently had progressed during short taxane exposure, and supports preclinical data that suggest variability in efficacy and resistance patterns to pac litaxel based on duration of exposure.
Abstract: PURPOSEA phase II trial of paclitaxel infused over 96 hours in patients with metastatic breast cancer with demonstrated disease progression (PD) during short-infusion taxane treatment was performed to evaluate schedule-dependent activity with prolonged drug exposure. The tolerability of this strategy and its pharmacokinetic profile and pharmacodynamic correlates were also investigated.PATIENTS AND METHODSPaclitaxel was administered to 26 patients with metastatic breast cancer at 120 to 140 mg/m2 intravenously over 96 hours. Twenty-three patients had demonstrated PD while receiving prior 3-hour paclitaxel, two during 1-hour docetaxel, and one during infusions of docetaxel and then paclitaxel. Twenty-one patients (81%) had no prior response to the short taxane infusion (primary resistance) and five (19%) had prior partial responses (PRs) of brief duration before PD (secondary resistance). Plasma paclitaxel concentrations were assessed at 24, 48, 72, and 96 hours.RESULTSAfter delivery of 195 cycles, seven of...
TL;DR: Clinical data concerning amifostine suggest that cytotoxic chemotherapy-induced haematological toxicity and cisplatin-induced neurotoxicity, nephrotoxicity and ototoxicity are decreased upon administration of am ifostine prior to cytot toxic drugs.
Abstract: Amifostine (WR-2721) was originally developed as a radioprotective agent. In animals, it protects normal tissues from the damaging effects of irradiation and, as shown in more recent studies, of several cytotoxic agents. Protection of tumours is generally reduced compared with that of normal tissues in animals, suggesting that amifostine may increase the therapeutic window of cytotoxic therapies. Clinical data concerning amifostine suggest that cytotoxic chemotherapy-induced haematological toxicity and cisplatin-induced neurotoxicity, nephrotoxicity and ototoxicity are decreased upon administration of amifostine prior to cytotoxic drugs. Similarly, amifostine reduces damage to normal tissues caused by radiotherapy. Available data show that this protection is achieved without adversely affecting tumour response or patient survival. In 1 large trial, the reduction in cyclophosphamide- and cisplatin-related toxicities manifested as a decrease in the incidence and severity of neutropenia-related fever and sepsis and in the number of patients with ovarian cancer who discontinue therapy before completion of treatment, thus improving the tolerability of this antineoplastic regimen. In addition, the incidences of cisplatin-induced nephro- and neurotoxicity were reduced. Increased doses of cytotoxic therapy have also been administered when amifostine was given prior to therapy, which may increase tumour response. The predominant adverse effect associated with amifostine are hypotension, nausea and vomiting, somnolence and sneezing. Thus, amifostine is likely to be a useful adjuvant to the treatment of patients with malignancy, particularly those receiving cyclophosphamide plus cisplatin. discontinued therapy before completion of treatment, thus improving the tolerability of this antineoplastic regimen. In addition, the incidences of cisplatin-induced.
TL;DR: In this paper, the authors designed a phase II trial to evaluate the efficacy of gabapentin in slowing the rate of decline in muscle strength of patients with ALS and to assess safety and tolerability.
Abstract: We designed a phase II trial to evaluate the efficacy of gabapentin in slowing the rate of decline in muscle strength of patients with amyotrophic lateral sclerosis (ALS) and to assess safety and tolerability. Gabapentin (800 mg) or placebo was administered t.i.d. in a randomized, double-blinded, placebo-controlled, trial for 6 months. We enrolled 152 patients at eight sites in the United States. The primary outcome measure was the slope of the arm megascore, the average maximum voluntary isometric strength from eight arm muscles standardized against a reference ALS population. A secondary outcome measure was forced vital capacity. Slopes of arm megascores for patients on gabapentin were compared with slopes of those taking placebo using a two-way ANOVA. We observed a nonstatistically significant trend (p = 0.057-0.08) toward slower decline of arm strength in patients taking gabapentin compared with those taking placebo (mean difference 24%, median 37%). We observed no treatment effect on forced vital capacity. Gabapentin was well tolerated by patients with ALS. These results suggest that further studies of gabapentin in ALS are warranted.
TL;DR: The antimigraine effect of 10- and 20-mg rizatriptan was superior to placebo, and comparable with that of 100-mg sum atriptan succinate, although it was associated with a high frequency of adverse events.
Abstract: Background: Rizatriptan (MK-462) is a new 5-hydroxytryptamine1D(serotonin1D; 5-HT1D) receptor agonist for the acute treatment of migraine that has improved pharmacokinetic properties compared with sumatriptan succinate. Objective: To assess the efficacy and tolerability of 10-, 20-, and 40-mg doses of oral rizatriptan vs a 100-mg dose of oral sumatriptan succinate and placebo for the acute treatment of migraine. Design: Randomized, double-blind, parallel-group, placebo-controlled, outpatient trial. Setting: Ten US and 4 Dutch investigator centers. Patients: Patients who had migraine with or without aura (N=449). Main Outcome Measure: The proportion of patients whose conditions improved from severe or moderate headache immediately before dosing to mild or no headache at 2 hours after drug administration (ie, headache relief). Results: The proportion of patients with headache relief was 18% for placebo; 46% for sumatriptan; and 52% for 10-mg, 56% for 20-mg, and 67% for 40-mg rizatriptan. All differences with placebo were statistically significant (P Conclusions: The antimigraine effect of 10- and 20-mg rizatriptan was superior to placebo, and comparable with that of 100-mg sumatriptan succinate; the efficacy of 40-mg rizatriptan was superior to that of both placebo and 100-mg sumatriptan succinate, although it was associated with a high frequency of adverse events.
TL;DR: Itraconazole along with other established agents should be considered a first-line treatment for patients with extensive or recalcitrant cutaneous fungal infections, mixed dermatophyte and Candida onychomycosis or vaginal candidiasis.
Abstract: Itraconazole is an orally administered triazole antifungal agent. Its spectrum of activity includes dermatophyte, dimorphic and dematiaceous fungi, yeasts, and some moulds. In clinical trials, mycological cure was attained in approximately 70 to 80, > or = 70 and > or = 80% of patients with, respectively, fingernail and toenail onychomycosis (200 mg/day for 3 months), dermatophytosis (100 mg/day for 2 to 4 weeks) and vaginal candidiasis (400 mg/day for 1 day or 200 mg/day for 3 days). Approximately 20 to 30% of patients with onychomycosis may relapse after completion of therapy; relapse rate data are limited for the other indications. Recently developed intermittent regimens of itraconazole (400 mg/day for 1 week per month for 3 to 4 months) appear to have similar efficacy to standard regimens in the treatment of onychomycosis. Shorter, higher dosage itraconazole treatment regimens (200 or 400 mg/day for 1 week) are also beneficial in dermatomycoses. Discrepancies and limitations of study design hamper conclusions about efficacy relative to other antifungal drugs. Newer intermittent and short course higher dosage itraconazole regimens have also not been evaluated in comparative studies. Available studies show that the efficacy of itraconazole appears to be greater than that of griseofulvin, but similar to or lower than that of terbinafine in patients with dermatophyte onychomycosis or cutaneous fungal infections. Moreover, the efficacy of itraconazole may be similar to or lower than that of fluconazole in the treatment of cutaneous mycoses. Comparative data from patients with acute vaginal candidiasis suggest that itraconazole is at least as effective as intravaginal clotrimazole and oral fluconazole, and superior to intravaginal econazole. These results require confirmation. Prescription-event monitoring data indicate that itraconazole is generally well tolerated. Gastrointestinal disturbances, dizziness and headache occur most commonly; liver toxicity has been rarely described. Its usefulness in some clinical situations may be limited because of its ability to interact with various therapeutic agents. In conclusion, itraconazole along with other established agents should be considered a first-line treatment for patients with extensive or recalcitrant cutaneous fungal infections, mixed dermatophyte and Candida onychomycosis or vaginal candidiasis. It is currently considered a second-line drug for dermatophyte onychomycosis; the use of newer intermittent itraconazole treatment regimens may, however, extend its role in the management of this condition. Although itraconazole offers greater benefit than conventional therapies (griseofulvin and ketoconazole) in terms of efficacy and tolerability, wider clinical experience is required to determine its merits relative to the newer agents, terbinafine and fluconazole.
TL;DR: Valsartan proved to be both effective and safe in reducing blood pressure in adults with essential hypertension and the optimal dose range is 80 to 160 mg, given once daily.
TL;DR: A significant reduction of compulsive desire ("craving') was observed in parallel, as deduced from evaluation of a specific questionnaire, the Alcohol Craving Scale, and tolerability was fair in all patients.
Abstract: We report the results of an 'open' multicentre study evaluating the use, tolerability and therapeutic efficacy of the sodium salt of 4-hydroxybutyric acid (GHB) for the medium-term treatment of withdrawal symptoms in 179 patients with alcohol dependence followed up as outpatients. The follow-up of patients was 6 and 12 months after drug discontinuation. Following a daily oral administration of 50mg/kg for approximately 6 months, no serious systemic or single-organ consequences leading to drug discontinuation were reported, and tolerability was fair in all patients. Eleven subjects (10.1%) showed craving for the drug and voluntarily increased their doses (6-7 times the recommended levels). GHB led to complete abstinence during drug administration in 78.0% of the patients. A significant reduction of compulsive desire ('craving') was observed in parallel, as deduced from evaluation of a specific questionnaire, the Alcohol Craving Scale. At follow-up examination, 43 of the treated subjects remained abstinent at 6 months, and 30 subjects were abstinent for 1 year after drug discontinuation.
TL;DR: The data show 80 mg valsartanonce a day to be as effective as 20 mg enalapril once a day in the treatment of mild-to-moderate hypertension, and both of the treatments were tolerated well.
Abstract: ObjectiveTo compare the antihypertensive efficacy and systemic tolerability of valsartan, a new angiotensin II receptor antagonist, with placebo and with an angiotensin converting enzyme (ACE) inhibitor, enalapril.DesignA total of 348 adult outpatients with mild-to-moderate uncomplicated essential h
TL;DR: Preliminary data indicate that mirtazapine, with its novel mechanism of action, is a promising addition to currently available options for the treatment of depression.
Abstract: Synopsis Mirtazapine is a tetracyclic antidepressant with a novel mechanism of action; it increases noradrenergic and serotonergic neurotransmission via blockade of central α2-adrenergic auto- and heteroreceptors. The increased release of serotonin (5-hydroxytryptamine; 5-HT) stimulates serotonin 5-HT1 receptors because mirtazapine directly blocks 5-HT2 and 5-HT3 receptors. The enhancement of both noradrenergic- and 5-HT1 receptor-mediated neurotransmission is thought to be responsible for the antidepressant activity of mirtazapine. In short term (5 to 6 weeks) clinical trials in patients with depression. mirtazapine produces clinical improvements significantly superior to those of placebo, similar to those of tricyclic antidepressants (TCAs) [amitriptyline, clomipramine and doxepin] and possibly superior to those of trazodone. Short term clinical tolerability data suggest that mirtazapine produces fewer anticholinergic-, adrenergic- and serotonergic-related adverse events than TCAs. In rare cases, mirtazapine, in common with many antidepressants, was associated with potentially serious changes in haematological parameters (e.g. agranulocytosis and neutropenia). The drug appears to be safe in overdose and possesses a very low propensity for inducing seizures. Comparisons with other classes of antidepressants are needed to determine the relative position of mirtazapine in clinical practice. However, preliminary data indicate that mirtazapine, with its novel mechanism of action, is a promising addition to currently available options for the treatment of depression. Pharmacodynamic properties In vitro neurochemical studies have demonstrated that mirtazapine blocks central α2-adrenergic auto- and heteroreceptors, but has no effect on noradrenaline (norepinephrine) reuptake. The affinity of the drug was 10-fold higher for central presynaptic α2-adrenoceptors than for central postsynaptic and peripheral α2-adrenoceptors, and 30-fold higher for α2-adrenoceptors than for α1-adrenoceptors. Microdialysis and neurophysiological experiments as well as behavioural studies performed in rats support the α2-adrenoceptor antagonist properties of mirtazapine. Receptor binding studies have shown that mirtazapine has a high affinity for serotonin 5-HT2 and 5-HT3 receptors, central and peripheral histamine H1 receptors and a low affinity for 5-HT1, dopaminergic and muscarinic cholinergic receptors. Its activity at serotonin receptor subtypes has been confirmed in animal behaviour models. Mirtazapine activates 5-HT1 receptor-mediated serotonergic neurotransmission by enhancing the stimulatory effect of the noradrenergic system on serotonergic cell firing (an α1-adrenoceptor-mediated effect) as well as antagonising the inhibitory effect of the noradrenergic system on serotonin release (an α2-adrenoceptor-mediated effect). Electrophysiological experiments have demonstrated that mirtazapine enhances serotonergic transmission through blockade of presynaptic α2-adrenoceptors. The drug does not inhibit serotonin reuptake. Pharmacokinetic properties The bioavailability of mirtazapine is approximately 50%. Peak plasma concentrations are reached within 2.2 to 3.1 hours after single oral doses of 15 to 75mg and are dose-dependent. Mirtazapine is extensively metabolised in the liver; up to 85% of the drug is eliminated in the urine (up to 4% as unchanged drug) and the remaining 15% is eliminated in the faeces. The mean elimination half-life of mirtazapine is approximately 22 hours, making it suitable for once-daily administration. Therapeutic potential In randomised double-blind comparative trials including patients with major depression, short term (5 to 6 weeks) therapy with mirtazapine was significantly more effective than placebo, as effective as amitriptyline, clomipramine and doxepin, and at least as effective as trazodone. Results from a meta-analysis of 5 comparative trials in which 60% of patients were hospitalised with severe depression [mean baseline 17-item Hamilton Depression Rating Scale (HAMD) score ≥25] revealed no significant differences between mirtazapine and amitriptyline. The responder rates (≥50% decrease in HAMD score from baseline) at 6 weeks and study end-point were 70 and 61 %, respectively, for mirtazapine and 73 and 64%, respectively, for amitriptyline. In a comparative trial in older outpatients (mean age 61 to 63 years), reductions in rating scale scores of depression and the percentage of responders tended to be higher in mirtazapine than in trazodone recipients. Tolerability The tolerability profile of mirtazapine is based on results from short term (5 to 6 weeks) comparisons with placebo and other antidepressants; no longer term data are available. Drowsiness (23 vs 14%), excessive sedation (19 vs 5%), dry mouth (25 vs 16%), increased appetite (11 vs 2%) and bodyweight gain (10 vs 1%) occurred significantly more frequently with mirtazapine in placebo-controlled trials. Analysis of blood pressure, heart rate and symptoms of sexual dysfunction indicated no significant differences between mirtazapine and placebo recipients. In a meta-analysis, mirtazapine appeared to be better tolerated than amitriptyline, with significantly fewer patients experiencing anticholinergic (dry mouth, constipation, and abnormal accommodation and vision), cardiac (palpitations and tachycardia) and neurological (tremor and vertigo) adverse events. Mirtazapine was at least as well tolerated as clomipramine, doxepin and trazodone in comparative trials and appeared to be associated with slightly lower incidences of anticholinergic and neurological adverse events than these drugs. Clinical trial and postmarketing surveillance data suggest that mirtazapine has a very low potential for inducing seizures. Excessive but transient somnolence was the only symptom noted in 10 patients taking an overdose (up to 315mg) of mirtazapine. Mirtazapine is infrequently associated with clinically relevant changes in laboratory parameters. Granulocytopenia and elevated alanine aminotransferase levels have been reported; most were mild in severity and returned to normal values with continued administration of mirtazapine. Elevated cholesterol levels (mean 3 to 4%) have also been reported. Dosage and administration The recommended starting dosage of mirtazapine is 15 mg/day for 4 days, then 30 mg/day for 10 days. If effective, the drug should be continued unchanged at this dosage or, in patients assessed as insufficiently improved, the daily dosage may be further increased to 45 mg/day. In patients with hepatic or renal insufficiency, careful dosage titration as well as regular and close monitoring for adverse events is recommended. Concomitant use of mirtazapine and diazepam or alcohol (ethanol) may also impair cognitive and/or motor performance.
TL;DR: In this paper, the authors compared the efficacy and long-term tolerability of flecainide acetate versus quinidine for paroxysmal atrial fibrillation.
Abstract: In order to compare the efficacy and long-term tolerability of flecainide acetate versus quinidine, 239 patients with paroxysmal atrial fibrillation were prospectively treated with flecainide (n = 122) or quinidine (n = 117) in an open-label, randomized trial. All patients were followed for 1 year after initiation of therapy unless their antiarrhythmic drug was discontinued due to an inadequate therapeutic response or intolerable side effects. Although both drugs were equally effective in adequately controlling recurrences of atrial fibrillation (difference, p = 0.282; not significant), fewer flecainide patients had to have their therapy discontinued due to adverse experiences (p = 0.012). Based on both endpoints (efficacy and tolerability), an estimated 70.5% of flecainide versus 55.4% of quinidine patients would remain effectively treated at the end of 1 year on therapy (p < or = 0.007). The findings of this prospective study suggest that in the treatment of paroxysmal atrial fibrillation (1) flecainide and quinidine are equally effective in the acceptable suppression of symptomatic paroxysmal atrial fibrillation; (2) flecainide is better tolerated than quinidine and is less likely to be discontinued due to adverse effects; and (3) given the overall endpoint of efficacy and tolerability, more patients are likely to continue long-term therapy with flecainide than with quinidine.
TL;DR: In most patients, the effects of sumatriptan were consistent within subjects and over time, andSumatripta provided rapid headache relief and chest symptoms were frequent but usually not serious if patients were forewarned.
Abstract: The long-term and within-patient consistency of the efficacy and tolerability of subcutaneous and oral sumatriptan in migraine was studied by retrospective survey of 2 years with mailed self-administered questionnaires in our neurology outpatient clinic. Subjects were migraine patients with or without aura (N = 869). We measured long-term use of sumatriptan and within-patient consistency and change over time of headache relief, headache recurrence, and chest symptoms after sumatriptan. The questionnaire was returned by 735 (85%) patients; 453 had used sumatriptan for nearly 28,000 attacks during 25 (median) months (92% > 1 year). Sumatriptan provided headache relief, mostly within 2 hours, in 85% of patients in at least two-thirds of their attacks. Of all patients, 75% experienced (usually multiple) headache recurrences in at least some and 40% in (nearly) all attacks. Median time to recurrence was 8 to 12 hours (range 1 to 30). Recurrence of aura was reported as well. Over 2 years, efficacy of sumatriptan had waned in 18% of patients (mainly because of increase in headache recurrence) and improved in 12% (mainly because of reduction of headache recurrence or adverse events or increase of headache relief); the number of monthly doses of sumatriptan had increased in 20%, reduced in 35%, and not changed in 45% of patients. Chest symptoms occurred in up to 58% of patients in at least some and in up to 42% of patients in all attacks, causing discontinuation of sumatriptan in 10%. In total, 111 patients (25%) discontinued sumatriptan mainly because of headache recurrence, adverse events, insufficient headache relief, or high price. In most patients, the effects of sumatriptan were consistent within subjects and over time. In most patients, sumatriptan provided rapid headache relief. Multiple headache recurrence was the major limitation. Chest symptoms were frequent but usually not serious if patients were forewarned.
TL;DR: It is indicated that 3 g/day vigabatrin is more effective than placebo as add-on therapy in patients with focal epilepsy whose complex partial seizures were difficult to control with established antiepilepsy drug therapy.
Abstract: Article abstract-This study compared the efficacy and tolerability of vigabatrin 3 g/day as add-on therapy with that of placebo in patients with focal epilepsy whose complex partial seizures were difficult to control with established antiepilepsy drug therapy. We enrolled 203 patients; 182 (90 placebo; 92 vigabatrin) received drug therapy under double-blind conditions. We increased the daily dosage to 2.5 g/day during a 4-week titration segment and maintained it at 3 g/day during the 12-week maintenance segment. By analyses we found a statistically significant lower frequency of seizures (complex seizures plus partial seizures secondarily generalized) at the end of the study for patients receiving vigabatrin than for those receiving placebo. The median monthly frequency was reduced by three seizures per 28 days in the vigabatrin group (baseline, 8.3; end of study, 5.3) versus 0.8 seizures per 28 days in the placebo group (baseline, 8.3; end of study, 7.5) (p = 0.0002). Therapeutic success (a 50% reduction from baseline in mean monthly seizure frequency) was attained in 40 of the vigabatrin patients (43%) compared with 17 of those treated with placebo (19%) (p NEUROLOGY 1996;46: 54-61