Update on medical treatment of ejaculatory disorders.

Among the treatment modalities for ejaculatory disorders pharmacological treatment is the least invasive option. In this review, medical treatments for retrograde ejaculation (RE) and anejaculation (AE) are discussed systematically. Thirty-six studies dealing with patients with RE and 40 with AE evaluated the use of medical treatment and were included in this review. In addition four articles dealing with prostatic massage in anejaculatory patients were considered. Sperm quality in patients with retrograde and AE is often impaired. In patients with RE no differences in response to medical treatment could be detected between the different underlying diagnoses. Compared with ephedrine, imipramine and chlorpheniramine + phenylpropanalamine showed significantly higher reversal rates, while differences between the other treatments were not significant. Regarding the reversal of AE, the alpha agonistic drugs were significantly inferior to treatment with parasympathetic drugs. Of the different alpha agonistic medical treatments for the reversal of AE, milodrin showed significantly better rates than imipramine (p = 0.008), pseudoephidrine (p = 0.02) and ephedrine (p = 0.044), while all other treatments were not significantly different (p = 0.4). In conclusion, medical treatment for reversal of RE offers a realistic chance of conceiving offspring naturally and should be the treatment modality of first choice. In contrast, in AE, medical treatment cannot be recommended generally as treatment of first choice as it shows low overall success rates compared with electrovibration stimulation and electroejaculation. Under consideration of the mostly uncontrolled design of the majority of studies published, controlled clinical trials comparing different treatment options appear urgently warranted.

Brompheniramine maleate: a double-blind, placebo-controlled comparison with terfenadine for symptoms of allergic rhinitis.

This was a double-blind, randomized, placebo-controlled, multicenter, parallel study comparing the effectiveness, at recommended doses, of an extended-release formulation of brompheniramine maleate and terfenadine in the treatment of allergic rhinitis. Subjects with symptoms of seasonal and/or perennial allergic rhinitis received brompheniramine 12 mg (n = 106), 8 mg (n = 105), terfenadine 60 mg (n = 106), or placebo (n = 53) twice daily for 14 days. On treatment days 3, 7, and 14, symptom severity ratings (i.e., rhinorrhea, sneezing, nasal congestion, itchy nose, eyes or throat, excessive tearing, postnasal drip) were completed by the physician; subjects and physicians each completed a global efficacy evaluation. Brompheniramine 12 mg and 8 mg and terfenadine were more effective than placebo (p < or = 0.05) on the physicians' global: brompheniramine 12 mg was more effective than terfenadine (p < or = 0.05) on days 7 and 14 and brompheniramine 8 mg on day 3. On the subjects' global evaluation, brompheniramine 12 mg and 8 mg and terfenadine were more effective than placebo (p < or = 0.05); brompheniramine 12 mg was more effective than terfenadine (p < or = 0.05) on days 7 and 14 and brompheniramine 8 mg on day 3. In general, brompheniramine 8 mg was comparable to terfenadine. On days 3 and 7, the total symptom and total nasal symptom severity scores for subjects receiving brompheniramine 12 mg were significantly more improved than for placebo (p < 0.05); terfenadine was not different from placebo; brompheniramine 12 mg was significantly better than terfenadine on day 7 (p < 0.05) for reducing total symptom severity and on days 3, 7, and 14 for reducing total nasal symptom severity. Adverse experiences were reported by 155 (41.9%) of the 370 subjects enrolled in the study. The overall rate of adverse experiences in the brompheniramine 12 mg treatment group (57.5%) was significantly greater (p < 0.05) than for brompheniramine 8 mg (38.1%), terfenadine (31.1%), and placebo (39.6%). In conclusion, an extended-release formulation of brompheniramine 12 mg or 8 mg bid alleviates allergic rhinitis symptoms and brompheniramine 12 mg provides significantly better relief of these symptoms than terfenadine 60 mg bid.

Brompheniramine, loratadine, and placebo in allergic rhinitis: a placebo-controlled comparative clinical trial.

A double-blind, randomized, placebo-controlled, parallel-group, multicenter study was conducted to compare the effectiveness of an extended-release formulation of a classical antihistamine, brompheniramine, and a second-generation compound, loratadine, in the treatment of allergic rhinitis. Subjects with symptoms of allergic rhinitis received brompheniramine 12 mg twice daily (n = 112), loratadine 10 mg once daily (n = 112), or placebo twice daily (n = 114) for 7 days. Study medications were blinded using a double-dummy technique. Subjects completed an overall evaluation of symptom relief on a daily basis and returned on treatment days 3 and 7, at which times the investigator assessed symptom severity. The investigator and subject each completed a global efficacy evaluation, and subjects were interviewed regarding adverse experiences. The primary efficacy variable was the physicians' global efficacy evaluation on day 3. Symptoms also were analyzed as summed severity scores for all symptoms and for the nasal symptom cluster of rhinorrhea, sneezing, and nasal blockage. At all post-baseline evaluations (days 3, 7, and averaged over the two days), brompheniramine was significantly better than loratadine and placebo for both sets of summed symptom scores and all three global assessments. Loratadine was significantly better than placebo for physician ratings of total symptom severity averaged over the two days and for the physician and subject ratings of the nasal cluster on day 3. Central nervous system-related symptoms were the most frequently reported adverse experiences; somnolence was reported most frequently by patients taking brompheniramine, and its occurrence was less frequent as treatment continued. A nonprescription, extended-release formulation of brompheniramine 12 mg twice daily provided significantly better relief of symptomatic allergic rhinitis than loratadine 10 mg once daily.

Efficacy of brompheniramine maleate for the treatment of rhinovirus colds.

We tested the efficacy of brompheniramine maleate in a large randomized, controlled trial of volunteers with experimental rhinovirus colds. Brompheniramine (12 mg) or placebo was administered at 8:00 A.M. and 8:00 P.M. for < or = 4 days after the onset of symptoms (24, 36, or 48 hours after virus challenge). During the first 3 days of treatment (the first 4 days after virus challenge), nasal secretion weights were lower for infected evaluable subjects receiving brompheniramine (n = 113) than for controls (day 1: 4.3 g vs. 6.8 g; day 2: 4.8 g vs. 7.7 g; and day 3: 3.3 g vs. 5.3 g) (P < or = .03), as were rhinorrhea scores (day 1: 0.6 vs. 0.8; day 2: 0.5 vs. 0.8; and day 3: 0.3 vs. 0.5) (P < .03), sneeze counts (day 1: 1.8 vs. 3.6; day 2: 2.1 vs. 5.1; and day 3: 1.3 vs. 3.3) (P < or = .001), and sneeze severity scores (day 1: 0.3 vs. 0.6; day 2: 0.25 vs. 0.7; and day 3: 0.2 vs. 0.4) (P < .001) (n = 112). Cough counts were lower after day 1 of treatment for the brompheniramine group than for controls (4.7 vs. 7.9) (P = .05) (day 2 after virus challenge), and other symptoms were modestly reduced or were unaffected in the brompheniramine group. Total symptom scores were also lower for the brompheniramine group than for controls on treatment days 1 (4.8 vs. 6.0) (P = .03) and 2 (4.1 vs. 5.6) (days 2 and 3 after virus challenge) (P = .003). Treatment with brompheniramine was associated with the adverse effects of somnolence (n = 3) and confusion (n = 1). Brompheniramine was efficacious treatment for the sneezing, rhinorrhea, and cough associated with rhinovirus colds.

Is an antihistamine-decongestant combination effective in temporarily relieving symptoms of the common cold in preschool children?

OBJECTIVE: To determine whether an antihistamine-decongestant combination (ADC) is superior to placebo in temporarily relieving symptoms of upper respiratory tract infection (URI) in preschool children. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Four pediatric offices in the Seattle, Wash, area. PARTICIPANTS: Children 6 months through 5 years of age with a URI of less than 7 days' duration. METHODS: Children were randomly assigned to receive an ADC (brompheniramine maleate-phenylpropanolamine hydrochloride) or placebo as needed for URI symptoms. Two hours after each dose of study medication, changes in the child's runny nose, nasal congestion, cough, and sleep status were assessed by means of a standardized questionnaire. RESULTS: A total of 175 responses were recorded for 59 patients. There were no statistically significant differences in symptom improvement between the ADC and the placebo group (runny nose, p = 0.48; nasal congestion, p = 0.94; cough, p = 0.66). However, the proportion of children asleep 2 hours after receiving the ADC was significantly higher than the proportion receiving placebo (46.6% vs 26.5%; p = 0.01). Results were unchanged after control for the correlated nature of repeated responses, age, symptom duration, use of acetaminophen, time that the medication was given, and parental desire for medication. CONCLUSIONS: The ADC was equivalent to placebo in providing temporary relief of URI symptoms in preschool children. However, the ADC did have significantly greater sedative effects than did placebo.

The eternal triangle: benefit, risk, and cost of therapeutic agents.

Some people can undoubtedly tolerate a first-generation H1-receptor antagonist without sedation or other CNS adverse effects, but others cannot. There is no rapid, reliable way of differentiating these two populations. A history of presence or absence of subjective somnolence from one H1-receptor antagonist is not necessarily reliable and has no consistently useful predictive value for subsequent experience with other H1-receptor antagonists. As H1-receptor antagonists are used primarily to treat non-life-threatening disorders, safety should be a prime consideration in selecting one for use, and is surely as important a concern as efficacy and low cost. If your pilot is not permitted to take these medications before going to work, why should your taxi driver, your child's school bus driver, your dentist, your nurse, or your office assistant, to name a few examples, be allowed to do so? When the broad issue of safety is considered, first-generation H1-receptor antagonists may not be as cost-effective as they appear to be. The inherent benefit of any medication is inextricably linked with the inherent risk. It is incumbent on those promulgating the use of the older H1-receptor antagonists to define these benefits and risk further. Lowering the cost of the second-generation, relatively nonsedating H1-receptor antagonists so they are no longer the most expensive medications used in treatment of allergic rhinitis would also help solve the problem of the eternal triangle as it pertains to therapeutic use of H1-receptor antagonists.

Brompheniramine, terfenadine, and placebo in allergic rhinitis.

BACKGROUND: Second-generation antihistamines, reported to lack central nervous system depressant activity, may be considered to have a clinical advantage over traditional antihistamines. OBJECTIVE: To compare the effectiveness, at recommended doses, of an extended-release formulation of nonprescription brompheniramine and prescription terfenadine in the treatment of allergic rhinitis. METHODS: This was a double-blind, randomized, placebo-controlled, multicenter, parallel study. Subjects with symptoms of allergic rhinitis received brompheniramine 12 mg (n = 96), terfenadine 60 mg (n = 96), or placebo (n = 95) twice daily for 14 days. Subjects returned on treatment days 3, 7, and 14; at which times, the investigator assessed symptom severity (i.e., rhinorrhea; sneezing; nasal blockage; pruritus of the eyes, nose, or pharynx; watery eyes; and postnasal drip). The investigator and the subject each completed a global efficacy evaluation, and subjects were interviewed regarding the occurrence of adverse experiences. Symptoms were analyzed as summed severity scores for (1) all symptoms and (2) for the symptom cluster of rhinorrhea, sneezing, and nasal blockage. RESULTS: At all post-baseline evaluations (days 3, 7, and 14), brompheniramine was significantly better (P < or = .05) than terfenadine and placebo for both sets of summed symptom scores and for both global assessments. Terfenadine was significantly better (P < or = .05) than placebo on the physician's global at day 14. Central nervous system-related complaints were the most frequently reported adverse experiences among all three groups; somnolence was reported most frequently by brompheniramine-treated subjects. CONCLUSION: A nonprescription, extended-release formulation of brompheniramine, 12 mg bid, provided significantly better relief of symptomatic allergic rhinitis than terfenadine, 60 mg bid.

Astemizole in combination with pseudoephedrine in the treatment of seasonal allergic rhinitis.

The efficacy and side effects of once-daily astemizole-D, a combination of 10 mg astemizole and 240 mg pseudoephedrine, were compared with those of twice-daily brompheniramine-D, a combination of 12 mg brompheniramine and 50 mg phenylpropanolamine (Lunerin), in 64 patients with seasonal allergic rhinitis caused by birch pollen. Efficacy was monitored by patient's diary scores, investigator assessments of nasal and eye symptoms and need of rescue medication during the 4-week study period. Both astemizole-D and brompheniramine-D reduced nasal and eye symptoms of allergy. There were no significant differences between the treatment groups regarding obstruction, but brompheniramine-D alleviated symptoms of rhinorrhoea and itchy eyes significantly more than astemizole-D. On the other hand, the patients in the brompheniramine-D group reported dry mouth, tiredness and drowsiness more often than those in the astemizole-D group. The results indicate that the two drugs are effective in the treatment of seasonal allergic rhinitis, but astemizole-D is better tolerated than brompheniramine-D.

Effectiveness of an antihistamine-decongestant combination for young children with the common cold: a randomized, controlled clinical trial.

We tested the hypothesis that antihistamine-decongestant combinations cause no clinically significant relief of the symptoms of upper respiratory tract infections in young children by randomly assigning 96 children to one of three treatment groups: antihistamine-decongestant, placebo, and no treatment. There were no differences among the three study groups in the proportion of children considered "better" overall by the parent 48 hours after the initial assessment (drug, 67%; placebo, 71%; no treatment, 57%; p = 0.53). There were no differences among groups in individual or composite symptom score changes. Two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms. In the proportion of parents believing that their child needed medicine, there was no difference between those who consented to participate and those who refused. Parents who wanted medicine at the initial visit reported more improvement at follow-up, regardless of whether the child received drug, placebo, or no treatment. We conclude that there is no clinically significant improvement in symptoms of upper respiratory tract infection, including no significant placebo effect, in young children for whom an antihistamine-decongestant is prescribed.

Pregnancy after brompheniramine treatment of a diabetic with incomplete emission failure.

Ejaculation disorders in diabetic men are most frequently caused by retrograde ejaculation resulting from a damage of the sympathetic nerves at the level of the bladder neck. This results in incomplete or complete emission failure because of insufficient sperm transport. Diabetic ejaculatory sterility can be treated with anticholinergic drugs. The reported case shows that as a result of its antihistaminic and anticholinergic properties, brompheniramine can be successfully used in the treatment of men with diabetic ejaculatory sterility, particularly in patients with incomplete emission failure.

Cough and the common cold.

To determine whether the cough of the common cold arises from upper respiratory stimuli and whether antihistamine-decongestant therapy is an effective treatment for this cough, we prospectively evaluated volunteers with uncomplicated common colds in a randomized, double-blind, placebo-controlled study. After completing a standardized questionnaire and undergoing a physical examination, throat-culturing, and pulmonary function testing, subjects took the active drug or identical-appearing placebo for 7 days while they kept a diary in which they ranked the severity of 17 symptoms for 14 days. Pulmonary function testing was repeated, on average, on Days 4, 8, and 14. Forty-six percent of the variation in cough severity could be explained by throat-clearing and 47% of the variation in throat-clearing severity by postnasal drip. FIF50%, the only physiologic parameter that significantly correlated with cough, rose as cough severity fell. Antihistamine-decongestant therapy reduced postnasal drip and significantly decreased the severity of cough, nasal obstruction, nasal discharge, and throat-clearing during the first few days of the common cold. In addition, cough was 20 to 30% less prevalent in the active drug group within 3 days of starting therapy. We conclude that the cough of the common cold arose from upper respiratory tract stimuli and that cough and other cardinal symptoms of the common cold were reduced with antihistamine-decongestant therapy when these symptoms were at their worst.

Nasal pharmacodynamics of brompheniramine in perennial rhinitis.

This study evaluated the relationship between brompheniramine maleate and changes in nasal reactivity. Ten subjects with moderate-to-severe perennial rhinitis took brompheniramine for seven days using either a standard formulation or sustained-release preparation. Nasal aerodynamics and response to histamine were assessed at the end of the week. Despite varying doses of brompheniramine maleate (12 to 32 mg/d), there was no significant difference in nasal reactivity to histamine or in changes of nasal airflow, indicating that low doses of brompheniramine are highly effective in blocking histamine, receptors in the nasal mucosa.

Are antihistamine-decongestants of value in the treatment of acute otitis media in children?

Acute otitis media is the most common bacterial infection of childhood. The effectiveness of oral antihistamine-decongestant mixtures in the treatment of this illness remains controversial in clinical practice. In a double-blind randomized study, 82 children (aged under 15 years) with acute otitis media were treated with amoxicillin and either a decongestant-antihistamine mixture (Dimetapp) or placebo. All diagnoses required agreement between a family practice resident and the supervising family physician. Clinical course was assessed by symptom diaries completed by parents and by follow-up examination at approximately two weeks, which included pneumatic otoscopy. No statistically significant benefit of the antihistamine-decongestant mixture was shown in terms of resolution of the symptoms or prevention of the complications of acute otitis media. It is recommended that antihistamine-decongestants not be routinely added to an antibiotic in the treatment of acute otitis media in children.

Terfenadine and brompheniramine maleate in urticaria and dermographism.

The effects of brompheniramine maleate (12 mg twice daily in sustained release form) and terfenadine (60 mg twice daily) on the symptoms and well-being of 16 adults with urticaria with or without dermographism were assessed by symptom questionnaire. Following an initial 2-week period without therapy, each drug was taken for 2 weeks in a randomised double-blind cross-over study. Both drugs produced significant relief of itch and rash but only brompheniramine produced significant drowsiness. Brompheniramine maleate was more effective than terfenadine in the patients with dermographism.

A placebo-controlled comparative study of sustained-release brompheniramine maleate against clemastine fumarate in the treatment of chronic urticaria.

A partially-blind, three-way crossover study was carried out in 24 patients suffering from chronic urticaria to compare the efficacy and tolerance of brompheniramine maleate with that of clemastine fumarate. Patients received 4-week courses of treatment with 1 tablet twice daily of either 12 mg brompheniramine, 1 mg clemastine or placebo, in random order. Assessments were made by the physician of the patients' condition on entry and of response to treatment at the end of each 2-week period throughout the 12-week study period. At the end of the trial, patients were asked to state their preference, if any, for the different treatments. The results showed that both antihistamines were significantly effective compared to placebo and that at the dosage used brompheniramine was considered significantly better than clemastine in long-term control. Drowsiness was experienced by 4 patients whilst taking brompheniramine compared to 3 patients whilst taking clemastine. One patient experienced anorexia and vomiting with brompheniramine and 4 patients developed gastro-intestinal upsets whilst taking the placebo.

Effects of antidepressant treatments on dopamine turnover in depressed patients.

Effects of five antidepressant treatments--clorgyline, desipramine hydrochloride, electroconvulsive treatment, lithium carbonate, and zimelidine hydrochloride--on urinary outputs of dopamine, dihydroxyphenylacetic acid, and homovanillic acid (HVA) were investigated in unipolar and bipolar depressed patients. Clorgyline and lithium carbonate, which stabilized mood in bipolar patients, reduced the urinary output of HVA and whole-body dopamine turnover. Electroconvulsive treatment and zimelidine were without major effects, whereas desipramine had variable effects on these indexes of dopamine metabolism. Three patients, two receiving desipramine and one receiving clorgyline, who had increased HVA output during the drug treatments, became severely agitated and delusional.

A double-blind comparison of zimelidine and desipramine in endogenous depression.

Zimelidine, a specific 5HT uptake inhibitor (final dose 225 mg), and desipramine, mainly a noradrenaline uptake inhibitor (final dose 150 mg), were given in random order to 24 in- and out-patients fulfilling the Research Diagnostic Criteria for Major Depressive Disorder, definite or probable endogenous type, for a 3-week treatment period. Nonresponders were crossed over to the other drug for another 3 weeks. There was a nonsignificant trend towards more overall improvement on desipramine. Some patients in both groups showed very little change during 3 weeks, indicating a bimodal distribution of response to either drug. Several nonresponders improved markedly upon direct crossing over to the other drug. There were few and mild side effects on both drugs, with no significant difference between them. No significant correlation was found between improvement and plasma concentrations of zimelidine, norzimelidine, or desipramine, whereas a significant positive correlation was found between improvement and platelet serotonin uptake inhibition (measured in fresh platelets incubated in diluted plasma from the patients) in zimelidine-treated patients.