Evaluation of the efficacy of olopatadine hydrochloride 0.1% ophthalmic solution and azelastine hydrochloride 0.05% ophthalmic solution in the conjunctival allergen challenge model.

BACKGROUND: Olopatadine hydrochloride 0.1% ophthalmic solution and azelastine hydrochlofide 0.05% ophthalmic solution are 2 topical antiallergic agents indicated for the treatment of itching of the eye associated with allergic conjunctivitis. Olopatadine has recently received US Food and Drug Administration (FDA) approval for an expanded indication for the treatment of signs and symptoms of allergic conjunctivitis, including itching, tearing, eyelid swelling, redness, and chemosis. OBJECTIVE: The purpose of this study was to compare the efficacy of olopatadine hydrochloride versus azelastine hydrochloride and placebo (artificial tears) in the conjunctival allergen challenge (CAC) model. METHODS: This was a prospective, randomized, double-masked, contralaterally controlled, multicenter, allergen-challenge study. Itching was chosen as the primary efficacy variable since it is the only FDA-approved indication these 2 agents have in common. Subjects with a history of allergic conjunctivitis who responded to the CAC at screening visits 1 and 2 were randomized to 1 of 3 treatment groups: olopatadine in 1 eye and azelastine in the other eye; olopatadine in 1 eye and placebo in the other eye; or azelastine in 1 eye and placebo in the other eye. At the assessment visit (visit 3), subjects received masked study medication according to the randomization scheme. After 5 minutes, subjects were bilaterally challenged with the allergen concentration that had elicited a positive conjunctival allergic response at visits 1 and 2. Immediately after challenge, subjects gave itching assessments (scale, 0 = no itching to 4 = severe itching) every 30 seconds for a total period of 20 minutes. Mean itching scores for all eyes were compared by treatment. Mean itching scores at each time point were compared between treatments using 2 sample t tests. RESULTS: Of the 180 subjects screened, 111 responded to the CAC at visits 1 and 2 and completed the study; 65% (72/111) of patients were female, 87% (97/111) were white, and 49% (54/111) had brown irides. The mean age was approximately 40 years. Seventy-three eyes were treated with olopatadine, 75 with azelastine, and 74 with placebo. A single dose of 1 of the 3 study medications per eye was well tolerated by all subjects. Both treatments were significantly more effective than placebo at reducing itching postchallenge. Olopatadine was significantly more effective than azelastine in reducing itching at 3.5 minutes through 20 minutes postchallenge (average mean unit difference of -0.31; P < 0.05) in the CAC model. CONCLUSION: In this population, olopatadine was significantly more effective than azelastine in the management of itching associated with allergic conjunctivitis in the CAC model.

A comparison of the relative efficacy and clinical performance of olopatadine hydrochloride 0.1% ophthalmic solution and ketotifen fumarate 0.025% ophthalmic solution in the conjunctival antigen challenge model.

OBJECTIVE: The purpose of this study was to compare the relative efficacy and clinical performance of olopatadine hydrochloride 0.1% ophthalmic solution and ketotifen fumarate 0.025% ophthalmic solution in the conjunctival antigen challenge model. METHODS: This was a prospective, randomized, double-masked, contralaterally controlled, single-center, antigen challenge study. Of the 53 subjects screened, 32 were enrolled and completed the study. The study comprised 3 visits. Primary efficacy variables were ocular itching (assessed at visits 2 and 3) and subject satisfaction (assessed at visit 3). Tolerability variables were slit-lamp findings (all visits), visual acuity (all visits), ocular comfort after drug instillation (visit 3), and adverse events (visits 2 and 3). At visit 1, the antigen concentration that elicited a positive ocular allergic response was determined, and this concentration was confirmed at visit 2. Subjects graded itching on a 5-point scale at 3, 5, and 10 minutes postchallenge. The scores from this visit were used as baseline scores and compared with scores from visit 3 to determine drug efficacy. At visit 3, subjects were randomly assigned to 2 treatment groups. Group A received 1 drop of olopatadine in the right eye and I drop of ketotifen in the left eye. Group B received 1 drop of olopatadine in the left eye and 1 drop of ketotifen in the right eye. Following drug instillation, the subjects assessed the comfort level in each eye. Twelve hours after instillation, subjects were challenged with the antigen concentration that elicited a positive response at the previous visits. Itching was subjectively graded at 3, 5, and 10 minutes postchallenge. Subjects were asked to choose which therapy they were more satisfied with. RESULTS: Twelve hours after administration, efficacy scores for olopatadine were significantly higher than those for ketotifen at 3 and 5 minutes postchallenge (1.84 and 1.75 vs 1.25 and 1.34; P < 0.05). Olopatadine-treated eyes were rated significantly more comfortable than those treated with ketotifen immediately after drug instillation (1.25 vs 2.09; P < 0.05) and 12 hours later, as measured by patient ratings of ocular comfort. Of the 22 subjects who had a preference, 16 (73%) were more satisfied with olopatadine than with ketotifen. CONCLUSIONS: Olopatadine is more effective than ketotifen in reducing the itching associated with allergic conjunctivitis in the antigen challenge model. Olopatadine caused less ocular discomfort than ketotifen and was preferred by approximately 3 times as many patients as was ketotifen.

Does psychotherapy homework lead to improvements in depression in cognitive-behavioral therapy or does improvement lead to increased homework compliance?

The bidirectional causal relationships between psychotherapy homework (HW) compliance and changes in depression were assessed in 2 groups of depressed outpatients treated with cognitive-behavioral therapy using nonrecursive structural equation modeling techniques. The data were consistent with the hypothesis that HW compliance had a causal effect on changes in depression, and the magnitude of this effect was large. Patients who did the most HW improved much more than patients who did little or no HW. In contrast, depression severity did not appear to influence HW compliance. HW compliance did not appear to be a proxy for any other, unobserved (3rd) variable, such as motivation. Although the causal effect of HW on depression was large, the correlation between HW and depression was small. Some possible explanations, along with suggestions for future studies, are proposed.

Cognitive-behavioral therapy for bulimia nervosa: an illustration.

Cognitive-behavioral therapy for bulimia nervosa (BN) is a well-developed, theoretically grounded treatment for BN with the strongest empirical support for its efficacy of any form of treatment for BN. The treatment package comprises three distinct phases typically delivered over 20 weeks. Incorporating a variety of specific interventions, these three phases of treatment focus systematically on (i) dietary restraint, (ii) dysfunctional beliefs about body weight and shape, and (iii) reactions to recurrence of symptoms, which are thought to be the primary operative mechanisms that cause and maintain BN symptoms. Case material is presented to illustrate cognitive-behavioral treatment principles.

Comparison of cognitive models of depression: relationships between cognitive constructs and cognitive diathesis-stress match.

The authors examined the relationship between the cognitive components of the Beckian and Hopelessness models of depression by administering measures of dysfunctional attitudes, attributional style, and life stress to a sample of 59 depressed adults. Confirmatory factor analyses indicated that dysfunctional attitudes and attributional style load on separate factors as opposed to a single factor. Additional analyses revealed that depressed persons conforming to diathesis-stress criteria according to each model were largely independent of one another. Results supported the conclusion that the Beckian and Hopelessness models of depression describe distinct cognitive constructs and refer to distinct subsets of depressed persons.

Response to cognitive-behavioral therapy in depression: effects of pretreatment cognitive dysfunction and life stress.

Response to cognitive-behavioral therapy (CBT) for depression is variable and the factors that account for differences in response are not yet well established. Level of cognitive dysfunction and the occurrence of negative life stress have been theorized as patient variables, which may account for differences in response to CBT. The relationship between response to CBT and the interaction of cognitive dysfunction with negative life events was examined in a sample of 53 depressed outpatients. Overall, there was little support for the prediction of a difference in acute outcome between patients with or without pretreatment cognitive dysfunction and negative stressors.

Gender differences in cognitive diathesis-stress domain match: implications for differential pathways to depression.

The frequency of cognitive diathesis-stress match was compared in a sample of depressed women and men to investigate hypotheses positing gender differences in the relation of cognitive diathesis-stress factors to depression. Depressed women were more likely to have experienced a match between a cognitive diathesis and a preonset negative stressor compared with depressed men. Comparisons of women and men on the cognitive and stress variables singly yielded differences in stress variables but not in cognitive variables. Depressed women were more likely to have experienced a negative severe event before the onset of depression and had a greater frequency of negative interpersonal events. Results supported the hypothesis of gender differences in pathways to depression.

Evaluating the hopelessness model of depression: diathesis-stress and symptom components.

The hopelessness model of depression posits that latent attributional diatheses combine with stressors to produce a specific subtype of depression characterized by a specific set of symptoms. Associations between attributional diathesis, stress, and symptoms were examined to test the prediction that hopelessness depressions are characterized by a specific symptom profile. Fifty-seven depressed outpatients were categorized into subgroups on the basis of whether or not they met the criteria of L. Y. Abramson, L. B. Alloy, and G. I. Metalsky's (1988) hopelessness depression, defined as a match in content domain between attributional diathesis and negative stressor. Support for hopelessness depression was mixed. The hopelessness subtype differed from other major depressions with respect to symptom profile. However, the differences in symptomatology were not wholly consistent with the predictions of the hopelessness model.

Evaluation of tremor and efficacy of oral procaterol in adult patients with asthma.

Tremor, the most common side effect of ordinary doses of beta 2-agonists, was evaluated in a quantitative manner and compared to improvement in pulmonary function in respect to time of onset, duration, peak effect, and tachyphylaxis with procaterol in adults. Forty-five adult patients with reversible obstructive airway disease were studied during administration of three different dosages of procaterol, 25 micrograms escalating to 100 micrograms, and 100 micrograms twice daily. Tremor was quantitatively evaluated with a Grass model accelerometer. The patients were evaluated during 8 hours approximately every 2 weeks for 8 weeks. Daily diaries of symptoms and side effects were also maintained. The study demonstrated no direct relationship between tremor and pulmonary function as far as time of onset, peak effect, or duration. Although tachyphylaxis was demonstrated, much of the tolerance developed to the tremor was explained by an increase in baseline tremor. Procaterol was demonstrated to be an effective bronchodilator, and tolerance to tremor was demonstrated to develop with time but is highly variable. There was not a direct relationship between tremor and pulmonary function, indicating possible differences between lung and peripheral muscle beta 2-receptors. It appeared that the best way to minimize the problem of tremor is to begin with a lower dose and increase the dose gradually during a period of weeks.

Review of side effects associated with beta agonists.

Beta agonists are a primary drug of choice in the treatment of asthma. Nevertheless, there are significant concerns about side effects in using these medications, especially in certain disease states, in higher dosages, and in severe asthma episodes. Proper patient evaluations and monitoring can reduce significantly these side effects and reduce their health consequences.

The effect of diet on the efficacy onset and duration of action of procaterol hydrochloride tablets.

Procaterol hydrochloride, a new potent beta-2 agonist drug, was evaluated for effects of food absorption, onset of action, and efficacy in a single-dose non-blinded placebo controlled crossover design in 18 subjects. Three diet conditions, separated by a three to seven day washout period, were used and compared to a placebo treatment. The diets were standardized and included high fat, low fat, and a fasting condition. Spirometric determinations and vital signs were obtained at 0, 15, 30 minutes, and at one, two, four, six, eight hours post-dose to evaluate therapeutic availability since no technique for measuring serum levels of procaterol hydrochloride is currently available. Spirometry results indicated significant improvement in pulmonary function during all diet conditions except with the placebo treatment. A delay in onset of action was seen in the low fat diet and to a certain extent in the high fat diet as compared to the fasting condition. There was no effect of diet on procaterol hydrochloride's peak response or duration of action with improvement in pulmonary function demonstrated for up to eight hours. Tremor and headache were the most frequent side effects, and were mild and transient. No significant effects were noted in electrocardiograms, heart rate, or blood pressure. An elevation in serum glucose was seen in three subjects during the fasting challenge and was felt to be secondary to the beta-agonist effects of procaterol hydrochloride. Procaterol was found to be an effective drug with a delayed onset of action when administered with food, but no effect on subsequent efficacy or duration of action.

The use of ketotifen in the prophylaxis of seasonal allergic asthma.

This double-blind parallel group study evaluated ketotifen 1 mg bid versus placebo in the treatment of 30 adult seasonally allergic asthmatics during the course of the spring pollen season. Those individuals on placebo had a fall in FEV1 through the pollen season, those on Ketotifen generally did not, and some individuals, in fact, showed improvement. Those patients receiving ketotifen had fewer allergic symptoms, better exercise tolerance, and in general had a better spring. This study demonstrated that ketotifen may have some benefit in the treatment of adult allergic asthma.

Use of Seralyzer system for theophylline level determination in an office setting.

Theophylline levels were measured on 63 plasma samples by both high pressure liquid chromatography and Seralyzer methods with excellent correlation. Seralyzer results were obtained quickly and easily in an office setting and offered the additional advantage of allowing accurate measurements on finger-stick samples.

The effect of diet on the metabolism of long acting theophylline.

Recently some concern has been expressed of the effect of diet on the metabolism of theophylline. This brief trial in normal healthy adults observed the effect of fasting, high fat, low fat, and liquid fat/low carbohydrate diet on the metabolism of a sustained-release theophylline preparation (Theo-Dur). On analysis of the mean theophylline level values, there were no significant differences in the theophylline levels between the diets. However, in certain individuals there were differences in the theophylline absorption rates between diets. No consistent pattern was seen.

Comparison of nebulized terbutaline (TERB) and subcutaneous epinephrine (EPI) in the treatment of acute asthma.

The purpose of this study was to compare nebulized terbutaline 5 mg vs. subcutaneous epinephrine (1/1000, 0.3 cc) in the treatment of acute exacerbations of asthma in adult patients. Patients with a known diagnosis of asthma, who presented to the investigators in acute respiratory distress, without any previous adrenergic agents for six hours, were the subjects for this study. There were 33 patients enrolled in the study between 16 and 64 years of age. The results indicate both treatment groups gave significant increases in pulmonary function at all times when compared to baseline (p less than 0.001). Nebulized terbutaline and subcutaneous epinephrine appeared equally effective in the treatment of acute exacerbations of asthma, without significant differences in bronchodilator effectiveness or side effects.

Bioavailability of sustained-release theophylline granules in apple sauce in pediatric asthmatic patients.

To facilitate administration of sustained-release theophylline in pediatric patients fourteen children with asthma were studied using intact capsules versus the granular contents in apple sauce. In a cross-over study during multiple dose intervals the effectiveness of this administration technique was demonstrated for maintaining bioavailability and sustained-release characteristics.

Bioavailability and multiple dose characteristics of a new sustained release theophylline tablet.

Bioavailability and theophylline level variability were compared between a standard theophylline elixir and a new sustained release theophylline tablet. The results demonstrate a good bioavailability and a reduced dosage interval with less theophylline level variability for the sustained release tablet, administered every 12 hours, than with the immediate release product, every six hours.

Terbutaline in the treatment of chronic urticaria.

Eighteen patients with chronic urticaria were evaluated concerning the benefit of oral sympathomimetic therapy. No significant differences could be found between the sympathomimetic agent (terbutaline) and a placebo in the various clinical parameters evaluated. The authors conclude that the efficacy of this drug is doubtful in the treatment of chronic urticaria.

Compliance differences following administration of theophylline at six- and twelve-hour intervals.

This study evaluated the compliance differences between administration of theophylline at six- and 12-hour intervals in a pediatric outpatient population. Compliance was statistically better with the sustained release tablets than with the short acting tablets.

Use of a twelve-hour theophylline preparation in chronic adult asthmatics.

Twenty-one adult chronic asthmatic patients were studied while taking a 12-hour sustained-action theophylline tablet. Pulmonary function testing and serum theophylline levels were monitored for 12 weeks, including testing every two hours over one dosing interval on the final day of the study. Results indicate the preparation tested produced sustained stable theophylline levels for a full 12 hours, with pulmonary function also remaining elevated and stable during this period. There was minimal toxicity reported over the 12-week period and no evidence of tolerance.