Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response.

BACKGROUND: Selective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant effects. Post-synaptic 5-HT2A receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT2A/D4 antagonist when administered in low doses. The purpose of this study was to compare citalopram 40 mg once daily plus pipamperone 5 mg twice daily (PipCit) versus citalopram plus placebo twice daily for magnitude and onset of therapeutic effect. METHOD: An 8-week, randomized, double-blind study in patients with major depressive disorder was carried out. RESULTS: The study population comprised 165 patients (citalopram and placebo, n=82; PipCit, n=83) with a mean baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of 32.6 (s.d.=5.5). In the first 4 weeks, more citalopram and placebo than PipCit patients discontinued treatment (18% v. 4%, respectively, p=0.003). PipCit patients had significantly greater improvement in MADRS score at week 1 [observed cases (OC), p=0.021; last observation carried forward (LOCF), p=0.007] and week 4 (LOCF, p=0.025) but not at week 8 compared with citalopram and placebo patients. Significant differences in MADRS scores favoured PipCit in reduced sleep, reduced appetite, concentration difficulties and pessimistic thoughts. Mean Clinical Global Impression-Improvement scores were significantly improved after 1 week of PipCit compared with citalopram and placebo (OC and LOCF, p=0.002). CONCLUSIONS: Although the MADRS score from baseline to 8 weeks did not differ between groups, PipCit provided superior antidepressant effects and fewer discontinuations compared with citalopram and placebo during the first 4 weeks of treatment, especially in the first week.

British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders.

Sleep disorders are common in the general population and even more so in clinical practice, yet are relatively poorly understood by doctors and other health care practitioners. These British Association for Psychopharmacology guidelines are designed to address this problem by providing an accessible up-to-date and evidence-based outline of the major issues, especially those relating to reliable diagnosis and appropriate treatment. A consensus meeting was held in London in May 2009. Those invited to attend included BAP members, representative clinicians with a strong interest in sleep disorders and recognized experts and advocates in the field, including a representative from mainland Europe and the USA. Presenters were asked to provide a review of the literature and identification of the standard of evidence in their area, with an emphasis on meta-analyses, systematic reviews and randomized controlled trials where available, plus updates on current clinical practice. Each presentation was followed by discussion, aimed to reach consensus where the evidence and/or clinical experience was considered adequate or otherwise to flag the area as a direction for future research. A draft of the proceedings was then circulated to all participants for comment. Key subsequent publications were added by the writer and speakers at draft stage. All comments were incorporated as far as possible in the final document, which represents the views of all participants although the authors take final responsibility for the document.

Clinical milestones predict symptom remission over 6-month and choice of treatment of patients with major depressive disorder (MDD).

BACKGROUND: It is uncertain as to what short-term outcomes predict long-term treatment compliance and outcomes in patients with MDD. AIMS: To determine what treatment milestones predict symptom remission with long-term treatment with antidepressant medication. METHOD: Pooled analysis of four randomised, double-blind, active comparator, 6-month trials in MDD. RESULTS: Patients received double-blind treatment with escitalopram (N=699) or a comparator (citalopram, duloxetine, or paroxetine) (N=699). Onset of effect at week 2 was correlated with response at week 8, and response at week 8 with completion of 6-month treatment. Week 8 response was associated with a greater probability of achieving later remission. Week 24 remission (MADRS>or=10) was significantly (p<0.01) higher for patients treated with escitalopram (70.7%) than for the pooled comparators (64.7%). Week 24 complete remission (MADRS

Prophylactic effect of citalopram in unipolar, recurrent depression: placebo-controlled study of maintenance therapy.

BACKGROUND: Major depression is highly recurrent. Antidepressant maintenance treatment has proven efficacy against recurrent depression. AIMS: Comparison of prophylactic efficacy of citalopram versus placebo in unipolar, recurrent depression. METHODS: Patients 18-65 years of age with recurrent unipolar major depression (DSM-IV), a Montgomery-Asberg Depression Rating Scale score of > or =22 and two or more previous depressive episodes, one within the past 5 years, were treated openly with citalopram (20-60 mg) for 6-9 weeks and, if responding, continued for 16 weeks before being randomised to double-blind maintenance treatment with citalopram or placebo for 48-77 weeks. RESULTS: A total of 427 patients entered acute treatment and 269 were randomised to double-blind treatment. Time to recurrence was longer in patients taking citalopram than in patients taking placebo (P:<0.001). Prophylactic treatment was well tolerated. CONCLUSIONS: Citalopram (20, 40 and 60 mg) is effective in the prevention of depressive recurrences. Patients at risk should continue maintenance treatment at the dose necessary to resolve symptoms in the acute treatment phase.

Comparison of the efficacy, safety, and onset of action of mizolastine, cetirizine, and placebo in the management of seasonal allergic rhinoconjunctivitis. MIZOCET Study Group.

BACKGROUND: Mizolastine is a potent and selective H1-receptor antagonist with additional anti-allergic properties. OBJECTIVE: The aim of this European multicenter, randomized, double-blind study was to compare the efficacy of mizolastine 10 mg (n = 122), cetirizine 10 mg (n = 125), and placebo (n = 128) once daily for 28 days in patients with seasonal allergic rhinoconjunctivitis (SAR), with focus on the onset of action. METHODS: Symptoms were evaluated by the investigator using a total symptom score (TS) and by the patient (first week). Responders (R) were patients with a TS decrease of at least 50%. Safety was assessed according to the spontaneous reporting of adverse events. RESULTS: Both mizolastine and cetirizine were effective in relieving the symptoms of SAR. After 7 days of treatment, the improvement in TS and responder's rate were significantly (P < .05) greater in patients treated with mizolastine (TS change versus baseline, mean +/- SD: -6.40 +/- 5.71; R: 55%) and cetirizine (TS change versus baseline: -6.24 +/- 5.24; R: 53%) than with placebo (TS change versus baseline: -4.11 +/- 5.91; R: 40%). Both drugs acted rapidly, within 2 hours of the first intake. During the first 3 days, mizolastine relieved symptoms more effectively than cetirizine, the difference being significant on the second (P = .027) and third (P = .050) day. Both mizolastine and cetirizine were well tolerated. CONCLUSION: Mizolastine 10 mg once daily is at least as effective as cetirizine in relieving symptoms of SAR, onset of action is rapid with clinical effect evident within 2 hours.

Antidepressants in panic disorder.

Panic disorder is a serious and common illness affecting 1% of the population at any one time. Comorbidity with depression may be as high as 40%. The illness has been recognized as a separate entity since the 1960s and treatment with tricyclics being used since that time. Tricyclics, monoamine oxidase inhibitors, benzodiazepines, beta-blockers and anticonvulsants have all been used with varying degrees of success. Until recently, tricyclics and benzodiazepines were the treatments of choice but selective serotonin reuptake inhibitors (SSRIs) have recently been studied intensively and, based on studies of citalopram and paroxetine, must now be considered first line therapy. Both SSRIs and tricyclics suffer from a long latency period, possibly as long as 12 weeks before maximal benefit is obtained, which is in contrast to the benzodiazepines that produce almost instant symptom relief. The dependency potential of the benzodiazepines, however, limits their usefulness. Paroxetine and citalopram have good efficacy data over both the short and long term and are effective at standard dosages, the most effective for citalopram being 20-30 mg. Both drugs performed better than the comparator tricyclic antidepressant (chlomipramine) and must now be considered current drugs of choice. Despite the superior efficacy of these drugs, however, many patients are poorly controlled and investigation of combination therapies for resistant panic disorder is needed.

A controlled, prospective, 1-year trial of citalopram in the treatment of panic disorder.

BACKGROUND: The objective of this study was to evaluate the efficacy and tolerability of citalopram in the long-term treatment of adult outpatients with panic disorder with or without agoraphobia. METHOD: Patients in this double-blind, parallel-group trial were assigned to 1 of 3 fixed dosage ranges of citalopram (10 or 15 mg/day, 20 or 30 mg/day, or 40 or 60 mg/day), 1 dosage range of clomipramine (60 or 90 mg/day), or placebo. After the completed 8-week acute treatment period, the eligible patients could continue the treatment for up to 1 year. Of the 475 patients who were randomly assigned for the short-term trial, 279 agreed to continue double-blind treatment at their assigned doses. The primary efficacy measure used was the Clinical Anxiety Scale panic attack item, and the response was defined as no panic attacks (score of 0 or 1). The other key measures used were the Physician's Global Improvement Scale, the Patient's Global Improvement Scale, and the Hamilton Rating Scale for Anxiety (HAM-A). RESULTS: In all drug-treated groups, except the group receiving the lowest citalopram dose, the treatment outcome was generally better than with placebo. As determined by a life table analysis of response, the probability of response during the 12 months was significantly greater with all treatment regimens than with placebo (p < .05), with citalopram 20 or 30 mg/day demonstrating the best response. Panic attacks tended to disappear in all patients remaining in the study until the end of follow-up. Analysis of the difference in the number of patients in different treatment groups remaining in the study (perhaps the best measure of long-term efficacy) also demonstrated that the patients treated with citalopram in dosage ranges of 20 or 30 mg/day and 40 or 60 mg/day had better response than placebo-treated patients (p < .0002 and p < .004, respectively). HAM-A and Global Improvement Scale scores also showed that patients treated with active drug showed greater improvement than placebo-treated patients. All treatment groups showed no new or exceptional adverse event clusters. CONCLUSION: Citalopram in the dosage range of 20 to 60 mg/day is effective, well tolerated, and safe in the long-term treatment of patients who have panic disorder.

Nasal budesonide offers superior symptom relief in perennial allergic rhinitis in comparison to nasal azelastine.

BACKGROUND: Allergic rhinitis is usually treated with oral antihistamines or nasal steroids. Topically active nasal antihistamine is a new treatment modality for allergic rhinitis. The efficacy in comparison to well established topical treatment alternatives is not fully known. OBJECTIVE: To compare the efficacy of intranasally administered azelastine to budesonide, at their respectively recommended dosage, on the symptoms of perennial rhinitis patients. METHODS: A placebo-controlled, randomized, parallel group study was conducted to compare the efficacy and tolerability of intranasal budesonide aqueous suspension (256 microg once daily) with azelastine hydrochloride nasal spray (280 microg twice daily (560 microg/day)) and with placebo in the treatment of perennial allergic rhinitis. The 195 patients (with at least a 2-year history of perennial allergic rhinitis) recorded individual nasal symptom scores, the degree of symptom control achieved and any adverse events experienced over a 2-week baseline period and a 6-week treatment period. RESULTS: Following treatment, the reductions in mean combined and individual nasal symptom scores from baseline values were significantly greater in the budesonide group compared with the placebo group (P < .0001 for all variables except runny nose P = .01). In patients treated with budesonide, there were also significantly larger reductions from baseline values in combined nasal symptom scores (P < .01) and in scores for all individual nasal symptoms (P < or = .05) compared with those treated with azelastine. The reductions from baseline in both combined and individual nasal symptom scores did not differ between azelastine and placebo. The study medications were well tolerated, producing no unexpected or serious treatment-related adverse events. CONCLUSION: A once-daily dose of 256 microg of intranasal budesonide aqueous suspension is significantly more effective at relieving the symptoms of perennial allergic rhinitis compared with a twice daily dose of 280 microg of azelastine nasal spray.

The effect of citalopram in panic disorder.

BACKGROUND: Citalopram is a serotonin reuptake inhibitor which has been demonstrated to be highly selective and with a superior tolerability profile to the classical tricyclic antidepressants. This study was designed to test whether there was any difference in efficacy in the management of panic disorder (PD) between citalopram and placebo. METHOD: This was a double-blind, placebo and clomipramine controlled, parallel group eight-week study. A total of 475 patients with PD, with or without agoraphobia, were randomised to treatment with either placebo, clomipramine 60 or 90 mg/day, or citalopram 10 or 15 mg/day, or 20 or 30 mg/day, or 40 or 60 mg/day. Doses were increased over the first three weeks, stabilised during the fourth week and fixed between weeks five and eight. RESULTS: Treatment with citalopram at 20 or 30 mg, 40 or 60 mg and clomipramine were significantly superior to placebo, judged by the number of patients free of panic attacks in the week prior to the final assessment. All rating scales examined suggested that citalopram 20 or 30 mg was more effective than citalopram 40 or 60 mg. CONCLUSION: The most advantageous benefit/risk ratio for the treatment of PD was associated with citalopram 20 or 30 mg/day.

Nabumetone compared with indomethacin in the treatment of osteoarthritis in general practice.

In a double blind, randomized, parallel group study, 197 patients with osteoarthritis (OA) received nabumetone (1000 mg/day) or indomethacin (75 mg/day) for 6 weeks and doses could be doubled. Doubling the dose resulted in a 100 or 67% increase in pain relief with nabumetone or indomethacin, respectively. Significantly more patients experienced at least 1 severe adverse event with indomethacin than with nabumetone. With nabumetone, the incidence of adverse events did not increase with dose. However, with the increase in dose, the incidence of all adverse events and gastrointestinal events increased in indomethacin treated patients. Nabumetone was as effective as indomethacin for the treatment of OA. However, significantly fewer nabumetone treated patients experienced severe adverse events and the frequency of events did not increase with dose.

Long term management of duodenal ulcer in general practice: how best to use cimetidine?

Two hundred and sixty seven patients with duodenal ulceration were entered into a five year study of two strategies of treatment with cimetidine. Two thirds were treated continuously with 400 mg at bedtime supplemented by temporary increases in dosage if they had symptomatic relapses (group 1), and the remaining third were given intermittent "healing" doses for four to eight weeks if a symptomatic recurrence was judged to have occurred (group 2). Life table analysis showed that the probability of remaining free of clinically important symptoms five years after the start of treatment was 24% (95% confidence interval (CI) 15.5% to 32.6%) in group 1 compared with nil in group 2 (p less than 0.0001). The median values for the longest periods free from relapse for each patient were 108 weeks in group 1 and 32 weeks in group 2, respectively (p less than 0.0001; 95% CI of the median difference 36 to 76). Over the five years 10 patients suffered major complications, two requiring emergency surgery, while a further nine had elective surgery because of the failure of medical treatment. There were no deaths that could be attributed either to ulceration or to treatment with cimetidine. Medical management was therefore very satisfactory for most patients, though those treated continuously with cimetidine suffered considerably less from their ulcer symptoms. As 80% of patients studied relapsed during the two years after a healing course of cimetidine, continuous treatment will benefit many patients treated in general practice.

A double-blind comparison of meptazinol versus paracetamol and placebo in acute and chronic painful conditions presented to the general practitioner.

A double-blind study was carried out in 90 patients with acute or chronic painful musculoskeletal conditions of at least moderate severity to compare the effectiveness over a 72-hour period of oral treatment, 3 to 6 hourly, with 200 mg meptazinol, 1 g paracetamol and placebo. Assessments of pain by physicians and patients indicated that both active treatments produced effective analgesia compared with placebo. No significant differences were observed between meptazinol and paracetamol. The frequency of adverse effects reported was low and similar in all three treatment groups.

First impressions of the use of meptazinol in general practice.

Meptazinol which is a potent opiate antagonist analgesic has been assessed by the oral route at a dose of 200 mg 3-6 hourly. The analgesic profile shows a significant fall in pain score by 2 hours which was the earliest recording time. Satisfactory pain relief was maintained during 3 days of treatment. The side-effect profile was of a low order and there was no adverse effect on haematological and biochemical screens.