A placebo-controlled, randomized, double-blind study of adjunctive bupropion sustained release in the treatment of SSRI-induced sexual dysfunction

BACKGROUND: Sexual side effects are among the common reasons patients discontinue selective serotonin reuptake inhibitors (SSRIs). While many antidotes have been proposed, few have been subjected to double-blind trials. Some evidence has suggested that bupropion may be an effective antidote for SSRI-induced sexual dysfunction. In this double-blind trial, the efficacy of a standard dose of bupropion sustained release (SR) is evaluated in the treatment of SSRI-induced sexual dysfunction. METHOD: Patients with a history of SSRI-induced sexual side effects were randomly assigned to adjunctive treatment with either bupropion SR 150 mg daily or placebo for 6 weeks. Assessments of sexual function and interest included the Arizona Sexual Experiences Scale (ASEX), Brief Index of Sexual Functioning, and a 10-point visual analogue scale. Efficacy was defined as a 50% improvement on the ASEX at the end of 6 weeks. Data were collected from January 1999 to March 2001. RESULTS: Forty-one patients entered the study and completed the 6-week trial. No significant differences were seen between placebo and bupropion SR on the ASEX or on any measure of sexual functioning at the end of the trial. CONCLUSION: A fixed dose of 150 mg/day of bupropion SR taken in the morning does not appear to be effective in the treatment of SSRI-induced sexual dysfunction. Additional trials will be required to define what role, if any, bupropion might have in the treatment of SSRI-induced sexual side effects.     

A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia

Sexual dysfunction is common in people suffering from schizophrenia and is reported by patients to be a significant reason for medication nonadherence. This report contains data for 27 people with schizophrenia who participated in a randomized double-blind 12-week trial of risperidone (4 mg/day), quetiapine (400 mg/day) or fluphenazine (12.5 mg/day). At baseline and endpoint, subjects were rated on the Changes in Sexual Function Questionnaire (CSFQ), the Prolactin-Related Adverse Event Questionnaire (PRAEQ) and had prolactin levels drawn. Endpoint prolactin levels were 50.6 +/- 40.4, 24.4 +/- 18.5, and 8.2 +/- 4.4 mg/dl for risperidone (N = 12), fluphenazine (N = 9) and quetiapine (N=6), respectively (F = 7.5,df = 2, p = 0.005, controlling for sex). Orgasm quality/ability improved significantly for quetiapine as compared to fluphenazine and risperidone (F = 4.41, df = 2, p = 0.033). Seventy-eight percent of patients on fluphenazine reported sexual dysfunction whereas did only 42 and 50% of those on risperidone and quetiapine. Forty percent of quetiapine patients reported they felt better about their sexuality as compared to previous treatment, as did 55% on risperidone. Conversely, only 13% of fluphenazine subjects reported any improvement. Hormonal problems (menstrual problems, gynecomastia, galactorrhea) were predominately observed in risperidone-treated subjects. Overall, quetiapine was associated with a normalization of prolactin levels and had the greatest benefits among these drugs regarding sexual functioning.     

Comparison of Vivalan (viloxazine hydrochloride) with imipramine in the treatment of depression. A double-blind study.

Twenty-eight hospitalized patients with depressive illness entered a double-blind trial to compare viloxazine hydrochloride (Vivalan) with imipramine. Both drugs produced a statistically significant improvement in the depressive symptoms as early as the 7th day, measured by the HRS. A side effects check-list showed no significant difference between Vivalan and imipramine. A lack of anticholinergic effects was noted in the Vivalan group although upper gastro-intestinal side effects were more frequent. Two patients in the Vivalan group withdrew due to gastric symptoms.     

Atomoxetine for the treatment of executive dysfunction in Parkinson's disease: A pilot open‐label study

Executive dysfunction (ED) is a prominent and often disabling feature of cognitive impairment in Parkinson's disease (PD). Few studies have examined treatments. Given the role of noradrenergic pathology in ED, atomoxetine, a norepinephrine reuptake inhibitor indicated for attention deficit hyperactivity disorder (ADHD), may be a potential treatment for PD‐related ED. Twelve patients with PD and disabling ED completed an 8‐week pilot open‐label, flexible dose (25–100 mg/day) trial of atomoxetine. On primary outcome measures, atomoxetine was associated with improved ED based on the Clinical Global Impression‐Change Scale (75% positive response rate; 95% CI: 43–95%, P < 05) and behavioral measures of ED [Frontal Systems Behavior Scale (FrSBE) Executive Dysfunction and Connors Adult ADHD Rating Scale (CAARS) inattention/memory subscales]. Adverse effects included sleep and gastrointestinal disturbances and hypomania. Atomoxetine is tolerable in PD and may benefit clinical manifestations of ED, warranting further study in controlled trials. © 2008 Movement Disorder Society     

A pilot, double-blind, placebo-controlled trial of pregabalin (Lyrica) in the treatment of essential tremor.

We performed a pilot, double-blind, placebo-controlled, randomized trial to evaluate the efficacy and tolerability of pregabalin (PGB, Lyrica), an antiepileptic agent, in treating essential tremor (ET). Twenty two patients with ET were randomly assigned to receive PGB or placebo. PGB was initiated at 50 mg/day and was escalated by 75 mg/day every 4 days to a maximum dose of 600 mg/day. Patients were evaluated by accelerometry and the Fahn-Tolosa-Marin (FTM) rating scale. There was a significant reduction in tremor amplitude in the PGB group compared with the placebo group, as measured by accelerometry, at a mean dose of 286.76+/-100.05 mg/day. Action tremor limb scores on the FTM also improved in the PGB group compared with the placebo group (P-value for multilevel modeling=0.04). PGB was fairly well tolerated, with about one-third of patients dropping out of the study because of adverse events. PGB provided significant improvements in accelerometry and in action tremor limb scores on the FTM. However, larger studies are needed to further evaluate the potential effect of PGB on ET.     

Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial

Depression is one of the most common neuropsychiatric conditions, with a lifetime prevalence approaching 17%. Although a variety of pharmaceutical agents is available for the treatment of depression, psychiatrists find that many patients cannot tolerate the side effects, do not respond adequately, or finally lose their response. On the other hand, many herbs with psychotropic effects have far fewer side effects. They can provide an alternative treatment or be used to enhance the effect of conventional antidepressants. A number of recent preclinical and clinical studies indicate that stigma and petal of Crocus sativus have antidepressant effect. Our objective was to compare the efficacy of petal of C. sativus with fluoxetine in the treatment of depressed outpatients in an 8-week pilot double-blind randomized trial. Forty adult outpatients who met the DSM- IV criteria for major depression based on the structured clinical interview for DSM- IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind and randomized trial, patients were randomly assigned to receive capsule of petal of C. sativus 15 mg bid (morning and evening) (Group 1) and fluoxetine 10 mg bid (morning and evening) (Group 2) for a 8-week study. At the end of trial, petal of C. sativus was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F=0.03, d.f.=1, P=0.84). In addition, in the both treatments, the remission rate was 25%. There were no significant differences in the two groups in terms of observed side effects. The present study is supportive of other studies which show antidepressant effect of C. sativus.     

银杏叶提取物结合氟哌啶醇治疗慢性精神分裂症的双盲对照研究

目的探讨银杏叶提取物结合氟哌啶醇对慢性精神分裂症的治疗作用。方法采用随机、双盲、空白对照法，用银杏叶提取物３６０ｍｇ／ｄ结合氟哌啶醇（０２５ｍｇ／ｋｇ）对１１２例慢性精神分裂症患者进行治疗１２周，在治疗前后评定ＢＰＲＳ、ＳＡＰＳ、ＳＡＮＳ和ＴＥＳＳ量表。结果银杏叶提取物结合氟哌啶醇治疗慢性精神分裂症的疗效比单用氟哌啶醇要好，前者ＢＰＲＳ、ＳＡＰＳ和ＳＡＮＳ量表总分明显降低，而后者仅ＢＰＲＳ量表总分明显降低；同时前者治疗后ＳＡＰＳ量表评分显著低于后者；银杏叶提取物具有减轻氟哌啶醇锥体外系和行为毒性副反应的作用。结论银杏叶提取物可提高抗精神病药治疗慢性精神分裂症的疗效，并减轻抗精神病药副作用。     

Employment, medical absenteeism, and disability perception in Parkinson's disease: A pilot double-blind, randomized, placebo-controlled study of entacapone adjunctive therapy.

The objective of this study was to test the impact of entacapone (ENT) addition to levodopa with a decarboxylase inhibitor (LD) in full-time-employed patients with Parkinson's disease (PD), focusing on retirement rates, medical absenteeism, self-perception of disability, as well as motor assessments of parkinsonism, motor fluctuations, and dyskinesias. Thirty full-time-employed PD patients (disease onset before age 60 years) and on optimized monotherapy with LD exhibiting minor motor fluctuations or dyskinesias were entered into a 2-year randomized double-blind placebo-controlled study of ENT adjunctive therapy. The outcome measures were the number of full-time-employed patients at study end, cumulative days of medical absenteeism, patient-completed disability assessments, diary records, and the Unified Parkinson's Disease Rating Scale-based measures of motor fluctuations and dyskinesias. LD + ENT treatment was associated with a lower retirement rate (2 [17%] of 12 vs. 6 [50%] of 12; P = 0.12), lower absenteeism rate (21.5 vs. 43.5 days; P < 0.0001), improved self-perception of disability progression over 2 years (change score 1.0 vs. 4.5; P < 0.0001), and lower scores for both motor fluctuations and dyskinesia assessments compared to LD monotherapy. In this pilot study, LD with ENT adjunctive therapy positively influenced employment rate over 2 years; this effect was associated with reduced motor complications and patient perceptions of stabilized disability.     

Repetitive transcranial magnetic stimulation of the right parietal cortex for comorbid generalized anxiety disorder and insomnia: A randomized,double-blind,sham-controlled pilot study

Background

Repetitive transcranial magnetic stimulation (rTMS) has been considered to be a promising technique for the treatment of neuropsychiatric disorders. However, little is known about the effectiveness of rTMS in the treatment of generalized anxiety disorder (GAD). Moreover, treatment data on comorbid GAD and insomnia remain lacking. The aim of this study was to examine the therapeutic effects of 1?Hz rTMS applied over the right parietal lobe on both anxiety and insomnia symptoms in patients with comorbid GAD and insomnia.

A randomized, double-blind study of continuation treatment for attention-deficit/hyperactivity disorder after 1 year.

BACKGROUND: The efficacy of atomoxetine in maintaining symptom response following 1 year of treatment was assessed in children and adolescents (n = 163) with DSM-IV defined attention-deficit/hyperactivity disorder (ADHD). METHODS: Subjects had previously responded to atomoxetine acutely and had completed 1 year of double-blind atomoxetine treatment. They were then randomly assigned in double-blind fashion to continued atomoxetine or placebo substitution for 6 months. RESULTS: Atomoxetine was superior to placebo in preventing relapse (Wilcoxon test, p = .008) and in maintaining symptom response (ADHD Rating Scale IV score, p < .001). Among subjects assigned to discontinuation, the magnitude of symptom return was generally to a level of severity less than that observed at study entry. CONCLUSIONS: Following 1 year of treatment with atomoxetine, continued treatment over the ensuing 6 months was associated with superior outcomes compared with placebo substitution. However, there was considerable variability between individuals in the magnitude of symptom return after drug discontinuation, suggesting that some subjects treated with atomoxetine for a year with good results may consolidate gains made during drug treatment and could benefit from a medication-free trial to assess the need for ongoing drug treatment.     

Macrogol for the treatment of constipation in Parkinson's disease. A randomized placebo‐controlled study

Chronic constipation is the most frequent symptom of autonomic system involvement in Parkinson's disease (PD). Quite often the symptom is severe and impairs patients' quality of life. The objective of this study is to determine the efficacy and safety of an isosmotic macrogol solution for the treatment of constipation in PD patients, in a double‐blind, placebo‐controlled study. A total of 57 PD patients with constipation were randomly assigned to receive an isosmotic macrogol electrolyte solution (MC‐ES; 29 patients) or placebo (28 patients) for 8 weeks. Treatment efficacy was defined as complete relief of the symptom or a marked improvement of two of the following indicators: stool frequency, straining, stool consistency, use of rectal laxatives as a rescue therapy. The responder rates were significantly higher in the MC‐ES group both at the first (4 weeks; P < 0.0003) and at the final evaluation (8 weeks; P < 0.0012). The frequency of bowel movements (P < 0.002) and stool consistency (P < 0.006) were significantly changed in the MC‐ES group compared to the placebo group. At the final evaluation, a rectal laxative was used by 2 (12.5%) patients on placebo, whereas no use was recorded in the MC‐ES group. Responder rate for straining showed a favorable trend in patients treated with macrogol versus placebo. Unified Parkinson's Disease Rating Scale Part III and Parkinson's Disease Questionnaire (PDQ‐39) did not show any significant modification in either group during the 8‐week treatment period. The results of this placebo‐controlled study show the efficacy of MC‐ES in the treatment of constipation in PD. MC‐ES was well‐tolerated and did not affect the course of PD. © 2006 Movement Disorder Society     

A randomized, double-blind, placebo-controlled pilot study of i.v. immune globulins in combination with i.v. methylprednisolone in the treatment of relapses in patients with MS

BACKGROUND: Some patients with multiple sclerosis (MS) do not show a clear improvement of acute relapses after treatment with intravenous methylprednisolone (IVMP). We compared the efficacy of the combination of intravenous immunoglobulins (IVIg) and IVMP with the standard treatment of IVMP alone in promoting recovery from moderate to severe acute relapses in MS. METHODS: Patients with clinically definite MS having a relapse with at least a one point increase in Kurtzke's expanded disability status scale (EDSS) in comparison to the preattack EDSS were randomized to IVMP-IVIg or IVMP-placebo treatment. The primary outcome criterion was the EDSS grade at four weeks. A preplanned interim analysis was performed after inclusion of 19 consecutive MS patients to evaluate the sample size necessary for a larger trial. FINDINGS: Both groups had improved one point on the EDSS four weeks after start of treatment (P = 0.81) and one of the stopping rules of the interim analysis was fulfilled. There were also no differences in secondary outcomes: EDSS at eight and 12 weeks, time to improve > or = 1 EDSS points, difference in Scripps score and ambulation index. Five patients in the IVMP-IVIg group and two in the IVMP group had a new relapse in the six month follow-up. INTERPRETATION: Our study could not show superiority of IVMP-IVIg in the treatment of moderate to severe acute relapses in MS.     

Efficacy and safety of botulinum type A toxin (Dysport) in cervical dystonia: results of the first US randomized, double-blind, placebo-controlled study.

Botulinum toxin type A (Dysport) has been shown in European studies to be a safe and effective treatment for cervical dystonia. This multicenter, double-blind, randomized, controlled trial assessed the safety and efficacy of Dysport in cervical dystonia patients in the United States. Eighty patients were randomly assigned to receive one treatment with Dysport (500 units) or placebo. Participants were followed up for 4 to 20 weeks, until they needed further treatment. They were assessed at baseline and weeks 2, 4, 8, 12, 16, and 20 after treatment. Dysport was significantly more efficacious than placebo at weeks 4, 8, and 12 as assessed by the Toronto Western Spasmodic Torticollis Rating Scale (10-point vs. 3.8-point reduction in total score, respectively, at week 4; P < or = 0.013). Of participants in the Dysport group, 38% showed positive treatment response, compared to 16% in the placebo group (95% confidence interval, 0.02-0.41). The median duration of response to Dysport was 18.5 weeks. Side effects were generally similar in the two treatment groups; only blurred vision and weakness occurred significantly more often with Dysport. No participants in the Dysport group converted from negative to positive antibodies after treatment. These results confirm previous reports that Dysport (500 units) is safe, effective, and well-tolerated in patients with cervical dystonia.     

Qigong exercise for the symptoms of Parkinson's disease: a randomized, controlled pilot study.

Irrespective of limited evidence, not only traditional physiotherapy, but also a wide array of complementary methods are applied by patients with Parkinson's disease (PD). We evaluated the immediate and sustained effects of Qigong on motor and nonmotor symptoms of PD, using an add-on design. Fifty-six patients with different levels of disease severity (mean age/standard deviation [SD], 63.8/7.5 years; disease duration 5.8/4.2 years; 43 men [76%]) were recruited from the outpatient movement disorder clinic of the Department of Neurology, University of Bonn. We compared the progression of motor symptoms assessed by Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) in the Qigong treatment group (n = 32) and a control group receiving no additional intervention (n = 24). Qigong exercises were applied as 90-minute weekly group instructions for 2 months, followed by a 2 months pause and a second 2-month treatment period. Assessments were carried out at baseline, 3, 6, and 12 months. More patients improved in the Qigong group than in the control group at 3 and 6 months (P = 0.0080 at 3 months and P = 0.0503 at 6 months; Fisher's exact test). At 12 months, there was a sustained difference between groups only when changes in UPDRS-III were related to baseline. Depression scores decreased in both groups, whereas the incidence of several nonmotor symptoms decreased in the treatment group only.     

The Yakovlev Collection. A pilot study of its suitability for the morphometric documentation of the human brain

A pilot study on the Yakovlev Collection in Washington, D.C. was carried out in September/October, 1977, to determine its suitability for morphometric documentation of the growth of the human brain and its structural components. The Yakovlev Collection contains complete serial sections of approximately 800 human brains which are practically unexplored with morphometric methods. The extent and quality of the Collection present a unique opportunity for enlarging into a multinational data bank for morphometric brain research.     

Treatment of alcohol withdrawal symptoms in hospitalized patients. A randomized, double-blind comparison of carbamazepine (Tegretol) and barbital (Diemal)

Seventy-two hospitalized patients with alcohol withdrawal symptoms were treated with either carbamazepine (Tegretol) or barbital ( Diemal ) in a randomized, double-blind trial. The dose of trial medication as well as the duration of treatment was individual, corresponding to the conventional treatment schedule. During the trial period daily records were kept of target withdrawal symptoms, global evaluation, the patient's subjective feeling and unwanted effects. Sixty patients completed the treatment successfully. The two treatment groups were homogeneous as regards patient characteristics, pre-treatment disease severity and drop-out rate. No statistically significant differences were found in efficacy between the two treatments, and both drugs were well tolerated. It is concluded that carbamazepine is a valuable alternative drug in the treatment of mild and moderate alcohol withdrawal symptoms.