Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial

Riboflavin, which improves energy metabolism similarly to coenzyme Q10 (CoQ10), is effective in migraine prophylaxis. We compared CoQ10 (3 x 100 mg/day) and placebo in 42 migraine patients in a double-blind, randomized, placebo-controlled trial. CoQ10 was superior to placebo for attack-frequency, headache-days and days-with-nausea in the third treatment month and well tolerated; 50%-responder-rate for attack frequency was 14.4% for placebo and 47.6% for CoQ10 (number-needed-to-treat: 3). CoQ10 is efficacious and well tolerated.     

A randomized trial of coenzyme Q10 in mitochondrial disorders

Case reports and open-label studies suggest that coenzyme Q(10) (CoQ(10)) treatment may have beneficial effects in mitochondrial disease patients; however, controlled trials are warranted to clinically prove its effectiveness. Thirty patients with mitochondrial cytopathy received 1200 mg/day CoQ(10) for 60 days in a randomized, double-blind, cross-over trial. Blood lactate, urinary markers of oxidative stress, body composition, activities of daily living, quality of life, forearm handgrip strength and oxygen desaturation, cycle exercise cardiorespiratory variables, and brain metabolites were measured. CoQ(10) treatment attenuated the rise in lactate after cycle ergometry, increased (∽1.93 ml) VO(2)/kg lean mass after 5 minutes of cycling (P < 0.005), and decreased gray matter choline-containing compounds (P < 0.05). Sixty days of moderate- to high-dose CoQ(10) treatment had minor effects on cycle exercise aerobic capacity and post-exercise lactate but did not affect other clinically relevant variables such as strength or resting lactate.     

Intranasal sumatriptan in post-ECT headache: results of an open-label trial.

BACKGROUND: Significant headaches occur in up to 45% of patients receiving electroconvulsive therapy (ECT) as a result of treatment. Headaches may at times be severe and affect patient compliance with this treatment modality. The 5-HT(1B/1D) receptor agonist sumatriptan has been reported to be effective for post-ECT headache in several case reports. The aim of the present open-label study was to assess the efficacy and tolerability of intranasal sumatriptan for post-ECT headache. METHOD: Patients undergoing ECT who experienced moderate-to-severe post-ECT headache were enrolled in the study. Patients were asked to rate their headache severity and describe headache characteristics using a standard headache diary. Headaches rated as severe or moderate were treated with 20 mg of intranasal sumatriptan. Additional headache ratings were recorded at 0.25, 0.5, 1.0, 1.5, and 2 hours after sumatriptan administration and compared with baseline values. RESULTS: Eight female patients (ages 34-45 years old) participated in the trial and experienced a total of 13 post-ECT headaches, which were treated with intranasal sumatriptan. Of the headaches treated, six (46.2%) were described as severe and seven (53.8%) were characterized as moderate in severity. Twelve (92.3%) of the treated headaches responded by the 2 hour posttreatment time point and 11 (84.6%) had responded within 1 hour. Comparisons made at the 1- and 2-hour time point revealed a statistically significant improvement from baseline (p = 0.002). Of the 12 headaches that responded, 6 (50%) were reported as no pain and 5 (38.5%) were reported as only mild pain at 1 hour following treatment. At the 2-hour assessment, an additional headache, which had previously not responded, was rated at mild resulting in six (50%) headaches with complete resolution of pain and six (50%) with a decrease in pain symptoms from moderate or severe to mild. Overall, sumatriptan treatment was well tolerated, and no significant adverse effects or changes in vital signs were recorded. In no case was a second dose of sumatriptan given. The most common complaint was the taste of the medication (n = 4), which was not treatment limiting. No patient withdrew from the study due to an adverse event. CONCLUSION: Intranasal sumatriptan spray may be an effective, well-tolerated, and prompt treatment for patients experiencing moderate-to-severe post-ECT headache. Preventing post-ECT headache may contribute to patient compliance with the ECT treatment modality. Additionally, the known pharmacologic effects of sumatriptan and the generally positive results found in the present study suggest that ECT-induced headache is vascular in origin. Further placebo-controlled, double-blind studies are needed to confirm our open-label results.     

Short‐term effects of coenzyme Q10 in progressive supranuclear palsy: A randomized,placebo‐controlled trial

Mitochondrial complex I appears to be dysfunctional in progressive supranuclear palsy (PSP). Coenzyme Q₁₀ (CoQ₁₀) is a physiological cofactor of complex I. Therefore, we evaluated the short‐term effects of CoQ₁₀ in PSP. We performed a double‐blind, randomized, placebo‐controlled, phase II trial, including 21 clinically probable PSP patients (stage ≤ III) to receive a liquid nanodispersion of CoQ₁₀ (5 mg/kg/day) or matching placebo. Over a 6‐week period, we determined the change in CoQ₁₀ serum concentration, cerebral energy metabolites (by ³¹P‐ and ¹H‐magnetic resonance spectroscopy), motor and neuropsychological dysfunction (PSP rating scale, UPDRS III, Hoehn and Yahr stage, Frontal Assessment Battery, Mini Mental Status Examination, Montgomery Åsberg Depression Scale). CoQ₁₀ was safe and well tolerated. In patients receiving CoQ₁₀ compared to placebo, the concentration of low‐energy phosphates (adenosine‐diphosphate, unphosphorylated creatine) decreased. Consequently, the ratio of high‐energy phosphates to low‐energy phosphates (adenosine‐triphosphate to adenosine‐diphosphate, phospho‐creatine to unphosphorylated creatine) increased. These changes were significant in the occipital lobe and showed a consistent trend in the basal ganglia. Clinically, the PSP rating scale and the Frontal Assessment Battery improved slightly, but significantly, upon CoQ₁₀ treatment compared to placebo. Since CoQ₁₀ appears to improve cerebral energy metabolism in PSP, long‐term treatment might have a disease‐modifying, neuroprotective effect. © 2008 Movement Disorder Society     

CINRG pilot trial of coenzyme Q10 in steroid-treated Duchenne muscular dystrophy

Introduction: Corticosteroid treatment slows disease progression and is the standard of care for Duchenne muscular dystrophy (DMD). Coenzyme Q10 (CoQ10) is a potent antioxidant that may improve function in dystrophin‐deficient muscle. Methods: We performed an open‐label, “add‐on” pilot study of CoQ10 in thirteen 5–10‐year‐old DMD patients on steroids. The primary outcome measure was the total quantitative muscle testing (QMT) score. Results: Twelve of 16 children (mean age 8.03 ± 1.64 years) completed the trial. Target serum levels of CoQ10 (≥2.5 μg/ml) were shown to be subject‐ and administration‐dependent. Nine of 12 subjects showed an increase in total QMT score. Overall, CoQ10 treatment resulted in an 8.5% increase in muscle strength (P = 0.03). Conclusions: Addition of CoQ10 to prednisone therapy in DMD patients resulted in an increase in muscle strength. These results warrant a larger, controlled trial of CoQ10 in DMD. Muscle Nerve, 2011     

Ganaxolone for treating intractable infantile spasms: a multicenter, open-label, add-on trial

This is a multicenter, open-label, add-on trial, investigating the safety and efficacy of ganaxolone (GNX) in a population of children with refractory infantile spasms, or with continuing seizures after a prior history of infantile spasms. A total of 20 children aged 7 months to 7 years were enrolled in this dose-escalation study, after baseline seizure frequencies were established. Concomitant antiepilepsy drugs were maintained throughout the study period. The dose of GNX was progressively increased to 36 mg/kg/d (or to the maximally tolerated dose) over a period of 4 weeks, then maintained for 8 weeks before tapering and discontinuation. Seizure diaries were maintained by the families, and spasm frequency was compared with the baseline period. The occurrence of adverse events was clinically monitored, and global evaluations of seizure severity and response to treatment were obtained. A total of 16 of the 20 subjects completed the study, 15 of whom had refractory infantile spasms at the time of study enrollment. Spasm frequency was reduced by at least 50% in 33% of these subjects, with an additional 33% experiencing some improvement (25-50% reduction in spasm frequency). Ganaxolone was well tolerated, and adverse events attributed to GNX were generally mild. Ganaxolone was safe and effective in treating this group of refractory infantile spasms patients in an open-label, add-on trial. Further investigation with randomized, controlled study design is warranted.     

Nefazodone treatment of pathological gambling: a prospective open-label controlled trial

BACKGROUND: Pathological gambling is a disabling and highly prevalent impulse-control disorder not otherwise specified (NOS). According to the hypothesis of abnormal serotonin function in the pathophysiology of poor impulse control and pathological gambling, we assessed the efficacy and tolerability of nefazodone, a 5-HT antagonist reported to be effective in other impulse-control disorders NOS, in the treatment of pathological gambling. METHOD: Fourteen outpatients who met DSM-IV criteria for pathological gambling were enrolled in a prospective 8-week open-label oral nefazodone trial. Nefazodone was initiated at 50 mg/day and titrated upward to a maximum of 500 mg/day based on patient's response and side effects, with a minimum daily dose of 100 mg. Improvement in gambling was assessed via the pathological gambling modifications of the Yale-Brown Obsessive Compulsive Scale (PG-YBOCS), the Clinical Global Impressions-Improvement scale (PG-CGI-I), and self-rated gambling scales. Response was defined a priori as both a 25% reduction in PG-YBOCS score and a score of 1 (very much improved) or 2 (much improved) on the PG-CGI-I scale. RESULTS: Twelve subjects completed the study, and 2 subjects were early dropouts who did not receive the minimum required dose. Significant improvements were noted in all gambling outcome measures, as well as in depression and anxiety ratings (which did not significantly correlate with gambling reduction). Nine (75%) of 12 patients were rated as responders according to a priori criteria. Side effects (dry mouth and sedation) of moderate severity occurred in 4 subjects. CONCLUSION: These preliminary results suggest that nefazodone may be effective in reducing symptoms of pathological gambling and is well tolerated.     

Topiramate in add-on therapy: results from an open-label, observational study.

An open-label, observational prospective study assessed the effectiveness of topiramate (TPM) as add-on therapy. A total of 450 patients aged 12 and above with a diagnosis of epilepsy and at least one epileptic seizure during the 12-week retrospective baseline were to be documented. After baseline evaluation, topiramate was added. Ninety-five percent of patients had at least one baseline AED, most commonly Carbamazepine (53%) or Valproate (34%). In 5% TPM was started in monotherapy. Topiramate dose titration and target dose was determined by clinical response and side effect profile. Patients were intended to be followed for a total of 1 year which included 6 visits during which seizure frequency, adverse events, weight as well as clinical global impression were recorded. During the 12 weeks retrospective baseline, a median of 2.8 seizures per month were recorded which reduced significantly to 0.7 per month during the complete treatment phase (p < 0.0001). Seventy-two percent of patients had a > or =50% seizure reduction. Ten percent of patients were seizure free during the study. The most commonly reported adverse events were difficulties with memory (4.2%), somnolence (3.6%), and dizziness (2.7%). Overall, topiramate was well tolerated, and only 5% of patients discontinued treatment due to an adverse event. Retention in the study was higher than previously reported during randomized, dose controlled studies and is likely due to individualized doses as well as slower titration used.     

Yoga therapy as an add-on treatment in the management of patients with schizophrenia--a randomized controlled trial

OBJECTIVE: Treatment of schizophrenia has remained unsatisfactory despite the availability of antipsychotics. This study examined the efficacy of yoga therapy (YT) as an add-on treatment to the ongoing antipsychotic treatment. METHOD: Sixty-one moderately ill schizophrenia patients were randomly assigned to YT (n = 31) and physical exercise therapy (PT; n = 30) for 4 months. They were assessed at baseline and 4 months after the start of intervention, by a rater who was blind to their group status. RESULTS: Forty-one subjects (YT = 21; PT = 20) were available at the end of 4 months for assessment. Subjects in the YT group had significantly less psychopathology than those in the PT group at the end of 4 months. They also had significantly greater social and occupational functioning and quality of life. CONCLUSION: Both non-pharmacological interventions contribute to reduction in symptoms, with YT having better efficacy.     

Zonisamide in the treatment of binge-eating disorder: an open-label, prospective trial

BACKGROUND: Binge-eating disorder is characterized by recurrent episodes of uncontrollable overeating without compensatory weight-loss behaviors. It commonly co-occurs with obesity. Zonisamide is a novel antiepileptic drug associated with weight loss. The purpose of this study was to preliminarily assess zonisamide in the treatment of binge-eating disorder. METHOD: Fifteen outpatients with DSM-IV-TR binge-eating disorder were enrolled from Jan. 25, 2002, through Sept. 10, 2002, in an open-label, prospective, 12-week, flexible dose (100-600 mg/day) study of zonisamide. The primary outcome measure was binge-eating episode frequency. Secondary measures included binge day frequency, body mass index (BMI), weight, Clinical Global Impressions-Severity of Illness scale (CGI-S) scores, Yale-Brown Obsessive-Compulsive Scale Modified for Binge Eating (YBOCS-BE) scores, Three Factor Eating Questionnaire (TFEQ) scores, and Hamilton Rating Scale for Depression scores. Safety measures included adverse events, routine blood chemical and hematology laboratory values, urinalyses, plasma zonisamide levels, physical examination findings, and electrocardiograms. Outcome measures were analyzed by a repeated-measures random regression analysis using all data and an endpoint analysis using last observation carried forward. RESULTS: Eight subjects completed the 12 weeks of treatment. The mean (SD) zonisamide daily dose at endpoint evaluation was 513 (103) mg/day. Both the random regression and endpoint analyses found a highly significant decrease in binge-eating episode frequency, binge day frequency, BMI, weight, CGI-S scores, YBOCS-BE total scores, and TFEQ hunger and disinhibition scores (p <.0001 for all measures in both analyses except p =.001 for endpoint analysis of binge eating frequency, p =.0001 for endpoint analysis of TFEQ disinhibition, and p =.0008 for endpoint analysis of TFEQ hunger). The 7 subjects who discontinued zonisamide prematurely did so due to lack of response (N = 1), protocol non-adherence (N = 2), and adverse events (N = 4). CONCLUSION: Zonisamide was effective in reducing binge-eating frequency, severity of illness, and weight and was generally well tolerated in an open trial of binge-eating disorder. Controlled trials appear warranted.     

Gabapentin treatment for muscle cramps: an open-label trial

To evaluate the efficacy and safety of gabapentin in the treatment of muscle cramps, we engaged an open-label trial with a group of 30 patients with frequent (> 5 cramps/week), stable, long-lasting cramps, associated with different diseases. Gabapentin was effective in reducing the frequency and severity of muscle cramps and associated sleep disturbances (clinical outcome measures) within the first 2 weeks of medication at 600 mg/d. At the 1 month control (mean dosage, 825 +/- 35 mg), almost every patient had responded to treatment and two thirds experienced a total remission of symptoms. After 3 months of therapy (mean dosage, 892 +/- 180 mg), cramps disappeared in 100% of patients and this benefit persisted as long as 6 months. Additionally, we evaluated in 10 patients the Cramps Threshold Frequency (CTF) (neurophysiological outcome measure) before and during gabapentin treatment. Gabapentin significantly increased the CTF, returning it to normal values. With the limitation of an open-label methodology, our clinical and neurophysiologic experience suggests that a gabapentin dose of 600-1200 mg/d would be helpful in the treatment of muscular cramps.     

Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson's disease

The safety and tolerability of high dosages of coenzyme Q10 were studied in 17 patients with Parkinson's disease (PD) in an open label study. The subjects received an escalating dosage of coenzyme Q10--1200, 1800, 2400, and 3000 mg/day with a stable dosage of vitamin E (alpha-tocopherol) 1200 IU/day. The plasma level of coenzyme Q10 was measured at each dosage. Thirteen of the subjects achieved the maximal dosage, and adverse events were typically considered to be unrelated to coenzyme Q10. The plasma level reached a plateau at the 2400 mg/day dosage and did not increase further at the 3000 mg/day dosage. Our data suggest that in future studies of coenzyme Q10 in PD, a dosage of 2400 mg/day (with vitamin E/alpha-tocopherol 1200 IU/day) is an appropriate highest dosage to be studied.     

Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q(10) in Parkinson disease

BACKGROUND: Major hallmarks in the pathophysiology of Parkinson disease are cellular energy depletion and oxidative stress leading to cellular dysfunction and death. Coenzyme Q(10) (CoQ(10)) is an electron acceptor bridging mitochondrial complexes I and II/III and a potent antioxidant that consistently partially recovers the function of dopaminergic neurons. OBJECTIVE: To determine whether nanoparticular CoQ(10) is safe and displays symptomatic effects in patients with midstage Parkinson disease without motor fluctuations. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, stratified, parallel-group, single-dose trial. SETTING: Academic and nonacademic movement disorder clinics. PATIENTS: One hundred thirty-one patients with Parkinson disease without motor fluctuations and a stable antiparkinsonian treatment. Intervention Random assignment to placebo or nanoparticular CoQ(10) (100 mg 3 times a day) for a treatment period of 3 months. Stratification criterion was levodopa treatment. MAIN OUTCOME MEASURE: The subjects underwent evaluation with the Unified Parkinson's Disease Rating Scale (UPDRS) at each visit on a monthly basis. The primary outcome variable was the change of the sum score of the UPDRS parts II and III between the baseline and 3-month visits. RESULTS: One hundred thirty-one subjects were randomized according to the protocol. The mean changes of the sum UPDRS parts II/III score were -3.69 for the placebo group and -3.33 for the CoQ(10) group (P = .82). Statistical analysis according to the stratification did not result in significant changes of the primary outcome variable. No secondary outcome measure showed a significant change between the placebo group and the CoQ(10) group. The frequency and quality of adverse events were similar in both treatment groups. CONCLUSIONS: Nanoparticular CoQ(10) at a dosage of 300 mg/d is safe and well tolerated and leads to plasma levels similar to 1200 mg/d of standard formulations. Add-on CoQ(10) does not display symptomatic effects in midstage Parkinson disease.