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ABSTRACT: Limitations of existing pharmacological treatments for opioid dependence include low adherence, medication diversion, and emergence of withdrawal symptoms.
To determine the efficacy of buprenorphine implants that provide a low, steady level of buprenorphine over 6 months for the treatment of opioid dependence.
A randomized, placebo-controlled, 6-month trial conducted at 18 sites in the United States between April 2007 and June 2008. One hundred sixty-three adults, aged 18 to 65 years, diagnosed with opioid dependence. One hundred eight were randomized to receive buprenorphine implants and 55 to receive placebo implants.
After induction with sublingual buprenorphine-naloxone tablets, patients received either 4 buprenorphine implants (80 mg per implant) or 4 placebo implants. A fifth implant was available if a threshold for rescue use of sublingual buprenorphine-naloxone treatment was exceeded. Standardized individual drug counseling was provided to all patients.
The percentage of urine samples negative for illicit opioids for weeks 1 through 16 and for weeks 17 through 24.
The buprenorphine implant group had significantly more urine samples negative for illicit opioids during weeks 1 through 16 (P = .04). Patients with buprenorphine implants had a mean percentage of urine samples that tested negative for illicit opioids across weeks 1 through 16 of 40.4% (95% confidence interval [CI], 34.2%-46.7%) and a median of 40.7%; whereas those in the placebo group had a mean of 28.3% (95% CI, 20.3%-36.3%) and a median of 20.8%. A total of 71 of 108 patients (65.7%) who received buprenorphine implants completed the study vs 17 of 55 (30.9%) who received placebo implants (P < .001). Those who received buprenorphine implants also had fewer clinician-rated (P <.001) and patient-rated (P = .004) withdrawal symptoms, had lower patient ratings of craving (P <.001), and experienced a greater change on clinician global ratings of severity of opioid dependence (P<.001) and on the clinician global ratings of improvement (P < .001) than those who received placebo implants. Minor implant site reactions were the most common adverse events: 61 patients (56.5%) in the buprenorphine group and 29 (52.7%) in the placebo group.
Among persons with opioid dependence, the use of buprenorphine implants compared with placebo resulted in less opioid use over 16 weeks as assessed by urine samples.
clinicaltrials.gov Identifier: NCT00447564.
JAMA The Journal of the American Medical Association 10/2010; 304(14):1576-83. · 30.03 Impact Factor
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ABSTRACT: Buprenorphine, a mu-opioid receptor partial agonist, has been shown to be safe and effective for treatment of opioid dependence. A novel implantable formulation of buprenorphine (Probuphine), using a polymer matrix sustained-release technology, has been developed to offer treatment for opioid dependence while minimizing risks of patient noncompliance and illicit diversion. The goal of the current study was to conduct an initial, open-label, evaluation of the safety, pharmacokinetics, and efficacy of two doses of Probuphine in subjects with opioid dependence maintained on sublingual buprenorphine. Two doses of Probuphine were evaluated in 12 heroin-dependent volunteers switched from daily sublingual buprenorphine dosing to either two or four Probuphine implants based upon their buprenorphine daily maintenance dose of 8 mg or 16 mg respectively, and were monitored for 6 months. Probuphine implants provided continuous steady state delivery of buprenorphine until their removal at 6 months. Withdrawal symptoms and craving remained low throughout the 6 months. For the 12 subjects, an average of 59% of urines were opioid-negative across the 6 month treatment period. Injection site reactions were present in half of patients, but none were serious. No safety concerns were evident. These results suggest that Probuphine implants offer significant promise for enhancing delivery of effective opioid substitution treatment while minimizing risk for abuse of medication.
Drug and alcohol dependence 05/2009; 103(1-2):37-43. · 3.60 Impact Factor
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ABSTRACT: We investigated the efficacy and tolerability of paroxetine controlled release, a selective serotonin reuptake inhibitor in fibromyalgia.
After excluding patients with current major depression and anxiety disorders, 116 subjects with fibromyalgia were enrolled in a 12-week, randomized, double-blind, placebo-controlled, trial of paroxetine controlled release (12.5-62.5 mg/day). The primary outcome measure was proportion of responders as defined as a> or =25% reduction in scores on the Fibromyalgia Impact Questionnaire (FIQ) from randomization to end of treatment. Secondary outcome measures included changes in FIQ scores, Clinical Global Impression -Improvement (CGI-I) and Severity (CGI-S) scores, Visual Analogue Scale for pain scores, number of tender points, and scores on the Sheehan Disability Scale (SDS).
Significantly more patients in paroxetine controlled release group (57%) showed a> or =25% reduction in FIQ compared to placebo (33%) (P=.016). Paroxetine controlled release was significantly superior to placebo in reducing the FIQ total score (P =.015). The CGI-I ratings significantly favored the drug over placebo (P<.005). The improvements on other secondary outcome measures between the 2 groups were not statistically significant. Drowsiness, dry mouth, blurred vision, genital disorders, and anxiety were reported more frequently with paroxetine controlled release. The mean dose of paroxetine controlled release was 39.1 mg/day.
Paroxetine controlled release appears to be well-tolerated and improve the overall symptomatology in patients with fibromyalgia without current mood or anxiety disorders. However, its effect on pain measures seems to be less robust.
The American journal of medicine 06/2007; 120(5):448-54. · 4.47 Impact Factor
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P Murali Doraiswamy,
Indira Varia,
Caroline Hellegers,
H Ryan Wagner,
Greg L Clary,
John L Beyer,
L Kristin Newby,
John F O'Connor, Katherine L Beebe,
Christopher O'Connor,
K Ranga Krishnan
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ABSTRACT: Noncardiac chest pain occurs frequently in medical practice and is often difficult to treat. We conducted a randomized double-blind, placebo-controlled, 8-week trial of paroxetine in 50 patients with noncardiac chest pain. None of the patients met criteria for panic disorder or major depression. Paroxetine-treated patients showed greater (P < .05) improvements than placebo-treated patients on the Clinical Global Impressions (CGI) scale. Both paroxetine and placebo-treated patients improved to a similar extent on selfrated pain measures, although baseline differences limited the interpretation of this outcome variable. There were no differences on other outcome ratings. Treatment was well tolerated. These preliminary findings extend other data on the potential of selective serotonin reuptake inhibitors for the acute treatment of noncardiac chest pain. Some recommendations for future studies to definitively test this potential are presented.
Psychopharmacology bulletin 01/2006; 39(1):15-24. · 1.35 Impact Factor
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ABSTRACT: Effects of paroxetine treatment of comorbid depression and posttraumatic stress disorder (PTSD) on subjective symptoms, autonomic reactivity, and diurnal salivary cortisols were assessed prospectively. Cross-sectional baseline psychophysiologic assessments of 22 patients with depression + PTSD, 21 with depression alone, and 20 asymptomatic, previously traumatized controls found that comorbid patients had higher blood pressure and heart rate reactivity to individualized trauma scripts than purely depressed and control groups. On discriminant analyses comparing comorbid patients with each other group, combined autonomic variables correctly classified 55% of comorbid patients (sensitivity) and 75% of traumatized, healthy subjects (specificity) as well as 55% of comorbid patients (sensitivity) and 86% of purely depressed patients (specificity). Although baseline AM and PM salivary cortisol levels were within reference range and did not differ significantly across groups, depression + PTSD patients differed from the other 2 groups in having a flattened diurnal pattern. After 10 weeks of open-label paroxetine, comorbid patients significantly improved in all PTSD symptom evaluations and physiologic reactivity measures but did not change cortisol levels or acquire a robust diurnal cortisol pattern. Ten treated depressed patients did not change in physiologic or cortisol measures. Results demonstrate that sampled comorbid patients had autonomic reactivity patterns similar to PTSD that responded to selective serotonin reuptake inhibitor treatment but had diurnal cortisol secretion patterns different from depression or that expected for PTSD, which did not change with treatment. Results suggest a complexity in the neurobiology of comorbid PTSD and major depression and its response to treatment.
Journal of Clinical Psychopharmacology 05/2004; 24(2):131-40. · 4.10 Impact Factor
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ABSTRACT: Standard therapy for hot flashes has been hormone replacement with estradiol or progestational agents, but recent data suggest that antidepressants inhibiting serotonin reuptake may also be effective.
To evaluate a selective serotonin reuptake inhibitor (paroxetine controlled release [CR]) in treating the vasomotor symptoms displayed by a general cross-section of menopausal women.
Randomized, double-blind, placebo-controlled, parallel group study conducted across 17 US sites, including urban, suburban, and rural clinics.
A total of 165 menopausal women aged 18 years or older experiencing at least 2 to 3 daily hot flashes and must have discontinued any hormone replacement therapy for at least 6 weeks. Women were excluded if they had any signs of active cancer or were undergoing chemotherapy or radiation therapy.
After a 1-week placebo run-in phase, study participants were randomized to receive placebo or receive 12.5 mg/d or 25.0 mg/d of paroxetine CR (in a 1:1:1 ratio) for 6 weeks.
Mean change from baseline to week 6 in the daily hot flash composite score (frequency x severity).
Fifty-six participants were randomly assigned to receive placebo and 51 to receive 12.5 mg/d and 58 to receive 25.0 mg/d of paroxetine CR. The mean reductions in the hot flash frequency composite score from baseline to week 6 were statistically significantly greater for those receiving paroxetine CR than for those receiving placebo. By week 6, the mean daily hot flash frequency went from 7.1 to 3.8 (mean reduction, 3.3) for those in the 12.5-mg/d and from 6.4 to 3.2 (mean reduction, 3.2) for those in the 25-mg/d paroxetine CR groups and from 6.6 to 4.8 (mean reduction, 1.8) for those in the placebo group. Mean placebo-adjusted reduction in hot flash composite scores were -4.7 (95% confidence interval, - 8.1 to -1.3; P =.007) comparing 12.5-mg/d paroxetine CR with placebo; and -3.6 (95% confidence interval, -6.8 to -0.4; P =.03) comparing 25.0-mg/d paroxetine CR with placebo. This corresponded to median reductions of 62.2% for those in the 12.5-mg/d and 64.6% for those in the 25.0-mg/d paroxetine CR groups compared with 37.8% for those in the placebo group.
Paroxetine CR may be an effective and acceptable alternative to hormone replacement and other therapies in treating menopausal hot flash symptoms.
JAMA The Journal of the American Medical Association 07/2003; 289(21):2827-34. · 30.03 Impact Factor
