A randomized controlled trial of interim methadone maintenance

CONTEXT: Effective alternatives to long waiting lists for entry into methadone hydrochloride maintenance treatment are needed to reduce the complications of continuing heroin dependence and to increase methadone treatment entry. OBJECTIVE: To compare the effectiveness of interim methadone maintenance with that of the usual waiting list condition in facilitating methadone treatment entry and reducing heroin and cocaine use and criminal behavior. DESIGN: Randomized, controlled, clinical trial using 2 conditions, with treatment assignment on a 3:2 basis to interim maintenance-waiting list control. SETTING: A methadone treatment program in Baltimore. PARTICIPANTS: A total of 319 individuals meeting the criteria for current heroin dependence and methadone maintenance treatment. INTERVENTIONS: Participants were randomly assigned to either interim methadone maintenance, consisting of an individually determined methadone dose and emergency counseling only for up to 120 days, or referral to community-based methadone treatment programs. MAIN OUTCOME MEASURES: Entry into comprehensive methadone maintenance therapy at 4 months from baseline; self-reported days of heroin use, cocaine use, and criminal behavior; and number of urine drug test results positive for heroin and cocaine at the follow-up interview conducted at time of entry into comprehensive methadone treatment (or at 4 months from baseline for participants who did not enter regular treatment). RESULTS: Significantly more participants assigned to the interim methadone maintenance condition entered comprehensive methadone maintenance treatment by the 120th day from baseline (75.9%) than those assigned to the waiting list control condition (20.8%) (P<.001). Overall, in the past 30 days at follow-up, interim participants reported significantly fewer days of heroin use (P<.001), had a significant reduction in heroin-positive drug test results (P<.001), reported spending less money on drugs (P<.001), and received less illegal income (P<.02) than the waiting list participants. CONCLUSION: Interim methadone maintenance results in a substantial increase in the likelihood of entry into comprehensive treatment, and is an effective means of reducing heroin use and criminal behavior among opioid-dependent individuals awaiting entry into a comprehensive methadone treatment program.     

Depressive symptoms during buprenorphine vs. methadone maintenance: findings from a randomised, controlled trial in opioid dependence

Research suggests that buprenorphine may possess antidepressant activity. The Beck Depression Inventory was completed at baseline and 3 months by heroin dependent subjects receiving either buprenorphine or methadone maintenance as part of a larger, pre-existing, double blind trial conducted by NDARC (Australia). Depressive symptoms improved in all subjects, with no difference between methadone and buprenorphine groups, suggesting no differential benefit on depressive symptoms for buprenorphine compared to methadone.     

A randomized effectiveness trial of stepped collaborative care for acutely injured trauma survivors

CONTEXT: Although posttraumatic stress disorder (PTSD) and alcohol abuse frequently occur among acutely injured trauma survivors, few real-world interventions have targeted these disorders. OBJECTIVE: We tested the effectiveness of a multifaceted collaborative care (CC) intervention for PTSD and alcohol abuse. DESIGN: Randomized effectiveness trial. PARTICIPANTS: We recruited a population-based sample of 120 male and female injured surgical inpatients 18 or older at a level I trauma center. INTERVENTION: Patients were randomly assigned to the CC intervention (n = 59) or the usual care (UC) control condition (n = 61). The CC patients received stepped care that consisted of (1) continuous postinjury case management, (2) motivational interviews targeting alcohol abuse/dependence, and (3) evidence-based pharmacotherapy and/or cognitive behavioral therapy for patients with persistent PTSD at 3 months after injury. MAIN OUTCOME MEASURES: We used the PTSD symptomatic criteria (PTSD Checklist) at baseline and 1, 3, 6, and 12 months after injury, and alcohol abuse/dependence (Composite International Diagnostic Interview) at baseline and 6 and 12 months after injury. RESULTS: Random-coefficient regression analyses demonstrated that over time, CC patients were significantly less symptomatic compared with UC patients with regard to PTSD (P =.01) and alcohol abuse/dependence (P =.048). The CC group demonstrated no difference (-0.07%; 95% confidence interval [CI], -4.2% to 4.3%) in the adjusted rates of change in PTSD from baseline to 12 months, whereas the UC group had a 6% increase (95% CI, 3.1%-9.3%) during the year. The CC group showed on average a decrease in the rate of alcohol abuse/dependence of -24.2% (95% CI, -19.9% to -28.6%), whereas the UC group had on average a 12.9% increase (95% CI, 8.2%-17.7%) during the year. CONCLUSIONS: Early mental health care interventions can be feasibly and effectively delivered from trauma centers. Future investigations that refine routine acute care treatment procedures may improve the quality of mental health care for Americans injured in the wake of individual and mass trauma.     

Heroin craving and its correlations with clinical outcome indicators in people with heroin dependence receiving methadone maintenance treatment

BackgroundCraving for substance use has been added as one of the diagnostic criteria of substance use disorders in DSM-5. However, further research is necessary to examine and expand the clinical potential of craving in the assessment and treatment for heroin users. This study aimed to examine the psychometrics of the Desire for Drug Questionnaire–Chinese Mandarin version (DDQ-CM) and its clinical utility of assessing craving for heroin measured among heroin users with methadone maintenance treatment (MMT).MethodSelf-reported craving for heroin use was measured on the DDQ-CM and visual analog scale among 314 intravenous heroin users receiving MMT. Self-reported heroin dependence, attitude toward heroin use, readiness to change heroin use, and depression were collected.ResultsThe results found that although the original three-factor model was acceptable for applying the DDQ-CM for heroin users with MMT, only the concurrent validity of the subscales of Desire and Intention and Negative Reinforcement was supported but not that of Control. Meanwhile, the levels of craving on the subscales of Desire and Intention and of Negative Reinforcement on the DDQ-CM were positively associated with the levels of heroin dependence, positive and negative attitudes toward heroin use, and depression, but negatively associated with readiness to change heroin use.ConclusionsThis study supported the application of the subscales of Desire and Intention and Negative Reinforcement on the DDQ-CM to measure heroin craving in Taiwanese-Chinese heroin users and supported the clinical implication of craving in heroin users with MMT.     

Differential regional effects of methadone maintenance compared to heroin dependence on mu-opioid receptor desensitization in rat brain

Methadone maintenance therapy has been the mainstay of treatment for heroin addiction since the 1970s. Recent studies indicate that methadone is of greater relative intrinsic efficacy than the active metabolites of heroin at mu-opioid receptors and that the extent of mu-opioid receptor desensitization is dependent upon agonist efficacy. Regional differences have been found for mu-opioid receptor desensitization with chronic heroin self-administration, and a similar paradigm was employed to compare regional differences between the effects of heroin and methadone. Rats were trained to self-administer heroin i.v., and the dose available was increased incrementally to a terminal value of 6 mg/kg for each infusion. Half of these rats were allowed to continue to self-administer heroin, while dependence was maintained in the others by hourly infusions of 3 mg/kg of methadone. A separate group of animals was kept on a low dose of heroin. Activation of G-proteins by the high efficacy agonist DAMGO was decreased to a greater extent in animals treated chronically with methadone compared with those allowed to self-administer heroin in amygdala, periaqueductal gray, and subicular nucleus. Activation of G-proteins by the partial agonist endomorphin was decreased in striatum, thalamus, and amygdala in rats from all drug treatment groups, but to a greater extent in the striatum in methadone treated rats compared with the heroin groups. Elucidating the mechanisms by which methadone induces differential desensitization of mu-opioid receptors across brain regions compared with heroin could provide insights to improve the pharmacotherapy of heroin addiction.     

美沙酮联用丁丙诺啡对海洛因依赖重度药瘾戒毒治疗临床研究

目的　探索对海洛因依赖重度药瘾较理想的戒毒治疗方法。　　方法　采用美沙酮与丁丙诺啡联合用药方案 ,对海洛因依赖重度药瘾 41例行戒毒治疗 ,1 2天为一疗程 ,并与单用美沙酮组 2 0例进行比较。　　结果　联合用药组控制症状较彻底 ,鸦片类药物戒断症状量表 (OWS)总分平稳下降 ,症状波动小 ,减药顺利 ,两药替换平稳 ,戒毒成功率 73 2 %。　　结论　我们认为美沙酮联用丁丙诺啡是一种值得推荐的戒毒治疗方法。     

Postpartum depression recurrence versus discontinuation syndrome: observations from a randomized controlled trial

OBJECTIVE: To differentiate characteristics of a discontinuation syndrome from a recurrence of major depressive disorder in the context of a randomized trial. METHOD: We performed a randomized clinical trial to compare the efficacy of sertraline versus placebo for the prevention of recurrent postpartum DSM-IV major depressive disorder. Women whose depression did not recur in the initial 17-week active treatment trial were followed through the taper phase (weeks 18-20). At week 17, 3 women assigned to placebo and 8 assigned to sertraline remained in the trial. Nine symptoms that characterize discontinuation syndrome were extracted from the 25-item Asberg Rating Scale for Side Effects (ASE) and assessed weekly during the taper phase. The 21-item Hamilton Rating Scale for Depression was used to evaluate depressive symptoms. RESULTS: In the taper phase, there were no significant differences between the sertraline- and placebo-treated women on the sum of the ASE-derived symptoms. Both groups had low levels of symptoms on the ASE during the weeks of taper. None of the 3 women assigned to placebo and 2 of the 8 women assigned to sertraline suffered a depressive recurrence within 6 weeks of the end of the study. CONCLUSIONS: A gradual taper of sertraline (75 mg) over 3 weeks did not lead to discontinuation syndrome; however, the systematic dissection of symptoms resulted in our conclusion that the duration of preventive therapy should be extended to 26 weeks (about 6 months) in subsequent randomized trials, consistent with the treatment guidelines for a single episode of depression.     

Habit reversal versus supportive psychotherapy for Tourette's disorder: a randomized controlled trial

OBJECTIVE: The authors investigated the efficacy of habit reversal for Tourette's disorder, which is characterized by multiple motor and vocal tics. METHOD: Thirty-two patients with Tourette's disorder were randomly assigned to 14 sessions of either habit reversal or supportive psychotherapy. Habit reversal consisted of awareness training, self-monitoring, relaxation training, competing response training, and contingency management. Changes in severity of Tourette's disorder and psychosocial impairment were investigated over the course of the 14-session treatment for the 29 patients who completed at least eight treatment sessions. RESULTS: In contrast to the 13 patients in the supportive psychotherapy group, the 16 patients in the habit reversal group improved significantly. The habit reversal patients remained significantly improved over pretreatment at 10-month follow-up. CONCLUSIONS: Habit reversal may be an effective behavioral treatment for Tourette's disorder.     

海洛因依赖的亚冬眠疗法与美沙酮疗法对照观察

对自愿戒断海洛因依赖住院患者１１６例，分别用亚冬眠与美沙酮替代递减进行治疗。结果表明：亚冬眠和美沙酮替代递减之间效果存在着明显差异；后者能有效控制戒断症状，且容易递减和停药，病人依从性好，不影响病人意识，生活能自理，情绪平稳，副反应极少。     

Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial

OBJECTIVE: The authors compared the efficacy of olanzapine and lithium in the prevention of mood episode relapse/recurrence. METHOD: Patients with a diagnosis of bipolar disorder (manic/mixed), a history of two or more manic or mixed episodes within 6 years, and a Young Mania Rating Scale total score > or =20 entered the study and received open-label co-treatment with olanzapine and lithium for 6-12 weeks. Those meeting symptomatic remission criteria (Young Mania Rating Scale score < or =12; 21-item Hamilton depression scale score < or =8) were randomly assigned to 52 weeks of double-blind monotherapy with olanzapine, 5-20 mg/day (N=217), or lithium (target blood level: 0.6-1.2 meq/liter) (N=214). RESULTS: Symptomatic relapse/recurrence (score > or =15 on either the Young Mania Rating Scale or Hamilton depression scale) occurred in 30.0% of olanzapine-treated and 38.8% of lithium-treated patients. The noninferiority of olanzapine relative to lithium (primary objective) in preventing relapse/recurrence was met, since the lower limit of the 95% confidence interval on the 8.8% risk difference (-0.1% to 17.8%) exceeded the predefined noninferiority margin (-7.3%). Secondary results showed that compared with lithium, olanzapine had significantly lower risks of manic episode and mixed episode relapse/recurrence. Depression relapse/recurrence occurred in 15.7% of olanzapine-treated and 10.7% of lithium-treated patients. Mean weight gain during open-label co-treatment was 2.7 kg; during double-blind monotherapy, weight gain was significantly greater with olanzapine (1.8 kg) than with lithium (-1.4 kg). CONCLUSIONS: These results suggest that olanzapine was significantly more effective than lithium in preventing manic and mixed episode relapse/recurrence in patients acutely stabilized with olanzapine and lithium co-treatment. Both agents were comparable in preventing depression relapse/recurrence.     

Effectiveness of multidisciplinary care for Parkinson's disease: A randomized,controlled trial

Multidisciplinary care is considered an optimal model to manage Parkinson's disease (PD), but supporting evidence is limited. We performed a randomized, controlled trial (RCT) to establish whether a multidisciplinary/specialist team offers better outcomes, compared to stand‐alone care from a general neurologist. Patients with PD were randomly allocated to an intervention group (care from a movement disorders specialist, PD nurses, and social worker) or a control group (care from general neurologists). Both interventions lasted 8 months. Clinicians and researchers were blinded for group allocation. The primary outcome was the change in quality of life (Parkinson's Disease Questionnaire; PDQ‐39) from baseline to 8 months. Other outcomes were the UPDRS, depression (Montgomery‐Asberg Depression Scale; MADRS), psychosocial functioning (Scales for Outcomes in Parkinson's disease‐Psychosocial; SCOPA‐PS), and caregiver strain (Caregiver Strain Index; CSI). Group differences were analyzed using analysis of covariance adjusted for baseline values and presence of response fluctuations. A total of 122 patients were randomized and 100 completed the study (intervention, n = 51; control, n = 49). Compared to controls, the intervention group improved significantly on PDQ‐39 (difference, 3.4; 95% confidence interval [CI]: 0.5–6.2) and UPDRS motor scores (4.1; 95% CI: 0.8–7.3). UPDRS total score (5.6; 95% CI: 0.9–10.3), MADRS (3.7; 95% CI: 1.4–5.9), and SCOPA‐PS (2.1; 95% CI: 0.5–3.7) also improved significantly. This RCT gives credence to a multidisciplinary/specialist team approach. We interpret these positive findings cautiously because of the limitations in study design. Further research is required to assess teams involving additional disciplines and to evaluate cost‐effectiveness of integrated approaches. © 2012 Movement Disorder Society     

Intravenous immunoglobulin maintenance treatment in myasthenia gravis: A randomized,controlled trial sample size simulation

Introduction: In cases of exacerbation or crisis, myasthenia gravis (MG) patients can be treated with intravenous immunoglobulin (IVIg), plasmapheresis, or immunoadsorption. However, IVIg efficacy data in maintenance treatment are sparse. Methods: We prospectively observed 16 index patients with chronic and insufficiently controlled MG under standard immunosuppressant therapy and symptomatic treatment. The IVIg treatment response was measured using changes in quantitative myasthenia gravis (QMG) score and surrogates. Based on these results, a sample size calculation for a future randomized, controlled trial (RCT) was simulated. Results: There was an enduring decline in QMG score and other parameters of about 50% under IVIg maintenance treatment. RCT sample size calculation results in 73 or 33 patients per arm to detect at least a 20% vs. 30% clinical difference in QMG score. Conclusion: We recommend using the QMG score as a primary endpoint for an RCT of IVIg maintenance for chronic MG. Muscle Nerve 50: 999–1004, 2014     

Family focused grief therapy: a randomized, controlled trial in palliative care and bereavement

OBJECTIVE: The aim of family focused grief therapy is to reduce the morbid effects of grief among families at risk of poor psychosocial outcome. It commences during palliative care of terminally ill patients and continues into bereavement. The authors report a randomized, controlled trial. METHOD: Using the Family Relationships Index, the authors screened 257 families of patients dying from cancer: 183 (71%) were at risk, and 81 of those (44%) participated in the trial. They were randomly assigned (in a 2:1 ratio) to family focused grief therapy (53 families, 233 individuals) or a control condition (28 families, 130 individuals). Assessments occurred at baseline and 6 and 13 months after the patient's death. The primary outcome measures were the Brief Symptom Inventory, Beck Depression Inventory, and Social Adjustment Scale. The Family Assessment Device was a secondary outcome measure. Analyses allowed for correlated family data and employed generalized estimating equations based on intention to treat and controlling for site. RESULTS: The overall impact of family focused grief therapy was modest, with a reduction in distress at 13 months. Significant improvements in distress and depression occurred among individuals with high baseline scores on the Brief Symptom Inventory and Beck Depression Inventory. Global family functioning did not change. Sullen families and those with intermediate functioning tended to improve overall, whereas depression was unchanged in hostile families. CONCLUSIONS: Family focused grief therapy has the potential to prevent pathological grief. Benefit is clear for intermediate and sullen families. Care is needed to avoid increasing conflict in hostile families.     

单、双侧后外侧椎弓根钉置入并植骨融合治疗退变性腰椎滑脱的随机对照

背景：节段融合辅以椎弓根钉置入内固定治疗退变性腰椎疾病可提高融合率。 目的：比较单、双侧椎弓根钉置入内固定并植骨融合治疗退变性腰椎滑脱的临床疗效和融合率。 方法：将退变性腰椎滑脱患者随机分为2组,分别行双侧与单侧椎弓根钉置入内固定并植骨后外侧融合。 结果与结论：两组患者失血量、输血量、住院时间、手术并发症、临床疗效、融合率和对临近间盘的影响方面差异无显著性意义。单侧内固定组手术操作时间较双侧内固定组明显缩短(P < 0.001)。双侧内固定组置入186枚椎弓根螺钉中有3枚穿透皮质刺激神经根而行二次手术;单侧内固定组置入90枚螺钉未发生与螺钉置入相关的并发症。表明退变性腰椎滑脱患者行单侧和双侧椎弓根钉置入并植骨内固定后外侧融合效果相同,但单侧内固定成本费用低、节省手术时间,置钉时穿破椎弓根皮质刺激神经根的风险小。