Evidenced-based treatment of opioid-dependent patients.

OBJECTIVE: To provide an overview of treatment options for opioid-dependent patients. METHOD: We screened all published studies on the treatment of opioid dependence, with a special focus on systematic literature reviews, formal metaanalyses, and recent trials. RESULTS: Both clinical experience and neurobiological evidence indicate that opioid dependence is a chronic relapsing disorder. Treatment objectives depend on the pursued goals: crisis intervention, abstinence-oriented treatment (detoxification and relapse prevention), or agonist maintenance treatment. The high quality of solid evidence in the literature demonstrates that there are numerous effective interventions available for the treatment of opioid dependence. Crisis intervention, frequently necessary owing to the high overdose rate, can be effectively handled with naloxone. Abstinence-oriented interventions are effective for only a few motivated patients with stable living conditions and adequate social support. Agonist maintenance treatment is considered the first line of treatment for opioid dependence. Numerous studies have shown efficacy for methadone and buprenorphine treatment, while maintenance with other agonists is also becoming available to a greater extent. Maintenance treatment with diamorphine should be made available for the small group of treatment-resistant, severely dependent addicts. Other harm-reduction measures can serve to engage individuals with opioid addiction who are not in treatment. CONCLUSION: Opioid dependence is a chronic relapsing disease that is difficult to cure, but effective treatments are available to stabilize patients and reduce harm, thereby increasing life expectancy and quality of life.     

Yohimbine-induced withdrawal and anxiety symptoms in opioid-dependent patients.

BACKGROUND: Alteration in noradrenergic regulation as well as alteration in the hypothalamic-pituitary-adrenal (HPA) axis have been associated with opioid dependence and acute abstinence symptoms. METHODS: This double-blind, placebo-controlled study evaluated subjective, physiologic, and biochemical responses to yohimbine (.4 mg/kg, IV) in eight patients receiving methadone and compared results to those from a pool of nine healthy volunteers. All subjects were compared for panic anxiety symptom scale (PASS) scores, systolic and diastolic blood pressure, heart rate, plasma 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol. RESULTS: Yohimbine elicited objective and subjective opioid withdrawal and elevated craving for opioid drugs in methadone patients. Significant yohimbine effects were seen across the combined subject group for PASS, physiologic measures, MHPG, and cortisol. Methadone patients had lower baseline MHPG levels. Methadone group interactions with yohimbine were seen for systolic blood pressure and cortisol levels. CONCLUSIONS: Methadone-maintained patients are sensitive to the postsynaptic effects of noradrenergic-facilitating medications, experiencing greater physiologic and psychological symptoms, including an increase in craving. The effect on cortisol supports the above conclusion and is consistent with HPA axis perturbation in opioid dependence as reported in other studies and extends these observations to stable methadone-maintained patients. Medications that increase synaptic noradrenaline should be used with care in opioid-dependent patients.     

Women in treatment: within-gender differences in the clinical presentation of opioid-dependent women

Despite consistent evidence of gender differences in the nature of drug dependence, there has been little consideration of within-gender differences in the clinical presentation of drug-abusing women. In this study, cluster analysis and standardized ratings obtained from 153 women seeking methadone maintenance treatment were used to define four groups of women with different profiles of problem severity. The four clusters were characterized as Unemployed, Medically Ill, Psychiatrically Distressed, and Higher Functioning. When the validity of this four-cluster solution was examined, there were significant differences in the ethnic composition of the four groups, and the four clusters differed in terms of a) psychiatric status, b) medical status, c) vocational-educational history, d) lifetime history of maltreatment, and e) perception of social support available from friends and family. The findings suggest that, although understanding of gender differences cannot be ignored, understanding of ways women differ from one another may be as important in the development of gender-sensitive treatment programs.     

立体定向术对阿片类药物依赖者心理障碍治疗前后的对照研究

目的观察立体定向手术治疗对阿片类药物依赖病人术后近期病理性心理症状的影响。方法选择自愿要求手术的戒毒病人26例,采用90项症状自评量表（SCL-90）进行评估。治疗前后选择自身配对t检验,治疗前后与国内常模比较、治疗后与强制戒毒、冷火鸡脱毒、美沙酮脱毒治疗后比较采用单样本t检验。结果术后73.1%病人总体病理性心理障碍症状完全改善。57.7%病人的躯体不适症状、73.1%病人的强迫症状得到矫治。手术消除了80.8%病人的抑郁症状、69.2%病人的焦虑症状。同时手术也改善了69.2%病人的人际关系、57.7%病人的恐怖、73.1%病人的敌对、61.5%病人的偏执、57.7%病人的精神病和65.4%病人其他不良症状。与常模比较,术前SCL-90各项差异均有统计学意义（P〈0.05）,术后仅躯体症状差异有统计学意义（P〈0.001）。与强制戒毒组比较,术后SCL-90各项差异均有统计学意义（P〈0.05）;与冷火鸡组比较,仅躯体症状差异有统计学意义;与美沙酮组比较,躯体症状、抑郁、焦虑差异有统计学意义。结论手术能够不同程度地矫治阿片类药物依赖病人的病理性心理障碍,且近期疗效好于强制戒毒、冷火鸡和美沙酮疗法。     

Cognitive function is largely intact in methadone maintenance treatment patients

Objectives: To confirm our previous findings of less cognitive impairments (based on cognitive screening tools) among methadone maintenance treatment (MMT) patients who achieved take-home dose (THD) privileges.

Methods: a random sample of 65 Israeli MMT patients were studied using computerised, age and education standardised, cognitive domains (attention, executive function, memory, motor skills), and non-computerised phonetic and semantic verbal fluency.

Results: Cognitive scores were within?±1 standard deviation (SD) of average for most domains, including non-verbal IQ, attention and motor skills. Verbal fluency and memory were?>1 SD below average (mean?=?84; z?=?–1.1 for both). Females were younger than the males and had poorer motor skills (P?=?0.005) but better verbal memory (P?P?=?0.05) and inversely with verbal memory (P?=?0.01). Overall cognitive function was poorest among 25 (38.5%) current drug users, and 6 (9.2%) lifetime schizophrenia patients. Cognitive domains were comparable between THD privileges subgroups.

Conclusions: Despite heterogeneity in MMT duration, abuse duration, substance use and psychiatric comorbidity, all performed within?±1 SD of average for age and education in most cognitive domains. Our findings challenge the notion of MMT as being synonymous with compromised cognition and may lead to reduced bias regarding cognitive function of MMT patients.     

Innovations in research for treatment of late-life anxiety

Objectives: While psychosocial interventions for late-life anxiety show positive outcomes, treatment effects are not as robust as in younger adults. To date, the reach of research has been limited to academic and primary care settings, with homogeneous samples. This review examines recently funded and ongoing late-life anxiety research that uses innovative approaches to reach unique patient populations and tailor treatment content and delivery options to meet the unique needs of older adults.

Method: A systematic search was conducted using electronic databases of funded clinical trials to identify ongoing psychosocial intervention studies targeting older adults with anxiety. The principal investigators (PIs) of the studies were contacted for study details and preliminary data, if available. In some cases, the PIs of identified studies acted as referral sources in identifying additional studies.

Results: Eleven studies met inclusion criteria and represented three areas of innovation: new patient groups, novel treatment procedures, and new treatment-delivery options. Studies and their associated theoretical bases are discussed, along with preliminary results reported in published papers or conference presentations.

Conclusion: Psychosocial intervention trials currently in progress represent promising new strategies to facilitate engagement and improve outcomes among unique subsets of older adults with anxiety. Continued investigation of evidence-based treatments for geriatric anxiety will allow greater understanding of how best to tailor the interventions to fit the needs of older adults.     

Aripiprazole treatment for patients with schizophrenia: from acute treatment to maintenance treatment

The most current treatment guidelines for schizophrenia recommend more than 1 year of maintenance therapy after the first psychotic episode, and more than 5 years of maintenance therapy after multiple psychotic episodes. Approximately two-thirds of such patients are known to relapse within 1 year and almost 90% of such patients may recur within 2 years. To maintain adequate consistent treatment, balancing the efficacy and safety/tolerability should be one of the most important clinical issues. In this respect, aripiprazole appears to be a good treatment option owing to its comparable efficacy, favorable safety and tolerability profile, including low incidence of parkinsonian symptoms, lack of prolactin elevation, decreased adrenergic and anticholinergic side effects, less weight gain and low incidence of metabolic syndrome. Hence this article aims to summarize the currently available clinical trial data of aripiprazole published from a number of large-scale randomized controlled studies, including a newer formulation of intramuscular injection as well as a once-monthly intramuscular depot formulation, to update knowledge of treatment options in patients with schizophrenia.     

Pain management in the opioid-dependent patient

The opioid-dependent patient presents great challenges for pain management. These challenges are not limited to potential addictive behaviors. In contrast to the profound pain relieving effects of acute opioid intake, chronic opioid intake can promote a counterintuitive state of enhanced pain sensitivity. Multiple biologic mechanisms inducing opioid tolerance and hyperalgesia have recently been elucidated. The potential hyperalgesic state accompanying opioid dependence complicates pain management somewhat for acute pain and cancer pain, but it especially does so for chronic pain. Guidelines for treatment of opioid dependence in the pain patient are proposed. Treatment oriented toward the long term requires limit setting and psychologic support that go beyond simple medication management.     

Adjunctive imipramine maintenance treatment in schizophrenic patients with remitted postpsychotic depression

Ten patients with histories of postpsychotic depression responsive to adjunctive imipramine added to fluphenazine decanoate and benztropine underwent a double-blind trial of imipramine discontinuation 6 months after responding to the adjunctive imipramine. Discontinuation of imipramine was associated with depressive relapse.     

B-HT 920--a novel dopamine autoreceptor agonist in the treatment of patients with schizophrenia

In an open clinical trial the azepine derivative B-HT 920 was administered to patients with schizophrenia, paranoid type (according to ICD-9 and DSM-III criteria), in order to examine whether dopamine autoreceptor stimulation exerts antipsychotic effects. Twelve patients participated in the study and received the test drug orally for up to 28 days in a dose range from 0.3 to 1.2 mg/day. The following results emerged: in four patients a significant amelioration (reduction of initial BPRS scores by more than 50%) of psychotic symptomatology was observed; eight patients remained without improvement of psychopathology. Psychomotor activation was observed in seven patients, and prompted termination of the trial in two cases. No other marked adverse effects of B-HT 920 were noted, including EEG, ECG, and clinical chemistry parameters. As it was to be expected from the pharmacology of B-HT 920, plasma prolactin concentrations were significantly reduced two hours after oral application of a single dose of the drug. It remains to be clarified whether chronic treatment with B-HT 920 induces antipsychotic efficacy within as yet unidentified subsamples of schizophrenic patients. The observed activating effects of B-HT 920 may focus future investigative efforts toward study samples where negative symptoms predominate.     

Innovations and recent trends in the treatment of ADHD

Initiatives to develop better-tolerated, more efficacious pharmacological agents with improved drug delivery systems have driven recent research in attention-deficit hyperactivity disorder (ADHD). While stimulants are the primary pharmacotherapy for ADHD, these drugs have a limited duration of action and a subset of patients will either fail to respond to these medications or have side effects that preclude their use. The development of atomoxetine, the first nonstimulant approved for ADHD, has been followed by additional innovative research, such as the methylphenidate transdermal system, modafinil, NRP-104 and cholinergic agents. This review highlights some of the recent trends in ADHD treatment and the current status of promising treatment options that may help to shape the future of ADHD treatment.     

拉莫三嗪维持治疗双相障碍躁狂发作的疗效评价

目的评价拉莫三嗪维持治疗双相障碍躁狂发作的疗效。方法将73例维持期双相障碍躁狂发作患者随机分为两组，研究组用拉莫三嗪系统治疗，对照组用碳酸锂系统治疗，共治疗12周，并在入组时和治疗后第4、12、24周末评定蹂狂量表（BRMS）和社会功能缺陷筛查量表（SDSS），分别评估躁狂症状严重程度和社会功能受损情况，副反应量表（TESS）评定不良反应。结果在治疗第4周末及第12周末，研究组BRMS和SDSS评分均较治疗前有显著性降低（P〈0.05），而对照组无显著性变化。治疗第4周末、第12周末及第24周末，研究组的BRMS和SDSS评分均显著低于对照组（P〈0.05）。结论拉莫三嗪对双相障碍躁狂发作的维持期治疗有显著疗效，且可有效改善患者的社会功能。     

精神分裂症病人维持治疗中的依从性研究

为了研究门诊精神分裂症病人在维持治疗中的依从性，对３９７例门诊精神分裂症病人在维持治疗中的服药依从性采用直接面询法进行了研究。结果显示，完全依从的有２９９例，占７５．３％，部分依从和不依从的有９８例，占２４．７％。＞３０岁组的依从性较≤３０岁组的好（Ｐ＜０．０１），家庭人际关系好的病人依从性优于家庭人际关系差的病人（Ｐ＜０．０１），目前精神症状严重的病人、维持治疗药物剂量（折合氯丙嗪剂量）＞３００ｍｇ／ｄ的病人、ＭｏｒｎｉｎｇＳｉｄｅ康复状态量表评分高的病人依从性差。经逐步多元回归分析，影响服药依从性的主要因素为：家庭人际关系、维持治疗药物剂量、维持治疗时间、慢性精神病病人标准化精神症状量表评分。认为提高病人的依从性能减少疾病的复发。     

Long-term outcome of depot neuroleptic maintenance treatment among chronic psychotic patients

A total of 51 chronic psychotic out-patients, with a median age of 51 years and median duration of psychosis of 23 years, treated with depot neuroleptics, entered a 5-year follow-up study with assessments of symptoms, side-effects and plasma concentration of the depot drug (follow-up (FU) patients). The outcome for 38 non-eligible (NE) patients was obtained from hospital case reports. The relapse rate was higher for NE than for FU patients (71% vs. 50%). The mortality rate was 9%, and the median age at death was 47 years. Half of the FU patients completed 3 years of treatment uneventfully. Of the total of 89 patients, only 18% remained stable over a period of 5 years. The depot dose was approximately the same after 3 years (median 255 mg, range 50–1018 mg chlorpromazine equivalents).     

Clinical outcome of patients with schizophrenia without maintenance treatment in a nonindustrialized society

The outcome of 51 patients with schizophrenia (DSM-III-R) consecutively admitted to Bangli State Mental Hospital (Bali) with no prior psychiatric treatment was assessed by the Positive and Negative Syndrome Scale (PANSS) and Eguma's Social Adjustment Scale (ESAS) at a 5-year followup evaluation. The subjects were divided into two groups according to their medication patterns determined at the assessment. Mann-Whitney U test revealed no significant differences in the PANSS scores between the treated group (n = 22) and the nontreated group (n = 29), whereas a significant difference in the distribution of the scores was observed (Kolomorov-Smirnoff test, p < 0.05). Subjects in the nontreated group showed a greater tendency to be scored either high or low in the PANSS than did subjects in the treated group. Moreover, subjects in the nontreated group tended to be classified more often into the best or worst outcome categories when the ESAS was performed than subjects in the treated group (chi-square analysis, p < 0.05). In the present study, nontreatment may reflect a good outcome in terms of no requirement for continuing treatment but still be causally related to poor outcome in terms of absence of the necessary treatment. The results suggest the importance of therapeutic intervention for schizophrenia patients who have severe psychopathology without maintenance treatment in nonindustrialized societies.     

Methadone maintenance as a therapeutic approach in the treatment of opiate dependent patients

Treatment of opiate addicts is still difficult, and often has only limited success. Methadone therapy offers an alternative, in particular for patients who have repeatedly attempted conventional treatment without success. According to experience in Switzerland, about two-thirds of these patients become medically stable and socially rehabilitated during methadone therapy, or even drug-free in the long term following therapy. The therapy does not consist solely in a daily dose of methadone, but also involves intensive psychosocial care. In Germany, methadone therapy has been under discussion for more than 20 years. In this discussion doubts have been expressed about the criteria used to assess the indications for and the degree of success attained with methadone therapy. In addition, ethical arguments question whether social rehabilitation should be a primary goal of therapy. In order to objectify the discussion, methadone therapy is now being tested in Germany. A social consensus must be sought on goals and strategies in the treatment of opiate addicts.     

Endogenous opioids in cerebrospinal fluid of opioid-dependent humans

Endogenous opioid systems may be altered as a consequence of addiction, but evidence to support this idea is meager so far. We obtained 136 cerebrospinal fluid (CSF) samples from 72 opioid addicts during four distinct states: methadone maintenance, detoxification from methadone, opioid antagonist treatment, and drug-free status. CSF endorphins were measured in 86 patients samples using a radioreceptor assay (RRA), and beta-endorphin levels were measured in 85 patient samples using a radioimmuno assay (RIA). During detoxification, both RRA fraction I and beta-endorphin showed a generally similar pattern of changes. Both were lowest when measured 40-50 hr after the last opioid dose, and both showed an apparent rebound to higher than methadone maintenance values at 60-70 hr following the last dose. During methadone maintenance and drug-free states, the addicts' levels of fraction I RRA endorphins in the CSF were higher than levels found in a normal control group. Fraction II endorphins were also elevated in the addicts who were drug free. In contrast, CSF beta-endorphin during both methadone maintenance and drug-free states was lower in the addicts as compared to the normal, drug-naive group. Except for the pattern found during detoxification, there were no consistent changes in endorphin levels across different states of addiction.