Safety, effectiveness and tolerance of buprenorphine-naloxone in the treatment of opioid dependence: results from a nationwide non-interventional study in routine care.

INTRODUCTION: Buprenorphine is well known in the treatment of opioid dependence. Despite a high safety profile and good tolerance buprenorphine has been subject to misuse and diversion. To reduce misuse the antagonist naloxone was added and the 4:1 combination of buprenorphine-naloxone was launched in Germany in March 2007. On the basis of the results from international clinical trials a non-interventional study was conducted to gather data on safety, effectiveness, retention and acceptability of buprenorphine-naloxone in the treatment of opioid dependent patients in routine care. METHODS: A nationwide multicentre 12-month prospective, non-interventional, post-marketing, surveillance study was carried out with 12 assessment points in N=384 opioid dependent patients currently in maintenance treatment from N=69 general practitioners, clinics and outpatient clinics in Germany. RESULTS: N=337 data sets were eligible for analysis. The rates of patients with serious and non-serious adverse events were low with 1.2% and 17.5%, respectively. No deaths occurred during the observational period and only one hospitalization was documented. Concomitant drug use decreased for all illicit substances. Mental health and quality of life measured with standardized self-assessment questionnaires improved significantly. The 12-month retention rate was 57.1%. Of the n=181 patients still in treatment at the end of the observation period, 96.7% continued treatment with buprenorphine-naloxone. CONCLUSION: The findings of the non-interventional study indicate high effectiveness and safety of buprenorphine-naloxone in the treatment of opioid dependence. The medication was well accepted by opioid dependent patients in long-term substitution treatment with substantial reductions of concomitant drug use and measurable improvement in quality of life.

[Efficacy of exercise therapy to reduce cardiometabolic risk factors in overweight and obese children and adolescents: a systematic review]. / Wirksamkeit von Trainingsinterventionen zur Reduktion kardiometabolischer Risikofaktoren bei Kindern und Jugendlichen mit Übergewicht und Adipositas.

BACKGROUND AND OBJECTIVE: Excess weight in the younger population is associated with the various cardiovascular risk factors including hypertension, dyslipidemia and even metabolic syndrome early in life. Since these cardiometabolic profiles in children and adolescents track into adulthood they can give rise to the development of cardiovascular diseases and non-insulin-dependent diabetes. METHOD: A systematic literature search was performed in 4 electronic databases, Pubmed, PEDro, Cochrane Library und SPORTDiscus, looking for data on the efficacy of training programmes to improve cardiometabolic outcome parameters in overweight and obese children and adolescents. RESULTS: 12 randomized controlled trials were assessed eligible for inclusion. 9 of 12 trials documented improvements of at least one clinical or cardiometabolic marker in overweight children or adolescents upon completion of the training programme. CONCLUSION: Aerobic training programmes have the potential to effectively improve cardiovascular risk factors in overweight or obese children and juveniles. The evidence from previous studies is moderate. Further studies of high methodological quality are needed.

[Measuring sleep duration and sleep quality]. / Messung von Schlafdauer und Schlafqualität.

Restorative functions of sleep are of special interest for sleep medicine. For the assessment of these restorative functions, various parameters are taken into account, among which sleep duration and sleep quality play the most important roles. Both terms are essential for sleep perception, expressing the subjective satisfaction of the individual with the time spent asleep. In recent decades, sleep medicine and sleep research have developed methods for the assessment of both objective and subjective dimensions of sleep. Among subjective methods, taking of the medical history focusing on the patient's sleep is important. Standardized and validated questionnaires play a supportive role. Objective methods are, for example, estimation of the sleep-wake cycle by means of actigraphy and polygraphy. Especially in multimorbid patients, polysomnography is still the gold standard method for diagnostics. An important approach during recent years is shifting from bothering overnight examinations into less disturbing procedures for patients that include performing ambulatory, outpatient examinations in the patients' home rather than inpatient surveillance within sleep centers.

[Daytime sleepiness in patients with Obstructive Sleep Apnoea (OSA) - pathogenetic factors]. / Tagesschläfrigkeit bei obstruktiver Schlafapnoe (OSA) - pathogenetische Faktoren.

Excessive daytime sleepiness (EDS) is one of the most frequent symptoms in patients with obstructive sleep apnoea (OSA). EDS can lead to substantial impairments in quality of life and is a major cause of fatal accidents. However, not all patients with OSA develop EDS. The aim of this paper is to review the current literature to identify factors having an impact on sleepiness in patients with OSA. Interestingly, a substantial heterogeneity of the results was found. Summarising these results, causes of EDS in patients with OSA are multifactorial. Severity of obesity and breathing disorders (apnoea/hypopnoea index) seem to be the most important predictors. Continuous positive airway pressure therapy significantly reduces sleepiness in patients with OSA.

[Insufficient involvement of psychiatrists in substitution treatment]. / Die unzureichende Beteiligung von Psychiatern an der Substitutionsbehandlung.

Results of a nationally representative study in 2,694 patients reveal that most physicians (n=223) involved in substitution treatment of opioid-dependent patients are general practitioners, while only 16% have a psychiatric/psychotherapeutic background and only 21% of the addictive patients are treated by psychiatrists. This contrasts with the remarkably complex pattern of co- and multimorbidity with other mental disorders in such patients. Most psychiatrists engaged in substitution treatment work in specialized outpatient wards (51.3%), and few were operative in their own or private practice (7.2%). Implications of these critical findings are discussed.

[Psychopharmacology and clinical aspects of benzodiazepine dependence]. / Psychopharmakologie und Klinik der Benzodiazepin-Abhängigkeit.

Recent aspects of mechanism of benzodiazepines (BDZ) via indirect GABA-mimetic inhibitory effects at brain-specific BDZ-GABA receptors may contribute to an understanding of pathophysiological mechanisms of anxiety disorders and drug dependencies. The development of various BDZ receptor ligands with diverse psychopharmacological properties may lead to safer drugs with regard to "drug seeking" and "maintaining" properties. This paper reviews recent research of BDZ receptor pharmacology and clinical aspects of abstinence syndromes including also prospective studies.

Treatment of benzodiazepine withdrawal symptoms with carbamazepine.

In 18 patients with a benzodiazepine (BZD) dependency the drug was withdrawn. The dose of BZD was gradually reduced in nine of the patients, while the others were additionally treated with carbamazepine (CBZ) for a further 15 days after BZD discontinuation. Withdrawal symptoms were assessed every third day during the study period. When comparing results in both groups, a clear trend towards less severe withdrawal symptoms could be observed in the group treated with CBZ. Some of the differences were statistically significant on days 9-12 after BZD withdrawal. Fundamental withdrawal symptoms (like hypersensitivity to sensory stimuli, abnormal perception of movement, depersonalisation or derealisation) were also less severe in the group treated with CBZ compared with the group not receiving that treatment. These findings support the results of previous reports indicating a therapeutical effect of CBZ in BZD withdrawal.

Preference for alprazolam as opposed to diazepam in benzodiazepine-dependent psychiatric inpatients.

Fourteen inpatients with long-term benzodiazepine (BDZ)-dependency were gradually withdrawn from their medication. During a four-day study period patients received 5 mg diazepam t.d.s. Under double-blind conditions the 5 mg diazepam was replaced twice, by either 0.5 mg or 0.37 mg alprazolam. When the hypothetically realistic alprazolam to diazepam equivalent ratio of 1:10 with regard to hypnosedative and anxiolytic properties was used, alprazolam was clearly preferred to diazepam in three sensitive tests. When alprazolam and diazepam were tested using the altered equivalent ratio of 1:14, "liking" and "seeking potentials" revealed no significant differences. However, also under these test conditions alprazolam tended to be preferred in a drug choice test. It is concluded that alprazolam appears to implicate somewhat higher reinforcing properties, possibly leading to a higher abuse liability in BDZ-dependent patients as compared to diazepam.

Carbamazepine as an adjunct of antipsychotic therapy.

The effect of low-dose haloperidol combined with the anticonvulsant carbamazepine was investigated in a 5-week placebo-controlled, double-blind study in acute schizophrenic patients. Weekly ratings showed a clinically pronounced and statistically significant improvement in both the carbamazepine and placebo groups. However, the patients on carbamazepine needed less neuroleptic and anticholinergic medication and experienced fewer side effects compared to the patients on placebo. Moreover, patients in the carbamazepine group showed a clear deterioration after discontinuation of carbamazepine (but maintenance of neuroleptic medication), while the placebo group did not change after discontinuation of placebo. Concomitant treatment with carbamazepine in psychotic patients may help to reduce neuroleptic dosages and unwanted side effects.

Characterization of benzodiazepine withdrawal in high- and low-dose dependent psychiatric inpatients.

Fourteen patients with high- (n = 7) and low-dose (n = 7) benzodiazepine (BDZ) dependency presented predominantly with anxious and depressive neurotic symptoms which caused long-term BDZ medication. Their BDZ dependency was characterized by giving preference to the abuse of benzodiazepines with long elimination half-life. Significant enlargement of CSF spaces was only found in high-dose dependent patients. Withdrawal after long-term BDZ medication revealed no differences between high- and low-dose BDZ dependency with respect to onset of withdrawal reaction and the correlation between onset of withdrawal and peak fall of BDZ serum level. The peak of withdrawal was reached 3-4 days later in high-dose BDZ dependent patients compared with those with a low-dose dependency. The peak withdrawal in high-dose dependent patients appeared when the serum BDZ metabolite nordiazepam dropped significantly. No such concomitant appearance of peak withdrawal and drop of serum nordiazepam level could be found in low-dose dependent patients. Specificity and intensity of BDZ withdrawal symptoms were the same for those dependent upon high doses of BDZs and those dependent upon low doses, but a protracted withdrawal was only observed in low-dose BDZ-dependent patients. During the withdrawal period psychopathometric measurements consistently revealed parallel changes in the scores for physical withdrawal symptoms, anxiety and depression. It is not clear whether anxiety and depression are "typical" BDZ withdrawal reactions or represent a "reactivated" state of the psychopathological disturbance which lead to the BDZ dependency. Possible implications for the therapeutical management of BDZ-dependent patients are discussed.