Medicines and the drug control treaties: is buprenorphine for opioid addiction at risk of being lost?

Over the past century, a worldwide system for the control of drugs with abuse potential has developed through the adoption of a series of international treaties. The important multilateral conventions currently in force are the United Nations Single Convention on Narcotic Drugs, 1961 (Single Convention), the United Nations Convention on Psychotropic Substances, 1971 (Psychotropic Convention) and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances, 1988. From the beginning, the aim of these drug control treaties has been to control the abuse and trafficking of substances with abuse potential while assuring that the availability of these drugs for medical and scientific purposes is not unduly restricted. There is activity in the World Health Organization and the International Narcotics Control Board to determine whether the international control of buprenorphine, a partial mu-opioid agonist used as an analgesic and for the treatment of opioid addiction, should be changed from the Psychotropic Convention to the Single Convention. This change would result in the classification and regulation of buprenorphine as a narcotic drug rather than a psychotropic substance. Such a move is unwarranted medically and scientifically and would provoke increased controls on buprenorphine that would fundamentally disrupt the medical practice of pain management and opioid replacement therapy around the world. The negative impact of inappropriate regulatory controls when licensed medicines come under such scrutiny are described.

Evidence-based analysis of the worldwide abuse of licit and illicit drugs.

In order to place the issues of drug abuse in a proper perspective and to allow rational, evidence-based decision-making, an analysis of the international data on the use of illicit drugs and the misuse of legally prescribed psychotropic drugs was undertaken. The data show that by far the most widely abused drug is cannabis, followed, according to region, by amphetamine-type stimulants or cocaine. While opiate abuse is far less widespread, it accounts for a disproportionately large proportion of medical and social problems. The illicit use of licit medicines is a very small, and declining, problem. The implications of these data for physicians, politicians, regulators and administrators are discussed.

Olanzapine as alternative therapy for patients with haloperidol-induced extrapyramidal symptoms: results of a multicenter, collaborative trial in Latin America.

Conventional antipsychotic agents can induce extrapyramidal symptoms (EPS) that may be alleviated by switching patients to novel agents such as olanzapine. Patients with schizophrenia and related disorders (ICD-10) who were taking haloperidol (N = 94; mean dose = 12.7 mg/day) and had EPS (Simpson-Angus Scale [SAS] > 3) were directly switched to 6 weeks of open-label olanzapine treatment (mean dose = 11.4 mg/day). There were significant mean improvements (p <0.001 for all measurements) from baseline to endpoint on the SAS (-9.69+/-5.33; percentage change, 87.2%), the Barnes Akathisia Scale (-1.00+/-1.19; percentage change, 82.5%), and the Abnormal Involuntary Movement Scale (-1.48+/-2.89; percentage change, 81.1%), and anticholinergic use decreased from 47.9% to 12.8% (mean baseline to endpoint change: -1.52+/-1.91-mg equivalents of benztropine; p < 0.001). Significant mean baseline to endpoint improvements (p < 0.001 for all measurements) were observed on the Positive and Negative Syndrome Scale (PANSS; -25.28+/-18.67; percentage change, 30.3%), the PANSS-extracted Brief Psychiatric Rating Scale (0-6 scale, -13.41+/-10.16; percentage change, 54.4%), and the Clinical Global Impressions Severity scale (-1.16+/-1.19; percentage change, 26.4%). Spontaneously reported treatment- emergent adverse events with a greater than 5% incidence were somnolence (16.0%), increased appetite (14.9%), weight gain (11.7%), headache (8.5%), anxiety (7.4%), dizziness (6.4%), and insomnia (5.3%). Criteria for a successful switch were met by 90.5% of patients. Psychotic symptom exacerbation was experienced by 30.9% of patients at any time during the study and by 11.7% of patients at endpoint. Results suggest that a direct switch to olanzapine is a therapeutic option when patients with haloperidol-induced EPS are unable to tolerate a more gradual switch.

Sleep and cognitive (memory) function: research and clinical perspectives.

The field of memory and sleep is controversial and extremely interesting, and the relationships between thought processes, i.e. cognition and sleep, have recently been examined in a variety of clinical and basic research settings, as well as being the object of intense interest by the general public. For example, there are data which demonstrate that insomnia, as well as specific sleep disorders, can have a negative impact on sleep cognition as well as affect daytime patterns of cognitive functioning. Thus, sleep, disturbed sleep and the lack of sleep appear to affect cognitive and memory functions. An International Workshop dealing with Sleep and Cognitive Function: Research and Clinical Perspectives was convened in Cancún, Mexico, 1-4 March 1999 under the auspices of the World Health Organization Worldwide Project on Sleep and Health and the World Federation of Sleep Research Societies. A great number of areas of intersection between sleep and cognitive function were examined during the course of the Workshop, such as aging, cognition and sleep and the dream process and sleep. The results of these discussions are included in a WHO publication (WHO Doc.: MSD/MBD/00.8). In the present report we concentrate on presenting a summary of a coherent set of data which examine memory consolidation during sleep and the impact of insomnia on cognitive functions. Based upon these data, a review of memory and drug effects that are sleep-related, and an examination of the relationship between hypnotics and cognitive function are included. Finally, a summary of recommendations of the Workshop participants is presented.

Efficacy and safety of tianeptine in the treatment of depressive disorders in comparison with fluoxetine*

Depression is treated by a great variety of antidepressant treatments. SSRIs (such as fluoxetine) are well known: it is, however, sure that further progress is needed and the search for antidepressants with other mechanisms of action (such as tianeptine) or different efficacy is still of interest. A multinational study compared tianeptine with fluoxetine in 387 patients with Depressive Episode, or Recurrent Depressive Disorder, or Bipolar Affective Disorder (ICD-10), in a double-blind parallel group design. They were treated for six weeks. At inclusion, no significant difference between groups was shown. Final MADRS scores were 15.7 and 15.8 with tianeptine and fluoxetine, respectively (ITT population) (p = 0.944). MADRS responders were 58% and 56% with tianeptine and fluoxetine, respectively (p = 0.710). No statistical difference was observed for the other efficacy parameters. Thirty-six withdrawals occurred in each group, without any difference for the reasons of discontinuation. There was no major difference between groups for the other safety parameters. In this study, both tianeptine and fluoxetine exhibited a good efficacy and safety. Copyright 1999 Elsevier Science B. V. All rights reserved.

Sleep and health: research and clinical perspectives.

Overall, the Workshop covered most of the principal areas which will be the focus of the Worldwide Project on Sleep and Health. Presentations ranged from the basic science of melatonin receptors to the epidemiology of untreated insomnia, and finally, to the education of primary care physicians. It was emphasized that there is a need for more data, and new experimental paradigms are necessary for successful public health initiatives dealing with sleep disorders.

The public health impact of anxiety disorders: a WHO perspective.

Anxiety disorders, which may constitute anywhere from one quarter to one half of all mental illnesses in the community, are most commonly seen in the primary care sector. Despite their significant impact on the functioning of individual patients, the plethora of unnecessary medical procedures to which these sufferers are subjected, and the large indirect economic burden, these disorders continue to be grossly underdiagnosed and undertreated in this sector. Effective treatments for anxiety disorders have been available for at least two decades. Concerted efforts by the World Health Organization (WHO), the World Psychiatric Association and similar organizations are needed to change this picture.

The World Health Organization's global initiative on neurology and public health.

In 1993, the World Health Organization launched a global initiative aimed at increasing public and professional awareness of the public health aspects of neurological disorders. The initial phase of this project has been carried out through the organization of a series of symposia on prevalence, severity and costs of neurological disorders including dementia, stroke, epilepsy and headache. The main objective of the next phase of the project is to develop an international educational programme on neurology and public health and to establish a network of training centres in different regions of the world.

Placebo-controlled study of tianeptine in major depressive episodes.

The efficacy and safety of tianeptine were compared, in the course of a multicentre randomised, double-blind, parallel group study, to those of placebo in the treatment of Major Depressions and Bipolar Disorder, Depressed with or without melancholia, without psychotic features. After a 1-week run-in placebo period, 126 depressed out-patients presenting DSM-III-R Major Depression or Bipolar Disorder, Depressed, with a total MADRS score of at least 25, were treated for 42 days with either tianeptine (25-50 mg/day) or placebo. Efficacy assessments were MADRS, CGI, HARS, Zung Depression Self Rating Scale and a VAS. Better efficacy of tianeptine was shown, and confirmed by covariance analyses, in final MADRS scores of the intention-to-treat population, of patients treated for at least 14 days and of completers; also in CGI items 1 and 2, MADRS item 10, and VAS. The results confirmed the efficacy of tianeptine (mean dosage: 37.5 mg/day) in the treatment of Major Depression and Bipolar Disorder, Depressed, with or without melancholia, compared to placebo. Tianeptine's acceptability did not differ from that of placebo. For adverse events, a higher incidence of headaches was found with tianeptine.

Dysthymia in neurological disorders.

Dysthymia is characterized by long-lasting periods of lowered mood. Epidemiological studies in the USA and Europe have demonstrated that the prevalence of dysthymia is at least 3% of the general population. Its pervasive occurrence makes dysthymia a public health problem worldwide. One feature of this disorder is its co-occurrence with medical and neurological disorders. A World Health Organization meeting on dysthymia in neurological disorders was held in Geneva, 1-3 July 1996 to address this topic. Some of the major goals of this meeting were to clarify the definition of dysthymia in the presence of neurological disorders and to evaluate current research in the field, to point out new areas for investigation, and to discuss current psychological and pharmacological treatments for dysthymia in neurological disorders. The potential roles of neuroendocrine and molecular mechanisms in dysthymia were identified through specific problems related to dysthymia occurring in disorders such as Parkinson's disease, Alzheimer's disease, stroke, multiple sclerosis and epilepsy. This meeting provided direction and opportunity for future studies in the under-recognized and under-investigated relationship between dysthymia and neurological disorders.

Medically unexplained somatic symptoms in different cultures. A preliminary report from phase I of the World Health Organization International Study of Somatoform Disorders.

The World Health Organization has recently launched an international study of somatoform disorders in different cultures. Five centres representing distinct cultures participated in phase I of the project, the main objective of which was to test the cross-cultural applicability and reliability of instruments for the assessment of somatoform disorders. The analysis of the assessed somatic symptoms showed that various aches and pains in different parts of the body represented cross-culturally the most frequent symptoms for which there was no medical explanation. Such symptoms may indicate the presence of an underlying mental disorder but can also represent a means for culture-specific expression of psychosocial distress. This bears particular significance for health professionals in primary and general medical care, who are most likely to encounter patients presenting with multiple, persistent and medically unexplained somatic symptoms.

An international study of psychological problems in primary care. Preliminary report from the World Health Organization Collaborative Project on 'Psychological Problems in General Health Care'.

This article describes a large longitudinal multicenter collaborative study that investigated the form, frequency, course, and outcome of psychological problems that were seen in primary health care settings in 15 different sites around the world. The research employed a two-stage sampling design in which the 12-item General Health Questionnaire was administered to 26,422 persons aged 18 to 65 years who were consulting health care services. Of these persons, 5604 were selected for detailed examinations using standardized instruments and were followed up at 3 months and 1 year to provide information on course and outcome. All assessment instruments have been translated into 13 different languages. The project has produced a database that allows for the exploration of the nature of psychological disorders experienced by patients in general medical care and their association with physical illness, illness behavior, and disability over time.

Amineptine (Survector 100) in the treatment of depression in Brazil.

Amineptine was studied in open, simple, and comparative trials in several Latin American countries, primarily in Brazil, Uruguay, and Chile. These countries developed studies with this antidepressant in an individualized way in different centers as well as multicenter studies under single coordination. The author analyzes the results of two of these studies. Generally, amineptine showed a positive result in depression in which the inhibition symptom is predominant. This drug also showed a good tolerance: it may be prescribed to elderly patients with depression and to people who suffer from diseases for which the classic antidepressants cannot be recommended. Many other studies on this drug were developed among the general practitioners in view of its rapid onset of action and also its easy clinical handling. Many people who suffer from depression are not treated by psychiatrists; it is very important that other specialists take notice of these effective and safe antidepressants. It is also very interesting to compare these studies to others that have already been developed in several other countries so that a better comprehension of the phenomenon of depression and its treatment can be reached.

Midazolam and triazolam in out-patients: a double-blind comparison of hypnotic efficacy.

The hypnotic efficacy and the effect on the condition after morning awakening of midazolam 15 mg and of triazolam 0.5 mg were studied in a multicentre, double-blind cross-over study in 198 out-patients with sleeping difficulties of various origin. The subjects received each drug for two consecutive nights, and completed a questionnaire each day on awakening. Both midazolam and triazolam significantly shortened the sleep-onset latency, reduced the number of awakenings, and increased the total sleep time. The state on awakening was also significantly improved after both compounds for several self-rated items. There was a difference only with regard to the patients' feeling of being under drug influence, which was reported as being significantly more marked after triazolam. In conclusion, both compounds were effective and well tolerated in the doses used, only a few side-effects being reported.