Journal of Psychopharmacology

The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.

Risk assessment is a core skill in psychiatry. Risk prediction for suicide in schizophrenia is known to be complex. We undertook a systematic review of all original studies concerning suicide in schizophrenia published since 2004. We found 51 data-containing studies (from 1281 studies screened) that met our inclusion criteria, and ranked these by standardized quality criteria. Estimates of rates of suicide and risk factors associated with later suicide were identified, and the risk factors were grouped according to type and strength of association with suicide. Consensus on the lifetime risk of suicide was a rate of approximately 5%. Risk factors with a strong association with later suicide included being young, male, and with a high level of education. Illness-related risk factors were important predictors, with number of prior suicide attempts, depressive symptoms, active hallucinations and delusions, and the presence of insight all having a strong evidential basis. A family history of suicide, and comorbid substance misuse were also positively associated with later suicide. The only consistent protective factor for suicide was delivery of and adherence to effective treatment. Prevention of suicide in schizophrenia will rely on identifying those individuals at risk, and treating comorbid depression and substance misuse, as well as providing best available treatment for psychotic symptoms.

These British Association for Psychopharmacology guidelines cover the range and aims of treatment for anxiety disorders. They are based explicitly on the available evidence and are presented as recommendations to aid clinical decision making in primary and secondary medical care. They may also serve as a source of information for patients and their carers. The recommendations are presented together with a more detailed review of the available evidence. A consensus meeting involving experts in anxiety disorders reviewed the main subject areas and considered the strength of evidence and its clinical implications. The guidelines were constructed after extensive feedback from participants and interested parties. The strength of supporting evidence for recommendations was rated. The guidelines cover the diagnosis of anxiety disorders and key steps in clinical management, including acute treatment, relapse prevention and approaches for patients who do not respond to first-line treatments.

Một cuộc sửa đổi hướng dẫn dựa trên bằng chứng của Hiệp hội Tâm thần học Anh năm 2000 về việc điều trị các rối loạn trầm cảm bằng thuốc chống trầm cảm đã được thực hiện để kết hợp các bằng chứng mới và cập nhật các khuyến nghị khi cần thiết. Một cuộc họp đồng thuận với sự tham gia của các chuyên gia về rối loạn trầm cảm và quản lý của chúng đã được tổ chức vào tháng 5 năm 2006. Các lĩnh vực chính trong điều trị trầm cảm đã được xem xét, và sức mạnh của bằng chứng cùng với các tác động lâm sàng đã được xem xét. Hướng dẫn đã được xây dựng sau khi nhận được phản hồi rộng rãi từ các tham gia viên và các bên liên quan. Một cuộc tổng quan tài liệu được cung cấp, xác định chất lượng bằng chứng để thông báo các khuyến nghị, sức mạnh của chúng dựa trên mức độ bằng chứng. Những hướng dẫn này bao gồm bản chất và phát hiện các rối loạn trầm cảm, điều trị cấp tính bằng thuốc chống trầm cảm, lựa chọn thuốc so với điều trị thay thế, các vấn đề thực tiễn trong việc kê đơn và quản lý, điều trị bước tiếp theo, phòng ngừa tái phát, điều trị tái phát và dừng điều trị.

The dopamine hypothesis of schizophrenia is the principal explanatory model of antipsychotic drug action. Recent discoveries extend our understanding of the neurochemistry of schizophrenia, with increasing evidence of dysfunction in glutamate and GABA as well as dopamine systems. In this review, we study the evidence for dopaminergic dysfunction in schizophrenia, drawing data from neurochemical imaging studies. We also review the NMDA receptor hypofunction hypothesis of schizophrenia as a supplementary explanatory model for the illness. We examine predictions made by the NMDA receptor hypofunction hypothesis and consider how they fit with current neurochemical findings in patients and animal models. We consider the case for glutamatergic excitotoxicity as a key process in the development and progression of schizophrenia, and suggest ways in which glutamate and dopamine dysregulation may interact in the condition.

The effects of drugs and substances of abuse on central dopamine (DA) transmission studied by in vivo monitoring techniques have been examined and compared with those of conventional reinforcers and in particular with food. The similarities and differences in the action of drugs and conventional reinforcers on DA transmission can provide the basis for an hypothesis of the mechanism of drug addiction and compulsive drug use. This hypothesis states that drug addiction is due to excessive control over behaviour exerted by drug- related stimuli as a result of abnormal motivational learning induced by repeated drug exposure. Such abnormal motivational learning would derive from the repetitive non-habituating property of drugs of abuse to activate DA transmission phasically in the nucleus accumbens (NAc) 'shell'. Thus, activation of DA transmission by conventional reinforcers is under strong inhibitory control by previous exposure to the reinforcer (habituation); this, however, is not the case with drug reinforcers. Repetitive, non-adaptive release of DA in the NAc 'shell' by drugs of abuse would result in abnormal strengthening of stimulus-reward (incentive learning) and stimulus-response associations (habit learning) that constitute the basis for craving and compulsive drug use.

The frontal cortex (FCX) plays a key role in processes that control mood, cognition and motor behaviour, functions which are compromised in depression, schizophrenia and other psychiatric disorders. In this regard, there is considerable evidence that a perturbation of monoaminergic input to the FCX is involved in the pathogenesis of these states. Correspondingly, the modulation of monoaminergic transmission in the FCX and other corticolimbic structures plays an important role in the actions of antipsychotic and antidepressant agents. In order to further understand the significance of monoaminergic systems in psychiatric disorders and their treatment, it is essential to characterize mechanisms underlying their modulation. Within this framework, the present commentary focuses on our electrophysiological and dialysis analyses of the complex and reciprocal pattern of autoand heteroreceptor mediated control of dopaminergic, noradrenergic and serotonergic transmission in the FCX. The delineation of such interactions provides a framework for an interpretation of the influence of diverse classes of antidepressant agent upon extracellular levels of dopamine, noradrenaline and serotonin in FCX. Moreover, it also generates important insights into strategies for the potential improvement in the therapeutic profiles of antidepressant agents.

Compulsive drug use, which is typically portrayed as a defining quality of addictive behavior, has been described as a pattern of drug consumption that is stimulus bound, stereotyped, difficult to regulate and identified by a loss of control over intake. It is widely assumed that compulsive drug use is caused by drug craving. This assumption is supported by numerous findings of a general correspondence between measures of craving and drug-use behavior. A more focussed analysis of the available data, however, reveals that craving and drug use are not coupled to the degree required by the hypothesis that craving is the source of all drug use in the addict. As an alternative to this craving-based view, compulsive drug use could be characterized as a form of automatized behavior. Automatic performance is assumed to develop over the course of repeated practice of motor and cognitive skills. Automatized behavior, like compulsive drug use, tends to be stimulus bound, stereotyped, effortless, difficult to control and regulated largely outside of awareness. The formulation of drug compulsion as a manifestation of automaticity rather than craving allows addiction researchers to apply methods and measures derived from cognitive sciences to investigate the fundamental organization of compulsive drug-use behavior.

Recently, several reports have indicated instability of the ecstasy market in the Netherlands and other EU countries. In the current study, we demonstrate this instability in the Netherlands, showing a decrease of ecstasy tablets containing 3,4-methylenedioxymetamphetamine (MDMA) by more than 50% in 2009. In addition, we describe a partial replacement of MDMA in tablets sold as ecstasy by a previously unseen substance, mephedrone (or 4-methylmethcathinone). Mephedrone was quantified and ecstasy tablets contained between 96 and 155 mg of this new compound. So far, no studies about mephedrone’s effects have been published. For this study, we gathered information on the acute subjective effects of mephedrone from 70 regular ecstasy users. Overall, the majority of users considered the effects enjoyable. Mephedrone seemed to evoke effects similar to other amphetamine type psychostimulants, including MDMA. In contrast to MDMA, however, mephedrone induced strong feelings of craving in most users. If the unstable ecstasy market situation persists, the potential of mephedrone to substitute for MDMA might be substantial. Mephedrone, sold as ecstasy, is therefore likely to be a valid cause for health concern.