The common occurrence of comorbid substance misuse and other psychiatric disorders has challenged the diagnostic and therapeutic skills of professionals concerned with the care of patients with these dual disorders. Combined pharmacological and psychological treatment approaches have evolved empirically drawing upon standard treatments with emphasis on psychosocial approaches to substance misuse for psychotic disorders and pharmacological approaches for mood disorders. Advances in the biology of both disorders have started to inform their psychopharmacology. The specific role of atypical antipscychotics is highlighted. Further studies of the biology of comorbidity will impact the use of effective pharmaceuticals such as clozapine with dual effects on schizophrenia and substance misuse.

There has been growing interest in the role of serotonin (5-hydroxytryptamine, 5-HT) in anxiety, including pathological states such as panic disorder. The technique of tryptophan depletion (TD), which causes an acute, temporary and reversible reduction in brain 5-HT levels, is a useful minimally invasive paradigm to aid the research of the role of 5-HT in various disorders. This review discusses the evidence supporting the hypothesis that 5-HT function is of importance in the neurobiology of panic disorder and considers in more detail how our understanding has been influenced by work using the technique of TD. Possible avenues for future research are also discussed.

Buprenorphine is a partial μ-opioid receptor agonist that is being increasingly used in clinical practice in the treatment of opioid dependence in the UK, USA, and, elsewhere. Its unique pharmacological properties mean it is a relatively safe drug, it can be given by alternate day dispensing, and it is associated with relatively mild symptoms on withdrawal. The interpretation of the research literature on buprenorphine is however, complex, and often appears to be in conflict with how buprenorphine is used in clinical practice. This article describes these apparent contradictions, their likely explanations, and how these may further inform our clinical practice. The article also describes the clinically relevant pharmacological properties of buprenorphine, compares it to methadone, relates the evidence to clinical experience, and provides practical advice on how to manage the most common clinical techniques. The best quality evidence suggests that very rapid buprenorphine induction is not associated with a higher drop-out rate than methadone, that buprenorphine is probably as good as methadone for maintenance treatment, and is superior to methadone and α-2 adrenergic agonists for detoxification. However, buprenorphine cannot yet be considered the ‘gold standard’ treatment for opiate dependence because of the higher drop-out rates that may occur on induction using current techniques, its high-cost relative to methadone, and because the place of buprenorphine in treatment is still continuing to evolve.

In order to more effectively treat substance use disorders in persons with severe mental illness, integrated treatment models have been developed for these ‘co-occurring disorders.’ The nature of clinical services provided in these programs is described in this article, with brief attention to research on these programs. Clinical services are generally guided by a stage model of change, in which the client's motivation to change (or stage of treatment: engagement, persuasion, active treatment, relapse prevention) informs the optimal selection of appropriate interventions. Psychotherapeutic services for co-occurring disorders include a range of individual (motivational interviewing, cognitive-behavioral counseling), group (stage-wise groups, social skills training, self-help), and family (single family, multifamily formats) interventions. Supplementary interventions are also commonly provided, including psychopharmacological, residential, coerced and involuntary, and vocational rehabilitation. Access to a range of different interventions for co-occurring disorders may improve the ability of clinicians to engage and tailor treatment to meet clients' unique needs. The research base supporting integrated treatment for co-occurring disorders is limited at this time owing to the small number of methodologically rigorous studies from which to draw conclusions. Nevertheless, the available evidence suggests that integrated treatment programs improve outcomes compared with nonintegrated approaches, and that more research is needed to evaluate the benefits of these programs.

Physicians' attitudes to depot medication are often focused on improved compliance (adherence), and thus, short- and long-term treatment outcomes. By contrast, patients receiving such formulations tend to have a quite different viewpoint of medication. Factors such as convenience, side-effects and their beliefs about their illness play an important role in determining whether patients will adhere to their prescribed treatment regimen. The relationship between the patient and physician is of crucial importance in determining a patient's attitude to their medication; it is becoming increasingly clear that managing the illness in the long-term and avoiding relapse, while ensuring compliance, should be reframed as a collaborative process between the patient and physician.

Heroin has been prescribed in England for the treatment of heroin addiction for almost 100 years. For many years, England was almost the only country where this occurred, and the British system was consequently the subject of international curiosity. In spite of this long history, very little research has been carried out locally, and until recently, there were no guidelines as to best practice. In 1965, it was decided that only doctors with a Home Office license could prescribe heroin. Since that time, the proportion of opiate addicts treated with heroin has greatly diminished, as has the number of doctors willing to prescribe. One doctor in particular remained an enthusiastic proponent of heroin prescription. His claims impressed some Swiss clinicians, who proceeded to establish a multicentre trial in Switzerland. This was followed by a similar trial in the Netherlands. These trials apparently indicated that a proportion of treatment-resistant opiate addicts could respond well to heroin, although the researchers' conclusions have been disputed. The National Treatment Agency in England is now developing guidelines for good practice based on this new information and is planning to set up some pilot sites. It is likely that practise in England will remain somewhat different from continental practice, particularly with respect to long-term supervised injecting. It is unclear how much funding will be released to support heroin prescription. Without adequate funding, it is likely to disappear.

Evidence for implication of cholecystokinin (CCK) in the neurobiology of panic disorder is reviewed through animal and human pharmacological studies. The results of these investigations raise two issues: (i) selectivity of action of CCK-2 agonists in anxiety disorders; and (ii) aberrations of the CCK system in anxiety disorders, both of which are discussed.

Neuroleptic malignant syndrome (NMS) is associated with the administration of antipsychotic agents and other drugs such as l-dopa, antidepressants, and antihistaminic agents. Unexpected changes in mental status, new-onset catatonia, episodic tachycardia, tachypnea, hypertension, dysarthria, dysphagia, diaphoresis, sialorrhea, incontinence, low-grade temperature elevations, and rigidity should arouse suspicion. Several lines of evidence provide support for the involvement of dopamine. Most of the drugs implicated in NMS are D2 dopamine receptor antagonists. Central noradrenergic activity is also possibly related to the disorder, as sympathetic hyperactivity is associated with the active phase of NMS. Currently, the definitive role of GABA deficiency in NMS is yet to be established. Differential diagnosis should include malignant hyperthermia, lethal catatonia, lithium toxicity, serotonin syndrome, and heat stroke. A high degree of suspicion and the discontinuation of antipsychotic agents even if the diagnosis is not established are essential for the safety of the patient. Treatment of NMS should be individualized and be based empirically on the character, duration, and severity of the clinical signs and symptoms noted. The initial step in the treatment of NMS is the removal of the offending agent. Full-blown NMS is a serious condition and requires immediate supportive, nutritive, and electrolyte therapies. The administration of drugs that can improve NMS, such as IV dantrolene and/or oral bromocriptine, may also be taken into consideration, based on the severity and nature of the NMS.

Co-occurring severe mental illness and substance use disorder has been recognized as a common problem in the U.S. since the early 1980s (1–3). For these individuals with co-occurring disorders, research demonstrates the effectiveness of various forms of combining, blending, or integrating mental health and substance abuse treatments (4). The evolving U.S. service model for integrated dual disorders treatment emphasizes several key elements: implementation, leadership, training, engagement, assessment, counseling for all patients, ancillary treatments for those with multiple needs, secondary treatments for patients who are nonresponders, and quality assurance regarding process and outcomes.

Chronic disorders such as schizophrenia require long-term treatment programs in order to maintain patients at the lowest level of symptomatology, reduce the likelihood of psychotic relapse, and support achievement of remission and recovery. Evidence suggests that treatment with long-acting injectable antipsychotics reduces the impact of partial compliance and provides predictable release of medication, assuring continuous therapeutic coverage. Until recently, only conventional antipsychotic agents were available in long-acting formulations, thereby foregoing the advantages of the atypical class. Atypical agents which are given orally have been shown to provide long-term efficacy and tolerability benefits compared with conventional agents, but are limited by the need for daily administration. The most recent pharmacological strategy to achieve optimal maintenance treatment has been to combine the benefits of an atypical antipsychotic with delivery in a water-based long-acting formulation. The first antipsychotic to achieve this combination – long-acting risperidone – may thus represent an important advance in the optimization of long-term treatment outcomes in patients with schizophrenia.

The relationship between olanzapine metabolism by CYP1A2/CYP2D6 and hyperglycaemia was investigated. The higher blood olanzapine concentration may be effected by the abnormal metabolism, but not always caused by hyperglycaemia.

The co-occurrence of substance misuse and other psychiatric disorder (dual diagnosis) has been increasingly recognized in the UK. Clinical studies of patients with severe mental disorders showed high rates of substance misuse with poor clinical and social outcome. These patients often fall ‘between the cracks’ of the separate general psychiatric and addiction services. This has necessitated the development of a national policy advocating the provision of integrated care within mainstream psychiatric services. There are emergent models of good practice that require evaluation of effectiveness and cost effectiveness.