This editorial introduces the BJPsych Advances special issue on biological psychiatry.

Depression has a large socioeconomic burden, affecting an estimated 280 million people worldwide. Up to 55% remain symptomatic following pharmacological and psychological treatment and may be classified as having treatment-resistant depression. This commentary assesses two treatment options for this group – electroconvulsive therapy (ECT) and a novel approach, magnetic seizure therapy (MST) – with reference to a Cochrane Review comparing the two. The Cochrane analysis showed no clear benefit for MST, but the evidence is currently insufficient to draw firm conclusions.

Lithium is a gold standard maintenance treatment in bipolar affective disorder. It has a narrow therapeutic range, and at higher serum lithium levels there is a risk of adverse effects and toxicity. There are three patterns of lithium intoxication: acute, acute-on-chronic and chronic. We describe risk factors for lithium intoxication, mechanisms of toxicity and clinical symptoms seen in lithium intoxication. We describe both the acute and chronic effects of lithium toxicity. Lithium intoxication may be life-threatening and associated with longer-term sequelae. The management of lithium intoxication involves determining the type of intoxication. We discuss treatment strategies aimed at reducing absorption and increasing elimination of lithium. We discuss clinical indications for extracorporeal methods such as dialysis, which are used to limit the time and degree of exposure of the central nervous system to toxic lithium concentrations. Haemodialysis is the most rapid method of eliminating lithium from the body, but careful monitoring is required. Preventive strategies to mitigate the risk for lithium intoxication are discussed.

Clozapine dose assessment in treatment-refractory schizophrenia is complicated. There is a narrow margin between an effective and a potentially toxic dose and wide inter-individual variation in clozapine metabolic capacity. Moreover, factors such as changes in smoking habit, infection/inflammation, co-prescription of certain drugs, notably fluvoxamine, and age alter the dose requirement within individuals. Therapeutic drug monitoring (TDM) of plasma clozapine and N-desmethylclozapine (norclozapine) can help assess adherence, guide dosage and guard against toxicity. This article gives an overview of clozapine pharmacokinetics and factors affecting clozapine dose requirements. It then outlines the procedures and processes of clozapine TDM, from taking the blood sample for laboratory assay or point-of-contact (finger-prick) testing (POCT) to interpreting and acting on the results.

Genetic testing in psychiatry is becoming more common, but psychiatrists often receive little training in it. Given the pace of change in genetics, understanding the current methods of testing and their associated merits and limitations can therefore be challenging for some. This narrative, written for psychiatrists in the clinic, aims to cut through the jargon and describe current genetic testing techniques and their evolution from previous methods. It discusses benefits and risks of testing, how geneticists decide whether genetic variants are pathogenic, terminology found in genetic test results and how best to support patients with genetic diagnoses. It also describes methods used to study the genetics of polygenic disorders. It is anticipated this will facilitate a greater understanding of genetic testing and promote confidence among psychiatrists to discuss its clinical utility and implications with patients.

This review highlights some of the recent advances in the psychopharmacology of major depressive disorder (MDD). We synthesise evidence on emerging pharmacological therapies targeting the serotonergic system, before exploring several novel treatment targets: the glutamatergic system, the GABAergic system and inflammation. When describing new treatment avenues, we examine the evidence base and how far these new treatments are from routine practice.

Autism spectrum disorders (ASDs) are a group of lifelong neurodevelopmental disorders characterised by difficulties in social interactions and social communication, and restricted and repetitive behaviours. Relative to the general population, individuals with ASDs are likely to be overrepresented in secure psychiatric care and custodial settings. Outcomes vary and can be problematic in the context of co-occurring intellectual disability, psychiatric disorder and challenging behaviours. To date, there is little in the way of specialised clinical guidance on the prescription of psychotropic medicines for individuals with ASDs, particularly information on any differences in efficacy and/or tolerability of specific medications. This review summarises the key research to date on the prescription of psychotropic medication in ASD with and without comorbid psychiatric or neurodevelopmental disorders, within the context of the existing clinical guidance. Some critical analysis is provided to aid clinicians in following a safe, effective and individualised approach to prescribing for people with ASDs.

This article discusses dopamine partial agonism, which is the main mechanism of action of the psychiatric drugs aripiprazole, brexpiprazole and cariprazine. It outlines the principles of receptor theory and the structure of dopamine receptors; characterises agonists, antagonists and partial agonists; and summarises the dopamine hypothesis of psychosis and the role of dopamine and serotonin in depression.

Aripiprazole, brexpiprazole and cariprazine are partial dopamine (and serotonin) agonists developed as novel antipsychotics. This article discusses their pharmacology, evidence on their licensed and off-licence uses (including psychosis, mania, bipolar depression, Tourette syndrome and autism spectrum disorder) and side-effects. In schizophrenia, they have a low risk of Parkinsonism or hyperprolactinaemia, cause modest increases in body weight and are of moderate efficacy.

Partial agonists such as aripiprazole are often used in addition to a full antagonist such as amisulpride, risperidone or olanzapine in an attempt to mitigate side-effects such as sedation, hyperprolactinaemia and weight gain. However, there can be unintended consequences, including worsening of psychosis. Moreover, previous exposure to a partial agonist may impair the subsequent response to a potent antipsychotic such as haloperidol used to control symptoms of relapse. To understand the mechanisms involved, a method is needed to compare potency in the pharmacological effects of different drugs used in combinations. This article is intended to explore and explain the theoretical principles based on the dopamine hypothesis of schizophrenia. We apply the method to analyse a recently described trial in which two full antagonists (olanzapine and amisulpride) are compared individually and in combination.

Partial agonists of dopamine receptors are used in combination with full antagonists in treating psychosis, either to mitigate side-effects or in the hope of increasing effectiveness. We examine how combinations may affect the occupancy of D2/D3 dopamine receptors and explore how these can explain the outcomes in the light of the dopamine hypothesis of psychosis. The combinations considered here are from published studies combining aripiprazole with amisulpride, with risperidone in people with hyperprolactinaemia and with olanzapine to mitigate weight gain. We discuss possible worsening of symptoms by the addition of a partial agonist or switching. We also examine the potentially adverse interaction with a full antagonist such as haloperidol given during a subsequent relapse to control severe agitation.