What is Buprenorphine/Samidorphan?


Buprenorphine/samidorphan (developmental code name ALKS-5461) is a combination formulation of buprenorphine and samidorphan which is under development as an add on to antidepressants in treatment-resistant depression (TRD).

ALKS-5461 failed to meet its primary efficacy endpoints in two trials from 2016. On the basis of a third study that did meet its primary endpoints, Alkermes initiated a rolling New Drug Application with the FDA.

In November 2018, a US Food and Drug Administration (FDA) panel voted against recommending approval, finding that evidence was insufficient. As such, approval of the medication was rejected in 2019. It is a κ-opioid receptor (KOR) antagonist and is being developed by Alkermes.

Brief History

ALKS-5461 was granted Fast Track Designation by the FDA for treatment-resistant depression in October 2013. During June and July 2014, three phase III clinical trials were initiated in the United States for treatment-resistant depression. Alkermes reported that the first two trials failed in 2016. In August 2017, based on the third trial, Alkermes announced the initiation of a rolling submission of a New Drug Application for ALKS-5461 to the FDA. On 31 January 2018, Alkermes submitted a New Drug Application for ALKS-5461 to the FDA for the adjunctive treatment of major depressive disorder. The submission was accepted by the FDA on 09 April 2018 after initially serving a refuse-to-file letter due to insufficient evidence of overall effectiveness.

In November 2018, an FDA advisory committee voted 21-2 against recommending approval of ALKS-5461 for MDD, setting the medication up for likely rejection. The main reason cited was insufficient evidence of effectiveness. The panel voted in favour of adequate safety having been demonstrated.



ALKS-5461 is a (1:1 ratio) combination of:

  1. Buprenorphine, a weak partial agonist of the μ-opioid receptor (MOR), antagonist/very weak partial agonist of the κ-opioid receptor (KOR), and, to a lesser extent, antagonist of the δ-opioid receptor (DOR) and weak partial agonist of the nociceptin receptor (NOP); and
  2. Samidorphan, a preferential antagonist of the MOR (but also, to a slightly lesser extent, weak partial agonist of the KOR and DOR).

The combination of these two drugs putatively results in what is functionally a blockade of KORs with negligible activation of MORs.

κ-Opioid Receptor Antagonism

It has been known since the 1980s that buprenorphine binds to at high affinity and antagonizes the KOR.

Through activation of the KOR, dynorphins, opioid peptides that are the endogenous ligands of the KOR and that can, in many regards, be figuratively thought of as functional inverses of the morphine-like, euphoric and stress-inhibiting endorphins, induce dysphoria and stress-like responses in both animals and humans, as well as psychotomimetic effects in humans, and are thought to be essential for the mediation of the dysphoric aspects of stress. In addition, dynorphins are believed to be critically involved in producing the changes in neuroplasticity evoked by chronic stress that lead to the development of depressive and anxiety disorders, increased drug-seeking behaviour, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. In support of this, in knockout mice lacking the genes encoding the KOR and/or prodynorphin (the endogenous precursor of the dynorphins), many of the usual effects of exposure to chronic stress are completely absent, such as increased immobility in the forced swimming test (a widely employed assay of depressive-like behaviour) and increased conditioned place preference for cocaine (a measure of the rewarding properties and addictive susceptibility to cocaine). Accordingly, KOR antagonists show robust efficacy in animal models of depression, anxiety, anhedonia, drug addiction, and other stress-related behavioural and physiological abnormalities.

A mouse study found that knockout of the MOR or DOR or selective pharmacological ablation of the NOP did not affect the antidepressant-like effects of buprenorphine, whereas knockout of the KOR abolished the antidepressant-like effects of the drug, supporting the notion that the antidepressant-like effects of buprenorphine are indeed mediated by modulation of the KOR by the drug (and not of the MOR, DOR, or NOP). However, a subsequent study found that the MOR may play an important role in the antidepressant-like effects of buprenorphine in animals.

Buprenorphine is not a silent antagonist of the KOR but rather a weak partial agonist. In vitro, it has shown some activation of the KOR at concentrations of ≥ 100 nM, with an Emax of 22% at 30 μM; no plateau in maximal response (EC50) was observed at concentrations up to 30 μM. Samidorphan similarly shows activation of the KOR in vitro, but to an even greater extent, with an EC50 of 3.3 nM and an Emax of 36%. As such, ALKS-5461 may possess both antagonistic and agonistic potential at the KOR. Because antagonism of the KOR seems to be responsible for the antidepressant effects of ALKS-5461, this property could in theory limit the effectiveness of ALKS-5461 in the treatment of depression.

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What is Amitriptyline/Perphenazine?


Amitriptyline/perphenazine (Duo-Vil, Etrafon, Triavil, Triptafen) is a formulation that contains the tricyclic antidepressant amitriptyline and the medium-potency typical (first-generation) antipsychotic, perphenazine. In the United States amitriptyline/perphenazine is marketed by Mylan Pharmaceuticals Inc. and Remedy Repack Inc.

Medical Uses

In the United States amitriptyline/perphenazine is indicated for the treatment of patients with:

  • Moderate-severe anxiety and/or agitation and depression
  • Depression and anxiety in association with chronic physical disease
  • Schizophrenia with prominent depressive symptoms

Adverse Effects

Common (>1% incidence) Adverse Effects Include

  • Sedation
  • Hypertension — high blood pressure.
  • Neurological impairments (such as extrapyramidal side effects which include dystonia, akathisia, parkinsonism, muscle rigidity, etc.)
  • Anticholinergic side effects such as:
    • Blurred vision
    • Constipation
    • Dry mouth
    • Nasal congestion
  • Increased appetite
  • Weight gain
  • Nausea
  • Dizziness
  • Headache
  • Vomiting

Unknown Frequency Adverse Effects Include

  • Diarrhoea
  • Alopecia — hair loss
  • Photophobia
  • Pigmentation
  • Eczema up to exfoliative dermatitis
  • Urticaria
  • Erythema
  • Itching
  • Photosensitivity (increased sensitivity of affected skin to sunlight)
  • Hypersalivation — excessive salivation.
  • Hyperprolactinaemia — elevated blood prolactin levels. This may present with the following symptoms:
    • Galactorrhoea — the release of milk that is not associated with pregnancy or breastfeeding
    • Gynaecomastia — the development of breast tissue in males
    • Disturbances in menstrual cycle
    • Sexual dysfunction
  • Pigmentation of the cornea and lens
  • Hyperglycaemia — elevated blood glucose (sugar) levels.
  • Hypoglycaemia — low blood glucose (sugar) levels.
  • Disturbed concentration
  • Excitement
  • Anxiety
  • Insomnia
  • Restlessness
  • Nightmares
  • Weakness
  • Fatigue
  • Diaphoresis — excessive/abnormal sweating.

Uncommon/Rare Adverse Effects Include

  • Tardive dyskinesia, an often irreversible adverse effect that usually results from chronic use antipsychotic medications, especially the high-potency first-generation antipsychotics. It is characterised by slow (hence tardive), involuntary, repetitive, purposeless muscle movements.
  • Neuroleptic malignant syndrome, a potentially fatal complication of antipsychotic drug use. It is characterised by the following symptoms:
    • Muscle rigidity
    • Tremors
    • Mental status change (e.g. hallucinations, agitation, stupor, confusion, etc.)
    • Hyperthermia — elevated body temperature
    • Autonomic instability (e.g. tachycardia, high blood pressure, diaphoresis, diarrhoea, etc.)
  • Urinary retention — the inability to pass urine despite having urine to pass.
  • Blood dyscrasias e.g. agranulocytosis (a potentially fatal drop in white blood cell count), leukopenia (a drop in white blood cell counts but not to as extreme an extent as agranulocytosis), neutropoenia (a drop in neutrophil [the cells of the immune system that specifically destroy bacteria] count), thrombocytopaenia (a dangerous drop in platelet [a cell found in the blood that plays a crucial role in the blood clotting process] counts), purpura (the appearance of red or purple discolouration’s of the skin that do not blanch when pressure is applied), eosinophilia (raised eosinophil [the cells of the immune system that specifically fights off parasites] count)
  • Hepatitis — inflammation of the liver
  • Jaundice
  • Pigmentary retinopathy
  • Anaphylactoid reactions
  • Oedema — the abnormal build-up of fluids in the tissues
  • Asthma
  • Coma
  • Seizures
  • Confusional states
  • Disorientation
  • Incoordination
  • Ataxia
  • Tremors
  • Peripheral neuropathy — nerve damage
  • Numbness, tingling and paraesthesia of the extremities
  • Dysarthria
  • Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
  • Tinnitus — falsely hearing ringing in the ears.
  • Alteration in EEG patterns
  • Paralytic ileus — cessation of the peristaltic waves that propel partially digested food through the digestive tract.
  • Hyperpyrexia (elevated body temperature)
  • Disturbance of accommodation
  • Increased intraocular pressure
  • Mydriasis

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What are Treatment Improvement Protocols?


Treatment Improvement Protocols (TIPs) are a series of best-practice manuals for the treatment of substance use and other related disorders.

The TIP series is published by the Substance Abuse and Mental Health Services Administration (SAMHSA), an operational division of the US Department of Health and Human Services.

SAMHSA convenes panels of clinical, research, and administrative experts to produce the content of TIPs, which are distributed to public and private substance abuse treatment facilities and individuals throughout the United States and its territories. TIPs deal with all aspects of substance abuse treatment, from intake procedures to screening and assessment to various treatment methodologies and referral to other avenues of care. TIPs also deal with administrative and programmatic issues such as funding, inter-agency collaboration, training, accreditation, and workforce development. Some TIPs also cover ancillary topics that tend to be associated with substance abuse treatment, such as co-occurring mental health problems, criminal justice issues, housing, and primary care. Once the content of a TIP has been finalised and approved by SAMHSA, the publications are printed through the US Government Printing Office.

As of February 2023, 62 TIPs have been published (although the most recent is numbered #63; see below). Most are available through the SAMHSA ‘Store.’ SAMHSA also makes newer TIPs available for download in Portable Document Format (PDF), or accessible online through the National Library of Medicine. Although TIPs frequently show up on internet auction sites and through used book sellers for varying costs, they are intended to be available for free to the public. SAMHSA does not charge for them.

The TIP Series

  • TIP 1: State Methadone Treatment Guidelines (replaced by TIP 43)
  • TIP 2: Pregnant, Substance-Using Women (replaced by TIP 51)
  • TIP 3: Screening and Assessment of Alcohol- and Other Drug-Abusing Adolescents (replaced by TIP 31)
  • TIP 4: Guidelines for the Treatment of Alcohol- and Other Drug-Abusing Adolescents (replaced by TIP 32)
  • TIP 5: Improving Treatment for Drug-Exposed Infants
  • TIP 6: Screening for Infectious Diseases Among Substance Abusers
  • TIP 7: Screening and Assessment for Alcohol and Other Drug Abuse Among Adults in the Criminal Justice System (replaced by TIP 44)
  • TIP 8: Intensive Outpatient Treatment for Alcohol and Other Drug Abuse (replaced by TIPs 46 and 47)
  • TIP 9: Assessment and Treatment of Patients with Coexisting Mental Illness and Alcohol and Other Drug Abuse
  • TIP 10: Assessment and Treatment Planning for Cocaine-Abusing Methadone-Maintained Patients
  • TIP 11: Simple Screening Instruments for Outreach for Alcohol and Other Drug Abuse and Infectious Diseases
  • TIP 12: Combining Substance Abuse Treatment with Intermediate Sanctions for Adults in the Criminal Justice System (replaced by TIP 44)
  • TIP 13: Role and Current Status of Patient Placement Criteria in the Treatment of Substance Use Disorders
  • TIP 14: Developing State Outcomes Monitoring Systems for Alcohol and Other Drug Abuse Treatment
  • TIP 15: Treatment for HIV-Infected Alcohol and Other Drug Abusers (replaced by TIP 37)
  • TIP 16: Alcohol and Other Drug Screening of Hospitalised Trauma Patients
  • TIP 17: Planning for Alcohol and Other Drug Abuse Treatment for Adults in the Criminal Justice System (replaced by TIP 44)
  • TIP 18: The Tuberculosis Epidemic: Legal and Ethical Issues for Alcohol and Other Drug Treatment Providers
  • TIP 19: Detoxification From Alcohol and Other Drugs (replaced by TIP 45)
  • TIP 20: Matching Treatment to Patient Needs in Opioid Substitution Therapy (replaced by TIP 43)
  • TIP 21: Combining Alcohol and Other Drug Abuse Treatment With Diversion for Juveniles in the Justice System
  • TIP 22: LAAM in the Treatment of Opiate Addiction (replaced by TIP 43)
  • TIP 23: Treatment Drug Courts: Integrating Substance Abuse Treatment With Legal Case Processing
  • TIP 24: A Guide to Substance Abuse Services for Primary Care Clinicians
  • TIP 25: Substance Abuse Treatment and Domestic Violence
  • TIP 26: Substance Abuse Among Older Adults
  • TIP 27: Comprehensive Case Management for Substance Abuse Treatment
  • TIP 28: Naltrexone and Alcoholism Treatment
  • TIP 29: Substance Use Disorder Treatment For People With Physical and Cognitive Disabilities
  • TIP 30: Continuity of Offender Treatment for Substance Use Disorders from Institution to Community
  • TIP 31: Screening and Assessing Adolescents for Substance Use Disorders
  • TIP 32: Treatment of Adolescents with Substance Use Disorders
  • TIP 33: Treatment for Stimulant Use Disorders
  • TIP 34: Brief Interventions and Brief Therapies for Substance Abuse
  • TIP 35: Enhancing Motivation for Change in Substance Abuse Treatment
  • TIP 36: Substance Abuse Treatment for Persons with Child Abuse and Neglect Issues
  • TIP 37: Substance Abuse Treatment for Persons with HIV/AIDS
  • TIP 38: Integrating Substance Abuse Treatment and Vocational Services
  • TIP 39: Substance Abuse Treatment and Family Therapy
  • TIP 40: Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction
  • TIP 41: Substance Abuse Treatment: Group Therapy
  • TIP 42: Substance Abuse Treatment for Persons With Co-Occurring Disorders
  • TIP 43: Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs
  • TIP 44: Substance Abuse Treatment for Adults in the Criminal Justice System
  • TIP 45: Detoxification and Substance Abuse Treatment
  • TIP 46: Substance Abuse: Administrative Issues in Outpatient Treatment
  • TIP 47: Substance Abuse: Clinical Issues in Intensive Outpatient Treatment
  • TIP 48: Managing Depressive Symptoms in Substance Abuse Clients During Early Recovery
  • TIP 49: Incorporating Alcohol Pharmacotherapies Into Medical Practice
  • TIP 50: Addressing Suicidal Thoughts and Behaviours in Substance Abuse Treatment
  • TIP 51: Substance Abuse Treatment: Addressing the Specific Needs of Women
  • TIP 52: Clinical Supervision and Professional Development of the Substance Abuse Counsellor
  • TIP 53: Addressing Viral Hepatitis in People With Substance Use Disorders
  • TIP 54: Managing Chronic Pain in Adults With or in Recovery From Substance Use Disorders
  • TIP 55: Behavioural Health Services for People Who Are Homeless
  • TIP 56: Addressing the Specific Behavioural Health Needs of Men
  • TIP 57: Trauma-Informed Care in Behavioural Health Services
  • TIP 58: Addressing Foetal Alcohol Spectrum Disorders (FASD)
  • TIP 59: Improving Cultural Competence
  • TIP 60: Using Technology-Based Therapeutic Tools in Behavioural Health Services
  • TIP 61: Behavioural Health Services for American Indians and Alaska Natives
  • TIP 63: Medications for Opioid Use Disorders

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An Overview of the Ladywell Unit


University Hospital Lewisham (formerly known as Lewisham Hospital) is a teaching hospital run by Lewisham and Greenwich NHS Trust and serving the London Borough of Lewisham. It is now affiliated with King’s College London and forms part of the King’s Health Partners academic health science centre. It is situated on Lewisham High Street between Lewisham and Catford.

Facilities at University Hospital Lewisham

The hospital offers a wide range of services including adult and children’s Emergency departments and specialist services including neonatology, paediatric surgery, cystic fibrosis treatment, haemophilia treatment and Ear Nose and Throat (ENT) services. The hospital provides teaching and training for medical staff and gained university status in 1997.

The Ladywell Unit is an inpatient unit of South London and Maudsley NHS Foundation Trust but physically located at University Hospital Lewisham and managed by Lewisham and Greenwich NHS Trust.

Overview of the Ladywell Unit


  • Adult mental illness.
  • Community mental health services.
  • Inpatient mental health services.
  • Old age psychiatry.
  • Older people’s services.
  • Perinatal community mental health service.
  • Psychiatric intensive care unit.

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An Overview of the National Psychosis Unit


The National Psychosis Unit is a national treatment centre for patients with schizophrenia and other psychotic disorders, in the United Kingdom. The unit is a tertiary referral centre in the National Health Service. It is located at the Bethlem Royal Hospital, part of the South London and Maudsley NHS Foundation Trust. It is closely affiliated to the Institute of Psychiatry, King’s College London, and forms part of the Psychosis Clinical Academic Group of King’s Health Partners.

Brief History

The Unit was set up in the early 1990s. It was one of the first units in the UK to offer the antipsychotic drug clozapine, following its reintroduction in the UK in 1990.


The service has a multidisciplinary team of doctors, nurses, pharmacists and psychologists, many of whom work part of their time as clinical scientists and researchers, investigating the causes of psychotic disorders, and the effectiveness of both existing and new treatments.

Sir Robin Murray, Professor of Psychiatric Research at the Institute of Psychiatry at King’s College London, is a prominent member of staff at National Psychosis Unit.


The National Psychosis Unit specialises in evidence-based treatment for people with schizophrenia, bipolar disorder and other similar disorders, particularly where local treatment has been unsuccessful or only partially successful in relieving symptoms. Anyone receiving NHS treatment can access the service free of charge following a referral by the person’s psychiatrist or general practitioner

The service provides second opinions on medication, diagnosis or any other aspect of care. The service has an outpatient clinic and 24-bedded inpatient facility. As well as pharmaceutical treatments, there is a strong focus on psychological treatments, rehabilitation and recovery, and reducing the risk of readmission through exploring what has led to breakdowns in the past and how to avoid this happening in future. The Unit also hosts research into the treatment of psychosis, including clinical trials of new treatments for psychosis. The National Psychosis Carers’ Group, which meets monthly, supports the carers and families of people with psychosis and allows them a forum for discussion.

Links with Other Organisations

The National Psychosis Unit has strong links with the Department of Psychosis Studies at the Institute of Psychiatry, King’s College London. The Unit also has longstanding links with mental health charities, including Rethink and SANE.


The Unit won the Hospital Doctor Psychiatric Team of the Year Award in 1997.

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An Overview of Lambeth Hospital


Lambeth Hospital is a mental health facility in Landor Road, South London. It was previously known as the “Landor Road hospital” and is now operated by the South London and Maudsley NHS Foundation Trust and is affiliated with King’s College London’s Institute of Psychiatry. It is also part of the King’s Health Partners academic health science centre and the National Institute for Health and Care Research (NIHR) Biomedical Research Centre for Mental Health.

Brief History

There were originally two hospitals on the site:

  • The Stockwell Smallpox Hospital, which opened in 1871; and
  • The Stockwell Fever Hospital, which opened shortly thereafter.

These two hospitals combined in 1884 to form the South Western Fever Hospital.

It joined the National Health Service in 1948 as the South Western Hospital and contained an out-patient facility, known as the “Landor Road Day Hospital” for psychiatric patients. It closed in the early 1990s and, following demolition in 1996, was replaced by a new mental health facility known as Lambeth Hospital. The new mental health facility was named after a previous Lambeth Hospital, which had opened on the site of Lambeth Workhouse in Renfrew Road, in 1922.

In 2014, the Triage ward of the new hospital was featured in an episode of the Channel 4 documentary series Bedlam.

The NHS South East London Clinical Commissioning Group announced in May 2020 that Lambeth hospital would close with the services moved to a new building on the Maudsley Hospital site. South London and Maudsley NHS Foundation Trust announced a consultation in July 2020 on proposals to sell land so that 570 houses could be built on the site.


Lambeth Hospital is situated in Stockwell, within walking distance of Clapham High Street railway station and Clapham North tube station. The hospital site includes the following buildings:

  • Bridge House: Spring Ward (Female Forensic, Medium Secure Service)
  • Oak House: Luther King Ward (Male Acute), Nelson Ward (Female Acute), Rosa Parks Ward (Mixed Acute) and Eden Psychiatric Intensive Care Unit (Male PICU)
  • Reay House: Early Intervention in Psychosis Unit and Tony Hillis Unit
  • Mckenzie House (Ward in the Community)
  • Orchard House (Outpatient Services)
  • Landor House

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An Overview of the Institute of Psychiatry, Psychology and Neuroscience


The Institute of Psychiatry, Psychology and Neuroscience (IoPPN) is a research institution dedicated to discovering what causes mental illness and diseases of the brain. In addition, its aim is to help identify new treatments for them and ways to prevent them in the first place. The IoPPN is a faculty of King’s College London, England, previously known as the Institute of Psychiatry (IoP).

The institute works closely with South London and Maudsley NHS Foundation Trust. Many senior academic staff also work as honorary consultants for the trust in clinical services such as the National Psychosis Unit at Bethlem Royal Hospital.

The impact of the institute’s work was judged to be 100% ‘world-leading’ or ‘internationally-excellent’ in the Research Excellence Framework (REF 2014). The research environment of the institute was also rated 100% ‘world-leading’. King’s College London was rated the second for research in Psychology, Psychiatry and Neuroscience in REF 2014. According to the 2021 US News Ranking, King’s College London was ranked second in the world in Psychiatry and Psychology.

Brief History

The IoPPN shares a great deal of its history with the Maudsley Hospital, with which it shares the location of its main building. It was part of the original plans of Frederick Mott and Henry Maudsley – inspired by the Munich institute of Emil Kraepelin – that the hospital would include facilities for teaching and research in 1896. In 1914, London County Council agreed to establish a hospital in Denmark Hill and Mott’s plan began to take shape. The Maudsley Hospital was opened in 1923 as a result of a donation by Henry Maudsley.

Originally established as the “Maudsley Hospital Medical School” in 1924, it changed its name to the Institute of Psychiatry in 1948, with Aubrey Lewis appointed to the inaugural Chair of Psychiatry (which he held until his retirement in 1966). The main Institute building was opened in 1967 and contains lecture theatres, administrative offices, library and canteen.

In 1959 a group of genetic researchers led by Eliot Slater were given Medical Research Council funding to establish themselves as the ‘MRC Psychiatric Genetics Unit’. Although this closed down in 1969, psychiatric genetics continued, eventually as the MRC Social, Genetic and Developmental Psychiatry Centre (SGDP Centre) which moved into new purpose-built building in 2002.

In 1997, the institute had split from the Maudsley and become instead a school of King’s College London. The Henry Wellcome building was opened in 2001 and houses most of the IoPPN’s psychology department. In 2004, a new Centre for Neuroimaging Sciences (CNS) was opened which provides offices, lab space, and access to two MRI scanners for neuroimaging research. In 2014 the institute was renamed to the Institute of Psychiatry, Psychology and Neuroscience (IoPPN), as the remit of the institute was broadened to include all brain and behavioural sciences.



The Addictions Department specialises in research into tobacco, alcohol and opiate addiction policy and treatment. In March 2010 the addiction research unit and the sections of alcohol research, tobacco research and behavioural pharmacology were brought together to form the current The Addictions Department, also known as the National Addiction Centre (NAC).


This department provides advice in the interpretation and use of statistical techniques in psychological research. They work closely with members of the Neuroimaging section in their work using brain scanners.

The Biostatistics department opened in 1964, then as the Biometrics Unit. The department holds particular expertise in multivariate statistical methods for measurement, life-course epidemiology and the analysis of experimental, genetic and neuropsychiatric data.

The department provides both introductory and advanced training in applied statistical methodology, collaborate on studies of mental health based here and internationally, and undertake research in relevant applied methodology.

The department also hosts the UKCRN accredited King’s Clinical Trials Unit which provides randomisation, data management, analysis and trial management – all of which are available to researchers across King’s Health Partners. The CTU provides support to both medicinal and non-medicinal clinical trials assisting researchers in the conduct of carrying out clinical trials.

Child and Adolescent Psychiatry

The department is dedicated to the study of developmental disorders such as ADHD, clinical depression, autism and learning difficulties. The department has close links with the Michael Rutter Centre for Children and Young People at the Maudsley Hospital which has a number of specialist services for children and adolescents.

Forensic Mental Health Science

Forensic Mental Health Science is the study of antisocial, violent, and criminal behaviours among people with mental disorders. The department’s research focuses on antisocial behaviour as it appears in people with either major mental disorders or personality disorders. The department is closely allied to the Forensic Psychiatry Teaching Unit.


Researchers in this department carry out a range of studies into diseases such as Alzheimer’s disease and motor neuron disease. The Institute of Psychiatry now houses the Medical Research Council Centre for Neurodegeneration Research, where pioneering research is conducted investigating disease of the CNS. The Department of Clinical Neuroscience in Windsor Walk also contains the MRC London Neurodegenerative Disease Brain Bank.

Department of Neuroimaging and Centre for Neuroimaging Sciences

The Centre for Neuroimaging Sciences (CNS) is a joint venture of the King’s College London Institute of Psychiatry and the South London and Maudsley NHS Trust (SLAM). Completed in early 2004, the centre provides an interdisciplinary research environment.

The Clinical Neuroimaging Department, situated at the Maudsley Hospital, provides a full range of neuroradiographic imaging services, including Magnetic Resonance Imaging (MRI). Within the CNS, the academic Department of Neuroimaging’s Major Research Facility (MRF) manages a range of MRI facilities for research studies. The Department of Neuroimaging also runs an EEG laboratory, re-launched in 2010.


The IoPPN Psychology department was founded in 1950. The department conducts research in neuropsychology, forensic psychology, and cognitive behavioural therapy. Hans Eysenck set up the UK’s first qualification in clinical psychology in the department, which has now evolved into a three-year doctoral ‘DClinPsych’ qualification.

Clinically, members of the department offer expert services to the Maudsley Hospital, Bethlem Royal Hospital, King’s College Hospital, Guy’s Hospital and community mental health teams in the South London area. Members of the department also teach psychology to undergraduate medical students from the United Medical and Dental Schools of Guy’s and St Thomas’ Hospitals. Psychiatric geneticist Peter McGuffin was awarded a fellowship at the institute.

Psychological Medicine

The Department of Psychological Medicine, chaired by Professor Ulrike Schmidt, addresses many of the commonest mental disorders which affect adults including depression, anxiety, post traumatic stress disorder, eating disorders, somatoform disorders, and medically unexplained symptoms and syndromes. Its research spans basic science, experimental medicine, epidemiology and public policy. It includes the King’s Centre for Military Health Research, led by the department’s former chair, Professor Simon Wessely, and is responsible for studying the psychological impacts of the 2003 Iraq War. The department also contains a programme of work on liaison psychiatry and studies the many complex interactions between mental and physical illness.

Social, Genetic and Developmental Psychiatry

The SGDP centre is a multi-disciplinary research centre devoted to the study of the interplay between “nature” (genetics) and “nurture” (environment) as they interact in the development of complex human behaviour. Research at the SGDP acknowledges that there is no simple solution to the “nature versus nurture” debate; instead, expertise is combined across fields such as social epidemiology, child and adult psychiatry, developmental psychopathology, development in the family, personality traits, cognitive abilities, statistical genetics, and molecular genetics. In this way it is hoped that a greater understanding can be achieved in risk factors that might predispose an individual to depression, ADHD, or autism.

Brief History

The MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre was founded in 1994 by the Medical Research Council, in partnership with the Institute of Psychiatry (now a school of King’s College London).

The research in social, genetic and developmental psychiatry have already existed at the Institute of Psychiatry since its establishment in 1948. However, the streams of research were not integrated and there have even been times when genetic researchers and social psychiatrists were in a state of hostility. The intellectual warfare between nature and nurture reached its peak in the 1960s and 1970s.

Aubrey Lewis, who was the first Professor of Psychiatry at the institute and the director of the MRC Social Psychiatry Research Unit (first MRC unit at the institute), noticed that social psychiatry was a broad field that included both biological substrate of disorders and social causes. Eliot Slater, the ‘founding father’ of psychiatric genetics in the United Kingdom, was encouraged by Lewis to study genetics in 1930s. In 1959, Slater established another MRC unit at the institute (MRC Psychiatric Genetics Unit), but the unit was closed in 1969 on Slater’s retirement. In 1984, MRC Child Psychiatry Unit was established at the Institute of Psychiatry by Michael Rutter, a member in the MRC Social Psychiatry Research Unit led by Lewis. The unit brought together experts in many overlapping fields, and the mix proved highly successful as the unit had a major impact on child psychiatric research throughout the world.

The MRC Social Psychiatry Research Unit was closed in 1993. The MRC and the institute found that there was a need for refocusing and reintegration with other strands of research including psychiatric genetics and disorders of adult life. Rutter and David Goldberg discussed with the MRC about the establishment of an interdisciplinary research centre that could comprehensively study the interplay of nature and nurture in the development of psychiatric disorders. In 1994, MRC SGDP Centre was established in Denmark Hill, and Rutter was appointed as the first director of the centre. The SGDP Centre has moved into its new purpose-built building in 2002.

Psychosis Studies

The department is the most highly cited group of scientists working on schizophrenia and related disorders. Work focuses on integrating cognitive measures and multimodal neuroimaging techniques, with perinatal, genetic and developmental data. The central aim is to characterise the core pathophysiological dimensions of schizophrenia and bipolar disorder. The section has initiated or participated a number of such treatment studies of new atypical antipsychotics and potential mood stabilising medication and is also developing computerised and web-based applications for disease self-management.

Maurice Wohl Clinical Neuroscience Institute

The Maurice Wohl Clinical Neuroscience Institute is a centre for neuroscience research opened by The Princess Royal in 2015. It is one of the leading neuroscience institutes in the world. The centre is named after British philanthropist Maurice Wohl, who supported many medical projects and had a long association with King’s College London, and was funded by several philanthropic donors, organisations and King’s Health Partners.

The Maurice Wohl Clinical Neuroscience Institute focuses on the development of new treatments to patients affected by neurodegenerative diseases (such as Alzheimer’s disease, Parkinson’s disease and motor neurone disease), mental disorders (depression, schizophrenia) and neurological diseases (including epilepsy and stroke), and the understanding of disease mechanisms. The research institute has 250 clinicians and research scientists from neuroimaging, neurology, psychiatry, genetics, molecular and cellular biology and drug discovery.

The current three major goals of the institute is to determine the underlying genetic and environmental risk factors for disease, to identify tests for early diagnosis and biomarkers that measure disease progression, and to develop informative cellular and animal disease models of disease to accelerate drug discovery.


Approximately 70% of the IoPPN’s income comes from the research it conducts. Approximately 20% is from clinical work performed for the South London and Maudsley NHS Foundation Trust. Approximately 10% of gross income is from taught courses offered to postgraduate students.

Sources include the government’s National Institute for Health and Care Research (NIHR) and Higher Education Funding Council for England, grant-giving bodies such as the Medical Research Council (UK) and the Wellcome Trust, as well as other governmental, charitable and private-sector organisations. Individual research teams secure around £130 million of funds for their projects each year. Many projects are carried out in partnership with other university and health services, charities and private companies.

The IoPPN and the pharmaceutical company Lundbeck are led one of the largest ever academic-industry collaborations in research, known as NEWMEDS – Novel Methods leading to New Medications in Depression and Schizophrenia. The project is part of the Innovative Medicines Initiative developed by the European Federation of Pharmaceutical Industries and Associations and the European Commission. NEWMEDS aims to facilitate the development of new psychiatric medications by bringing top scientists and academics together in partnership with nearly every major global drug company.

Another key project is the KCL and Janssen led pre competitive public private consortium RADAR-CNS (Remote Measurement of Disease and Relapse in Central Nervous System Disorders), which uses smartphones and wearable devices to track clinical outcomes in disorders like depression, multiple sclerosis and epilepsy.

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An Overview of South London and Maudsley NHS Foundation Trust


South London and Maudsley NHS Foundation Trust (also known as SLaM), is an NHS foundation trust based in London, England, which specialises in mental health. It comprises:

SLaM forms part of the institutions that make up King’s Health Partners, an academic health science centre. In its most recent inspection of the Trust, the CQC gave SLaM a ‘good’ rating overall, but a ‘requires improvement’ rating in area of safety. In 2019, Southwark Coroner’s Court ruled that SLaM was guilty of “neglect and serious failures” in relation to the death of a patient in 2018. In 2020, a further investigation into the Trust’s conduct was opened following the death of a patient in its care.


Each year the South London and Maudsley NHS Foundation Trust provides about 5,000 people with hospital treatment and about 40,000 people with community services. In partnership with King’s College London, the Trust has major research activities. This academic partnership enables the Trust to develop new treatments and to provide specialist services to people from across the UK such as the National Psychosis Unit at Bethlem Royal Hospital. The Trust forms part of the King’s Health Partners academic health science centre and together with the Institute of Psychiatry, Psychology and Neuroscience at King’s College London and University College London is host to the UK’s only specialist National Institute for Health Research Biomedical Research Centre for mental health. In 2009/10 the Trust had a turnover of £370 million.

The Trust’s work on promoting mental health and well-being, developed in partnership with the new economics foundation, has featured in the national media.

It was named by the Health Service Journal as one of the top hundred NHS trusts to work for in 2015. At that time it had 4218 full-time equivalent staff and a sickness absence rate of 3.74%. 58% of staff recommend it as a place for treatment and 59% recommended it as a place to work.

As of 2018, the trust employed 5,328 staff.

Select Chronology

The following are some important historical dates:

  1. The Priory of St Mary of Bethlehem, Bishopsgate, was founded on land given by Alderman Simon Fitzmary. It later became a place of refuge for the sick and infirm. The names ‘Bethlem’ and ‘Bedlam’, by which it came to be known, are early variants of ‘Bethlehem’. It is first referred to as a hospital for ‘insane’ patients in 1403, after which it has a continuous history of caring for people with mental distress.
  2. In 1867, the Southern Districts Hospital (or Stockwell Fever Hospital as it became known) opened on the site which is today known as Lambeth Hospital.
  3. Henry Maudsley wrote to the London County Council offering to contribute £30k towards the costs of establishing a “fitly equipped hospital for mental diseases.” The Maudsley initially opened as a military hospital in 1915 to treat cases of shell shock and became a psychiatric hospital for the people of London in 1923.
  4. Bethlem Royal Hospital moved to a new site at Monks Orchard, where it has been situated to this day.
  5. With the introduction of the National Health Service in 1948, the Bethlem Royal Hospital and Maudsley Hospital were merged to form a postgraduate psychiatric teaching hospital. The Maudsley’s medical school became the Institute of Psychiatry.
  6. Sister Lena Peat and Reginald Bowen became the first community psychiatric nurses, following up patients at home who had been discharged from Warlingham Park Hospital in Croydon.
  7. The Ladywell Unit, located at University Hospital Lewisham, was refurbished for use by adult inpatient mental health services. The development brought together inpatient services which had previously been spread across other hospital sites (Hither Green, Guy’s and Bexley).
  8. South London and Maudsley NHS Trust was formed – providing mental health and substance misuse services across Croydon, Lambeth, Lewisham and Southwark; substance misuse services in Bexley Greenwich and Bromley; and national specialist services for people from across the UK.
  9. South London and Maudsley became the 50th NHS Foundation Trust in the UK under the Health and Social Care [Community Health and Standards] Act 2003.
    2007 The Maudsley Hospital closed its 24-hour emergency mental health clinic, amidst protest from patient groups and politicians who continued campaigning for several years for a promised replacement at nearby KCL Hospital.
  10. South London and Maudsley is part of one of the five Academic Health Sciences Centres (AHSCs) in the UK to be accredited by the Department of Health. King’s Health Partners AHSC consists of SLaM, King’s College London, and Guy’s and St Thomas’ and King’s College Hospital NHS Foundation Trusts.
  11. South London and Maudsley is fined by the Parliamentary and Health Service Ombudsman for its failure to properly assess mental capacity.


The Chief Executive appointed in 2013 is Matthew Patrick, a psychiatrist with a background in psychoanalysis who was formerly head of the Tavistock and Portman NHS Foundation Trust.

Former Member of Parliament Sir Norman Lamb was appointed chair of the trust in December 2019.


The Trust provides a wide range of mental health and substance misuse services. The Trust provides care and treatment for a local population of 1.3 million people in south London, as well as specialist services for people from across the country. The Trust provides mental health services for people of all ages from over 100 community sites in south London, three psychiatric hospitals (the Bethlem Royal Hospital, Lambeth Hospital and the Maudsley Hospital) and specialist units based at other hospitals.

In March 2016 it established a joint venture with the Macani Medical Centre in Abu Dhabi to provide child and adolescent services with specialisms in autism, Obsessive Compulsive Disorder and eating disorders. Maudsley International also signed an agreement with the Ministry of Public Health in Qatar for expert advice to help advance Qatar’s national mental health strategy.

It established a joint venture limited liability partnership with Northumbria Healthcare Facilities Management, run by Northumbria Healthcare NHS Foundation Trust in 2019. This will run its private and international work, develop its capital assets and employ its facilities staff. It will initially employ 192 existing staff. It plans rapid growth in the United Arab Emirates (UAE) and China.


255 patients were injured in 2016-17 through use of restraints on psychiatric patients in South London and Maudsley NHS Foundation Trust. This was the third largest number in England, There were more injuries in Southern Health NHS Foundation Trust and Mersey Care NHS Foundation Trust. Critics say restraints are potentially traumatic even life threatening for patients.


The Trust’s research activities take place in close partnership with the Institute of Psychiatry, King’s College London and University College London. In the 2008 Research Assessment Exercise the Institute was judged to have the highest research power of any UK institution within the areas of psychiatry, neuroscience and clinical psychology.

Biomedical Research Centre

The Trust manages the NIHR Maudsley Biomedical Research Centre, the UK’s only Specialist Mental Health Biomedical Research Centre, in partnership with the Institute of Psychiatry at King’s College London. The Centre, which is based on the Maudsley Hospital campus, is funded by the National Institute for Health and Care Research (NIHR). Its aim is to speed up the pace that latest medical research findings are turned into improved clinical care and services.

The team at the Centre are working towards ‘personalised medicine’ – developing treatments based on individual need. The aim is to diagnose illness more effectively and much earlier, assess which treatments will work best for an individual and then tailor the care they receive accordingly.

The BRC’s development of an advanced computer programme to accurately detect the early signs of Alzheimer’s disease from a routine clinical brain scan was reported in the media in 2011. The ‘Automated MRI’ software automatically compares or benchmarks someone’s brain scan image against 1200 others, each showing varying stages of Alzheimer’s disease. Another study has concerned the reduced life expectancies of people diagnosed with different mental illnesses.

In 2011 the Department of Health announced that the Trust and the Institute of Psychiatry, King’s College London would receive a further £48.8m to continue running the Biomedical Research Centre for Mental Health for a further five years from 01 April 2012. An additional £4.5m was awarded to the Trust to launch for a new NIHR Biomedical Research Unit for Dementia.

King’s Health Partners

The Trust is a member of the King’s Health Partners academic health sciences centre, together with King’s College London, Guy’s and St Thomas’ NHS Foundation Trust and King’s College Hospital NHS Foundation Trust.

In December 2013 it was announced that a proposed merger with Guy’s and St Thomas’ and King’s College Hospitals had been suspended because of doubts about the reaction of the Competition Commission.

National Addiction Centre

In partnership with the Institute of Psychiatry, Psychology and Neuroscience, King’s College London, the Trust runs the National Addiction Centre (NAC), which aims to develop new treatment services for alcohol, smoking and drug problems. This work ranges from trials of new therapies and preventative treatments, to studies seeking to understand the genetic and biological basis of addictive behaviour. An example of research conducted is the Randomised Injecting Opioid Treatment Trial (RIOTT).


The services provided by the Trust feature in a four-part observational television documentary to be broadcast on Channel Four in Autumn 2013. Produced by the makers of 24 Hours in A&E, Bedlam focuses on the work of the Anxiety Disorders Residential Unit at Bethlem Royal Hospital, the Triage ward at Lambeth Hospital, adult community mental health services in Lewisham and services for people over the age of 65.

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An Overview of Cassel Hospital


The Cassel Hospital is a psychiatric facility in a Grade II listed building at 1 Ham Common, Richmond, Ham in the London Borough of Richmond upon Thames. It is run by the West London NHS Trust.

Brief History

The Hospital

The hospital was founded and endowed by Ernest Cassel in England in 1919. It was initially for the treatment of “shell shock” victims (aka combat stress reaction). Originally at Swaylands in Penshurst, Kent, it moved to Stoke-on-Trent during the Second World War. In 1948 it relocated to its present site at No. 1 Ham Common, Ham.

The Building

The present hospital was originally a late 18th-century house known as Morgan House after its owner, philanthropist and writer, John Minter Morgan. Morgan died in 1854 and is buried in nearby St Andrew’s Church, Ham. In 1863 it became home to the newly married Duc de Chartres. In 1879 it became West Heath Girls’ School. The school moved to its present site in Sevenoaks, Kent in the 1930s, and the building became the Lawrence Hall Hotel until its purchase by the Cassel Foundation in 1947. The building was Grade II listed in 1950.


The hospital developed approaches informed by psychoanalytic thinking alongside medicinal interventions, techniques of group and individual psychotherapy. It was here that Tom Main along with Doreen Wedell pioneered the concept of a therapeutic community in the late 1940s. Together they pioneered & developed the concept of psychosocial nursing. By promoting and being proud of the role of the nurse – rather than try to imitate therapists; working alongside the patient in everyday activities, Weddell & Main developed a whole new way of working that reduced dependence upon services and fostered patient’s working collaboratively. Nurses were supported and taught to understand their reparative need, to challenge their sense of omnipotence and to rely on the patient group as the most useful resource. In 1948 Eileen Skellern came for her training and joined the staff in 1949.

The hospital formally established a research department in 1995 and has collaborative relationships with University College London, Imperial College and the Centre for the Economics of Mental Health at the Institute of Psychiatry, London. It is now a psychotherapeutic community which provides day, residential, and outreach services for young people and adults with severe and enduring personality disorders.

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What is Milieu Therapy?


Milieu therapy is a form of psychotherapy that involves the use of therapeutic communities.


Patients join a group of around 30, for between 9 and 18 months. During their stay, patients are encouraged to take responsibility for themselves and the others within the unit, based upon a hierarchy of collective consequences. Patients are expected to hold one another to following rules, with more senior patients expected to model appropriate behavior for newer patients. If one patient violates the rules, others who were aware of the violation but did not intervene may also be punished to varying extents based upon their involvement.

Milieu therapy is thought to be of value in treating personality disorders and behavioural problems, and can also be used with a goal of stimulating the patient’s remaining cognitive-communicative abilities.

Organisations known to use milieu therapy include:

  • Cassel Hospital, in London, UK.
  • Forest Heights Lodge in Evergreen, Colorado, US.
  • The United States Veteran’s Administration, US.
  • The Kansas Industrial School for Girls in Beloit, Kansas, US.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Milieu_therapy >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.