Alcohol and substance misuse

Overview of alcohol and substance misuse

Alcohol and substance misuse disorders describe substance use that continues despite harmful consequences. These include injury, physical illness, mental illness and functional impact. Cannabis is the globally most used drug, second is amphetamines. In recreational drug users, polysubstance use is common. National alcohol intake recommendations are a maximum of 14 units per week for any gender.

The patient may present seeking help for the substance dependence itself, its harmful consequences, or substance withdrawal.

Risk factors for alcohol and substance misuse include:

• History of other alcohol or substance misuse
• History of mental illness
• Alcohol: family history of alcohol or substance misuse, anxiety traits, pre-existing anti-social behaviours
• Opioids: male, young, history of prescribed opioid therapy

Risk assessment is always important, including physical, psychological, social and neglect-related harms. If the patient is responsible for the care of children or dependents, safeguarding must be considered.

Clinical features of alcohol and substance misuse

Short and long-term effects

Clinical features associated with abuse of alcohol and key illicit drugs are shown in Table 1. Other commonly misused drugs include inhalants, hallucinogens, anabolic steroids and prescribed drugs.

Drug	General effect and toxicity	Specific long-term health risks
Alcohol	Depressant: neurological deficits in attention, concentration, consciousness Antisocial behaviour, e.g. aggression, disinhibition	Poor dental hygiene, obesity, malnutrition Gastrointestinal and liver disorders Neurological: peripheral neuropathy, Wernicke-Korsakoff syndrome
Cannabis Also, marijuana, Mary-J, pot, grass, dope, hashish	Impaired attention, concentration, memory Nausea, postural hypotension, anxiety Delirium, acute psychosis	Cognitive impairment Schizophrenia, social anxiety (↑ risk) Chronic bronchitis and exacerbation of other respiratory conditions
Amphetamine derivatives E.g. speed, crystal meth, MDMA (methylenedioxymethamphetamine), ecstasy	Cerebral oedema Skin excoriation and lesions Trismus (lockjaw), bruxism (teeth grinding)	Dental and gum disease (“meth mouth”)
Features in common: amphetamine and cocaine	Hyperarousal, hypervigilance, anxiety, paranoia, hallucinations, agitation, psychosis Hypertension, hypotension, tachycardia, chest pain, myocardial infarction Hyperthermia, sweating, mydriasis Serotonin syndrome Focal neurology, seizure, stroke, ICH Rhabdomyolysis	Cardiac: cardiomyopathy, arrhythmias, ACS, sudden cardiac death Serotonin syndrome when used with other serotonergic drugs, e.g. SSRIs Inhalation: chronic bronchitis and exacerbation of other respiratory conditions
Cocaine	Formication (tactile hallucination of “skin crawling”)	Insufflation (snorting): epistaxis, nasal septal ulceration and perforation Inhalation (smoking): suspicious burns, “crack lip” and “crack thumb” Injection: site infection, abscess, necrosis, septicaemia, blood-borne diseases (e.g. HIV, HBV, HCV)
Opioids e.g. heroin, morphine, oxycodone, opium	Euphoria and pain management Altered consciousness: confusion to coma, sedation, coma Miosis (pinpoint pupils) Respiratory depression, death	Injection: site infection, abscess, necrosis, septicaemia, blood-borne diseases (e.g. HIV, HBV, HCV) Weight loss, insomnia, memory impairment, chronic constipation, vomiting

Table 1 Short and long-term effects of alcohol and key illicit drugs

For most of the above toxicity presentations, management is supportive, with a couple of exceptions:

• Opioid toxicity: naloxone (opioid antagonist) is a life-saving treatment given in respiratory depression
• Orally ingested drugs: activated charcoal can be given within 1 h of ingestion to prevent further absorption

Wernicke-Korsakoff syndrome

This is a reversible-to-irreversible cognitive deficit syndrome resulting from thiamine deficiency, often in the context of alcohol misuse. The classic triad of symptoms in Wernicke’s encephalopathy is acute confusion, gaze palsy and gait ataxia. Korsakoff’s syndrome describes the progression to chronic irreversible cognitive impairment. They can be thought of as a single condition with a spectrum of presentations.

Withdrawal

The most important substance withdrawal syndromes are with alcohol and opioids. These can occur unexpectedly in patients admitted for unrelated reasons, as they may not openly admit to heavy alcohol or opioid use.

Substance	Features of withdrawal	Management
Alcohol	Anxiety, agitation, tremor, sweating Nausea and vomiting Tactile, auditory and visual hallucinations or sensitivity Headache Delirium tremens (medical emergency; suspect with altered consciousness): confusion, seizures (increased risk with a background of epilepsy), coma, death Onset can be <24 h after last intake of alcohol, but altered consciousness typically appears >48 h after	Long-acting benzodiazepine: chlordiazepoxide, diazepam CIWA-Ar score monitoring
Opioid	Agitation Nausea and vomiting, diarrhoea, abdominal cramps Muscle cramps Sweating Mydriasis (dilated pupils) Rarely, arrhythmias Onset can be within hours or days and varies with opioid	Long-acting opioids (methadone or buprenorphine) Treat acute symptoms, e.g. loperamide, ondansetron, ibuprofen, dicycloverine (antispasmodic)

Table 2 Alcohol and opioid withdrawal syndromes

Investigations in alcohol and substance misuse

There are no laboratory tests for harmful use or dependence, as these depend on an assessment of drinking or drug-taking behaviours. The below can support diagnosis, monitoring and treatment.

• Alcohol: 
  • LFTs: deranged in chronic alcohol use, particularly GGT elevation
  • FBC, B12, folate, thiamine: macrocytic anaemia resulting from dietary deficiencies
• Drugs: urine drug screen

Management of alcohol and substance misuse

Psychological interventions are the mainstay of treatment for many substance misuse disorders, with a supportive, non-judgemental doctor-patient relationship as the first step towards this. In alcohol and opioid misuse, pharmacological therapies can be used alongside psychological therapies, particularly for more severe cases. 

Psychological interventions

These include patient education, motivational interviewing, psychological therapies (e.g. cognitive behavioural therapy, CBT, behavioural therapy, family therapy, group drug counselling) and psychosocial services (e.g. counselling, employment, housing).

Alcohol: pharmacological interventions

At any opportunity, oral or parenteral thiamine supplementation should be provided to prevent Wernicke-Korsakoff syndrome.

Following successful alcohol withdrawal, the medications below can be continued for 6 months or longer and are used in combination with psychological interventions, not in isolation:

• First-line: acamprosate or naltrexone – reduce craving and relapse
• Second-line: disulfiram – induces unpleasant symptoms such as vomiting if alcohol is consumed. This carries additional risks of arrhythmias and hepatotoxicity

Alcohol: withdrawal management

Long-acting benzodiazepines (e.g. chlordiazepoxide, diazepam) reduce withdrawal symptoms and increase detoxification success. These can be given as a tapering-dose regimen or a variable-dose regimen based on symptoms (assessed using the CIWA-Ar scale, Clinical Institute Withdrawal Assessment of Alcohol Scale, revised).

Doses should be reduced in patients who are very young, very old or have liver impairment. Lorazepam is preferable in liver impairment as it relies less on hepatic metabolism.

Comorbidity

In concurrent alcohol misuse and substance misuse with opioids, stimulants, benzodiazepine or cannabis, both conditions should be actively treated. There is added risk of mortality in combined alcohol and opioid use.

With comorbidity of alcohol misuse and mood disorders, alcohol misuse should be treated first. If the patient has a significant and/or high risk mood disorder, psychiatry referral may be needed. Otherwise, they should be reassessed after 3-4 weeks of abstinence or reduction, as alcohol habits disrupt psychological interventions for mood.

References

• Editorial Team, BMJ Publishing Group. Overview of substance use disorders and overdose [Internet]. BMJ Best Practice. 2022 [cited 2022 Mar 1]. Available from: https://bestpractice.bmj.com/topics/en-gb/986
• Patkar AA, Lee JC, Burgess DM, Bhatia K, Musham S. Opioid use disorder [Internet]. BMJ Best Practice. 2020 [cited 2022 Mar 1]. Available from: https://bestpractice.bmj.com/topics/en-gb/200
• Karch SB, Wolff K. Cocaine use disorder [Internet]. BMJ Best Practice. 2022 [cited 2022 Mar 1]. Available from: https://bestpractice.bmj.com/topics/en-gb/199
• Stolbach A. Cocaine overdose [Internet]. BMJ Best Practice. 2021 [cited 2022 Mar 1]. Available from: https://bestpractice.bmj.com/topics/en-gb/340
• Albertson TE. Amfetamine use disorder [Internet]. BMJ Best Practice. 2020 [cited 2022 Mar 1]. Available from: https://bestpractice.bmj.com/topics/en-gb/201
• NHS. Alcohol Support [Internet]. NHS. 2018 [cited 2022 Mar 1]. Available from: https://www.nhs.uk/live-well/alcohol-support/calculating-alcohol-units/
• National Institute for Health and Care Excellence. Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence [Internet]. NICE. 2011 [cited 2022 Mar 1]. Available from: https://www.nice.org.uk/guidance/cg115/chapter/1-Guidance
• National Institute for Health and Care Excellence. Alcohol-use disorders: diagnosis and management of physical complications [Internet]. NICE. 2010 [cited 2022 Mar 1]. Available from: https://www.nice.org.uk/Guidance/CG100
• Wang GS. Cannabis (marijuana): Acute intoxication[Internet]. Burns MM, Traub SJ, Ganetsky M, editors. UpToDate. 2019 [cited 2022 Mar 1]. Available from: https://www.uptodate.com/contents/cannabis-marijuana-acute-intoxication
• Cocaine [Internet]. Talk to Frank. 2019 [cited 2022 Apr 10]. Available from: https://www.talktofrank.com/drug/cocaine
• Heroin [Internet]. Talk to Frank. 2018 [cited 2022 Apr 10]. Available from: https://www.talktofrank.com/drug/heroin

Delirium

Overview of delirium

Delirium is an acute confusional state which is common in healthcare settings and associated with worse outcomes. It can cause significant distress to patients and staff.

Patient-related risk factors include age ≥65, underlying dementia or cognitive impairment, visual or hearing impairment, frailty or immobility and current hip fracture. Screening for these risk factors at presentation to an inpatient setting allows at-risk individuals to be identified and monitored for features of delirium.

Modifiable risk factors include unfamiliar surroundings, sensory factors including lack of usual sensory aids, physiological factors (dehydration, constipation, hypoxia, pain, infection) and medical factors (severe illness of any kind, electrolyte imbalance, medications, drug or alcohol withdrawal).

Diagnosis of delirium

To meet DSM (Diagnostic and Statistical Manual of Mental Disorders)-5 criteria for a delirium diagnosis, the patient must show all 4 of the following:

• Attention deficit, e.g. poor concentration, distractible
• Cognitive deficit, e.g. memory, language, disorientation OR abnormal perceptions, e.g. hallucinations
• Acute timeline (i.e. hours or days) to develop, from their usual baseline
• Features suggesting a physiological cause, as discerned by history, examination and/or laboratory tests

The following additional features are also commonly present:

• Altered consciousness: drowsy or heightened arousal
• Altered physiological processes: altered sleep, appetite and mobility
• Behavioural change: agitation, aggression, altered communication, withdrawal
• Fluctuant nature: symptoms vary throughout the day

Delirium can be divided into clinical subtypes based on a comparison to the patient’s baseline:

• Hyperactive: increased arousal, agitation and aggression
• Hypoactive: lethargic, withdrawn, inactive or incoherent
• Mixed delirium includes features of both hyperactive and hypoactive delirium

Investigations in delirium

Brief cognitive assessments such as the 4AT or short Confusion Assessment Method (CAM) can be used to support the diagnosis, although abnormal results are not specific to delirium, and differentiating delirium from dementia (or delirium-on-dementia) can be challenging. A collateral history is particularly crucial, and also more specific tests such as the Observational Scale of Level of Arousal (over 80% specific).

After a diagnosis of delirium is made, further investigation is needed for any underlying cause. There is a wide differential diagnosis for confusion, which can be found in the Dementia section (see Presentation and diagnosis of dementia). Although an acute condition is more likely in delirium, long-term comorbidities and medications should also be reviewed.

General blood tests (including bone profile, TFTs, B12, folate) and a septic screen are usually performed. CT brain and ECG should be considered. Context-specific investigations may include:

• Drug levels for patients on digoxin, lithium or quinidine
• LP or EEG if suspecting meningitis, seizure activity or encephalopathy
• Urine drug screen

Management of delirium

Management is generally supportive. Any contributing factors should be addressed, including alcohol or drug withdrawal. Medications should be reviewed, as some may worsen delirium, e.g. sedatives, opioids, antidepressants, steroids, stimulants, anti-Parkinson drugs or anticholinergics.

If it is unclear whether the diagnosis is delirium or dementia, treatment for delirium should be initiated first. If symptoms are ongoing, risk factors should be reviewed and a diagnosis of dementia considered.

Patients with delirium may have significant distress and pose a risk to themselves or others, in which case management should be escalated as follows:

• Start conservative: verbal and non-verbal communication with the aim of de-escalation
• If necessary and safe, use pharmacological measures: low-dose haloperidol, titrated up as necessary. Antipsychotic drugs should ideally be avoided in patients with Parkinson’s disease or Lewy body dementia

References

• National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management [Internet]. NICE. 2010 [cited 2022 Mar 1]. Available from: https://www.nice.org.uk/guidance/CG103
• Pisani M, Dosa DM. Assessment of delirium [Internet]. BMJ Best Practice. 2021 [cited 2022 Mar 1]. Available from: https://bestpractice.bmj.com/topics/en-gb/241

Dementia

Overview of dementia

Dementia describes a syndrome of cognitive and functional symptoms, rather than a specific disease. Mild cognitive impairment (MCI) refers to cognitive impairment not yet impacting functional status. Patients with MCI are over five times more likely to develop dementia than those without.

Presentation and diagnosis of dementia

As well as hearing the patient’s own account, a collateral history is essential. Timeline is important: gradual onset points to a degenerative cause whereas sudden onset points to vascular or other acute causes.

Cognitive symptoms may include deficits in memory, attention or language, e.g. word-finding difficulties. Functional symptoms are generally described as a reduced ability to carry out activities of daily living (ADL).

Differential diagnosis

There is a wide differential diagnosis in dementia. This includes medical conditions that affect organs or systems other than the brain, sometimes referred to as organic causes. This is a misnomer originating in mind-body dualism, as clearly the brain is an organ.

Over 10% of dementia presentations are caused by reversible conditions; a careful approach to history, physical examination and investigations is essential to look for these. In particular, acute or subacute presentation (days to months) should raise suspicion for medical conditions originating outside the brain, including:

• Infection: neurosyphilis, tuberculous meningitis, HSV encephalitis, Lyme disease, CJD
• Inflammation: multiple sclerosis, systemic lupus erythematosus, sarcoidosis, Sjögren’s, limbic encephalitis
• Endocrine: thyroid, pituitary disease, parathyroid disease, Cushing’s
• Metabolic and nutritional: B12 or folate deficiency, uraemia, Wilson’s disease, porphyria
• Traumatic: subdural haematoma, traumatic brain injury
• Toxicity: alcohol, heavy metals, carbon monoxide sequelae, lithium
• Iatrogenic

Neurological and psychiatric differentials include:

• Alzheimer’s disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia, Korsakoff’s
• Pseudodementia: cognitive and functional deficit due to mental illness such as depression or schizophrenia
• Delirium
• Stroke, normal pressure hydrocephalus (classic triad is urinary incontinence, gait and cognitive disturbance)

Common neuropsychiatric causes of dementia

The dementia subtypes below are common and ordered by prevalence. Mixed dementia refers to dementia caused by two or more underlying aetiologies. 

	History features	Examination features
Alzheimer’s disease	Memory loss (short-term memory first) Disorientation to time and place Aphasia (word-finding difficulties) Social withdrawal Risk factors: cardiovascular, Down’s syndrome, FHx family history	Unremarkable in early stages Late disease: slow, shuffling gait and stooped posture (similar to Parkinsonian features) Mental state: anxiety, paranoia
Vascular dementia	Stepwise cognitive decline, or gradual decline after vascular event, e.g. stroke Executive function and attention deficits, apathy, disinhibition Cardiovascular risk factors: stroke, HTN, diabetes, coronary artery disease, AF, smoking, obesity etc.	Transient neurological symptoms: hemiparesis, aphasia, visual field deficits, gait abnormalities Cardiovascular findings, e.g. arrhythmia, hypertension Mental state: labile mood
Dementia with Lewy bodies (DLB)	Fluctuation in cognition, attention, arousal and speech Visual hallucinations, typically people or animals Mood disturbance: anxiety, depression Autonomic disturbance: orthostatic hypotension, syncope, falls, urinary incontinence, constipation REM sleep disorder, e.g. vivid dreams, restless legs syndrome	Onset of Parkinsonian symptoms (tremor, rigidity, bradykinesia) simultaneous with or after the cognitive decline Note that rigidity and bradykinesia can be seen in later-stage Alzheimer’s dementia
Frontotemporal dementia (FTD)	Earlier age of onset, average 45-65 years Memory deficit, disorientation and apraxia Behavioural and personality changes: social disinhibition, inappropriateness, impulsivity, apathy, withdrawal Progressive self-neglect and social withdrawal, including occupation Family history of FTD	Language fluency deficit, although the most common cause of this presentation is Alzheimer’s
Wernicke- Korsakoff syndrome	Significant alcohol history with poor nutrition Medical conditions that can impact nutrition: GI surgery, cancer, recurrent vomiting or diarrhoea	Ataxia, nystagmus Lateral gaze palsy Vestibulo-ocular reflex impaired

Table 3 Common causes of dementia with key features of the history and examination

Investigations in dementia

Bedside blood tests and imaging are needed to rule out organic causes (see Investigations in delirium).

Cognitive screening tests such as MMSE (Mini Mental State Examination) or ACE (Addenbrooke’s Cognitive Examination) should be completed before specialist referral.

Management of dementia

Non-pharmacological intervention

Management in the early stages of dementia is mainly education for the patient and their relatives or carers, in relation to what can be expected as the condition progresses and the support available.

There are various non-pharmacological interventions, namely therapies and activities aimed at preserving cognition, independence and wellbeing. These are most suited to patients with mild-to-moderate dementia.

As a progressive, irreversible condition, advance care planning is important at all stages. Patients should be counselled on options such as: Lasting Power of Attorney (LPA), advance statement (wishes, preferences, values), advance decisions to refuse treatment, and, when near end of life, their preferred place of death.

Pharmacological intervention

	Pharmacological options
	Mild or moderate	Severe
Alzheimer’s	1st line: Acetylcholinesterase (AChE) inhibitor – donepezil, galantamine, rivastigmine 2nd line: Memantine Moderate: AChE inhibitor and memantine	Memantine ± AChE inhibitor
Vascular dementia	None in isolated vascular dementia If mixed vascular and another subtype, treat as per second subtype
Dementia with Lewy bodies	1st line: Donepezil or rivastigmine 2nd line: Galantamine 3rd line: Memantine	1st line: Donepezil or rivastigmine 2nd line: Memantine
Frontotemporal dementia	None, even if mixed with another subtype

Table 4 Pharmacological interventions for different causes of dementia

It is important to deprescribe medications that may worsen cognition, especially those with anticholinergic effects. Common examples include:

• Antimuscarinics: tolterodine, darifenacin, solifenacin, oxybutynin, procyclidine
• Antipsychotics: olanzapine, chlorpromazine
• Tricyclic antidepressants: amitriptyline, nortriptyline
• Antihistamines: chlorphenamine, cetirizine, cyclizine, promethazine

Patients with dementia may have significant distress and pose a risk to themselves or others. Reversible causes should always be explored first, e.g. pain, delirium or environment. If necessary and safe, acute pharmacological measures may be required, with the lowest effective dose. Note that antipsychotic use is off label, and that these drugs should be avoided in patients with Parkinson’s disease or Lewy body dementia.

References

• National Institute for Health and Care Excellence. Dementia: assessment, management and support for people living with dementia and their carers. [Internet]. NICE. 2018 [cited 2022 Jan 15]. Available from: https://www.nice.org.uk/guidance/ng97
• NHS Choices. Symptoms of Dementia – Dementia Guide [Internet]. NHS. 2019 [cited 2022 Jan 15]. Available from: https://www.nhs.uk/conditions/dementia/symptoms/
• Liberty Protection Safeguards: what they are [Internet]. GOV.UK. 2021 [cited 2022 Jan 15]. Available from: https://www.gov.uk/government/publications/liberty-protection-safeguards-factsheets/liberty-protection-safeguards-what-they-are
• Alzheimer’s Society. How many people have dementia and what is the cost of dementia care? [Internet]. Alzheimer’s Society. 2019 [cited 2022 Jan 15]. Available from: https://www.alzheimers.org.uk/about-us/policy-and-influencing/dementia-scale-impact-numbers
• Alzheimer’s Society. What is dementia? [Internet]. Alzheimer’s Society. 2021 [cited 2022 Jan 15]. Available from: https://www.alzheimers.org.uk/about-dementia/types-dementia/what-is-dementia
• Benrimoh D, Pomerleau VJ, Demoustier A, Poulin S, Maltais J-R, Brouillette J, et al. Why We Still Use “Organic Causes”: Results From a Survey of Psychiatrists and Residents. The Journal of Neuropsychiatry and Clinical Neurosciences. 2019 Jan;31(1):57–64
• Gupta A, Tampi R, Taskiran S, Lopez J, Muralee S. Assessment of dementia [Internet]. BMJ Best Practice. 2021 [cited 2022 Mar 1]. Available from: https://bestpractice.bmj.com/topics/en-gb/242

Somatic symptom disorders

Overview of somatic symptom disorders

These controversial and poorly understood psychiatric disorders feature a complex interplay of physical symptoms, thoughts, emotions and behaviours. The patient presents with an otherwise medically unexplained physical symptom, which is thought to be caused by underlying psychological distress.

They are distinct from syndromes that involve deliberate falsification of symptoms, either for material gain (malingering) or for the psychological reward of occupying the sick role (factitious disorder, also known as Munchausen’s syndrome).

They can result in significant distress and functional deficits. Although the physical symptom may not have a traditional medical cause, the distress and suffering is always real.

Risk factors include female sex, specific personality traits (‘repressed’, i.e. reduced ability to express or describe emotion, ‘distressed’ or ‘neurotic’, i.e. increased tendency to experience negative emotions), recent or past stressors (including childhood abuse), and trauma-related psychiatric illness, e.g. PTSD, dissociative disorder.

Diagnosis of somatic symptom disorders

Presentation of somatic symptom disorders

The presence of a medically unexplained physical (or ‘somatic’) symptom is not sufficient for diagnosis. It must be accompanied by a set of maladaptive cognitive, emotional and behavioural responses for the diagnosis to apply. These responses may perpetuate or emphasise the physical symptom. 

The DSM-5 requires all three of the following criteria to be met for diagnosis of somatic symptom disorder:

• Presence of physical symptom(s) that cause distress or disruption to daily life 
• Thoughts, anxiety or time/energy spent in relation to the symptom(s), which is excessive for severity
• A continuous symptomatic state, usually for at least 6 months, even if no single symptom is continuous for this time (i.e. different symptoms may feature across this period)

The most well-known examples of somatic symptom disorders involve symptoms in the neurological domain:

• Conversion disorder: sensory or motor function deficit, e.g. limb paralysis, vision loss
• Non-epileptic seizures, also known as pseudoseizures, functional or psychogenic seizures

However, somatic symptom disorders can affect any organ system and can be non-specific. For example, unexplained cough, swallowing difficulty, abdominal pain, nausea or tiredness. Terminology is often controversial and multiple in relation to these disorders, as in the case of non-epileptic seizures, due to varying and controversial focus on the psychological origin of the condition.

Examination in somatic symptom disorders

This varies according to the symptom. In conversion disorder, examination reveals ‘pseudo-neurological’ signs:

• Variability, e.g. movement disorders with erratic patterns of movement
• Distractibility: variation in symptoms when the patient’s attention is directed elsewhere
• Inconsistency, e.g. leg weakness on formal examination that does not limit mobility as much as expected
• Unusual distribution, not in keeping with physiology, e.g. motor deficit in an abnormal distribution

Investigations in somatic symptom disorders

Somatic symptom disorder is a diagnosis of exclusion: there is no diagnostic test for it. Instead, clinicians need to first search for any objectively measurable medical conditions that could explain the condition.

The extent of investigations will heavily depend on the organ system involved. Conversion disorder is one of the best understood somatic symptom disorders because objective neurological testing is more readily available than in other body systems. For example, nerve conduction studies and electromyogram (EMG) can objectively demonstrate functional peripheral nerves and muscles to rule out disorders originating there. Video-EEG can objectively capture or rule out epileptic seizures.

Management of somatic symptom disorders

The dynamic of the doctor-patient relationship is key, including empathy for the patient’s suffering and demonstrating trust that the patient is not faking symptoms. It is also a necessary foundation for setting clear boundaries to avoid unnecessary investigations or treatments. If indulged, these can perpetuate the patient’s maladaptive response to the physical symptom and may cause harm in other ways, e.g. radiation exposure.

Cognitive behavioural therapy will help the patient to develop coping strategies and self-modulation of cognitive, emotional and behavioural responses to the physical symptom. Any other psychiatric conditions should also be treated. Physical therapy may also have a role.

References

• O’Sullivan S. It’s all in your head: true stories of imaginary illness. London: Vintage Books; 2016
• Stonnington C, Driver-Dunckley E, Noe K, Locke D. Conversion and somatic symptom disorders – Symptoms, diagnosis and treatment. [Internet]. BMJ Best Practice. 2021 [cited 2022 Apr 10]. Available from: https://bestpractice.bmj.com/topics/en-gb/989

Neuroleptic malignant syndrome and serotonin syndrome

Overview of neuroleptic malignant syndrome (NMS)

Rather than a psychiatric presentation, NMS is an uncommon iatrogenic condition resulting from the medications used to treat psychiatric conditions. It is a medical emergency and requires rapid intervention.

The single most important diagnostic factor is the presence of relevant psychotropic drug treatment:

• Presence of dopamine modulator therapy, especially if started or increased in the last 10 days: 
  • Antipsychotics, especially first generation, e.g. haloperidol
  • Antidepressants, especially tricyclic antidepressants, e.g. amitriptyline, imipramine
  • Metoclopramide, lithium, amantadine, tolcapone
• Cessation of dopamine agonists, usually Parkinson’s treatments, e.g. levodopa, bromocriptine, ropinirole

Risk factors include male sex and pre-existing brain pathology, e.g. Parkinson’s, dementia, delirium, traumatic injury.

Diagnosis of NMS

Examination in NMS

Typical features on examination include:

• Altered conscious level, e.g. agitation, confusion, coma
• Autonomic instability, e.g. hyperthermia (sweating), tachycardia, tachypnoea, labile blood pressure, drooling
• Respiratory distress
• Muscle rigidity*: lead-pipe rigidity, dysphagia

Presentation of NMS is very similar to SS, and some drugs can cause both. The main discriminators are the longer onset time in NMS from drug initiation or dose change, and features marked with *.

Investigations in NMS

NMS is a clinical diagnosis with no specific test, although the below support diagnosis and screen for complications.

Bedside tests:

• ECG: NMS and associated metabolic changes and autonomic instability can trigger cardiac issues
• Urinalysis: myoglobinuria indicates poor prognosis

Blood tests:

• FBC, U&Es, LFTs, clotting, blood cultures: for AKI, electrolyte abnormalities, infection, liver failure
• Creatine kinase (CK): 4x above upper limit of normal range due to muscle damage (non-specific)
• Blood gas: screen for respiratory failure
• Blood glucose: rule out hypoglycaemia

Tests to rule out infection or other causes of confusion should be considered, e.g. CXR, CT head, LP.

Management of NMS

The most important step is to stop the psychotropic drug trigger or, in cases triggered by cessation of dopamine agonists, to restart the dopamine agonist.

Supportive care includes IV or oral rehydration, NGT insertion if dysphagia is limiting food, fluid and medication intake, and cooling. Physical cooling measures must be used as antipyretics are ineffective. Invasive measures might be required in severe hyperthermia, such as cold fluid gastric lavage or intravascular cooling.

Rhabdomyolysis should be treated if present.

Pharmacological treatment may include:

• Sedation: with agitation, severe hyperthermia or poor toleration of therapy consider a benzodiazepine
• Dopamine agonist (bromocriptine or amantadine) or dantrolene (postsynaptic muscle relaxant)

Escalation to ICU (intensive care unit) is required with severe hyperthermia >38.5℃, ineffective ventilation due to muscle rigidity, AKI or coma.

After recovery from the acute illness psychotropic drugs should not be started for 2 weeks, and the causative agent should be avoided.

Overview of serotonin syndrome

As with NMS, this is an iatrogenic toxicity condition resulting from the medications used to treat psychiatric conditions. It shows a spectrum of severity and can be a medical emergency.

Diagnosis of SS

The single most important diagnostic factor is the presence of serotonergic drugs, particularly if started or increased in the past 24 hours. This might be in the form of:

• Serotonergic drug therapy
  • Selective serotonin reuptake inhibitors (SSRI), e.g. fluoxetine, paroxetine, sertraline, citalopram
  • Serotonin and norepinephrine reuptake inhibitors (SNRI), e.g. duloxetine, venlafaxine
  • Other antidepressants: imipramine
  • Opioids: tramadol, fentanyl
  • Monoamine oxidase inhibitors (MAO-I)
  • Others: lithium, lamotrigine, tryptophan
  • Drug interactions: multiple serotonergic drug therapy increases the likelihood of SS
• Illicit drug use, e.g. amphetamines, methamphetamine, ecstasy, cocaine
• Deliberate or accidental overdose of the above

Examination in SS

Typical features may include the following, but anywhere along the spectrum of severity:

• Altered conscious level: anxiety, agitation, confusion, coma
• Autonomic instability: hyperthermia, tachycardia, hyper/hypotension, sweating, mydriasis*
• Respiratory distress
• Neuromuscular excitability*: clonus, progression to spontaneous clonus (can appear similar to muscle rigidity or a generalised tonic-clonic seizure), tremor, hyperreflexia

Presentation of SS is very similar to NMS, and some drugs can cause both SS and NMS. The main discriminators are the shorter onset time in SS from drug initiation or dose change and features marked with *.

Investigations in SS

NMS is a clinical diagnosis with no specific test, although the below support diagnosis and screen for complications.

Bedside tests:

• ECG: autonomic instability can trigger cardiac issues
• Urine toxicology screen: for illicit drug causes of SS

Blood tests:

• FBC, U&Es, LFTs, clotting, blood cultures: screen for infection
• Blood glucose: rule out hypoglycaemia
• Consider CK if NMS is a differential diagnosis

Tests to rule out infection or other causes of confusion should be considered, e.g. CXR, CT head, LP.

Management of SS

The most important step is to stop the serotonergic drug trigger. In mild cases of SS, dose reduction is another option, and none of the below may be required.

Supportive care includes rehydration and cooling. The latter requires physical measures as antipyretics are ineffective; invasive measures for severe hyperthermia include cold fluid gastric lavage and intravascular cooling.

Pharmacological treatment may include:

• Sedation (one of the following options, from low to high SS severity): cyproheptadine (antihistamine), benzodiazepine ± morphine, propofol
• Activated charcoal: if overdose taken in preceding 1 hour
• Chlorpromazine: first-generation antipsychotic with serotonin antagonist properties (limited evidence)

Escalation to ICU may be required in severe SS for airway management and sedation.

Differential diagnosis of NMS and SS

Key differentials to consider and potentially rule out for both NMS and SS include:

• Sepsis
• Malignant hyperthermia
• Non-convulsive status epilepticus
• Hypoglycaemia
• Delirium

References

• Mitchell J, Jenkins-Welch M, Gurrera R. Neuroleptic malignant syndrome [Internet]. BMJ Best Practice. 2021 [cited 2022 Jan 15]. Available from: https://bestpractice.bmj.com/topics/en-gb/3000227
• Benzer T. Neuroleptic Malignant Syndrome: Practice Essentials, Background, Pathophysiology [Internet]. eMedicine. 2021 [cited 2022 Feb 28]. Available from: https://emedicine.medscape.com/article/816018-overview
• Isbister G. Serotonin syndrome [Internet]. BMJ Best Practice. 2019 [cited 2022 Feb 28]. Available from: https://bestpractice.bmj.com/topics/en-gb/991
• Khan SS, Kattan A. Serotonin Syndrome: Practice Essentials, Problem, Management [Internet]. eMedicine. 2019 [cited 2022 Feb 28]. Available from: https://emedicine.medscape.com/article/2500075-overview