QuestionSBA
QuestionChoice
This is incorrect because lithium levels are taken if there are concerns regarding a lithium overdose. Lithium is a mood stabiliser indicated for the long-term treatment of bipolar disorder. This question stem states that this patient has Schizophrenia. It is important to note that therapeutic levels of lithium is associated with a fine tremor whereas a coarse tremor is associated with lithium toxicity. Other features of lithium toxicity include ataxia and seizures.
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b
Lithium levels
QuestionChoice
This is incorrect because imaging is not routinely used to diagnose neuroleptic malignant syndrome. It can be used to exclude other conditions such as structural lesions within the brain, intracranial haemorrhage, or trauma. These are examples of differential diagnoses for NMS which can cause a change in mental state and extra-pyramidal symptoms. However, NMS should be the primary differential in this case given evidence of recent treatment with neuroleptics, hyperthermia, and muscle rigidity.
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CT Head
QuestionChoice
This is incorrect because blood tests are useful to show complications of NMS including acute renal failure secondary to rhabdomyolysis but they are not specific to the diagnosis.
53275
d
Urea and electrolytes
QuestionChoice
This is incorrect because an ECG is not likely to aid the diagnosis of neuroleptic malignant syndrome. It can show evidence of tachycardia because NMS can cause autonomic instability, but this is not specific.
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Electrocardiogram
QuestionChoice
This patient has neuroleptic malignant syndrome (NMS). Neuroleptic malignant syndrome is a life-threatening complication of taking dopamine antagonist medication. Most cases start within 4-14 days of commencing the medication, but some cases may occur many years after taking the same drug, at the same dose. It is likely this patient has been started on an antipsychotic medication, which has triggered his NMS. Clinical signs and symptoms include fever, muscle rigidity, confusion, rhabdomyolysis (hence the raised creatine kinase and subsequent electrolyte derangements such as hyperkalaemia and hypocalcaemia), metabolic acidosis, autonomic lability, and a raised white cell count. It takes up to 2 weeks to recover after stopping the medication. Treatment is with supportive measures (fluids, keeping the patient cool), dopamine agonists such as bromocriptine, or dantrolene.

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Creatine kinase
QuestionComment
I know we don't really need to know it in this much detail yet but how would the patient's schizophrenia be managed when the antipsychotics are stopped and then would they eventually be restarted on a different one?
55539
QuestionComment
start them on 2nd gen like aripip or olan as they have lowered risk of NMS, then usual stuff like start low dose and taper up etc.
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# Summary



# Typical antipsychotics

- Also known as 'first-generation' antipsychotics, these not only act as antagonists to D2 receptors but also on cholinergic, adrenergic and histaminergic receptors. The most commonly used medication in this class is **Haloperidol**, though other examples include Chlorpromazine and flupentixol. 
- Side effects can therefore be grouped according to receptor blockade (see below).

### Dopamine D2 Receptor Blockade:

1. **Extrapyramidal Symptoms (EPS):**
   - **Acute Dystonia:** Involuntary muscle contractions causing spasms.
   - **Akathisia:** Restlessness and an inability to sit still.
   - **Parkinsonism:** Tremors, rigidity, and bradykinesia (slowed movements).
   - **Tardive Dyskinesia:** Involuntary, repetitive movements, especially of the face.

2. **Hyperprolactinemia:**
   - Elevated levels of prolactin, leading to:
     - Menstrual irregularities in women.
     - Gynecomastia (breast enlargement) in men.
     - Sexual dysfunction in both genders.

### Other Receptors:

1. **Histamine H1 Receptor Blockade:**
   - **Sedation:** Drowsiness and sleepiness.

2. **Alpha-1 Adrenergic Receptor Blockade:**
   - **Orthostatic Hypotension:** A sudden drop in blood pressure upon standing, leading to dizziness or fainting.

3. **Muscarinic Receptor Blockade:**
   - **Anticholinergic Effects:**
     - Dry mouth.
     - Constipation.
     - Blurred vision.
     - Urinary retention.


# Atypical antipsychotics

- Also known as 'second-generation' antipsychotics, these are D2, D3 and 5-HT2A antagonists, with less overspill into other receptors. 
- As effective as typical antipsychotics (even slightly better at negative symptoms), and have a more favourable side effect profile with reduced extrapyramidal effects, but increased metabolic side-effects. 
- They are 1st line for new-onset psychosis. Examples include risperidone, quetiapine, olanzapine, aripiprazole and clozapine (see below). 

### Dopamine Receptor Blockade:

1. **D2 Receptor Blockade:**
   - **EPS (Extrapyramidal Symptoms):**
     - Atypicals generally have a lower risk of causing EPS compared to typicals.
     - Lower risk of tardive dyskinesia.

### Serotonin Receptor Blockade:

1. **5-HT2A Receptor Blockade:**
   - **Lower Risk of EPS:** Atypicals have a reduced risk of causing EPS due to serotonin receptor blockade.

### Other Receptors:

1. **Histamine H1 Receptor Blockade:**
   - **Sedation:** Although less common than with typicals, some atypicals can cause drowsiness.

2. **Alpha-1 Adrenergic Receptor Blockade:**
   - **Orthostatic Hypotension:** Some atypicals may cause a drop in blood pressure upon standing.

3. **Muscarinic Receptor Blockade:**
   - **Anticholinergic Effects:**
     - Generally less pronounced compared to typicals.
     - Mild dry mouth, constipation, or blurred vision.

### Metabolic Effects:

1. **Weight Gain:**
   - **Common Side Effect:** Atypical antipsychotics, in general, have a higher risk of causing weight gain compared to typicals.
   - **Varying Degrees:** The degree of weight gain can vary among different atypicals.

2. **Dyslipidemia and Glucose Metabolism:**
   - **Increased Risk:** Some atypicals are associated with an increased risk of dyslipidemia and impaired glucose metabolism.

3. **Prolactin Elevation:**
   - **Variable:** Some atypicals may elevate prolactin levels, leading to menstrual irregularities and sexual dysfunction.

### Other side effects:

1. **Seizures:**
   - **Low Risk:** Generally, atypicals have a lower risk of lowering the seizure threshold compared to typicals.

2. **QT Prolongation:**
   - **Potential Risk:** Some atypicals may have a mild effect on the QT interval, but the clinical significance varies.

3. **Increased risk of VTE and stroke in elderly**

### Monitoring

* Weight should be measured at the start of therapy, then weekly for the first 6 weeks, then at 12 weeks, at 1 year, and then yearly.
* Fasting blood glucose, HbA1c, and blood lipid concentrations should be measured at baseline, at 12 weeks, at 1 year, and then yearly. 
* Prolactin concentrations should also be measured at baseline.
* Before initiating antipsychotic drugs, an ECG may be required, particularly if there are cardiovascular risk factors (e.g. high blood pressure), if there is a personal history of cardiovascular disease, or if the patient is being admitted as an inpatient.
* Blood pressure monitoring before starting therapy, at 12 weeks, at 1 year and then yearly during treatment and dose titration of antipsychotic drugs.

# Clozapine

- Clozapine is an atypical antipsychotic that is indicated if there is failure of treatment of 2 other antipsychotic medication, known as treatment-resistant schizophrenia.
- Treats both positive and negative symptoms, slightly more effective than other antipsychotics.
- Important side effects include: **agranulocytosis**, neutropenia, reduced seizure threshold, myocarditis, slurred speech (due to hypersalivation), constipation (most common cause of mortality when related to clozapine use).

### Monitoring

- Due to its unique and potentially serious side effect profile, monitoring while on clozapine is very important.
- Patients should have weekly FBC (to look at white cell counts) for the first 18 weeks of treatment then fortnightly for up to one year, and then monthly.
- Blood lipids and weight should be measured at baseline, every 3 months for the first year, and then yearly.
- Fasting blood glucose should be tested at baseline, after one months’ treatment, then every 4–6 months.


# Neuroleptic Malignant Syndrome

Neuroleptic Malignant Syndrome (NMS) is a rare, but potentially life-threatening, idiosyncratic reaction to antipsychotic medications, particularly those that block dopamine receptors. It typically occurs as a response to the introduction or an increase in the dosage of neuroleptic medications.

### Clinical Features

1. **Hyperthermia:**
   - Profound elevation of body temperature is a hallmark feature.
   
2. **Altered Mental Status:**
   - Fluctuating levels of consciousness, ranging from confusion to catatonia.

3. **Autonomic Dysregulation:**
   - Dysautonomia characterized by fluctuations in blood pressure, tachycardia, and diaphoresis.

4. **Rigidity:**
   - Generalized muscle stiffness, often described as "lead-pipe" rigidity.

### Differential Diagnosis

- **Malignant Hyperthermia** - a rare, genetic condition triggered by certain medications, often during anaesthesia.

- **Serotonin Syndrome** similar to NMS but associated with serotoninergic medications. Presents with hyperthermia, autonomic dysregulation, and altered mental status.

### Investigations 

- Bloods:
	- FBC - Monitoring for potential leukocytosis or signs of infection.
   - **Creatine Kinase (CK) Levels:**  Markedly elevated CK levels are often observed due to muscle breakdown.
   - Renal and Liver Function Tests: monitoring organ function due to the potential systemic effects.
   
### Management

1. **Discontinuation of Causative Agent:**
   - Immediate cessation of the implicated neuroleptic medication.

2. **Supportive Care:**
   - Aggressive cooling measures to address hyperthermia, including cooling blankets and IV fluids to prevent renal failure.

3. **Benzodiazepines:**
   - Administering benzodiazepines to manage agitation and muscle rigidity.

4. **Dantrolene:**
   - Consideration of dantrolene, a skeletal muscle relaxant, in severe cases.

5. **Intensive Monitoring:**
   - Continuous monitoring of vital signs, fluid balance, and laboratory parameters.
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Antipsychotics
Topic
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Psychiatry
Condition
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Schizophrenia
UkmlaTopic
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Mental health
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Neuroleptic malignant syndrome is a life-threatening reaction to antipsychotic medications characterized by hyperthermia, muscle rigidity, altered mental status, and autonomic dysfunction, often with a significant elevation in creatine kinase levels due to muscle breakdown.
A 42-year-old male presents to A&E feeling unwell for the past 48 hours. He feels feverish and is concerned as he has developed a tremor. He was recently diagnosed with schizophrenia and commenced on medication last week, but he cannot remember the name or the dose. On examination, there is evidence of muscle rigidity. His AMTS is 4/10. His vital signs are: HR 103bpm, RR 21 breaths per min, O2 saturations on air 98%, BP 138/82mmHg, temperature of 38.5.

Which of the following investigations is likely to aid the diagnosis?
a