Severe Mental Illness — MCQs
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A 27-year-old woman with bipolar affective disorder presents for medication review. She has had three manic episodes and two severe depressive episodes over the past 4 years. She has previously taken lithium (stopped due to tremor and polyuria) and sodium valproate (stopped due to significant weight gain and hair loss). She is currently on lamotrigine 200mg daily but had a hypomanic episode 3 months ago. In comparing the neuroprotective and neurocognitive effects of long-term mood stabilizer therapy, which statement represents the most accurate interpretation of current evidence?
A 36-year-old man with schizophrenia on clozapine 450mg daily attends A&E with 2-day history of severe constipation, abdominal distension, vomiting, and no bowel movements for 4 days. Examination reveals tachycardia (110/min), abdominal distension with reduced bowel sounds, and tympanic percussion. Abdominal X-ray shows grossly dilated large bowel (caecal diameter 11cm) with no evidence of mechanical obstruction. What is the most appropriate immediate management of this life-threatening complication?
A 41-year-old woman with bipolar affective disorder type I has been stable on lithium carbonate 800mg twice daily for 2 years. She presents to her GP with a 6-week history of polyuria, polydipsia (drinking 5-6 litres daily), and nocturia (waking 4-5 times per night). Urine dipstick shows no glucose, blood tests reveal: sodium 148 mmol/L, serum osmolality 298 mOsm/kg, urine osmolality 120 mOsm/kg, lithium level 0.8 mmol/L, creatinine 98 μmol/L. What is the most likely underlying diagnosis?
A 29-year-old man with a 5-year history of schizophrenia presents to his GP requesting medication review. He has been taking risperidone depot 25mg fortnightly with good symptom control but complains of gynaecomastia, galactorrhoea, reduced libido, and erectile dysfunction for 8 months. Blood tests show prolactin level 2,850 mU/L (normal range 86-324 mU/L). His psychotic symptoms are well-controlled and he has good treatment adherence. What underlying mechanism best explains his symptoms?
A 33-year-old man with paranoid schizophrenia has been treated with multiple antipsychotics over 6 years with persistent positive symptoms despite adequate trials of risperidone, olanzapine, and quetiapine at therapeutic doses for appropriate durations. He has adherence confirmed by depot medication and plasma levels. Which criterion must be met before defining his condition as treatment-resistant schizophrenia and initiating clozapine?
A 52-year-old woman with bipolar disorder type II is reviewed in outpatient clinic. She has had four episodes of major depression in the past 3 years and two hypomanic episodes. Her current mood is euthymic on lamotrigine 200mg daily. She reports the depressive episodes are severely debilitating and seeks optimization of her treatment to reduce future episodes. What is the most appropriate evidence-based modification to her medication regimen?
A 26-year-old woman presents with a 4-month history of social withdrawal, hearing her dead grandmother's voice telling her she is worthless, and believing that strangers can read her thoughts. She meets criteria for schizophrenia and agrees to start antipsychotic medication. Her BMI is 32 kg/m², fasting glucose 5.8 mmol/L, and she has a family history of type 2 diabetes. Which atypical antipsychotic would be the most appropriate first-line choice given her metabolic risk profile?
A 45-year-old man with chronic schizophrenia presents with 3-day history of fever (39.2°C), confusion, muscle rigidity, and profuse sweating. He was started on haloperidol 15mg daily 10 days ago after non-compliance with depot medication. Observations show: BP 168/102 mmHg, pulse 118/min, temperature 39.2°C. Blood tests reveal: WCC 16.5 × 10⁹/L, creatine kinase 8,500 U/L, creatinine 185 μmol/L. What is the most critical immediate management priority?
A 38-year-old woman with bipolar affective disorder has been stable on lithium for 3 years. She attends for pre-conception counselling as she and her partner are planning pregnancy. Her current lithium level is 0.7 mmol/L with normal renal and thyroid function. She is particularly concerned about risks to the fetus and maintaining her mood stability. What is the most evidence-based recommendation regarding her lithium therapy during pregnancy?
A 30-year-old woman with treatment-resistant schizophrenia has been taking clozapine 400mg daily for 8 weeks. She attends for routine blood monitoring. Her full blood count shows: Hb 125 g/L, WCC 2.8 × 10⁹/L, neutrophils 1.2 × 10⁹/L, platelets 245 × 10⁹/L. She is asymptomatic with no signs of infection. Previous FBC 4 weeks ago showed WCC 4.5 × 10⁹/L and neutrophils 2.5 × 10⁹/L. What is the most appropriate immediate management according to clozapine monitoring guidelines?
Severe Mental Illness UK Medical PG Practice Questions and MCQs
Question 151: A 27-year-old woman with bipolar affective disorder presents for medication review. She has had three manic episodes and two severe depressive episodes over the past 4 years. She has previously taken lithium (stopped due to tremor and polyuria) and sodium valproate (stopped due to significant weight gain and hair loss). She is currently on lamotrigine 200mg daily but had a hypomanic episode 3 months ago. In comparing the neuroprotective and neurocognitive effects of long-term mood stabilizer therapy, which statement represents the most accurate interpretation of current evidence?
- A. Lithium demonstrates unique neuroprotective properties by increasing grey matter volume and reducing progression of cognitive decline in bipolar disorder (Correct Answer)
- B. Sodium valproate provides superior cognitive preservation compared to lithium due to its anti-inflammatory mechanisms in the central nervous system
- C. All mood stabilizers equally prevent cognitive decline through stabilization of mood episodes alone with no direct neuroprotective effects
- D. Lamotrigine has the strongest evidence for neuroprotection through glutamate modulation preventing excitotoxic neuronal damage
- E. Atypical antipsychotics demonstrate greater neuroprotective effects than traditional mood stabilizers through BDNF upregulation
Explanation: ***Lithium demonstrates unique neuroprotective properties by increasing grey matter volume and reducing progression of cognitive decline in bipolar disorder***- **Lithium** is the most robustly associated mood stabilizer with neuroprotection, evidenced by increased **grey matter volume** in the hippocampus and prefrontal cortex.- It acts through multiple mechanisms, including inhibition of **GSK-3β**, increasing **BDNF** levels, and enhancing **anti-apoptotic** factors like bcl-2.*Sodium valproate provides superior cognitive preservation compared to lithium due to its anti-inflammatory mechanisms in the central nervous system*- While **sodium valproate** has some neuroprotective properties, current clinical evidence does not support its superiority over lithium for **cognitive preservation**.- High-dose valproate therapy may actually be associated with **cognitive impairment** and is not as thoroughly linked to brain volume increases as lithium.*All mood stabilizers equally prevent cognitive decline through stabilization of mood episodes alone with no direct neuroprotective effects*- Although preventing **mood episodes** reduces excitotoxic neurotoxicity, evidence shows that **lithium** has direct cellular neuroprotective effects that exceed simple mood stabilization.- Different mood stabilizers have distinct **molecular targets**, leading to varying levels of biochemical and structural neuroprotection.*Lamotrigine has the strongest evidence for neuroprotection through glutamate modulation preventing excitotoxic neuronal damage*- **Lamotrigine** modulates **glutamate release**, which may offer theoretical neuroprotection, but large-scale structural neuroimaging evidence remains less substantial than that of lithium.- It is primarily effective for preventing **bipolar depression** and lacks the robust evidence for increasing cortical thickness seen with lithium.*Atypical antipsychotics demonstrate greater neuroprotective effects than traditional mood stabilizers through BDNF upregulation*- While some studies show **atypical antipsychotics** might increase BDNF, long-term use has also been paradoxically linked to **brain volume reductions** in some populations.- **Lithium** remains the gold standard for neuroprotective evidence in bipolar disorder compared to antipsychotics which have more **heterogeneous results**.
Question 152: A 36-year-old man with schizophrenia on clozapine 450mg daily attends A&E with 2-day history of severe constipation, abdominal distension, vomiting, and no bowel movements for 4 days. Examination reveals tachycardia (110/min), abdominal distension with reduced bowel sounds, and tympanic percussion. Abdominal X-ray shows grossly dilated large bowel (caecal diameter 11cm) with no evidence of mechanical obstruction. What is the most appropriate immediate management of this life-threatening complication?
- A. Continue clozapine, commence regular laxatives, and arrange routine surgical outpatient review
- B. Stop clozapine, insert nasogastric tube for decompression, commence IV fluids, and request urgent surgical review (Correct Answer)
- C. Reduce clozapine dose by 50%, give high-dose lactulose and bisacodyl, and observe for 24 hours
- D. Continue clozapine, give phosphate enema and oral polyethylene glycol, and arrange colonoscopy
- E. Stop clozapine temporarily, give IV metoclopramide for prokinetic effect, and arrange CT abdomen
Explanation: ***Stop clozapine, insert nasogastric tube for decompression, commence IV fluids, and request urgent surgical review*** - The patient presents with **clozapine-induced paralytic ileus** or **toxic megacolon**, a surgical emergency due to severe constipation and bowel dilation (caecal diameter **11cm**, indicating high perforation risk). - Immediate management involves **stopping the offending agent** (clozapine), **resuscitation with IV fluids**, **bowel decompression** via a nasogastric tube, and **urgent surgical consultation** to prevent bowel ischemia, perforation, or death. *Continue clozapine, commence regular laxatives, and arrange routine surgical outpatient review* - Continuing **clozapine** is contraindicated as its potent **antimuscarinic effects** are the cause of the severe gut hypomotility and will exacerbate the condition, increasing perforation risk. - A **routine outpatient review** is entirely inappropriate for a patient presenting with an acute abdomen, significant bowel dilation, and **systemic tachycardia**, indicating a medical emergency. *Reduce clozapine dose by 50%, give high-dose lactulose and bisacodyl, and observe for 24 hours* - Merely **reducing the clozapine dose** is insufficient when the patient has established **life-threatening intestinal obstruction** with features of systemic distress. - Osmotic and stimulant laxatives like **lactulose** and **bisacodyl** can worsen intestinal distension and intraluminal pressure in a dilated, paralytic bowel, potentially increasing the risk of **bowel perforation**. *Continue clozapine, give phosphate enema and oral polyethylene glycol, and arrange colonoscopy* - Continuing **clozapine** is incorrect. **Enemas and oral polyethylene glycol (PEG)** are appropriate for simple constipation but are ineffective and potentially harmful in severe **paralytic ileus** with significant bowel dilation. - **Colonoscopy** is generally contraindicated in cases of acute megacolon due to the substantial risk of **iatrogenic perforation** from air insufflation and instrumentation of a compromised bowel wall. *Stop clozapine temporarily, give IV metoclopramide for prokinetic effect, and arrange CT abdomen* - While stopping clozapine is correct, **metoclopramide** is a dopamine receptor antagonist and its use in patients on antipsychotics, particularly clozapine, carries an increased risk of **extrapyramidal side effects**. - Prokinetics like metoclopramide are typically ineffective and may even be harmful in severe **clozapine-induced paralytic ileus** where anticholinergic effects cause widespread gut paralysis, and are not indicated for immediate management of acute megacolon.
Question 153: A 41-year-old woman with bipolar affective disorder type I has been stable on lithium carbonate 800mg twice daily for 2 years. She presents to her GP with a 6-week history of polyuria, polydipsia (drinking 5-6 litres daily), and nocturia (waking 4-5 times per night). Urine dipstick shows no glucose, blood tests reveal: sodium 148 mmol/L, serum osmolality 298 mOsm/kg, urine osmolality 120 mOsm/kg, lithium level 0.8 mmol/L, creatinine 98 μmol/L. What is the most likely underlying diagnosis?
- A. Lithium-induced nephrogenic diabetes insipidus due to impaired aquaporin-2 expression in collecting ducts (Correct Answer)
- B. Lithium-induced primary polydipsia due to direct stimulation of hypothalamic thirst centres
- C. Lithium-induced chronic interstitial nephritis causing osmotic diuresis
- D. Central diabetes insipidus due to lithium toxicity affecting posterior pituitary ADH release
- E. Lithium-induced hyperparathyroidism causing hypercalcaemia and polyuria
Explanation: ***Lithium-induced nephrogenic diabetes insipidus due to impaired aquaporin-2 expression in collecting ducts***- The patient presents with **polyuria**, **polydipsia**, and **nocturia** alongside **hypernatremia** (148 mmol/L) and **high serum osmolality** (298 mOsm/kg).- Crucially, the **urine osmolality is low** (120 mOsm/kg), indicating an inability of the kidneys to concentrate urine despite the body's dehydrated state, a classic sign of **nephrogenic diabetes insipidus (NDI)**, a known side effect of long-term lithium that impairs **aquaporin-2 (AQP2)** channel function in the **collecting ducts**.*Lithium-induced primary polydipsia due to direct stimulation of hypothalamic thirst centres*- **Primary polydipsia** is characterized by excessive fluid intake leading to **hyponatremia** and **low serum osmolality** due to water intoxication, which contradicts this patient's **hypernatremia** and elevated serum osmolality.- In primary polydipsia, the kidneys are typically able to concentrate urine if dehydrated; this patient's **dilute urine** despite hypernatremia points to a **renal concentrating defect**, not just increased thirst.*Lithium-induced chronic interstitial nephritis causing osmotic diuresis*- **Osmotic diuresis** occurs when unreabsorbed solutes (like glucose or mannitol) in the renal tubules draw water, leading to polyuria with a **relatively high urine osmolality** (e.g., >250-300 mOsm/kg), which is not consistent with this patient's **very dilute urine** (120 mOsm/kg).- While lithium can cause chronic interstitial nephritis, leading to impaired concentrating ability, the primary mechanism of **osmotic diuresis** is different, and the patient's **normal creatinine** makes severe interstitial nephritis less likely as the primary driver of polyuria.*Central diabetes insipidus due to lithium toxicity affecting posterior pituitary ADH release*- **Central diabetes insipidus (CDI)** is caused by a deficiency in **ADH (vasopressin)** production or release from the posterior pituitary, which is not a typical direct effect of lithium.- Lithium primarily causes **nephrogenic diabetes insipidus (NDI)** by making the kidney's collecting ducts resistant to ADH, rather than affecting ADH synthesis or release from the pituitary.*Lithium-induced hyperparathyroidism causing hypercalcaemia and polyuria*- While long-term lithium therapy can induce **hyperparathyroidism** and subsequent **hypercalcaemia**, and **hypercalcaemia** itself can impair renal concentrating ability (leading to nephrogenic DI), there are no data provided in the case for serum calcium or PTH levels.- The most direct and common mechanism of polyuria in stable lithium therapy, with the given lab findings, is direct lithium toxicity on the collecting duct's response to ADH, rather than secondary effects via calcium.
Question 154: A 29-year-old man with a 5-year history of schizophrenia presents to his GP requesting medication review. He has been taking risperidone depot 25mg fortnightly with good symptom control but complains of gynaecomastia, galactorrhoea, reduced libido, and erectile dysfunction for 8 months. Blood tests show prolactin level 2,850 mU/L (normal range 86-324 mU/L). His psychotic symptoms are well-controlled and he has good treatment adherence. What underlying mechanism best explains his symptoms?
- A. Risperidone's strong 5-HT2A receptor antagonism causing disruption of the hypothalamic-pituitary axis
- B. Risperidone's potent D2 receptor blockade in the tuberoinfundibular pathway removing dopamine's inhibitory effect on prolactin (Correct Answer)
- C. Risperidone's anti-muscarinic properties causing indirect stimulation of lactotroph cells in the anterior pituitary
- D. Risperidone's alpha-1 adrenergic blockade leading to increased prolactin synthesis and release
- E. Risperidone's effect on histamine H1 receptors causing downstream stimulation of prolactin-releasing hormone
Explanation: ***Risperidone's potent D2 receptor blockade in the tuberoinfundibular pathway removing dopamine's inhibitory effect on prolactin***- **Dopamine** normally acts via the **tuberoinfundibular pathway** to provide tonic inhibition of prolactin release from the **anterior pituitary** lactotrophs.- **Risperidone** has a high affinity for **D2 receptors**; by blocking these receptors, it removes the inhibitory signal, leading to **hyperprolactinaemia** and clinical symptoms like **gynaecomastia** and **galactorrhoea**.*Risperidone's strong 5-HT2A receptor antagonism causing disruption of the hypothalamic-pituitary axis*- While risperidone is a potent **5-HT2A antagonist**, this specific mechanism is associated with a reduction in **extrapyramidal side effects** rather than causing prolactin elevation.- **Serotonin** typically stimulates prolactin release, so **antagonism** at these receptors would actually tend to **lower** prolactin levels rather than increase them.*Risperidone's anti-muscarinic properties causing indirect stimulation of lactotroph cells in the anterior pituitary*- Risperidone possesses very **low affinity** for **muscarinic receptors**, unlike low-potency typical antipsychotics or clozapine.- Even in drugs with strong **anticholinergic** effects, this mechanism does not directly influence the secretion of **prolactin** from the pituitary gland.*Risperidone's alpha-1 adrenergic blockade leading to increased prolactin synthesis and release*- **Alpha-1 adrenergic blockade** by antipsychotics is primarily responsible for side effects such as **orthostatic hypotension** and reflex tachycardia.- There is no clinical or physiological evidence linking **alpha-1 blockade** to the synthesis or pathological release of **prolactin**.*Risperidone's effect on histamine H1 receptors causing downstream stimulation of prolactin-releasing hormone*- Blockade of **H1 receptors** is a common feature of many antipsychotics that primarily leads to **sedation** and **weight gain**.- **Histaminergic activity** is not a primary regulator of the **tuberoinfundibular pathway**, and its blockade does not explain the significant **prolactin elevation** seen with risperidone.
Question 155: A 33-year-old man with paranoid schizophrenia has been treated with multiple antipsychotics over 6 years with persistent positive symptoms despite adequate trials of risperidone, olanzapine, and quetiapine at therapeutic doses for appropriate durations. He has adherence confirmed by depot medication and plasma levels. Which criterion must be met before defining his condition as treatment-resistant schizophrenia and initiating clozapine?
- A. Failure to respond to at least two different antipsychotics, one of which should be a second-generation agent, each tried for 6-8 weeks at therapeutic doses
- B. Failure to respond to at least two different antipsychotics from different classes, each tried for at least 4-6 weeks at minimum effective doses
- C. Failure to respond to at least two different antipsychotics, each tried sequentially for 6-8 weeks at adequate doses, with one being an atypical agent (Correct Answer)
- D. Failure to respond to trials of both typical and atypical antipsychotics for at least 3 months each at maximum licensed doses
- E. Failure to respond to adequate trials of at least three different antipsychotics, each for at least 6 weeks at therapeutic doses
Explanation: ***Failure to respond to at least two different antipsychotics, each tried sequentially for 6-8 weeks at adequate doses, with one being an atypical agent***- **Treatment-resistant schizophrenia (TRS)** is formally defined by the failure of at least **two different antipsychotic medications** at adequate therapeutic doses for a duration of **6-8 weeks** each.- At least one of these trials must involve a **second-generation (atypical) antipsychotic**, and **medication adherence** must be confirmed (as seen with this patient's depot and plasma levels).*Failure to respond to at least two different antipsychotics, one of which should be a second-generation agent, each tried for 6-8 weeks at therapeutic doses*- While very similar, the standard clinical definition emphasizes the **sequential nature** of these trials to ensure individual efficacy is assessed.- This option is technically less precise than the correct answer regarding the **sequential trial requirement** established by international consensus.*Failure to respond to at least two different antipsychotics from different classes, each tried for at least 4-6 weeks at minimum effective doses*- A trial duration of **4-6 weeks** is considered too short to definitively establish treatment resistance, as full clinical response can take longer.- Using only the **minimum effective dose** may not provide a sufficient challenge to the symptoms before labeling the patient as treatment-resistant.*Failure to respond to trials of both typical and atypical antipsychotics for at least 3 months each at maximum licensed doses*- Requiring **3 months** for each trial exceeds the standard guideline of **6-8 weeks**, potentially delaying the initiation of Clozapine.- **Maximum licensed doses** are not strictly required; the medications only need to be at a **therapeutic dose** within the standard licensed range.*Failure to respond to adequate trials of at least three different antipsychotics, each for at least 6 weeks at therapeutic doses*- Although the patient in this scenario has failed three agents, the formal definition of TRS only requires the failure of **two different antipsychotics**.- Requiring **three trials** would unnecessarily delay the use of **Clozapine**, which is the gold-standard treatment for resistant cases.
Question 156: A 52-year-old woman with bipolar disorder type II is reviewed in outpatient clinic. She has had four episodes of major depression in the past 3 years and two hypomanic episodes. Her current mood is euthymic on lamotrigine 200mg daily. She reports the depressive episodes are severely debilitating and seeks optimization of her treatment to reduce future episodes. What is the most appropriate evidence-based modification to her medication regimen?
- A. Add lithium carbonate as combination therapy is superior for preventing depressive episodes (Correct Answer)
- B. Switch from lamotrigine to quetiapine as monotherapy for better depression prophylaxis
- C. Continue lamotrigine alone as it provides optimal prophylaxis for bipolar II disorder
- D. Add sodium valproate as it has specific efficacy for rapid cycling bipolar disorder
- E. Switch to high-dose lamotrigine 400mg daily to maximize antidepressant effect
Explanation: ***Add lithium carbonate as combination therapy is superior for preventing depressive episodes*** - For patients with **Bipolar II disorder** experiencing breakthrough depressive episodes on monotherapy, adding **Lithium** is the most evidence-based strategy to enhance **prophylaxis**. - Studies show the combination of **Lithium and Lamotrigine** is more effective at preventing depressive relapses and reducing **suicidal ideation** than either agent alone. *Switch from lamotrigine to quetiapine as monotherapy for better depression prophylaxis* - While **Quetiapine** is effective for bipolar depression, switching agents risks losing the partial stability the patient has already achieved on **Lamotrigine**. - Evidence generally supports **combination therapy** over switching to a different monotherapy when a patient remains symptomatic despite a standard therapeutic dose. *Continue lamotrigine alone as it provides optimal prophylaxis for bipolar II disorder* - Although **Lamotrigine** is useful for preventing depression, four major depressive episodes in three years indicate that **monotherapy** is insufficient for this patient. - Maintenance treatment must be optimized when there is a high frequency of **breakthrough episodes** to reduce long-term morbidity. *Add sodium valproate as it has specific efficacy for rapid cycling bipolar disorder* - **Sodium Valproate** is primarily effective for preventing **manic episodes** and has less robust evidence for the prevention of the depressive phase of Bipolar II. - It is generally not the first-choice adjunct for someone whose primary burden is **recurrent depression** rather than mania or mixed states. *Switch to high-dose lamotrigine 400mg daily to maximize antidepressant effect* - The standard daily maintenance dose for **Lamotrigine** is typically **200mg**; titrating to 400mg offers marginal benefit while increasing the risk of adverse effects. - Dose escalation does not address the need for a **mechanistically different** mood stabilizer to achieve better therapeutic coverage.
Question 157: A 26-year-old woman presents with a 4-month history of social withdrawal, hearing her dead grandmother's voice telling her she is worthless, and believing that strangers can read her thoughts. She meets criteria for schizophrenia and agrees to start antipsychotic medication. Her BMI is 32 kg/m², fasting glucose 5.8 mmol/L, and she has a family history of type 2 diabetes. Which atypical antipsychotic would be the most appropriate first-line choice given her metabolic risk profile?
- A. Olanzapine 10mg daily due to superior efficacy in first episode psychosis
- B. Quetiapine 300mg daily due to lower risk of extrapyramidal side effects
- C. Aripiprazole 10mg daily due to favorable metabolic profile (Correct Answer)
- D. Risperidone 4mg daily due to established efficacy and NHS cost-effectiveness
- E. Amisulpride 400mg daily due to specific efficacy for negative symptoms
Explanation: ***Aripiprazole 10mg daily due to favorable metabolic profile*** - **Aripiprazole** is a **partial dopamine agonist** known for having the most favorable metabolic profile with minimal risk of **weight gain**, dyslipidemia, or hyperglycemia. - This makes it the ideal choice for a patient with a **BMI of 32**, elevated fasting glucose (pre-diabetic range), and a significant family history of **Type 2 Diabetes**, mitigating her metabolic risk. *Olanzapine 10mg daily due to superior efficacy in first episode psychosis* - **Olanzapine** is associated with the highest risk of **metabolic syndrome**, leading to significant **weight gain** and worsening of lipid/glucose profiles. - Its use is generally avoided as a first-line option in patients who already possess multiple **metabolic risk factors** like obesity and pre-diabetes. *Quetiapine 300mg daily due to lower risk of extrapyramidal side effects* - While **Quetiapine** has a low risk of **Extrapyramidal Side Effects (EPSE)**, it carries a moderate-to-high risk of **weight gain** and metabolic disturbances. - In this clinical scenario, the patient's existing **obesity** makes Quetiapine a less suitable choice compared to more metabolically neutral agents. *Risperidone 4mg daily due to established efficacy and NHS cost-effectiveness* - **Risperidone** carries an intermediate metabolic risk and is frequently associated with significant **hyperprolactinemia** and moderate weight gain. - Although effective, it is less desirable than Aripiprazole for a patient at high risk for **cardiovascular and metabolic complications** given her profile. *Amisulpride 400mg daily due to specific efficacy for negative symptoms* - **Amisulpride** is effective for negative symptoms but is notorious for causing marked elevations in **prolactin levels**. - While it has a lower metabolic impact than Olanzapine, it still lacks the **weight-neutral** benefits provided by **Aripiprazole** in the context of a patient with a high BMI and other metabolic risk factors.
Question 158: A 45-year-old man with chronic schizophrenia presents with 3-day history of fever (39.2°C), confusion, muscle rigidity, and profuse sweating. He was started on haloperidol 15mg daily 10 days ago after non-compliance with depot medication. Observations show: BP 168/102 mmHg, pulse 118/min, temperature 39.2°C. Blood tests reveal: WCC 16.5 × 10⁹/L, creatine kinase 8,500 U/L, creatinine 185 μmol/L. What is the most critical immediate management priority?
- A. Stop haloperidol, commence dantrolene 1mg/kg IV, and arrange urgent ICU admission (Correct Answer)
- B. Commence broad-spectrum antibiotics for suspected sepsis and arrange lumbar puncture
- C. Stop haloperidol, give benzodiazepines for muscle rigidity, and arrange urgent CT head
- D. Administer procyclidine for acute dystonia and continue haloperidol at reduced dose
- E. Stop haloperidol, provide supportive care with IV fluids and cooling measures only
Explanation: ***Stop haloperidol, commence dantrolene 1mg/kg IV, and arrange urgent ICU admission*** - The patient's presentation with **fever**, **confusion**, severe **muscle rigidity**, profuse sweating, **autonomic instability**, and extremely elevated **creatine kinase (CK 8,500 U/L)** after starting haloperidol is highly consistent with **Neuroleptic Malignant Syndrome (NMS)**. - Immediate management for NMS includes **discontinuation of the causative antipsychotic**, administration of specific agents like **dantrolene** (a direct muscle relaxant) or bromocriptine, and **urgent ICU admission** for comprehensive supportive care due to the high risk of complications like **rhabdomyolysis** and **acute kidney injury**. *Commence broad-spectrum antibiotics for suspected sepsis and arrange lumbar puncture* - While fever and confusion are present, the extreme **muscle rigidity** and significantly elevated **CK levels** are not typical for uncomplicated sepsis or meningitis; these findings strongly point towards a neuromuscular disorder like NMS. - Delaying specific NMS treatment by solely pursuing a sepsis workup would be detrimental given the rapid progression and life-threatening nature of the syndrome. *Stop haloperidol, give benzodiazepines for muscle rigidity, and arrange urgent CT head* - While stopping haloperidol is correct, **benzodiazepines** are generally insufficient for the severe, generalized "lead-pipe" **muscle rigidity** characteristic of NMS and do not address the underlying pathophysiology or prevent complications like rhabdomyolysis. - An **urgent CT head** is not the primary diagnostic or management priority in a patient with a clear history of antipsychotic use and laboratory evidence (elevated CK) strongly suggesting NMS. *Administer procyclidine for acute dystonia and continue haloperidol at reduced dose* - **Procyclidine** is indicated for **acute dystonic reactions**, which are typically localized and self-limiting muscle spasms, not the diffuse rigidity, hyperthermia, and systemic features of NMS. - **Continuing haloperidol**, even at a reduced dose, is strictly contraindicated as it is the precipitating agent for NMS and would exacerbate the syndrome, increasing morbidity and mortality. *Stop haloperidol, provide supportive care with IV fluids and cooling measures only* - **Stopping haloperidol** and providing **aggressive supportive care** with intravenous fluids and cooling measures are essential components of NMS management to prevent complications like dehydration and hyperthermia. - However, in severe cases with marked muscle rigidity and significant CK elevation, **supportive care alone is often inadequate**; specific pharmacological interventions such as **dantrolene** are critical to reverse the muscle rigidity and mitigate the systemic effects of NMS.
Question 159: A 38-year-old woman with bipolar affective disorder has been stable on lithium for 3 years. She attends for pre-conception counselling as she and her partner are planning pregnancy. Her current lithium level is 0.7 mmol/L with normal renal and thyroid function. She is particularly concerned about risks to the fetus and maintaining her mood stability. What is the most evidence-based recommendation regarding her lithium therapy during pregnancy?
- A. Continue lithium throughout pregnancy as the risk of relapse outweighs fetal risks, with careful monitoring (Correct Answer)
- B. Stop lithium and remain medication-free during first trimester, then restart in second trimester
- C. Switch to sodium valproate before conception as it has a better safety profile in pregnancy
- D. Gradually discontinue lithium over 4 weeks before conception and remain medication-free throughout pregnancy
- E. Stop lithium immediately and switch to lamotrigine for pregnancy and breastfeeding
Explanation: ***Continue lithium throughout pregnancy as the risk of relapse outweighs fetal risks, with careful monitoring*** - Stopping **lithium** in stable patients with **bipolar disorder** carries a high **relapse risk** (up to 70%), which can lead to severe manic or depressive episodes and poor self-care during pregnancy. - While lithium is associated with **Ebstein's anomaly**, the absolute risk is much lower than previously thought (0.05-0.1%), making the **benefit-risk ratio** favor continuation with **fetal echocardiography** and frequent **serum level monitoring**. *Stop lithium and remain medication-free during first trimester, then restart in second trimester* - Discontinuing medication during the first trimester significantly increases the risk of **maternal relapse**, which poses a greater threat to the pregnancy than the low risk of **teratogenicity**. - Abrupt or temporary cessation is often followed by a high rate of **recurrence**, making it difficult to regain **mood stability** later in the pregnancy. *Switch to sodium valproate before conception as it has a better safety profile in pregnancy* - **Sodium valproate** is strictly contraindicated in pregnancy due to its high risk of major **malformations** (like **neural tube defects**) and significant **neurodevelopmental delay**. - It has the worst safety profile among mood stabilizers for fetal outcomes, whereas lithium's risks are manageable through **prenatal screening**. *Gradually discontinue lithium over 4 weeks before conception and remain medication-free throughout pregnancy* - Remaining medication-free throughout pregnancy carries a dangerously high risk of **postpartum psychosis** and relapse, which are medical emergencies. - Clinical guidelines recommend maintaining effective treatment for patients with a history of **severe mental illness** rather than attempting drug-free pregnancies. *Stop lithium immediately and switch to lamotrigine for pregnancy and breastfeeding* - **Lamotrigine** is primarily effective against **bipolar depression** but is significantly less effective than lithium at preventing **mania**. - Switching a patient who is stable on lithium to a different agent just before pregnancy risks **breakthrough symptoms** during a vulnerable physiological period.
Question 160: A 30-year-old woman with treatment-resistant schizophrenia has been taking clozapine 400mg daily for 8 weeks. She attends for routine blood monitoring. Her full blood count shows: Hb 125 g/L, WCC 2.8 × 10⁹/L, neutrophils 1.2 × 10⁹/L, platelets 245 × 10⁹/L. She is asymptomatic with no signs of infection. Previous FBC 4 weeks ago showed WCC 4.5 × 10⁹/L and neutrophils 2.5 × 10⁹/L. What is the most appropriate immediate management according to clozapine monitoring guidelines?
- A. Continue clozapine, repeat FBC in 1 week, and provide patient with infection warning advice
- B. Stop clozapine immediately, admit for urgent haematology review, and start broad-spectrum antibiotics
- C. Stop clozapine immediately, repeat FBC daily, and do not rechallenge with clozapine (Correct Answer)
- D. Reduce clozapine dose to 200mg daily, repeat FBC in 3 days, and monitor for signs of infection
- E. Continue clozapine, repeat FBC in 3 days, and advise patient to report fever or sore throat immediately
Explanation: ***Stop clozapine immediately, repeat FBC daily, and do not rechallenge with clozapine*** - The patient's **absolute neutrophil count (ANC)** is **1.2 × 10⁹/L**, which falls below the critical threshold of **1.5 × 10⁹/L** for clozapine monitoring, placing her in the **RED zone**. - According to clozapine monitoring guidelines, an ANC in the RED zone necessitates **immediate cessation of clozapine**, daily FBC monitoring until recovery, and a **permanent contraindication** to rechallenge due to the high risk of severe agranulocytosis. *Continue clozapine, repeat FBC in 1 week, and provide patient with infection warning advice* - Continuing clozapine is inappropriate for a **RED zone** result; this level of neutropenia requires immediate cessation to prevent further bone marrow suppression. - Repeating FBC in **one week** is too infrequent for such a significant drop in neutrophil count, as rapid deterioration can occur. *Stop clozapine immediately, admit for urgent haematology review, and start broad-spectrum antibiotics* - While stopping clozapine is correct, **admission and broad-spectrum antibiotics** are typically reserved for patients with **febrile neutropenia** or clear signs of infection, which are not present as the patient is asymptomatic. - Urgent haematology review is important, but the immediate priority is stopping the drug and **daily monitoring** to track recovery, rather than proactive septic management for an asymptomatic patient. *Reduce clozapine dose to 200mg daily, repeat FBC in 3 days, and monitor for signs of infection* - **Dose reduction** is not an appropriate measure for clozapine-induced neutropenia; the drug must be stopped due to the idiosyncratic nature of the adverse reaction. - Continuing clozapine, even at a reduced dose, when the patient is in the **RED zone** for neutropenia poses an unacceptable risk of progressing to **agranulocytosis**. *Continue clozapine, repeat FBC in 3 days, and advise patient to report fever or sore throat immediately* - This management strategy is typically for **AMBER zone** results (ANC between 1.5 and 2.0 × 10⁹/L), where clozapine may be continued with increased monitoring. - Given the ANC of **1.2 × 10⁹/L**, the patient is in the **RED zone**, making continued clozapine therapy clinically unsafe and contrary to safety protocols.
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