Psych - Antipsychotics

Question 1

Broadly, how do all current antipsychotics work? Which brain pathways are targeted by these drugs? What are the main side effects common to all antipsychotics?

Answer 1

• All current antipsychotics reduce levels of dopamine activity at D2 receptors.
• Target pathways: dopaminergic mesocortical and Mesolimbic pathways (sensory expression and emotions)
• Unwanted targets: nigostrial pathway (movement) and tuberoinfudibular (HPA(adrenal) pathway)
• SEs: sedation, extrapyramidal (tremor, slurred speech, akathesia, dystonia, anxiety, distress and bradyphrenia) and Wt gain

Question 2

What is the difference between typical and atypical antipsychotics? Name a few of each

Answer 2

-Both block dopaminergic pathways in brain

Typical:

• Anti-dopaminergic SE: extra-pyramidal SEs (Parkinsonism [bradykinesia, muscle stiffness and tremor], tardive dyskinesia and akathesia), wt gain and sexual dysfunction/hyperprolactinaemia, increased muscle tone,
• bind more to muscarinic and histamine receptors
• Haloperidol, Flupenthixol, Zuclopenthixol, Chlorpromazine, Sulpride

Atypical:

• SE profile is more metaboli: wt gain (esp Olanzapine and clozapine), dyslipidaemia and DM
• Have more serotonergic activity
• Clozapine, Risperidone, Quetiapine, Amisulpride, aripriprazole (v long T1/2 of 150h - partial D2 agonist)

Question 3

What monitoring should you do for patients taking antipsychotics?

Answer 3

• Baseline: FBC, lipids, U&Es, LFT, HBA1c, wt, ECG, BP and HR, prolactin
• Weekly: weight, lithium levels (lithium) and FBC (clozapine)
• 3/12: FBC, lipids, U&Es, LFT, HBA1c, wt, ECG, BP and HR, prolactin
• 12/12: FBC, lipids, U&Es, LFT, HBA1c, wt, ECG, BP and HR, prolactin

Question 4

What is neuroleptic malignant syndrome? What are some risk factors? What blood markers will become deranged?

Answer 4

• Rare, life threatening reaction to neuroleptic Tx, can occur any time after treatment initiation
• Symptoms: fever, confusion, muscle rigidity (lead pipe rigidity - doesn’t occur in serotonin syndrome, which gives you hyper reflexia and clonus), sweating, autonomic instability
• Death can occur as result of rhabdo, renal failure or seizures
• Bloods: raised CK and WCC
• Risk factors: potent dopamine antagonists (esp typical antipsychotics) in antipsychotic naive, high doses, young men

Question 5

What is the treatment for neuroleptic malignant syndrome?

Answer 5

• Emergency referral to A+E
• Initial management: fluid resuscitation and temperature reduction (eg with cooling blankets)
• Stop antipsychotics
• Give benzos (for acute behavioural disturbance)
• O2 if required
• If rhabdo present: fluids and NaHCO3 (will alkalise the urine)
• If muscles are very rigid: dantrolene or lorazepam

Question 6

What treatment can you offer to patients who are suffering from antipsychotic induced extra pyramidal side effects? Name a drug of this class. In what situation should these drugs not be prescribed?

Answer 6

• Anticholinergics: work by decreasing the amount of acetylcholine in nigostrial pathway.
• The ratio between dopamine : acetylcholine is more important than absolute quantities. If dopamine levels are suppressed, anticholinergics re-establish this balance
• Procycline (most common)
• Should not be prescribed in tardive dyskinesia because is not effective and may even exacerbate it.

Question 7

What is acute dystonia? What are the symptoms and treatment?

Answer 7

• Sustained, often painful, muscular spasms producing twisted abnormal postures - neck, tongue, jaw, occulogyric crisis
• 50% cases in first 48h of introducing an antipsychotic
• Treatment: stop antipsychotic, administer IM/IV anticholinergics (Procyclidine), continue for 1-2 days after dystonia and consider as long term prophylactic

Question 8

What is Clozapine? What important SE should we consider?

Answer 8

• Drug which has demonstrated superior efficacy to other antipsychotics - substantially reduces overall mortality from schizophrenia (reduction in ate of suicide)
• Must be titrations slowly upward over two weeks and monitor obs for signs of autonomic dysregulation
• Can only be prescribed after 2 other antipsychotics have been tried - must never ever give as depo
• SE: seizures, agranulocytosis (weekly FBC for 18/52, every 2 weeks for 12/12, then monthly), hypersalivation, constipation (potentially fatal bowel obstruction), hypo/hypertension, wt gain, fever, nausea, urinary incontinence

Question 9

What is the treatment for clozapine induced agranulocytosis?

Answer 9

• Stop clozapine and any other potentially marrow suppressing drugs (Na valproate)
• Avoid other psychotics for several weeks but can use aripirazole if needed
• Call haematology consultant ASAP
• Consider broad spectrum ABX cover
• Can give lithium (increases WCC and neutrophil count) or G-CSF (increases WCC)