Psychiatric prescribing

Pregunta	Respuesta
Which of the following antipsychotics is least likely to cause sedation? Aripiprazole, Clozapine, Olanzapine, Quetiapine, Risperidone, Sulpiride, Trifluoperazine.	Aripiprazole.
Which of the following antipsychotics is most likely to cause a raised prolactin? Aripiprazole, Clozapine, Olanzapine, Quetiapine, Risperidone, Sulpiride, Trifluoperazine.	Risperidone.
Which of the antipsychotic is indicated in treatment resistant schizophrenia?	Clozapine.
What kinds of things are antipsychotics used to treat (thought not always 1st line or a licensed indication)?	Psychosis, mood disorders, anxiety disorders, insomnia, rapid tranquillisation, nausea and vomiting, hiccups, tics including in Tourette's.
What is the MOA pf antipsychotics?	Through postsynaptic competetitive receptor antagonism at dopaminergic synapses.
Explain why the classic side effects of anti-psychotics occur	3 dopaminergic pathways in the brain: tuberoinfundibular, mesocortical/mesolimbic and nigrostriatal. The MOA of antipsychotics is through antagonism of the mesocortical/mesolimbic pathway. However, antagonism of the tuberoinfundibular and nigrostriatal pathways is responsible for some of the common side effects. Blockade of the tuberoinfundibular pathway can result in hyperprolactinaemia and the nigrostriatal pathway can result in extrrapyramidal side effects.
What are the general treatment aims for the use of antipsychotics in psychosis?	Alleviation of positive symptoms of psychosis. Alleviation of negative symptoms of psychosis. Minimise side-effects including metabolic disturbances. One of the challenges in psychiatry is the achieve these aims with an individual patient and is often made more difficult as the individual may have limited insight into their condition. Antipsychotics are effective (though less so for negative symptoms), however the side effects can be troublesome and can lead to non-concordance with treatment and subsequent relapse.
Which baseline investigations would be good to check before initiating treatment with antipsychotics?	ECG. Weight/height. BP. FBC. U&Es. LFTs. Prolactin. Glucose/HbA1c. Fasting lipids.
Describe the difference between typical and atypical antipsychotics.	Two broad categories of antipsychotics: typical and atypical. TYPICALS: Initially developed in the 50s. The first antipsychotics and the first effective treatments for schizophrenia. In more recent years, the second generation of antipsychotics have been developed, the 'atypicals'. Their MOA is dopamine receptor 2 (D2) antagonism. ATYPICALS: These have a different side effect profile yet overall are no more effective than the typicals. Their MOA is D2 antagonism +/- 5-HT receptor antagonism. Atypical antpsychotics are currently more frequently prescribed.
Name some typical antipsychotics.	Haloperidol. Pipothiazine. Flupentixol. Trifluperazine. Sulpiride. Chlorpromazine.
Name some atypical antipsychotics.	Clozapine, aripiprazole, quetiapine, risperidone, olanzapine.
What are some side effects of typical antipsychotics?	NEURO: neuroleptic malignant syndrome, lowered seizure threshold (fits), sedation, EPSEs. AUTONOMIC: BP, temperature. HYPERSENSITIVITY REACTIONS: Liver, bone marrow, skin. ENDOCRINE: Hyperprolactinaemia. PSYCHIATRIC: Apathy, confusion, depression. PERIPHERAL AUTONOMIC NS: Muscarinic receptor blockade, alpha1 adrenoceptor blockade. CARDIAC: Arrhythmia, especially long QT.
What are the 4 EPSEs?	Most widely reported side effect of typicals. AKATHISIA: subjective feeling of restlessness, often associated with objective signs eg pacing, rocking, repeatedly crossing legs. PARKINSONISM: tremor, rigidity and bradykinesia. Over days to weeks. ACUTE DYSTONIA: involuntary muscle spasms whih produce briefly sustained abnormal postures. Usually occurs within 48 hours of initiation. TARDIVE DYSKINESIA: Most concerning as may be irreversible. Abnormal involuntary hyperkinetic movements. Abnormal movements include tongue movements (fly-catching sign, bon-bon sign), pouting/smacking of lips, chewing, head-nodding, grimacing, rocking movements.
What are the features of metabolic syndrome and what is the relevance?	Most antipsychotics increase the risk of developing a metabolic syndrome. Aetiology is not well understood, but it is known that some antipsychotics are more likely to increase the risk (olanzapine clozapine). Features are: Central obesity. Insulin resistance. Impaired glucose regulation. Hypertension. Raised plasma triglycerides. Raised LDL cholesterol level, and/or low HDL cholesterol level. The presence of a metabolic syndrome can affect morbidity and mortality. Thus, as a clinician you must carry out a risk:benefit analysis, then subsequently monitor for evidence of metabolic syndrome.
What is Neuroleptic Malignant Syndrome?	Another important and potentially fatal SE of all antipsychotics. This idiosyncratic reaction has an incidence of 0.07-0.2% per year, with a mortality of 5-20%. This most frequently occurs when initiating treatment but can occur at any time. This should be treated as a medical emergency, all antipsychotics should be stopped immediately. Symptoms: Hyperthermia, muscle rigidity, confusion, tachycardia, hyper/hypotension, tremor, raised CK, low pH - metabolic acidosis.
Why might you give an antipsychotic as a depot? Which antipsychotics can you give this way?	An IM form of an antipsychotic may be preferred to oral preparations, usually due to poor compliance but may also just be patient choice. Usually given between weekly and monthly. Limited range available: TYPICALS: Haloperidol, flupentixol, zuclopenthixol, fluphenazine. ATYPICALS: Risperidone. Olanzapine.
What are some side effects of olanzapine (an atypical antipsychotic)?	probably the most widely prescribed atypical. As well as treating psychosis it can be used in rapid tranquillisation (IM). Usual oral dose 5-20mg nocte. Side effects: Sedation +++, weight gain +++ raised triglycerides, proglycaemic, dizziness, anticholinergic side effects.
What are some side effects of risperidone (an atypical antipsychotic)?	Usual dose 4-6mg. Usually given in divided doses. Depot preparation available - Risperidone Consta. Side effects: Sedation +, weight gain +, hyperprolactinaemia, sexual dysfunction ++, EPSE ++.
What are some side effects of quetiapine (an atypical antipsychotic)?	Requires titration. Usual dose 300-600mg/day in divided doses. Also available as once daily XL preparation. As well as psychosis, quetiapine has been shown to be effective in bipolar depression. Side effects: Sedation ++, weight gain ++, less metabolic disturbance than olanzapine, possible QT prolongation.
What is the MOA and what are some side effects of aripiprazole (an atypical antipsychotic)?	Dose usually 5-30mg. Long half-life. Side effects: Nausea, insomnia, ?initial exacerbation of psychosis, ?no weight gain, ?no metabolic effect. The MOA is partial dopamine agonist - limits the maximum response.
describe the features of clozapine	First introduced in the 60s. Indicated in treatment resistant schizophrenia. Improved efficacy over other antipsychotics. Positive effect on symptomatology and suicide risk. MOA is D4 blockade in addition to other sites (though the reason for its improved efficacy is not entirely clear).
What are the potential side effects of clozapine?	SERIOUS SIDE EFFECTS: Myocarditis/cardiomyopathy. Orthostatic hypotension. Agranulocytosis (this requires regular monitoring with initially weekly FBC). OTHERS: Sedation ++++, weight gain ++++, raised trigkycerides, pro-glycaemic, hypersalivation, reduced seizure threshold. Initiation requires careful dose titration, usually in hospital.
What do the NICE guidelines suggest for 1st, 2nd and 3rd line medications for psychosis?	1ST LINE: Atypical or typical antipsychotic. Decision based on discussion with patient. Several weeks trial. 2ND LINE: Atypical or typical antipsychotic. Decision based on discussion with patient. Several weeks trial. 3RD LINE: Clozapine.
What are the considerations in women of childbearing age?	Prefer them to be on LARC. Current evidence favours typicals in pregnancy.
How long should a patient stay on antipsychotics?	60-70% with chronic symptoms will relapse within 1 year of stopping medication vs 10-30% who continue on treatment. Continue medication for at least 1-2 years following recovery from an acute episode. Do not stop medication abruptly.
Which of the following is a tricyclic antidepressant? Aripiprazole, Citalopram, Dosulepin, Fluoxetine, Paroxetine, Mirtazapine, Sertraline, Venlafaxine	Dosulepin
Prescription of which of the following is most likely to be associated with weight gain? Amytriptylline, Citalopram, Dosulepin, Fluoxetine, Paroxetine, Mirtazapine, Sertraline, Venlafaxine	Mirtazapine
Which of the following has consistently been reported as a teratogen? Amitriptyline, Citalopram, Dosulepin, Fluoxetine, Paroxetine, Mirtazapine, Sertraline, Venlafaxine	Paroxetine
List some indications for antidepressants	Depressive illness (more effective in moderate/severe depression). Anxiety disorders. Neuropathic pain. Insomnia. Bulimia nervosa. Migraines. Chronic fatigue syndrome. Irritable bowel syndrome. Narcolepsy. NB: Antidepressants are NOT addictive.
What is the general mechanism of action of antidepressants?	Serotonin, noradrenalin and dopamine are all neurotransmitters that re implicated in depression and anxiety disorders. Antidepressants assert their effect mainly through the serotonin and noradrenaline systems. Most commonly prescribedantidepressants (SSRIs, TCAs, and SNRIs) inhibit the reuptake of serotonin, norad or both. (Serotonin pathway - raphe nuclei, Norad pathway - locus coeruleus).
Describe the mechanism of action of SSRIs.	SSRIs are by far the most commonly prescribed antidepressants in the UK. As the name suggests they primarily assert their effect on the serotonin system, however SSRIs also have a varying affinity for norad and dopamine transporters.
List some SSRIs.	Fluoxetine, Paroxetine, Citalopram, Sertraline, Fluvoxamine, Escitalopram.
Describe the side effect profile of SSRIs.	Probably the best tolerated antidepressants, but still not without side effects. Transient side-effects such as nausea and exacerbation of anxiety are common on initiation. There have also been reports of increase suicidal ideation with initiation. Others include: Nausea, insomnia, apathy and fatigue, diarrhoea, sweating, restlessness (akathesia), sexual dysfunction, cardiac defects with 1st trimester exposure (Paroxetine).
Describe the side effect profile of SNRIs.	SNRIs are the second most commonly prescribed class of antidepressants. The side effects are comparable to SSRIs but patients may notice more sedation and greater withdrawal symptoms. SNRIs are also associated with fewer sexual side-effects. SNRIs are generally reserved for 2nd or 3rd line treatments.
Name 2 SNRIs.	Venlafaxine, Duloxetine.
Describe the side effect profile of TCAs.	TCAs were discovered in the 50s and were very frequently prescribed. In more recent years SSRIs and SNRIs have largely replaced TCAs in routine clinical practice due to their preferable side effects. TCAs are toxic in overdose, therefore you should tke into account a person's risk of suicide when deciding on an appropriate antidepressant (Lofepramine is less toxic). TCAs have not been associated with teratogenic effects, therefore are often used 1st line in pregnancy. ANTTICHOLINERGIC SEs: dry mouth, constipation, impaired visual accommodation (blurred vision), difficulty in micturition. ALPHA-ADRENOCEPTOR BLOCKING SEs: Drowsiness, postural hypotension, sexual dysfunction. CV SEs: Tachycardia, hypotension, cardiac conduction deficits, arrhythmia. OTHER: Seizures, weight gain.
What are some contraindications for prescribing TCAs?	Agranulocytosis, severe liver damage, glaucoma and prostatic hypertrophy. Use cautiously in epileptic patients because they cause hypotension, and post-MI because of the CV effects.
List some tricyclic antidepressants.	Amitriptyline, Imipramine, Clomipramine, Dosulepin, Lofepramine.
Why has the use of monoamine oxidase inhibitors (MAOIs) now largely been superseded?	Because they carry a significant risk of serious drug/food interactions, commonly known as the "cheese reaction". This is because many foods, including cheese, contain a substance called tyramine, which is usually inactivated in the body by monoamine oxidase. This means that when on an MAOI the tyramine is not broken down and exerts its effect of releasing norad, with a pressor effect. This can result in a hypertensive crisis and, occasionally a cerebral haemorrhage if large amounts of tyramine are ingested. They do however continue to be used for treating resistant depression and atypical depression.
List some MAOIs.	Phenelzine, Tranylcypromine, Isocarboxazid, Moclobemide (the 'reversible MAOI').
Describe the features of Mirtazapine.	A Noradrenergic and Specific Serotonergic Antidepressant (NaSSA). Mirtazapine is effective in a variety of psychiatric disorders, there is also evodence to suggest that Mirtazapine may be superior to SSRIs in the treatment of depression. Mirtazapine can be combined with other antidepressants in treatment resistant depression; it is also a useful medication to reduce anxiety. Mirtazapine is moderately well tolerated. However, patients may experience significant sedation and/or weight gain on relatively low doses, which may not be acceptable to some patients.
What is St John's Wort?	St John's Wort is an unlicensed herbal remedy for the treatment of depression. RCTs have demonstrated efficacy, though probably less effective than SSRIs. Preparations are not standardised, therefore it is difficult to guide on dosing. It has several important drug reactions. It induces cytochrome P450 leading to loss of therapeutic effect of: OCP, digoxin, warfarin, HIV protease inhibitor, anticonvulsants (phenytoin, carbamazepine).
How should an antidepressant be started?	When initiating antidepressant treatment, it is important to select a medication that a patient is likely to tolerate. Initially commence an effective tolerated dose. Initial improvement can start within 1st week of treatment. At least 3-4 weeks (up to 12 weeks in elderly) at an effective dose are required before deciding whether a treatment has failed. If a partial improvement has occurred by 4 weeks it is advisable to continue treatment for another 2 to 4 weeks before considering alternative treatments. 70% will respond to first medication. It is advisable to continue the antidepressant at the same dose for at least 6 months following resolution of symptoms.
What might withdrawal from an antidepressant look like?	Withdrawal effects are recognised with all antidepressants, however are seen more frequently and with greater severity with paroxetine and venlafaxine. The symptoms are generally mild and transient but more severe and disabling withdrawal symptoms have been reported. The symptoms include dizziness, numbness, tingling, nausea, vomiting, headache, sweating, anxiety, sleep disturbance, strange dreams, shaking and electric-shock like sensations. Tapering the dose gradually over a period of at least 4 weeks can help reduce the symptoms.
Rate the likelihood of the following types of antidepressants to cause weight gain: NaSSA, SNRI, SSRI, TCA.	NaSSA ++++ SNRI + SSRI + TCA ++
For each of the antidepressants rate between (-) not present and (++++) severe for the risk of causing sexual dysfunction.	NaSSA - SNRI + SSRI ++ TCA +
For each of the antidepressants rate between (-) not present and (++++) severe for the risk of causing sedation.	NaSSA +++ SNRI +++ SSRI + TCA ++
Which of the following is not recommended for prophylaxis for bipolar disorder? Aripiprazole, Carbamazepine, Diazepam, Lithium, Quetiapine, Olanzapine, Valproate	Diazepam
Which of the following is most likely to affect renal function? Aripiprazole, Carbamazepine, Diazepam, Lithium, Quetiapine, Olanzapine, Valproate	Lithium
Exposure with which drug in the 1st trimester is associated with the highest rate of major congenital malformations. Aripiprazole, Carbamazepine, Diazepam, Lithium, Quetiapine, Olanzapine, Valproate	Valproate
Which drugs are referred to as mood stabilisers?	(LVLC): Lithium, Valproate, Lamotrigine, Carbamazepine
What are the indications for mood stabilisers?	Prophylaxis for bipolar disorder: Single manic episode associated with significant risk. Illness with significant impact on functioning. Two or more acute episodes. Treatment of an acute mania/hypomania (Generally not first line). Treatment of bipolar depression. Augmentation for antidepressants in treatment resistant depression.
What are the indications for Lithium?	MoA unclear. Indicated in acute mania/hypomania (good evidence), prophylaxis in bipolar disorder. Bipolar depression. Treatment resistant depression. A meta-analysis has shown that lithium treatment can reduce the risk of attempted and completed suicide by 80%.
What is the therapeutic range for lithium?	Narrow therapeutic range; it is therefore essential to titrate lithium dosing and monitor lithium levels after a minimum of 5 days, aiming for a range of 0.4-1.2mmol/L
What are the common side effects of lithium?	Due to the narrow therapeutic range it is key to distinguish between common and toxic side effects. GI upset, fine tremor, polyuria, polydipsia, metallic taste in mouth, weight gain, oedema.
What are the toxic side effects of lithium?	Lithiu toxicity is associated with low sodium diets, dehydration, drug interactions (NSAIDs, thiazide and loop diurectics) nd some physical illnesses such as Addison's. Lithium toxicity occurs with plasma concentrations over 1.5mmol/L. Symptoms of toxicity include course tremor, ataxia, nystagmus, dysarthria, confusion, convulsions. Plasma concentrations >2.5mmol/L are usually associated with serious toxicity requiring emergency treatment including haemodialysis.
What monitoring is required for a patient on lithium?	Narrow therapeutic range + nephrotoxicity + thyrotoxicty = Monitor lithium levels, U&Es and TFTs.
Describe the use of lithium in pregnancy.	Lithium is a known teratogen, with an increased risk of major congenital malformations (~6%), and therefore it is recommended that where possible lithium should be withdrawn prior to conception. The vast majority of the malformations are cardiac defects (ASDs and VSDs). The most widely quoted, but not the most common, is Ebstein's anomaly (of the tricuspid valve), with lithium exposure in the first trimester the rate of Ebstein's anomaly increases from 0.00005% to 0.1%.
What are the indications for Valproate?	Valproate is commonly used in two preparations sodium valproate and valproate semi-sodium (Depakote). Indicated in acute mania/hypomania and for prophylaxis in bipolar disorder (weaker evidence than lithium).
Describe the use of valproate in pregnancy	Known teratogen. Therefore adequate contraception, e.g. a LARC is essential when prescribing valproate. Ideally valproate should be withdrawn prior to conception. Antenatal valproate exposure is associated with adverse outcomes: Congenital malformation 8-10% NTDs 3% Low verbal IQ 30% Autism 6% Valproate syndrome 6%
What are the indications for lamotrigine in psychiatry?	Bipolar depression. Prophylaxis in bipolar disorder (limited evidence). Augmentation of antidepressants in treatment resistant depression. Clozapine augmentation.
What are the side effects of lamotrigine?	Generally well tolerated. However the dose must be titrated due to concerns with the development of Steven-Johnsons syndrome. Lamotrigine is probably the least teratogenic of the mood stabilisers, however there is possibly an increased risk of cleft lip/palate with first trimester exposure.
What are the MoA and indications for Carbamazepine in psychiatry?	Blocks voltage-gated sodium channels. Indicated in: Acute mania/hypomania (weaker evidence than lithium or valproate), prophylaxis in bipolar disorder (weak evidence), bipolar depression, augmentation of antidepressants in treatment resistant depression.
Which of the following is most likely to be associated with increased side-effects during foreign travel to tropical countries? Aripiprazole, Carbamazepine, Diazepam, Lithium, Quetiapine, Olanzapine, Valproate	Lithium

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