DRUGS USED IN PSYCHIATRY

Question 1

SSRIs:

1. Examples
2. Indications
3. Side-effects
4. Contraindications
5. Recommendations
6. Drug interactions

*Venlafaxine which is a serotonin-noradrenaline reuptake inhibitor has similar but more severe side-effects, promotes hypertension in 10%

Answer 1

1. Fluoxetine, Sertraline, Paroxetine, Citalopram
2. Depression, Anxiety Disorders, OCD, Bulimia nervosa(fluoxetine)
3. a) GI disturbance(early)
   - nausea, vomiting, diarrhoea, pain
   b) Agitation/anxiety(early)
   - increased risk of suicide in adolescents, hence only fluoxetine in <18s
   c) Insomnia
   d) Appetite loss
   e) Weight loss/gain
   f) Sweating
   g) Sexual dysfunction
   h) Bleeding diathesis
   i) hyponatraemia(SIADH): fatigue/drowsiness/weakness/confusion/fits
   - rare but esp in elderly and can be fatal
   * Long QTc with high dose citalopram
4. Mania
5. Patients with cardiac disease(sertraline has best evidence for safe use post MI) , better for patients at risk of overdose compared to TCA
6. a) PPI if patient is also taking NSAID
   b) warfarin/heparin
   - avoid SSRI and consider mirtazapine
   c) Triptans
   - avoid SSRIs

Question 2

NORADRENERGIC AND SPECIFIC SEROTONERGIC ANTIDEPRESSANT(NaSSA):

1. Example
2. Side effects
3. Contraindication

Answer 2

1. Mirtazapine(tetracyclic antidepressant)
2. a) Histamine antagonism leading to increased appetite, weight gain and sedation
   b) Headache
   c) Dry mouth
   d) Less common: Dizziness, postural hypotension, tremor, peripheral oedema
3. Mania

Question 3

TRICYCLIC ANTIDEPRESSANTS:

1. Mechanism
2. Examples
3. Side-effects
4. Recommendations and Other indications
5. Contraindications

• Trazodone(tricyclic-related antidepressant) is a good sedative and is usually used as an adjunct in those receiving non-sedating primary antidepressant
• Lofepramine less potent and shorter half-life

Answer 3

1. Presynaptic blockade of noradrenaline and serotonin reuptake pumps. Also blocks muscarinic, histaminergic and alpha-adrenergic receptors
2. Amitriptyline, clomipiramine, imipramine, lofepramine
3. a) Anticholinergic: constipation, dry mouth, blurred vision(exacerbation of angle-closure glaucoma), urinary retention
   b) Histaminergic receptor blockade: Weight gain, sedation
   c) Alpha-adrenergic receptor blockade: Postural hypotension leading to dizziness, syncope.
   d) Cardiotoxic: QT interval prolongation, arrhythmias
4. Patients with insomnia, Also used in small doses for treating neuropathic pain(esp amitriptyline) and prophylaxis of headaches(migraine and tension headaches); Anxiety states; OCD(esp clomipramine); ADHD(esp imipramine); noctural eneuresis
5. Mania, recent MI, severe liver disease, high risk of overdose, arrhythmias

Question 4

MONOAMINE OXIDASE INHIBITORS(MAOI)/REVERSIBLE INHIBITOR OF MONOAMINE OXIDASE A(RIMA)

1. Examples
2. Side-effects
3. Contraindications

Answer 4

1. Phenelzine, tranylcypromine, isocarboxazid, mocloblemide(RIMA)
2. a) Precipitation of hypertensive crisis
   - avoid tyramine-containing food and certain drugs
   b) Anticholinergic side-effects; Constipation, dry mouth, blurred vision, urinary retention
   c) Postural hypotension
3. Phaeochromocytoma, cerebrovascular disease, hepatic impairment, mania

Question 5

TYRAMINE-CONTAINING FOODS AND DRUGS TO BE AVOIDED WITH MAOIs

Answer 5

1. Cheese
2. Pickled herring, smoked chiken, liver
3. Chianti wine, beer
4. Broad bean pods
5. Soya bean extract
6. Overripe/unfresh food
7. Drugs:
   - Adrenaline including local anaesthetics containing adrenaline
   - Amfetamines
   - Cocaine
   - Ephedrine, pseudoephedrine, phenylpropanolamine(cough mixtures, decongestants)
   - L-dopa, dopamine

Question 6

SEROTONIN SYNDROME:

1. Precipitants
2. Clinical features
3. Prevention

Answer 6

1. a) When SSRIs/clomipramine/imipramine administered with MAOI
   b) Coadministration of opioids(pethidine and tramadol) with MAOI
2. Triad of neuromuscular abnormalities, altered consciousness and autonomic instability
3. a) Start other antidepressants 2w after stopping MAOI(3w if clomipramine/imipramine)
   b) Start MAOI 2w after stopping other antidepressants(3w if clomipramine/imipramine)(5w if fluoxetine)

Question 7

DISCONTINUATION SYNDROME(SSRI):

1. Symptoms
2. Prevention

Answer 7

1. GI disturbance, dizziness, unsteadiness, agitation, headache, tremor, insomnia, paraesthesia
2. When stopping SSRI, gradually taper down over 4w
   - not necessary with fluoxetine
   - paroxetine has highest incidence of discontinuation symptoms

Question 8

LITHIUM(Priadel/Camcolit):

1. Indications
2. Side-effects
3. Signs of toxicity
4. Drug-interactions
5. Starting Lithium
6. Contraindications/Cautions

Answer 8

1. a) Acute mania
   b) Prophylaxis in bipolar affective disorder
   c) Augmentation in treatment-resistant depression
   d) Adjunct to antipsychotics in schizophrenia, schizoaffective disorder, aggression/impulsivity
2. Nephrotoxicity(nephrogenic diabetes insipidus): Thirst, polydipsia, polyuria, weight gain, oedema, fine tremor, precipitates/worsens skin problems, concentration and memory problems, hypothyroidism, impaired renal function, cardiac: T-wave flattening/inversion, leucocytosis, teratogenicity, idiopathic intracranial hypertension.
3. a)(Toxic) 1.5-2 mmol/L: nausea, vomiting, apathy, coarse tremor, ataxia, muscle weakness
   b) (Dangerously toxic) >2 mmol/l: nystagmus, dysarthria, impaired consciousness, hyperactive tendon reflexes, oliguria, hypotension, convulsions, coma
   c) Management:
   - Fluid resus in mild-moderate toxicity
   - Haemodialysis may be needed in severe toxicity
   - Sodium bicarbonate(limited evidence)
4. NSAIDs, Diuretics(especially thiazides), ACE-inhibitors, metronidazole, Antipsychotics(Increase Li-induced neurotoxicity)
5. a) Do following investigations prior to initiation:
   - FBC, U&E’s, TFT, Pregnancy test, ECG
   b) Monitor blood Li levels weekly until therapeutic level stable for 4w
   c) Monitor blood Li levels(therapeutic level: 0.4-1.0 mmol/L) every 3/12, measure levels at 12h post-dose; renal function every 6/12; TFT every 6/12; issue patients info booklet, alert card and record book
6. Pregnancy, breastfeeding, impaired renal function, thyroid disease, cardiac condtions, neurological conditions(eg Parkinson’s/Huntington’s)

Question 9

OTHER MOOD STABILIZIERS:

1. Valproate
   a) Indication
   b) Side-effects
2. Carbamazepine
   a) Indication
   b) Side-effects
3. Lamotrigine
   a) Indication
   b) Side-effects

Answer 9

• Check liver and haematological functions prior to initiating
  1. a) Epilepsy, Acute mania, Prophylaxis in bipolar affective disorder
  b) Increased appetite, weight gain, dizziness, nausea and vomiting, tremor, haematological abnormalities(thrombocytopenia, prolonged bleeding time, leucopenia), raised liver enzymes,

2. a) Epilepsy, prophylaxis in bipolar affective disorder
   b) Nausea and vomiting, skin rashes, Steven Johnson syndrome, blurred vision/diplopia, dizziness and ataxia, drowsiness, fatigue, hyponatraemia and fluid retention, haematological abn.(leucopenia, thrombocytopenia, eosinophilia), raised liver enzymes, agranulocytosis, SIADH
3. a) Epilepsy, prophylaxis of depressive episode in bipolar affective disorder
   b) Nausea and vomiting, skin rashes(consider withdrawal as risk of Stevens-Johnson syndrome), headache, aggression, irritability, sedation and dizziness, tremor

Question 10

ANTIPSYCHOTIC EXAMPLES:

1. 1st generation
2. 2nd generation

Answer 10

1. a) Chlorpromazine
   b) Sulpiride
   c) Haloperidol
   d) Flupentixol
   e) Zuclopenthixol
2. a) Clozapine
   b) Olanzapine
   c) Quetiapine
   d) Risperidone
   e) Amisulpiride

*Haloperidol, Flupentixol, Zuclopenthixol and Risperidone can be given as long-acting IM

Question 11

ANTIPSYCHOTIC MECHANISM OF ACTION:

Answer 11

1. D2-receptor antagonism in mesolimbic pathway
   - most antipsychotics other than clozapine
2. 5-HT2 receptor blockade
3. Clozapine
   - 5-HT2 and D4 receptors antagonism

Question 12

ANTIPSYCHOTIC SIDE-EFFECTS:

Answer 12

1. Worsening of negative and cognitive symptoms of schizophrenia
2. Extrapyramidal side-effects:
   - Parkinsonian symptoms
   - Acute dystonia
   - Akathisia
   - Tardive dyskinesia(40% of patients)(increased risk in elderly)
   - Neuroleptic malignant syndrome
3. Hyperprolactinaemia
   - Galactorrhoea
   - Amenorrhoea and infertility
   - Impaired glucose tolerance
   - Sexual dysfunction
4. Anticholinergic
   - Dry mouth
   - Constipation
   - Urinary retention
   - Blurred vision
5. Antihistaminergic
   - Sedation
   - Weight Gain
6. Cardiac effects
   - QT prolongation(especially haloperidol)
   - Arrhythmias
   - Myocarditis
   - Sudden death
7. Increased risk of metabolic syndrome
   - esp olanzapine, clozapine
8. Lowers seizure threshold
   - greater risk with 2nd gen
9. Hepatotoxicity
10. Cholestatic jaundice
11. Increased risk of stroke(especially olanzapine and risperidone) and VTE in elderly patients
12. Postural hypotension
13. Sexual dysfunction
14. Allergic rx
    - exp to phenothiazines(eg chlorpromazine) and clozapine

Question 13

CLOZAPINE:

1. Important side-effects
2. Contraindications/Cautions
3. Monitoring

Answer 13

1. a) Increased risk of metabolic syndrome
   - obesity, hypertension, dyslipidaemia, diabetes
   - increases cardiovascular mortality
   b) Agranulocytosis(0.8%), neutropaenia(3%)
   c) Myocarditis
   d) Cardiomyopathy
   e) constipation
   - large bowel hypostasis
2. a) Severely reduced conscious level
   b) Phaeochromocytoma
   c) Parkinson’s disease
   d) Epilepsy
   - reduces seizure threshold, induces seizures in up to 3% of patients
   e) Cardiac disease
   f) Metabolic syndrome
3. a) FBC prior to starting
   b) Weekly FBC for several weeks then monthly throughout treatment
   - reduces risk of agranulocytosis to <1 in 5000

Question 14

MANAGING ANTIPSYCHOTIC-INDUCED EXTRAPYRAMIDAL SIDE-EFFECTS:

1. Acute dystonia(days)
2. Parkinsonian motor symptoms(days-weeks)
3. Akathisia(days-weeks)
4. Tardive dyskinesia(months-years)
5. Neuroleptic malignant syndrome

Answer 14

1. a) Anticholinergics eg procyclidine(IV/IM/ORAL)
   b) Dose reduction
   c) Switch antipsychotic
2. Same as 1
3. a) Propanolol/short-term benzodiazepine
   b) Dose reduction
   c) Switch antipsychotic
4. a) Withdraw antipsychotic if possible
   b) Consider clozapine
   c) Consider benzodiazepines
   * Avoid anticholinergics

Question 15

NEUROLEPTIC MALIGNANT SYNDROME VS SEROTONIN SYNDROME:

1. Defining features
2. Neuromuscular abnormalities
3. Onset
4. Medication History
5. Typical blood results
6. Treatment
7. Mortality

Answer 15

1. Triad of neuromuscular abnormalities, altered consciousness level and autonomic dysfunction(sweating, hyperthermia, tachycardia, unstable BP)
2. Reduced activity: severe rigidity, dysphagia, dyspnoea, bradyreflexia vs increased activity: myoclonus/clonus, hyperreflexia, tremor, less severe muscular rigidity
3. Insidious vs Acute
4. Usually within 4-11d of initiation/dose increase of dopamine antagonist OR stopping/reducing dose of levodopa vs usually after 1-2 doses of new serotonergic medication
5. Elevated CK, WCC, hepatic transaminases, metabolic acidosis
6. a) Discontinue offending drugs
   b) Cool patient
   c) Monitor and manage hydration and haemodynamics. IV fluids to prevent renal failure. Consider ITU
   d) Monitor for complications ie pneumonia and renal failure
   e) Benzodiazepines for sedation if agitated
   f) i) in neuroleptic malignant syndrome
   - Bromocriptine to reverse dopamine blockade
   - Dantrolene to reduce muscle spasm
   - ECT
   ii) in serotonin syndrome
   - Cyproheptadine(5HT-2A antagonist)
7. 20% if untreated vs Low

Question 16

INDICATIONS FOR ANTIPSYCHOTICS:

1. Psychiatric
2. Non-psychiatric

Answer 16

1. a) Schizophrenia, schizoaffective disorder, delusional disorder
   b) Depression/mania with psychotic features
   c) Psychosis secondary to medical condition or psychoactive substance use
   d) Delirium
   - caution in alcohol withdrawal as antipsychotics reduce seizure threshold
   e) Behavioural disturbance in dementia
   - caution as increased risk of cerebrovascular accident
   f) Severe agitation, anxiety, violent/impulsive behaviour where benzodiazepines are CI
   - eg: EUPD-borderline type
2. a) Motor tics
   b) Nausea and vomiting
   - prochlorperazine
   c) Intractable hiccups and pruritus
   - chlorpromazine, haloperidol

Question 17

ANXIOLYTIC AND HYPNOTIC DRUGS:

1. Mechanism
2. Examples:
   a) Benzodiazepines
   b) Z drugs
3. Indications
   a) Benzodiazepines
   b) Z drugs
4. Side-effects

Answer 17

1. Potentiates GABA action hence chloride entry into post-synaptic cell.
2. a) - Oxazepam
   - Temazepam
   - Lorazepam(Short half-life, can be given IM/IV)
   - Chlordiazepoxide(short half-life but metabolite up to 100h)
   - Diazepam(long half-life, can give PR/IV/IM)
3. a) - Insomnia(short-term use, not longer for >2-4w, short-acting benzodiazepines): flurazepam, loprazolam, lormetazepam, nitrazepam, temazepam
   - Anxiety disorders(alprazolam, chlordiazepoxide, diazepam, lorazepam, midazolam, oxazepam)
   - Alcohol withdrawal(chlordiazepoxide, oxazepam)
   - Akathisia
   - Sedation during acute mania/psychosis
   - Epilepsy prophylaxis, seizures, muscle spasm(anticonvulsants: clobazam, clonazepam. avoid in anxiety states)
   - anaesthetic premedication(midazolam)

b) Insomnia(short-term use)

4. a) Dependence
   b) Ataxia, drowziness, reduced motor coordination
   - caution about driving and operating machinery
   c) may precipitate respiratory depression
   - caution in chronic respiratory disease
   - effects enhanced by alcohol, opiates, barbiturates, TCA, antihistamines
   d) benzodiazepines can cause anterograde amnesia

*Flumazenil can reverse effects but give as slow IV bolus

Question 18

OTHER HYPNOTIC AND ANXIOLYTIC AGENTS:

1. Buspirone
2. Sedating antihistamines

Answer 18

1. • 5-HT1a receptor antagonist
     - used in treating generalised anxiety disorder
     - no hypnotic, anticonvulsant or muscle relaxant properties
     - not associated with dependence/abuse
     - response to treatment can take up to 2w
2. • diphenhydramine(Nytol) available without prescription and can be used for insomnia
     - drowsiness on following day

Question 19

TCA OVERDOSE:

• Amitriptyline and dosulepin(dothiepin) are most dangerous
• Lofepramine lower incidence of toxicity in overdose
  1. Features:
  2. Management

Answer 19

1. a) Early: Anticholinergic(dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision)
   b) Other features: arrhythmias, seizures, metabolic acidosis, coma, ECG changes(tachycardia, long QT, wide QRS)
2. a) IV bicarbonate to reduce risk of seizures and arrhythmias
   - correction of metabolic acidosis is 1st line tx for tricyclic-induced arrhythmia
   b) Lignocaine if bicarbonate is ineffective

Question 20

BENZODIAZEPINE WITHDRAWAL SYNDROME:

1. Features
2. How to withdraw benzodiazepine

Answer 20

1. Insomnia, irritability, anxiety, tremor, appetite loss, tinnitus, perspiration, perceptual disturbances(distoroted visual relationships/walking on cotton wool), seizures.
2. Withdraw in steps of 1/10 to 1/4 of daily dose every 2w.
   - time needed can vary from 4w to 1y
   - if having difficulty, switch to equivalent dose of diazepam, reduce dose every 2-3w in steps of 2 or 2.5 mg

Question 21

ACETYLCHOLINESTERASE INHIBITORS:

1. Examples
2. Indications
3. Side effects;
4. Cautions
5. Interactions

Answer 21

1. Donepezil, Rivastigmine, Galantamine
2. Mild-moderate Alzheimer’s Disease
3. a) Nausea, vomiting, diarrhoea
   b) Weight loss
   c) Agitation
   d) Muscle cramps
   e) Insomnia
4. Cardiac conduction problems, peptic ulcer, bladder outflow obstruction, asthma/COPD, Seizures, gallstones
5. Muscle relaxant in anaesthesia, beta-blockers, cholinergic and anticholinergic drugs

Question 22

NMDA RECEPTOR MODULATOR:

1. Example
2. Indication

Answer 22

1. Memantine

2. Moderate-severe Alzheimer’s