Psychiatry - Psychopharmacology Flashcards
Examples of SSRIs
Citalopram
Fluoxetine
Paroxetine
Sertraline
Indications for using SSRIs
Depression (treatment and prophylaxis in recurrent episodes)
Anxiety disorders (e.g. GAD, panic disorder)
Bulimia (fluoxetine)
OCD
PTSD
What side effects are associated with SSRIs?
GI disturbances (dose related, usually transient) - nausea, vomiting, anorexia, weight loss, diarrhoea - increase risk of GI bleeding so gastric protection should be given if patients also taking an NSAID
Sexual - loss of libido, delayed orgasm
Hypersensitivity reaction
Others - headache, anxiety, sleep disturbance, restlessness
Contraindications for using SSRIs
Mania, use with caution in bipolar disorder
Important prescribing notes to remember about SSRIs
Once daily
Used as first line treatment for depression
May take up to 2 weeks before any effect, and 6 weeks for full effect
- should be reviewed 2 weeks after starting (1 week if under 30 or severe depression)
- continue treatment for 6 months after remission to reduce relapse
Withdrawal or discontinuation symptoms are common (especially with paroxetine)
Relatively safe in overdose but some patients report suicidal ideation
What are discontinuation symptoms?
Symptoms experienced after stopping SSRIs They include: - increased mood change - restlessness - difficulty sleeping - sweating - GI symptoms: pain, cramping, diarrhoea and vomiting - paraesthesia
What side effect is associated with citalopram?
Dose dependent QT interval prolongation
Should not be used in patients with congenital long QT syndrome, known pre existing QT interval prolongation or in combination with other drugs that can prolong the QT
Which SSRI is safest after MI?
Sertraline
What SSRI is safest for use in children or adolescence?
SSRIs should be used with caution in children and adolescence, but if they need to be used fluoxetine is the safest
What drugs do SSRIs interact with?
NSAIDs/ aspirin: do not normally offer SSRIs, but if given co prescribe a PPI
Warfarin/ heparin: avoid SSRIs and use mertazapine
Triptans: avoid SSRIs
Examples of tricyclic antidepressants
Amitriptyline
Imipramine
Lofepramine
Clomipramine
Indications for TCA use
Depression
OCD (clomipramine)
Neuropathic pain (amitriptyline)
Noctunral enuresis in children (imipramine)
Side effects associated with TCAs
Antimuscarinic - dry mouth, blurred vision, urinary retention, constipation
Drowsiness
Cardiovascular - postural hypotension, arrhythmia
Toxicity in OD - cardiotoxic, respiratory failure, seizures, convulsions, coma (amitriptyline most dangerous)
Contraindications of TCAs
Recent MI
Arrhythmias
Severe liver disease
Mania - use with caution in bipolar disorder
Important prescribing notes about TCAs
Given in divided doses or a single dose before bed
May take up to 2 weeks before any effect and 6 weeks for full effect
May cause drowsiness - advise patient to avoid driving
Avoid if high suicide risk in outpatient as can be lethal in overdose (lofepramine is the safest in OD)
Examples of MAOIs
Phenelzine
Moclobemide
Indications for using MAOIs
Refractory/ atypical depression
Side effects of MAOIs
Postural hypotension
Antimuscarinic
Increased appetite and weight gain
Hepatotoxicity
Hypertensive crisis - due to interactions between MAOIs and tyramine containing foods
- release of NA causes tacchycardia, hypertension, and vasoconstriction
- may lead to intracerebral haemorrhage or subarachnoid haemorrhage
- hypertensive crisis may also be precipitated by: sympathomimetics, TCAs, amphetamines, L-dopa
Serotonin syndrome - due to interactions between MAOIs and 5-HT enhancing drugs (e.g. SSRIs)
NB - side effects and interactions are less common with moclobemide as it is reversible
What is serotonin syndrome?
Precipitated by:
- MAOIs
- SSRIs
- amphetamine
- ecstasy
Features:
- neuromuscular excitation (e.g. hyperreflexia, myoclonus, rigidity)
- autonomic nervous system excitation (e.g. hyperthermia)
- altered mental state
Contraindications for using MAOIs
Mania - use with caution in bipolar disorder
Hepatic impairment
Cerebrovascular disease
Phaeochromocytoma
What foods should patients avoid when taking MAOIs?
Cheese Non fresh fish, meat and poultry Broad beans Marmite, bovril and Oxo Alcohol
How long after stopping other anti-depressants can an MAOI be started?
MAOIs should not be started until at least 1 week after cessation of other anti-depressants
Other antidepressants should not be prescribed until 2 weeks after discontinuing MAOIs
What is venlafaxine?
SNRI - serotonin and noradrenaline reuptake inhibitor
Used to treat depression and GAD
Side effects of venlafaxine
Constipation Nausea Dizziness Sleep disturbance Hypertension
Contraindications to using venlafaxine
High risk of cardiac arrhythmia
Uncontrolled hypertension
Pregnancy
What is mirtazapine?
Presynaptic alpha 2 antagonist
Indicated in depression
Side effects of mirtazapine
Increased appetite
Oedema
Sedation
Important prescribing notes for venlafaxine and mirtazapine
Mirtazapine is given before bedtime as it aids sleep
It has few antimuscarinic side effects so can be useful in elderly patients
Venlafaxine can be given as a once daily modified release prep
It should be used as a second line treatment under specialist supervision
Requires monitoring of BP
How should you switch between SSRIs?
(Maudesly hospital guidelines)
Switching between citalopram, sertraline or paroxetine and other SSRIs
- first SSRI should be withdrawn (gradually reduce the dose then stop) before the others are given
Switching from fluoxetine to other SSRIs
- withdraw then leave a gap of 4-7 days (as it has a long half life) before starting a low dose of the alternative SSRI
How should you switch between an SSRI and a TCA?
Cross tapering is recommended - current dose is reduced slowly whilst the dose of the new drug is increased slowly
The exception is fluoxetine which should be withdrawn prior to TCAs being started
How do you switch between an SSRI and venlafaxine
Cross taper cautiously. Start venlafaxine 37.5mg per day and taper up slowly
Fluoxetine is the exception. Withdraw and then start venlafaxine at 37.5mg per day and increase slowly
Examples of atypical antipsychotics
Olanzapine Risperidone Queitiapine Aripiprazole Amisulpride
Indications for using atypical antipsychotics
Schizophrenia Other psychotic illnesses Mania Prophylaxis in bipolar affective disorder (olanzapine) Agitation
Atypical antipsychotics are preferred 1st line over typicals due to their more favourable side effect profile
What side effects are associated with atypical antipsychotics?
Weight gain Postural hypotension Drowsiness Extrapyramidal side effects do occur but are less common than with typical antipsychotics Diabetes
Contraindications for atypical antipsychotics
Use with caution in those with cardiovascular disease, epilepsy and the elderly
What monitoring is recommended for atypical antipsychotics?
Weight BP ECG Lipids Glucose/ HbA1c FBC U&E LFTs
Examples of typical antipsychotics
Phenothiazines - chlorpormazine, fluphenazine, thioridazine, prochlorperazine
Butyrophenones - haloperidol, droperidol
Thioxanthine - flupenthixol
Benzamide - sulpride
Indications for using typical antipsychotics
Schizophrenia
Other psychotic illness
Mania
Agitation
What extrapyramidal side effects are associated with typical antipsychotics?
Extra pyramidal symptoms occur because typical antipsychotics block dopamine D2 receptors in the mesolimbic pathway.
1) Acute dystonia
- presents with grimacing, abnormal movements and facial spasms, especially masseter muscles
- may even lead to jaw dislocation, torticolis, limb rigidity, and altered behaviour
- treat with procyclidine bolus 5 mg i.m. Symptoms should improve quickly, then continue with oral procyclidine 8 hourly as necessary
2) Parkinsonism
- tremor
- rigidity
- bradykinesia
- treated with procyclidine or another antimuscarinic drug
3) Akathisia (restlessness)
- difficult to treat
- review medication
- consider propranolol
4) Tardive dyskinesia (involuntary movements usually of the oral-lingual region)
- consider changing medication
- tends to be reversible
What is neuroleptic malignant syndrome? How does it present?
Rare but potentially fatal complication of antipsychotic treatments
Presents with hyperthermia, fluctuating levels of consciousness, muscular rigidity, autonomic dysfunction with pallor, tachycardia, labile BP, sweating and urinary incontinence
Increased white cells and creatine phosphokinase
Stop antipsychotic and provide cardiovascular and respiratory support (ideally on ITU). Bromocriptine and dantrolene may be used but there is no proven effective treatment
Usually lasts for 5-7 days after discontinuation of the antipsychotic
Other side effects of typical antipsychotics
Antimuscarinic: dry mouth, blurred vision, urinary retention, constipation
Sedation, weight gain
Raised prolactin: galactorrhoea, impaired glucose tolerance
Reduced seizure threshold (greater with atypicals)
Prolonged QT interval (particularly haloperidol)
What are the indications for using clozapine?
Clozapine is an atypical antipsychotic used for treatment resistant schizophrenia (psychotic symptoms which have failed to respond to adequate trials of two antipsychotics, at least one of which is atypical)
Side effects associated with clozapine
Agranulocytosis (rare but potentially fatal)
Constipation (laxatives can be used)
Tachycardia (can be treated with beta blockers)
Hypersalivation (can be treated with hyoscine)
Sedation (give smaller doses in the morning)
Hypertension
Weight gain
Diabetes (treat accordingly)
Convulsions (valproate can be given)
Myocarditis
What are the contraindications for treatment with clozapine?
Severe cardiac disease
Active liver disease
Severe renal impairment
History of bone marrow disorders
What monitoring is required for clozapine?
Clozapine is effective and reduces mortality (largely by reducing suicide rate) but it can cause considerable side effects. Risk of agranulocytosis is well managed by the mandatory clozipine monitoring systems. These involve the patient having regular blood tests and results being checked before clozapine is dispensed. Blood tests are for the first 18 weeks, then fortnightly for the remainder of the year, then monthly thereafter
All side effects are more likely to occur in early stages so careful monitoring and dose titration are needed
BP, pulse and temperature are monitored very closely during titration of dose. Long term monitoring requires:
- weight
- ECG
- lipids
- glucose/ HbA1c
- LFTs
If the patient misses more than 2 days of clozipine they will need to be recommenced on their treatment at the beginning with dose titration
Examples of anxiolytics
Diazepam, nitrazepam - prolonged action
Lorazepam, temazepam - short action
What are the indications for anxiolytic therapy?
Short term relief of anxiety Insomnia (hypnotic effect) Alcohol withdrawal (chlordiazepoxide) Status epilepticus (diazepam) Premedication before surgery
What are the side effects of anxiolytics?
Drowsiness Paradoxical agitation and aggression Confusion Dependence and tolerance with prolonged use, so should only be prescribed for the short term Withdrawal syndrome after prolonged use
Features that characterise the withdrawal syndrome of anxiolytics
Insomnia Anxiety Loss of appetite and weight Tremor Sweating Perceptual disturbances
Transfer patients to equivalent daily dose of diazepam and withdraw in gradual steps
Contraindications of anxiolytics
Respiratory depression
Severe hepatic impairment (benzodiazepines are metabolised in the liver, so accumulation of active metabolites occurs
What other factors should you consider when prescribing anxiolytics?
Care with alcohol and other minor tranquilizers as they enhance the sedative effect of benzodiazepines
Hangover effect can impair the ability to drive and operate machinery
Flumazenil is a benzodiazepine antagonist that can be given as an antidote in overdose
Administered orally, i.m., i.v., or p.r., in divided daily doses depending on particular drug and clinical circumstances
Medications used for ADHD
Methylphenidate - ADHD
Dexamphetamine - refractory ADHD and narcolepsy
Atomoxetine
All should be prescribed under strict specialist supervision
What side effects are associated medication used to treat ADHD?
Decreased appetite with resultant weight loss and possible growth retardation
Rebound hyperactivity
Depression
Insomnia
Headache
GI symptoms (e.g. stomach pain/ GI upset)
Theoretically may worsen epilepsy
Contraindications to ADHD medication
Cardiovascular disease
Hyperthyroidism
Predisposition to tics or Tourette’s syndrome
Factors to consider when prescribing ADHD medication
Very rarely prescribed for children under 6
Drug treatment should be reserved for severe cases that have not responded to other measures
High doses may cause growth retardation
Drugs may be needed for months to years and careful monitoring of height and weight is essential
Need to give doses every 4 hours (morning, lunchtime and evening) as methylphenidate has a short half life
What is ECT? When is it used?
A medical procedure used under controlled conditions to treat some major psychiatric disorders including severe depressive illness, mania, puerperal psychosis and catatonic schizophrenia
Used when illness remains unresponsive to other treatments or when a very rapid response is needed (e.g. patient not eating or drinking due to depressive stupor)
Patient is anaesthetised and given a muscle relaxant; seizures are then induced by delivering brief electrical stimuli to the brain via scalp electrodes
Patients usually receive a total of 6-12 treatments, given twice weekly
Under what circumstances can ECT be performed?
Amended MHA:
- patient understands the treatment and consents
- the patient does not have capacity to consent and a second opinion approved doctor is consulted and agrees and it does not conflict with an advance directive by the patient
Emergency ECT can be given under section 62 while awaiting a second opinion if:
- it is immediately necessary to prevent serious suffering
- it is immediately necessary to prevent the presenting a danger to themselves or others
What should be done prior to ECT?
Patients must have a full operative workup, including any necessary investigations - e.g. CXR, U&E, FBC, ECG
Antiepileptics and benzodiazepines should be discontinued before treatment if possible as they increase the risk of seizure threshold
Side effects of ECT
Confusion
Headache
Short term memory loss
Complications of ECT
Anaesthetic problems
Status epilepticus
The risk is the same as that for a general anaesthetic for other minor procedures (NB: 10% of those with depression will commit suicide)
Contraindications of ECT
Serious anaesthetic risk Raised ICP (as ICP rises further during treatment)
Examples of medication used to treat dementia
Acetylcholine esterase inhibitors: donepezil, galantamine, rivastigmine
NMDA receptor antagonists: memantine
What are the indications for using the anti-dementia medications?
Acetylcholine esterase inhibitors:
- mild to moderate dementia related to AD
- mild to moderate dementia related to PD (rivastigmine only)
Memantine: moderate to severe dementia related to AD
What side effects are associated with acetylcholine esterase inhibitors?
GI - nausea, vomiting, gastric and duodenal ulcers, GI haemorrhage
Cardiovascular - dizziness, syncope, bradycardia, AV heart blocks, MI
Psychiatric - hallucinations, agitation
Others - rash, muscle cramps
Side effects associated with memantine
Constipation Hypertension Seizures Dizziness Depression
Contraindications to anti-dementia medication
Acetylcholine esterase inhibitors:
- renal impairment (galantamine)
- caution in cardiac disease and those with susceptibility to peptic ulcers
Memantine:
- caution in renal impairment and those with history of seizures
Factors to consider when prescribing anti-dementia medication
Start with the lowest dose possible and gradually increase whilst monitoring for side effects
With acetylcholine esterase inhibitors, monitor congition and pulse regularly (at least every 6 months)
Review appropriateness of acetylcholine esterase inhibitors in severe dementia (MMSE < 10)
Examples of hypnotic medication
Zopiclone
Zolpidem
Also temazepam and diazepam (as anxiolytics)
Indicated only for short term treatment of insomnia
Hangover effect occurs
Should only be prescribed when other methods have failed
Side effects of hypnotic medication
GI disturbances
Headache
Dependence
Memory disturbances
What are the contraindications to using hypnotic medication?
OSA Respiratory failure Myasthenia gravis Pregnancy and breast feeding Caution in a history of alcohol or drug abuse Caution in hepatic or renal impairment
What medication is used for alcohol dependence?
Disulfiram (aversive)
Acamprosate (anti-craving)
Indicated for maintaining abstinence from alcohol in dependence
What are the side effects associated with drugs used for alcohol dependence?
Disulfiram - fatigue, halitosis, reduced libido, rarely psychosis
Acamprosate - GI disturbance, rash
Contraindications for using alcohol dependence drugs
Disfulfiram - cardiac disease, hypertension, previous CVA, psychosis
Acamprosate - severe hepatic or renal failure
What is important to counsel a patient when taking drugs used to treat alcohol dependence?
Consuming even a small amount of alcohol while taking disulfiram leads to a build up of acetaldehyde, causing an extremely unpleasant reaction, including:
- facial flushing
- headache
- palpitations
- nausea and vomiting
Compliance is increased if it is monitored by a spouse or family member
Discontinue acamprosate if the patient returns to regular drinking
What drugs are used to treat opioid dependence?
Methadone Buprenorphine (partial opioid agonist)
Indicated as substitute prescribing for opiates as a means of harm reduction
Side effects associated with drugs used to treat opioid dependence
Methadone
- fatal overdose
- QT prolongation
Buprenorphine
- abdominal pain
- fatigue
- anxiety
What are the contraindications to prescribing drugs to treat opioid dependence?
Caution when prescribing methadone and buprenorphine in those using alcohol and benzodiazepines as this will increase mortality
Caution with severe hepatic and renal failure which will reduce the metabolism and elimination of methadone and so increase the risk of overdose
Methadone is considered safer than buprenorphine in pregnancy and breastfeeding
What should be done before initiating drugs to treat opioid dependence?
Before prescribing, confirm opioid dependence by positive urine results and objective signs of withdrawel (lactorrhoea, rhinorrhea, agitation, sweating, yawning, dilated pupils)
First 2 weeks of methadone treatment are associated with a substantially increased risk of death due to overdose, and so careful assessment, titration of dose and monitoring are essential
Initial dose is low to reduce risk of OD and gradually increased depending on withdrawel symptoms
Supervised daily consumption is recommended for the first 3 months
Once patients are stable and not using ellicit drugs, consideration should be given to gradually reducing the dose with the aim of discontinuing treatment
What should be prescribed alongside buprenorphine or methadone?
Naloxone in the event of buprenorphine or methadone OD
How should buprenorphine be started?
Commencing buprenorphine may cause precipitated withdrawal and so the first dose
should be given when the patient is experiencing withdrawal symptoms to reduce this risk.
What are the indications for using carbamazepine?
Prophylaxis of bipolar disorder
Treatment of epilepsy and trigeminal neuralgia
What are the side effects of carbmazepine?
Erythematous rash may occur in a large number of patients
GI disturbances - diarrhoea, nausea, vomiting, anorexia
Neurological - dizziness, headache, ataxia, diplopia
Haematological - leucopenia, thrombocytopaenia, agranulocytosis (1 in 20,000), aplastic anaemia (1 in 20,000)
Biochemical - hyponatraemia
What are the contraindications to carbamazepine therapy?
Atrioventricular conduction abnormalities (unless paced) History of bone marrow depression Acute porphyria Pregnancy Pregnancy and breast feeding
What investigations are required before carbamazepine therapy can be started?
Blood tests - FBC, LFT, U&E
Pregnancy test
ECG
Regular blood monitoring is required throughout treatment
What are the indications for sodium valproate therapy?
Mania in bipolar affective disorder
Prophylaxis in bipolar affective disorder
Refractory depression
Epilepsy
Side effects of sodium valproate
Vomiting Alopecia Liver toxicity Pancreatitis/ pancytopaenia Retention of fats (weight gain) Oedema Anorexia Tremor Enzyme inhibitor
Contraindications to sodium valproate treatment
Hepatic dysfunction
Porphyria
Pregnancy and breast feeding
Important prescribing features of sodium valproate
It may be particularly useful in patients who undergo rapid cycling (four or more episodes per year)
Liver function tests should be checked regularly
Fewer adverse side effects than other anti-epileptics
Patients should be given a leaflet about recognising haematological/ hepatic side effects
It is teratogenic and most foetal malformations are neural tube defects. Adequate contraception should be ensured in women of child bearing age, particularly as manic women can be sexually disinhibited
What are the indications for lithium therapy?
Prophylaxis in bipolar effective disorder (decreases frequency and severity of manic and depressive episodes)
Augments antidepressants in treatment of refractory depression
Mania (use limited by difficulties achieving therapeutic serum levels rapidly)
Aggressive or self mutilating behaviours
Side effects of lithium
General - weight gain, oedema, fine tremor, muscle weakness, worsening of acne and psoriasis
Gastrointestinal - diarrhoea, nausea, vomiting, metallic taste
Renal - nephrogenic diabetes insipidus (polyuria and polydipsia), long term use can result in impaired renal function
Endocrine - hypothyroidism, hyperparathyroidism
Cardiac - T wave inversion
Haematological - leucocytosis
What are the contraindications to lithium therpay?
Pregnancy
Caution in renal disease and cardiac disease
Caution in conditions causing sodium imbalance such as Addison’s disease
What is the therapeutic range of lithium?
Lithium has a narrow therapeutic index
0.6-1.0 mmol/L
Increased side effects above 1.2 mmol/L
Risk of toxic effects above 1.5 mmol/L
What investigations are needed before and during lithium therapy?
Before lithium therapy:
- medication review (NSAIDs and ACEi interact)
- blood tests - FBC, U&E, thyroid screen, pregnancy test
- ECG
Investigations during treatment:
- lithium plasma level (every 3 months after dose has stabilised)
- regular monitoring of FBC, U&E, Ca and TFT
Advise patients to consume adequate fluid intake and avoid diets with excess sodium
Why is good adherence important for lithium therapy?
Long term treatment with lithium reduces the risk of suicide in bipolar affective disorder to the level of the general population
There is some evidence that intermittent treatment with lithium may worsen the natural course of bipolar affective disorder and so it should only be commenced if it is intended to continue for the long term
When does lithium toxicity occur?
Toxic levels occur over 1.5 mmol/L
Antidepressants, anticonvulsants, antipsychotics, and Ca channel blockers as well as any cause of dehydration can all precipitate toxicity
Presentation of lithium toxicity
Severe nausea Vomiting Diarrhoea Disorientation Seizures Drowsiness
Management of lithium toxicity
Lithium should be stopped and an urgent lithium level obtained and fluids given. Specialist input should be sought as haemodialysis may be needed.
