Psychopharmacology: Antidepressants & Antipsychotics Flashcards
Remind yourself of some conditions antidepressants are used for
- Moderate to severe depression
- Dysthmia
- Anxiety disorders
- OCD
- PTSD
- Eating disorders
- Chronic pain
State the 7 different classes of antidepressants
What route are all antidepressants given via?
Oral
Describe the mechanism of action of SSRIs
State some examples
- Inhibit re-uptake of serotonin into presynaptic neurones to increase the cocentration of serotonin in the synaptic cleft
- Examples:
- Fluoxetine
- Sertraline
- Citalopram
- Escitalopram
- Paroxetine
- Fluvoxamine
Why is fluvoxamine not regulary prescribed anymore?
Cytochrome P450 enzyme inhibitor so commonly interacts with other medications potentating their side effects
State some common side effects of SSRIs
*HINT: categorise your answers into GI side effects, CNS side effects & sexual side efffects
- Nausea
- Flatulence
- Diarrhoea
- Insomnia
- Restlessness
- Irritability
- Agitation
- Tremor
- Headache
- Acute dystonia (uncommon)
- Ejaculatory delay
- Anorgasmia
What are the risks of SSRI use in:
- 1st trimester
- 3rd trimester
- 1st trimester= increased risk of congenital heart defects
- 3rd trimester= increased risk of persistent pulmonary hypertension
What must you also prescribe if someone is taking both an SSRI and an NSAID and why?
PPI e.g. omeprazole as SSRIs increase risk of bleeding in GI tract in particular when combined with NSAIDs
State a contraindication to using an SSRI
- Mania
Cautions include:
- History of mania
- Epilepsy
- Acute angle glaucoma
- Diabetes mellitus (monitor glycaemic control after initiation)
- GI bleeding
- Increased suicide risk in young adults
Give some example doses of common SSRI drugs
*Just so you have an idea
- Sertraline: 50-200mg/day
- Fluoxetine: 20-60mg/day
- Citalopram: 20-40mg/day
- Escitalopram: 10-20mg/day
- Paroxetine: 20-50mg/day
*Citalopram is lowest dose, sertraline is highest. Rest sit roughly between these two doses.
Describe the mechanism of action of SNRIs
State some examples of SNRIs
Prevent reuptake of noradrenaline and serotonin into presynaptic neurone to increase concentration of both in the synaptic cleft
Examples:
- Venlafaxine
- Duloxetine
State some common side effects of SNRIs
- Nausea
- Dry mouth
- Headache
- Dizziness
- Sexual dysfunction
- Hypertension
- Decreased appetite
- Arrhythmias/palpitations
State some contraindications for SNRIs
- Uncontrolled hypertension
Caution with conditions associated with high risk of cardiac arrhythmia. Other cautions similar to SSRIs.
Describe mechanism of action for tricyclic antidepressants
State some examples
Inhibit reuptake of noradrenaline and serotonin into pre-synaptic neurone to increase concentration of both in synaptic cleft. Also have affinity for cholinergic receptors (contributes to side effect profile).
Examples:
- Amitriptyline
- Clomipramine
- Nortriptyline
- Dosulepin
State some common side effects of TCAs
*HINT: group side effects into anticholinergic, cardiovascular, hypersensitivity, psychiatric, metabolic, neurological & others
- Anticholinergic: dry mouth, constipation, urinary retention (which may lead to overflow incontinence), blurred vision
- Cardiovascular: arrhythmias, postural hypotension, syncope
- Hypersensitivity: urticarial, photosensitivity
- Psychiatric: hypomania/mania, delerium or confusion
- Metabolic: increased appetite & weight gain
- Neurological: convulsions, taste disturbances
- Others: headache, sexual dysfunction, tremor
*Key ones to inform pts of: urinary retention, cardiac, convulsions as these are serious/can be problematic
State some contraindications to TCAs
- Arrhythmias (particulary heart block- seek cardiologist input if need to start)
- Mania
- Agranulocytosis
- Severe liver disease
Cautions include: history of epilepsy, cardiac disease, preg & breast feeing, history of main, glaucoma, history urinary retention
Describe the mechanism of action of MAOI
State some examples
Inactivate monoamine oxidase enzymes that oxidize the monoamine neurotransmitters dopamine, noradrenaline, serotonin & tyramine hence increasing availabity of the neurotransmitters.
Examples:
- Moclobemide (reversible)
- Phenelzine (irreversible)
- Isocarboxide (irreversible)
State some common side effects of MAOIs
- GI: constipation, diarrhoea, nausea, hepatotoxicity
- CNS: headahce, parasthesia, dry mouth, postural hypotension
- Hypertensive reactions with tyramine containing foods
Explain why a hypertensive crisis may occur if pt taking MAOI ingests tyramine containing foods
What are the features of a hypertensive crisis?
State some tyramine containing foods
Tryamine, found in some food & drinks, is usually inactivated in body by monoamine oxidases; if taking MAOIs these enzymes are inhibited hence tyramine is not broken down. Tyramine causes the release of noradrenaline which has a pressor effect causing raised BP.
Features: headache, palpitations, fever, convulsions, coma
Few examples of tyramine containing foods:
- Most cheeses
- Some red wines & beer
- Cured & smoked meats
- Marmite
MAOIs interact with certain drugs; state some examples
- SSRIs
- TCAs
- Opiates
- Anti-epileptics
- Insulin
State 2 contraindications to MAOIs
Acute confusional states
Phaeochromocytoma
Mirtazapine is now recongised as a class of its own however used to be called a noradrenaline serotonin specific antidepressant (NASSA), disucss:
- Mechanism of action
- Common side effects
- Who it is ideal for
Alpha-1 and alpha-2 antagonist hence enhances central adrenergic & serotonergic transmission. Also has weak noradrenaline re-uptake inhibiting effect and strong anti-histaminergic properties.
Common side effects:
- Dry mouth
- Nausea
- Diarrhoea/constipation
- Increased appetite and weight gain
- Sedation
- Fatigue
- Insomnia
- Abnormal dreams
- Tremor
Ideal if pt nds to gain weight and suffers from insomia (as although it can cause insomnia it can also aid sleep in some)
How long does it take for antidepressants to have an effect?
Begin to take effect by one week however benefit is usually only clinically detectable at 4-6 weeks (hence tell pts take 4-6 weeks till you start to feel better)
Discuss some key points to consider when deciding which antidepressant to prescribe (9)
- Safety profile: guidelines sugest SSRIs as 1st choice due to safety & effectiveness
- Patient preference
- Prior treatment: if previously used antidepressant and was beneficial should try that; if wasn’t beneficial don’t try it
- Type & severity of depression: use SSRIs first. If SSRI-resistant try SNRIs. If insomnia present or weight gain desired mirtazapine is appropriate.
- Suicidal ideation: if person has suicidal ideation avoid drugs which are toxic overdoses e.g. TCAs, MAOIs
- Age & co-morbidities: SSRI’s safest in elderly. Sertraline safest post-MI
- Drug-drug interactions: may need to avoid blood thinning agents in SSRIs
- Pregnancy & breastfeeding: take caution and use lowest dose. Sertraline safest in preg and breast feeding.
- History of mania: SSRIs usually safest. Avoid TCAs
What is serotonin syndrome?
What are symptoms?
What causes serotonin syndrome?
State clinical features of serotonin syndrome (describe triad)
What is the management?
- Rare, life-threatening syndrome due to excess synaptic serotonin in the CNS that clinically manifests as the triad of neuromuscular excitation, autonomic effects, and altered mental status. Best thought of as spectrum of toxicity. Occurs within mins-hours of taking meds.
- Symptoms:
- Neuromuscular excitation: hypereflexia, myoclonus, tremor
- Altered mental status: agitation, confusion, hypomania, coma
- Autonomic: tachycaradia, hyperthermia, sweating, shivering, nausea, diarrhoea
- Caused by therapeutic use, overdose or drug-drug interactions of serotonergic drugs. Most commonly caused by SSRIs but others (e.g. TCAs, lithium) can cause
- Clinical features:
- Cognitive effects: headache, agitation, confusion, coma
- Autonomic effects: sweating, shivering, hyperthermia, hypertension, tachycardia
- Neuromuscular effects: myoclonus, tremor, hyperreflexia, convulsions
- Management:
- Stop offending drug
- Supportive e.g. fluids, cooling, sedation & intubation & ventilation if necessary
- Medications:
- Mild= benzodiazepines e.g. diazepam
- Moderate to severe= benzodiazepines and cyproheptadine or chlorpromazine
Why are benzodiazepines used in treatment of serotonin syndrome?
Why is cyproheptadine used in treatment of serotonin syndrome?
- Benzodiazepines for agitation & tremor
- Cyproheptadine is an H1 blocking antihistamine, but it also has serotonin receptor blocking activity.
Which antidepressant is drug of choice in children & adolescents?
Fluoxetine
Which antidepressant is drug of choice post MI?
Sertraline
How long after initiation of SSRI should you review pts?
- 2 weeks
- BUT if pt <30yrs age or at increased risk suicide see after 1 week
Which SSRIs should you not prescribe in pts with prolonged QT
- Citalopram
- Escitalopram
Which antidepressants are toxic in overdose and so should be avoided in pts with suicidal ideation?
- TCAs
- MAOIs
You can stop SSRIs suddenly; true or false?
False; if stopping should gradually reduce dose over at least 4 week period (not necessary with fluoxetine).
What is discontinuation syndrome?
Include symptoms
Condition that can occur when you reduce or stop taking antidepressants.
Summary of do’s and don’ts SSRIs
Give a generic summary of what order antidepressants usually tried in
*ONLY GENERIC DEPENDS ON FACTORS DISCUSSED
- First line: SSRIs
- Second line:
- SNRIs (more rapid onset & more effective)
- Mitrazapine
- Third line:
- TCAs
- MAOIs
When talking about antipsychotics, we often talk about typical (first generation) and atypical (second generation):
- What is the difference between the two
- State some examples of tpyical and atypicals
Difference is the etent to which they cause extrapyramidal side effects:
- Typical (1st generation): more extra-pyramidal side effects, tend to bind to muscuranic & histaminic
- Atypical (2nd generation): less extra-pyramidal side effects, tend to have more serotonergic activity
The efficacy of different antipsychotics is similar therefore choice of drug is determined by factors such as side effect profile and previous efficacy- with the exception of _____?
Clozapine- it is the only antipyshchotic that has been found to be superior
State some example conditions that we treat with antipsychotics
- Schizophrenia
- Mania
- Acute & transient psyhcotic disorders
- Delusional disorders
- Depression with psychosis
- Delerium
- Dementia
- People with violent or dangerously impulsive behaviour and psychomotor agitation
Describe the mechanism of action of antipsychotics; include any differences for typicals and atypicals
- Block dopamine receptors- particulary D2 receptors- in brain to varying degrees; degree to which they bind may account for therapetuic effect and the extra-pyramidal side effects
- Target mesolimbic & mesocortical pathways in brain
- Antipsychotics also block adrenergic, muscarinic, histaminergic and 5HT2a receptors to varying degrees.
Typicals have their therapeutic effect by binding to D2 receptors.
Atypicals have their therapeutic effect by binding to D2 (weak) & D4 and 5HT receptors.
*NOTE: aripiprazole is exception in that it is partial D2 agonist and full bindingn decreases dopamine availability by up to 30%
Compare typical & atypical antipsychotics
Discuss the effects of D2 antagonists on the following pathways in brain:
- Nigrostriatal
- Mesocortical
- Mesolimbic
- Tuberoinfundibular
State some side effects of antipsychotics as a result of blocking muscuranic receptors
- Urinary retention
- Constipation
- Dry mouth
- Blurred vision
State some side effects of antipsychotics as a result of blocking histaminergic receptors
- Sedation
- Weight gain
State some side effects of antipsychotics as a result of blocking adrenergic receptors
- Tachycardia
- Postural hypotension
- Ejaculatory failure
Typical antipsychotics are more likely to cause ____ and _____
Atypical antipsychotics are more likely to cause _____ and _____
- Typicals: extra-pyramidal side effects & hyperprolactinaemia
- Atypicals: anti-cholinergic & metabolic
State some metabolic side effects of antipsychotics (more likely in atpyicals)
- Impaired glucose tolerance
- Hypercholesterolaemia
Which antipsychotics are the worst for metabolic side effects (e.g. weight gain, impaired glucose tolerance, hypercholesterolaemia etc…)?
Olanzapine
Clozapine
Antipsychotics cause endocrine side effects- such as hyperprolactinaemia- via what pathway in brain?
Typical antipsychotics are more likely to cause hyperprolactinaemia, however which of the atypcials is most likely to cause hyperprolactinaemia?
Tuberofundibular pathway
Risperidone
State some symptoms of hyperprolactinaemia
- Sexual dysfunction
- Galactorrhoea
- Breast enlargment
- Menstrual disturbances (irregular or absent)
- Reduced bone mineral density
Which atypical antipsychotic has greatest prevelance of hyperprolactinaemia?
Risperidone
State some extra-pyramidal side effects that can occur with antipsychotics
HINT: PADT
-
Parkinsonism:
- Bradykinesia
- Increase rigidity
- Coarse tremor
- Masked facies/expressionles face
- Shuffling gait
- Akasthisia (feeling of restlessness/can’t keep still)
-
Dystonia (acute painful contractions/sustained muscle contractions usually of muscles in neck, jaw & eyes):
- Grimacing
- Tongue protrusion
- Spasm of occular muscles
- Torticollis
-
Tardive dyskinesia (abnormal involutary movements):
- Most commonly presents as chewing & pouting of jaw but may also present as lip smacking, excessive blinking
What is acute dystonia?
Uncontrollable muscle spasms triggered by incorrect signals from the brain; can affect any region of the body including the eyelids, face, jaw, vocal cords, torso, limbs, hands, and feet.
For each of the extra-pyramidal side effects of antipsychotics, state roughly when they occur (following initiation of drug):
- Parkinsonism
- Akasthisia
- Dystonia
- Tardive dyskinesia
- Parkinsonism: weeks-months
- Akasthisia: first few months
- Dystonia: days
- Tardive dyskinesia: late onset (years)
What % of pts on antipsychotics are affected by tardive dyskinesia?
Is it reversible?
What is treatment?
- 25-40%
- Irreversible
- Stop antipsychotic drug when state of mental health allows and tetrabenazine
What medication can be used to treat moderate/severe tardive dyskinesia?
Tetrabenazine
Antipsychotics cause EPSE via what pathway in brain?
Nigrostriatal
Its the ratio of dopamine:acetylcholine in nigrostriatal pathway that is important (not the absolute quantities). If there is too much acetylcholine in relation to dopamine and you cannot increase dopamine activity then antagonise acetylcholine receptors using e.g. procyclidine
Discuss the management of acute dystonias as a result of antipsychotic medication
- Stop antipsychotic
- Administer IM or IV anticholinergics (procyclidine is firs line)
- Continue for 1-2 days after dystonia
- Consider long term prophylaxis with anticholinergics
Clozapine has some specific side effects you need to be aware of; state these
- Agranulocytosis (low white blood cells- particularly neutrophils)
- Gastrointestinal hypo-mobility causing constipation and with potential to cause fatal bowel obstruction (most common cause death in clozapine pts)
- Hypersalivation
- Myocarditis
- Induce seizures
Which antipsychotic can induce/increase risk of seizures & why?
Clozapine- it reduces seizure threshold
Dicuss why you must explore smoking & alcohol habits in pts taking clozapine
- Smoking induces the enzymes that metabolise clozapine and hence increase metaobolism of clozpaine- reducing plasma levels
- Alcohol binges can increase level of clozapine so it pt stops drinking it may reduce clozapine level
Hence if pt changes any of the above then dose may need to be altered
Why must clozapine e started in hospital?
Can cause profound hypotension when you start it hence in hospital to monitor.
Similary if you stop clozapine, even for 48hrs, you will have to go back to a low dose and work up and this too would require hosp admission
Discuss the acute management of clopazine induced agranulocytosis
- Contact consultant haematologist as emergency
- Stop clozapine
- Stop any other potentially bone marrow supressing drugs e.g. sodium valporate
- Avoid other antipsychotics for a couple of weeks where possible (use aripiprazole if this not possible)
- Avoid sources of infection (e.g. isolate pt)
- Consider prophylactic broad spectrum antibiotics
- G-CSF can be used
- Lithium can be used to increase WCC and neutrophil count
QT prolongation can occur with antipsychotics; which antipscyhotics are worst for prolonging QT interval
- Pimozide
- Haloperidol
State some cautions when prescribing antipsychotics
- Cardiovascular disease
- Parkinson’s disease
- Epilepsy & other conditions predisposing to seizures
- Diabetes
- Myasthenia gravis
- Prostatic hypertrophy
- Depression
Discuss what blood test monitoring is required for antipsychotic drugs
FBC, U&Es, LFTs
- Start
- Annually
- EXCEPT clozapine which requires FBC (for WCC) weekly for 18weeks, then fortnightly up to 1yr/rest of first year, then monthly thereafter
Fasting blood glucose
- Baseline
- 4-6 months
- Then yearly
- EXCEPT clozapine or olanzapine in which have at baseline, 1 month and then every 4-6month
Blood lipids
- Baseline
- 3 months
- Then yearly
Creatine kinase
- Baseline
- Then if neuroleptic malignant syndrome suspected
Discuss what non-blood test monitoring is required for pts taking antipsychotics
ECG
- Before initiation
- Monitoring mandatory for pimozide
- Monitoring recommended for haloperidol
Blood pressure
- Before initiation
- Frequently during dose titration
- *Not required for aripiprazole
Prolactin
- Start of therapy
- 6 months
- Yearly
Weight
- Baseline
- Frequently for first 3 months
- Then yearly
Discuss how antipsychotics can be administered
- PO or IM
- Try PO then do IM if can’t; IM improves adherence for people who find it difficult to take PO
- IM long acting slow release usually given every 4-6 weeks
*NOTE: start on lowest possible dose & titrate up to minimum effective dose
State two commonly used antipsychotics that can’t be given as DEPOT
- Quietiapine
- Clozapine
How long should pts continue antipsychotics for following episode of psychosis?
If stopping antipsychotics, how should you do it?
- 1-2yrs but some may be recommended to take for longer e.g. 5yrs to prevent relapse
- Taper medication off over approx 3 weeks (if don’t relapse rate in first 6 months doubles)
Compare typical & atypical antipsychotics in terms of:
- EPSE
- Tolerability
- Efficacy against depressive & cognitive symptoms
- Metabolic side effects
- Stroke risk in elderly
- Hyperprolactinaemia risk
What medication can be given to help with EPSE/parkinsonism side effects?
Anticholinergics such as procyclidine
HOWEVER, note that they will add to the anti-cholinergic side effects of antipsychotics
Which antipsychotic is known to have few side effects?
Aripiprazole (less so than risperidone & olanzapine)
For neuroleptic malignant syndrome, discuss:
- What it is/who seen in
- Mortality
- Onset
- Potentially life-threatening complication of treatment with antipsychotic drugs (more common in typical antipsychotics), or abrupt withdrawal of dopamine agonists.
- 10% mortality
- Withiin first 10 days of treatment or after dose alteration (increasing antipsychotic or decreasing dopaminergic drug).
State clinical features of neuroleptic malignant syndrome (tetrad)
Principal feautures
- Pyrexia/hyperthermia
- Muscular rigidity
- Altered mental status
- Autonomic instability (e.g. tachycardia, fluctuating BP- often hypertensive-, excessive sweating, salivation)
Associated features
- Hyporeflexia
- Dsyphagia
- Mutism
What investigations do you need to do if you suspect NMS and what would the results be?
- Creatine kinase: increased
- FBC: leucocytosis
- LFTs: deranged
Discuss the management of NMS
- Stop antipsychotic
-
Supportive:
- IV fluids (prevent renal failure)
- Cooling
- NG tube for feeding if dysphagia
-
Additional medications may be used:
- Muscle relaxants:
- First line= Dantrolene or lorazepam
- Second line= Bromocriptine (dopamine agonist)
- Sodium bicarb for rhabdomyolysis
- Muscle relaxants:
- Wait at least 2 weeks after full recovery before restarting antipsychotics
Compare serotonin syndrome & neuroleptic malignant syndrome, include:
- Similarities
- Key differences
State some potential complications of NMS (4)
- PE
- Renal failure
- Pneumonia
- Shock
Summary of Do’s & Don’ts for antipsychotics
Why must you not co-prescribe triptans and MAOIs?
Increased risk of sertonin syndrome
