7 - Psychiatric Drugs (Antidepressants and Mood Stabilisers) Flashcards
What are the side effects of clozapine?
- Constipation - fatal
- Sedation
- Hypersalivation
- Changes in BP
- Tachycardia – usually benign but could be cardiomyopathy so ECG
- Weight gain
- Seizures
- Urinary incontinence
What is paliperidone and how is it started?
- Depot version of Risperidone
- Does not require oral medication (Risperidone) to be taken during initiation, so is a good choice in a patient who is currently refusing all oral medications
- Loading doses of IM injections (Day 1 and Day 8 of treatment, then monthly thereafter)
- If a patient remains stable for at least four months on monthly dose can be given 3 monthly dose
What is a CTO?
Community Treatment Order
This can be used to specify conditions to which the patient is subject to on discharge, and the patient may be recalled to hospital if the conditions are not met, even if not under MHA
Means clinicians needn’t wait for the patient to relapse and become risky before re-admitting them to hospital, thus avoiding relapses and possible consequences of relapses
Sangita is a 27 year old woman who presents with her first episode of psychosis. She is extremely worried about gaining weight and does not want to take any medication if it causes weight gain.
What would be an appropriate antipsychotic?
Aripiprazole as this is the only weight neutral choice
- A 47 year old man is admitted to hospital with a diagnosis of a Delusional Disorder. He has a significant cardiac history.
Which would be the safest antipsychotic to prescribe?
a. Aripiprazole
b. Chlorpromazine
c. Haloperidol
d. Sulpiride
e. Zuclopenthixol
Answer : A the others all cause QTc prolongation.
Which of the following SSRI’s is only recommended in reduced doses in the elderly?
a.) Citalopram b.) Fluoxetine c.) Fluvoxamine d.) Paroxetine e.) Sertraline
A
Citalopram in higher doses is thought to prolong the QT interval which could lead to cardiac arrhythmia’s
Which of the following drugs should not be routinely prescribed for a patient on Lithium?
a. ) Aspirin
b. ) Codeine Phosphate
c. ) Gabapentin
d. ) Paracetamol
e. ) Tramadol
A
Aspirin is an NSAID. NSAID’s may increase the concentration of lithium.
- Which of the following is not a recommended treatment for mania?
a. ) Lamotrigine
b. ) Lithium
c. ) Olanzapine
d. ) Quetiapine
e. ) Sodium Valproate
A
Lamotrigine can be used to treat bipolar depression. The remaining treatments are all recommended for the treatment of mania
- Stevens Johnson Syndrome is a rare side effect of which of the following?
a. ) Lamotrigine
b. ) Lithium
c. ) Lorazepam
d. ) Paroxetine
e. ) Sodium Valproate
A
Stevens-Johnson syndrome & toxic epidermal necrolysis are rare side effects with Lamotrigine, which can be used sometimes for treatment resistant depression
Patients are advised to see their doctor immediately if they develop a rash.
How long do people ideally need to stay on antidepressants before they are weaned off?
Depression: 6 months (12 in elderly)
Anxiety: 12 months
Recurrent Depression: 2 years
What route are antidepressants given and how long do they take to work?
PO
Takes 2 weeks minimum but can take up to 6 weeks to feel effect
Can have Mirtazapine Bucally and Selegeline (MAOi) transdermally but rare
Give 3 examples of an SSRI and indications for this drug.
Examples: Sertraline, Citalopram, Fluoxetine, Escitalopram
Indications: First line antidepressant, Panic attacks, Anxiety, OCD, Eating disorders, Hot flushes in menopause
Sertraline is best for depression in IHD
What are some contraindications to SSRIs?
Absolute
- Mania in bipolar
- Poorly controlled epilepsy
- MAOI use in last 2 weeks
- Long QT (Citalopram)
- Severe hepatic impairment
Relative
- Early pregnancy (congenital heart defects)
- Hyponatraemia in elderly
- Bleeding disorders
What are the risks of using SSRIs in the third trimester of pregnancy?
- Peristent pulmonary hypertension of baby
- Neonatal withdrawal symptoms
What are the side effects of SSRIs?
Initial
- Increase in anxiety/depression
- Suicidal thoughts
Long-term
- Dry mouth
- Weight changes
- Insomnia
- Nausea and Vomiting/GI upset
- Sexual dysfunction
- Palpitations
- Drowsy
- Shaky
- Constipation/Diarrhoea
- Anorgasmia, ED, Reduced libido that can persist after cessation
- Hyponatraemia
- Gastric ulcer
- Long QT (Citalopram)
What are some side effects for the SSRI Citalopram?
What are some drug interactions with SSRIs?
- Anti-epileptics: reduces seizure threshold
- Aspirin/NSAIDs/Antiplatelets: increased risk of bleeding
- Carbamazepine: lower level of Sertraline
- Grapefruit juice: higher level of Sertraline
- Lithium: concurrent use Serotonin syndrome and Long QT
- MAOI: high risk of NMS and SS, CI
Which SSRIs have a risk of QT prolongation and Torsades De Pointes?
- Citalopram
- Escitalopram
What monitoring needs to be done on SSRIs?
None
Follow up in first 1-2 weeks then weekly for 4 weeks due to suicide risk on starting
Do ECG before starting Citalopram/Escitalopram
How may SSRI toxicity present?
Very hard to OD, few symptoms and unlikely to cause coma
Symptoms: tremor, tachycardia, vomiting
Screen for symptoms of Serotonin syndrome
May cause wide complex bradycardia and torsade de pointes if Citalopram or Escitalopram so do ECG
Why are SSRIs usually preferred over TCA?
Have the same efficacy
- Better tolerated side effects
- Safer in overdose
- Less sedating
- Less cardiovascular side effects
TCAs are second-line treatments for depression.
What is the mechanism of action of TCAs? Give 3 examples of a TCA and indications for this drug.
Block the re-uptake of both serotonin and noradrenaline
Examples
Sedative: amitriptyline, clomipramine
Less Sedative: lofepramine, and nortriptyline.
Indications
- Depression (not Amitriptylline as high toxicity)
- Neuropathic pain
- OCD
- PTSD
- GAD (better to use sedative ones)
- Nocturnal enuresis
What are the contraindications for TCAs?
- Arrhythmias (Long QT)
- Heart block
- Severe hepatic impairment
- During the manic phase of bipolar disorder
- In the immediate recovery period after myocardial infarction
- Taking a monoamine oxidase inhibitor (MAOI)
- Enlarged prostate
What are some side effects with tricyclic antidepressants?
- Anticholinergic syndrome: Urinary retention, Blurred vision, Constipation, Dry mouth
- Drowsiness
- Orthostatic hypertension
- Palpitations
- Long QT syndrome
What patient group needs to be careful with TCAs?
Elderly: Prone to more side effects so cardiac monitoring, Use half doses
Depression: Avoid Amitriptylline and Dosulepin as high toxicity risk
What monitoring needs to be done whilst on TCAs?
- Suicide risk in first 1-2 weeks so follow up weekly for first 4 week
- ECG: Annually if on high doses or if taking other QT prolonging drugs as well
What is the toxicity like with TCAs and what are the side effects with toxicity?
Narrow Therapeutic Index (easy to OD)
SE: Arrhythmias and reduced cardiac contractility, CNS depression and seizures
Need sodium bicarbonate treatment to alkalise blood
What are some drug interactions with TCAs?
- Lithium — Serotonin syndrome, or NMS In addition. QT prolongation or torsades de pointes
- Monoamine oxidase inhibitors (MAOIs) — concurrent use is contraindicated
- Other sedative drugs (alcohol, barbiturates, benzodiazepines) — TCAs are sedating and co-administration with other sedating drugs may have a synergistic effect.
- Phenylephrine — blood pressure effects of phenylephrine may be increased by TCAs, leading to increased risk of arrhythmias
What over the counter medication should you avoid with antidepressants?
St John’s Wort
It is an enzyme inducer so decreases amount of antidepressant. If patient stopped taking this whilst on anti-depressants could lead to toxicity
What are some examples of SNRIs and what are some indications for this?
Examples: Venlafaxine, Duloxetine
Indications: Severe depression, ADHD, Neuropathic pains
What are some contraindications for SNRIs?
- High risk of cardiac arrhythmia
- Uncontrolled hypertension
- Glaucoma
- Epilepsy
- Hepatic impairment (duloxetine)
- Severe renal impairment <30ml/min (duloxetine)
What are some side effects of SNRIs (Venlaxafine and Duloxetine)?
- Nausea
- Headaches
- Sweating
- Dry mouth
- Constipation
- Blood pressure increases, flushing
- Blurred vision
- Cholesterol level increases
- Decreased appetite/Weight loss
- Sexual dysfunction
- Sedation
- Hyponatraemia (SIADH)
What antidepressants are favoured in severe depression?
- TCAs
- Venlaxafine
What antidepressants have an increased risk of PPH in pregnant women?
SSRI and SNRI if used a month before birth
What do you need to think about when taking SNRIs with other drugs?
- Risk of Long QT
- Risk of Serotonin Syndrome
- Risk of Sedation
What monitoring needs to be done with SNRIs?
BP: Take BP before, control it before starting, regularly check BP
Blood sugars: If diabetic need to check more frequently
Doses over 300mg should only be prescribed by mental health doctor
What is the toxicity like with SNRIs (Venlafaxine and Duloxetine)?
Usually causes seizures and serotonin syndrome but not often fatal
Do ECG monitoring and paracetamol levels
What are some examples of NASSA antidepressants, what is their MOA and what are their indications?
Noradrenergic and specific serotonergic antidepressant (NaSSA) that blocks alpha-2, 5HT3 and 5HT2 receptors
Example: Mirtazapine
Indications: Major Depression
What are some contraindications to Mirtazapine (NASSA)
Under the age of 18
Prescribe mirtazapine with caution in the elderly and people with:
- Cardiac disorders
- Diabetes mellitus
- Hepatic impairment
- Hypotension
- History of bipolar depression
- History of seizures
- History of urinary retention
- Psychosis
- Renal impairment
- Susceptibility to closed-angle glaucoma
- Susceptibility to hyponatraemia
What are the side effects of Mirtazapine?
SEDATION AND WEIGHT GAIN
- Anticholinergic syndrome (dry mouth, constipation, blurred vision, sedation)
- Abnormal dreams
- Appetite increase and weight gain
- Sedation
- Arthralgia and myalgia
- Liver enzyme increases
- Oedema
- QT interval prolongation
- Urinary retention
What is the toxicity like with Mirtazapine?
Very hard to overdose
Overdose is associated with tachycardia, mild hypertension and mild CNS depression
No association with QT prolongation, seizure activity, serotonin toxicity, delirium or any need for intervention
What monitoring needs to be done with Mirtazapine?
- Agranulocytosis or severe neutropenia (such as stomatitis, sore throat, other possible signs of infection, or a low WBC)
- Renal function
- Hepatic function
- Signs/symptoms of serotonin syndrome
- Lipid profile and weight gain
What drugs can interact with Mirtazapine?
- Antiepileptics —can reduce the seizure threshold
- Chlorpromazine — increased risk of agranulocytosis. Monitor for blood dyscrasias.
- Monoamine oxidase inhibitors (MAOIs) — increased risk of developing serotonin syndrome. Avoid concurrent use (and for 2 weeks after stopping either drug)
- Rifampicin — decreases levels of mirtazapine. Dose adjustments may be necessary
- Other sedative drugs (alcohol, barbiturates, benzodiazepines) — mirtazapine is sedating
What are some examples of NARI antidepressants, what is their MOA and what are their indications and contraindications?
Selective inhibitor of noradrenaline re-uptake
Example: Reboxetine
Indication: Major depression
What are some side effects of Reboxetine?
- Accommodation disorder
- Palpitations
- Blood pressure increases, flushing
- Chills
- Decreased appetite
- Hyponatraemia.
- Erectile dysfunction, ejaculatory problems, testicular pain.
- Vasodilation, hypotension
- Vertigo
What are some drug interactions with Reboxetine and what is it’s toxicity like?
Very low risk for overdose, just get sweating and tachycardia
- Diuretics (loops and thiazides) — hypokalaemia may occur if used concomitantly with reboxetine
- Linezolid — increased risk of acute hypertensive crisis
- Monoamine oxidase inhibitors (MAOIs) — increased risk of acute hypertensive crisis
What monitoring needs to be done with NARIs (Reboxetine)?
Mental state (assess for suicidal thoughts)
What is the highest to lowest toxicity in overdose with antidepressants?
- Highest: TCA and MAOi
- Mirtazapine and Venlaxafine
- SSRI
- Lowest: Reboxetine
What are some examples of MAOis, what is their MOA and what are their indications and contraindications?
Inhibit monoamine oxidase A and B to increase serotonin, NE and dopamine. Moclobemide reversibly inhibits
Examples: Moclobemide, Tranylcypromine
Indications: Severe depression (secondary care), Social Anxiety
CI: Acute confusional state, phaeochromocytoma
What are the side effects of MAOIs?
- QT interval prolongation.
- Nausea
- Constipation
- Dry mouth
- Dizzy
- Headache
- Sleep disorders
- Rash
- Decreased appetite, hyponatraemia
- Galactorrhoea
- Hypotension, flushing
- Irritability
- Serotonin syndrome
- Visual impairment
What are some interactions with MAOIs?
- Cimetidine — levels of moclobemide increased.
-
Serotonin syndrome — increased risk if moclobemide is taken concurrently with other drugs which can also cause serotonin syndrome,
- Opioids (pethidine, tramadol) — concurrent use is contraindicated.
- SNRIs (venlafaxine, duloxetine) — avoid concurrent use.
- SSRIs (paroxetine, sertraline) — monitor for symptoms of serotonin syndrome (such as fever, tremors, diarrhoea, agitation).
- Sympathomimetics (pseudoephedrine, phenylephrine) — avoid concurrent use.
- Tricyclic antidepressants (clomipramine, amitriptyline) — avoid concurrent use.
- Triptans (sumatriptan, naratriptan) — concurrent use is contraindicated.
- Tyramine-rich foods — tyramine (150 mg) increases systolic blood pressure by 30 mmHg when given with moclobemide. People should avoid consuming large amounts of tyramine-rich foods (such as mature cheese, salami, pickled herring, Bovril®, Oxo®, Marmite®, beers, lagers or wines).
How toxic are MAOi?
Highest toxicity in OD
What foods need to be avoided with MAOIs?
Tyramine Rich Foods as can raise Sys BP by 30mmHg
How long do you need to wait before starting a MAOi?
DUE TO RISK OF SEROTONIN SYNDROME
Other antidepressants should not be started for 2 weeks after treatment with MAOIs has been stopped (3 weeks if starting clomipramine or imipramine)
Conversely, an MAOI should not be started until:
- at least 2 weeks after a previous MAOI has been stopped
- at least 7–14 days after a TCA has been stopped
- at least a week after an SSRI or related antidepressant (at least 5 weeks in the case of fluoxetine) has been stopped
What are some examples of mood stabilisers and what conditions are they used for?
Used in Bipolar Affective disorder to prevent depression and mania
- Lithium
- Quetiapine (SGA)
- Sodium Valproate (Antiepileptic)
- Carbamazepine (Antiepileptic)
- Lamotrigine (Antiepileptic)
How long do mood stabilisers take to work and how long do they need to be taken for?
2 weeks but take 4-6 weeks to take full effect so may be given antipsychotics to control mania until mood stabilisers come into affect
Need to be taken for at least 6 months but encouraged for life to prevent relapse
What is the ‘best’ mood stabiliser and why?
Lithium as can be good for both depressive and manic episodes
Valproate is only for manic episodes
What are the side effects of Lithium (Lithium Carbonate/Lithium Citrate)?
- Decreased kidney function (irreversible)
- Increased thirst and urination (DI)
- Hypothyroidism (reversible)
- Metallic taste
- Weight gain
- Muscle Weakness
- Fine tremor
- Hyperparathyroidism
- Acne and Psoriasis
- Leucocytosis
- Renal tumours
What are some contraindications for Lithium?
- Renal Impairment
- Brugada Syndrome (T wave changes)
- Addison’s disease
- Cardiac disease associated with rhythm disorder
- Untreated hypothyroidism
- Low salt diets
- Breastfeeding and Pregnancy
- People refusing to have blood tests
- High risk of OD
What advice should you give someone on Lithium?
- Maintain adequate fluid intake (especially abroad)
- Avoid dietary changes which reduce or increase sodium intake
- Avoid pregnancy
- Monitor for signs of Lithium Toxicity
- Avoid NSAIDs
What are some signs of Lithium toxicity?
- Severe N+V
- Severe/Coarse hand tremors
- Confusion
- Vision changes
- Abnormal reflexes
- Incontinence, hypernatraemia
Severe overdosage: seizures, cardiac arrhythmias (including sino-atrial block, bradycardia and first-degree heart block), blood pressure changes, circulatory failure, renal failure, coma and sudden death
How is Lithium toxicity treated?
Usually due to long-term therapy and reduced excretion of the drug (e.g dehydration, deterioration of renal function, infections, and co-administration of diuretics or NSAIDs)
Aim to maintain electrolyte balance, monitoring renal function and seizure control:
- IV Fluids for osmotic diuresis
- Haemodialysis if neurological symptoms or renal failure
- Benzodiazepines for seizure prophylaxis
- Gastric Lavage if within 1 hour of ingestion
- Whole-bowel irrigation if significant ingestion
- Measure lithium levels every 6-12 hours
What are the complications of Lithium Toxicity?
Lithium Toxicity when over 1.5mmol/L, if over 2.0mmol/L then severe
What monitoring needs to be done whilst on Lithium?
Before initiation: FBC, U+Es, TFTs, BMI, ECG if CVD
Serum level: Take 12 hours after dose, aim for 0.4-1.0 mmol/litre (0.8-1.0 if acute mania)
Need to take weekly when initiated and after dose change, then every 3 months for a year, then every six months
Additional measurements if significant intercurrent disease or if there is a significant change in a patient’s sodium or fluid intake.
After initiation: BMI, serum electrolytes, eGFR, and TFTs every 6 months during treatment
What are some drug interactions with Lithium?
- Diuretics (Thiazide and Loop) can cause a rapid increase in serum lithium levels (7–10 days) by reducing clearance of lithium
- NSAIDs — may increase serum lithium levels
- ACE inhibitors decrease the excretion of lithium. They can also precipitate renal damage
- Haloperidol — severe neurotoxicity
- Carbamazepine - neurotoxic reactions
- Antidepressants - Serotonin syndrome
What antipsychotics are often used to treat acute mania in bipolar disorder?
Olanzapine, Quetiapine, and Risperidone
Used as a monotherapy or in conjunction with Valproate or Lithium if not working alone
What are some contraindications to using Valproate for mania?
Used second line if lithium is CI or not tolerated
- Child bearing women without PPP
- Active liver disease.
- Personal or family history of severe, drug-related, hepatic dysfunction.
- Acute porphyria
- Mitochondrial disorders
What are some side effects of Valproate?
- Drowsiness
- Dizziness
- Nausea (from gastric irritation and hyperammonaemia)
- Blurred vision
- Mild hair loss
- Weight gain
- Bruising or bleeding
- Liver problems
- Hyperandrogenism (development of PCOS)
- Suicidal thoughts
What monitoring needs to be done whilst on Valproate?
- Drowsiness
- Dizziness
- Nausea (from gastric irritation and hyperammonaemia)
- Blurred vision
- Mild hair loss
- Weight gain
- Bruising or bleeding
- Liver problems
- Hyperandrogenism (development of PCOS)
- Suicidal thoughts
- Pancreatitis
What monitoring needs to be done whilst on valproate?
- Before starting: FBC, LFTs, BMI
- After 6 months: LFTs, Prothrombin time, BMI, FBC then every 12 months there after
What drug interactions does sodium valproate have?
- Valproate is highly protein-bound and other drugs that are also highly protein bound (e.g. aspirin) may displace valproate from albumin and precipitate toxicity
- Less strongly protein-bound drugs (for example warfarin) can be displaced by valproate; this may lead to higher free levels and increased therapeutic effect or toxicity of the concomitant drug.
- Erythromycin, fluoxetine, and cimetidine can increase valproate levels
- Valproate can increase the plasma levels of some drugs, possibly by inhibition of their metabolism (e.g TCAs)
- Nimodipine — the levels of this drug can be increased when taken with valproate. A dose reduction of nimodipine should be made
- Lamotrigine — valproate increases the exposure to lamotrigine. Monitor for rash
- Quetiapine — co-administration may increase the risk of neutropenia/leucopenia.
Why is co-prescribing valproate and lamotrigine risky?
High risk of Steven Johnson Syndrome
What are some contraindications for prescribing Lamotrigine for bipolar and what are some side effects? Also, what monitoring is needed?
Cautions (No CIs)
- Parkinson’s (can exacerbate)
- Myoclonic seizures (can exacerbate)
Side effects:
- Skin rash (SJS and TEN in first 8 weeks)
- Suicidal thoughts
- Nausea, Vomiting, Diarrhoea
- Drowsy
- Insomnia
- Nightmares
- Hallucinations
Is Lamotrigine used for depression or mania in bipolar?
Depression
When is Carbamazepine used in bipolar and what are the contraindications and side effects of this drug?
Used for prophylaxis of mania when lithium hasn’t worked or when the person is irritable
CI
- History of bone marrow depression
- Cardiac disease
- History of haematological reactions to other drugs
- Absence or myoclonic seizures (may exacerbate) absence
- Angle closure glaucoma
Side Effects
Common: dizziness, drowsiness, blurred vision, confusion, muscle tremor, nausea, vomiting or mild cramps, increased sensitivity to sun, skin sensitivity and rashes, ataxia
Rare: Agranulocytosis. Soreness of the mouth, gums or throat, mouth ulcers or sores, and fever or flu-like symptoms can be a sign of this effect and should be reported immediately
What monitoring needs to be done whilst on Carbamazepine?
- Baseline: FBC, LFTs, U+ES
- Check plasma concentration after 1-2 weeks
- Every 6 months: LFTs, FBC, U+Es (hypoNa), Plasma concentration
What drug interactions are there with Carbamazepine?
- Enzyme inducer so avoid hormonal contraception as not effective
- Drugs that increase Carbamazepine: Fluoxetine, Fluconazole, Cimetidine, Erythromycin, Clarithromycin
If someone is on an SSRI and an anti platelet/anticoagulant, what is another drug they also need to be taking?
PPI
Risk of bleeding as serotonin receptors in GI tract
Which antidepressants are used for neuropathic pain?
- SNRI (first line as better tolerated and less toxicity)
- TCA
Mirtazapine is associated with sedation and weight gain. Can you lower the dose to reduce this?
No - have sedation even at low doses
What is the risk of eating high tyramine foods whilst on MAOi’s?
Hypertensive crisis
What is Vortioxetine good for?
Treats difficult to treat cognitive symptoms of depression
How do you decide which antidepressant to use?
- What are patients expectations? (placebo effect)
If no major weight loss, sleep difficulty or neuropathic pain then start with SSRI
Should you increase the dose of an antidepressant if it is not working?
Depression
- If at typical dose and no effect after 4 weeks switch, increasing dose has no effect
Anxiety (especially OCD)
- Increasing dose works if no initial benefit
What is the effect of Lithium on suicide?
Reduces suicide and self harm!!!
Why do you check FBC when taking valproate and carbamazepine?
Can cause thrombocytopenia
What important side effect do you need to warn patients of with Lamotrigine?
Steven Johnson Syndrome
This is why it is not used in manic patients as dose slowly increased over 2 weeks. Need to report any rashes.
