Depression Flashcards
How is less severe depression managed?
As well as drug treatment, what else should patients with more severe depression be treated with?
Psychological therapy (CBT)
Should antidepressants be used routinely for mild depression?
No, psychological treatment should be considered initially
(However, can consider a trial if patient preference, have a hx of moderate-severe depression, refractory to CBT or if associated with psychosocial or medical problems)
How is severe depression managed?
What are the three major classes of antidepressants?
- TCAs
- SSRIs
- MAOIs
Little difference in efficacy, make choice based on patient requirements
How long can it take for antidepressant action to take place after starting drug treatment? What may be required in interim in severe depression?
2 weeks
Electroconvulsive treatment may be required in severe depression during this time
Which class of antidepressants are better tolerated and safer in overdose than the others?
SSRIs
They should be considered as first line
TCAs have similar efficacy to SSRIs so why are they more likely to be discontinued?
- Less tolerable side effects
2. Toxicity in overdose
Which 3 effects do SSRIs have less of compared with TCAs?
- Less sedation
- Less antimuscarinic effects
- Less cardiotoxic
Which class of antidepressants has dangerous interactions with foods and drugs, should be reserved for use by specialists?
MAOIs
Which popular natural remedy for depression should NOT be prescribed or recommended for depression?
St John’s Wort
Enzyme inducer and different preparations have different amounts of the active ingredient
What effect does St John’s Wort have on metabolising enzymes?
Enzyme INDUCER
How often should patients be reviewed at the start of antidepressant treatment?
Every 1-2 weeks
How long should treatment be continued before considering whether to switch due to lack of efficacy?
What about in the elderly or partial response?
4 weeks
6 weeks in the elderly
Partial response - continue for a further 2-4 weeks
Following remission, how long should antidepressant treatment be continued for at least?
What about in elderly/generalised anxiety disorder?
6 months at the same dose
12 months in elderly and at least 12 months in people receiving treatment for GAD
How long should patients with a history of recurrent depression, severe functional impairment, health/social problems or incomplete response receive maintenance treatment for?
At least 2 years
Also consider referral for psychological treatments to prevent relapse (group CBT or MBCT)
Continuation of antidepressants or psychological therapies after full or partial remission may reduce patient’s risk of relapse.
True or False?
True
Which electrolyte effect has been associated with all classes of antidepressant, especially SSRIs?
Hyponatreamia (usually in elderly)
If a patient on antidepressants (especially SSRIs) presents with drowsiness, confusion, or convulsions, what should be considered?
Hyponatreamia
What is there a particular risk of at the beginning of treatment or if a dose is changed?
Suicidal thoughts and behaviour
Children and young adults (18-25) most at risk
What is serotonin syndrome?
A relatively uncommon adverse drug reaction caused by excessive serotonergic activity
Symptoms can be mild or life threatening and develop within hours or days
When is serotonin syndrome most likely to occur?
- Initiation of treatment
- Dose increase
- Overdose
- Addition of new serotonergic drug
- Replacement of one serotonergic drug without allowing a long enough wash-out period between drugs (esp. if irreversible MAOI)
Severe toxicity usually occurs when a combination of serotonergic drugs is used - involving which particular drug?
MAOI
What are the main areas which symptoms of serotonin syndrome fall under?
Usually a symptom triad
- Neuromuscular hyperactivity
(tremor, rigidity, involuntary movement) - Autonomic dysfunction
(tachycardia, hyperthermia/sweating, shivering, blood pressure changes, diarrhoea) - Altered mental state
(Agitation, confusion, mania)
What are the neuromuscular hyperactivity symptoms of serotonin syndrome?
- Tremor
- Hyperreflexia (overresponsive reflexes)
- Clonus (involuntary and repetitive muscle contractions)
- Myoclonus (involuntary jerking)
- Rigidity
What are the autonomic dysfunction symptoms of serotonin syndrome?
- Blood pressure changes
- Hyperthermia
- Tachycardia
- Shivering
- Diarrhoea
What are the altered mental state symptoms of serotonin syndrome?
- Confusion
- Mania
- Agitation
What are the options if there is failure to respond to initial treatment with an SSRI?
- Increase the dose
- Different SSRI
- Mirtazapine
2nd line: Lofepramine, moclobemide, and reboxetine
Other TCAs and venlafaxine should be considered for more severe forms of depression
Which drugs can be considered for more severe forms of depression
- TCAs
2. Venlafaxine
Who can prescribe irreversible MAOIs?
Specialists only
What are the options if there is failure to respond to treatment with two antidepressants (each trialled for at least 4 weeks)?
Consider seeking specialist advice
- Adding another of a different class
- Using an augmenting agent (lithium, aripiprazole [unlicensed], olanzapine [unlicensed], quetiapine, or risperidone [unlicensed])
- Use Vortioxetine
Give some examples of augmenting agents used when antidepressant treatment fails with 2 drugs
LAROQ
- Lithium
- Aripiprazole
- Risperidone
- Olanzapine
- Quetiapine
Which 2 drugs are generally used to treat acute anxiety?
- Benzodiazepines
- Buspirone (if on CYP3A4 inhib reduce dose to 2.5mg BD) - contraindicated in epilepsy
How long does anxiety have to last for it to be considered chronic?
4 weeks
If anxiety lasts longer than 4 weeks, it is considered chronic. Which drugs may it be appropriate to start treatment with?
Antidepressants
Combined treatment with a benzodiazepine may be required until the antidepressant takes effect
Which drug class do duloxetine and venlafaxine fall under?
SNRI
What is first line for GAD?
SSRIs
Escitalopram, paroxetine, or sertraline [unlicensed]
After SSRIs, what can be used to treat GAD?
SNRIs
Duloxetine and venlafaxine
If a patient cannot tolerate SSRIs and SNRIs, what is used to treat GAD?
Pregabalin - licensed
What is first line for panic disorder, PTSD, social anxiety and OCD?
SSRIs
What MAOI is licensed for treatment of social anxiety disorder?
Moclobemide
Which two groups can TCAs be roughly divided into?
- Sedating
- Less-sedating
TCAs which call into which group will benefit agitated and anxious patients?
Sedating
Examples:
- Clomipramine
- Trazodone
- Amitriptyline and dosulepin - but dangerous in overdose so not recommended for depression
TCAs which call into which group will benefit apathetic patients?
Less-sedating
Examples:
- Imipramine
- Nortriptyline
- Lofepramine
Give examples of sedating TCAs
- Amitriptyline (dangerous in overdose, not recommended for depression)
- Clomipramine
- Trazadone
- Trimipramine
- Dosulepin (dangerous in overdose, specialist use)
- Doxepin
In most patients, long half life of TCAs allows for what?
Once daily administration
MR preparations unnecessary
At which time of day are TCAs usually administered?
At night
Apart from depression, TCAs can also be used in which conditions?
- Panic and anxiety disorders
- Nocturnal enuresis
- Neuralgia
Are TCAs recommended for treating depression in children?
No, studies have shown they are not effective
What are the dangers of MAOIs?
Interactions with drugs and food
Give 4 examples of MAOIs
- Tranylcypromine
- Phenelzine
- Isocarboxazid
- Moclobenide
Which crisis is associated with MAOIs?
Hypertensive crisis
Throbbing headache, chest pain, blurred vison, shortness of breath
How long may response to treatment with MAOIs take to show?
3 weeks
After the 3 weeks it takes to show a response in treatment for MAOI, how many additional weeks can it take for response to become maximal?
Additional 1-2weeks
After stopping a MAOI, how long should we wait before starting another anti-depressent?
MAOI -> Different antidepressant
2 weeks
3 weeks if starting clomipramine or imipramine
How long after stopping a MAOI should we wait if the patient is starting clomipramine or imipramine (TCAs)?
MAOI -> clomipramine or imipramine
3 weeks
How long should we wait before starting a new MAOI after stopping an old MAOI?
MAOI -> MAOI
2 weeks (0 weeks for moclobemide as reversible)
Start new MAOI at a reduced dose
How long should we wait before starting a MAOI after stopping a TCA?
TCA -> MAOI
1-2 weeks
3 weeks for clomipramine and imipramine
How long should we wait before starting a MAOI after stopping an SSRI?
SSRI -> MAOI
1 week
5 weeks for fluoxetine
How long should we wait before starting a MAOI after stopping fluoxetine?
Fluoxetine -> MAOI
5 weeks
Which class of antidepressants carries a risk of postural hypotension as well hypertensive crisis?
What should be monitored?
MAOI
Monitor blood pressure
Which side effects should patients be aware of when taking MAOIs as they can be sign of postural hypotension and hypertensive responses?
- Headaches
- Palpitations
Discontinue use if experience either
Can MAOIs be stopped suddenly?
No
What are the withdrawal symptoms of MAOIs?
- Agitation
- Irritability
- Movement disorder
- Ataxia
- Insomnia
- Drowsiness
- Vivid dreams
- Cognitive impairment
- Slowed speech
Can occur within 5 days of stopping treatment
Symptoms increased after treatment of 8 weeks or more.
How long should the dose of MAOIs be withdrawn over? (what about if used long term?)
4 weeks (6 months if have used long term)
How should antidepressants be weaned down?
- Slowly reduce the dose to zero, at each step prescribing a proportion of the previous dose (for example, 50%)
- Take into account the pharmacokinetic profile (antidepressants with a short half-life need to be tapered more slowly) and duration of treatment
- Consider using smaller reductions (for example, 25%) as the dose becomes lower
- If slow tapering cannot be achieved using tablets or capsules, consider using liquid preparation
Regarding food, what should patients taking MAOIs be counselled on?
- Only eat fresh food, avoid food that is stale or gone off
- Avoid tyramine rich food (mature cheese, wine, pickled/fermented food, marmite/bovril, meat stock, broad bean pods, game)
- No alcohol or “de-acoholised/low alcohol” drinks
Interactions can persist for 2 weeks after discontinuing treatment (except Moclobemide as reversible)
Which foods should patients taking MAOIs be particularly cautious of?
- Meat (esp. Game)
- Fish
- Poultry
- Offal
Which are the irreversible MAOIs?
- Isocarboxazid
- Phenelzine
- Tranylcypromine
Which is the only reversible MAOI?
Moclobomide
Does not need a washout period
What is a sign of a nhypersensitivity reaction with SSRIs?
Rash
What are the signs of SSRI overdose?
- Nausea
- Vomiting
- Drowsiness
- Sinus tachycardia
- Convulsions
What are the signs of SSRI abrupt withdrawal? (9)
- GI disturbance
- Headache
- Anxiety
- Electric shock sensation in the head
- Tinnitus
- Sleep disturbance
- Fatigue
- Flu-like symptoms
- Sweating
How long should the SSRI dose be tapered over?
4 weeks, (6 months if long term)
What can citalopram prolong?
QT interval
What is the dose equivalence of citalopram oral drops compared with tablets?
8 drops = 16mg drops = 20mg tablets
What class of drug is Venlafaxine?
SNRI
What are the symptoms of TCA overdose (can also occur as side effects at normal doses)?
- Dry mouth
- Coma
- Hypotension
- Hypothermia
- Convulsions
- Cardiac conduction defects
- Arrhythmias
- Dilated pupils
- Urinary retention
If a patient with bipolar is being treated with a TCA, when should it be stopped?
If they enter a manic phase
What is the mechanism of action of Mirtazapine?
Presynaptic alpha-adrenoceptor antagonist which increases noradrenergic and serotonergic nuerotransmission
Which drug is used to treat inappropriate sexual behaviour?
Benperidol
Which antidepressant is preferred in people with unstable angina or have had a recent MI?
Sertraline
List some of the side effects that may occur within the first few weeks of treatment in those taking antidepressants
Increased potential for agitation, anxiety, and suicidal ideation
Give 4 examples of SSRIs
Citalopram/Escitalopram, Fluoxetine, Sertraline, Paroxetine
Give 4 examples of TCAs
Amitriptyline, clomipramine, imipramine, lofepramine
Why are antipsychotics or anxiolytics not generally used in depression?
Anxiety is often present in depressive illness, these drugs might mask the true diagnosis
However, may be necessary if have psychotic symptoms (specialist)
How is serotonin syndrome treated?
Withdrawal of the serotonergic medication and supportive care
Seek specialist advice
How is generalised anxiety disorder treated?
GAD is a form of chronic anxiety
Treated with:
- Psychological therapy
- SSRI (Escitalopram, Paroxetine, sertraline [unlicensed])
- SNRIs (Duloxetine, Venlafaxine)
- Pregabalin
Which SNRI is licensed for panic disorder?
Venlafaxine
What is used second line for panic disorder?
clomipramine [unlicensed] or imipramine [unlicensed] (TCAs)
Give examples of Less-sedating TCAs
- Imipramine
- Nortriptyline
- Lofepramine
TCAs have varying degrees of antimuscarinic side-effects and cardiotoxicity in overdose.
Which one has the lower incidence of side-effects and is less dangerous in overdose?
Lofepramine
Has a lower incidence of side-effects and is less dangerous in overdose but is infrequently associated with hepatic toxicity
Which TCA has the most antimuscarinic side effects?
Imipramine
Which TCAs are particularly dangerous in overdose?
Amitriptyline and Dosulepin
Not recommended for treatment of depression
Which TCAs are not recommended for the treatment of depression?
Amitriptyline and Dosulepin
Mechanism of action of TCAs?
TCAs block the re-uptake of both serotonin and noradrenaline
Different TCAs are selective for each one to different extents
- Clomipramine more selective for serotonin (sedative)
- Imipramine more selective for noradrenaline (less-sedative)
TCA doses should be sufficiently high enough for effective treatment.
But who would normally be prescribed lower doses of TCAs initially?
Elderly patients
What is the STOPP criteria for TCAs in elderly patients?
- If prescribed in those with:
- Dementia
- Narrow angle glaucoma
- Cardiac conduction abnormalities
- Prostatism
- History of urinary retention
Due to risk of worsening these conditions
- If initiated as first-line (higher risk of ADRs than with SSRIs or SNRIs)
Which MAOI is most likely to cause a hypertensive crisis?
Tranylcypromine (greater stimulant action)
Discontinue if experience throbbing headache
Which MAOIs are most likely to hepatotoxicity?
Isocarboxazid and phenelzine
Which MAOI should be reserved for second line treatment?
Moclobemide
What is Flupentixol (Fluanxol ®) indicated for?
Has antidepressant properties when given by mouth in low doses
Also used for treatment of psychoses
Which antidepressant can be used for patients whose condition has responded inadequately to 2 antidepressants within the current episode?
Vortioxetine
Which antidepressants are used for neuropathic pain?
Amitriptyline
Nortriptyline
Which antidepressant is licensed in children (8 - 18 years)?
Fluoxetine
Which antidepressants can cause QT prolongation?
Citalopram, Escitalopram
Which antidepressants have the greatest risk of withdrawal?
Paroxetine (SSRI) and Venlafaxine (SNRI) due to their shorter half lives
Which antidepressant is also used in diabetic retinopathy?
Duloxetine
avoid in patients with uncontrolled hypertension
Which MAOI does not need a wash out period? Why?
Moclobemide
What are the irreversible and reversible MAOI?
Phenelzine, Isocarboxazid, Tranylcypromine (irreversible inhibition)
Moclobemide (reversible inhibition)
SSRI side effects? (GASH)
G - GI disturbances (nausea, vomiting, diarrhoea)
A - Appetite or weight loss/gain
S - Serotonin syndrome
H - Hypersensitivity reactions (stop if rash occurs)
Also:
- Hyponatraemia
- Lowers seizure threshold
- Bleeding risk
- Sexual dysfunction
- QT prolongation (citalopram and escitalopram)
- Insomnia (take in the morning)
- Movement disorders and dyskinesia
When should SSRIs be taken? What about TCAs? What about Mirtazepine?
SSRIs - take in the morning as can cause insomnia
TCAs - take at night as can cause drowsiness
Mirtazapine (tetracyclic)- take at night as can cause drowsiness
Key interactions for SSRIs
CYP450 enzyme inhibitors (SICKFACES.COM)
- Grapefruit juice (inhibitor)
Drugs which increase BLEEDING RISK
- NSAIDs/Aspirin/Anticoagulants
Drugs which increase risk of QT PROLONGATION (for citalopram and escitalopram)
- Macrolides, Anti-arrhythmics, Lithium, TCAs, Chloroquine and Mefloquine, antipsychotics
- Drugs which cause hypokalaemia e.g. theophylline, steroids, B2 agonists, loop/thiazide diuretics (increased risk of QT prolongation)
Drugs which increase risk of HYPONATRAEMIA
- Loop/thiazide diuretics, carbamazepine, NSAIDs, trimethoprim, desmopressin
Drugs which increase risk of SEROTONIN SYNDROME
- Sumatriptan, Tramadol, Lithium, Ondansetron, TCAs/MAOIs, St John’s Wort, Amphetamines
What are SSRIs cautioned in?
Cardiac disease
Bleeding- especially GI
Epilepsy as they can lower seizure threshold
What are the symptoms of TCA overdose?
Hypotension Hypothermia Convulsions Respiratory failure Dilated pupils Urinary retention
Side effects of TCAs? (TCAS)
T - Toxic in overdose (more so than SSRIs)
C - Cardiac side effects (QT prolongation, arrhythmias, hypotension, heart block)
A - Antimuscarinic side effects (dry mouth, constipation, urinary retention, raised intraocular pressure, blurred vision)
S - Seizures
Can also cause:
- Hallucinations and mania
- Sexual dysfunction
Key interactions for TCAs
CYP450 enzyme inhibitors and inducers
- Cimetidine (inhibitor)
- Carbamazepine (inducer)
- Grapefruit juice (inhibitor)
Drugs which increase risk of QT PROLONGATION (for Clomipramine)
- Citalopram, escitalopram
- Macrolides, Anti-arrhythmics, Lithium, TCAs, Chloroquine and Mefloquine, antipsychotics
- Drugs which cause hypokalaemia e.g. theophylline, steroids, B2 agonists, loop/thiazide diuretics (increased risk of QT prolongation)
Drugs which increase risk of HYPONATRAEMIA
- Loop/thiazide diuretics, carbamazepine, NSAIDs, trimethoprim, desmopressin
Drugs which increase risk of HYPOTENSION
- antihypertensives, SGLT2 inhibitors, diuretics, Sildenafil, antipsychotics
Drugs which increase risk of ANTIMUSCARINIC side effects
- antimuscarinic drugs, antihistamines, atropine, antipsychotics
Drugs which increase risk of SEROTONIN SYNDROME
- Sumatriptan, Tramadol, Ondansetron, TCAs/MAOIs, St John’s Wort, Selegiline, Amphetamines
Mechanism of action of MAOIs?
Block monoamine oxidase enzymes which leads to accumulation of monoamines (dopamine, serotonin, noradrenaline)
Combination of MAOIs with which other drugs could cause a hypertensive crises?
- Phenylepherine/Pseudoephedrine (DO NOT GIVE SUDOFED)
- Sumatriptan
- TCAs
- Adrenaline/noradrenaline
- Levodopa
- MAO-B inhibitors (resegiline, selegiline)
Interaction between TCAs and MAOIs could be potentially fatal
- AVOID TRANYLCYPROMINE AND CLOMIPRAMINE - FATAL
What is post-natal depression?
Similar to other forms of depression, patients may experience a persistent low mood, lack of interest and enjoyment in usual activities, low self-esteem or lack of energy
They may feel as though they are a bad parent, are unable to cope with their baby or may feel indifferent to their baby
Symptoms of PND can persist for months or years without treatment
Mothers should be routinely assessed for signs of PND when interacting with healthcare professionals and should be referred to their GP or mental health team if they demonstrate any red flags
Many women will be emotional or experience mild mood changes in the first week after having a baby (referred to as the ‘baby blues’), but these feelings should be self-limiting. True or False?
True
What are risk factors for post natal depression?
- Previous history of depression or PND (greatest risk factor)
- Poor social support
- Having more than one child
- Financial instability
- Having a poor relationship with their partner
- Recent stressful life events (e.g. break up of a relationship, job loss, family bereavement)
- History of abuse (e.g. physical, sexual or emotional abuse, neglect)
When are women at the greatest risk of PND?
In the first four to six weeks after birth
Increased risk of developing depression by as much as 3x. In addition, the risk of a first presentation of psychosis is higher in the first four weeks after birth than at any other point in a woman’s life
In men, PND in their partner is a significant risk factor for them also developing PND. True or False?
True
As is feeling excluded from the bond between the mother and baby, and a lack of a good male role model in a male parent’s life
What are red flag symptoms for post natal depression?
- Recent significant change in mental state or emergence of new psychiatric symptoms
- New thoughts or acts of violent self-harm
- New and persistent expressions of incompetency as a mother, such as estrangement from the infant, being overly self-critical and feelings of incompetence.
Patients with suicidal thoughts must be referred immediately to specialist perinatal mental health services.
What is postpartum psychosis?
Severe illness that shows similarities to bipolar disorder (e.g. an elated or depressed mood that can cycle rapidly, irritability, hallucinations or delusions)
It usually presents in the days or weeks after childbirth.
Prompt treatment is essential; if left untreated it can put both the mother and baby at risk
Hyperthyroidism and hypothyroidism can present alongside mood disorders, with episodes of thyrotoxicosis (excess thyroid hormone) presenting similarly to postpartum psychosis.
True or False?
True
How is PND screened for?
** Whooley questions or Patient Health Questionnaire-2**
Recommended by NICE and can be used by any healthcare professional
- During the past month, have you often been bothered by feeling down, depressed or hopeless?
- During the past month, have you often been bothered by having little interest or pleasure in doing things
If the questions below identify possible depressive symptoms, it is useful to ask if the patient would like any help with this and make a referral where possible:
**Generalised Anxiety Disorder scale **
Two questions about anxiety symptoms:
- Over the past two weeks, how often have you been bothered by feeling nervous, anxious or on edge?
- Over the past two weeks, how often have you been bothered by not being able to stop or control worrying
This should be followed by asking:
- Do you find yourself avoiding places or activities and does this cause you problems?
If the patient says they have experienced these feelings, they should be referred for further clinical assessment.
Patient Health Questionnaire
A follow on from the Patient Health Questionnaire-2 that is more commonly used to monitor severity of established depression, rather than diagnose it
- Nine questions based DSM-5 criteria for depression
- Patient rates how frequently they have experienced symptoms over the past two weeks
Edinburgh Postnatal Depression Scale
- Ten-question scale
- Asks the patient to rate how they feel about the questions asked, based on how frequently they have felt like that over the past week, scoring 0–3 for each question
- The maximum score is 30 and a score of 11 or more is indicative of PND. The scale has also been validated for use in men
The Bromley Postnatal Depression Scale
- A specific questionnaire for PND that looks at diagnosing previous episodes of PND, as well as the current one
- It asks the patient to write down when the previous episodes started, when episodes were worse and how long they lasted. The scale also contains a ten-item questionnaire.
