Antidepressant Drugs Flashcards
Antidepressant drugs are effective for treating moderate to severe depression associated with __________ and ____________ changes such as loss of appetite and sleep disturbance
psychomotor
physiological
Antidepressant drugs are effective for treating moderate to severe depression associated with psychomotor and physiological changes such as _____________ and ____________
loss of appetite
sleep disturbance
What is typically the first benefit of antidepressant therapy?
Improvement in sleep
Ideally, patients with moderate to severe depression should be treated with ____________ in addition to drug therapy.
psychological therapy
What is dysthymia?
lower grade chronic depression; typically of at least 2 years duration
Dysthymia is a type of ________ (higher/lower) grade chronic depression that is typically of at least __________ duration
Lower
2 years
Antidepressant drugs should not be used routinely in _________ depression
mild
*psychological therapy should be considered initially
When are antidepressants used in the treatment of mild depression?
psychological therapy should be considered initially; however, a trial of antidepressant therapy may be considered in cases refractory to psychological treatments or in those associated with psychosocial or medical problem
In addition to patients with MILD depression in whom depression is refractory to psychological treatment, which other patients may be considered for antidepressant therapy?
Patients with a history of moderate or severe depression
What are the major classes of antidepressants? (4)
- TCAs
- SSRIs
- MAOIs
- SNRIs
Since there may be an interval of ________ before the antidepressant action takes place, electroconvulsive treatment may be required in severe depression when delay is hazardous or intolerable
2 weeks
Since there may be an interval of 2 weeks before the antidepressant action takes place, ____________ may be required in severe depression when delay is hazardous or intolerable
electroconvulsive treatment
During the first few weeks of treatment with antidepressants, there is an increased potential for _________, __________, and __________.
agitation
anxiety
suicidal ideation
__________ are better tolerated and are safer in overdose than other classes of antidepressants and should be considered first-line for treating depression.
SSRIs
In patients with unstable angina or who have had a recent myocardial infarction, ____________ has been shown to be safe in the treatment of depression
sertraline
______________ have similar efficacy to SSRIs but are more likely to be discontinued because of side-effects; toxicity in overdosage is also a problem
Tricyclic antidepressants
SSRIs are less __________ and have fewer ________ and ________ effects than tricyclic antidepressants.
sedating
antimuscarinic
cardiotoxic
__________ (class of antidepressants) have dangerous interactions with some foods and drugs, and should be reserved for use by specialists
MAOIs
___________ or __________ drugs should be used with caution in depression due to the risk of masking the true diagnosis, but they are useful adjuncts in agitated patients
Anxiolytics
antipsychotic
Augmenting antidepressants with __________ under specialist supervision may also be necessary in patients who have depression with psychotic symptoms
antipsychotics
Augmenting antidepressants with antipsychotics under specialist supervision may also be necessary in patients who have depression with ____________ symptoms
psychotic
Although anxiety is often present in depressive illness (and may be the presenting symptom), the use of an antipsychotic or an anxiolytic may _____________.
mask the true diagnosis
What is St John’s wort?
A popular herbal remedy for treating mild depression
Also a CYP450 inducer
St John’s wort can _________ (induce/inhibit) drug metabolising enzymes and a number of important interactions with conventional drugs, including conventional antidepressants, have been identified.
Induce
If a patient stops taking St John’s wort, the concentration of interacting drugs may _______ (increase/decrease), leading to toxicity.
Increase
What are the most commonly prescribed SSRIs? (5)
- Citalopram
- Escitalopram
- Fluoxetine
- Paroxetine
- Sertraline
What are the most commonly prescribed SNRIs? (2)
- Venlafaxine
2. Duloxetine
What are the most commonly prescribed TCAs? (5)
- Amitriptyline
- Clomipramine
- Nortriptyline
- Imipramine
- Lofepramine
What are the most commonly prescribed MAOIs? (4)
- Tranylcypromine
- Phenelzine
- Isocarboxazid
- Moclobemide
Patients should be reviewed every _________ at the start of antidepressant treatment
1–2 weeks
Treatment should be continued for at least __________ (________ in the elderly) before considering whether to switch antidepressant due to lack of efficacy
4 weeks
6 weeks
In patients being treated with antidepressants, how should partial response be managed?
In cases of partial response, continue for a further 2–4 weeks (elderly patients may take longer to respond)
Following remission, antidepressant treatment should be continued at the same dose for at least _________ (about __________ in the elderly), or for at least __________ in patients receiving treatment for generalised anxiety disorder (as the likelihood of relapse is high).
6 months
12 months
12 months
Patients with a history of recurrent depression should receive maintenance treatment for at least __________.
2 years
Which electrolyte disturbance has been associated with all types of antidepressants?
Hyponatremia, usually in elderly
Hyponatremia has been reported more frequently with ________ than with other antidepressants
SSRIs
_____________ should be considered in all patients who develop drowsiness, confusion, or convulsions while taking an antidepressant
Hyponatraemia
Hyponatraemia should be considered in all patients who develop ___________, ___________, or __________ while taking an antidepressant
drowsiness
confusion
convulsions
The use of antidepressants has been linked with suicidal thoughts and behaviour; which patient demographics are particularly at risk? (3)
- Children
- Young adults
- Patients with a history of suicidal behavior
Where necessary patients being treated with antidepressants should be monitored for suicidal behaviour, self-harm, or hostility, particularly at the __________ of treatment or if ___________
beginning
the dose is changed
What is serotonin syndrome?
a relatively uncommon adverse drug reaction caused by excessive central and peripheral serotonergic activity
What are the symptoms of serotonin syndrome? (3)
Range from mild to life-threatening
- Neuromuscular hyperactivity: tremor, hyperreflexia, clonus, myoclonus, rigidity
- Autonomic dysfunction: tachycardia, BP changes, hyperthermia, diaphoresis, shivering, diarrhea
- Altered mental state: agitation, confusion, mania
What factors may precipitate serotonin syndrome in a patient? (5)
Can occur within hours or days following:
- Initiation of treatment
- Dose escalation
- Overdose of serotonergic drugs
- Addition of a new serotonergic drug
- Replacement of one serotonergic drug by another without allowing a long enough washout period in between (particularly when the forest drug is in irreversible MAOI or a drug with a long half-life)
Severe toxicity, which is a medical emergency, usually occurs with a combination of serotonergic drugs, one of which is generally a(n) _________.
MAOI
What is the treatment of serotonin syndrome?
- Withdrawal of serotonergic medication
2. Supportive care
What are the main classes of serotonergic drugs? (10)
- SSRIs
- SNRIs
- Bupropion
- TCAs
- MAOIs
- Anti-migraine medications eg carbamazepine, valproate, triptans
- Pain medications eg opioids including over-the-counter cough syrups
- Lithium
- Antiemetics including 5-HT antagonists and D2 antagonists
- St John’s wort
What is the mechanism of action of bupropion?
Norepinephrine and dopamine reuptake inhibitor (SNDRI)
Failure to respond to initial treatment with an SSRI may require _____________, or ____________.
an increase in the dose
switching to a different SSRI or mirtazapine
In which drug class is the antidepressant mirtazapine?
Alpha-2 antagonist
____________ and __________ should be considered for more severe forms of depression
tricyclic antidepressants
venlafaxine
______________ may be initiated in severe refractory depression
Electroconvulsive therapy
Failure to respond to a second antidepressant may require the addition of ____________, or use of an augmenting agent like _________, __________, ____________, __________, or __________ under specialist supervision
another antidepressant of a different class
Lithium
Aripiprazole (unlicensed)
Olanzapine (unlicensed)
Quetiapine
Risperidone (unlicensed)
Management of acute anxiety generally involves the use of a ____________ or _____________.
benzodiazepine
buspirone hydrochloride
For chronic anxiety (of longer than 4 weeks’ duration) it may be appropriate to use a(n) _____________
antidepressant; particularly SSRI or SNRI
For patients with newly diagnosed anxiety, combined therapy with a ____________ may be required until the antidepressant takes effect
benzodiazepine
Patients with generalised anxiety disorder, a form of chronic anxiety, should be offered _____________ before initiating an antidepressant.
psychological treatment
For patients with chronic anxiety, a(n) ___________ such as ____________, ___________, or __________ [unlicensed], can be used if drug treatment is needed
SSRI
escitalopram
paroxetine
sertraline
In addition to SSRIs escitalopram, paroxetine, and sertraline, _____________ and ____________ (SNRIs) are also recommended for the treatment of generalised anxiety disorder
Duloxetine
venlafaxine
In patients with chronic anxiety, if SSRIs or SNRIs are not tolerated (or if treatment has failed to control symptoms), ____________ can be considered
pregabalin
Panic disorder is treated with _________
SSRIs
_______________ or __________ can be used second-line in the treatment of panic disorder. ____________, an SNRI, is also licensed for panic disorder.
clomipramine hydrochloride [unlicensed]
imipramine hydrochloride [unlicensed]
Venlafaxine
Obsessive-compulsive disorder, post-traumatic stress disorder, and phobic states such as social anxiety disorder are treated with ______________
SSRIs
What is the first line treatment for OCD?
SSRIs
What is the first line treatment for PTSD?
SSRIs
What is the first line treatment for phobic states eg social anxiety disorder?
SSRIs
_______________ can be used second-line for obsessive-compulsive disorder
Clomipramine hydrochloride (TCA)
______________ is licensed for the treatment of social anxiety disorder
Moclobemide (MAOI)
Moclobemide is licensed for the treatment of ______________
social anxiety disorder
What is the mechanism of action of TCAs?
Block re-uptake of both serotonin and noradrenaline
Tricyclic and related antidepressant drugs can be roughly divided into those with additional __________ properties and those that are less __________
sedative
sedating
Agitated and anxious patients tend to respond best to the TCAs with _____________, whereas withdrawn and apathetic patients will often obtain most benefit from the less _________ ones
Sedative activity
Sedating
TCAs with greater sedative activity are better for depressed patients who also have _________ and __________ symptoms
Agitated
Anxious
TCAs with less sedative activity are better for depressed patients who also have _________ and __________ symptoms
Withdrawn
Apathetic
Which TCAs have sedative properties? (7)
- Amitriptyline
- Clomipramine
- Dosulepin
- Doxepin
- Mianserin
- Trazodone
- Trimipramine
Which TCAs have less sedating properties? (3)
- Imipramine
- Lofepramine
- Nortriptyline
____________ (TCA) has a lower incidence of side-effects and is less dangerous in overdosage but is infrequently associated with hepatic toxicity
Lofepramine
Imipramine hydrochloride has more marked _________________ side-effects than other tricyclic and related antidepressants
antimuscarinic
______________ and ______________ are effective but they are particularly dangerous in overdosage and are not recommended for the treatment of depression
Amitriptyline
dosulepin
Amitriptyline hydrochloride and dosulepin hydrochloride are effective but they are particularly dangerous in overdosage and are not recommended for the treatment of _____________
depression
Low doses of TCAs should be used for initial treatment in _____________ (patient population).
the elderly
In most patients the long half-life of tricyclic antidepressant drugs allows once-daily administration, usually ______________
at night
Studies have shown that tricyclic antidepressants are not effective for treating depression in ___________ (patient population).
children
The use of tricyclic antidepressants in elderly patients is potentially inappropriate (STOPP criteria):
If prescribed in those with… (5)
- Dementia
- Narrow angle glaucoma
- Cardiac conduction abnormalities
- Prostatism
- History of urinary retention
Can TCAs be used as first line antidepressant treatment in the elderly?
No; more appropriate to prescribe SSRIs or SNRIs which have a lower risk of adverse drug reactions
It is easier to prescribe __________ (MAOIs/TCAs) when ___________ (MAOIs/TCAs) have been unsuccessful than vice versa.
MAOIs
TCAs
_______________ has a greater stimulant action than phenelzine or isocarboxazid and is more likely to cause a hypertensive crisis
Tranylcypromine
all MAOIs
Tranylcypromine has a greater stimulant action than phenelzine or isocarboxazid and is more likely to cause a _____________
hypertensive crisis
_____________ and ___________ are more likely to cause hepatotoxicity than tranylcypromine.
Isocarboxazid
phenelzine
(All MAOIs)
Isocarboxazid and phenelzine are more likely to cause ____________ than tranylcypromine.
hepatotoxicity
______________ (MAOI) should be reserved as a second line treatment
Moclobemide
Phobic patients and depressed patients with atypical, hypochondriacal, or hysterical features are said to respond best to ___________ (class of antidepressants)
MAOIs
____________ patients and depressed patients with ____________, ____________, or ___________ features are said to respond best to MAOIs
Phobic
atypical
hypochondriacal
hysterical
__________ should be tried in any patients who are refractory to treatment with other antidepressants as there is occasionally a dramatic response
MAOIs
Response to treatment with MAOIs may be delayed for __________ or more and may take an additional 1 or 2 weeks to become maximal.
3 weeks
Response to treatment with MAOIs may be delayed for 3 weeks or more and may take an additional ___________ to become maximal.
1 or 2 weeks
Other antidepressants should not be started for ___________ after treatment with MAOIs has been stopped (___________ if starting clomipramine or imipramine)
2 weeks
3 weeks
An MAOI should not be started until at least ___________ after a previous MAOI has been stopped (then started at a reduced dose)
2 weeks
An MAOI should not be started until at least ___________ after a TCA (___________ in the case of clomipramine or imipramine) has been stopped
7-14 days
3 weeks
An MAOI should not be started until at least ___________ after an SSRI (at least ___________ in the case of fluoxetine) has been stopped
1 week
5 weeks
An MAOI should not be started until at least 2 weeks after a ___________ has been stopped (then started at a reduced dose)
previous MAOI
An MAOI should not be started until at least 7–14 days after a __________ (3 weeks in the case of _____________ or __________) has been stopped
TCA
clomipramine
imipramine
An MAOI should not be started until at least a week after a(n) ____________ (at least 5 weeks in the case of ____________) has been stopped
Fluoxetine
_____________, an antidepressant thought to directly modulate serotonergic receptor activity and inhibit the re-uptake of serotonin, is recommended in patients whose condition has responded inadequately to 2 antidepressants within the current episode
Vortioxetine
_____________ is licensed for use in treatment-resistant depression, used as monotherapy and as an adjunct to other antidepressant drugs
Tryptophan
Should be initiated by hospital specialists
SSRIs and SNRIs are correlated with a small increased risk of __________ when used in the month before delivery
Postpartum hemorrhage
*SSRIs are known to increase the risk of bleeding due to their effect on platelet function; this may be significant in patients with other risk factors for bleeding disorders
** Anticoagulant medication in women at high risk of thrombotic events should not be stopped, however, prescribers should be aware of the risk identified.
What are the contraindications to use of SSRIs? (2)
- Poorly controlled epilepsy
2. Mania
SSRIs should be prescribed with caution in which patients? (7)
- Cardiac disease
- Concurrent ECT
- DM
- Epilepsy (discontinue if convulsions develop)
- History of bleeding disorders, esp. GI bleeding
- History of mania
- Susceptibility to angle-closure glaucoma
What are the side effects associated with SSRIs? (5)
- Neuro/Psych: anxiety, impaired concentration, confusion, depersonalization, drowsiness, headache, mydriasis, paresthesias, visual impairment, sleep disorders, tinnitus
- GI: change in appetite and taste, constipation, diarrhea, discomfort, nausea, vomiting, weight changes, hemorrhage, dry mouth
- MSK: arthralgia, myalgia, tremor, skin reactions, hyperhydrosis
- Other: arrhythmias/QT interval prolongation, fever, urinary disorders, sexual dysfunction
Sexual dysfunction is most commonly associated with which class of antidepressant?
SSRIs
May persist after treatment has stopped
Symptoms of poisoning by ____________ include nausea, vomiting, agitation, tremor, nystagmus, drowsiness, and sinus tachycardia; convulsions may occur.
selective serotonin re-uptake inhibitors
Rarely, severe poisoning with ________ results in ___________, with marked neuropsychiatric effects, neuromuscular hyperactivity, and autonomic instability; hyperthermia, rhabdomyolysis, renal failure, and coagulopathies may develop.
SSRIs
serotonin syndrome
Which common or very common side effects are specifically associated with the SSRI, sertraline? (6)
- Chest pain
- Depression
- GI disorders
- Increased risk of infection
- NM dysfunction
- Vasodilation
What serious side effects have been associated with sertraline? (4)
- Cerebrovascular insufficiency
- Leukopenia
- NMS
- Pancreatitis
Are SSRIs safe to use in pregnancy and breastfeeding?
Avoid in pregnancy unless benefit outweighs risk
Not known to be harmful but consider is continuing breastfeeding
If SSRIs are used during the third trimester there is a risk of _____________, and _____________ has been reported.
neonatal withdrawal symptoms
persistent pulmonary hypertension in the newborn
Does dosing of SSRIs in hepatic and/or renal dysfunction need to be adjusted?
Prolonged half-life in hepatic impairment; caution
Avoid sertraline in severe impairment and reduce dose in mild to moderate disease
What are the symptoms of abrupt withdrawal of SSRIs? (13)
- GI disturbance
- Headache
- Anxiety
- Dizziness
- Paresthesias
- Electric shock sensation in the head, neck, and spine
- Tinnitus
- Sleep disturbances
- Fatigue
- Flu-like symptoms
- Sweating
- Visual disturbances
- Palpitations
The dose of SSRIs should be tapered over at least _____________ to avoid the effects of rapid withdrawal
a few weeks
*longer if sertraline
Withdrawal effects may occur within __________ of stopping treatment with SSRIs; they are usually mild and self-limiting, but in some cases may be severe
5 days
Sertraline should preferably be reduced gradually over about ___________, or longer if withdrawal symptoms emerge (_________ in patients who have been on long-term maintenance treatment).
4 weeks
6 months
Patients and carers should be advised that patients taking SSRIs may have impaired ability to ___________
Drive and perform skilled tasks eg operating machinery
____________, __________ and _______________ increase the risk of bleeding when used in combination with SSRIs
NSAIDs
Anticoagulants
Antiplatelets
Escitalopram is the active enantiomer of __________.
citalopram (both SSRIs)
What is the main contraindication specific to escitalopram?
QT-prolongation
What is a common side effects associated with paroxetine (SSRI)?
Blurred vision
Paroxetine is associated with a __________ (higher/lower) risk of withdrawal reactions compared to other SSRIs
Higher
Which antidepressants are LEAST likely to cause sexual side effects? (4)
- Bupropion
- Mirtazapine
- Vortioxetine
- Vilazodone
Which antidepressants are MOST likely to cause sexual side effects? (4)
- SSRIs
- SNRIs
- TCAs
- MAOIs
What are the contraindications to the use of TCAs? (5)
- Acute porphyrias
- Arrhythmias
- Mania
- Heart block
- Immediate recovery period after MI
TCAs should be prescribed with caution in which patients? (13)
- CVD
- Chronic constipation
- Epilepsy
- History of bipolar disorder
- History of psychosis
- Hyperthyroidism (risk of arrhythmia)
- Increased IOP
- Significant suicide risk
- Phaeochromocytoma (risk of arrhythmias)
- Prostatic hypertrophy
- Risk of QT prolongation (correct hypokalemia before initiating treatment)
- Susceptibility to angle closure glaucoma
- Urinary retention
For patients taking TCAs, treatment should be stopped or dose reduced if the patient enters a _____________
Manic phase
____________ patients are particularly susceptible to many of the side-effects of tricyclic antidepressants
Elderly
*low initial doses should be used, with close monitoring, particularly for psychiatric and cardiac side-effects
What are the common or very common side effects of TCAs? (5)
- Neuropsychiatric: aggression, anxiety, impaired concentration, confusion, delirium, depersonalization, exacerbation of depression, drowsiness, fatigue, hallucinations, headache, hot flushes, hyperhydrosis, memory loss, altered mood, movement disorders, mydriasis, sexual dysfunction, sleep disorders, altered taste, tinnitus, vision disorders, speech disorder
- CV: arrhythmias, hypotension, palpitations
- GI/GU: constipation, diarrhea, dry mouth, nausea, urinary disorders
- Endocrine: breast enlargement, galactorrhea, weight increased
- MSK: muscle tone increased, muscle weakness, skin reactions
What are the dangerous side effects associated with TCAs? (6)
- Agranulocytosis
- NMS
- Vaginal hemorrhage
- Rhabdomyolysis
- Serotonin syndrome
- Suicidal behaviors
Patient taking TCAs should be encouraged to ____________ treatment if side-effects develop
Continue
*some tolerance to side-effects seems to develop; the risk of side-effects is reduced by titrating slowly to the minimum effective dose (every 2–3 days)
Overdose of _____________ cause dry mouth, coma of varying degree, hypotension, hypothermia, hyperreflexia, extensor plantar responses, convulsions, respiratory failure, cardiac conduction defects, and arrhythmias. Dilated pupils and urinary retention also occur
TCAs
Antimuscarinic effects among other symptoms of autonomic dysregulation
____________ have been reported when TCAs are used during the third trimester of pregnancy
Neonatal withdrawal symptoms
Are TCAs safe to use in breastfeeding?
Yes
Can TCAs be used in hepatic impairment?
Use caution; avoid in severe impairment due to risk of hypertensive crisis
Is monitoring required with TCA use?
Monitoring of cardiac and hepatic function during long-term use
Manufacturer advises monitoring of __________ and ___________ function during long-term use of TCAs
Cardiac
Hepatic
The risk of withdrawal symptoms is increased if the antidepressant is stopped suddenly after regular administration for __________ or more.
8 weeks
Limited quantities of ___________ should be prescribed at any one time because their cardiovascular and epileptogenic effects are dangerous in overdosage.
TCAs
Limited quantities of tricyclic antidepressants should be prescribed at any one time because their ___________ and _________ effects are dangerous in overdosage.
cardiovascular
epileptogenic
Effects of alcohol are enhanced when patients are taking _____________ (class of antidepressant)
TCAs
Overdosage with _____________ (antidepressant) is associated with a relatively high rate of fatality.
Amitriptyline
*Symptoms of overdosage may include dry mouth, coma of varying degree, hypotension, hypothermia, hyperreflexia, extensor plantar responses, convulsions, respiratory failure, cardiac conduction defects, and arrhythmias; Dilated pupils and urinary retention also occur
What are the symptoms of NMS? (6)
- Muscle rigidity (diffuse “lead pipe”)
- Fever
- Tachycardia
- Diaphoresis
- Hyporeflexia
- Hypertension
*gradual onset
(VS serotonin syndrome which is characterized by hyperreflexia, myoclonus, nausea, diarrhea)
What is the mechanism of action of MAOIs?
MAOIs inhibit monoamine oxidase, thereby causing an accumulation of amine neurotransmitters.
What are the contraindications to MAOIs? (4)
- Cerebrovascular disease
- Mania
- Phaeochromocytoma
- Severe CVD
What are the side effects associated with MAOIs?
Akathisia; anxiety; appetite increased; arrhythmia; asthenia; behaviour abnormal; blood disorder; confusion; constipation; dizziness; drowsiness; dry mouth; dysuria; hallucination; headache; hyperhidrosis; insomnia; jaundice; nausea; paraesthesia; peripheral neuritis; postural hypotension (more common in elderly); reflexes increased; skin reactions; suicidal behaviours; tremor; vision blurred; vomiting; weight increased
Discontinue MAOIs if __________ or __________ occur
Palpitations
Frequent headaches
Are MAOIs safe in pregnancy?
Increased risk of neonatal malformations; avoid unless compelling reasons
Are MAOIs safe to use in hepatic and/or renal impairment?
Avoid in hepatic impairment
What monitoring is advised for patients taking MAOIs?
Monitor BP due to risk of hypotension and hypertensive responses
What are the symptoms of abrupt MAOI withdrawal? (10)
- agitation
- irritability
- ataxia
- movement disorders
- insomnia
- drowsiness
- vivid dreams
- cognitive impairment
- slowed speech
- Hallucinations and paranoid delusions
What additional information should be given to patients and carers regarding MAOIs?
- Patients should be advised to eat only fresh foods and avoid food that is suspected of being stale or ‘going off’. This is especially important with meat, fish, poultry or offal; game should be avoided. The danger of interaction persists for up to 2 weeks after treatment with MAOIs is discontinued.
- Patients should also be advised to avoid alcoholic drinks or de-alcoholised (low alcohol) drinks.
- Drowsiness may affect performance of skilled tasks (e.g. driving).
