Depression Flashcards
What are the psychological and physical symptoms of depression?
Psychological symptoms:
- Low self esteem
- Worry and anxiety
- Suicidal thoughts
Physical symptoms:
- Lack of energy
- Changes in weight/appetite
- Insomnia: early morning wakens
What are the different classes of antidepressants?
TCAs
- Amitriptylline*
- Doselupin*
- Nortriptylline*
- Imipramine*
TCA-related antidepressants
- Mianserin*
- Trazodone*
SSRIs
- Citalopram*
- Fluoxetine*
- Escitalopram*
- Sertraline*
- Paroxetine*
- Fluvoxamine*
Irreversible MAOs
- Phenelzine*
- Isocarboxazid*
- Tranylcypromine*
Reversible MAOs (short-acting)
Moclobemide
SNRI
- Duloxetine*
- Venlafaxine*
Other antidepressant drugs
Mirtazepine
What antidepressants are first line in depression and why?
SSRIs
- Better tolerated and safer in overdose than other classes
- Less sedating, antimuscularinic, epileptogenic, cardiotoxic than TCAs
- MAOIs rarely used as dangerous food and drug interactions
How long do antidepressants take to work?
- *4 weeks**
- *6 weeks in elderly**
Review every 1-2 weeks
Initially feel worse, increased agitation, anxiety and suicidal ideation
How long should antidepressants be continued after remission? (+ in elderly)
6 months
12 months elderly
How long should antidepressants be continued after remission in generalised anxiety disorder?
12 months - at high risk of relapse
How long should antidepressants be continued after remission in recurrent depression?
2 years
What if patient does not respond to first line treatment for depression?
Second-line
Increase SSRI dose
OR
Different SSRI
OR
Mirtazepine
Third-line
Add another antidepressant class
OR
Augmenting agent e.g. lithium or antipsychotic
OR
ECT
What are the side effects of antidepressants?
- Hyponatraemia:
drowsiness, confusion, convulsions
especially SSRIs
- Suicidal ideation and behaviour
- Serotonin syndrome
What are the serotonin syndrome symptoms?
- Neuromuscular hyperactivity (tremor, hyperreflixia, clonus, myoclonus, rigidity)
- Autonomic dysfunction (tachycardia, BP changes, hyperthermia, diaphoresis, shivering)
- Altered mental state (agitation, confusion, mania)
When is a washout period needed?
When antidepressant is stopped before switching to different antidepressant class to avoid serotonin syndromew
Washout out period for:
MAOIs
SSRIs
TCAs
MAOIs - wait 2 weeks. (Moclobemide no washout)
SSRIs - wait 1 week (2 weeks sertraline, 5 weeks fluoxetine)
TCAs - wait 1-2 weeks (3 weeks imipramine or clomipramine)
Which anti-depressants have greatest risk of withdrawl reaction and why
Paroxetine and venlaxfaxine - shorter half life
When do withdrawal reactions normally occur
Within 5 days of stopping antidepressant
What increases the risk of withdrawal reactions of antidepressants?
Stopped suddenly after taking for > 8 weeks
How to withdraw antidepressants safely
Reduce dose gradually over 4 weeks, longer if withdrawl (6 months in pts on long-term tx)
How do SSRIs work?
Inhibit reuptake of serotonin, increasing serotonin activity
List some SSRIs (6)
Citalopram, Escitalopram, paroxetine, fluoxetine, sertraline, fluvoxamine
Side effects of SSRIs
G - GI disturbances - N, V, D A
A - Appetite or weight disturbance
S - serotonin syndrome
H - Hypersensitivity reactions - stop if rash
Others - bleeding, QT interval, lower seizure threshold, movement disorders, dyskinesia, sexual dysfunction (may persist after stopping)
What the symptoms of SSRI overdose
N, V, agitation, tremor, nystagmus, drowsiness, sinus tachycardia, convulsions
Rare - results in serotonin syndrome (neuropsychiatric effects, neurmuscular hyperactivity and autonomic instability, hyperthermia, rhabdomyolysis, renal failure and coagulopahies (bleeding disorders)
MHRA SSRIs
Small increased risk of postpartum haemorrhage when used in the month before delivery
Compared to TCAs SSRIs are less .. (4)
Sedating
Anti-muscarinic
Cardiotoxic
Epilpetogenic
Which is the only anti depressant licensed in children?
Fluoxetine
Which two SSRIs increase the risk of QT interval pro-longation
Citalopram and escitalopram
Which SSRI has greatest risk of withdrawl
Paroxetine
Interactions of SSRIs
Increased plasma concentration
- Grapefruit juice (enzyme inhibitor)
Increased risk of bleeding
- NSAIDs, anticoagulants, anti-platelets
For escitalopram/citalopram
- Drugs that increase risk of QT prolongation
Increased risk of hyponatraemia
- Diuretics
Increased risk of seretongeric effects/serotonin syndrome
- St Johns Wort (not recommended), amphetamines, sumatriptan, tramadol, ondansetron, TCA/MAOI
What drugs increase risk of serotonin syndrome
St john’s wort, amfetamines, sumatriptan, selegiline, tramadol, TCAs/MAOIs/SSRIs, ondansetron
Which anti-depressant is safe to use after an MI? Which class to avoid immediately after MI
Sertraline
Avoid TCAs
What is the dosing of TCAs
OD - long half life
Name the least sedating TCAs
Imipramine, lofepramine, notriptylline
Which TCA is least dangerous in overdose
Lofepramine
Which TCA is most dangerous in overdose + not recommended in tx of depression
Dosulepin (+ Amitriptylline)
Which TCAs can also be used to treat neuropathic pain
Amitriptylline and notriptylline
Which TCA has the most marked anti-muscarinic SEs
Imipramine
Which compounds do agitated/anxious people and apathetic patients respond to? (sedating vs non-sedating compounds)
Agitated and anxious patients tend to respond best to the sedative compounds, whereas withdrawn and apathetic patients will often obtain most benefit from the less sedating ones
Interactions of TCAs
Reduced plasma concentration
Carbamazepine (enzyme inducers)
Increased plasma concentrations
Cimetidine (enzyme inhibitors)
Increased risk of hyponatraemia
Diuretics e.g. loop/thiazide
Increased risk of QT interval prolongation
Amiodarone, sotalol, antipsychotics, citalopram/escitalopram
Increased risk of hypotension
Antihypertensives, NSAIDs, antipsychotics
Increased antimuscarinic effects
Antimuscarinic drugs, antihistamines, atropine, antipscyhotics
Increased risk of serotonin syndrome
List the sedating TCAs (5)
Amitriptylline, clomipramine, dosulepin, doxepin, trimipramine
Side effects of TCAs
More sedating, epileptogenic, cardiotoxic and antimuscarinic than SSRIs
T - Toxic (more) in overdose than SSRIs
C - Cardiac SEs (QT pro-longation, arrythmias, heart block HTN)
A - Anti-muscarinic (dry mouth, blurred vision, constipation, tachycardia, urinary retention, increased IOP, glaucoma)
S - Seizures
Others - hallucinations, mania, hypotension, sexual dysfunction, breast changes, EPSE
Mechanism of action of TCAs
Blocks reuptake of two monoamine neurotransmitters - serotonin + NA. Blocks ACh.
List the irreversible MAOIs
Phenelezine, isocarboxid, tranylcypromine
List the reversible MAOIs and what does this mean
Moclobemide - no wash out period
Side effects of MAOIs
Hepatoxicity
More likely with phenelzine and isocarboxazid
Postural hypotension/hypertensive responses
Discontinue if palpitations or frequent headaches
Hypertensive crisis
Discontinue if hypertensive crisis with throbbing headache occurs
More likely with tranylcypromine
Which two MAOIs are more likely to cause hepatoxicity
Phenelzine and isocarboxaid
Which MAOI has greatest stimulatory action and what does this cause? Avoid with what other drugs
Tranylcypromine - hypertensive crisis (report throbbing headache) Stimulants - pseuderphredine, levodopa, DRAs, MAO-Bi, TCAs, esp tran + clomipramine (lethal)
Which two anti-depressant classes do you never prescribe together
TCA + MAOI = FATAL
Patient counselling MAOI (food related) + how long to food + drug intereactions last for
Tyramine containing foods (mature cheese, wine, pickled herring, game, broad bene pods) Eat only fresh food
Avoid stale
Avoid alcohol
Two weeks after stopping irreversible MAOI
When would you deem SSRI ineffective
4 weeks (6 weeks elderly)
How often is SSRI reviewed at start of therapy
Every 1-2 weeks
Over which time period is paroxetine withdrawn over
4 weeks - 6 months if long term therapy
Hyponatremia occurs more in which drug class
SSRIs
What antidepressant is also used to treat menopausal symptoms associated with breast cancer?
Venlafaxine
