Clinical Knowledge Summaries (CKS) Depression: Managing Antidepressants For Depression in Primary Care

Clinical Knowledge Summaries
(CKS)
Depression
Managing antidepressants for depression in primary
care
The management of antidepressants during pregnancy or when breastfeeding is not discussed.
Educational slides based on the CKS topic Depression (August 2013) and NICE guidance (2009); Depression the treatment and
management of depression in adults (CG90), and Depression in adults with a chronic physical health problem (CG91).
Key learning points and objectives
• To be able to:
o Describe which antidepressant should be offered initially
and what factors influence choice.
o Outline how to titrate the dose of an antidepressant, when
to consider changing treatment, and how long treatment
should be continued for.
o Describe how to:
o Switch from one antidepressant to another.
o Stop an antidepressant.
o Recognise discontinuation symptoms and describe how to
manage them.
Based on the CKS topic Depression (August 2013) and NICE guidance (2009); Depression the treatment and management of depression
in adults (CG90), and Depression in adults with a chronic physical health problem (CG91).
Which antidepressant?
• Efficacy of antidepressants is largely
equivalent.
• Choice is based on:
o The person's preference.
o Adverse effect profile (e.g. sedation, sexual
adverse effects, weight gain).
o Safety in overdose – avoid TCAs or venlafaxine if
risk of overdose.
o Previous response to therapy.
o Presence of a chronic physical health problem.
• First episode
o Generic SSRIs preferred – better tolerated and
safer in overdose.
o For example citalopram, fluoxetine, paroxetine, or
sertraline.
• Recurrent episode of depression
o Consider an antidepressant the person has
responded well to in the past.
• Chronic physical health problem
o Sertraline preferred (lower risk of drug
interactions).
• Dosulepin
o If dosulepin is being considered it should only be
started by specialists.
o Increased cardiac risk and toxicity in overdose.
Based on the CKS topic Depression (August 2013) and NICE guidance (2009); Depression the treatment and management of depression in
adults (CG90), and Depression in adults with a chronic physical health problem (CG91).
Adverse effects of SSRI and TCAs
• SSRIs
o Common – nausea, vomiting, abdominal pain, dyspepsia,
constipation diarrhoea, dizziness, agitation, anxiety, insomnia,
and tremor.
o Sexual dysfunction – more common with SSRIs.
o Hyponatraemia – more common with SSRIs.
o Increase risk of GI bleeding – especially in older people or if
taking an NSAID.
o QT prolongation – citalopram/escitalopram.
• TCAs
o Common – dry mouth, blurred vision, constipation, urinary
retention, sedation, and postural hypotension.
o Cardiovascular effects – ECG changes, postural hypotension,
arrhythmias, heart block, tachycardia.
o Arrhythmias and severe hypotension with high dose or
overdose.
Adverse effects
• For more information on the adverse effects
of TCAs, SSRIs, and other antidepressants see:
o The CKS website (www.cks.nice.org.uk).
o The individual manufacturers Summary of Product
Characteristics (SPCs) available on
www.medicines.org.uk/emc.
Starting an antidepressant
• Prescribe a starting dose and titrate up (if
necessary).
• Examples of SSRI starting doses for depression:
o Citalopram 20 mg.
o Fluoxetine 20 mg.
o Paroxetine 20 mg.
o Sertraline 50 mg.
• Starting doses can be effective.
• Titration may not be needed for:
o SSRIs.
o Mirtazapine.
o Moclobemide.
o Reboxetine.
o Venlafaxine.
Starting an antidepressant
• Starting a TCA:
o Start with a low dose and titrate.
o Starting doses range from 10 mg to 75 mg daily.
o Lower starting doses required for elderly.
o Increase dose slowly (every 3-7 days) to the
minimum effective dose.
o Slow titration avoids adverse effects.
o Minimum effective dose of TCAs at least 75 mg to
100 mg (possibly 125 mg).
When to change treatment
• Antidepressant effect is usually seen within 2
weeks.
• If no effect is seen after 2-4 weeks:
o Check adherence and enquire about adverse effects.
• If there is still no response after 4 weeks of a
therapeutic dose, consider:
o Increasing the dose.
o Switching to an SSRI (if not already taking one).
o Switching to a different class of antidepressant.
adults (CG90), and Depression in adults with a chronic physical health problem (CG91)..
When to change treatment
• If there is some response at 4 weeks:
o Continue for another 2-4 weeks, then check response.
• If response is not adequate at 6-8 weeks:
o Consider switching to another antidepressant.
• Before switching, choice is influenced by:
o Comorbid conditions.
o Potential drug interactions.
o Adverse effect profiles (e.g. sedation, weight gain, sexual
adverse effects).
o Toxicity in overdose (e.g. TCAs).
How to switch antidepressants
• Avoid abrupt withdrawal when switching.
• Use a gradual cross tapering regimen for most
switches, for example:
Pre-switch Week 1 Week 2 Week 3 Week 4
dose
Withdrawing 40 mg daily 20 mg daily 10 mg daily 5 mg nil

citalopram daily
Introducing nil 15 mg daily 30 mg daily 30 mg 45 mg daily

mirtazapine daily (if required)
Based on the CKS topic Depression (August 2013) and NICE guidance (2009); Depression the treatment and management of
depression in adults (CG90), and Depression in adults with a chronic physical health problem (CG91).
How to switch antidepressants
• Occasionally it is possible to stop current
drug and start new one on the next day for
example:
o When switching from one SSRI to another SSRI
(except fluoxetine as it has a long half life).
• Caution required when switching from any
antidepressant to moclobemide
o Reports of serotonin syndrome.
Stopping antidepressants
• If possible, reduce gradually over 4 weeks.
o Reduce dose or frequency of administration.
o The aim is to minimize discontinuation symptoms.
• Discontinuation symptoms:
o Include dizziness, nausea, paraesthesiae, anxiety,
diarrhoea, flu symptoms, and headache.
o Usually start within 5 days of stopping.
o Common with longer treatment courses.
o More likely if short half life (paroxetine), anxiety
symptoms, or taking other centrally acting drugs.
o Rare with short courses (less than 8 weeks).
Stopping antidepressants
• Shorter tapering may be possible if:
o Severe adverse reaction (e.g. cardiac arrhythmia
on a TCA).
o Taking fluoxetine 20 mg as it has a longer half life
(but higher doses require gradual withdrawal).
• Longer tapering (over 6 months) may be
needed if:
o Taking longer-term maintenance treatment.
Managing discontinuation symptoms
• Mild symptoms
o Reassure the person that they will pass in a few
days — this is often all that is required.
• Severe symptoms
o Consider reintroducing the antidepressant at a
dose not associated with discontinuation
symptoms (or another antidepressant with a
longer half-life from the same class).
o Then taper more slowly while monitoring
symptoms.
Managing key adverse effects
• Suicidal thoughts and attempts – all
antidepressants
o Small absolute increased risk with adolescents and
young adults, and people with a history of suicidal
behaviour.
o Monitor closely for suicidal behaviour, self-harm,
or hostility. Particularly at the start of treatment
and dose changes.
• Anxiety, agitation, or insomnia
o Consider a short-term benzodiazepine (less than
2 weeks).
• Sexual dysfunction (e.g. erectile dysfunction,
decreased libido):
o A common symptom of depression and a common adverse
effect of all antidepressants.
o Most common with SSRIs and venlafaxine.
• Manage sexual dysfunction caused by
antidepressants, by:
o Watchful waiting (10% spontaneous remission).
o Reducing the dose of antidepressant.
o Switching antidepressant to another less likely to cause the
specific problem.
o Prescribing sildenafil if person has erectile dysfunction.
• Hyponatraemia
o Possible with all antidepressants, but most
common with SSRIs.
o Usually occurs within 30 days.
o Symptoms include – dizziness, drowsiness,
confusion, nausea, muscle cramps, or seizures.
• Management:
o Stop treatment.
o Manage according to the severity and duration of
symptoms, and state of hydration.
• Persistent, severe, or distressing adverse effects,
consider:
o Dose reduction and re-titration (if possible).
o Switching antidepressants to an antidepressant less likely to
cause that adverse effect.
o Non drug management (e.g. weight gain – diet and exercise).
• Mild and transient adverse effects (e.g. nausea with
SSRIs)
o Manage by explanation, reassurance and, if necessary, dose
reduction and re-titration.
• Bleeding
o Avoid aspirin, oral anticoagulants, or non-steroidal anti-
inflammatory drugs (NSAIDs).
o Consider gastroprotection.
Based on the CKS topic Depression (August 2013) and NICE guidance (2009); Depression the treatment and management of
depression in adults (CG90), and Depression in adults with a chronic physical health problem (CG91).
Key advice to patients
• Watch for worsening symptoms and suicidal ideas.
o Particularly when starting and changing medications.
• Usually takes 2-4 weeks for improvements.
o Some people improve within a few days.
• Need to continue treatment for 6 months after recovery.
• Antidepressants are not addictive, but withdrawal
symptoms may occur if stopped abruptly.
• Do not stop treatment suddenly (especially paroxetine).
• May experience sedation at the start of treatment or after
dose increase.
o Do not drive during this time if affected.
• Do not use St John’s wort.
o Uncertainty about doses.
o Great variation in the products that can be purchased.
Summary
• Generic SSRIs are preferred (e.g. citalopram, fluoxetine, paroxetine, or
sertraline), but
• Choice will also depend on:
o Personal preference, adverse effects, and toxicity in overdose.
o Dosulepin should only be started by a specialist.
o Increased cardiac risk and toxicity in overdose.
• Antidepressant effect is usually seen within 2 weeks.
• Be aware of the increased risk of suicide at the beginning of treatment or
after dosage changes.
• Consider switching if:
o No response has been seen after about 4-8 weeks.
o Patient has severe or persistent adverse effects.
• If switching – cross tapering is usually required.
• If stopping – gradual reduction is required if taking for longer than 8
weeks.

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Copyright:

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Clinical Knowledge Summaries

The management of antidepressants during pregnancy or when breastfeeding is not discussed.

Withdrawing 40 mg daily 20 mg daily 10 mg daily 5 mg nil

Introducing nil 15 mg daily 30 mg daily 30 mg 45 mg daily

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