Fatima (Depression and its management 2)

Question 1

NICE guidance on depression treatment

Answer 1

Less severe:
- Antidepressants should not be routinely used as first line unless the person prefers it
- SSRI should be first line medication

More severe:
- CBT with antidepressant therapy is preferred choice
- Antidepressant therapy alone is also suitable
- The first line medication is an SSRI but can also be other antidepressants in specific situations

Question 2

Antidepressant counselling

Answer 2

NICE emphases the importance of counselling patient thoroughly before starting medication due to concerns about their withdrawal effect.
The withdrawal effects of antidepressants can be severe.
Treatment options should be discussed with patient, and the most appropriate one should be chosen.
Before prescribing an antidepressant written information about the medication should be provided and a management plan should be documented in the clinical record and a copy given to the patient.

Information should cover:
- Expected side effects
- Next steps if the medication is ineffective
- Issues around withdrawal
- safe storage
- Issues relating to pregnancy

Documentation should cover:
- Indiction and intended outcomes of treatment
- Starting dose and intervals between adjustments
- Time to onset of action
- Who to contact if there are any problems
- Anticipated duration of therapy and duration of each prescription
- Risks of taking more than the prescribed dose, signs and symptoms of an overdose and what to do
- Plans for reviewing the medication

Question 3

Follow up and review of antidepressant use

Answer 3

Initial follow up should be around 2 weeks.
If the effect is not seen from initial treatment at 4-6 weeks, further action should be taken.
- If, after 4 weeks of treatment there has been no response and the patient is adherent, increase dose or switch to another SSRI or any other antidepressant suitable for primary care
- Do not use St. John’s wort and advise patients do not take anything OTC
If the patient becomes well
- continue any medication usually for 6 months, then weight the risk and benefits from stopping vs longer term treatment
- psychosocial relapse prevention strategies e.g. consider CBT

Question 4

Choosing an antidepressant

Answer 4

• SSRIs are usually the first line in primary care initiation. They are the safest in overdose
• It is acceptable to start an non-SSRI drug first time in severe depression (such as duloxetine, venlafaxine, and mirtazapine) but they should only used when there is compelling reason not to use an SSRI (contraindications such as pregnancy, breastfeeding, poorly controlled epilepsy)
• Antidepressants should not be combined in primary care without advice form secondary care

Factors to consider
- Risk of side effects
- Interactions
- Ease of stopping the medication
- Response to a previous drug

Question 5

Antidepressants

Answer 5

Can help with the acute phase of the treatment of an episode of depression and with relapse prevention.
Little difference in overall effect between classes, but risk and tolerability differ.
Onset of action should occur after 1st week with maximal effect after 4-6 weeks of therapeutic dose.
Antidepressants relieve symptoms of depression, they do not make you happy.
Antidepressants are not addictive, although stopping abruptly may increase withdrawal symptoms.

Question 6

Different types of antidepressants

Answer 6

SSRI- selective serotonin reuptake inhibitor
TCA- tricyclic acid
SNRI- serotonin and noradrenaline reuptake inhibitor
MAOI- monoamine oxidase inhibitor
RIMA- reversible inhibitor of MAO-A
NARI- noradrenaline reuptake inhibitor
NASSA- noradrenaline and specific serotonin antidepressant

Question 7

SSRIs

Answer 7

Inhibition of serotonin transporter (SERT).
More effective than placebo for moderate to severe depressive episodes.
Better tolerability than TCA.
Examples- citalopram, sertraline, escitalopram, fluoxetine, paroxetine

Question 8

SSRI challenges

Answer 8

Side effects:
- Abnormal appetite
- Headache
- GI discomfort
- Sleep disorders
- Weight changes
- Anxiety
- Sexual dysfunction
- Nausea and vomiting

Citalopram- prolonged QTc
Fluoxeting- CYP450 interactions, long half life
Paroxetine- discontinuation syndrome, short half life

Question 9

TCA

Answer 9

Tertiary amines exert more adverse effects than secondary amines.
Block NA reuptake and antagonise H1, alpha 1 and muscarinic cholinergic receptors.
More effective than placebo for moderate to severe depressive episodes
Examples- amitriptyline, imipramine, clomipramine

Question 10

TCA drug problems

Answer 10

Muscarinic receptor antagonism
- cardiotoxicity (especially in overdose)
- dry mouth, constipation

H1 antagonism
- sedation

Na a1 antagonism
- sedation, hypotension

Dose titration to minimise adverse effects
- time to effective dose

Question 11

MAOI

Answer 11

Inhibits metabolism of enzyme that metabolises monoamines.
Similar efficacy to TCA.
Drug interactions- washout period >2 weeks)
Impairs tyrannie metabolism.
Examples- phenelzine, tranylcypromine

Question 12

Mirtazapine

Answer 12

Comparable efficacy to TCA and SSRI in moderate to severe depression.
NA a1 antagonism (competitive), H1 antagonism and post-synaptic 5-HT2 antagonism.
Increases appetite which can lead to weight gain.
Risk of blood dycrasias.

Question 13

Venlafaxine

Answer 13

Equivalent efficacy to TCAs and slightly more effective than SSRIs in severe depression.
Similar effect to TCAs, with less sedation or orthostatic hypotension.
Baseline ECG and blood pressure monitoring required.

Question 14

Antipsychotics

Answer 14

Beneficial when used with an antidepressant for psychotic depression.
Fluphenthixol shows some antidepressant effects.

Question 15

Lithium

Answer 15

Limited effect for monotherapy in depression.
Used in severe depression in patients who are high risk of suicide.
Increased effect when added to antidepressant therapy

Question 16

St John’s Wort

Answer 16

Not routinely used.
Proposed MAOI effect.
Evidence for benefit in mild to moderate depressive episodes compared to placebo.
Unstandardised preparations.
Interactions with oral contraceptive pill, theophylline, and cyclosporin. (it is an enzyme inducer)

Question 17

Withdrawal symptoms

Answer 17

Caused by all classes of antidepressants. Experienced more by stopping SSRI treatment, with rate varying between individual drugs.
Severity of the withdrawal symptoms depends on factors such as the dose, half lives, and duration.
NICE states that patient should be counselled about the potential for withdrawal effects before starting an antidepressant drug, which includes discussing non-pharmacological approaches to treatment.

Range from mild severe.
Often appear within a few days of dose reduction or stopping.
Include restlessness, irritability, anxiety, insomnia, unsteadiness, sweating, arthralgia/myalgia, altered mood.
Severe withdrawal effects may include suicidal ideation.

Ways of reducing risk of withdrawal effects:
- tapering the dose slowly
- using liquid preparations may be helpful
- considerations should be given to the antidepressants’ pharmacokinetics

Question 18

Serotonin syndrome

Answer 18

Particular impact when switching between antidepressants, or multiple drugs with serotonergic effects.
Symptoms include:
- Shivering and sweating
- Autonomic instability- tachycardia
- Agitation, confusion and delirium
- Tremor, myoclonus

Question 19

Adherence

Answer 19

Treatment is only effective if taken
- cost of avoidable non-adherence is £100 million
- non-adherence can be partial or not al all
Depression is a risk factor for poor adherence.
Explore, educate, empower, and enable
- asks opinions on medicine taking and clarify expectations

Question 20

Relapse prevention

Answer 20

Continue medication for at least 6 months after symptoms resolution.
After subsequent episodes, with high risk of relapse, or high risk factors, consider for up to 2 year.
Consider lifelong for multiple episodes of relapse.

Support and encourage a person who has benefited from taking an antidepressant to continue medication for at least 6 months after remission of an episode of depression. Discuss with the person that this greatly reduces the risk of relapse and that antidepressants are not associated with addiction.
Review with the person with depression the need for continued depression treatment beyond 6 months after remission taking into account the number of previous episodes of depression, the presence of residual symptoms, concurrent physical health problems and psychosocial difficulties.

In those with multiple relapses consider continuing treatment for at least 2 years. Before doing this the person should be reevaluated, considering age, comorbid condition, and other risk factors.

Question 21

Pregnancy

Answer 21

Major depression is common in pregnancy and the postpartum period.
Post-natal depression can have an adverse effect on the mother infant relationship and, if untreated, could bring harm to the infant.

For major depression treatment is the same as normal. Important to optimise psychosocial support and psychological therapy. Antidepressant use is reserved for patients with severe depression as there are some risk associated with them used in post-natal period. If antidepressants started during pregnancy then SSRIs are used. Sertraline is usually preferred. Avoid fluoxetine in breastfeeding. Involve a specialist.

Question 22

Children and adolescents

Answer 22

For major depression
- Psychological therapy is preferred
- Should be managed with CBT or IPT
- If medications used then they should be used in combination with psychotherapy.
- Need to closely monitor the patient because young people are more susceptible to suicidal thoughts and activation symptoms

Question 23

Older people

Answer 23

For major depression consider
- Falls risk
- Renal and hepatic function
- Bleeding risk
- SIADH - syndrome of inappropriate diuretic hormone secretion
- QT prolongation
- Polypharmacy