Antidepressants: SNRIs

Question 1

What are antidepressants used to treat?

Answer 1

Antidepressants are drugs used for the treatment of moderate to severe depressive episodes and dysthymia.

They are also used for a range of other conditions including severe anxiety and panic attacks, obsessive– compulsive disorder (OCD), chronic pain, eating disorders and posttraumatic stress disorder (PTSD) .

Question 2

Briefly describe how antidepressants work

Answer 2

All antidepressants work on the basis of the monoamine hypothesis by enhancing the activity of the monoamine neurotransmitters, noradrenaline (NA) and serotonin (5-HT).

Question 3

Give examples of classes of antidepressants

Answer 3

SSRI: selective serotonin reuptake inhibitor

SNRI: serotonin and noradrenaline reuptake inhibitor

TCA: tricyclic antidepressant

MAOI: monoamine oxidase inhibitor

Question 4

Which class of antidepressant are the first line? Why?

Answer 4

SSRIs are better tolerated, work more quickly and have lower risk of inducing mania with other antidepressants. Therefore, they are generally considered first-line for depression.

Question 5

How long does it take for antidepressants to start working?

Answer 5

Research suggests that antidepressants begin to take effect by one week and at 4-6 weeks the benefit is clinically detectable.

Question 6

Give examples of SNRIs

Answer 6

Venlafaxine and duloxetine.

Question 7

What are the indications of SNRIs?

Answer 7

Second or third-line in the treatment of depression and anxiety disorders. SNRIs have a more rapid onset of action and are more effective than SSRIs (for major depression).

Question 8

What is the mechanism of action of SNRIs?

Answer 8

SNRIs work by preventing the reuptake of noradrenaline and serotonin but do not block cholinergic receptors and therefore do not have as many anti-cholinergic side effects as TCAs.

Question 9

What are the side effects of SNRIs?

Answer 9

• Nausea
• Dry mouth
• Headache
• Dizziness
• Sexual dysfunction
• Hypertension

Question 10

Whar are the contraindications and cautions of SNRIs?

Answer 10

Cautions (similar to SSRIs): history of mania, epilepsy, cardiac disease (sertraline is the safest), acute angle-closure glaucoma, diabetes mellitus (monitor glycaemic control after initiation), concomitant use with drugs that cause bleeding, GI bleeding (or history of GI bleeding), hepatic/renal impairment, pregnancy and breast-feeding, young adults (possible ↑ suicide risk) and suicidal ideation.

Contraindications: conditions associated with high risk of cardiac arrthymia and uncontrolled hypertension.

Question 11

What are the doses of the following SNRIs?

1. Venlafaxine
2. Duloextine

Answer 11

Venlafaxine: 75 mg/day in divided doses.

Duloxetine: 60-120 mg/day.

Question 12

What factors need to be taken into consideration before choosing the right antidepressant?

Answer 12

There are a number of factors which influence the type of antidepressant prescribed to a patient:

1. Overall safety profile: most national and local guidelines suggest SSRIs as first choice because of their safety profile in overdose as well as their effectiveness.
2. Patient preference: after discussing side effects of each antidepressant, it is appropriate and important to involve the patient in the decision making.
3. Prior treatment: if a patient has had benefit from a previously used antidepressant, that same one should be used, provided no contraindications have developed; equally if an antidepressant has already been tried and not benefited, another one should be trialled.
4. Type and severity of depression: SSRIs are usually indicated for all severities of depression and when there is mixed anxiety and depression. In SSRI-resistant cases, SNRIs should be tried. When insomnia is present or weight gain is desired, mirtazapine can be given.
5. Suicidal ideation: avoid drugs that are toxic in overdose such as TCAs and MAOIs. SSRIs should still be used with caution and appropriate review.
6. Age and co-morbidities: SSRIs are usually the safest in elderly. Sertraline is the safest drug post-MI.
7. Drug– drug interactions: avoid SSRIs in those on blood-thinning agents such as warfarin, heparin and the newer anticoagulant agents (e.g. rivaroxaban, apixaban and dabigatran), as well as NSAIDs.
8. Pregnancy and breast feeding: all antidepressants should be used with caution and if required, the lowest effective dose should be used. Sertraline and fluoxetine are the safest during pregnancy along with some TCAs such as amitriptyline. The SSRIs paroxetine and sertraline are most likely suitable first-line agents during breast feeding.
9. History of mania: all antidepressants have the potential to trigger a manic episode but SSRIs are usually the safest (avoid TCAs).

Question 13

What is serotonin syndrome? What can cause serotonin syndrome?

Answer 13

The serotonin syndrome is a rare but life-threatening complication of increased serotonin activity, usually rapidly occurring within minutes of taking the medication.

It is most commonly caused by SSRIs but can be caused by other drugs such as TCAs and lithium.

Question 14

What are the clinical features of serotonin syndrome?

Answer 14

Clinical features include:

1. Cognitive effects→ headache, agitation, hypomania, confusion, hallucinations and coma.
2. Autonomic effects→ shivering, sweating, hyperthermia, hypertension and tachycardia.
3. Somatic effects→ myoclonus (muscle twitching), hyperreflexia and tremor.

Question 15

How is serotonin syndrome treated?

Answer 15

Management involves stopping the offending drug and supportive measures.

Question 16

How does cardiac disease affect SNRI prescribing?

Answer 16

SNRIs should not be used in patients with cardiac disease and uncontrolled hypertension. Blood pressure measurement should be taken before starting venlafaxine and should be monitored regularly thereafter.