Antidepressants: TCAs

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 TCAs

Answer 6

Amitriptyline, clomipramine, dosulepin, doxepin, imipramine, lofepramine, nortriptyline and trimipramine.

Question 7

What are the indications of TCAs?

Answer 7

Depressive illness, nocturnal enuresis in children, neuropathic pain (unlicensed) and migraine prophylaxis (unlicensed).

Question 8

What is the mechanism of action of TCAs?

Answer 8

TCAs work by inhibiting the reuptake of adrenaline and serotonin in the synaptic cleft. They also have affinity for cholinergic receptors and 5HT2 receptors and these contribute to side effects.

Question 9

What are the side effects of TCAs?

Answer 9

Anticholinergic: dry mouth, constipation, urinary retention, blurred vision, and confusion.

Cardiovascular: arrhythmias, postural hypotension, tachycardia, syncope and sweating.

Hypersensitivity reactions: urticarial and photosensitivity.

Psychiatric: hypomania/mania, confusion or delirium (especially in elderly).

Metabolic: ↑ appetite and weight gain and changes in blood glucose levels.

Endocrine: testicular enlargement, gynaecomastia and galactorrhoea.

Neurological: convulsions, movement disorders and dyskinesias, dysarthria, paraesthesia, taste disturbances and tinnitus.

Others: headache, sexual dysfunction and tremor.

Question 10

Whar are the contraindications and cautions of SSRIs?

Answer 10

Cautions: cardiac disease, history of epilepsy, pregnancy, breast-feeding, elderly, hepatic impairment, thyroid disease, phaeochromocytoma, history of mania, psychoses (may aggravate psychotic symptoms), susceptibility to angle-closure glaucoma, history of urinary retention, concurrent electroconvulsive therapy and drowsiness may affect performance of skilled tasks (e.g. driving); effects of alcohol enhanced.

Contraindications: recent myocardial infarction, arrhythmias (particularly heart block), mania, severe liver disease and agranulocytosis.

Question 11

What are the doses of the following TCAs?

1. Amitriptyline

Answer 11

Amitriptyline: 50-200 mg/day.

Question 12

What is the route for TCAs?

Answer 12

Oral.

Question 13

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

Answer 13

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).