Antidepressants: MAOIs Flashcards
What are antidepressants used to treat?
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) .
Briefly describe how antidepressants work
All antidepressants work on the basis of the monoamine hypothesis by enhancing the activity of the monoamine neurotransmitters, noradrenaline (NA) and serotonin (5-HT).
Give examples of classes of antidepressants
SSRI: selective serotonin reuptake inhibitor
SNRI: serotonin and noradrenaline reuptake inhibitor
TCA: tricyclic antidepressant
MAOI: monoamine oxidase inhibitor
Which class of antidepressant are the first line? Why?
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.
How long does it take for antidepressants to start working?
Research suggests that antidepressants begin to take effect by one week and at 4-6 weeks the benefit is clinically detectable.
Give examples of MAOIs
Irreversible: phenelzine and isocarboxide.
Reversible: moclobemide.
What are the indications of MAOIs?
Third-line for depression: atypical or treatment-resistant depression.
Social phobia.
Note: its use is substantially limited by toxicity, interaction with food and inferior efficacy compared to SSRIs and TCAs.
What is the mechanism of action of MAOIs?
MAOIs inactivate monoamine oxidase enzymes that oxidize the monoamine neurotransmitters dopamine, noradrenaline, serotonin (5-HT) and tyramine.
There are two main forms of MAO enzymes: MAO-A and MAO-B. Moclobemide is comparatively recent compared with the other MAOIs and binds selectively to MAO-A, therefore nullifying the need for dietary restrictions.
What are the side effects of MAOIs?
Cardiovascular: postural hypotension and arrhythmias.
Neuropsychiatric: drowsiness/insomnia and headache.
GI: ↑ appetite and weight gain.
Sexual: anorgasmia.
Hepatic: ↑ LFTs.
Hypertensive reactions with tyramine containing foods.
What are the contraindications and cautions of MAOIs?
Cautions: avoid in agitated or excited patients (or give with sedative for up to 2– 3 weeks), thyrotoxicosis, hepatic impairment, in bipolar disorders (may provoke manic episodes), pregnancy and breast-feeding.
Contraindications: acute confusional states, phaeochromocytoma.
What is the route for MAOIs?
Oral.
What factors need to be taken into consideration before choosing the right antidepressant?
There are a number of factors which influence the type of antidepressant prescribed to a patient:
- 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.
- Patient preference: after discussing side effects of each antidepressant, it is appropriate and important to involve the patient in the decision making.
- 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.
- 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.
- Suicidal ideation: avoid drugs that are toxic in overdose such as TCAs and MAOIs. SSRIs should still be used with caution and appropriate review.
- Age and co-morbidities: SSRIs are usually the safest in elderly. Sertraline is the safest drug post-MI.
- 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.
- 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.
- History of mania: all antidepressants have the potential to trigger a manic episode but SSRIs are usually the safest (avoid TCAs).
What is serotonin syndrome? What can cause serotonin syndrome?
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.
What are the clinical features of serotonin syndrome?
Clinical features include:
- Cognitive effects→ headache, agitation, hypomania, confusion, hallucinations and coma.
- Autonomic effects→ shivering, sweating, hyperthermia, hypertension and tachycardia.
- Somatic effects→ myoclonus (muscle twitching), hyperreflexia and tremor.
How is serotonin syndrome treated?
Management involves stopping the offending drug and supportive measures.
