Antidepressants

Antidepressants

Monoamine Oxidase Inhibitors

  • e.g. Phenelzine, tranylcypromine, isocarboxazid, moclobemide
  • Mode of action
    • Irreversible (phenelzine) or reversible (moclobemide) inhibitors of MAO-A and MAO-B
  • Side effects
    • ‘Cheese reaction’
      • Caused by inhibition of MAO-A in gut (& liver) by irreversible inhibitors preventing the breakdown of dietary tyrosine
        • Severe dietary restrictions
        • Can cause headaches, palpitations, difficulty breathing
    • Drugs containing amines e.g. pseudoephedrine, should also be avoided for a similar reason
  • Uses
    • Because of the serious side-effect profile, they are not often used in classic depression (definitely not before trials of SSRIs and TCAs)
    • May be of use in severe depression associated with Social Anxiety Disorder

Tricyclic Antidepressants (TCAs)

  • e.g. imipramine, amitriptyline (often used for neuropathic pain), lofepramine
  • Mode of action
    • Block the reuptake of monoamines (mainly Noradrenaline and serotonin) into presynaptic terminals
  • Side effects
    • Fewer and safer than MAO-Is
    • Muscarinic blockade: dry mouth, blurred vision, constipation and urinary retention
    • Sedation
    • Cardiac effects (arrhythmias and postural hypotension)
  • Uses
    • As mentioned above, amitrityline is often used in neuropathic pain
    • Some patients have a better response to TCAs than SSRIs

Selective Serotonin Reuptake inhibitors (SSRIs)

  • e.g. fluvoxamine, fluoxetine, paroxetine, sertraline, citalopram
  • Mode of action
    • Selectively inhibit the reuptake of serotonin from the synaptic cleft
  • Side effects
    • Less sedative/cardiac effects than TCAs (less dangerous in overdose)
    • Nausea
    • Insomnia
    • Sexual Dysfunction

Others

  • Dual reuptake inhibitors (serotonin and noradrenaline reuptake inhibitors- SNRIs) e.g. venlafaxine, duloxetine
    • NB Venlafaxine is often used in GAD.
  • Noradrenaline reuptake inhibitors (NRI) e.g. reboxetine (less side effects)
  • (Melatonergic agonists- agomelatine; not often used)
  • Atypicals (post-synaptic receptor effects) e.g. mirtazapine (blocks α-2 and 5-HT2 receptors) and bupropion (dopamine uptake inhibitor)

Which one is best??

SSRIs should be used first line for most conditions that require antidepressant use (i.e. for a mood component).  For a major depressive episode, the choice is largely arbitrary, although some considerations could be made in certain cases:

 

SSRIs

Mechanism of Action

  • SSRIs inhibit 5HT1A (serotonin) receptors in the brain at the cell body and axons (not at the terminals).  This initially reduces the rate of firing of serotonergic neurons due to blockade of autoreceptors at the cell body.  Longer term, neuron firing increases due to down-regulation of autoreceptors and blockade of serotonin reuptake (this can take 3-6 weeks)

Indications

  • First line pharmacological treatment for depression, OCD, anxiety disorders
    • NB There may be lifestyle and psychological treatment which is more appropriate first line.
    • NB Citalopram and fluoxetine are the currently preferred antidepressants.  TCAs are rarely used.

Contraindications/Cautions

  • Contraindicated in Mania/hypomania (NB SSRIs can be used in patients with bipolar disorder but the patient must be on a mood stabiliser first and must have predominantly depressive symptoms/features)
  • Caution in
    • Epilepsy (may prolong seizures or increase risk of seizures)
    • Heart disease (use sertraline if needed)
    • Acute angle closure glaucoma
    • Diabetes (monitor blood sugar)
    • Concomitant use of drugs that cause GI bleeding
    • Hepatic/renal impairment
    • Pregnancy and breast feeding (risk of a) teratogenicity and b) baby withdrawal)
    • Suicidal ideation and young adults (where this may worsen thoughts)

Interactions

  • DO NOT USE WITH MAO INHIBITORS/MOCLOBEMIDE (serious toxicity risk)
    • Start 5 weeks after cessation of fluoxetine; 2 weeks after cessation of sertraline and 1 week after other SSRIs
    • Risk of serotonin syndrome
      • Altered mental state; autonomic dysfunction and neuromuscular dysfunction
  • May interact with antiplatelets and increase bleeding risk (this can be beneficial in ACSs)
    • Consider a PPI if patient is already taking an NSAID
  • Not recommended for use with warfarin (consider mirtazepine instead)
  • Avoid with triptans

Side effects

  • GI upset is common
  • Anxiety and agitation can occur and may be a reason to consider switching medication
  • Citalopram and QT interval- citalopram can prolong the QT interval and increase the risk of VT in patients with prolonged QT or on drugs that prolong the QT interval.

Follow-up and Changing medications

  • Review after 2 weeks to check for adverse side effects; remind the patient that effect may take 4-8 weeks to appear so persistence is important
  • Continue for at least 6 months if effective after 8 weeks. If not
  • sssri
  • Withdrawal symptoms include
    • increased mood change
    • restlessness
    • difficulty sleeping
    • unsteadiness
    • sweating
    • gastrointestinal symptoms: pain, cramping, diarrhoea, vomiting
    • paraesthesia

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