Introduction to Antidepressant Medications

Introduction to Antidepressant Medications

• Antidepressants work by increasing the availability of monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) in the synapses.
• While the increase in monoamines occurs quickly, the effects on mood take time to appear.
• Other mechanisms, such as receptor regulation and intracellular signaling, are likely involved.

Monoamine Synapses

• Monoamines are released from vesicles when they fuse with the presynaptic membrane.
• They bind to receptors on the postsynaptic membrane.
• Neurotransmitters are then reabsorbed into the presynaptic neuron via transporters.
• They can be repackaged into vesicles or broken down by monoamine oxidase (MAO).

Mechanisms of Action

• Enhancing presynaptic release of monoamines.
• Blocking reuptake transporters in presynaptic membranes.
• Blocking monoamine breakdown by inhibiting MAO.

General Considerations

• Many antidepressants aren't selective; they often bind to multiple receptors and lead to side effects.

Starting Antidepressant Medication

• Patients should be reviewed weekly (or biweekly if under 25, due to increased suicide risk).
• Treatment should continue for at least 4 weeks (6 weeks for the elderly).
• If partial response, continue for 2-4 more weeks (elderly may take longer).
• Continued treatment after remission should last at least 6 months or 12 months for patients with GAD.
• Some patients may initially feel worse in the first 2 weeks, including increased suicidal thoughts.

Choosing a Medication

• Shared decision-making with patients is crucial.
• Factors to consider include efficacy, tolerability, presentation (e.g., insomnia, weight loss), drug interactions, and previous medical history.

Stopping Antidepressant Treatment

• Antidepressants should not be stopped abruptly; instead, the dosage should be reduced gradually over at least 4 weeks.
• Discontinuation symptoms can occur within 2-3 days, usually resolving within 1-2 weeks.
• Common symptoms : flu-like symptoms, electric shock-like sensations, irritability, insomnia, and vivid dreams.

Switching Antidepressants

• Always consult guidelines (e.g., BNF) for correct switching procedures.
• Some antidepressants can be switched directly; others need a gradual, cross-tapered approach.

Selective Serotonin Reuptake Inhibitors (SSRIs)

• SSRIs block the reuptake of serotonin in the presynaptic membrane.
• They are generally well-tolerated and safer in overdose compared to other types of antidepressants.
• Examples include sertraline, citalopram, escitalopram, fluoxetine, and paroxetine.
• Fluoxetine is often the first-line choice for children/adolescents.
• Potential side effects include gastrointestinal issues, headaches, sexual dysfunction, anxiety, increased risk of bleeding, and insomnia.

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

• SNRIs block the reuptake of both serotonin and norepinephrine.
• Examples include venlafaxine and duloxetine.
• Potential side effects are similar to SSRIs, including the increased risk of hypertension and, in some cases, liver/kidney damage.

Tricyclic Antidepressants (TCAs)

• TCAs block the reuptake of both serotonin and norepinephrine, but also affect other receptors (M1, H1).
• Examples include amitriptyline, nortriptyline, imipramine, and lofepramine.
• Used for neuropathic pain at lower doses, while higher doses treat mood disorders.
• Contraindicated in certain cardiac conditions and severe liver/kidney issues.
• Potential side effects include drowsiness, dry mouth, blurred vision, constipation, urinary retention.

Monoamine Oxidase Inhibitors (MAOIs)

• MAOIs irreversibly block the enzyme monoamine oxidase, which prevents the breakdown of monoamines.
• They are generally a last-resort due to potential side effects and dietary restrictions (to avoid hypertensive crises from tyramine).
• Examples include isocarboxazid, moclobemide, phenelzine, and tranylcypromine.
• Patients must avoid foods high in tyramine.
• A washout period is essential when switching from MAOIs to other antidepressants.

Atypical Antidepressants

• These medications have diverse mechanisms, often targeting different neurotransmitter systems.
• An example is mirtazapine, which blocks presynaptic alpha receptors and postsynaptic serotonin receptors.
• Potential side effects include sedation and increased appetite.

This quiz explores the mechanisms of action of antidepressant medications, focusing on monoamine neurotransmitters like serotonin and norepinephrine. It covers the release, reuptake, and breakdown of these neurotransmitters, as well as general considerations regarding antidepressant selectivity. Test your knowledge on how these medications impact mood and mental health.