Neurotransmitters and Antidepressants

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Questions and Answers

What are the main categories of antidepressants mentioned in the content, and provide one example for each?

The main categories are SSRIs (e.g., Sertraline), SNRIs (e.g., Duloxetine), and TCAs (e.g., Amitriptyline). Less frequently used include MAOIs (e.g., Phenelzine) and others like Agomelatine.

Describe the mechanism of action of Selective Serotonin Reuptake Inhibitors (SSRIs).

SSRIs selectively inhibit the presynaptic reuptake of serotonin, increasing its availability in the synaptic cleft. This action helps enhance serotonergic neurotransmission.

Compare the side effects between SSRIs and TCAs.

SSRIs commonly cause nausea, insomnia, and sexual dysfunction, while TCAs often have more severe side effects such as greater toxicity in overdose and anticholinergic effects. SSRIs are generally considered safer in overdose situations than TCAs.

What factors influence the choice of antidepressant for a patient?

Factors include previous response to medications, concurrent medical and psychiatric conditions, side effects, potential drug interactions, and toxicity in overdose. This ensures tailored treatment for each individual. Signup and view all the answers

What is serotonin syndrome, and what might trigger it?

Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonergic activity in the brain, often triggered by the use of multiple serotonergic drugs or an overdose of SSRIs. Symptoms can include confusion, rapid heart rate, and muscle rigidity. Signup and view all the answers

What are the primary classes of antidepressants that can lead to serotonin syndrome?

Antidepressants, specifically SSRIs, SNRIs, and TCAs, can lead to serotonin syndrome. Signup and view all the answers

How do SNRIs increase serotonin and noradrenaline levels in the synapse?

SNRIs inhibit the reuptake of both serotonin and noradrenaline, leading to increased levels of these neurotransmitters in the synapse. Signup and view all the answers

What are the common side effects associated with Tricyclic Antidepressants (TCAs)?

Common side effects of TCAs include sedation, anticholinergic effects, orthostatic hypotension, and potential QT interval prolongation. Signup and view all the answers

What factors should be considered when changing between different antidepressants?

It is important to ensure an anti-depressant free period to minimize interactions and avoid serotonin syndrome. Signup and view all the answers

What is serotonin syndrome and what can cause it?

Serotonin syndrome is a medical emergency characterized by overstimulation of serotonin receptors, usually caused by high doses of a single drug or combinations of serotonergic agents. Signup and view all the answers

Study Notes

Neurotransmitters in Depression

Neurotransmitter imbalances might not fully explain depression.
Antidepressants may have unknown mechanisms beyond affecting neurotransmitters.

Presynaptic Regulation of Neurotransmitters

Noradrenaline: Regulated by monoamine oxidase (MAO) and vesicular monoamine transporter (VMAT). Noradrenaline is transported out of the synapse by the noradrenaline transporter (NET).
Serotonin: Regulated by MAO and VMAT. Serotonin is transported out of the synapse by the serotonin transporter (SERT).

Antidepressants

Time to clinical benefit: Some symptom improvement within 1-3 weeks, full effect in 1-2 months.
Factors affecting drug choice: Previous response, concurrent medical and psychiatric illnesses, side effects, drug interactions, overdose toxicity.
Changing antidepressants: Need for anti-depressant free period; consider drug interactions.

Common Antidepressants

Selective Serotonin Reuptake Inhibitors (SSRIs): Citalopram, escitalopram, sertraline, fluoxetine, fluvoxamine, paroxetine.
Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs): Venlafaxine, desvenlafaxine, duloxetine.
Tricyclic Antidepressants (TCAs): Amitriptyline, imipramine, nortriptyline, dosulepin, clomipramine, doxepin.
Mono-Amine Oxidase Inhibitors (MAOIs): Tranylcypromine, phenelzine, moclobemide.
Other: Agomelatine, mianserin, mirtazapine, reboxetine, vortioxetine.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Mechanism: Inhibit the reuptake of serotonin (5-HT) at the synapse.
Side effects: Nausea, vomiting, diarrhea, insomnia/drowsiness, dry mouth/sweating, sexual dysfunction.
Drug interactions: Fluoxetine, fluvoxamine, and paroxetine are potent inhibitors of various CYP450 enzymes.
Serotonin syndrome/toxicity: Risk increases with increased dose, multiple serotonergic agents, or inadequate washout period between antidepressants.

Serotonin Toxicity/Serotonin Syndrome

Cause: Increased levels of serotonin in the synapse, overstimulating serotonin receptors.
Risk: Increased dosage of a single drug, multiple serotonergic agents, switching antidepressants without adequate washout.
Symptoms: Medical emergency, can be fatal.
Common medications: SSRIs, SNRIs, MAOIs, some opioids, illicit drugs, linezolid, lithium, etc.

Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs)

Mechanism: Inhibit the reuptake of serotonin (5-HT) and noradrenaline (NA) at the synapse.
Side effects: Nausea, constipation, dry mouth, sweating, cardiovascular effects (hypertension, tachycardia, orthostatic hypotension), hyponatremia.

Tricyclic Antidepressants (TCAs)

Mechanism: Inhibit the reuptake of 5-HT and NA. Block cholinergic, histaminergic, and alpha-1 adrenergic receptors.
Side Effects: Sedation, anticholinergic effects (dry mouth, constipation, blurred vision), orthostatic hypotension, QT prolongation, seizure threshold lowering.
Other uses: Pain, migraine, bed-wetting.

Monoamine Oxidase Inhibitors (MAOIs)

Mechanism: Inhibit MAO-A and MAO-B enzymes responsible for breaking down neurotransmitters. Increase synaptic concentrations of NA, DA, and 5-HT.
Side effects: Insomnia/fatigue, dry mouth/constipation, orthostatic hypotension.
Interaction with Tyramine: Foods containing tyramine can lead to a hypertensive crisis due to increased NA release.

Tyramine Content

Avoid foods containing tyramine while taking non-selective irreversible MAOIs (tranylcypromine, phenelzine).

Reversible MAOI: Moclobemide

Mechanism: Competitively and reversibly inhibits MAO-A.
Side effects: Nausea, diarrhea/constipation, dry mouth, insomnia.
Serotonin syndrome: Risk present.
Dietary restrictions: Not required; low affinity and easily displaced.

Agomelatine

Mechanism: Melatonin receptor agonist and 5HT2c receptor antagonist.
Side effects: Dizziness, blurred vision, paraesthesia.
Contraindications: Combination with CYP1A2 inhibitors.

Mianserin

Mechanism: Tetracyclic antidepressant: many effects, including antagonist at histamine, serotonin, and adrenergic receptors, and NA reuptake inhibitor.
Side effects: Sedation.
Precautions: May increase the risk of seizures.

Mirtazapine

Mechanism: Tetracyclic antidepressant: blocks serotonin receptors, α2 adrenergic autoreceptors, and is a potent H1 antagonist.
Side effects: Increased appetite and weight, sedation, peripheral edema.

Reboxetine

Mechanism: Selectively blocks NA reuptake, increasing NA at the synapse.
Side Effects: Orthostatic hypotension, increased diastolic BP, tachycardia, urinary retention, dry mouth, constipation.

Vortioxetine

Mechanism: Inhibits SERT and acts as an agonist or antagonist at various 5-HT receptors.
Side effects: Nausea/vomiting, constipation, dry mouth, itch.
Notes: Mechanism poorly understood due to recent introduction.

Antidepressant Withdrawal Effects

MAOIs: Nausea, vomiting, nightmares, panic, restlessness, hallucinations, delirium, and even dependence with tranylcypromine.
SSRIs: Dizziness, nausea, paraesthesia, anxiety, agitation, tremor, sweating, confusion, electrical shock-like sensations. Most common with paroxetine, least common with fluoxetine.
TCAs: Cholinergic rebound: hypersalivation, runny nose, abdominal cramping, diarrhea, sleep disturbance. More common with amitriptyline and doxepin.
SNRIs: Effects similar to SSRIs. More common with venlafaxine.
Mirtazapine: Anxiety, headache, dizziness, nausea. More common with mirtazapine, rare with moclobemide.

Overview

Depression affects 1 in 7 Australians in their lifetime.
Depression is a mood disorder involving severe distress, intensity, and impairment.
Diagnosis and treatment are often initiated by general practitioners.
Treatment involves psychotherapy, usually CBT, and antidepressants.
Goal of treatment: Alleviate psychological and physical symptoms, increase functional capacity, and reduce self-harm and suicide risk.
Key neurotransmitters involved in mood regulation: Norepinephrine/noradrenaline (NE/NA), serotonin (5-HT), dopamine (DA), and GABA.

Depressive Disorders: Classification

Mild: Marked symptoms, some difficulty with daily activities.
Moderate: Considerable symptoms, considerable difficulty with daily activities.
Severe: Unable to continue daily activities beyond minimal extent.

Before Starting Treatment

Rule out other causes of distress, such as grief, alcohol/drug misuse, hypothyroidism, and adverse drug effects.

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Description

Explore the complex role of neurotransmitters in depression and how various antidepressants function. This quiz covers regulatory mechanisms, the timeline for clinical benefits, and considerations for choosing antidepressants. Test your understanding of these crucial concepts in mental health.