Introduction to Antidepressants and Their Mechanisms

In this discussion, we will delve into the major classes of antidepressants, starting with the most widely prescribed: the serotonin-specific reuptake inhibitors (SSRIs). These drugs have well-defined neurotransmitter profiles and are crucial in treating major depressive disorder (MDD).

Diagnosing Depression: The SIG E CAPS Mnemonic

To diagnose MDD, remember the mnemonic SIG E CAPS:

• Sleep disturbances
• Interest loss (anhedonia)
• Guilt or feelings of worthlessness
• Energy loss
• Concentration difficulties
• Appetite changes
• Psychomotor agitation or retardation
• Suicidal thoughts

A patient must exhibit at least five of these symptoms for at least two weeks to qualify for an MDD diagnosis.

Serotonin-Specific Reuptake Inhibitors (SSRIs)

Mechanism of Action

SSRIs work by inhibiting the serotonin transporter on presynaptic neurons, increasing the amount of active serotonin in the synaptic cleft.

Common SSRIs

1. Fluoxetine (Prozac)
   • Long half-life: beneficial for patients who forget to take medications regularly.
   • Risk of serotonin syndrome if switched too quickly to another serotonergic drug.
   • Mnemonic: “Flu” and its association with a one-week duration helps remember the long-lasting effect.
2. Sertraline (Zoloft)
   • Notable for causing gastrointestinal side effects (nausea, diarrhea).
   • Safer for pregnant or breastfeeding women due to lower levels in breast milk.
   • Mnemonic: “Squirt-raleen” for the GI side effects.
3. Paroxetine (Paxil)
   • Rapid absorption leading to more pronounced initial side effects.
   • Rapid withdrawal can lead to uncomfortable symptoms.
   • Mnemonic: “Pair of oxen” for rapid onset and withdrawal.
4. Citalopram (Celexa)
   • High tolerability, considered a good first-line agent.
   • Can prolong the QTc interval, necessitating EKG monitoring at higher doses.
   • Mnemonic: “Celexa” and “car” to remember the need for an electrocardiogram.
5. Escitalopram (Lexapro)
   • The S-enantiomer of citalopram, with fewer enzyme interactions.
   • Mnemonic: “Lexapro” as the “awesome younger sibling” of Celexa.
6. Fluvoxamine (Luvox)
   • Approved for treating obsessive-compulsive disorder (OCD) in the U.S.
   • Mnemonic: “Luvox” with “OC” for obsessive-compulsive.

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

1. Venlafaxine (Effexor)
   • Inhibits the reuptake of both serotonin and norepinephrine.
   • Useful for symptoms of low energy, decreased interest, and impaired concentration.
   • Risk of hypertension due to norepinephrine effects.
   • Mnemonic: “Venlafaxine” and the “N” sound for norepinephrine.
2. Duloxetine (Cymbalta)
   • Dual action on serotonin and norepinephrine.
   • Also used for chronic pain conditions.
   • Mnemonic: “Dul” for dual mechanism, and “dulls” the pain.

Other Antidepressants

1. Mirtazapine (Remeron)
   • Enhances sympathetic output by inhibiting inhibitory inputs.
   • Increases appetite and decreases nausea, useful in cancer and HIV patients.
   • Mnemonic: “Meal-tazapine” for its effect on appetite.
2. Bupropion (Wellbutrin)
   • Works on dopamine and norepinephrine.
   • No significant serotonergic effects, less sexual dysfunction.
   • Helps with smoking cessation.
   • Mnemonic: “Butane” for the dopamine and norepinephrine effects.
3. Trazodone (Desyrel)
   • Used as an antidepressant and a sleep aid.
   • Can cause priapism (prolonged erection).
   • Mnemonic: “Trouser-bone” for the priapism side effect.

Tricyclic Antidepressants (TCAs)

• Complex binding profiles affecting serotonin, norepinephrine, acetylcholine, histamine, sodium, and calcium ion channels.
• Effective but with significant side effects and toxicity in overdose.
• Mnemonic: “Trans, Chan’s, and Anne’s” for the multiple neurotransmitter effects and ion channels.

Common TCAs

1. Imipramine
   • Used for nocturnal enuresis (bedwetting) in children.
   • Mnemonic: “I’m peeing-Ramin.”
2. Clomipramine
   • Approved for OCD treatment.
   • Mnemonic: “Clomipramine” for OCD.
3. Amitriptyline and Nortriptyline
   • Also used for chronic pain conditions.

Monoamine Oxidase Inhibitors (MAOIs)

• Effective for atypical depression but with severe side effects.
• Can cause hypertensive crisis when combined with tyramine-rich foods.
• Mnemonic: “Maui with Tyra Banks” for MAOIs and tyramine.

Common MAOIs

1. Selegiline (Eldepryl)
   • Selective for MAO-B.
   • Mnemonic: “Select-a-lien” for selectivity.
2. Phenelzine (Nardil)
   • Non-selective, affecting both MAO-A and MAO-B.
   • Preferable for depression treatment.

Review and Referral Criteria (PSYCH MD)

• P: Psychosis
• S: Suicidality
• Y: “Why isn’t this working?” (treatment-resistant)
• C: Comorbid psychiatric disorders
• H: Highs and lows of bipolar disorder
• MD: Monitoring drugs like lithium