15.3: Antidepressant Drugs: Tricyclics, SSRIs, and SNRIs

Tricyclic Antidepressants (TCAs), including Desipramine (Norpramin), Imipramine (Tofranil), Clomipramine (Anafranil), and Amitriptyline (Elavil), inhibit serotonin and norepinephrine reuptake and also block other receptors. They are used for depression, pain conditions, and insomnia. Common adverse effects include anticholinergic effects, sedation, orthostatic hypotension, and weight gain. They have a narrow therapeutic window and so require plasma-level monitoring. Abrupt discontinuation can cause a cholinergic rebound and flu-like symptoms. Drug interactions are possible, particularly with MAOIs.

Selective Serotonin Reuptake Inhibitors (SSRIs), such as Fluoxetine (Prozac) and Paroxetine (Zoloft), primarily inhibit serotonin reuptake and treat depression, OCD, anxiety and panic disorder, and bulimia nervosa. Common adverse effects include headache, sweating, gastrointestinal effects, and sexual dysfunction. They can be sedating or activating, depending on the specific drug. Caution is advised when using SSRIs in children and teenagers due to the potential worsening of depression and suicidal thinking.

Serotonin-norepinephrine reuptake Inhibitors (SNRIs), including Venlafaxine (Effexor), Reboxetine (Edronax) and Duloxetine (Cymbalta), inhibit both serotonin and norepinephrine reuptake. They are used for depression, anxiety disorders, pain syndromes, and fibromyalgia. Adverse effects include nausea, headache, sexual dysfunction, dizziness, insomnia, sedation, and constipation. Abrupt discontinuation may cause a discontinuation syndrome.

Tricyclic antidepressants, or TCAs, are first-generation antidepressants.

They block serotonin and norepinephrine reuptake transporters while inhibiting muscarinic, α-adrenergic, and histaminic H₁ receptors.

TCAs are not first-line antidepressants due to their nonselective nature and larger side effect profile, though they help mitigate pain syndromes and insomnia.

Serotonin-norepinephrine reuptake inhibitors, or SNRIs, also inhibit serotonin and norepinephrine reuptake.

These agents can cause noradrenergic stimulation-related adverse effects such as hypertension, tachycardia, insomnia, anxiety, and agitation.

Selective serotonin reuptake inhibitors, or SSRIs, predominantly block serotonin reuptake without significantly affecting norepinephrine.

SSRIs are mainly used to treat obsessive-compulsive disorders, panic, and social anxiety disorders.

However, they can cause side effects like headaches, sweating, gastrointestinal effects, and sexual dysfunction. In combination with other serotonergic drugs, SSRIs may cause rare side effects like serotonin syndrome and seizures.

They should be used cautiously in young patients as they may worsen depression and induce suicidal tendencies.