Antidepressants

Antidepressant medications are prescribed to alleviate symptoms of depression.

Depression is a prevalent mental disorder characterized by persistent feelings of low mood, worthlessness, guilt, sadness, emptiness, or loss of interest.

Depression is one of the most common mental disorders worldwide.

The primary uses of antidepressant medications include:

• Treating depression, particularly major depressive disorder.
• Managing panic attacks and anxiety disorders.
• Obsessive-compulsive disorder (OCD).
• Eating disorders such as bulimia or anorexia.

Antidepressant medications can be categorized in two main groups:

1. Classic antidepressants
   • Irreversible monoamine oxidase inhibitors (MAOIs): Tranylcypromine.
   • Reversible monoamine oxidase A inhibitors (RIMA): Moclobemide.
   • Heterocyclic antidepressants:
     • Tricyclic antidepressant.
     • Tetracyclic antidepressant.
2. New antidepressants
   • Selective serotonin reuptake inhibitor (SSRIs).
   • Serotonin-norepinephrine reuptake inhibitor (SNRIs).
   • Norepinephrine-dopamine reuptake inhibitor (NDRI): Bupropion.
   • Serotonin antagonist and reuptake inhibitors (SARIs): Trazodone.
   • Norepinephrine reuptake inhibitor (NRI, NERI): Reboxetine.
   • Melatonin receptor agonist: Agomelatine.

These types of drugs were the first to be used as antidepressants but are currently not widely used due to their numerous side effects and serious interactions.

They are prescribed for major depression in patients who have not responded to other medications.

They can be classified as:

• Nonselective monoamine oxidase inhibitors such as phenelzine, tranylcypromine, and isocarboxazid.
• Selective monoamine oxidase A (MAO-A) inhibitors such as moclobemide.
• Selective monoamine oxidase B (MAO-B) inhibitors such as selegiline, which is used particularly as adjunctive treatment in Parkinson's disease.

For example, moclobemide is used for the treatment of major depression.

Heterocyclic antidepressants are inhibitors of the reuptake of certain neurotransmitters such as noradrenaline, serotonin, or dopamine. These drugs improve mood, alleviate sadness, and can help with appetite and sleep disturbances.

They can be classified in two groups:

• Tricyclics:
  • Tertiary amines (amitriptyline, clomipramine, doxepin, imipramine, trimipramine, lofepramine).
  • Secondary amines (amoxapine, desipramine, nortriptyline, protriptyline).
• Tetracyclics: These have effects similar to tricyclic antidepressants. The most well-known in this family is maprotiline, but mianserin is also used.

They are classic drugs whose effectiveness has not been surpassed by other drug families, but they come with many side effects such as sedation, drowsiness, dry mouth, blurred vision, constipation, and risk of ventricular arrhythmias.

Amitriptyline is used in psychotic and chronic depression, imipramine for chronic treatment of recurrent depressions, and clomipramine for phobias, obsessive-compulsive disorder and depression.

The effectiveness of SSRIs in treating depression is very similar to that of tricyclic and tetracyclic antidepressants, but they have fewer adverse effects and are the most commonly prescribed antidepressants nowadays. They are also used in the treatment of obsessive-compulsive disorders.

Common side effects may include nausea, insomnia, or loss of libido.

The first medication in this group to become famous was fluoxetine, sold under the brand name Prozac^®.

Fluoxetine is used for depression, eating disorders (like bulimia), and obsessive-compulsive disorder.

Other drugs included in this family are paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram.

• Paroxetine is used for the treatment of depression, social phobia, obsessive-compulsive disorders (OCD), generalized anxiety disorder, and post-traumatic stress disorder (PTSD).
• Sertraline is used for major depression, anxiety, obsessive-compulsive disorder (OCD), social phobia, and post-traumatic stress disorder (PTSD).
• Citalopram is used for depression and its recurrences, anxiety, and obsessive-compulsive disorder (OCD).
• Escitalopram is used for major depression, anxiety, and obsessive-compulsive disorder (OCD).

The SNRIs increase the levels or certain neurotransmitters in the brain and are used to treat anxiety and other mood disorders.

The most commonly used include duloxetine, levomilnacipran, venlafaxine, and desvenlafaxine.

• Duloxetine is used for the treatment of major depressive disorder and generalized anxiety disorder.
• Venlafaxine is used for depression and its recurrences, generalized and social anxiety disorders, and panic disorder.
• Desvenlafaxine is used for the treatment of major depressive disorder in adults.

There are other antidepressants used in the treatment of depression and other mood disorders:

• Trazodone: It belongs to the group of serotonin antagonists and reuptake inhibitors (SARIs) like nefazodone. Trazodone is used to treat endogenous depression associated with insomnia.
• Bupropion: Bupropion is the most well-known representative of Norepinephrine-dopamine reuptake inhibitor (NDRI) family. It is used for the treatment of major depressive disorder.
• Reboxetine: Used for the acute treatment of depression and for maintenance therapy of depression. It is a norepinephrine reuptake inhibitor (NRI, NERI).
• Mianserin: An atypical antidepressant used to improve symptoms of depression.
• Mirtazapine: Used for the treatment of major depression and it is often prescribed in combination with venlafaxine.
• Tianeptine: An antidepressant with anxiolytic effects used for the treatment of major depression in adults.
• Agomelatine: Acts on the melatonin hormone in the brain and is used in the treatment of major depression.
• Vortioxetine: Used for the treatment of major depressive disorder in adults.
• Esketamine: In combination with an SSRI or SNRI, it is used for adults with treatment-resistant major depressive disorder who have not responded to at least two different antidepressant treatments.

The recommended medication regimen involves initiating treatment with a low dose, for example, 50-75 mg/day for drugs like imipramine, amitriptyline, or maprotiline.

The dose is quickly increased to reach the maximum dose (150-200 mg/day) during the second week of treatment. This depends on whether there are any side effects.

The maximum dose is maintained for 4 to 6 weeks, even if clinical improvement has been achieved earlier.

Then, the dose is gradually reduced between the sixth and twelfth week of treatment, and the treatment may be interrupted or continued depending on the degree of remission, motivations, etc.

Often, it is necessary to continue treatment with decreasing doses for up to 6 months.

Improvement is usually evident by the third week and reaches its most effective level between the fourth and fifth weeks.