Trade Names: Mirtazapine Teva, Mirtazapine Aurovitas, Mirtor, Mirtagen, Mirzaten, Remirta, Mirtasad, Mirtamerck, Remeron, Esprital
Mirtazapine: An Antidepressant with a Unique Approach
Mirtazapine is one of the tetracyclic antidepressants with an interesting and unusual mechanism of action. Unlike most antidepressants, which work by blocking the reuptake of monoamines, mirtazapine acts on presynaptic alpha-2 adrenergic receptors. What does this mean? Imagine that when the level of serotonin or norepinephrine in the synaptic cleft reaches a certain point, these alpha-2 receptors “understand” that the release of new neurotransmitters can stop. However, mirtazapine blocks these receptors, and the release of serotonin and norepinephrine continues, leading to their increased concentration.
But its action doesn’t stop there. Mirtazapine affects many other receptors. For example, it blocks serotonin receptors 5-HT2 and 5-HT3. This is important because this action reduces the risk of gastrointestinal side effects such as nausea or vomiting. It also stimulates 5-HT1 receptors, which further enhances its antidepressant and anxiolytic effects.
Another key aspect is the blocking of H1 histamine receptors, which explains its strong sedative effect, increased appetite, and consequently, weight gain. On the other hand, it does not affect alpha-1 adrenergic receptors, which differentiates it from tricyclic antidepressants and reduces the risk of orthostatic hypotension and dizziness.
Main Effects
The antidepressant effect occurs relatively quickly. First changes can be observed within a week, although the full effect develops over 3-4 weeks. This makes mirtazapine particularly valuable in cases of depression with anhedonia, psychomotor retardation, and lack of energy. Patients often report mood improvement, increased motivation, and activation at doses of 30-45 mg.
The sedative effect is another important aspect. This medication literally helps you sleep, but it’s important to understand the difference between a sedative and a hypnotic effect. The sedative effect fades over time (especially when the dose is increased), while the hypnotic effect persists throughout the entire treatment.
What’s characteristic of this hypnotic action is that it doesn’t occur immediately after taking the pill. If the drug is taken on an empty stomach, the effect appears faster—within an hour. If taken with food, it may take 2-3 hours. That’s why the medication is taken at night.
When Is Mirtazapine Indicated:
- Hard-to-treat depression, especially with pronounced psychomotor retardation and anhedonia.
- Anxiety-depressive disorders, especially in the initial stages of therapy.
- Hypochondriacal depression, where it provides stable remission and reduces the risk of relapses.
- Sleep disorders (both primary and secondary).
Mirtazapine is particularly useful in geriatric practice. In elderly patients, depression with anxiety, insomnia, and hypochondriacal complaints is common, and mirtazapine works exceptionally well on these symptoms. Moreover, it does not exhibit anticholinergic effects, which is important for this patient group.
This medication is also used to treat sexual dysfunction that arises from depression or the use of other antidepressants (e.g., SSRIs). When combined with them, it helps alleviate anorgasmia, decreased libido, and other problems.
Combinations and Synergistic Effect
One of the most well-known combinations is the “California rocket fuel” – a combination of mirtazapine and venlafaxine. Venlafaxine blocks the reuptake of serotonin and norepinephrine, while mirtazapine further increases their concentration by acting on alpha-2 receptors. Additionally, they both increase dopamine levels, significantly enhancing the overall antidepressant effect.
Mirtazapine is also often combined with SSRIs to mitigate side effects and enhance anxiolytic effects. This combination minimizes the risk of apathy and anhedonia, which can occur due to dopamine suppression from high serotonin levels.
Side Effects
Weight gain is probably the biggest problem. Mirtazapine stimulates appetite by blocking H1 histamine receptors and alters metabolic processes, leading to weight gain. To counteract this, metformin or betahistine is used. However, it should be noted that these drugs only prevent weight gain but do not help reduce it.
Drowsiness is another common side effect, which usually subsides after a few weeks.
Bloating is an individual reaction that can occur regardless of the dose. If bloating is very bothersome, a change in medication may be necessary.
Interestingly, mirtazapine almost doesn’t cause side effects such as sexual dysfunction, nausea, vomiting, dry mouth, or constipation. This is a major advantage over SSRIs and tricyclic antidepressants.
Dosage Guidelines
The initial dose is 15 mg at night. At this dose, it acts as a sedative and hypnotic, but the antidepressant effect is unlikely at such doses. If an antidepressant effect is required, the dose should be increased to 30-45 mg.
In severe cases, the dose can be increased to 60-90 mg. The drug’s half-life is 30-40 hours, so one dose per day is sufficient.
The first signs of improvement appear within a week, but the full effect develops by the end of the first month. The hypnotic effect is noticeable from the first day of use.
Conclusion
Mirtazapine is a powerful antidepressant that works quickly and effectively, especially in cases of depression with pronounced psychomotor retardation, anhedonia, and sleep disturbances. Due to its unique mechanism of action, it is safe for elderly patients, well-tolerated, and can be combined with other antidepressants to enhance effectiveness and minimize side effects.
If you want to understand what’s happening with your condition or discuss appropriate treatment, visit the Plexus center in Warsaw — we have a psychiatrist who speaks Polish and Russian, who will help you find a solution that suits you best.