Alpha-2 antagonists as serotonin and norepinephrine disinhibitors
How it works:
Boosts the effects of the neurotransmitters serotonin, and norepinephrine. It works differently than other medications. Blocking alpha-2 receptors leads to an increase of serotonin and norepinephrine release.
What makes it unique:
The unique mechanism enables this medication to be used alone or in conjunction with other antidepressant medications. This medication makes people sleepy and is used for sleep, especially at lower doses.
Sedation, weight gain, constipation, increased appetite. Mirtazapine can also cause confusion, abnormal dreams, flu-like symptoms, and low blood pressure.
Rare side effects include seizures, induction of mania, and activation of suicidal ideation in people age 24 and younger.
How effective is it:
(1) A meta-analysis of 8 studies was conducted to review Mirtazapine in the treatment of depression. Mirtazapine was found to be superior to placebo and comparable to the TCA medication, Amitriptyline, in the treatment of depression with symptoms of anxiety.
(2) Another large meta-analysis of 25 studies was conducted. Mirtazapine was compared against SSRI medications and the SNRI, Venlafaxine. Mirtazapine showed a faster onset, but similar overall response to the other medications. The medications compared all had similar dropout rates due to side effects.
This is commonly seen as an add-on medication to another antidepressant. The combination of Mirtazapine with Venlafaxaine is sometimes called “California Rocket Fuel” due to the punch it can pack against depression. Low doses are more sedating than higher doses because the antihistamine effects seem to carry more weight. But as the dose is increased, the norepinephrine energy boost can outweigh the antihistamine effect. Pharmaceuticals should never be used as the sole treatment for mental illnesses. Therapy, exercise, meditation or other treatments should always accompany prescriptions.
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1. Fawcett J, Barkin RL. A meta-analysis of eight randomized, double-blind, controlled clinical trials of mirtazapine for the treatment of patients with major depression and symptoms of anxiety. J Clin Psychiatry. 1998 Mar;59(3):123-7.
2. Watanabe N, Omori IM, Nakagawa A, et al. Mirtazapine versus other antidepressants in the acute-phase treatment of adults with major depression: systematic review and meta-analysis. J Clin Psychiatry. 2008 Sep;69(9):1404-15.