From the Research
Taking amitriptyline 25mg and mirtazapine 7.5mg together nightly for depression should only be done under close medical supervision due to potential interaction concerns, as the most recent and highest quality study 1 suggests that low-dose mirtazapine provided a statistically significant and clinically relevant reduction of insomnia severity at 6 weeks, but not at later time points, and low-dose amitriptyline resulted in a statistically significant reduction at 6 weeks only which was not clinically relevant. This combination can increase the risk of serotonin syndrome, a potentially serious condition characterized by agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and in severe cases, seizures or loss of consciousness. Both medications affect serotonin levels in the brain and also have overlapping side effects including sedation, dry mouth, constipation, and urinary retention, which may be intensified when taken together. If your doctor has prescribed this combination, they have likely determined that the potential benefits outweigh the risks for your specific situation. You should report any unusual symptoms promptly, especially excessive drowsiness, confusion, tremors, sweating, or rapid heartbeat. Never adjust the dosage or stop taking either medication without consulting your healthcare provider, as abrupt discontinuation can cause withdrawal symptoms. The study 2 also found that amitriptyline appeared more effective in reducing core symptoms of depression than mirtazapine and possibly also than SSRIs, but this outcome should be interpreted with caution due to the indirect nature of the comparison. Another study 3 found that mirtazapine was at least as well tolerated as clomipramine, doxepin and trazodone in comparative trials and appeared to be associated with slightly lower incidences of anticholinergic and neurological adverse events than these drugs. However, the most recent study 1 should be prioritized when making a definitive recommendation, as it provides the most up-to-date and high-quality evidence. In general, the use of sedative antidepressants like amitriptyline and mirtazapine should be carefully considered, as they can have different effects on sleep and may be associated with increased risk of serotonin syndrome when used in combination 4. Therefore, close medical supervision is essential when taking amitriptyline 25mg and mirtazapine 7.5mg together nightly for depression.