Trazodone has strong sleep-inducing (hypnotic) effects and is primarily indicated for insomnia.
Trazodone can also be used in higher doses in the treatment of major depressive disorder (MDD).
Trazodone works to balance serotonin levels in depressed patients in two primary ways. First, Trazodone is considered a weak serotonin reuptake inhibitor and delays the metabolism of serotonin in the post-synaptic cleft, so there is more neurotransmitter available for use, the same mechanism of action utilized in SSRIs. Secondly, it potently inhibits the excitatory receptors of 5-HT2A, which are more numerous in depressed patients.
Trazodone inhibits specific serotonin receptors called 5-HT2A and 5-HT2C. Interestingly, this antagonistic effect only occurs in low doses, whereas it demonstrates agonist behavior in high doses.
Though the mechanism isn't fully understood, part of Trazodone's effects is attributed to the drug's α1-adrenergic receptor-blocking activity.
This medication also inhibits histamine, or H1, receptors. It is thought that this effect is responsible for the associated sedation, which proves beneficial for use as a sleep aid.
A common side effect of Trazodone is sedation, largely thought to result from the histamine (H1) receptor blockade.
Trazodone may cause orthostatic hypotension in some patients, possibly due to its blockage of α1-adrenergic receptors.
While Trazodone's antihistamine effect proves useful in treating insomnia, it can also commonly cause dry mouth as a side effect.
Priapism is a side effect of Trazodone that is a common exam question regarding potential adverse effects of this medication and may be remembered by the mnemonic, TrazoBONE. This condition occurs when the erect penis does not return to the flaccid state within four hours and is thought to be facilitated by Trazodone's inhibition of α1-adrenergic receptors.
While it remains a rarely seen side effect, it is important to be aware that there have been cases of atrial and ventricular arrhythmias in patients treated with Trazodone. As such, exercise caution when considering prescribing Trazodone to cardiac patients.
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