Trazodone high
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Understanding the Effects of High Doses of Trazodone
Pharmacokinetics of High Dose Trazodone
Trazodone is an antidepressant commonly used for its sedative properties. A study examining the pharmacokinetics of a single 100 mg oral dose of trazodone under fed conditions found that the drug's absorption was consistent and met bioequivalence criteria when compared to a reference product. The maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were within the acceptable range, indicating reliable absorption and bioavailability1.
Trazodone and Prolonged Penile Erection
One of the notable side effects of trazodone, especially at higher doses, is its potential to cause prolonged penile erection or priapism. Research involving healthy volunteers showed that trazodone significantly increased the duration of nocturnal erectile activity. This effect is likely due to trazodone's alpha-adrenoceptor blocking properties, which interfere with the sympathetic control of penile detumescence, thereby prolonging erections2.
Trazodone's Impact on Sleep in Chronic Insomnia
Trazodone is also used to treat chronic insomnia. A pilot study comparing trazodone to cognitive-behavioral treatment for insomnia (CBT-I) found that trazodone significantly decreased high-frequency EEG activity during non-rapid eye movement (NREM) sleep. This suggests that trazodone may reduce cortical and physiological hyperarousal more effectively than CBT-I, making it a potent option for improving sleep continuity in insomnia patients3.
Efficacy and Safety of Trazodone in Insomnia
Despite its widespread use, the evidence supporting trazodone's efficacy in treating insomnia is limited. Many studies are small and often conducted in populations with comorbid depression, raising concerns about their generalizability. Additionally, trazodone is associated with several side effects, including sedation, dizziness, and psychomotor impairment, which are particularly concerning for elderly patients. The risk of tolerance also questions its long-term efficacy4.
Trazodone and Obstructive Sleep Apnea (OSA)
Trazodone has been studied for its effects on obstructive sleep apnea (OSA). A study involving OSA patients found that trazodone significantly reduced the apnea/hypopnea index (AHI) without worsening oxygen saturation or the duration of respiratory events. However, trazodone did not significantly change the non-REM arousal threshold. These findings suggest that trazodone could be a beneficial treatment for OSA, potentially improving sleep quality without exacerbating hypoxemia5.
Conclusion
High doses of trazodone have diverse effects, from improving sleep in chronic insomnia to potentially treating OSA. However, its side effects, particularly the risk of prolonged erections and psychomotor impairment, necessitate careful consideration. While trazodone shows promise in several areas, further research is needed to fully understand its benefits and risks, especially in non-depressed patients with insomnia.
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Most relevant research papers on this topic
Pharmacokinetics of single oral dose trazodone: a randomized, two-period, cross-over trial in healthy, adult, human volunteers under fed condition
The test product and reference product show bioequivalence in the extent of absorption of trazodone under fed condition.
RCTPathophysiology of prolonged penile erection associated with trazodone use.
Trazodone can enhance penile erection in men, potentially due to its alpha-adrenoceptor blocking properties and interference with sympathetic control of penile detumescence.
RCT
Highly CitedEffect of trazodone versus cognitive‐behavioural treatment on high‐ and slow‐frequency activity during non‐rapid eye movement sleep in chronic insomnia: A pilot, randomized clinical trial
Trazodone effectively decreases fast-frequency EEG activity during NREM sleep, reducing cortical and physiological hyperarousal in chronic insomnia patients compared to cognitive-behavioral treatment.
RCT
Rigorous JournalA review of the evidence for the efficacy and safety of trazodone in insomnia.
Trazodone's efficacy in treating insomnia is limited and its side effects, such as sedation, dizziness, and psychomotor impairment, raise concerns for its use in nondepressed patients.
Systematic ReviewHighly CitedTrazodone Effects on Obstructive Sleep Apnea and Non-REM Arousal Threshold.
Trazodone effectively reduces obstructive sleep apnea severity without worsening hypoxemia, but does not significantly affect non-REM arousal threshold.
RCTHighly CitedTrazodone for Insomnia: A Systematic Review.
Low-dose trazodone is effective and generally safe for treating insomnia, with the most common side effect being drowsiness.
Systematic ReviewHighly CitedTrazodone--a new antidepressant.
Trazodone is a new, potentially safe antidepressant with an unusual chemical structure and comparable potency to existing medications.
Estimation of brain receptor occupancy for trazodone immediate release and once a day formulations
Trazodone's dose-dependent receptor coverage supports its multimodal activity and contributes to its fast antidepressant action and effectiveness in controlling different symptoms in depressed patients.
In Vitro StudyRigorous JournalTrazodone in Sexual Medicine: Underused and Overdosed?
The optimal dose of extended-release Trazodone for hypoactive sexual desire disorder (HSDD) is about 4-20 mg, which may be treated without over-sedation with a dose of 150-mg TRZ matrix tablets or 50-mg IR TRZ tablets.
Literature ReviewTrazodone for agitation in dementia.
There is insufficient evidence to recommend trazodone as a treatment for behavioral and psychological manifestations of dementia.
Meta-AnalysisHighly Cited