Trazodone – StatPearls – NCBI Bookshelf

Continuing Education Activity

Trazodone is a medication used in the management and treatment of major depressive disorder. It is in the serotonin-antagonist-and-reuptake-inhibitor class of medications. This activity reviews the indications, action, and contraindications for trazodone as a valuable agent in managing major depression. This activity will highlight the mechanism of actions, adverse effects, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions), pertinent for members of the interprofessional team in the treatment of patients with depression and related conditions.

Objectives:

• Identify the indications for trazodone, including off-label indications.

• Describe the common adverse effects associated with trazodone use.

• Review the treatment considerations for patients on trazodone.

• Explain the importance of collaboration and communication amongst interprofessional team members to improve outcomes for patients affected by severe hepatic impairment who are candidates for trazodone use.

Access free multiple choice questions on this topic.

Indications

FDA-approved Indications

Trazodone is an FDA-approved antidepressant for treating major depressive disorders.[1] It can be used as part of combination therapy with other drugs or psychotherapies or used by itself for treating depression.

Non-FDA-approved Uses

Trazodone is used to induce sedation in patients with sleep problems. These patients may or may not have concurrent depression. Because of a lack of sufficient clinical data for justifying its use as a sleep aid, trazodone is not FDA-approved for sleep disorders. Trazodone is also used off-label for anxiety, Alzheimer disease, substance abuse, bulimia, and fibromyalgia due to its serotonergic receptor antagonism and serotonin reuptake inhibiting effects.[2]

Trazodone has also been used for post-traumatic stress disorder (PTSD) if the first-line treatment use of SSRIs does not show efficacy. The dose of 50 mg to 200 mg of trazodone has been demonstrated to reduce episodes of nightmares as well as improve sleep habits in studies involving PTSD patients. However, various studies show patients with panic symptoms have suffered exacerbation in some instances, which is why SSRIs, instead of trazodone, are preferred as the first-line treatment for PTSD. Additionally, research has shown trazodone to improve apnea and hypopnea episodes in patients with obstructive sleep apnea (OSA), and the drug does not worsen hypoxemic episodes.[3] It raises the respiratory threshold, lowering the risk of respiratory instability.[4]

Mechanism of Action

Trazodone is an antidepressant that works by inhibiting both serotonin transporter and serotonin type 2 receptors. It is a triazolopyridine derivative. Trazodone inhibits the reuptake of serotonin and blocks the histamine and alpha-1-adrenergic receptors. It also induces significant changes in 5-HT presynaptic receptor adrenoreceptors. The full spectrum of trazodone’s mechanism of action is not fully understood, explaining its off-label uses. Trazodone is in the category of SARI drugs (serotonin antagonist and reuptake inhibitors), with other members being phenylpiperazine, etoperidone, lorpiprazole, and mepiprazole. [5]

Clinical studies have shown trazodone to be comparable in efficacy to other drug classes, such as TCAs (tricyclic antidepressants), SSRIs (selective serotonin reuptake inhibitors), and SNRIs (serotonin-norepinephrine receptor inhibitor) in treating major depressive disorders. Also, trazodone has better tolerance than second-generation SSRIs, which are highly associated with insomnia, anxiety, and sexual dysfunction.[6] The unique property of trazodone, where it simultaneously inhibits SERT, 5-HT2A, and 5-HT2C receptors, avoids the issue of sexual dysfunction, insomnia, and anxiety that commonly presents with SSRIs and SNRIs therapy. Trazodone reduces levels of neurotransmitters associated with arousal effects, such as serotonin, noradrenaline, dopamine, acetylcholine, and histamine. Low-dose trazodone use exerts a sedative effect for sleep through antagonism of 5-HT-2A receptor, h2 receptor, and alpha-1-adrenergic receptors. 

Furthermore, a recent study on human astrocytes showed trazodone helps decrease inflammatory mediator release and helps normalize trophic and metabolic support during inflammation of neurons, which is associated with major depression.

Administration

Trazodone administration is via the oral route. It is available in oral tablets of trazodone hydrochloride 50 mg, 100 mg, 150 mg, and 300 mg in the US. It may be administered after meals to decrease lightheadedness and postural hypotension. Begin with evening administration of 75 mg to 150 mg before bedtime, as a prolonged-release once-a-day administration. This regimen helps optimize its purpose as an antidepressant, eliciting higher compliance.[7] The dose may be increased every third day, up to 300 mg per day. The dose may be up to 600 mg per day in hospitalized patients. The dose in the elderly should be down to 100 mg per day. Results of multi-drug regiment studies showed that using citalopram and fluoxetine with trazodone had no significant impact on any alteration of serum level and no increased risk of headache, sedation, or serotonin syndrome.

Studies showed that administering 50 mg to 100 mg per day of trazodone helped nonorganic insomnia due to depressive disorder, with 100 mg dosage as most effective to improve sleep. Trazodone may be available as immediate-release (IR) tablets and, in some countries, prolonged-release tablets, oral drops, and injection solutions.

Pediatric Patients
 

There is a boxed warning on an increased risk of suicidal thoughts and behaviors in pediatric patients with antidepressant medication use. However, effectiveness and safety in the pediatric population have not been established for trazodone. 

Geriatric Patients

It should be used carefully in elderly patients as serotonergic antidepressants are associated with hyponatremia in elderly patients, who are already at greater risk for this adverse reaction. 

Pregnancy Consideration

Healthcare providers should register pregnant patients with depression in the National Pregnancy Registry for Antidepressants by calling 1-844-405-6185, which monitors pregnancy outcomes in patients exposed to antidepressants during pregnancy. Published literature on trazodone use in pregnant women has not found any associated risks of miscarriage, major congenital disabilities, and adverse maternal or fetal outcomes. [8] The clinical study was conducted on 201 pregnant patients with major depressive disorder history who become euthymic while using antidepressants at the beginning of pregnancy. It showed that patients who discontinued antidepressants during pregnancy have more chances to experience a relapse of major depression than women who continued treatment with antidepressants. Therefore, it is advisable to consider the risk of untreated depression if planning to discontinue or change antidepressant treatment while a patient is pregnant or postpartum

Breastfeeding Consideration

Trazodone is excreted into human milk, and there is a lack of data on its effect on milk production.[9] Postmarketing reports have limited data, and it has not identified an association of adverse effects of trazodone use on the breastfed child. Maternal need of trazodone should be accessed along with risk on development and health benefits of breastfeeding to the child. According to the safety scoring system use of trazodone should be used cautiously while breastfeeding, especially infants. [10]

Hepatic Impairment

Trazodone use is not studied in patients with liver impairment, and it is recommended to use trazodone with caution in this population.

Renal Impairment

Trazodone use is not studied in patients with renal impairment, and it is recommended to use trazodone with caution in this population.[11]

Adverse Effects

The primary adverse effects of trazodone include headaches, fatigue, dizziness, and drowsiness/somnolence. Other risks include anticholinergic effects (dry mouth), orthostatic hypotension, QT prolongation, torsades, priapism, and an increase in suicidal thoughts. QT prolongation and arrhythmia risks are due to the interaction of trazodone with hERG potassium channels. Antidepressants are associated with an increased risk of suicidal thinking, especially in younger adults, adolescents, and children. Despite the presence of anticholinergic side effects, the risk is less than tricyclic antidepressants, such as imipramine or amitriptyline.  The risk for orthostatic hypotension is higher in the elderly, especially those with pre-existing heart conditions, due to the adrenergic α1-receptor blockade. Patients show adverse effects of somnolence and hypotension during the first week of administration. Special care is necessary for men with sickle cell anemia, multiple myeloma, leukemia, autonomic dysfunction, hypercoagulable state, or those who have a penile anatomic variation as angulation, cavernosal fibrosis, or Peyronie disease, as it can cause priapism.[12]

In some cases, trazodone use has correlated with visual hallucinations. Hallucinations generally resolve with the discontinuation of trazodone, and physicians should switch the patient to another antidepressant medication.[13]

Contraindications

Trazodone therapy requires careful consideration for patients treated with any class of monoamine oxidase inhibitors (MAOIs), including linezolid or intravenous methylene blue. MAO inhibitors impair the metabolism of serotonin, and concurrent administration increases serum levels of serotonin. Therefore, one must have 14 days of the MAOI-free period to reduce the risk of serotonin syndrome before initiating treatment with trazodone. In addition, concomitant use of other serotonergic drugs, such as triptans, TCA, or fentanyl, will also increase serotonin levels. Trazodone use requires caution in patients with compromised liver function and renal function.[14]

Monitoring

Baseline liver functions require monitoring before or periodically during therapy in patients taking trazodone. Patients receiving trazodone should also be monitored for suicide ideation, especially at the beginning of the treatment or when the dose is modified. Monitor also for signs or symptoms of serotonin syndrome. In addition, concomitant administration of CYP 3A4 inhibitors can lead to increased levels of trazodone, increasing the risk of serotonin syndrome and cardiovascular adverse effects.[15] Health care providers should assess the response to trazodone therapy and consider augmenting or switching antidepressants if inadequate response.

Toxicity

Due to trazodone’s hepatic and renal metabolism, special care is necessary for patients with severe hepatic impairment and severe renal impairment. Serotonin syndrome, while rare, is potentially life-threatening, presenting as a triad of mental status alteration, neuromuscular abnormality, and autonomic instability. Initial clinical suspicion varies from presenting tremor, clonus, or akathisia. The first step to address this should be discontinuation of serotonergic agents, hydration, and control of agitation with anxiolytics. The risk is higher with certain antidepressants, antibiotics, migraine medications, antiemetics, and analgesics. The idiopathic drug-induced liver injury may result from trazodone administration. The timeframe typically is three months, but reported cases require liver transplantation.[16]

Trazodone overdose can precipitate arrhythmias, respiratory arrest, coma, and priapism. Treatment is usually symptomatic and supportive in the case of hypotension and excessive sedation. If priapism occurs, it requires urgent urologist interventuon. Intracavernosal injection (phenylephrine injection) is indicated in patients with ischemic priapism. The medical team should call the local poison center for up-to-date guidance on trazodone overdose.[17]

Enhancing Healthcare Team Outcomes

To properly administer medications for the appropriate population, the presence of clear communication and instruction is necessary. In addition to healthcare providers being able to communicate with each other, patients must feel comfortable enough to be involved in the treatment process. Providers having appropriate empathy for patients is necessary for patients to disclose their needs to providers.[18] An interprofessional healthcare team incorporating clinicians, mid-level practitioners, nurses, psychological professionals, and pharmacists will lead to optimal patient care with minimal adverse events. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

Schwasinger-Schmidt TE, Macaluso M. Other Antidepressants. Handb Exp Pharmacol. 2019;250:325-355. [PubMed: 30194544]

2.

Khouzam HR. A review of trazodone use in psychiatric and medical conditions. Postgrad Med. 2017 Jan;129(1):140-148. [PubMed: 27744763]

3.

Smales ET, Edwards BA, Deyoung PN, McSharry DG, Wellman A, Velasquez A, Owens R, Orr JE, Malhotra A. Trazodone Effects on Obstructive Sleep Apnea and Non-REM Arousal Threshold. Ann Am Thorac Soc. 2015 May;12(5):758-64. [PMC free article: PMC4418332] [PubMed: 25719754]

4.

Eckert DJ, Malhotra A, Wellman A, White DP. Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold. Sleep. 2014 Apr 01;37(4):811-9. [PMC free article: PMC4044741] [PubMed: 24899767]

5.

Mandrioli R, Protti M, Mercolini L. New-Generation, Non-SSRI Antidepressants: Therapeutic Drug Monitoring and Pharmacological Interactions. Part 1: SNRIs, SMSs, SARIs. Curr Med Chem. 2018;25(7):772-792. [PubMed: 28707591]

6.

Fagiolini A, Comandini A, Catena Dell’Osso M, Kasper S. Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs. 2012 Dec;26(12):1033-49. [PMC free article: PMC3693429] [PubMed: 23192413]

7.

Fiorentini A, Rovera C, Caldiroli A, Arici C, Prunas C, Di Pace C, Paletta S, Pozzoli SM, Buoli M, Altamura AC. Efficacy of oral trazodone slow release following intravenous administration in depressed patients: a naturalistic study. Riv Psichiatr. 2018 Sep-Oct;53(5):261-266. [PubMed: 30353201]

8.

Einarson A, Bonari L, Voyer-Lavigne S, Addis A, Matsui D, Johnson Y, Koren G. A multicentre prospective controlled study to determine the safety of trazodone and nefazodone use during pregnancy. Can J Psychiatry. 2003 Mar;48(2):106-10. [PubMed: 12655908]

9.

Saito J, Ishii M, Mito A, Yakuwa N, Kawasaki H, Tachibana Y, Suzuki T, Yamatani A, Sago H, Murashima A. Trazodone Levels in Maternal Serum, Cord Blood, Breast Milk, and Neonatal Serum. Breastfeed Med. 2021 Nov;16(11):922-925. [PMC free article: PMC8817729] [PubMed: 34348038]

10.

Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Apr 18, 2022. Trazodone. [PubMed: 30000237]

11.

Nagler EV, Webster AC, Vanholder R, Zoccali C. Antidepressants for depression in stage 3-5 chronic kidney disease: a systematic review of pharmacokinetics, efficacy and safety with recommendations by European Renal Best Practice (ERBP). Nephrol Dial Transplant. 2012 Oct;27(10):3736-45. [PubMed: 22859791]

12.

Haria M, Fitton A, McTavish D. Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders. Drugs Aging. 1994 Apr;4(4):331-55. [PubMed: 8019056]

13.

Santos G, Moreira AM. Distressing Visual Hallucinations after Treatment with Trazodone. Case Rep Psychiatry. 2017;2017:6136914. [PMC free article: PMC5494093] [PubMed: 28702268]

14.

Carvalhana S, Oliveira A, Ferreira P, Resende M, Perdigoto R, Barroso E. Acute Liver Failure due to Trazodone and Diazepam. GE Port J Gastroenterol. 2017 Jan;24(1):40-42. [PMC free article: PMC5553376] [PubMed: 28848778]

15.

Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jabłońska J, Rybakowski J. [Trazodon–the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [PubMed: 22232986]

16.

Jurek L, Nourredine M, Megarbane B, d’Amato T, Dorey JM, Rolland B. [The serotonin syndrome: An updated literature review]. Rev Med Interne. 2019 Feb;40(2):98-104. [PubMed: 30243558]

17.

Wen CC, Munarriz R, McAuley I, Goldstein I, Traish A, Kim N. Management of ischemic priapism with high-dose intracavernosal phenylephrine: from bench to bedside. J Sex Med. 2006 Sep;3(5):918-922. [PubMed: 16942536]

18.

Nichol JR, Sundjaja JH, Nelson G. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Sep 5, 2022. Medical History. [PubMed: 30484996]

Disclosure: Justin Shin declares no relevant financial relationships with ineligible companies.

Disclosure: Abdolreza Saadabadi declares no relevant financial relationships with ineligible companies.

Trazodone – StatPearls – NCBI Bookshelf

Continuing Education Activity

Trazodone is a medication used in the management and treatment of major depressive disorder. It is in the serotonin-antagonist-and-reuptake-inhibitor class of medications. This activity reviews the indications, action, and contraindications for trazodone as a valuable agent in managing major depression. This activity will highlight the mechanism of actions, adverse effects, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions), pertinent for members of the interprofessional team in the treatment of patients with depression and related conditions.

Objectives:

• Identify the indications for trazodone, including off-label indications.

• Describe the common adverse effects associated with trazodone use.

• Review the treatment considerations for patients on trazodone.

• Explain the importance of collaboration and communication amongst interprofessional team members to improve outcomes for patients affected by severe hepatic impairment who are candidates for trazodone use.

Access free multiple choice questions on this topic.

Indications

FDA-approved Indications

Trazodone is an FDA-approved antidepressant for treating major depressive disorders. [1] It can be used as part of combination therapy with other drugs or psychotherapies or used by itself for treating depression.

Non-FDA-approved Uses

Trazodone is used to induce sedation in patients with sleep problems. These patients may or may not have concurrent depression. Because of a lack of sufficient clinical data for justifying its use as a sleep aid, trazodone is not FDA-approved for sleep disorders. Trazodone is also used off-label for anxiety, Alzheimer disease, substance abuse, bulimia, and fibromyalgia due to its serotonergic receptor antagonism and serotonin reuptake inhibiting effects.[2]

Trazodone has also been used for post-traumatic stress disorder (PTSD) if the first-line treatment use of SSRIs does not show efficacy. The dose of 50 mg to 200 mg of trazodone has been demonstrated to reduce episodes of nightmares as well as improve sleep habits in studies involving PTSD patients. However, various studies show patients with panic symptoms have suffered exacerbation in some instances, which is why SSRIs, instead of trazodone, are preferred as the first-line treatment for PTSD. Additionally, research has shown trazodone to improve apnea and hypopnea episodes in patients with obstructive sleep apnea (OSA), and the drug does not worsen hypoxemic episodes.[3] It raises the respiratory threshold, lowering the risk of respiratory instability.[4]

Mechanism of Action

Trazodone is an antidepressant that works by inhibiting both serotonin transporter and serotonin type 2 receptors. It is a triazolopyridine derivative. Trazodone inhibits the reuptake of serotonin and blocks the histamine and alpha-1-adrenergic receptors. It also induces significant changes in 5-HT presynaptic receptor adrenoreceptors. The full spectrum of trazodone’s mechanism of action is not fully understood, explaining its off-label uses. Trazodone is in the category of SARI drugs (serotonin antagonist and reuptake inhibitors), with other members being phenylpiperazine, etoperidone, lorpiprazole, and mepiprazole.[5]

Clinical studies have shown trazodone to be comparable in efficacy to other drug classes, such as TCAs (tricyclic antidepressants), SSRIs (selective serotonin reuptake inhibitors), and SNRIs (serotonin-norepinephrine receptor inhibitor) in treating major depressive disorders. Also, trazodone has better tolerance than second-generation SSRIs, which are highly associated with insomnia, anxiety, and sexual dysfunction.[6] The unique property of trazodone, where it simultaneously inhibits SERT, 5-HT2A, and 5-HT2C receptors, avoids the issue of sexual dysfunction, insomnia, and anxiety that commonly presents with SSRIs and SNRIs therapy. Trazodone reduces levels of neurotransmitters associated with arousal effects, such as serotonin, noradrenaline, dopamine, acetylcholine, and histamine. Low-dose trazodone use exerts a sedative effect for sleep through antagonism of 5-HT-2A receptor, h2 receptor, and alpha-1-adrenergic receptors. 

Furthermore, a recent study on human astrocytes showed trazodone helps decrease inflammatory mediator release and helps normalize trophic and metabolic support during inflammation of neurons, which is associated with major depression.

Administration

Trazodone administration is via the oral route. It is available in oral tablets of trazodone hydrochloride 50 mg, 100 mg, 150 mg, and 300 mg in the US. It may be administered after meals to decrease lightheadedness and postural hypotension. Begin with evening administration of 75 mg to 150 mg before bedtime, as a prolonged-release once-a-day administration. This regimen helps optimize its purpose as an antidepressant, eliciting higher compliance.[7] The dose may be increased every third day, up to 300 mg per day. The dose may be up to 600 mg per day in hospitalized patients. The dose in the elderly should be down to 100 mg per day. Results of multi-drug regiment studies showed that using citalopram and fluoxetine with trazodone had no significant impact on any alteration of serum level and no increased risk of headache, sedation, or serotonin syndrome.

Studies showed that administering 50 mg to 100 mg per day of trazodone helped nonorganic insomnia due to depressive disorder, with 100 mg dosage as most effective to improve sleep. Trazodone may be available as immediate-release (IR) tablets and, in some countries, prolonged-release tablets, oral drops, and injection solutions.

Pediatric Patients
 

There is a boxed warning on an increased risk of suicidal thoughts and behaviors in pediatric patients with antidepressant medication use. However, effectiveness and safety in the pediatric population have not been established for trazodone. 

Geriatric Patients

It should be used carefully in elderly patients as serotonergic antidepressants are associated with hyponatremia in elderly patients, who are already at greater risk for this adverse reaction. 

Pregnancy Consideration

Healthcare providers should register pregnant patients with depression in the National Pregnancy Registry for Antidepressants by calling 1-844-405-6185, which monitors pregnancy outcomes in patients exposed to antidepressants during pregnancy. Published literature on trazodone use in pregnant women has not found any associated risks of miscarriage, major congenital disabilities, and adverse maternal or fetal outcomes.[8] The clinical study was conducted on 201 pregnant patients with major depressive disorder history who become euthymic while using antidepressants at the beginning of pregnancy. It showed that patients who discontinued antidepressants during pregnancy have more chances to experience a relapse of major depression than women who continued treatment with antidepressants. Therefore, it is advisable to consider the risk of untreated depression if planning to discontinue or change antidepressant treatment while a patient is pregnant or postpartum

Breastfeeding Consideration

Trazodone is excreted into human milk, and there is a lack of data on its effect on milk production.[9] Postmarketing reports have limited data, and it has not identified an association of adverse effects of trazodone use on the breastfed child. Maternal need of trazodone should be accessed along with risk on development and health benefits of breastfeeding to the child. According to the safety scoring system use of trazodone should be used cautiously while breastfeeding, especially infants.[10]

Hepatic Impairment

Trazodone use is not studied in patients with liver impairment, and it is recommended to use trazodone with caution in this population.

Renal Impairment

Trazodone use is not studied in patients with renal impairment, and it is recommended to use trazodone with caution in this population.[11]

Adverse Effects

The primary adverse effects of trazodone include headaches, fatigue, dizziness, and drowsiness/somnolence. Other risks include anticholinergic effects (dry mouth), orthostatic hypotension, QT prolongation, torsades, priapism, and an increase in suicidal thoughts. QT prolongation and arrhythmia risks are due to the interaction of trazodone with hERG potassium channels. Antidepressants are associated with an increased risk of suicidal thinking, especially in younger adults, adolescents, and children. Despite the presence of anticholinergic side effects, the risk is less than tricyclic antidepressants, such as imipramine or amitriptyline. The risk for orthostatic hypotension is higher in the elderly, especially those with pre-existing heart conditions, due to the adrenergic α1-receptor blockade.  Patients show adverse effects of somnolence and hypotension during the first week of administration. Special care is necessary for men with sickle cell anemia, multiple myeloma, leukemia, autonomic dysfunction, hypercoagulable state, or those who have a penile anatomic variation as angulation, cavernosal fibrosis, or Peyronie disease, as it can cause priapism.[12]

In some cases, trazodone use has correlated with visual hallucinations. Hallucinations generally resolve with the discontinuation of trazodone, and physicians should switch the patient to another antidepressant medication.[13]

Contraindications

Trazodone therapy requires careful consideration for patients treated with any class of monoamine oxidase inhibitors (MAOIs), including linezolid or intravenous methylene blue. MAO inhibitors impair the metabolism of serotonin, and concurrent administration increases serum levels of serotonin. Therefore, one must have 14 days of the MAOI-free period to reduce the risk of serotonin syndrome before initiating treatment with trazodone. In addition, concomitant use of other serotonergic drugs, such as triptans, TCA, or fentanyl, will also increase serotonin levels. Trazodone use requires caution in patients with compromised liver function and renal function.[14]

Monitoring

Baseline liver functions require monitoring before or periodically during therapy in patients taking trazodone. Patients receiving trazodone should also be monitored for suicide ideation, especially at the beginning of the treatment or when the dose is modified. Monitor also for signs or symptoms of serotonin syndrome. In addition, concomitant administration of CYP 3A4 inhibitors can lead to increased levels of trazodone, increasing the risk of serotonin syndrome and cardiovascular adverse effects.[15] Health care providers should assess the response to trazodone therapy and consider augmenting or switching antidepressants if inadequate response.

Toxicity

Due to trazodone’s hepatic and renal metabolism, special care is necessary for patients with severe hepatic impairment and severe renal impairment. Serotonin syndrome, while rare, is potentially life-threatening, presenting as a triad of mental status alteration, neuromuscular abnormality, and autonomic instability. Initial clinical suspicion varies from presenting tremor, clonus, or akathisia. The first step to address this should be discontinuation of serotonergic agents, hydration, and control of agitation with anxiolytics. The risk is higher with certain antidepressants, antibiotics, migraine medications, antiemetics, and analgesics. The idiopathic drug-induced liver injury may result from trazodone administration. The timeframe typically is three months, but reported cases require liver transplantation.[16]

Trazodone overdose can precipitate arrhythmias, respiratory arrest, coma, and priapism. Treatment is usually symptomatic and supportive in the case of hypotension and excessive sedation. If priapism occurs, it requires urgent urologist interventuon. Intracavernosal injection (phenylephrine injection) is indicated in patients with ischemic priapism. The medical team should call the local poison center for up-to-date guidance on trazodone overdose.[17]

Enhancing Healthcare Team Outcomes

To properly administer medications for the appropriate population, the presence of clear communication and instruction is necessary. In addition to healthcare providers being able to communicate with each other, patients must feel comfortable enough to be involved in the treatment process. Providers having appropriate empathy for patients is necessary for patients to disclose their needs to providers.[18] An interprofessional healthcare team incorporating clinicians, mid-level practitioners, nurses, psychological professionals, and pharmacists will lead to optimal patient care with minimal adverse events. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

Schwasinger-Schmidt TE, Macaluso M. Other Antidepressants. Handb Exp Pharmacol. 2019;250:325-355. [PubMed: 30194544]

2.

Khouzam HR. A review of trazodone use in psychiatric and medical conditions. Postgrad Med. 2017 Jan;129(1):140-148. [PubMed: 27744763]

3.

Smales ET, Edwards BA, Deyoung PN, McSharry DG, Wellman A, Velasquez A, Owens R, Orr JE, Malhotra A. Trazodone Effects on Obstructive Sleep Apnea and Non-REM Arousal Threshold. Ann Am Thorac Soc. 2015 May;12(5):758-64. [PMC free article: PMC4418332] [PubMed: 25719754]

4.

Eckert DJ, Malhotra A, Wellman A, White DP. Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold. Sleep. 2014 Apr 01;37(4):811-9. [PMC free article: PMC4044741] [PubMed: 24899767]

5.

Mandrioli R, Protti M, Mercolini L. New-Generation, Non-SSRI Antidepressants: Therapeutic Drug Monitoring and Pharmacological Interactions. Part 1: SNRIs, SMSs, SARIs. Curr Med Chem. 2018;25(7):772-792. [PubMed: 28707591]

6.

Fagiolini A, Comandini A, Catena Dell’Osso M, Kasper S. Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs. 2012 Dec;26(12):1033-49. [PMC free article: PMC3693429] [PubMed: 23192413]

7.

Fiorentini A, Rovera C, Caldiroli A, Arici C, Prunas C, Di Pace C, Paletta S, Pozzoli SM, Buoli M, Altamura AC. Efficacy of oral trazodone slow release following intravenous administration in depressed patients: a naturalistic study. Riv Psichiatr. 2018 Sep-Oct;53(5):261-266. [PubMed: 30353201]

8.

Einarson A, Bonari L, Voyer-Lavigne S, Addis A, Matsui D, Johnson Y, Koren G. A multicentre prospective controlled study to determine the safety of trazodone and nefazodone use during pregnancy. Can J Psychiatry. 2003 Mar;48(2):106-10. [PubMed: 12655908]

9.

Saito J, Ishii M, Mito A, Yakuwa N, Kawasaki H, Tachibana Y, Suzuki T, Yamatani A, Sago H, Murashima A. Trazodone Levels in Maternal Serum, Cord Blood, Breast Milk, and Neonatal Serum. Breastfeed Med. 2021 Nov;16(11):922-925. [PMC free article: PMC8817729] [PubMed: 34348038]

10.

Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Apr 18, 2022. Trazodone. [PubMed: 30000237]

11.

Nagler EV, Webster AC, Vanholder R, Zoccali C. Antidepressants for depression in stage 3-5 chronic kidney disease: a systematic review of pharmacokinetics, efficacy and safety with recommendations by European Renal Best Practice (ERBP). Nephrol Dial Transplant. 2012 Oct;27(10):3736-45. [PubMed: 22859791]

12.

Haria M, Fitton A, McTavish D. Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders. Drugs Aging. 1994 Apr;4(4):331-55. [PubMed: 8019056]

13.

Santos G, Moreira AM. Distressing Visual Hallucinations after Treatment with Trazodone. Case Rep Psychiatry. 2017;2017:6136914. [PMC free article: PMC5494093] [PubMed: 28702268]

14.

Carvalhana S, Oliveira A, Ferreira P, Resende M, Perdigoto R, Barroso E. Acute Liver Failure due to Trazodone and Diazepam. GE Port J Gastroenterol. 2017 Jan;24(1):40-42. [PMC free article: PMC5553376] [PubMed: 28848778]

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Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jabłońska J, Rybakowski J. [Trazodon–the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [PubMed: 22232986]

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Wen CC, Munarriz R, McAuley I, Goldstein I, Traish A, Kim N. Management of ischemic priapism with high-dose intracavernosal phenylephrine: from bench to bedside. J Sex Med. 2006 Sep;3(5):918-922. [PubMed: 16942536]

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Disclosure: Justin Shin declares no relevant financial relationships with ineligible companies.

Disclosure: Abdolreza Saadabadi declares no relevant financial relationships with ineligible companies.

Use of trazodone (trittico) | News and promotions of the European Medical Center “UMMC-Health”

Erectile dysfunction is a disease characterized by “persistent inability to achieve or maintain an erection sufficient for satisfactory sexual intercourse” (1). It is difficult to overestimate the psychological significance for a man and for family relations of this disease (2).

Until the beginning of the twentieth century, psychogenic erectile dysfunction was considered the main cause of erectile dysfunction. Currently, 80% of patients are diagnosed with organic causes of the disease (3).

The occurrence of erectile dysfunction has a very clear age dependence.

The Massachusetts male aging study showed that 12.4% had erectile dysfunction between the ages of 40 and 49, 29.8% between the ages of 50 and 59, and 29.8% between the ages of 60 and 69. in 46.6% of patients (4). In addition to age, diseases such as diabetes mellitus, vascular heart disease, hypertension, depression are directly related to the occurrence of erectile dysfunction (5).

According to the doctor of medical sciences, president of PAAR Shcheplev PA, erectile dysfunction in 25% of cases is of a purely organic nature (vascular disorders, diabetes mellitus, medications, neurological and endocrine disorders, operations on the pelvic organs), 25% is purely psychogenic and in 50% of cases is the result of several reasons.

Thus, the significance of psychogenic causes in the structure of erectile dysfunction, although it has decreased, remains quite high. Of particular relevance are issues related to the treatment of depression in combination with erectile dysfunction.

Depressed men have a risk of developing erectile dysfunction ranging from 25% for mild depression to 90% for severe depression (6).

The frequency and variety of forms of psychogenic erectile dysfunction (7) in the practice of an andrologist determines the search for drugs that simultaneously affect both the psychogenic factor of the disease (anxiety, depression, asthenic syndrome) and the erection mechanisms themselves.

Trazodone hydrochloride (trittico) is used as an antidepressant and has anti-anxiety (anxiolytic), sedative and hypnotic effects. Because of the reported improvement in erectile function with trazodone, this drug has been used to treat erectile dysfunction (8).

The mechanism of action of trazodone (trittiko) is associated with selective suppression of serotonin reuptake and a powerful blockade of 5HT2a receptors _, , which causes its antidepressant effect. Antagonism towards α2-adrenergic receptors of the smooth muscles of the vessels of the penis and smooth muscles of the cavernous bodies, leading to their relaxation, possibly causes the effect of trazodone to induce an erection and improve erectile function. (9,10) .

Moderate blockade of 5HT1a serotonin receptors (10 times less than 5HT2a), reduces the likelihood of their hyperstimulation effect, and the manifestation of side effects characteristic of selective serotonin reuptake inhibitors, such as psychomotor agitation, restlessness, insomnia, headache, anxiety , loss of appetite, nausea, vomiting and diarrhea.

Thus, the mechanism of action of trazodone (trittico) suggests the possible effectiveness of the use of this drug in the complex treatment of psychogenic erectile dysfunction and erectile dysfunction of mixed origin, where the psychogenic component is clinically significant.

In the foreign literature, there are a number of studies on the use of trazodone for the treatment of erectile dysfunction.

G. A. Fink et al conducted a meta-analysis of the Medline database and the Cochrane Library from January 1966 to May 2002 (11). Six studies with 396 male subjects met the inclusion criteria. Three studies showed a significant clinical effect of trazodone in the treatment of erectile dysfunction compared with placebo. Two studies showed a statistically significant efficacy of trazodone compared with placebo (37% versus 20%). The analysis performed suggested that men with psychogenic erectile dysfunction are more likely to have satisfactory results from taking trazodone than men with mixed or organic erectile dysfunction. The effectiveness of trazodone in the treatment of erectile dysfunction also depended on the dose of the drug, the best result was achieved when taking 150-200 mg per day than when taking 50 mg. The conclusion from this work is that trazodone may improve erectile quality in men with erectile dysfunction, especially at higher doses and in men with psychogenic erectile dysfunction (10).

A study by Kurt W 1994 (12) showed a greater likelihood of three or more successful intercourse attempts in patients with psychogenic erectile dysfunction treated with trazodone compared to those treated with placebo .

In a study by Montorsi F. 1994 (13) in men with psychogenic erectile dysfunction, trazodone 50 mg daily in combination with yohimbine 5 mg three times daily had more likely to have a satisfactory erection than with placebo (50% versus 11%).

At the same time, in a study by Costabile R.A. 1999 (14), in which men with organic erectile dysfunction participated, treatment with trazodone at a dose of 50 mg per day improves erection no better than placebo.

In a meta-analysis of 6 studies, Fink et al. G. A. 2003 (11) report the following side effects of trazodone: dry mouth (19% vs. 11% with placebo), sedation (16% vs. 6%) , dizziness (16% vs 0%) and fatigue (15% vs 8%). Priapism was observed in only one man taking trazodone in one of the studies, in the placebo groups this effect was never seen.

In the domestic literature there are separate studies on the use of the drug trazodone (trittiko) for the treatment of erectile dysfunction.

Tak Tkachuk V. N., Lukyanov A.E 2006 (15) in his study involving 135 patients with psychogenic erectile dysfunction aged 22 to 56 years (mean was 32.2±3.4 years ) Trittico was used at a dose of 150 mg once a day for 6 weeks. The IIEF scale was used to assess the effectiveness of treatment.

Erectile function after treatment with trazodone (trittiko) was satisfactory.

Materials and methods.

The data of our study at the polyclinic base of the Clinic LLC “City Hospital No. 41” and the Clinic “Health 365” from 2007 to 2010 include 36 patients who were prescribed trittiko due to various sexual problems, the age of the patients was from 17 up to 53 years old.

All patients were divided into three groups.

The first group included patients suffering from various sexual disorders, predominantly of psychogenic origin, but with satisfactory erectile function, a total of 6 patients.

The second group included patients suffering from purely psychogenic erectile dysfunction, a total of 20 patients.

The third group included patients with mixed erectile dysfunction, where the psychogenic component was clinically significant, in total 10 patients.

All patients in the complex of treatment included rational and suggestive psychotherapy, selective partner sex therapy and the drug trazodone (trittiko) 150 mg per day for 30-60 days. In addition, depending on the nature of the etiological factor and the severity of the disease, the treatment complex included adaptogens, type 5 phosphodiesterase inhibitors, and local decompression courses.

Results were assessed using the International Erectile Function Index (IIEF).

Results.

First group.

It included 6 patients aged 17 to 33 years. All of them suffered from neurosis of expectation of failure, and in 2 patients the neurosis was combined with a depressive syndrome and decreased libido, in another 2 patients with psychogenic anejaculatory syndrome and in 2 patients with premature ejaculation syndrome. All patients were prescribed trazodone (trittiko) at a dose of 150 mg for 60 days as monotherapy. Against the background of drug therapy for the treatment of failure expectation neurosis, rational and suggestive psychotherapy was carried out, and for the treatment of psychogenic anejaculatory syndrome and premature ejaculation syndrome, partner sex therapy was carried out.

General satisfaction with sexual function in patients of this group after treatment increased from 4 to 9 points.

Second group.

It included 23 patients with psychogenic erectile dysfunction aged 20 to 52 years. All of them suffered from failure expectation neurosis of varying degrees. At the same time, in one patient, neurosis was combined with an organic personality disorder, in two – with severe onanophobia, which led to social maladaptation of patients, in two – with a syndrome of coded sexual reactions, and in one – with a hysterical syndrome. The patients of this group were divided into three subgroups according to the degree of erectile dysfunction.

1. Of seven patients with mild erectile dysfunction, trazodone (trittico) was given as monotherapy, and five were given in combination with phosphodiesterase type 5 inhibitors with good effect.

Erectile function score increased from 17 to 23 points.

2. Of the eight patients with moderate erectile dysfunction, in addition to trazodone (trittico) and phosphodiesterase type 5 inhibitors, two were prescribed aphrodisiacs, and two additionally received a course of local decompression.

In six patients the result was satisfactory. The evaluation of erectile function has risen from 11 to 23 points.

In one patient with psychogenic erectile dysfunction, which included hysterical neurosis, the administration of trazodone (trittiko) and type 5 phosphodiesterase inhibitors in combination with rational and suggestive psychotherapy did not lead to an improvement in erectile function. Subsequently, the patient was referred to the Clinic of Neurosis for specialized psychotherapeutic treatment.

In one patient with psychogenic erectile dysfunction due to coded sexual response syndrome and prolonged sexual abstinence, despite the appointment of trazodone (trittiko), phosphodiesterase type 5 inhibitors, adaptogens in combination with rational and suggestive psychotherapy did not lead to an improvement in erectile function. He refused further treatment.

3. Of the eight patients with severe erectile dysfunction, in addition to trazodone (trittico) and phosphodiesterase type 5 inhibitors, two additionally received a course of local decompression. In 7 patients the result was satisfactory. The evaluation of erectile function has risen from 8 to 22 points.

One patient, despite taking trazodone (trittico), type 5 phosphodiesterase inhibitors, adaptogens, as well as multiple sessions of rational and suggestive psychotherapy, the failure expectation neurosis turned out to be extremely resistant, and there was no improvement in erectile function, he was offered endophalloprosthetics.

Third group.

It included 7 patients with mixed erectile dysfunction aged 21 to 51 years. All patients in this group were diagnosed with failure expectation neurosis, while in 4 patients erectile dysfunction had a significant vasculogenic factor, 2 had androgen deficiency, and 1 had a neurogenic factor (Thompson’s myopathy). All of them had a predominantly severe degree of erectile dysfunction.

Patients with androgen deficiency, in addition to testosterone replacement therapy, were prescribed trazodone (trittiko) and phosphodiesterase type 5 inhibitors with good effect.

A patient with Thompson’s myotonia, in addition to the main neurological treatment, was also prescribed trazodone (trittiko) and phosphodiesterase type 5 inhibitors with good effect.

Of the four patients with a vasculogenic component of erectile dysfunction, two received trazodone (trittico) in combination with a phosphodiesterase type 5 inhibitor, and another two were treated with local decompression. In two patients, the course of treatment was effective. Erectile function score rose from 7 to 22 points. Two patients with venous erectile dysfunction had no effect from the treatment.

Subsequently, due to the distal form of venous insufficiency of erection, an operation was performed to ligate the deep dorsal vein and circumflex veins with a good effect.

In the second patient, surgical treatment of venous erectile dysfunction did not give any effect, and the patient underwent endofalloprosthesis.

Conclusions.

1. In general, the drug trazodone (trittico) showed good efficacy in the treatment of psychogenic erectile dysfunction and erectile dysfunction of mixed origin, where the psychogenic component is clinically significant.

2. In some cases of psychogenic erectile dysfunction, in addition to the standard complex of treatment, including rational and suggestive psychotherapy, trazodone (trittiko), phosphodiesterase type 5 inhibitors, adaptogens, local decompression, specialized psychotherapeutic treatment is indicated when the sexological syndrome is only a component of a psychopathological disorder .

3. In cases of erectile dysfunction of mixed origin, with a significant vasculogenic component, treatment of vasculogenic dysfunction should be carried out first, despite the large clinical significance of the psychogenic component.

Literature.

1. NIH Consensus Conference. Impotence. NIH round table on consensus building on impotence. JAMA, 1993; 270: 83-90

2. Litvin M.S., Nid R.J., Dhanani N. The impact of health status on quality of life in men with erectile dysfunction. Journal of General Medicine of Internal Diseases, 1998; 13: 159-66

3. Melman A., Gingell J.C. The epidemiology and pathophysiology of erectile dysfunction // J. Urol. – 1999.

4 . Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB.

Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the

Massachusetts male aging study. J Urol 2000;163(2):460-3. PMID: 10647654

5. Feldman H. A., Goldstein I., Hatzichristou D. G. et al. Impotence and its medical ad psychosocial correlates: results of the Massachusetts Male Aging Study. J. Urol. (Baltimore) 1994; 151:54-61.

6. Pushkar D.Yu. Rasner P.I. Drug treatment of erectile dysfunction: a preliminary comparison of existing methods. Pharmateka. 2004. No. 3/4. C. 1-4.

7. Lizza E.F., Rosen R.C. Definition and classification of erectile dysfunction: Report of the Nomenclature Committee of the International Society of Impotence Research. // Int J Impot Res – 1999.

8. Lance R., Apbo M., Kostable R. A., Stears W. D. Oral trazodone as empiric treatment for erectile dysfunction: a retrospective review. Urology, 1995; 46: 117-20

9. Erdpi I. New oral therapies for the treatment of erectile dysfunction. British Journal of Urology, 1998; 81: 122-7

10. Krege S., Göpel M., Sperling G., Michel M. K. Affinity of trazodone for α1-α2 adrenoceptors of the penis in humans. BJU Int, 2000; 85: 959-61

11. . A. Fink, R. McDonald, I. R. Rootks, and T. J. Wilt. Trazodone as a treatment for erectile dysfunction: a systematic review and meta-analysis Minneapolis, USA. BJU International, 2003.

12. Kurt U., Ozkardes G., Altug U., Germiyanoglu J., Gurdal M., Erol D. Effectiveness of antiserotonergic substances in the treatment of erectile dysfunction. Journal of Urology, 1994; 152: 407-9

13. Montorsi F., Strumbi L. F., Guazzoni G. and colleagues. The effect of yogimbin-trazodone on psychogenic impotence: a randomized, double-blind, placebo-controlled study. Urology, 1994; 44: 732-6

14. Kostabile R.A., Spevak M. Oral trazodone is not effective for erectile dysfunction: a double-blind, placebo-controlled study. Journal of Urology, 1999; 161: 1819-22

15. Tkachuk V.N., Lukyanov A.E. The effectiveness of the drug “Trittico” in the treatment of erectile dysfunction of psychogenic origin. Abstracts of the conference “Men’s Health” Moscow, 2006

Trazodone – description of the substance, pharmacology, use, contraindications, formula

Contents

• Structural formula

• Russian name

• English title

• Latin name

• chemical name

• Gross formula

• Pharmacological group of the substance Trazodone

• Nosological classification

• CAS code

• pharmachologic effect

• Characteristic

• Pharmacology

• The use of the substance Trazodone

• Contraindications

• Application restrictions

• Use during pregnancy and lactation

• Side effects of Trazodone

• Interaction

• Overdose

• Dosage and administration

• Precautionary measures

• Trade names with the active ingredient Trazodone

Structural formula

Russian name

Trazodone

English name

Trazodone

Latin name

Trazodonum ( genus Trazodoni)

Chemical name

-on (as hydrochloride)

Gross formula

C ₁₉ H ₂₂ ClN ₅ O

Pharmacological group of the substance Trazodone

Antidepressants

Nosological classification

ICD-10 code list

CAS code

19794-93-5

Pharmacological action

Pharmacological action –

antidepressant .

Characteristic

Thiazolopyridine derivative; according to its chemical structure, it does not belong to tricyclic, tetracyclic or other groups of antidepressants. Trazodone hydrochloride is a white, odorless, crystalline powder that is readily soluble in water. Molecular weight 408.33.

Pharmacology

The mechanism of action is not fully understood. Preclinical studies have shown that trazodone selectively inhibits the reuptake of serotonin by brain synaptosomes and acts as a 5-HT _2A/2C serotonin receptor antagonist. Does not inhibit MAO, does not stimulate the central nervous system. It is an antagonist of alpha ₁ -adrenergic receptors.

Relieves mental (affective tension, fear, insomnia) and somatic (palpitations, headache, myalgia, frequent urination, increased sweating) manifestations of anxiety. Increases the depth and duration of sleep in depressed patients, restores the physiological structure of sleep.

Well absorbed from the gastrointestinal tract. Taking trazodone during or immediately after a meal slows down the absorption rate, reduces max “> C _max of trazodone in the blood and increases max”> T _max (T _max is 0.5–2 hours). Plasma protein binding 89-95%. Passes through histohematic barriers, including the BBB. It is metabolized in the liver, mainly with the participation of the CYP3A4 isoenzyme of cytochrome P450, the active metabolite is m-chlorophenylpiperazine. 1/2″>T _1/2 biphasic: early phase 3-6 hours, late 5-9h; in some patients cumulation is possible. Excreted in bile (20%) and urine (75%, including 70% as inactive metabolites) within 98 hours after ingestion.

There is evidence of the effectiveness of trazodone in bulimia, kleptomania, diabetic neuropathy pain syndrome and other types of chronic pain, phobias, incl. agoraphobia, panic attacks, acute withdrawal syndrome in alcoholism and for the prevention of migraine.

The use of the substance Trazodone

Depressive states of various etiologies (endogenous, psychotic, neurotic, somatogenic, etc. ) with severe anxiety, tension.

Contraindications

Hypersensitivity, alcohol intoxication and intoxication with sleeping pills, age up to 6 years.

Restrictions on use

Myocardial infarction (early recovery period), AV blockade, arterial hypertension (dose adjustment of antihypertensive drugs may be required), ventricular arrhythmia, history of priapism, liver and / or kidney failure, age up to 18 years.

Use in pregnancy and lactation

Should not be used by pregnant women. Animal studies have shown that trazodone at doses 30 to 50 times the MRHD causes congenital malformations and increases the rate of fetal resorption.

FDA fetal category C.

Stop breastfeeding during treatment. Trazodone and its metabolites are found in the milk of lactating rats. It is not known whether trazodone is secreted into human breast milk.

Side effects of the substance Trazodone

From the nervous system and sensory organs: fatigue, weakness, headache, dizziness, insomnia, drowsiness, agitation, psychosis, hypomania, hallucinations, tremor, muscle twitching, grand mal seizures (grand mal) , aphasia, ataxia, akathisia, dyskinesia, paresthesia, confusion, syncope, blurred vision, diplopia.

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): arterial hypotension, incl. orthostatic; atrial fibrillation, arrhythmias (including tachycardia and bradycardia, ectopic ventricular rhythms), congestive heart failure, leukocytosis or leukopenia, neutropenia (usually minor), hemolytic anemia, methemoglobinemia.

From the digestive tract: increased appetite, dryness and unpleasant taste in the mouth, hypersalivation, caries, diseases of the periodontal tissues, candidiasis of the oral cavity, nausea, vomiting, flatulence, diarrhea, constipation, cholestasis, increased levels of bilirubin and amylase in plasma blood, jaundice.

From the genitourinary system: urinary retention, increased urination, hematuria, premature menstruation, hirsutism, increased libido, priapism, impotence, retrograde ejaculation.

Allergic reactions: skin rash, urticaria.

Other: myalgia, chest pain, alopecia, psoriasis, edema.

Interaction

Unlike typical antidepressants, it does not reduce the depriming effects of reserpine, weakens the central effect of amphetamine and the peripheral effect of norepinephrine. Potentiates the effect of drugs that depress the central nervous system (including barbiturates, tricyclic antidepressants, antihistamines, clonidine, alcohol), anticholinergics and muscle relaxants. When taken simultaneously with antihypertensive drugs, the risk of orthostatic hypotension increases. Weakens the effect of psychostimulants. Increases the plasma concentration of digoxin and phenytoin. It should not be used simultaneously with MAO inhibitors.

Overdose

Symptoms: nausea, vomiting, drowsiness, dizziness, lowering blood pressure, impaired coordination, priapism, epileptiform seizures, ECG changes, respiratory arrest, worsening of adverse reactions.

Treatment: gastric lavage, forced diuresis, activated charcoal, maintenance of vital functions, symptomatic therapy. There is no specific antidote.

Dosage and Administration

Orally . Adults: the initial dose is 100 mg, once at bedtime, if necessary, the dose is increased by 50 mg / day every 3-4 days until a therapeutic effect is achieved. The maximum daily dose on an outpatient basis is 450 mg, in stationary conditions – 600 mg. For elderly and debilitated patients, the initial dose is up to 100 mg / day, if necessary, can be increased to 300 mg / day. Children 6–18 years: 1.5–2 mg/kg/day, if necessary, increase the dose to 6 mg/kg/day.

Precautions

During treatment, a complete blood count should be performed regularly (for the timely detection of leuko- and neutropenia), ECG monitoring is desirable in patients with cardiovascular diseases. Careful monitoring of patients with suicidal tendencies is required, especially in the first weeks of treatment. Treatment is immediately stopped with the development of priapism, severe neutro- and leukopenia; in other cases, drug withdrawal should be carried out gradually.