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Trazodone (Oleptro) - Uses, Dose, Side effects, MOA, Brands

Trazodone (Oleptro) is a tetracyclic antidepressant medication that is used for treating patients with unipolar depression, aggression, and insomnia.

Trazodone (Oleptro) Uses:

Major depressive disorder (unipolar):
for the treatment of major depressive illness that is unipolar.

Off Label Use of Trazodone in Adults:
- For the treatment of aggression and restlessness in patients of dementia
- Insomnia

Trazodone (Oleptro) Dose in Adults

Trazodone (Oleptro) Dose as an alternative agent in the treatment of Aggressive or agitated behavior associated with dementia (off-label): Oral:

Immediate release:
- Initial: 25 to 50 mg OD at bedtime;
- depending on reaction and tolerance, titrate up to 300 mg/day in 1 to 3 split doses.
- Some experts prefer not going beyond 100 to 150 mg/day.

Trazodone (Oleptro) Dose as an alternative agent in the treatment of Insomnia (off-label): Oral:

Immediate release:
- Usual dose: 50 mg to 100 mg at bedtime.
- Note: may begin with 12.5 to 50 mg eg for patients on palliative care.
- The dose may be up titrated up to 200 mg according to tolerance and response. (eg, in patients with drug abuse history)
- In such patients, trazodone is more preferable because of decreased potential for dependence.

Trazodone (Oleptro) Dose in the treatment of insomnia in patients with depression (as an adjunct to other appropriate antidepressant treatment [eg SSRI]): Oral:

Immediate release:
- Usual dose: 50 to 300 mg at bedtime.
- May titrate up to 600 mg/day however no added benefit is established and there is an increased risk for toxicity.

Trazodone (Oleptro) Dose as an alternative agent in the treatment of major depressive disorder (unipolar): Oral:

Immediate-release:
- Initial: 50 mg twice daily; can be up titrated by 50 mg/day every 3 to 7 days until total 75 to 150 mg BD.
- usual dosage range 200 to 400 mg/day;
- The maximum 600 mg/day.
- However, increased potential for toxicity with a higher dose.
- >400 mg/day is Contraindicated in patients with cardiovascular disease.
- To avoid sedation, divide the daily dose and administer the smaller amount during the day and the bigger dose just before bed.
- Manufacturer’s labeling:
  - Dosing in the prescribed material could not follow current clinical recommendations.
    - Initial: 150 mg/day in divided doses;
    - highest dosage: 400 mg per day; 600 mg per day (patients) (outpatients).
Extended-release:
- Initial: 150 mg once daily at bedtime;
- Depending on the clinical response and tolerance, the dose may be increased by 75 mg/day every three days.
- The maximum dose: 375 mg/day
Discontinuation of therapy:
- To avoid withdrawal symptoms don't stop at once, down-titrate slowly over 2 to 4 weeks.
- Resuming the previously prescribed dose or reducing the dose more gradually are the two options to consider if intolerable withdrawal symptoms develop after a dose reduction.
- Tapering over more than three months may be beneficial for some individuals receiving long-term treatment (>6 months), such as those with a history of discontinuation syndrome.
- Evidence supporting ideal taper rates is limited.
Switching antidepressants:
- Limited data are available.
- Consider the degree of symptom management desired, the risk of discontinuation symptoms, potential drug interactions, half-life, side effects, and pharmacodynamics.
- Crose titration: while gradually increasing the new antidepressant, cease the previous antidepressant).
- immediate switch (suddenly stop the first antidepressant and then start a new antidepressant at an equal or lower dose with slow up-titration).
- Cross-titration is common for most switches but is not advised when transitioning to or from an MAOI (e.g., over 1 to 4 weeks depending on tolerance and withdrawal symptoms).
- While switching drugs within the same or related classes (e.g., switching two SSRIs), when taking an antidepressant for less than a week, or when discontinuing because of side effects, a direct switch is preferred.
Switching to or from an MAOI:
- Give a 14-day break between stopping an MAO inhibitor and starting trazodone, and the opposite is true.

Trazodone (Oleptro) Dose in Childrens

Trazodone (Oleptro) Dose in the treatment of Insomnia; sleep disturbances (in children with comorbid psychiatric disorders):

There are few data on this, although it is often used clinically in kids with co-occurring psychiatric illnesses (eg, mood disorder, anxiety disorder, developmental delay with ADHD): Oral:

Immediate-release formulation:
- Children 18 months to <3 years:
  - Initial: 25 mg/dose at bedtime; can be increased by 25mg every 2 weeks to a maximum dose: 100 mg/dose
- Children 3 to 5 years:
  - Initial dose of 50 mg at bedtime; maximum dose of 150 mg, which can be increased by 25 mg every two weeks. Do not exceed 200 mg/day; the range is 0.5 to 2 mg/kg/day.
- Children >5 years and Adolescents:
  - Initial: 0.75 to 1 mg/kg/dose or 25 to 50 mg at bedtime;
  - When used for palliative care, documented trials in young children with comorbid psychiatric illnesses (such as ADHD, autism, developmental delay), or sleep bruxism, multiple daily doses may be necessary; 25 to 50 mg/dose increase gradually to twice or three times daily as necessary (not to go beyond adult dose)

Trazodone (Oleptro) Dose in the prophylaxis of Migraine:

Children and Adolescents ≥7 years: Oral:
- Immediate-release formulation:
  - 1 mg/kg/day in 3 divided doses;
  - maximum dose: 150 mg/dose.

Discontinuation of therapy:

To avoid withdrawal symptoms do not stop at once, down titrate slowly.
No specific duration of taper established. According to the antidepressant's half-life, APA and NICE guidelines advise tapering therapy over at least a few weeks; antidepressants with a shorter half-life may require a slower taper.
WFSBP guidelines advise tapering over 4 to 6 months for those receiving long-term therapy.
If withdrawal symptoms appear, taper more gently, or stop using the drug if it is not tolerated.

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:

Give a 14-day break before starting trazodone after stopping an MAO medication, and vice versa.

Trazodone (Oleptro) Use with other MAO inhibitors (linezolid or IV methylene blue):

Patients taking IV methylene blue or linezolid should not take it.
If linezolid or IV methylene blue use cannot be avoided in patients on trazodone, stop trazodone at once and administer linezolid or IV methylene blue.
Until 24 hours following the last dosage of linezolid or IV methylene blue, or for a period of two weeks, keep an eye out for serotonin syndrome. 24 hours after the last linezolid or IV methylene blue dosage, start taking trazodone again.

Trazodone Pregnancy Category: C

Multidisciplinary approach is required to treat depression during pregnancy.
This includes mental health professionals, primary care providers, and pediatricians.
The American Psychiatric Association advises that pregnant women carefully weigh the risks and benefits of using trazodone, or any other treatment for depression, during pregnancy.
Women at high risk of postpartum depression can start treatment after they have given up on medication during pregnancy.

Use of Trazodone while breastfeeding

Breast milk contains Trazodone.
If RID is less than 10%, lactation can be continued. Other studies suggest that a cutoff of RID of 5% should be used for psychotropic drugs.
The RID of Trazadone was calculated with a 100 ng/mL milk concentration, indicating a daily infant dose via breastmilk of 0.015 mg/day.
This was achieved by giving a single dose to six healthy breastfeeding women of trazodone 50mg.
There are not many studies on the effects of trazodone on lactating women.
Monitor breastfeeding mothers who use psychotropic drugs daily to alter their sleep, dietary habits, or behavioral changes.
Also monitor infants' growth and neurodevelopment.
Before starting trazodone, it is important to consider the risks and benefits.
If there are no contraindications, breastfeeding mothers who have been successfully treated with trazodone in pregnancy will be able to continue taking it while they breastfeed.

Dose in Kidney Disease:

No data is available, use cautiously.

Dose in Liver disease:

No data is available, use cautiously.

Common Side Effects of Trazodone (Oleptro):

Central Nervous System:
- Drowsiness
- Dizziness
- Headache
- Nervousness
- Fatigue
Gastrointestinal:
- Xerostomia
- Nausea And Vomiting
Ophthalmic:
- Blurred Vision

Less Common Side Effects Of Trazodone (Oleptro):

Cardiovascular:
- Hypotension
- Syncope
- Palpitations
- Sinus Bradycardia
- Tachycardia
Central Nervous System:
- Confusion
- Ataxia
- Heavy Headedness
- Malaise
- Lack Of Concentration
- Disorientation
- Akathisia
- Chest Pain
- Delusions
- Hallucination
- Hypomania
- Memory Impairment
- Numbness
- Paresthesia
- Speech Disturbance
Endocrine & Metabolic:
- Weight Loss
- Weight Gain
- Change In Menstrual Flow
- Increased Libido
Gastrointestinal:
- Constipation
- Sialorrhea
- Increased Appetite
- Gastrointestinal Disease
- Diarrhea
- Flatulence
Genitourinary:
- Urinary Frequency
- Hematuria
- Retrograde Ejaculation
- Urinary Hesitancy
- Impotence
- Early Menses
Hematologic & Oncologic:
- Anemia
Hypersensitivity:
- Hypersensitivity Reaction
- Angioedema
Neuromuscular & Skeletal:
- Muscle Twitching
- Tremor
- Myalgia
Ophthalmic:
- Eye Redness
- Eye Pruritus
- Asthenopia
Respiratory:
- Dyspnea
- Paranasal Sinus Congestion
- Nasal Congestion

Frequency of side effects Not Defined:

Cardiovascular:
- Ventricular Premature Contractions
- Hypertension
Central Nervous System:
- Suicidal Tendencies
- Suicidal Ideation

Contraindications to Trazodone (Oleptro):

hypersensitivity to any ingredient in the recipe, including trazodone
The purpose of MAOIs is to treat psychiatric disorders (concurrently, or within 14 days after stopping trazodone)
Patient on intravenous or linezolid.

Warnings and precautions

Bleeding Risk:
- Serotonin reuptake inhibitors, such as SSRIs, have been related to bleeding.
- This can range from minor bruising and epistaxis, to potentially fatal hemorhage.
- In addition, the related drug trazodone may similarly hinder platelet aggregation, raising the risk of bleeding incidents.
Cardiac arrhythmias
- There is a low risk of conduction abnormalities in antidepressants.
- With immediate-release formulations, ventricular tachycardia and QT prolongation (with and without torsades-de-pointes) have been recorded.
- If you have a history of cardiac illness, such as a MI, a stroke, or faulty conduction, use with caution.
- It has also been reported that isolated PVCs, ventricular couplests and tachycardia have been reported.
- CYP3A4 inhibitors can increase QT prolongation risk and other cardiac arrhythmias.
- While recovering from acute recovery of MI, it is contraindicated.
Depression in the CNS:
- CNS depression can lead to decreased mental alertness and CNS depression.
Fractures
- An increase in bone fractures.
- Antidepressant users who also have unexplained bone pain, point tenderness, or edoema may develop fragility fractures.
Ocular effects
- In predisposed patients, narrow-angle glaucoma can occur.
- Patients with narrow angle glaucoma risk factors who have not undergone iridectomy should be assessed.
Orthostatic hypotension, syncope
- Orthostatic hypotension can lead to syncope (increased danger compared to other antidepressants); avoid these side effects if you have a high risk of developing them or if you are allergic to hypovolemia or any drugs that may cause hypotension or bradycardia.
Priapism
- Rarely, a painful erection can last more than six hours.
- For an erection lasting more than 4 hours, seek medical attention.
- Be careful when using this product in situations that could also lead to priapism, such as multiple myeloma or sickle cell anemia.
Serotonin syndrome
- When serotonergic drugs (such as SSRIs and SNRIs) are combined with other serotonergic drugs and substances that affect the metabolism of serotonin, such as triptans TCAs, fentanyl and buspirone, tramadol or buspirone, St. John's wort or tryptophan, serotonin syndrome (SS), a potentially fatal condition, may result (eg MAO inhibitors to treat psychiatric methylene blue, intravenous methyleneblue blue)
- Be on the lookout for SS in patients, including mental changes (such as agitation, hallucinations, or coma), autonomic stability (such as tachycardias, labile pressure, diaphoresis), neuromuscular disorders (such as tremors, rigidity, and myoclonus), GI symptoms (such as nausea, vomiting, and diarrhoea), and/or seizures.
- Stop using the product immediately if you notice any symptoms or signs.
Hyponatremia and SIADH
- SSRIs have been linked to severe hyponatremia and SIADH in patients with diuretics or elderly who are dehydrated.
Hepatic impairment
- Use caution in the presence of liver disease.
Hypomania/mania:
- Some patients may experience psychosis.
- Bipolar disorder can lead to hypomania and mania. Before you start treatment, make sure you rule out this condition.
- Bipolar disorder is not a condition that can be treated with a single agent.
- The FDA has not approved Trazodone for bipolar depression treatment.
Renal impairment
- Avoid kidney disease.
Seizure disorder
- Patients with seizure disorders, brain damage, brain trauma, alcoholism or any drugs that may lower the seizure threshold should be cautious.

Trazodone: Drug Interaction

Risk Factor C (Monitor therapy)
Alcohol (Ethyl)	may intensify TraZODone's negative or harmful effects. Effects on drowsiness, vertigo, and manual dexterity in particular may be improved.
Alizapride	CNS depressants may have an enhanced CNS depressant impact.
Antiemetics (5HT3 Antagonists)	could make serotonin modulators' serotonergic effects stronger. Serotonin syndrome might occur from this.
Antipsychotic Agents	Serotonin modulators might make antipsychotic drugs more harmful or toxic. Serotonin modulators, in particular, may enhance dopamine blockade, potentially raising the risk for neuroleptic malignant syndrome. Serotonin modulators' serotonergic effects may be strengthened by antipsychotic drugs. Serotonin syndrome might occur from this.
Antipsychotic Agents (Phenothiazines)	could intensify the negative or harmful effects of serotonin reuptake inhibitors and antagonists. This may specifically appear as signs of neuroleptic malignant syndrome or serotonin syndrome. Antipsychotic Agents may have a greater hypotensive effect when combined with Serotonin Reuptake Inhibitor/Antagonists (Phenothiazines).
Aprepitant	may elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Brexanolone	CNS Depressants may enhance the CNS depressant effect of Brexanolone.
Brexanolone	Serotonin Reuptake Inhibitor/Antagonists may enhance the CNS depressant effect of Brexanolone.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Bromopride	May enhance the CNS depressant effect of CNS Depressants.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CNS Depressants	Other CNS depressants' harmful or toxic effects might be exacerbated.
CYP3A4 Inducers (Moderate)	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	May slow down CYP3A4 substrate metabolism (High risk with Inhibitors).
Deferasirox	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Dimethindene (Topical)	CNS depressants may have an enhanced CNS depressant impact.
Doxylamine	CNS depressants may have an enhanced CNS depressant impact. Management: The producer of the pregnancy-safe drug Diclegis (doxylamine/pyridoxine) particularly advises against combining it with other CNS depressants.
Dronabinol	CNS depressants may have an enhanced CNS depressant impact.
Duvelisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Esketamine	May enhance the CNS depressant effect of CNS Depressants.
Fosaprepitant	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Fosnetupitant	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Fosphenytoin	May lower the level of TraZODone in the serum. Fosphenytoin's serum levels may rise in response to TraZODone.
Haloperidol	The QTcprolonging effect of haloperidol may be enhanced by QT-prolonging agents (Indeterminate Risk - Caution).
HydrOXYzine	CNS depressants may have an enhanced CNS depressant impact.
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Lofexidine	May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
Metaxalone	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Methylphenidate	Serotonin modulators' harmful or toxic effects could be exacerbated. In particular, there may be an increased risk of serotonin syndrome or serotonin poisoning.
Metoclopramide	Serotonin modulators may intensify Metoclopramide's harmful or hazardous effects. This could appear as signs of neuroleptic malignant syndrome or serotonin syndrome.
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Mirtazapine	CNS Depressants may enhance the CNS depressant effect of Mirtazapine.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
Netupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Phenytoin	May lower the level of TraZODone in the serum. TraZODone may raise the level of phenytoin in the blood.
Piribedil	Piribedil's CNS depressing effects may be enhanced by other CNS depressants.
Pramipexole	The sedative effects of pramipexole might be enhanced by CNS depressants.
QT-prolonging Agents (Highest Risk)	The QTc-prolonging action of QT-prolonging Agents may be enhanced by QT-prolonging Agents (Indeterminate Risk - Caution) (Highest Risk). When using these medications together, watch out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.
ROPINIRole	The sedative effects of CNS depressants may increase those of ROPINIRole.
Rotigotine	Rotigotine's sedative effects may be boosted by CNS depressants.
Rufinamide	CNS depressants' harmful or toxic effects could be increased. Particularly, drowsiness and lightheadedness could be worsened.
Sarilumab	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Serotonin Modulators	The negative or hazardous effects of other serotonin modulators might be increased. Serotonin syndrome may start to develop. Nicergoline and Tedizolid are exceptions.
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Tedizolid	Could make serotonin modulators' serotonergic effects stronger. Serotonin syndrome might occur from this.
Tetrahydrocannabinol	CNS depressants may have an enhanced CNS depressant impact.
Tetrahydrocannabinol and Cannabidiol	CNS depressants may have an enhanced CNS depressant impact..
Tocilizumab	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Trimeprazine	CNS depressants may have an enhanced CNS depressant impact.
Warfarin	Warfarin's anticoagulant action could be lessened by TraZODone.
Risk Factor D (Consider therapy modification)
Blonanserin	Blonanserin's CNS depressing effects may be enhanced by other CNS depressants.
Buprenorphine	The CNS depressing impact of buprenorphine may be enhanced by CNS depressants. Treatment: If a patient has a high risk of abusing or injecting themselves with buprenorphine, consider reducing the doses of other CNS depressants and avoiding such medications. Buprenorphine should be started at lower doses in individuals who are currently taking CNS depressants.
BusPIRone	Serotonin Reuptake Inhibitor/Antagonists may improve their serotonergic effects. Treatment: Buspirone should only be used in combination with a strong serotonin reuptake inhibitor or antagonist. When combination treatment is therapeutically necessary, keep a vigilant eye out for any symptoms of serotonin syndrome or toxicity.
Chlormethiazole	May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.
CYP3A4 Inducers (Strong)	May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
CYP3A4 Inhibitors (Strong)	TraZODone serum concentration can rise. Treatment: If coupled with potent CYP3A4 inhibitors, take into account using a lower dose of trazodone and keep an eye out for any enhanced adverse effects (such as sedation and QTc prolongation).
Dabrafenib	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: When possible, look for substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects).
Droperidol	May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Enzalutamide	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring.
Flunitrazepam	CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.
HYDROcodone	CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Linezolid	May augment TraZODone's serotonergic effects. Serotonin syndrome might occur from this. Management: Whenever possible, look into alternatives to this combination and stop taking trazodone before taking linezolid. Starting linezolid at least two weeks after stopping trazodone should reduce the chance of an interaction.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
Methotrimeprazine	CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established.
MiFEPRIStone	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.
Mitotane	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.
Opioid Agonists	Opioid agonists' CNS depressing effects may be amplified by CNS depressants. Management: When at all possible, refrain from using benzodiazepines or other CNS depressants concurrently with opioid agonists. Only in the event that other treatment choices are insufficient should these medications be combined. Limit the duration and dosage of each medicine when used together.
OxyCODONE	CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Perampanel	May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination.
Selective Serotonin Reuptake Inhibitors	Serotonin Reuptake Inhibitor/Antagonists may improve their serotonergic effects. It might result in serotonin syndrome. Management: Take a look at your options and start off slowly. Look out for any signs or symptoms of serotonin poisoning in individuals receiving these combinations.
Sodium Oxybate	May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated.
St John's Wort	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
Suvorexant	CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Venlafaxine	May augment TraZODone's serotonergic effects. Serotonin syndrome might occur from this.
Zolpidem	CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.
Risk Factor X (Avoid combination)
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Conivaptan	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Dapoxetine	Serotonin modulators' harmful or toxic effects could be exacerbated.
Fusidic Acid (Systemic)	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Idelalisib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Methylene Blue	The serotonergic action of Methylene Blue may be strengthened with TraZODone. Serotonin syndrome might occur from this.
Monoamine Oxidase Inhibitors	Could intensify the negative or harmful effects of serotonin reuptake inhibitors and antagonists. While interactions between methylene blue and linezolid are anticipated, their usage is not advised in the same way as other monoamine oxidase inhibitors. For more information, consult the monographs for those agents. Exceptions: Methylene Blue, Tedizolid, and Linezolid.
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
Saquinavir	May enhance the QTc-prolonging effect of TraZODone. Saquinavir may increase the serum concentration of TraZODone.
Thalidomide	The CNS depressing effect of thalidomide may be enhanced by CNS depressants.

Monitoring parameters:

liver function before starting therapy, maybe obtained during treatment as needed.
Monitor for suicidal thoughts especially when starting therapy or while changing dose.
Symptoms of serotonin syndrome
Monitor signs of hypotension or orthostasis

How to administer Trazodone (Oleptro)?

Oral:

Immediate-release tablet:
- Administer shortly after a meal; swallow whole.
- Can be broken along the scoreline.
Extended-release tablet:
- Administer in the fasting state; Tablet may be broken along the scoreline but avoid crushing or chewing. Do not take with food.

Mechanism of action of Trazodone (Oleptro):

Inhibition by 5HT receptor antagonist and changing adrenoreceptor sunlight sensitivity.
Also, has antihistamine activity and anti-alpha1 receptor activity.

The onset of action:

Therapeutic (antidepressant): may take 6 weeks.

Absorption:

Well absorbed.
Wwhen taken with food, there is an improvement in absorption and a reduction in peak concentration and peak time.
Extended-release: C-max increases ~86% when taken with high gat content food vs on an empty stomach

Protein binding:

89% to 95%

Metabolism:

Hepatic via CYP3A4 (extensive) to an active metabolite (mCPP)

Bioavailability:

100%.

Half-life elimination:

5 to 9 hours, prolonged in obese patients

Time to peak, serum:

30 to 100 minutes for immediate release; longer with food (up to 2.5 hours)
Extended-release: 9 hours; not significantly affected by food

Excretion:

Primarily urine (74%, <1% excreted unchanged);
secondarily feces (~21%)

International Brand Names of Trazodone:

Oleptro
APO-TraZODone
APO-TraZODone D
DOM-TraZODone
MYLAN-TraZODone
PHLTraZODone HCl
PHL-TraZODone
PMS-TraZODone
RATIO-TraZODone
TEVATraZODone
TraZODone-100
TraZODone-150
TraZODone-50
Azonz
Deprax
Deprel
Depresil
Desirel
Desyrel
Devidon
Donaren
Donaren Retard
Mesyrel
Molipaxin
Nestrolan
Oleptro
Pragmarel
Reslin
Taxagon
Taxagon AC
Tazodac
Thombran
Trazo
Trazodil
Trazodone-Continental
Trazolan
Trazone
Trazonil
Trittico
Trittico AC
Trittico CR
Trittico Prolonged-Release
Zodonrel

Trazodone Brand Names in Pakistan:

Trazodone 50 mg Tablets in Pakistan
Deprel	Adamjee Pharmaceuticals (Pvt) Ltd.
Trazolam	Organic Pharmaceuticals.
Trodine	Amarant Pharmaceuticals (Pvt)

Trazodone 100 mg Tablets in Pakistan
Deprel	Adamjee Pharmaceuticals (Pvt) Ltd.
Trazolam	Organic Pharmaceuticals.
Trodine	Amarant Pharmaceuticals (Pvt)

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