Side effects of Trazodone
From the nervous system and sensory organs:
fatigue, weakness, headache, dizziness, insomnia, drowsiness, agitation, psychosis, hypomania, hallucinations, tremor, muscle twitching, grand mal seizures,
aphasia
, ataxia, akathisia, dyskinesia, paresthesia, confusion, syncope, blurred vision, diplopia.
From the cardiovascular system and blood (hematopoiesis, hemostasis):
arterial hypotension, incl. orthostatic; atrial fibrillation, arrhythmias (including tachy- and bradycardia, ectopic ventricular rhythms), congestive heart failure, leukocytosis or leukopenia, neutropenia (usually minor), hemolytic anemia, methemoglobinemia.
From the gastrointestinal tract:
increased appetite, dryness and unpleasant taste in the mouth, hypersalivation, caries, diseases of the periodontal tissues, oral candidiasis, nausea, vomiting, flatulence, diarrhea, constipation, cholestasis, increased levels of bilirubin and amylase in the blood plasma, jaundice.
From the genitourinary system:
urinary retention, increased frequency of urination, hematuria, premature menstruation, hirsutism, increased libido, priapism, impotence, retrograde ejaculation.
Allergic reactions:
skin rash, urticaria.
Other:
myalgia, chest pain, alopecia, psoriasis, edema.
Why is it important?
Trazodone has no analogues, and it is one of the most popular drugs in its class. “It is difficult to reliably assess the popularity of trazodone among other psychopharmacological drugs, but I think I will not be mistaken if I say that it is among the top ten antidepressants and the top twenty of all psychotropic drugs. I prescribe it with approximately the same frequency: one out of ten to fifteen prescriptions for antidepressants,” says Maxim Marachev.
Based on the data from the State Register of Medicines (GRLS), no more drugs have been registered under the generic name trazodone, that is, there are no analogues with this active substance on the domestic market. However, the doctor urged not to panic. “There is no direct analogue of trazodone on the Russian market, but this does not mean that its absence in pharmacies will lead to fatal consequences, the range of psychopharmacological agents is quite wide, and you can always find a replacement without losing anything significant in effectiveness/tolerability,” said doctor.
Interaction
Unlike typical antidepressants, it does not reduce the depressive effects of reserpine, weakens the central effect of amphetamine and the peripheral effect of norepinephrine. Potentiates the effect of CNS depressants (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 plasma concentrations of digoxin and phenytoin. Should not be used simultaneously with MAO inhibitors.
Interaction with ritonavir
The effect of short-term administration of ritonavir (200 mg twice daily for 2 days) on the pharmacokinetics of a single dose of trazodone (50 mg) was studied in 10 healthy subjects. It was shown that Cmax of trazodone increased by 34%, AUC by 2.4 times, T1/2 by 2.2 times, clearance decreased by 52%. Adverse effects including nausea, hypotension, and syncope have been observed when ritonavir and trazodone were used together. If ritonavir and trazodone are used concomitantly, a dose reduction of trazodone may be necessary.
Interaction with CYP3A4 isoenzyme inhibitors
In vitro studies of the metabolism of trazodone indicate the possibility of its interaction with inhibitors of the cytochrome P450 isoenzyme CYP3A4, such as ketoconazole, ritonavir, indinavir sulfate and fluoxetine. Inhibitors of CYP3A4 may lead to significant increases in plasma concentrations of trazodone, thereby increasing the likelihood of adverse events. Therefore, when used in combination with potent CYP3A4 inhibitors, the dose of trazodone should be reduced.
Interaction with carbamazepine
After co-administration of the CYP3A4 inducer carbamazepine (at a dose of 400 mg / day) with trazodone (100-300 mg daily), carbamazepine reduced the plasma concentrations of trazodone and m-chlorophenylpiperazine (the active metabolite) by 60 and 76%, respectively. Patients receiving trazodone and carbamazepine concomitantly should be closely monitored.
Interaction with warfarin
There are reports of changes (increase or decrease) in PT with simultaneous use of warfarin and trazodone.
Where and why did the antidepressant disappear?
"Dear Customer! The requested product, unfortunately, is not currently available in pharmacies,” says many pharmacy websites when trying to buy trazodone (sold under the sole trade name Trittico).
As AIDS.CENTER wrote, the Italian pharmaceutical company Angelini, which produces the drug, associated the interruptions with a change in the structure of the supply chain and the launch of a labeling system in July. This has become the reason that the process of introducing drugs into civilian circulation takes much longer than before.
At the same time, representatives of the single operator of the labeling system (CPRT) stated that not a single labeled package of the drug has yet been put into circulation in Russia, but the pharmaceutical company received permission from the Roszdravnadzor commission to continue supplying unlabeled packages of the antidepressant. “At the same time, Angelini has already ordered 226,000 marking codes, but has not yet applied them to the packaging. To date, there has not been a single request from the company to the CRPT technical support service, which would indicate any difficulties,” said representatives of the operator.
According to the analytical company DSM Group, sales of trazodone began to fall in the first ten days of August; in September, sales growth doubled, but from the middle of the month sales began to decline again. If in October 2022 more than 18,000 packages were sold in Russia, then during the same period in 2022 - only 13,500.
“I don’t remember any interruptions in the availability of trazodone specifically, but interruptions in medications in general and psychotropic medications in particular sometimes happen. We mostly learn about such situations from our patients who cannot purchase medicine in pharmacies. I am not aware of any interruptions at present with any other medications,” says the psychiatrist.
Precautions for the substance Trazodone
During treatment, a general blood test should be performed regularly (for 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. During treatment you should avoid drinking alcohol.
Use with caution during work for vehicle drivers and people whose activities involve increased concentration.
Trittico
Use during pregnancy and breastfeeding
The drug is contraindicated for use during pregnancy and lactation (breastfeeding).
Use for liver dysfunction
The drug should be prescribed with caution to patients with liver failure.
Use for renal impairment
The drug should be prescribed with caution to patients with renal failure.
Use in children
The use of the drug in children and adolescents under 18 years of age is contraindicated (the safety of trazodone for children has not been established).
Use in elderly patients
For elderly and debilitated patients, the initial dose is up to 100 mg/day in fractional doses or 1 time/day before bedtime. The dose may be increased under medical supervision, depending on the effectiveness and tolerability of the drug. Usually no dose exceeding 300 mg/day is required.
special instructions
People with depression have an increased risk of suicidal thoughts, self-harm, or suicide. The risk may last until significant remission occurs. Since improvement may not occur for the first few weeks of treatment or more, patients should be closely monitored until such improvement occurs. It is common clinical experience that the risk of suicide may increase in the early stages of recovery. It is known that patients with a history of suicidal events, or patients who exhibit a significant degree of suicidal ideation even before treatment, have a higher risk of suicidal ideation or suicide attempts, and should be closely monitored during treatment. The results of a meta-analysis of placebo-controlled clinical trials of antidepressants used in adults with mental disorders showed an increased risk of suicidal behavior in patients under the age of 24 years while taking antidepressants compared with placebo. Careful monitoring of patients, especially those at high risk, should accompany drug therapy, especially in its early stages and after dose changes. Patients (and their caregivers) should be warned to monitor for any clinical deterioration, suicidal behavior or thoughts, or unusual changes in behavior, and to immediately seek professional advice if such symptoms occur.
Since the drug has some adrenergic blocking activity, bradycardia and a decrease in blood pressure may develop. Therefore, caution should be exercised when prescribing the drug to patients with a tendency to prolong the QT interval, AV block of varying severity, and patients with a recent myocardial infarction.
When treated with trazodone in patients with bipolar disorder, depressive episodes can range from manic-depressive to manic psychosis. In these cases, it is necessary to interrupt treatment.
If you have epilepsy, use trazodone with caution, in particular avoiding sudden increases or decreases in dose.
With simultaneous use of trazodone with drugs that have serotonergic activity (tricyclic antidepressants, selective serotonin reuptake inhibitors, norepinephrine and serotonin reuptake inhibitors and MAO inhibitors) and antipsychotics, serotonin syndrome may occur.
When trazodone is used simultaneously with drugs containing St. John's wort, side effects may be more frequent.
When using trazodone, agranulocytosis may develop, so it is recommended to conduct peripheral blood tests, especially if there is a sore throat when swallowing and fever.
Trazodone is effective for sleep disorders in patients with depression, increases the depth and duration of sleep, and restores its physiological structure and quality.
The use of the drug does not affect body weight.
The drug is not addictive.
Impact on the ability to drive vehicles and operate machinery
During the period of use of the drug, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
What do patients say about the drug?
“I was prescribed Trittico last year and within a few months I was able to sort out a lot of problems in my personal and professional life. Yes, it was more expensive than most other antidepressants and did not have generics, but it was definitely worth it,” one of the patients who took Trittico tells AIDS.CENTER on condition of anonymity. “Just the other day I needed an antidepressant again, and it had to be replaced with the more aggressive Rexetine.”
There are many reviews online from people who have taken trazodone, most of them are positive. “The drug changed my life. Removed the anxiety completely. I adjusted my sleep pattern and improved its quality. I didn’t know that I could be a completely different person - full of energy, happy, calm, balanced. I didn’t have a single side effect other than the expected one – sedation,” writes a user under the nickname alice.
During the disruption, some patients may have to stop taking the drug or replace it with another. According to Marachev, if you do this under the supervision of a doctor, there will be no negative or dangerous side effects. “If you do it yourself, then there are many factors to consider (total duration of use, current dosage, tolerability, presence of adverse events, previous history of drug withdrawal/replacement, interactions with other medications, individual characteristics of the body, and much more). All these indicators are assessed by the doctor when deciding whether to cancel/replace the medication, so that this process is as simple as possible,” notes the specialist.
The situation is worsened by the pandemic - it has had a bad impact on everyone. As Ministry of Health expert Vladislav Kuchma said, after the outbreak of the epidemic, almost 86% of children developed various phobias, 40% of children can be expected to develop depression, and another 30% were diagnosed with computer vision syndrome.
According to French Health Minister Olivier Veran, the pandemic has caused an increase in depression in the country. “During September and October, the mental health of the French deteriorated significantly. This phenomenon was accompanied by a strong increase in the number of depressive states. Moreover, this was observed in relation to all segments of the population,” the minister said, adding that the hardest time is for people with low incomes, young people aged 18 to 24 years, as well as those who already had mental disorders.
Maxim Marachev expressed a similar opinion. “The coronavirus situation has affected absolutely everyone. The virus has become an additional stressor that everyone is forced to reckon with, and people with a more sensitive psyche certainly react to this situation by intensifying existing or developing new (coronaphobia) mental health problems,” he explained.
What will happen now?
According to the manufacturer, the drug was imported to Russia and is in the process of being put into circulation. This means that it may appear in pharmacies in the near future. AIDS.CENTER sources in pharmaceutical circles say that we will have to wait until the end of the year for the medicine.
According to Roszdravnadzor, more than 49,000 packages of the medicine were released into civilian circulation this year. There have been no reports of suspension or discontinuation of production of the drug.
“We can’t do anything; logistics is a very complicated process. Literally the day before our conversation, I called the representative office of the supplier company, where the representative of the company responsible for trazodone assured me that everything in their power had been done and the medicine was now in the distributors’ warehouses; the next stage was shipment directly to pharmacies. It follows from this that within the next few days the shortage of medicine must be replenished,” the doctor said.
