Trazodone
https://www.ncbi.nlm...pubmed/25920951
Antidepressant-induced galactorrhea and increases in prolactin levels have rarely been reported. Trazodone can potentiate the serotonergic activity of citalopram. To our knowledge, no cases of galactorrhea associated with use of trazodone have been reported to date.
https://www.ncbi.nlm...les/PMC4418332/
These findings suggest that trazodone could be effective therapy for patients with OSA (obstructive sleep apnea) without worsening hypoxemia.
https://www.ncbi.nlm...pubmed/26017199
Trazodone and omeprazole interaction causing frequent second-degree Mobitz type 1 atrioventricular (AV) block (Wenckebach phenomenon) and syncope: a case report and literature review.
A 54-year-old man who was a former smoker, with dyslipidemia, coronary artery disease, and anxiety disorder developed lightheadedness and syncope the morning of admission. He was taking trazodone 50 mg daily, omeprazole 20 mg daily, and simvastatin 20 mg at bedtime. He doubled the dose of trazodone 50 mg on the night prior to presentation to calm his anxiety. An electrocardiogram revealed sinus rhythm at 60 beats per minute and second-degree Mobitz type 1 atrioventricular (AV) block with 5:4 AV conduction. Results of basic metabolic panel, thyroid-stimulating hormone, and chest radiograph were normal. A transthoracic echocardiogram revealed aortic valve sclerosis. We tested for Lyme disease given his history of hunting in the woods 8 months prior to presentation, but the titer was negative. Trazodone and omeprazole were discontinued. By the 3rd day of medication discontinuation, all symptoms had resolved and the frequency of second-degree AV Mobitz type 1 AV block had decreased to once per hour.
https://www.ncbi.nlm...pubmed/26088119
Although trazodone is approved and marketed in most countries worldwide for the sole treatment of Major Depressive Disorder, the use for this medication is very common for many other conditions, such as primary or secondary insomnia, Generalised Anxiety Disorder, Panic Disorder, Post-Traumatic Stress Disorder and Obsessive- Compulsive Disorder. Other, not officially approved, uses of trazodone include: the treatment of bulimia, benzodiazepine and/or alcohol dependence or abuse, fibromyalgia, degenerative diseases of the central nervous system such as dementia and other organic disorders, schizophrenia, chronic pain, and diabetic neuropathy. In addition, due to its 5HT2A receptor antagonistic action, trazodone may be used to prevent the occurrence of initial and long-term side effects of SSRI, such as anxiety, insomnia and sexual dysfunction.
https://www.ncbi.nlm...pubmed/26174731
It is very effective in the treatment of depression, in anxiety and insomnia. Its known side effects mainly occur with prolonged use of daily doses of 150-200 mg. The ability to enhance drowsiness may be associated with some risk in elderly patients. This
clinical case illustrates an acute extrapyramidal event (movement disorders, like tardives) induced by a low dose of trazodone.
https://www.ncbi.nlm...pubmed/25376160
Prolonged-release trazodone was more effective than placebo in MDD and was well tolerated.
https://www.ncbi.nlm...pubmed/24023050
The bioactive intermediate metabolites of trazodone might cause hepatotoxicity (Liver toxicity).
https://www.ncbi.nlm...pubmed/27147406
Trazodone and milnacipran are the active antidepressant drugs that are being used in the treatment of psychiatric disorders. In this study, the in vitro genotoxic effects of trazodone and milnacipran have been determined in human peripheral blood lymphocytes by using chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), micronuclei (MN), and comet assays. 3.13; 6.25; 12.50; 25.00; 50.00; and 75.00 μg/mL concentrations of trazodone and 2.50; 5.00; 10.00; 20.00; 30.00; and 40.00 μg/mL concentrations of milnacipran were used. Trazodone and milnacipran significantly increased the frequency of CAs and SCEs compared with the control. Both of the active ingredients raised the MN frequency in a dose-dependent manner. Mitotic index was significantly decreased, but replication and nuclear division indices were not affected at all treatments. Trazodone was statistically increased the mean comet tail intensity, tail length, and tail moment at three concentrations (6.25; 12.50; and 25.00 μg/mL) compared with control. Two highest concentrations (50 and 75 μg/mL) of trazodone were toxic in the comet assay. Milnacipran increased the comet tail intensity, tail length, and tail moment at all concentrations. It is concluded that trazodone and milnacipran have clastogenic, mutagenic, and cytotoxic effects on human lymphocytes in vitro.
https://www.ncbi.nlm...pubmed/26187900
The second-generation selective 5-HT2 receptor antagonists and reuptake inhibitors (SARIs) class antidepressants are known to have fewer cardiovascular side effects than the older ones. However, several case reports showed that trazodone, one of the second-generation SARIs, induces QT prolongation, cardiac arrhythmia, and ventricular tachycardia. Although these clinical cases suggested trazodone-induced cardiotoxicity, the toxicological actions of trazodone on cardiac action potentials (APs) beyond the human ether-a-go-go related gene (hERG) remain unclear. To elucidate the cellular mechanism for the adverse cardiac effects of trazodone, we investigated its effects on cardiac APs and ion channels using whole-cell patch clamp techniques in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and transiently transfected human embryonic kidney cells (HEK293) with cardiac ion channel complementary DNA. Trazodone dose-dependently decreased the maximum upstroke velocity (Vmax) and prolonged the AP duration, inducing early after depolarizations at 3 and 10 μM that triggered ventricular arrhythmias in hiPSC-CMs. Trazodone also inhibited all of the major ion channels (IKr, IKs, INa, and ICa), with an especially high inhibitory potency on hERG. These data indicate that the prolonged AP duration and decreased Vmax due to trazodone are mainly the result of hERG and sodium ion inhibition, and its inhibitory effects on cardiac ion channels can be exhibited in hiPSC-CMs.
https://www.ncbi.nlm...les/PMC3987616/
A 26-year-old female outpatient presenting with a depressive state suffered from auditory hallucinations at night. Her auditory hallucinations did not respond to blonanserin or paliperidone, but partially responded to risperidone. In view of the possibility that her auditory hallucinations began after starting trazodone, trazodone was discontinued, leading to a complete resolution of her auditory hallucinations.
https://www.ncbi.nlm...pubmed/23661283
Acute treatment of mirtazapine impaired road-tracking performance and increased sleepiness, but sedative effects disappeared under repeated administrations. Trazodone did not affect driving performance or cognitive function under acute or repeated administrations.
https://www.ncbi.nlm...pubmed/23450804
The number of individual impairment clues detected is increased with trazodone. Trazodone 100 mg may cause cognitive driving impairment.
https://www.ncbi.nlm...les/PMC3693429/
Trazodone is effective in controlling a wide range of symptoms of depression, while avoiding the negative effects on sleep seen with SSRI antidepressants. The recently approved prolonged-release formulation should provide further optimization of this antidepressant and may be useful for enabling an appropriate therapeutic dose to be administered with improved patient compliance.
https://www.ncbi.nlm...les/PMC3165092/
Trazodone produced small but significant impairments of short-term memory, verbal learning, equilibrium, and arm muscle endurance across time points. Relative to placebo across test days, trazodone was associated with fewer nighttime awakenings, minutes of Stage 1 sleep, and self-reports of difficulty sleeping. On Day 7 only, slow wave sleep was greater and objective measures of daytime sleepiness lower with trazodone than with placebo. Although trazodone is efficacious for sleep maintenance difficulties, its associated cognitive and motor impairments may provide a modest caveat to healthcare providers.
https://www.ncbi.nlm...pubmed/22239013
Its performance was analyzed in individuals dependent on alcohol, benzodiazepines and opiates, as well as mixed addictions. Also raised the problem of influence of trazodone on the experience of pain, which maybe helpful in relieving withdrawal symptoms. The data show a positive effect of trazodone in individuals addicted to the SPA, although the mechanism by which trazodone works in the body is very complex and not yet fully understood. Its advantage is the relatively small panel of side effects. Although many of the analyzed studies were not placebo-controlled, the results are so promising that you can recommend on the basis of trazodone therapy in individuals addicted to the SPA.
https://www.ncbi.nlm...pubmed/22574377
Yimusake combined with trazodone hydrochloride is highly efficacious for primary PE (premature ejaculation).
https://www.ncbi.nlm...pubmed/21740694
We found that patients taking trazodone can produce urine with sufficient m-CPP to result in false-positive Amphetamines II results.
https://www.ncbi.nlm...pubmed/22732813
The purpose of the study was to highlight the cytoarchitectural changes in the frontal cortex and hippocampus by comparing two antidepressant substances: amitriptyline with a strong anticholinergic effect and trazodone, without anticholinergic effect. The superior neuroprotective qualities of trazodone for the frontal cortex, hippocampus and dentate gyrus are revealed. The particular neurobiological vulnerability of depression in women requires a differentiated therapeutic approach, avoiding the use of antidepressants with anticholinergic action.
https://www.ncbi.nlm...pubmed/21575194
Trazodone significantly improved fibromyalgia severity and associated symptomatology. Its combination with pregabalin potentiated this improvement and the tolerability of the drugs in association was good.
https://www.ncbi.nlm...pubmed/22115401
Various other attributes of trazodone, including interaction with adrenergic receptors, formation of an active metabolite with potent serotonergic activity, low abuse potential and putative utility in various disorders, warrant further exploration. The adverse effects of trazodone generally mirror its serotonergic activity and include sedation, headache, sweating, weight changes and gastrointestinal effects such as nausea and vomiting. Clinicians and patients should be cognizant of the risk for potential, but rare, cardiovascular adverse effects of trazodone.
https://www.ncbi.nlm...pubmed/21220793
It is generally approved for the treatment of major depression, its efficacy is well-documented in elderly patients, and it has been widely used for replacement of benzodiazepines or benzodiazepine-type sleeping drugs due to its anxiolytic efficacy and sleep normalizing effect in depression. Trazodone was further found to be clinically useful in generalized anxiety disorder, agitation of patients with dementia and organic disorders, chronic pain disorders, alcohol and benzodiazepine dependence. Tolerability of trazodone is comparable to the novel antidepressants. It is weight neutral and does not decrease sexual function
https://www.ncbi.nlm...les/PMC2945951/
Trazodone markedly improved sleep quality, with large effect sizes in total PSQI score as well on sleep quality, sleep duration and sleep efficiency. Significant improvement, although with moderate effect sizes, were also observed in total FIQ scores, anxiety and depression scores (both HADS and BDI), and pain interference with daily activities. Unexpectedly, the most frequent and severe side effect associated with trazodone in our sample was tachycardia, which was reported by 14 (21.2%) patients
https://www.ncbi.nlm...pubmed/20712254
Sexual dysfunctions may be main cause of social disability. The knowledge of the rates of occurrence of sexual dysfunctions in the general population and the primary risk factors for these conditions is very important to assist in assessing the risk and planning treatment. Sexual dysfunctions are highly prevalent in our society worldwide, and that the occurrence of sexual dysfunctions increases directly with age for both men and women. Specific medical conditions and health behaviors represent major risk factors for sexual disorders. Trazodone is sedative antidepressant drug, which is effective, safe, fast acting, with a few side effects, with proved efficiency in the treatment of sexual dysfunction.
https://www.ncbi.nlm...pubmed/15816789
Evidence for the efficacy of trazodone in treating insomnia is very limited; most studies are small, conducted in populations of depressed patients, raise issues of design, and often lack objective efficacy measures. Side effects associated with trazodone are not inconsequential, with a high incidence of discontinuation due to side effects, such as sedation, dizziness, and psychomotor impairment, which raise particular concern regarding its use in the elderly. There is also some evidence of tolerance related to use of trazodone.
https://www.ncbi.nlm...pubmed/15291651
It is concluded that there are very few data to suggest that trazodone improves sleep in patients without mood disorder, though it does increase total sleep in patients with major depressive disorder. There are virtually no dose-response data for trazodone vis-à-vis sleep and, similarly, no available data on tolerance to its possible hypnotic effects. Areas of concern with its use include reports of significant dropout rates and induction of arrhythmias, primarily in patients with histories of cardiac disease, as well as the development of priapism (a potentially painful medical condition in which the erect penis does not return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours).
.
https://www.ncbi.nlm...pubmed/11518472
Trazodone appears effective for the treatment of insomnia and nightmares associated with chronic PTSD. However, controlled trials are needed before any definite conclusions can be drawn. The higher than expected occurrence of priapism warrants clinicians asking directly about this side effect.
https://www.ncbi.nlm.../pubmed/9315494
In a group of patients, that was not selected on the basis of the etiology of the erectile dysfunction, nor selected on the duration of the complaint, the efficacy of trazodone 150 mg/d, could not be shown.
https://www.ncbi.nlm.../pubmed/8057411
The effects of trazodone on penile erection may be due to a peripheral alpha adrenoceptor antagonism and central unknown mechanism. We conclude that trazodone may prove an effective treatment for impotent patients.
https://www.ncbi.nlm.../pubmed/3284752
Although unwanted effects were generally mild, the incidence of dizziness was greater in those patients receiving trazodone. Caution is advised, however, when prescribing either drug to patients with transient cerebral ischaemic attacks or those with coronary artery disease receiving medication.
http://www.lb7.uscou...IED/10-1191.pdf
Trazodone may cause side effects. Tell your doctor if any of these symptoms are severe or
do not go away:
headache or heaviness in head
nausea
vomiting
bad taste in mouth
stomach pain
diarrhea
constipation
changes in appetite or weight
weakness or tiredness
nervousness
decreased ability to concentrate or remember things
confusion
nightmares
muscle pain
dry mouth
sweating
blurred vision
tired, red, or itchy
Some side effects can be serious. If you experience any of the following symptoms or those
listed in the IMPORTANT WARNING section, call your doctor immediately:
chest pain
fast, pounding, or irregular heartbeat
shortness of breath
fever, sore throat, chills, or other signs of infection
hives
skin rash
itching
difficulty breathing or swallowing
swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
hoarseness
decreased coordination
uncontrollable shaking of a part of the body
numbness, burning, or tingling in the arms, legs, hands, or feet
dizziness or lightheadedness
fainting
painful erection that lasts longer than normal
Trazodone may cause painful, long lasting erections in males. In some cases emergency
and/or surgical treatment has been required and, in some of these cases, permanent
https://www.drugs.co...de-effects.html
In Summary
Commonly reported side effects of trazodone include: blurred vision, dizziness, drowsiness, nausea, vomiting, headache, and xerostomia. Other side effects include: syncope, edema, diarrhea, ataxia, insomnia, sedation, confusion, tachycardia, and hypotension.
More common:
⦁ Blurred vision
⦁ confusion
⦁ dizziness
⦁ dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
⦁ lightheadedness
⦁ sweating
⦁ unusual tiredness or weakness
Less common:
⦁ Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
⦁ confusion about identity, place, and time
⦁ decreased concentration
⦁ fainting
⦁ general feeling of discomfort or illness
⦁ headache
⦁ lack of coordination
⦁ muscle tremors
⦁ nervousness
⦁ pounding in the ears
⦁ shortness of breath
⦁ slow or fast heartbeat
⦁ swelling
Rare:
⦁ Skin rash
⦁ unusual excitement
Severity: Minor
Some trazodone side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:
More common:
⦁ Dry mouth (usually mild)
⦁ muscle or bone pain
⦁ trouble sleeping
⦁ trouble with remembering
⦁ unpleasant taste
Less common:
⦁ Constipation
⦁ continuing ringing or buzzing or other unexplained noise in the ears
⦁ diarrhea
⦁ hearing loss
⦁ muscle aches or pains
⦁ weight loss
For Healthcare Professionals
Applies to trazodone: compounding powder, oral tablet, oral tablet extended release
General
The most commonly reported side effects were dry mouth, nausea, vomiting, drowsiness, dizziness/light-headedness, headache, and nervousness.[Ref]
Cardiovascular
Common (1% to 10%): Hypertension, hypotension, syncope, tachycardia, palpitations
Frequency not reported: Sinus bradycardia, chest pain, ventricular couplets
Postmarketing reports: Cardiospasm, cerebrovascular accident, congestive heart failure, vasodilation, conduction block, orthostatic hypotension, atrial fibrillation, myocardial infarction, cardiac arrest, arrhythmia, ventricular ectopic activity, prolonged QT interval, torsade de pointes, ventricular tachycardia[Ref]
Psychiatric
Common (1% to 10%): Anger/hostility, excitement, insomnia, nightmares/vivid dreams
Frequency not reported: Hallucinations/delusions, mania/hypomania, impaired speech, suicidal ideation, disorientation, aggressive reaction, withdrawal syndrome
Postmarketing reports: Abnormal dreams, agitation, anxiety, paranoid reaction, psychosis[Ref]
Nervous system
Very common (10% or more): Drowsiness (up to 40.8%), dizziness/light-headedness (up to 28%), headache (up to 19.8%), nervousness (up to 14.8%)
Common (1% to 10%): Confusion, decreased concentration, disorientation, impaired memory, incoordination, paresthesia, tremors
Frequency not reported: Akathisia, muscle twitches, numbness, serotonin syndrome, convulsion, neuroleptic malignant syndrome, vertigo, restlessness, decreased alertness, cognitive/motor impairment
Postmarketing reports: Aphasia, ataxia, extrapyramidal symptoms, grand mal seizures, stupor, tardive dyskinesia, myoclonus,[Ref]
Genitourinary
Common (1% to 10%): Decreased libido, delayed urine flow, early menses
Frequency not reported: Hematuria, impotence, increased libido, increased urinary frequency, missed periods, retrograde ejaculation
Postmarketing reports: Breast enlargement or engorgement, clitorism, lactation, priapism, urinary incontinence, urinary retention[Ref]
Hematologic
Frequency not reported: Anemia, hemolytic anemia, granulocytosis, thrombocytopenia, eosinophilia, leucopenia
Postmarketing reports: Leukocytosis, methemoglobinemia[Ref]
Metabolic
Common (1% to 10%): Decreased appetite, weigh gain/loss
Frequency not reported: Increased appetite, anorexia, hyponatremia[Ref]
Ocular
Very common (10% or more): Blurred vision (up to 14.7%)
Common (1% to 10%): Red/tired/itching eyes
Frequency not reported: Angle-closure glaucoma
Postmarketing reports: Diplopia[Ref]
Dermatologic
Common (1% to 10%): Sweating/clamminess
Frequency not reported: Hyperhidrosis
Postmarketing reports: Alopecia, leuconychia, pruritus, psoriasis, rash, urticaria[Ref]
Endocrine
Postmarketing reports: Hirsutism, inappropriate ADH syndrome[Ref]
Gastrointestinal
Very common (10% or more): Dry mouth (up to 33.8%), nausea/vomiting (up to 12.7%)
Common (1% to 10%): Constipation, abdominal/gastric disorder, bad taste, diarrhea
Frequency not reported: Flatulence, increased salivation, dyspepsia, stomach pain, gastroenteritis, paralytic ileus
Postmarketing reports: Increased amylase[Ref]
Hepatic
Postmarketing reports: Cholestasis, hyperbilirubinemia, jaundice, liver enzyme alterations[Ref]
Hypersensitivity
Frequency not reported: Allergic reactions[Ref]
Musculoskeletal
Common (1% to 10%): Musculoskeletal aches/pains
Frequency not reported: Limb pain, back pain, myalgia, arthralgia[Ref]
Other
Very common (10% or more): Fatigue (up to 11.3%)
Common (1% to 10%): Edema, malaise, tinnitus
Frequency not reported: Chills, fever
Postmarketing reports: Unexplained death, weakness[Ref]
Respiratory
Common (1% to 10%): Shortness of breath, nasal/sinus congestion
Frequency not reported: Dyspnea
Postmarketing reports: Apnea
References
1. "Product Information. Desyrel (trazodone)." Bristol-Myers Squibb, Princeton, NJ.
2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
It is possible that some side effects of trazodone may not have been reported. These can be reported to the FDA. Always consult a healthcare professional for medical advice.
http://link.springer...45?view=classic
http://www.ncbi.nlm..../pubmed/3624211
http://www.ncbi.nlm..../pubmed/8056996
Three cases developed withdrawal symptoms of trazodone despite gradual discontinuation of therapeutic doses of the drug. This report suggests that effects of trazodone and its metabolite m-chlorophenylpiperazine on the serotonergic system, which may result in noradrenergic rebound after discontinuation, and short half-lives of these compounds are involved in the development of these symptoms. From a clinical point of view, we suggest that trazodone should be tapered off at a very slow rate.