Side Effects of nefazodone: A Synthesis of Findings from 23 Studies

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Original Abstract of the Article

Major findings

Nefazodone is a second-generation atypical antidepressant that is effective in treating depression, anxiety, and insomnia. 20 、 6 However, nefazodone carries some risk of side effects such as hepatotoxicity and cytotoxicity due to metabolic activation. 15 、 3 、 12 Nefazodone may also cause extrapyramidal symptoms, especially in older adults. 6 Additionally, nefazodone can cause sexual dysfunction. 9 、 13

Reasons for side effects

Side effects of nefazodone are related to its pharmacological action. Nefazodone inhibits serotonin reuptake and acts on serotonin receptors. 20 、 13 While these actions improve symptoms of depression and anxiety, they can also cause side effects. 20 Nefazodone also inhibits CYP3A4, potentially affecting the metabolism of other drugs. 12 This can lead to drug interactions and increase the risk of side effects. 14

Common side effects

Drowsiness

Nefazodone can cause drowsiness. 20 、 8 、 6 This is because nefazodone acts on serotonin receptors and produces a relaxing effect. 20 Drowsiness often occurs immediately after taking nefazodone and usually lessens over time. 20 Drowsiness requires special caution, especially in the elderly. 6

Gastrointestinal side effects

Nefazodone can cause gastrointestinal side effects. 19 、 6 These include nausea, vomiting, diarrhea, constipation, and loss of appetite. 19 、 6 These side effects are typically mild and decrease over time. 19 、 6

Sexual dysfunction

Nefazodone can cause sexual dysfunction. 9 、 13 This includes decreased libido, erectile dysfunction, and ejaculation problems. 9 、 13 These side effects are due to nefazodone acting on serotonin receptors and suppressing libido. 9 、 13

Extrapyramidal symptoms

Nefazodone can cause extrapyramidal symptoms, especially in older adults. 6 These include muscle stiffness, tremors, and involuntary movements. 6 These side effects are because nefazodone acts on dopamine receptors and inhibits the action of dopamine. 6

Hepatotoxicity

Nefazodone can cause hepatotoxicity. 15 、 3 These include abnormal liver function, jaundice, and hepatitis. 15 、 3 Nefazodone hepatotoxicity is thought to be caused by reactive metabolites generated by the metabolism of nefazodone. 15 、 3

Cytotoxicity due to metabolic activation

Nefazodone can be metabolically activated via CYP3A4 and cause cytotoxicity. 12 This includes cell death and tissue damage. 12 Nefazodone cytotoxicity is thought to be caused by reactive metabolites generated by the metabolism of nefazodone. 12

Side effect management

Drowsiness

To reduce drowsiness, nefazodone should be taken at bedtime. 20 Also, if drowsiness is severe, consult your doctor about reducing the dosage or considering alternative medications. 20

Gastrointestinal side effects

To reduce gastrointestinal side effects, nefazodone should be taken with meals. 19 Also, if these side effects are severe, consult your doctor about reducing the dosage or considering alternative medications. 19

Sexual dysfunction

To reduce sexual dysfunction, nefazodone should be avoided as much as possible. 9 、 13 Also, if these side effects are severe, consult your doctor about reducing the dosage or considering alternative medications. 9 、 13

Extrapyramidal symptoms

To reduce extrapyramidal symptoms, nefazodone should be avoided as much as possible. 6 Also, if these side effects are severe, consult your doctor about reducing the dosage or considering alternative medications. 6

Hepatotoxicity

To prevent hepatotoxicity, nefazodone should be avoided as much as possible. 15 、 3 Also, have regular liver function tests while taking nefazodone. 15 、 3

Cytotoxicity due to metabolic activation

To prevent cytotoxicity due to metabolic activation, nefazodone should be avoided as much as possible. 12 Also, have regular health checkups while taking nefazodone. 12

Comparison between studies

Common points

Multiple studies have shown that nefazodone is effective in treating conditions such as depression, anxiety, and insomnia. 21 、 23 、 18 、 22 However, they have also shown the risk of side effects such as hepatotoxicity and cytotoxicity due to metabolic activation. 15 、 3 、 12

Differences

The effectiveness and the severity of side effects of nefazodone vary between studies. 21 、 23 、 18 、 22 For example, in some studies, nefazodone has been shown to be effective in treating insomnia, while other studies show that it may worsen insomnia. 18 、 22 Also, nefazodone hepatotoxicity has been reported in some studies to be rare, while other studies show it to be more frequent. 15 、 3

Precautions for real-life application

Nefazodone is an effective medication for treating conditions such as depression, anxiety, and insomnia, but it carries the risk of side effects. 21 、 23 、 18 、 22 Consult your doctor to determine the appropriate dosage and how to take nefazodone. 21 、 23 、 18 、 22 Also, regularly monitor your health while taking nefazodone. 15 、 3 、 12 Be especially cautious with older adults as they have a higher risk of extrapyramidal symptoms. 6

Limitations of current research

There is still insufficient research on nefazodone. 21 、 23 、 18 、 22 In particular, there is a lack of sufficient data on the long-term side effects of nefazodone and the severity of side effects in specific populations. 15 、 3 、 12

Future research directions

Further research is needed to clarify the long-term side effects of nefazodone and the severity of side effects in specific populations. 21 、 23 、 18 、 22 Further research is also needed to understand the mechanism of nefazodone’s cytotoxicity due to metabolic activation and drug interactions. 15 、 3 、 12

Conclusion

Nefazodone is an effective medication for treating conditions such as depression, anxiety, and insomnia, but it carries the risk of side effects. 21 、 23 、 18 、 22 Consult your doctor to determine the appropriate dosage and how to take nefazodone. 21 、 23 、 18 、 22 Also, regularly monitor your health while taking nefazodone. 15 、 3 、 12 Be especially cautious with older adults as they have a higher risk of extrapyramidal symptoms. 6

Literature analysis of 23 papers
Positive Content
15
Neutral Content
3
Negative Content
5
Article Type
1
2
2
14
23
1.

New frontiers in the pharmacological treatment of social anxiety disorder in adults: an up-to-date comprehensive overview.

Author: CaldiroliAlice, CapuzziEnrico, TagliabueIlaria, LeddaLuisa, ClericiMassimo, BuoliMassimiliano

SAD
Side effects

This review summarizes data on the efficacy of unlabeled molecules for treating social anxiety disorder (SAD).

ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

2.

Side effect profile and comparative tolerability of 21 antidepressants in the acute treatment of major depression in adults: protocol for a network meta-analysis.

Author: TomlinsonAnneka, EfthimiouOrestis, BoadenKatharine, NewEmma, MatherSarah, SalantiGeorgia, ImaiHissei, OgawaYusuke, TajikaAran, KishimotoSanae, KikuchiSino, ChevanceAstrid, FurukawaToshi A, CiprianiAndrea

Major depression treatment
Adverse events

This study presents a protocol for a network meta-analysis comparing the efficacy, adverse events, and tolerability of all second-generation and selected first-generation antidepressants in the acute treatment of major depression in adults. The study aims to extend previous findings and update the evidence base for antidepressant treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Safety data and withdrawal of hepatotoxic drugs.

Author: BabaiSamy, AuclertLaurent, Le-LouëtHervé

DILI prediction
Drug induced liver injury

Predicting drug-induced liver injury (DILI) remains challenging due to limitations in in vitro cytotoxicity screening and animal studies. A comprehensive review of hepatotoxicity data is essential to identify factors that could predict the occurrence of serious DILI.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

4.

Psychopharmacology of chronic pain: a focus on antidepressants and atypical antipsychotics.

Author: KhouzamHani Raoul

Chronic pain relief
Side effects

Antidepressants, including tricyclics, SSRIs, SNRIs, and atypical antipsychotics, have been used in treating chronic pain. This review summarizes their effectiveness and associated side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

5.

Reactive Metabolites: Current and Emerging Risk and Hazard Assessments.

Author: ThompsonRichard A, IsinEmre M, OgeseMonday O, MettetalJerome T, WilliamsDominic P

Idiosyncratic adverse drug reactions

This review discusses reactive metabolites and their role in idiosyncratic adverse drug reactions.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

6.

Trazodone in the elderly: risk of extrapyramidal acute events.

Author: Sotto MayorJoana, PachecoAna Paula, EsperançaSofia, Oliveira e SilvaAntonio

Anxiety treatment
Depression treatment
Insomnia treatment
Extrapyramidal event

Trazodone is an antidepressant that can cause extrapyramidal symptoms, even at low doses.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

7.

Neuronal and immunological basis of action of antidepressants in chronic pain - clinical and experimental studies.

Author: MikaJoanna, ZychowskaMagdalena, MakuchWioletta, RojewskaEwelina, PrzewlockaBarbara

Antidepressant efficacy
Chronic pain treatment
Antidepressant side effects

Tricyclic antidepressants (TCAs) are often used to treat chronic pain, but they can have significant side effects. This review examines the evidence for the efficacy and safety of various antidepressants, including TCAs, tetracyclic antidepressants (TeCAs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and atypical antidepressants, for the treatment of neuropathic pain.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

Strategies for managing sexual dysfunction induced by antidepressant medication.

Author: TaylorMatthew J, RudkinLisa, Bullemor-DayPhilippa, LubinJade, ChukwujekwuChristopher, HawtonKeith

Improved sexual function
Sexual dysfunction

This review discusses the common side effect of sexual dysfunction associated with antidepressant medications. The review highlights various management strategies for addressing this issue.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

10.

Validation of a HTS-amenable assay to detect drug-induced mitochondrial toxicity in the absence and presence of cell death.

Author: SwissRachel, NilesAndrew, CaliJames J, NadanacivaSashi, WillYvonne

Early detection of mitochondrial toxicity

A new 384-well format cell-based dual parameter assay was validated to measure both mitochondrial toxicity and cytotoxicity, providing a rapid and early readout of drug-induced mitochondrial dysfunction.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Validation StudyResearch to assess the validity and reliability of new measurement methods or diagnostic tests.

Language : English

12.

Development of a highly sensitive cytotoxicity assay system for CYP3A4-mediated metabolic activation.

Author: HosomiHiroko, FukamiTatsuki, IwamuraAtsushi, NakajimaMiki, YokoiTsuyoshi

Detect drug-induced cytotoxicity

This study constructed a cell-based system to evaluate the cytotoxicity of reactive metabolites produced by CYP3A4. The study found that HepG2 cells showed the highest CYP3A4 protein expression and activity among seven hepatoma cell lines. The cytotoxicity of 23 drugs was evaluated in AdCYP3A4-infected HepG2 cells, with 11 drugs showing significant decrease in cell viability.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

The use of monoamine pharmacological agents in the treatment of sexual dysfunction: evidence in the literature.

Author: MollJennifer L, BrownCandace S

Improved sexual dysfunction
Side effects

Monoaminergic agents, such as bupropion, buspirone, and ropinirole, may be effective in treating sexual dysfunction, especially those caused by serotonergic reuptake inhibitors.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

14.

Managing menopausal symptoms and depression in tamoxifen users: implications of drug and medicinal interactions.

Author: DesmaraisJulie Eve, LooperKarl J

Drug interactions

Tamoxifen, a breast cancer medication, often causes menopausal symptoms. Certain medications and natural supplements used to alleviate these symptoms can interact with tamoxifen.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

15.

Can drug safety be predicted and animal experiments reduced by using isolated mitochondrial fractions?

Author: PereiraSusana P, PereiraGonçalo C, MorenoAntónio J, OliveiraPaulo J

Reduced animal use
Mitochondrial toxicity

This review highlights the importance of screening for mitochondrial toxicity during drug development. The use of isolated mitochondria as a screening tool can reduce animal use in pre-clinical studies, improve animal welfare, and enhance drug safety.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

17.

Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity.

Author: CosgroveBenjamin D, KingBracken M, HasanMaya A, AlexopoulosLeonidas G, FaraziParaskevi A, HendriksBart S, GriffithLinda G, SorgerPeter K, TidorBruce, XuJinghai J, LauffenburgerDouglas A

Idiosyncratic hepatotoxicity

This study presents a high-throughput in vitro approach for investigating drug-induced hepatotoxicity. It uses a combination of drug and cytokine treatments to mimic inflammatory conditions and identify drug-cytokine synergies, potentially leading to better preclinical screening methods for idiosyncratic drug hepatotoxicity.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Treatment of sleep dysfunction and psychiatric disorders.

Author: BeckerPhilip M

Benzodiazepines for insomnia
Cognitive behavioral therapy for insomnia
Eszopiclone for insomnia
Lifestyle changes for insomnia
Mirtazapine for insomnia
Nefazodone for insomnia
Olanzapine for insomnia
Quetiapine for insomnia
Trazodone for insomnia
Tricyclic antidepressants for insomnia
Zaleplon for insomnia
Zolpidem for insomnia
Agitation
Side effects of antidepressants

Sleep dysfunction is common in patients with neurologic disorders and psychiatric disorders, particularly insomnia. Insomnia is often a prominent symptom in anxiety disorders and major depression. Treatment for chronic insomnia should consider underlying psychiatric conditions. For patients with mild to moderate depression and insomnia, sedating antidepressants like mirtazapine, nefazodone, or tricyclic antidepressants can be beneficial, although side effects may limit their use. Cognitive behavioral therapy and lifestyle changes show long-term efficacy in treating chronic insomnia. Sedative hypnotic agents, such as benzodiazepines and zolpidem, are commonly used, but their long-term use should be carefully monitored. Trazodone is frequently prescribed to treat insomnia during antidepressant therapy, but research on its effectiveness in psychiatric patients is limited. Atypical antipsychotic agents like quetiapine or olanzapine may be used to address severe insomnia and agitation. It is essential to rule out underlying sleep disorders if insomnia or hypersomnia persists even after improvement in mood, anxiety, or thought disorders.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

19.

Dropouts versus completers among chronically depressed outpatients.

Author: ArnowBruce A, BlaseyChristine, ManberRachel, ConstantinoMichael J, MarkowitzJohn C, KleinDaniel N, ThaseMichael E, KocsisJames H, RushA John

Medication side effects

Ethnic and racial minorities and those with comorbid anxiety are at higher risk of premature termination from treatment for depression, particularly with pharmacotherapy.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

20.

Antidepressants and their effect on sleep.

Author: MayersAndrew G, BaldwinDavid S

Insomnia
REM sleep suppression
Sedation

Antidepressants can affect sleep. The effect depends on the class of antidepressant used and the dosage. Insomnia is often seen with monoamine oxidase inhibitors (MAOIs), with all tricyclic antidepressants (TCAs) except amitriptyline, and all selective serotonin reuptake inhibitors (SSRIs) with venlafaxine and moclobemide as well. Sedation has been reported with all TCAs except desipramine, with mirtazapine and nefazodone, the TCA-related maprotiline, trazodone and mianserin, and with all MAOIs. REM sleep suppression has been observed with all TCAs except trimipramine, but especially clomipramine, with all MAOIs and SSRIs and with venlafaxine, trazodone and bupropion.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

21.

[Review of antidepressants from the TCAs to the third generation drugs].

Author: AlmásiJános, RihmerZoltán

Depressive disorder treatment
Side effects

The paper discusses the pathomechanism of unipolar major depressive disorder (MDD) and various antidepressant medications, including tri- and teracyclic drugs (TCAs), dual-acting antidepressants, and selective serotonin reuptake inhibitors (SSRIs). The article emphasizes the pharmacodynamic properties, benefits, side effects, and characteristics of each antidepressant subgroup.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : Hungarian

22.

Nefazodone in primary insomnia: an open pilot study.

Author: WiegandMichael H, GalanakisPatrizia, SchreinerRalph

Improved sleep
Side effects

Nefazodone is an antidepressant that may improve sleep in people with insomnia, but this study found that high doses can cause negative effects on sleep quality. Further studies with lower doses are needed.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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