Research and Clinical Trials on Nefazodone (Serzone, Dutonin)

Nefazodone (Serzone, Dutonin) Clinical Research Trials

From our searchable database at ClinicalTrialsFeeds.org, this list includes all the latest information about clinical trials involving Nefazodone (Serzone, Dutonin).

• Nefazodone in the Treatment of Cocaine Dependence and Depression - 4
  Status: Completed, Condition Summary: Cocaine-Related Disorders; Substance-Related Disorders
• Effectiveness of Nefazodone and Bupropion in Treating Marijuana Dependent Individuals
  Status: Completed, Condition Summary: Marijuana Abuse
• Nefazodone in the Treatment of Social Phobia
  Status: Completed, Condition Summary: Social Anxiety Disorder (SAD)
• Effect of Nefazodone on Relapse in Females With Cocaine Abuse - 10
  Status: Completed, Condition Summary: Cocaine-Related Disorders
• Effects of Nefazodone on Treatment of Female Cocaine Abusers - 3
  Status: Completed, Condition Summary: Cocaine-Related Disorders

 

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Current Research Literature on Nefazodone (Serzone, Dutonin)

Here are abstracts for some of the latest research articles to have appeared on Nefazodone (Serzone, Dutonin):

Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: an update.

Clin Ther. 2008 Jul; 30(7): 1206-27
Spina E, Santoro V, D'Arrigo C
BACKGROUND: The second-generation antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and other compounds with different mechanisms of action. All second-generation antidepressants are metabolized in the liver by the cytochrome P450 (CYP) enzyme system. Concomitant intake of inhibitors or inducers of the CYP isozymes involved in the biotransformation of specific antidepressants may alter plasma concentrations of these agents, although this effect is unlikely to be associated with clinically relevant interactions. Rather, concern about drug interactions with second-generation antidepressants is based on their in vitro potential to inhibit > or = 1 CYP isozyme. OBJECTIVE: The goal of this article was to review the current literature on clinically relevant pharmacokinetic drug interactions with second-generation antidepressants. METHODS: A search of MEDLINE and EMBASE was conducted for original research and review articles published in English between January 1985 and February 2008. Among the search terms were drug interactions, second-generation antidepressants, newer antidepressants, SSRIs, SNRIs, fluoxetine, paroxetine, fluvoxamine, sertraline, citalopram, escitalopram, venlafaxine, duloxetine, mirtazapine, reboxetine, bupropion, nefazodone, pharmacokinetics, drug metabolism, and cytochrome P450. Only articles published in peer-reviewed journals were included, and meeting abstracts were excluded. The reference lists of relevant articles were hand-searched for additional publications. RESULTS: Second-generation antidepressants differ in their potential for pharmacokinetic drug interactions. Fluoxetine and paroxetine are potent inhibitors of CYP2D6, fluvoxamine markedly inhibits CYP1A2 and CYP2C19, and nefazodone is a substantial inhibitor of CYP3A4. Therefore, clinically relevant interactions may be expected when these antidepressants are coadministered with substrates of the pertinent isozymes, particularly those with a narrow therapeutic index. Duloxetine and bupropion are moderate inhibitors of CYP2D6, and sertraline may cause significant inhibition of this isoform, but only at high doses. Citalopram, escitalopram, venlafaxine, mirtazapine, and reboxetine are weak or negligible inhibitors of CYP isozymes in vitro and are less likely than other second-generation antidepressants to interact with co-administered medications. CONCLUSIONS: Second-generation antidepressants are not equivalent in their potential for pharmacokinetic drug interactions. Although interactions may be predictable in specific circumstances, use of an antidepressant with a more favorable drug-interaction profile may be justified.

Can in vitro metabolism-dependent covalent binding data in liver microsomes distinguish hepatotoxic from nonhepatotoxic drugs? An analysis of 18 drugs with consideration of intrinsic clearance and daily dose.

Chem Res Toxicol. 2008 Sep; 21(9): 1814-22
Obach RS, Kalgutkar AS, Soglia JR, Zhao SX
In vitro covalent binding assessments of drugs have been useful in providing retrospective insights into the association between drug metabolism and a resulting toxicological response. On the basis of these studies, it has been advocated that in vitro covalent binding to liver microsomal proteins in the presence and the absence of NADPH be used routinely to screen drug candidates. However, the utility of this approach in predicting toxicities of drug candidates accurately remains an unanswered question. Importantly, the years of research that have been invested in understanding metabolic bioactivation and covalent binding and its potential role in toxicity have focused only on those compounds that demonstrate toxicity. Investigations have not frequently queried whether in vitro covalent binding could be observed with drugs with good safety records. Eighteen drugs (nine hepatotoxins and nine nonhepatotoxins in humans) were assessed for in vitro covalent binding in NADPH-supplemented human liver microsomes. Of the two sets of nine drugs, seven in each set were shown to undergo some degree of covalent binding. Among hepatotoxic drugs, acetaminophen, carbamazepine, diclofenac, indomethacin, nefazodone, sudoxicam, and tienilic acid demonstrated covalent binding, while benoxaprofen and felbamate did not. Of the nonhepatotoxic drugs evaluated, buspirone, diphenhydramine, meloxicam, paroxetine, propranolol, raloxifene, and simvastatin demonstrated covalent binding, while ibuprofen and theophylline did not. A quantitative comparison of covalent binding in vitro intrinsic clearance did not separate the two groups of compounds, and in fact, paroxetine, a nonhepatotoxin, showed the greatest amount of covalent binding in microsomes. Including factors such as the fraction of total metabolism comprised by covalent binding and the total daily dose of each drug improved the discrimination between hepatotoxic and nontoxic drugs based on in vitro covalent binding data; however, the approach still would falsely identify some agents as potentially hepatotoxic.

Managing the patient with co-morbid depression and an anxiety disorder.

Drugs. 2008; 68(12): 1621-34
Schoevers RA, Van HL, Koppelmans V, Kool S, Dekker JJ
Depression and anxiety disorders frequently co-occur. This type of co-morbidity is associated with higher severity, suicidality, chronicity and treatment resistance. However, available treatment guidelines mainly focus on treatment for singular disorders. The current paper describes diagnostic and treatment issues relevant for adequately addressing patients with depression and an anxiety disorder, using information from both guidelines and a search of recent literature. Apart from differential diagnosis, the diagnostic evaluation should include a thorough assessment of the symptoms of both disorders, preferably by using a structured clinical interview, and an assessment of depression severity in terms of suicidality, psychotic symptoms and impairment. Treatment should first address the primary disorder in terms of severity and risk. As a rule, severe depression should be treated before the anxiety disorder, using antidepressant medication or combined treatment (plus psychotherapy). In less severe pathology, the primary focus may be determined by examining the temporal pattern and the subjective burden of each disorder as experienced by the patient. Treatment is often sequential. Treatment of the primary disorder may or may not relieve the co-morbid disorder as well. If the primary disorder is an anxiety disorder, co-morbid depression generally implies earlier use of an antidepressant. Co-morbid mild depression may also react favourably to psychotherapeutic treatment of the anxiety disorder. Recent literature on concurrent treatment of both depression and anxiety shows that modern antidepressants such as sertraline, paroxetine, fluoxetine, venlafaxine, nefazodone and bupropion have demonstrated efficacy in relieving both depressive and anxiety symptoms compared with placebo. Head-to-head comparisons, although relatively scarce, tend to show superiority over tricyclic antidepressants. Venlafaxine was found to be more effective than fluoxetine in some studies. However, these results should be interpreted with caution because studies vary considerably in terms of patient selection, assessment of anxiety and primary outcome measures. Only one randomized controlled trial compared atypical antipsychotics with placebo. Psychotherapy was generally shown to have a beneficial effect on the co-morbid conditions, and available evidence appears to favour combined treatment. The results should be interpreted with caution because the number of studies on this issue was relatively small, with considerable clinical and methodological heterogeneity.

Do new-generation antidepressants work?

Ir Med J. 2008 May; 101(5): 155
Kelly BD

High throughput and sensitive determination of trazodone and its primary metabolite, m-chlorophenylpiperazine, in human plasma by liquid chromatography-tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Aug 1; 871(1): 44-54
Patel BN, Sharma N, Sanyal M, Shrivastav PS
A precise, sensitive and high throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of trazodone (TRZ) and its primary metabolite, m-chlorophenylpiperazine (mCPP), in human plasma was developed and validated. The analytes and the internal standard-nefazodone were extracted from 500 microL aliquots of human plasma via liquid-liquid extraction in n-hexane. Chromatographic separation was achieved in a run time of 2.5 min on a Betabasic cyano column (100 mm x 2.1 mm, 5 microm) under isocratic conditions. Detection of analytes and IS was done by tandem mass spectrometry, operating in positive ion and multiple reaction monitoring (MRM) acquisition mode. The protonated precursor to product ion transitions monitored for TRZ, mCPP and IS were m/z 372.2-->176.2, 197.2-->118.1 and 470.5-->274.6 respectively. The method was fully validated for its sensitivity, selectivity, accuracy and precision, matrix effect, stability study and dilution integrity. A linear dynamic range of 10.0-3000.0 ng/mL for TRZ and 0.2-60.0 ng/mL for mCPP was evaluated with mean correlation coefficient (r) of 0.9986 and 0.9990 respectively. The intra-batch and inter-batch precision (%CV) across five validation runs (LLOQ, lower limit of quantitation; LQC, low quality control; MQC, middle quality control; HQC, high quality control and ULOQ, upper limit of quantitation) was < or =8.4% for both the analytes. The method was successfully applied to a bioequivalence study of 100mg trazodone tablet formulation in 36 healthy Indian male subjects under fasting and fed conditions.