CR Extras: Supplementary Materials for Counselling Resource Readers

CR Extras

Medication Reference Materials

Research and Clinical Trials on Nefazodone (Serzone, Dutonin)

This list of current clinical research trials on Nefazodone (Serzone, Dutonin) is followed by a short set of abstracts from the most recent research articles published on the drug.

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).

 

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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):

Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials.

J Clin Psychiatry. 2011 Dec; 72(12): 1660-8
Tedeschini E, Levkovitz Y, Iovieno N, Ameral VE, Nelson JC, Papakostas GI
Late-life depression is an important public health issue, given the growing proportion of the elderly relative to the general population in the developed world. The purpose of this study was to examine the efficacy of antidepressants for the treatment of major depressive disorder (MDD) in elderly patients.PubMed/MEDLINE was searched for randomized, double-blind, placebo-controlled trials of antidepressants for treatment of both adult (nonelderly) MDD (patients aged < 65 years) and late-life MDD (patients aged ≥ 55 years). The search was limited to articles published between January 1, 1980, and March 3, 2010 (inclusive). The year 1980 was used as a cutoff in our search to decrease diagnostic variability, since the DSM-III was introduced in 1980. Our search cross-referenced the term placebo with each of the following antidepressants: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. We also reviewed the reference lists of all studies identified through the PubMed/MEDLINE search.Articles were selected that reported on randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD and that met numerous a priori criteria pertaining to MDD diagnosis criteria, study duration, study design, drug formulation, original data, age thresholds, primary and secondary outcome measures, and exclusions of other disorders. Final inclusion of articles was determined by consensus between the authors. Seventy-four articles were found eligible for inclusion in our analysis (15 late-life MDD trials and 59 adult MDD trials).Antidepressants were found to be efficacious for late-life MDD (age 55 and older; P < .0001), although there was evidence for heterogeneity across studies (Q22 = 67.302, P < .001). However, antidepressants were not found to be efficacious in the subset of studies using age thresholds of 65 years or older (older late-life MDD) (P = .265). Finally, when we controlled for study design characteristics, antidepressant but not placebo response rates were lower among late-life MDD patients than among adult MDD patients.The present meta-analysis suggests that antidepressants are efficacious in late-life MDD, but significant study heterogeneity suggests that other factors may contribute to these findings. A secondary analysis raises the possibility that efficacy of these agents may be reduced in trials involving patients aged 65 years or older. Why antidepressants may be less efficacious in elderly versus younger subjects remains unclear.

Inhibition of G protein-activated inwardly rectifying K+ channels by different classes of antidepressants.

PLoS One. 2011; 6(12): e28208
Kobayashi T, Washiyama K, Ikeda K
Various antidepressants are commonly used for the treatment of depression and several other neuropsychiatric disorders. In addition to their primary effects on serotonergic or noradrenergic neurotransmitter systems, antidepressants have been shown to interact with several receptors and ion channels. However, the molecular mechanisms that underlie the effects of antidepressants have not yet been sufficiently clarified. G protein-activated inwardly rectifying K(+) (GIRK, Kir3) channels play an important role in regulating neuronal excitability and heart rate, and GIRK channel modulation has been suggested to have therapeutic potential for several neuropsychiatric disorders and cardiac arrhythmias. In the present study, we investigated the effects of various classes of antidepressants on GIRK channels using the Xenopus oocyte expression assay. In oocytes injected with mRNA for GIRK1/GIRK2 or GIRK1/GIRK4 subunits, extracellular application of sertraline, duloxetine, and amoxapine effectively reduced GIRK currents, whereas nefazodone, venlafaxine, mianserin, and mirtazapine weakly inhibited GIRK currents even at toxic levels. The inhibitory effects were concentration-dependent, with various degrees of potency and effectiveness. Furthermore, the effects of sertraline were voltage-independent and time-independent during each voltage pulse, whereas the effects of duloxetine were voltage-dependent with weaker inhibition with negative membrane potentials and time-dependent with a gradual decrease in each voltage pulse. However, Kir2.1 channels were insensitive to all of the drugs. Moreover, the GIRK currents induced by ethanol were inhibited by sertraline but not by intracellularly applied sertraline. The present results suggest that GIRK channel inhibition may reveal a novel characteristic of the commonly used antidepressants, particularly sertraline, and contributes to some of the therapeutic effects and adverse effects.

Which psychotropic medications induce hepatotoxicity?

Gen Hosp Psychiatry. 2012 Jan; 34(1): 53-61
Sedky K, Nazir R, Joshi A, Kaur G, Lippmann S
Safe prescribing practices to minimize pharmaceutically induced liver damage or worsening of preexisting conditions require knowledge about medicines with hepatotoxic potential. This paper reviews psychotropic medications and their effects on the liver.A MEDLINE search was performed utilizing the phrase "drug-induced liver injury" with various categories of psychiatric drugs. Only articles written in English were utilized.Hepatotoxicity can be acute or chronic in nature. Medication discontinuation is necessary in acute forms, while close monitoring is required in milder forms of medication-induced chronic liver damage. Nefazodone, pemoline and/or tacrine are the highest offenders. Carbamazepine and valproate products (e.g., divalproex) can lead to this adverse event and should be avoided in patients with liver disease, persons with alcohol misuse or those consuming high doses of acetaminophen.Knowing the risk levels associated with various medicines is important; prescribing multiple drugs with hepatotoxic effects should be avoided. One should educate patients about early warning signs of liver injury. Always provide clinical and laboratory monitoring before and during the use of hepatotoxic drugs. Clinical features and laboratory results govern medication prescribing with ongoing risk-to-benefit ratio assessment during pharmacotherapy.

[Depressive disorder, treatment and sexual dysfunction--part II].

Pol Merkur Lekarski. 2011 Oct; 31(184): 256-9
Gałecki P, Depko A, Woźniak A, Talarowska M
Depressive disorders and antidepressant therapy have been associated with sexual dysfunction. Sexual dysfunctions are recognized as a potential side effect of antidepressant therapy. Not reliable algorithms have been developed in the presence of sexual dysfunctions in the course of depressive disorders. The most commonly used methods of treatment of sexual dysfunction in depressive disorders include: waiting for spontaneous remission, reduction in dose of a repressive drug, the change of drug discontinuation for a short time, the use of the drug after having sexual intercourse, drug holidays and corrective medications (yohimbine, phosphodiesterase type 5 and anesthetic creams). Among the most effective agents used in the treatment sre: bupropion, trazodone, nefazodone, agomelatine, tianeptine and flibanserin. Optimal antidepressant treatment should result in remission of the symptoms of the underlying illness and minimize the potential for short-term and long-term adverse effects, including sexual dysfunction. Physicians should monitor their patients for antidepressant-induced sexual adverse effects, as these may affect compliance with therapy and ultimate treatment success.

The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the non-motor symptoms of Parkinson's disease.

Mov Disord. 2011 Oct; 26 Suppl 3: S42-80
Seppi K, Weintraub D, Coelho M, Perez-Lloret S, Fox SH, Katzenschlager R, Hametner EM, Poewe W, Rascol O, Goetz CG, Sampaio C
The Movement Disorder Society (MDS) Task Force on Evidence-Based Medicine (EBM) Review of Treatments for Parkinson's Disease (PD) was first published in 2002 and was updated in 2005 to cover clinical trial data up to January 2004 with the focus on motor symptoms of PD. In this revised version the MDS task force decided it was necessary to extend the review to non-motor symptoms. The objective of this work was to update previous EBM reviews on treatments for PD with a focus on non-motor symptoms. Level-I (randomized controlled trial, RCT) reports of pharmacological and nonpharmacological interventions for the non-motor symptoms of PD, published as full articles in English between January 2002 and December 2010 were reviewed. Criteria for inclusion and ranking followed the original program outline and adhered to EBM methodology. For efficacy conclusions, treatments were designated: efficacious, likely efficacious, unlikely efficacious, non-efficacious, or insufficient evidence. Safety data were catalogued and reviewed. Based on the combined efficacy and safety assessment, Implications for clinical practice were determined using the following designations: clinically useful, possibly useful, investigational, unlikely useful, and not useful. Fifty-four new studies qualified for efficacy review while several other studies covered safety issues. Updated and new efficacy conclusions were made for all indications. The treatments that are efficacious for the management of the different non-motor symptoms are as follows: pramipexole for the treatment of depressive symptoms, clozapine for the treatment of psychosis, rivastigmine for the treatment of dementia, and botulinum toxin A (BTX-A) and BTX-B as well as glycopyrrolate for the treatment of sialorrhea. The practical implications for these treatments, except for glycopyrrolate, are that they are clinically useful. Since there is insufficient evidence of glycopyrrolate for the treatment of sialorrhea exceeding 1 week, the practice implication is that it is possibly useful. The treatments that are likely efficacious for the management of the different non-motor symptoms are as follows: the tricyclic antidepressants nortriptyline and desipramine for the treatment of depression or depressive symptoms and macrogol for the treatment of constipation. The practice implications for these treatments are possibly useful. For most of the other interventions there is insufficient evidence to make adequate conclusions on their efficacy. This includes the tricyclic antidepressant amitriptyline, all selective serotonin reuptake inhibitors (SSRIs) reviewed (paroxetine, citalopram, sertraline, and fluoxetine), the newer antidepressants atomoxetine and nefazodone, pergolide, Ω-3 fatty acids as well as repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression or depressive symptoms; methylphenidate and modafinil for the treatment of fatigue; amantadine for the treatment of pathological gambling; donepezil, galantamine, and memantine for the treatment of dementia; quetiapine for the treatment of psychosis; fludrocortisone and domperidone for the treatment of orthostatic hypotension; sildenafil for the treatment of erectile dysfunction, ipratropium bromide spray for the treatment of sialorrhea; levodopa/carbidopa controlled release (CR), pergolide, eszopiclone, melatonin 3 to 5 mg and melatonin 50 mg for the treatment of insomnia and modafinil for the treatment of excessive daytime sleepiness. Due to safety issues the practice implication is that pergolide and nefazodone are not useful for the above-mentioned indications. Due to safety issues, olanzapine remains not useful for the treatment of psychosis. As none of the studies exceeded a duration of 6 months, the recommendations given are for the short-term management of the different non-motor symptoms. There were no RCTs that met inclusion criteria for the treatment of anxiety disorders, apathy, medication-related impulse control disorders and related behaviors other than pathological gambling, rapid eye movement (REM) sleep behavior disorder (RBD), sweating, or urinary dysfunction. Therefore, there is insufficient evidence for the treatment of these indications. This EBM review of interventions for the non-motor symptoms of PD updates the field, but, because several RCTs are ongoing, a continual updating process is needed. Several interventions and indications still lack good quality evidence, and these gaps offer an opportunity for ongoing research. © 2011 Movement Disorder Society.