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Treatment of OCD with comorbid depression should focus on amelioration of OCD symptoms. When OCD treatment is successful, depressive symptoms are likely to ameliorate as well.
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In this paper, a fast, sensitive and selective LC-MS/MS method is described for the simultaneous determination of amitriptyline, imipramine, clomipramine, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and venlafaxine, as well as some of their main metabolites (nortriptyline, desipramine, norclomipramine and norfluoxetine), in oral fluid and plasma. The sample (0.2 mL) was extracted with an automated solid-phase extraction system (ASPEC XL), using mixed mode OASIS MCX cartridges. Chromatographic separation was performed in a Sunfire C18 IS column (20 mmx2.1 mm, 3.5 microm), using a gradient of acetonitrile and ammonium formate (pH 3; 2 mM) as mobile phase, which allowed the elution of all the compounds in less than 5 min. The method has been fully validated in both specimens. This method was initially applied to the analysis of oral fluid and plasma samples from patients on antidepressant treatment in order to assess for which compounds it was likely to find a good correlation between both matrices. The best results were obtained for venlafaxine, so the study was extended for this compound, comparing the ratio between oral fluid and plasma concentrations (ROF/PL) in five patients on venlafaxine treatment when both samples were collected simultaneously on four different occasions. An important inter and intraindividual variability was found in oral fluid concentrations for 150 mg dose (mean=287.5 ng/m, range 58.8-531.2 ng/mL) and for 75 mg dose (mean=186.3 ng/mL, range=82.1-289.2 ng/mL). R(OF/PL) was calculated for each patient on the four different occasions, showing also a high variability (CV=24.2-69.6%).
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The number of patients who complained of adverse events in the FLV+TJ-43 group (n = 6) was significantly lower than the number complaining in the FLV group (n = 13) (P < 0.05). The number of patients who complained of nausea was also lower in the FLV+TJ-43 group (n = 3) than in the FLV group (n = 9) (P < 0.05). By two weeks after treatment, GSRS scores had improved in the FLV+TJ-43 group, but not in the FLV group. SDS scores were not different between the two groups at any of the assessment points.
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The author explains the development of specific inhibitors of serotonin re-uptake. Fluvoxamine differs from classical tricyclic antidepressants by a pharmacological profile of side-effects and safety of overdosage, while the therapeutic effect is comparable. The serotonin selectivity opens perspectives of further indications.
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The intravaginal ejaculation latency time (IELT) behaves in a skewed manner and needs the appropriate statistics for correct interpretation of treatment results.
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The pharmacokinetic-pharmacodynamic (PK-PD) correlation of the effect of fluvoxamine on para-chloroamphetamine (PCA)-induced behavior was determined in the rat. Rats (n=66) with permanent arterial and venous cannulas received a 30-min intravenous infusion of 1.0, 3.7 or 7.3 mg kg(-1) fluvoxamine. At various time points after the start of fluvoxamine administration, a single dose of PCA (2.5 mg kg(-1)) was injected in the tail vein and resulting behavioral effects, excitation (EXC), flat body posture (FBP) and forepaw trampling (FT), were immediately scored (scores: 0, 1, 2 or 3) over a period of 5 min. In each individual animal the time course of the fluvoxamine plasma concentration was determined up to the time of PCA administration. Observed behavioral effects were related to fluvoxamine plasma concentrations. Fluvoxamine pharmacokinetics was described by a population three-compartment pharmacokinetic model. The effects of fluvoxamine on PCA-induced behavior (probability of EXC, FBP and FT) were directly related to fluvoxamine plasma concentration on the basis of the proportional odds model. For EXC, EC(50) values for the cumulative probabilities P(Y<1), P(Y<2), P(Y<3) were 237+/-39, 174+/-28 and 100+/-20 ng ml(-1), respectively. Slightly higher EC(50) values were obtained for the corresponding effects on FBP and FT. This investigation demonstrates the feasibility of PK-PD modeling of categorical drug effects in animal behavioral pharmacology. This constitutes a basis for the future development of a mechanism-based PK-PD model for fluvoxamine in this paradigm.
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To determine the relationship between serotonin and sexual function, we investigated the role of serotonergic receptors on changes in intracavernous pressure (ICP) and systemic blood pressure (BP) in conscious and free-moving rats.
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A 53-year-old patient suffering from delusional disorder developed an anticholinergic syndrome 19 days after initiation of paroxetine in addition to a steady dose of clozapine. The clozapine plasma concentration had doubled and was in the toxic range. On re-exposition with a lower clozapine dosage the increase was significantly lower. The importance of a dose-dependent interaction of both drugs is emphasized and a possible pharmacological explanation described. With regard to interactions of SSRIs and clozapine, fluvoxamine, a potent inhibitor of cytochrome P450 1A2, gives rise to higher clozapine levels at an earlier time, compared to other SSRIs (paroxetine, fluoxetine and sertraline), which are potent cytochrome P450 2D6 inhibitors.
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Akathisia is a syndrome characterized by the unpleasant sensation of "inner" restlessness that manifests itself in the inability of sitting still or not moving. Many types of medicaments can cause akathisia as an adverse event of their use and they include: antipsychotics, antidepressants, antiemetics, antihistamines, and psychoactive substances. We will present the case of a 50 year old patient, treated on two occasions for psychotic depression. During the second hospitalization it is possible that antipsychotic treatment combined with an antidepressant caused akathisia or there were symptoms of agitated depression and akathisia present at the same time, which is very difficult to determine in everyday clinical practice. We can conclude that in this case, as in many others, akathisia as a possible adverse effect of psychopharmacs was very hard to identify. Therefore, it is necessary to have akathisia in mind when using certain medicaments, especially when combining several that use the same enzymatic system and consequently raise levels of at least one of them.
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In this open trial, fluvoxamine appeared to be well tolerated and was associated with a promising reduction in the depression and anxiety symptoms of pediatric patients with cancer.
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1 The effects of fluvoxamine to a maximum of 300 mg daily were compared with those of imipramine to a maximum of 200 mg daily, in 151 patients with primary major depression. 2 Four weeks of treatment with fluvoxamine resulted in 67.2% improvement (+/- s.d. 21.6) on the Hamilton Rating Scale for Depression (26 items). Treatment with imipramine showed 62.1% improvement (+/- s.d. 29.5) on this scale. 3 Fluvoxamine had no untoward effects on the cardiovascular system, while imipramine produced systematic increases in the postural fall in blood pressure. Dry mouth, nausea, daytime somnolence and tremor were seen with fluvoxamine treatment, while imipramine was associated with dry mouth, daytime somnolence, dizziness and tremor. 4 We conclude that fluvoxamine seems to have the same general antidepressant efficacy as imipramine. It was not associated with any safety problems and was generally well tolerated.
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Antidepressants were prescribed to 139 youths (0.24‰), significantly more to adolescents than pre-adolescents and for the treatment of depressive disorders in females, and mixed disorders of emotions and conduct in males. Sertraline was the most prescribed antidepressant for the treatment of major depressive disorder, followed by fluvoxamine and tianeptine. Fluvoxamine was the most prescribed antidepressant for the treatment of anxiety disorders and mixed disorders of emotions and conduct. Off-label prescribing of antidepressants was found in 85.6% of young patients.
There is evidence showing a reduction in the concentration of serum levels of fluvoxamine, duloxetine, mirtazapine and trazodone in smoking patients as compared to nonsmokers. The evidence regarding other commonly used antidepressants is scarce. Nonetheless, smoking status should be considered when choosing an antidepressant treatment, given the risk of pharmacokinetic interactions.
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Dopamine agonists have been implicated in the treatment of depression. Cabergoline is an ergot derivative with a high affinity to dopamine D(2)-like receptors; however, there have been few preclinical studies on its antidepressant-like effects.
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Changes in neuroplasticity have been involved in the pathogenesis of psychiatric disorders as well as in psychotropic drug action. Calcium/calmodulin-dependent protein kinase II (CaM kinase II), an enzyme with a pivotal role in synaptic plasticity and cognitive functions, has been implicated in the action of anticonvulsants, benzodiazepines, and antidepressants, but little is known as to its role in the action of different drugs employed for treatment of psychiatric disorders.
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We identified promising treatment effects with topiramate for self-injury and impulsive/aggressive behaviors, risperidone for psychotic symptoms associated with uniparental disomy (UPD), and N-acetyl cysteine for skin picking. The pharmacological approach of behavioral impairment in PWS has been poorly investigated to date. Further randomized controlled studies are warranted.
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Patients found all four treatments highly credible following their initial explanation. There was a significant difference both pre- and post-treatment in favour of patients finding treatment involving medication more credible than problem-solving from a nurse. Pre- and post-treatment scores of credibility were not associated with outcome.
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Naphthalene-2,3-dialdehyde (NDA) and anthracene-2,3-dialdehyde (ADA) were applied as pre-column labelling reagents for the peroxyoxalate chemiluminescence detection of primary amines. The advantages of these labels are the selective derivatization reaction with primary amines and the good chemiluminescence properties. A serious disadvantage is the formation of cyanide-induced side-products which are major interferences in reversed-phase chromatography. For normal-phase chromatography, the excess of reagent was removed by adding a polar amine after derivatization, with subsequent extraction of the labelled analyte with an apolar solvent. The detection limit for NDA-labelled fluvoxamine, an anti-depressant, was in the low femtomole range in standard solutions and in urine samples. For ADA-labelled analytes difficulties were obtained with linearity in peroxyoxalate chemiluminescence detection, probably owing to oxidation of the derivative by hydrogen peroxide.
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Obsessive-compulsive disorder is a chronic and often disabling disorder that affects 2 to 3 percent of the U.S. population. Optimal treatment involves a combination of pharmacologic and cognitive-behavioral therapies. Advances in psychopharmacology have led to safe and effective treatments for obsessive-compulsive disorder that provide clinically significant improvement in symptoms. In this article the authors review studies of pharmacologic treatments.
To assess the effects of drug treatment in BPD patients.
Single oral doses of 100 mg caffeine and 20 mg omeprazole were given separately to 5 EMs and 5 PMs of debrisoquin to assess the activity of CYP1A2 and CYP2C19, respectively. Initially, a single oral dose of fluvoxamine (25 mg to PMs and 50 mg to EMs) was given, followed by 1 week of daily administration of 25 mg x 2 to EMs and 25 mg x 1 to PMs. Caffeine (day 6) and omeprazole (day 7) were again administered at the steady state of fluvoxamine. Later the study protocol was repeated with a lower dose of fluvoxamine, 10 mg x 2 to EMs and 10 mg x 1 to PMs for 1 week. Concentrations of fluvoxamine, caffeine, omeprazole, and their metabolites were analyzed by HPLC methods in plasma and urine.