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Two hundred patients with PD were enrolled in our study. All subjects met DSM-IV criteria for PD or PD with agoraphobia (PDA). All patients were assigned to receive SSRI monotherapy for 12 months with either citalopram (n = 50), fluoxetine (n = 50), fluvoxamine (n = 50), or paroxetine (n = 50) in a randomized, nonblinded fashion. Both the treating psychiatrist and the patients were not blind to the assigned treatment, but the clinician raters were blind to the study medication. The study design allowed for assignment of a particular SSRI as indicated according to the clinical judgment of the study psychiatrists. The Panic Self-Questionnaire, which is a self-report scale, was administered at baseline and then once per month during the duration of the 12-month study. The visual analog scale and the Clinical Global Impression Scale were administered at baseline and then once per month during the period of the study. Reports of sexual dysfunction were assessed using a nonstructured clinical interview at monthly visits. The body weight of study subjects was measured at baseline, and then at the 12th month visit end point.
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In this systematic review we present information relating to the effectiveness and safety of the following interventions: addition of antipsychotics to serotonin reuptake inhibitors; behavioural therapy alone or with serotonin reuptake inhibitors; cognitive therapy or cognitive behavioural therapy (alone or with serotonin reuptake inhibitors); electroconvulsive therapy; serotonin reuptake inhibitors (citalopram, clomipramine, fluoxetine, fluvoxamine, paroxetine, sertraline); and optimum duration of maintenance treatment.
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ClinicalTrials.gov identifier: NCT00021528.
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Escitalopram did not affect immediate or delayed verbal memory score throughout treatment. During mirtazapine treatment, participants performed less well in the overall immediate recall score compared to placebo. This impairment was most pronounced in the final trial of the visual verbal learning task.
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The objective of this review was to evaluate the effectiveness of SSRIs in reducing premenstrual syndrome symptoms in women diagnosed with severe premenstrual syndrome.
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Medline and PubMed data search using the words sertraline, Zoloft, diplopia, double vision. A case summary of a patient who developed diplopia from sertraline.
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Eleven studies were included, totalling 190 patients. One study examined venlafaxine, one fluoxetine, one citalopram, one atomoxetine, one modafinil, one lithium, and five antipsychotics. No studies were of adequate duration, size, or outcome, and no controlled trial in a depressed population produced a positive result.
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A total of 50.9% of patients in the buspirone group and 46.7% in the placebo group responded after 4 weeks of treatment. The difference in response rate was not statistically significant. No statistically significant differences were found in the frequency of adverse events. At the follow-up of the open SSRI plus buspirone treatment, 69.4% of patients had responded.
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A literature search of PubMed (1947-November 2012), MEDLINE (1946-November 2012), EMBASE (1974-November 2012), and International Pharmaceutical Abstracts (1970-November 2012) was conducted using the terms linezolid, drug interaction, serotonin syndrome, serotonin toxicity, sympathomimetic, serotonergic agents, and adrenergic agents. Citations of retrieved articles were also reviewed.
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A sensitive and reproducible stir bar sorptive extraction and liquid chromatography (SBSE/LC-UV) method is described for the determination of sertraline, mirtazapine, fluoxetine, citalopram, paroxetine, imipramine, nortriptyline, amitriptyne, and desipramine in plasma samples. Important factors in the optimization of SBSE efficiency are discussed, such as extraction time, pH, ionic strength, influence of plasma proteins, and desorption conditions: solvents, modes (magnetic stir, ultrasonic), time, and number of desorption steps. The SBSE/LC-UV method showed to be linear in a concentration ranging from the limit of quantification (LOQ) to 1000.0 ng mL(-1). The LOQ values ranged from 10.0 ng mL(-1) to 40.0 ng mL(-1). The inter-day precision of the SBSE/LC-UV method presented coefficient of the variation lower than 15%. Based on figures of the merit results, the SBSE/LC-UV methodology showed to be adequate to the antidepressants analyses from therapeutic to toxic therapeutic levels. In order to evaluate the proposed method for clinical use, the SBSE/LC-UV method was applied to the analysis of plasma samples from elderly depressed patients.
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Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion.
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Considering the gene X environment hypothesis of depression, the present study investigated the effect of chronic ozone inhalation on depression and anxiety-related behavior, cognition, and brain markers of oxidative stress in the Flinders Sensitive Line (FSL) rat. In addition, response to the antioxidant melatonin, and the antidepressants desipramine or escitalopram, was assessed.
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1) to examine whether the prevalence of anti-thyroid peroxidase autoantibodies (anti-TPO) in depressive patients differs from that in healthy controls; 2) to investigate the possible relationship between thyroid autoimmunity, total T3, free T3, free T4, thyroid-stimulating hormone (TSH), clinical status and treatment outcome in depression.
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Phase III clinical trials for depression enroll participants with major depressive disorder according to stringent inclusion and exclusion criteria. These patients may not be representative of typical depressed patients seeking treatment. This analysis used data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project--which used broad inclusion and minimal exclusion criteria--to evaluate whether phase III clinical trials recruit representative depressed outpatients.
The marine environment is a valuable resource for drug discovery due to its diversity of life and associated secondary metabolites. However, there is very little published data on the potential application of marine natural products to treat neuropsychiatric disorders. Many natural products derived from chemically defended organisms in the marine environment have pharmacophores related to serotonin or clinically utilized antidepressant drugs. Therefore, in the present study, compounds selected for their structural similarity to serotonin or established antidepressants were evaluated for antidepressant-like activity using the forced swim and tail suspension tests in mice. The antidepressant positive controls, citalopram (selective serotonin reuptake inhibitor) and despiramine (tricyclic antidepressant) both dose-dependently reduced immobility time in the forced swim and tail suspension tests. Two marine natural product compounds tested, aaptamine and 5,6-dibromo-N,N-dimethyltryptamine, also produced significant antidepressant-like activity in the forced swim test. In the tail suspension test, the antidepressant-like effects of 5,6-dibromo-N,N-dimethyltryptamine were confirmed, whereas aaptamine failed to produce significant results. None of the tested compounds induced hyperlocomotion, indicating that nonspecific stimulant effects could not account for the observed antidepressant-like actions of the compounds. These studies highlight the potential to rationally select marine derived compounds for treating depression and other neuropsychiatric disorders.
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Citalopram provided no advantage over placebo in terms of treatment outcomes, and for some measures, citalopram produced poorer outcomes. Patients in the citalopram group had a higher number of heavy drinking days throughout the trial, and smaller changes in frequency and amount of alcohol consumption at 12 weeks. There was no influence of depression severity on outcomes in either medication group. Survival analyses also indicated no differences between depressed and nondepressed patients in the citalopram group for time to first slip or relapse. A diagnosis of personality disorder was associated with poorer treatment responses overall, regardless of treatment condition.
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In order to find appropriate doses for studying antidepressant-ethanol interaction in two mouse strains, spontaneous locomotor activity and rotarod performance were first studied in NMRI mice after amitriptyline 3-30 mg/kg, mianserin 3-30 mg/kg, nomifensine 1- 10 mg/kg, citalopram 3-100 mg/kg, and ethanol 1-3 g/kg intraperitoneally. Ethanol increased significantly locomotor activity at 1 g/kg and impaired rotarod performance at 2 and 3 g/kg. Amitriptyline and mianserin decreased dose-dependently locomotor activity at doses ≥ 10 mg/kg. Nomifensine and citalopram increased locomotor activity at 10 mg/kg and citalopram 100 mg/kg decreased it. Rotarod performance was affected only by amitriptyline 10 and 30 mg/kg and citalopram 100 mg/kg, which impaired performance. Interaction studies with the two strains using amitriptyline, mianserin, nomifensine and citalopram 10 mg/kg and ethanol 1 g/kg showed that C57BL/6 mice were less sensitive than NMRI mice to the stimu lating effects of ethanol and more sensitive to impairment of rotarod performance by amitrip tyline and mianserin. C57BL/6 mice had a significantly poorer baseline performance on rotarod, and the citalopram plus ethanol combination impaired their performance severely, although drugs alone did not impair this test. The results suggest that decreased locomotor activity as a measure of antidepressant-induced sedation does not parallel with impaired performance on rotarod and that significant strain differences can be seen in psy chopharmacological tests and responses to drugs in mice.
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The behavioural effects of selective serotonin reuptake inhibitors (paroxetine, sertraline, citalopram, fluvoxamine, fluoxetine) and reference compounds (N,N'-di(o-tolyl)guanidine, haloperidol, 3-(3-hydroxyphenyl)-N-(l-propyl)piperidine and chlorpromazine) were studied for their ability to produce dystonia and torticollis following direct micro injection into the left red nucleus of the rat, an area of the brain containing a high density of sigma2 receptors but relatively devoid of biogenic amine receptors. Each animal was monitored for abnormalities in posture and movement for a period of 30 min and then sacrificed 40 min following drug administation. Only fluvoxamine (100 nmol) and fluoxetine (100 nmol) elicited acute dystonic behaviour (1-5 min). The onset of dystonia was accompanied by facial spasticity, vacuous chewing movements and grooming behaviour which reflected the extent of dystonia. The dystonic behaviour following the direct intrarubal injection of fluvoxamine and fluoxetine suggest the possible activation of sigma2 receptors while citalopram, sertraline and paroxetine were without effect. The results of this study support the role of sigma2 receptors in the regulation and control of movement and coordination and provides preliminary evidence to suggest the in vivo activity of sigma receptors by fluoxetine and fluvoxamine.
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In rats treated daily for 14 days with citalopram (10 mg kg(-1) day(-1) s.c.), dialysate noradrenaline levels showed remarkable decreases in both the BLA and the LC to about 25 and 45% of controls, respectively. The stress-induced increase of noradrenaline was almost completely abolished in the BLA, but was relatively stable in the LC. The effect of local application of desipramine tended to be suppressed only in the LC. The effect of local application of clonidine was enhanced only in the BLA.
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One method to reduce drug costs is to promote dose form optimization strategies that take advantage of the flat pricing of some drugs, i.e., the same or nearly the same price for a 100 mg tablet and a 50 mg tablet of the same drug. Dose form optimization includes tablet splitting; taking half of a higher-strength tablet; and dose form consolidation, using 1 higher-strength tablet instead of 2 lower-strength tablets. Dose form optimization can reduce the direct cost of therapy by up to 50% while continuing the same daily dose of the same drug molecule.
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Serotonin plays a role in the regulation of emotional states in amygdala which in turn affect the function of hypothalamus. The physiological effects of emotions are mediated to autonomic nervous system by the hypothalamus, also innervated by the serotonergic Raphe nuclei.
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In this 8-week trial, subjects were initiated on 20 mg/day of citalopram and titrated up to 60 mg/day by the fourth week, if tolerated. The primary outcome measure was the Overt Aggression Scale-Modified (OAS-M), a scale used to quantify verbal and physical aggression, subjective irritability, and overt irritability. Secondary outcome measures included the Barratt Impulsiveness Scale and Buss-Durkee Hostility Inventory.
Caudate-putamen membranes of rhesus monkey were solubilized (1% digitonin; w/v) and [3H]WIN 35,428 ([3H]CFT: 2 beta-carbomethoxy-3- beta-(4-fluorophenyl)-N-[3H]methyltropane) binding assayed. Saturation analysis revealed high- and low-affinity binding components (KHIGH: 7.48 +/- 2.77 nM; KLOW: 292 +/- 788 nM; mean +/- SEM). Monoamine transport inhibitors and neurotransmitters had similar affinities for soluble and membrane [3H]CFT binding sites (r, 0.998; P < .001). The rank order of potency of these compounds for inhibiting [3H]CFT binding (Lu 19-005 > mazindol > CFT > GBR 12909 > (-)-cocaine > talsupram > dopamine > norepinephrine > citalopram) was consistent with [3H]CFT labeling cocaine binding sites on the dopamine transporter. [3H]CFT binding sites were separated into three protein fractions by anion-exchange chromatography. Monoamine transport inhibitors and neurotransmitters inhibited [3H]CFT binding in each fraction with a rank order of potency consistent with binding to the dopamine transporter. Detection of multiple binding components for [3H]CFT labeled sites by these drugs varied in each fraction. Size-exclusion chromatography indicated [3H]CFT bound to a single protein in each fraction (apparent molecular weight, 170 kDa). Therefore, multiple binding components for cocaine reside solely on the dopamine transporter and exhibit different affinities for drugs depending on the charge-state of the transporter.
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Genetic variabilities within the serotoninergic system may predict response or remission to antidepressant drugs. Several serotonin receptor (5-HTR) gene polymorphisms have been associated with susceptibility to psychiatric diseases. In this study, we analyzed the correlation between 5-HTR1A and 5-HTR2A polymorphisms and response or remission to selective serotonin reuptake inhibitors (SSRIs) drugs.
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The co-occurrence of obsessive-compulsive and psychotic symptoms in one patient often represents a diagnostic problem. Distinguishing among a schizophrenic disorder with comorbid obsessional symptoms, an OCD with comorbid psychotic symptoms, or an OCD and schizophrenia or any other psychotic disorder is of clinical importance, since the different diagnoses have different therapeutic as well as prognostic implications. In the following case report we describe a patient who suffered from a typical OCD for more than 18 years and then developed clear psychotic symptoms that completely remitted after treatment with citalopram.
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Clinical psychopharmacological research has focused on several aspects in the last decade in China. First, attention was paid to new drug trials, mainly on newly developed or imported antidepressants or antipsychotics. More and more newly developed antidepressants like SSRI, fluoxetine, paroxetine, sertraline, and citalopram are now available or under clinical observation. Second, studies on the relationship between blood level and clinical response of antidepressants, amitriptyline, or antipsychotics, haloperidol and clozapine were undertaken. Results on amitriptyline showed that the clinical antidepressive effect of the drug was correlated linearly to the parent compound, amitriptyline, and curvilinearly to the hydroxylated metabolite, 10-hydroxynortryptyline. It was found that the plasma level of haloperidol correlated curvilinearly to the clinical antipsychotic effect on schizophrenics with a therapeutic window ranging between 4.2 and 20 ng/mL. Third, pharmacokinetic studies on antidepressants, amitriptyline, imipramine, and maprotiline were undertaken. The results showed longer clearance rate and/or t(1/2) in Chinese literature than those reported in Western literature.
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The analytical measuring range for all analytes spanned from 5 to 1000ng/mL. Intra- and inter-assay precision across four quality control levels were ≤9.2% and ≤14.8%, respectively. A comparison to other LC-MS/MS methods resulted in a strong correlation with correlation coefficients ranging from 0.9929 to 0.9971. Carryover, stability, recovery, matrix effects, extraction and processing efficiency were also deemed acceptable in accordance with FDA recommendations.
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Clinical studies indicate that selective serotonin-reuptake inhibitors (SSRIs) may decrease alcohol intake and craving in particular subgroups of alcoholics. The aim of the present study was to compare the behavioral profile of various SSRIs in alcohol-preferring cAA rats, a genetic model of alcoholism. The effects of acute IP administration of fluoxetine (doses in mg/kg 1-10), citalopram (3-30), fluvoxamine (3-30) and paroxetine (1-10) on ethanol (EtOH) intake and preference, as well as food and total fluid intake, were determined in a 12-h access, water vs. 10% v/v EtOH two-bottle choice paradigm. Each compound reduced EtOH intake [Minimal Effective Doses (MEDs) 5, 10, 30 and 1 mg/kg for fluoxetine, citalopram, fluvoxamine, and paroxetine, respectively]. The degree of selectivity, that is, the extent to which reductions in EtOH intake could be separated from reductions in food and/or total fluid intake varied across the compounds. Thus, whereas EtOH intake was more markedly affected than food intake by fluoxetine, both parameters were equally affected by citalopram, and food intake was more markedly affected than EtOH intake by fluvoxamine and paroxetine. The anti-alcohol effect also differed with respect to specificity, that is, the degree to which effects on EtOH intake coincided with effects on EtOH preference. Whereas fluoxetine showed the highest level of specificity, followed by citalopram and fluvoxamine, the effect of paroxetine was nonspecific. The observed variation in the degree of selectivity and specificity of the anti-alcohol effect of SSRIs suggests that reductions in EtOH intake are not merely a consequence of a general suppressive effect on consummatory behavior. It is hypothesized that differences between the behavioral profiles of these compounds reflect a differential involvement of 5-HT receptor subtypes.
The first case is a young man, aged 20 year, who exhibits the typical picture of an ORS. He has probable olfactory hallucinations. He had good response to a treatment combining escitalopram 15mg and risperidone 1mg. The second case had a first appearance of BDD, but he had auditive hallucinations and the evolution showed a pattern more typical of schizophrenia, paranoid subtype. He responded initially to citalopram 20mg and ripseridone 2mg. Sleepy with risperidone, it was shifted to amisulpiride 200mg. After five years, it was possible to stop the amisulpiride, but we had to maintain it to avoid a relapse. The third case is typical of schizophrenia, with a pseudo neurotic aspect, and its course was terrible, with poor response to all neuroleptic therapy, including clozapine.