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We undertook the parallel-group, double-blind, placebo-controlled, Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial in participants from old-age psychiatry services in nine centres in England. Participants were eligible if they had probable or possible Alzheimer's disease, depression (lasting ≥4 weeks), and a Cornell scale for depression in dementia (CSDD) score of 8 or more. Participants were ineligible if they were clinically critical (eg, suicide risk), contraindicated to study drugs, on antidepressants, in another trial, or had no carer. The clinical trials unit at King's College London (UK) randomly allocated participants with a computer-generated block randomisation sequence, stratified by centre, with varying block sizes, in a 1:1:1 ratio to receive sertraline (target dose 150 mg per day), mirtazapine (45 mg), or placebo (control group), all with standard care. The primary outcome was reduction in depression (CSDD score) at 13 weeks (outcomes to 39 weeks were also assessed), assessed with a mixed linear-regression model adjusted for baseline CSDD, time, and treatment centre. This study is registered, number ISRCTN88882979 and EudraCT 2006-000105-38.
Sertraline appears to be the most cost-effective drug in the treatment of patients with GAD. However, this finding is based on limited evidence for sertraline (two published trials). Sertraline is not licensed for the treatment of GAD in the UK, but is commonly used by primary care practitioners for the treatment of depression and mixed depression and anxiety.
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Numerous studies have reported on pharmacogenetics of antidepressant response in depression. In contrast, little is known of response predictors in obsessive-compulsive disorder (OCD), a disorder with among the lowest proportion of responders to medication (40-60%). Our study is the largest investigation to date (N=184) of treatment response and side effects to antidepressants in OCD based on metabolizer status for CYP2D6 and CYP2C19. We observed significantly more failed medication trials in CYP2D6 non-extensive compared with extensive metabolizers (P=0.007). CYP2D6 metabolizer status was associated with side effects to venlafaxine (P=0.022). There were nonsignificant trends for association of CYP2D6 metabolizer status with response to fluoxetine (P=0.056) and of CYP2C19 metabolizer status with response to sertraline (P=0.064). Our study is the first to indicate that CYP genes may have a role in antidepressant response in OCD. More research is required for a future clinical application of genetic testing, which could lead to improved treatment outcomes.
Our results demonstrate that stimulus-induced response plasticity of VEPs can be induced in the human brain and is sharing properties with hebbian forms of synaptic plasticity. Major depression and antidepressant treatment of healthy control subjects differentially modulate amplitude and plasticity of evoked potentials. This study provides direct evidence in humans for a central role of synaptic plasticity in the pathophysiology of depression.
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Between 2000 and 2002, 40 subjects between 9 and 17 years old were randomized to receive GCBT (n = 20) or sertraline (n = 20). GCBT consisted of a manual-based 12-week cognitive-behavioral protocol adapted for groups, and treatment with sertraline involved medication intake for 12 weeks. Subjects were assessed before, during, and after treatment (at 1, 3, 6, and 9 months after treatment conclusion). Primary outcome measure was the Children's Yale-Brown Obsessive-Compulsive Scale. Repeated-measures analyses of variance were done.
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This article reviews new developments of pharmacotherapy in obsessive-compulsive disorder (OCD) and OC spectrum disorders of the past five years. New developments primarily involved the ex-tension of evidence of efficacy of serotonin reuptake inhibitors(SRIs), the use of atypical antipsychotics in addition to SRIs for treatment refractory patients, the combination of pharmacotherapy with behavior therapy, and studies assessing predictors of response. Today, frontline pharmacological treatment of OCD still consists of drugs with potent serotonin reuptake inhibition proper-ties. In case of non-response, treatment options comprise adding another drug, increasing the dose, switching drugs, or changing the mode of delivery.
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Previous studies indicate that selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, fluvoxamine, citalopram and paroxetine, suppress rapid eye movement sleep, and increased nocturnal arousals. There has been no published report of the impact of sertraline on the sleep of depressed patients. This study examines such effects. Forty-seven patients with major depressive disorder, randomized to double-blind treatment with sertraline or placebo, completed sleep studies before and after 12 weeks of pharmacotherapy. Groups were compared using multivariate analyses of covariance and/or analyses of covariance to examine 4 empirically defined sets of sleep measures. Compared to the placebo-treated group, patients who received sertraline experienced an increase in delta wave sleep in the first sleep cycle and prolonged rapid eye movement (REM) sleep latency. Although, sertraline therapy decreased the average number of REM periods (from 3.86 to 2.40), the activity of both REM period 1 and REM period 2 was significantly increased. Aside from an increase in sleep latency, sertraline therapy was not associated with a worsening of measures of sleep continuity. There was also no significant difference between the groups on a measure of subjective sleepiness. These findings are both similar and different from those observed in previous studies of other SSRIs. The increase in delta sleep ratio and consolidation of REM sleep may have some other clinical implications. However, the generalizability of these findings is limited because of a number of reasons. Further studies are needed to examine the effects of SSRIs in acute treatment of depressed patients with severe insomnia, and the relationship of acute changes and relapse prevention of recurrent depression.
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Background. Dementia is one of the most frequent disorders among elderly patients, reaching to epidemic proportions with an estimated 4.6 million new cases globally annually. Partially effective treatments are available for dementia. Aims & Objectives. We aim to study drugs used in dementia and find out frequency of types of Dementia. Method. This was an observational study conducted at rurally based tertiary care hospital. Prospective data was collected from outpatient department, while retrospective data was collected from medical records. Descriptive statistics were used to analyze data. Result. Total 125 prescriptions of patients diagnosed with dementia were analyzed. Alzheimer's dementia was most common (65.6%), followed by vascular dementia (21.6%), and frontotemporal dementia (10.4%), with the rarest being Lewy body dementia in (2.4%) cases. 60.57% of patients were males. Mini Mental Score Examination mean score was 15.93 ± 1.37. Frontal Battery Assessment mean score was 4.75 ± 1.01. Prescribed drugs were Donepezil (68.49%), Rivastigmine (13.63%), Donepezil + Memantine (6.43%) and Galantamine (12.83%), Quetiapine (38.46%), Lorazepam (23.07%), Clozapine (11.53%), Escitalopram (10.25%), Haloperidol (3.84%), Zolpidem, Sertraline, Olanzepine (2.56%), Nitrazepine, Lamotrigine, Fluoxetine, Tianeptine (1.28%), Folic acid, and Vitamin B12, respectively. Conclusion. Alzheimer's is the most common type of dementia while Donepezil was the most frequent drug.
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The in vitro antimicrobial activity of streptomycin, rifampicin, tetracycline, seven nonsteroidal anti-inflammatory agents (acetyl-salicylic acid, piroxicam, indomethacin, ibuprofen, ketoprofen, sulindac, and diclofenac), and eight phenotiazine derivatives and antidepressant agents (clorpromazine, fluphenazine, amitryptiline, clomipramine, imipramine, maprotiline, sertraline, and diazepam) against 62 strains of Brucella spp. was tested. Diclofenac was the most active of the anti-inflammatory agents (MIC90 = 16 micrograms/ml). The activity of the phenotiazines and antidepressants was heterogeneous, with MIC90s ranging from 16 micrograms/ml for sertraline and 32 micrograms/ml for fluphenazine and clomipramine to > 512 micrograms/ml for diazepam. When the six most active anti-inflammatory agents and the six most active psychiatric drugs were tested at pH 5 and pH 4, the MICs remained unchanged except for those of fluphenazine; the MIC50 and MIC90 of this agent increased by one dilution.
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Randomised studies of antidepressants alone or in combination with another treatment, compared with placebo or a psychosocial intervention in non-depressed pregnant women or women who had given birth in the previous six weeks (i.e. women at risk of postnatal depression)
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Vulnerability to delirium was potentially caused by coadministration of methadone, which can inhibit the CYP2D6 isozyme.
CYP2D6 poor metaboliser genotype and co-medication with inhibitors of CYP2D6 were associated with higher plasma concentrations than the drug-specific median plasma concentration when normalised to dose; plasma concentrations of CYP2C19 extensive metabolisers and smokers were significantly lower than the drug-specific median. Five of the six CYP2D6 poor metabolisers experienced side effects. Response was not associated with plasma concentrations above or below the lower limit of a presumed therapeutic range.
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1. Little is known about drug metabolism in carnivores. Although the domestic cat (Felis catus) is an obligate carnivore and is the most common companion animal, usage and dosage of many drugs are determined according to information obtained from humans and dogs. We determined the complete cDNA sequence of CYP2B6 from the feline lung. 2. Feline CYP2B6 consists of 494 deduced amino acids, showing highest identity with the dog CYP2B ortholog, followed by those of horse, pig, primate and human. 3. Feline CYP2B6 transcripts were expressed predominantly in the lung and slightly in the small intestine but not in the liver without significant sex-dependent differences. Western blot analysis with an anti-human CYP2B6 antibody confirmed the presence of CYP2B protein in the lung but not in the liver. 4. Feline CYP2B6 proteins heterologously expressed in Escherichia coli metabolized several substrates specific to human CYP2B6, including 7-ethoxy-4-(trifluoromethyl) coumarin (EFC). The metabolic activity was strongly inhibited by medetomidine and atipamezole, potent inhibitors of canine CYP2B11 (now officially CYP2B6) as well as by ticlopidine and sertraline, inhibitors selective to human CYP2B6. 5. The results suggest that feline CYP2B6 is a functional CYP2B ortholog that plays a role in the local defense mechanism in the cat respiratory system and intestine.
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Escitalopram (escitalopram oxalate; Cipralex(®), Lexapro(®)) is a selective serotonin reuptake inhibitor (SSRI) used for the treatment of major depressive disorder (MDD) and anxiety disorder. This drug exerts a highly selective, potent, and dose-dependent inhibitory effect on the human serotonin transport. By inhibiting the reuptake of serotonin into presynaptic nerve endings, this drug enhances the activity of serotonin in the central nervous system. Escitalopram also has allosteric activity. Moreover, the possibility of interacting with other drugs is considered low. This review covers randomized, controlled studies that enrolled adult patients with MDD to evaluate the efficacy of escitalopram based on the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. The results showed that escitalopram was superior to placebo, and nearly equal or superior to other SSRIs (eg, citalopram, paroxetine, fluoxetine, sertraline) and serotonin-noradrenaline reuptake inhibitors (eg, duloxetine, sustained-release venlafaxine). In addition, with long-term administration, escitalopram has shown a preventive effect on MDD relapse and recurrence. Escitalopram also showed favorable tolerability, and associated adverse events were generally mild and temporary. Discontinuation symptoms were milder with escitalopram than with paroxetine. In view of the patient acceptability of escitalopram, based on both a meta-analysis and a pooled analysis, this drug was more favorable than other new antidepressants. The findings indicate that escitalopram achieved high continuity in antidepressant drug therapy.
We analyzed data from the ARTIST study, a randomized controlled trial with naturalistic follow-up conducted in 37 primary care clinics. Participants were 573 clinically depressed patients randomized to one of three selective serotonin reuptake inhibitor (SSRI) antidepressants: fluoxetine, paroxetine, or sertraline. Depression as assessed by the Symptom Checklist-20 (SCL-20) was the primary outcome. Secondary outcomes included pain and health-related quality of life.
We suggest that the SSRIs may act as "antiworry" agents and reduce irritability, neuroticism and dysfunctional attributions.
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Major depression with high levels of anxiety (anxious depression) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment. It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors. For this reason, using head-to-head acute treatment comparison, we compared efficacy and tolerability of fluoxetine, sertraline, and paroxetine among depressed patients with high levels of anxiety.
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This study evaluated the safety and pharmacokinetics (PK) of donepezil HCl and sertraline HCl when administered separately and in combination.
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Overall, chromium treatment was associated with reduced mood symptoms and improved overall health satisfaction in most participants. In some cases, chromium alone was associated with marked clinical improvement; in others, chromium plus an antidepressant resulted in greater improvement than either chromium alone or an antidepressant alone.
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We studied reported withdrawal symptoms in a retrospective chart review of 352 patients treated in an outpatient clinic with the nonselective serotonin reuptake inhibitor clomipramine or with one of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine, fluvoxamine, paroxetine, or sertraline. In 171 patients who were supervised during medication tapering and discontinuation, the most common symptoms were dizziness, lethargy, paresthesia, nausea, vivid dreams, irritability, and lowered mood. When patients with at least one qualitatively new symptom were defined as cases, these symptoms occurred significantly more frequently in patients who had been treated either with one of the shorter half-life SSRIs, fluvoxamine or paroxetine (17.2%), or with clomipramine (30.8%), than in patients taking one of the SSRIs with longer half-life metabolites, sertraline or fluoxetine (1.5%). The rate was not significantly different between the different shorter half-life treatments. Cases treated with fluvoxamine or paroxetine had received a significantly longer period of treatment (median 28 weeks) than noncases (16 weeks), but there were no significant associations with age or with diagnostic grouping. There was a trend toward an association with male sex. The majority of cases occurred despite slowly tapered withdrawal. Symptoms persisted for up to 21 days (mean = 11.8 days) after onset. These symptoms were relieved within 24 hours by restarting the medication, but were not relieved by benzodiazepines or by moclobemide. A role has been suggested for serotonin in coordinating sensory and autonomic function with motor activity. We suggest that this may lead to useful hypotheses about the pathophysiology of withdrawal symptoms from serotonin reuptake inhibitors.
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To investigate the pharmacokinetics (PK) of sertraline in overdose and the effect of single dose activated charcoal (SDAC).
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The major drug binding site of sodium channels is inaccessible from the extracellular side, drug molecules can only access it either from the membrane phase, or from the intracellular aqueous phase. For this reason, ligand-membrane interactions are as important determinants of inhibitor properties, as ligand-protein interactions. One-way to probe this is to modify the pH of the extracellular fluid, which alters the ratio of charged vs. uncharged forms of some compounds, thereby changing their interaction with the membrane. In this electrophysiology study we used three different pH values: 6.0, 7.3, and 8.6 to test the significance of the protonation-deprotonation equilibrium in drug access and affinity. We investigated drugs of several different indications: carbamazepine, lamotrigine, phenytoin, lidocaine, bupivacaine, mexiletine, flecainide, ranolazine, riluzole, memantine, ritanserin, tolperisone, silperisone, ambroxol, haloperidol, chlorpromazine, clozapine, fluoxetine, sertraline, paroxetine, amitriptyline, imipramine, desipramine, maprotiline, nisoxetine, mianserin, mirtazapine, venlafaxine, nefazodone, and trazodone. We recorded the pH-dependence of potency, reversibility, as well as onset/offset kinetics. As expected, we observed a strong correlation between the acidic dissociation constant (pKa) of drugs and the pH-dependence of their potency. Unexpectedly, however, the pH-dependence of reversibility or kinetics showed diverse patterns, not simple correlation. Our data are best explained by a model where drug molecules can be trapped in at least two chemically different environments: A hydrophilic trap (which may be the aqueous cavity within the inner vestibule), which favors polar and less lipophilic compounds, and a lipophilic trap (which may be the membrane phase itself, and/or lipophilic binding sites on the channel). Rescue from the hydrophilic and lipophilic traps can be promoted by alkalic and acidic extracellular pH, respectively.