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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effectiveness of selective serotonin reuptake inhibitors for depression in remitted schizophrenia has not been clearly demonstrated. A randomized, double-blind, prospective placebo-controlled study was performed of 48 subjects meeting DSM-IV criteria for both schizophrenia in remission and for a major depressive episode. Twenty-seven patients were randomized to placebo and 21 to sertraline. All subjects had a 1-week anticholinergic phase before randomization. The treatment duration was 6 weeks. Sertraline was started at 50 mg/day; this could be increased to 100 mg after 4 weeks for an inadequate response. There were no statistically significant differences in symptoms between the two groups at randomization. There were no differences in outcome between treatment groups. In both groups, between 40% and 50% of subjects showed a 50% reduction in depression score. This study does not provide support for the efficacy of sertraline in the treatment of depression in remitted schizophrenia. The small sample size limits the strength of the conclusions that can be drawn from this study. The study design called for a sample size of 96 on the basis of an expected placebo response rate of 30%. Recruitment for the study was difficult because of the placebo design. The placebo response was 50%. Clinicians and patients underestimate the strength of the placebo response and may overestimate the risk of participating in such a study. Testing the efficacy of widely accepted but poorly evaluated treatments should be a research priority. Future studies require a larger sample size and longer duration of treatment.
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PMID:Double-blind, placebo-controlled comparison of the efficacy of sertraline as treatment for a major depressive episode in patients with remitted schizophrenia. 1179 38

Two surveys of individuals with fibromyalgia were conducted to assess the frequency and prevalence of symptoms (N = 99) as well as healthcare providers, medications, and self-care activities used to manage one's fibromyalgia (N = 54). The pervasiveness of symptoms was striking, with 24 various symptoms ranging from cognitive to intestinal problems occurring in at least 75% of the respondents. Significant correlations were present between health status and both physical (P = .002) and psychological (P =.008) symptoms. There was also a significant correlation between the total number of symptoms and the degree of life disruption attributed to fibromyalgia (P =.015). A variety of healthcare professionals were seen, with internists, family physicians, and rheumatologist most frequently used. Although at least 80% of the respondents reported difficulty with anxiety, confusion, irritability, depression, and cognitive difficulties, less than 10% of the respondents reported seeing a psychiatrist. Most frequently used medications were: amitriptyline, (fluoxetine HCl) Prozac, ibuprofen (Motrin), sertraline HCI (Zoloft), and zolpidem (Ambein). Self-care activities used with the most success were walking, stretching, and exercising. These studies indicate the need for more research and support for healthcare providers as well as patients with fibromyalgia.
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PMID:Fibromyalgia: patient perspectives on symptoms, symptom management, and provider utilization. 1183 25

The selective serotonin reuptake inhibitors (SSRIs) have become the most prescribed antidepressants in many countries. Although the SSRIs share a common mechanism of action, they differ substantially in their chemical structure, metabolism, and pharmacokinetics. Perhaps the most important difference between the SSRIs is their potential to cause drug-drug interactions through inhibition of cytochrome-P450 (CYP) isoforms. This paper provides an update on both the in vitro and in vivo evidence with respect to CYP-mediated drug-drug interactions with this class of antidepressants. The available evidence clearly indicates that the individual SSRIs display a distinct profile of cytochrome P450 inhibition. Fluvoxamine is a potent CYP1A2 and CYP2C19 inhibitor, and a moderate CYP2C9, CYP2D6, and CYP3A4 inhibitor. Fluoxetine and paroxetine are potent CYP2D6 inhibitors, whereas fluoxetine's main metabolite, norfluoxetine, has a moderate inhibitory effect on CYP3A4. Sertraline is a moderate CYP2D6 inhibitor; citalopram appears to have little effect on the major CYP isoforms. Fluoxetine deserves special attention as inhibitory effects on CYP-activity can persist for several weeks after fluoxetine discontinuation because of the long half-life of fluoxetine and its metabolite norfluoxetine. Drug combinations with SSRIs should be assessed on an individual basis. Knowledge regarding the CYP-isoforms involved in the metabolism of the co-administered drug may help clinicians to anticipate and avoid potentially dangerous drug-drug interactions. Anticipated interactions can usually be managed by appropriate dose adjustment and titration of the object drug. In some cases, therapeutic drug monitoring can be useful. Equally well, an SSRI with limited interaction potential may be selected to treat depression in patients that receive other medications.
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PMID:Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update. 1187 75

The neurotransmitter serotonin is involved in a variety of brain functions, and abnormal changes in serotonin neurotransmission are associated with an array of psychiatric disorders, including depression. Sertraline is a selective serotonin reuptake inhibitor (SSRI) and an effective antidepressant. Sertraline increases the serotonin concentration in the synaptic cleft by a short-term action; however, clinical improvement is observed only after several weeks, suggesting that the therapeutic effect may be caused by long-term alterations in serotonin transmission. We determined the effects of sertraline on serotonin synthesis in vivo and in vitro. Long-term treatment of rats with sertraline up-regulated mRNA and protein levels of the serotonin-synthesizing enzyme tryptophan hydroxylase (TPH), as determined by in situ hybridization and immunocytochemistry, respectively. In vitro studies using RBL-2H3 cells also showed an increase in mRNA and protein levels of TPH by sertraline, as determined by Northern blot and immunoblot analyses, respectively. This was accompanied by increases in the levels of TPH enzymatic activity and total serotonin. These data demonstrate that in addition to the known short-term action as an uptake blocker, sertraline also exerts a long-term effect on the serotonin neurotransmission by enhancing serotonin synthesis. A similar effect was observed with another SSRI, fluoxetine, but not with the non-SSRI chlorpromazine. The up-regulation of TPH gene expression by sertraline was attenuated by the protein kinase A (PKA) inhibitor N-[2-(p-bromocinnamylamine)-ethyl]-5-isoquinolinesulfonamine, suggesting that a mechanism involving the PKA signaling pathway might at least in part mediate the long-term therapeutic action.
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PMID:Up-regulation of tryptophan hydroxylase expression and serotonin synthesis by sertraline. 1190 Dec 16

Sertraline (SRT) has been shown to be an effective antidepressant in extensive clinical trial programs but data on plasma concentrations regarding clinical outcome and tolerability are lacking. Twenty-one out-patients of both sexes, with mean age of 50.23 years (S.D. = 17.37), affected by major depressive disorder, recurrent (Diagnostic and Statistical Manual of Mental Disorder--IV, DSM-IV), were treated with 25-150 mg of SRT once a day (mean=66.26 mg, S.D.=30.50) for 30 days. Clinical evaluation was assessed at baseline (T0), after 15 days (T15), and then after 30 days (T30). Plasma samples for SRT level determination were collected at T30. Brief Psychiatric Rating Scale (BPRS), Hamilton Rating Scale for Depression (HRS-D), and Hamilton Rating Scale for Anxiety (HRS-A) showed a significant improvement during the study (P<.01 vs. T0). The most commonly reported side effects were nausea (19%), cephalalgia (9.5%), dry mouth (9.5%), decreased libido (9.5%), tremor (4.7%), and tachycardia (4.7%). SRT plasma levels ranged from 2.82 to 112.20 ng/ml (mean=40.42 ng/ml, S.D.=26.93). No correlation between SRT plasma levels and clinical improvement or side effects were observed. Drug plasma level determination does not seem be strictly necessary from a clinical point of view but further research seems advisable in patients at risk like elderly and during long-term studies.
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PMID:Clinical outcome and tolerability of sertraline in major depression: a study with plasma levels. 1199 14

Sertraline (CAS 79617-96-2) is a relatively safe medication for patients suffering from depression. Data reporting the postmortal distribution of sertraline and desmethylsertraline remain rare as well as reports of risks of side effects following ingestion of the drug. In a case of a young woman found dead in her flat sertraline and desmethylsertraline were identified and quantified in body fluids and tissues by gas chromatography/mass spectrometry and high performance liquid chromatography with diode array detection after alkaline extraction. Sertraline and its desmethyl metabolite were found in the peripheral blood in levels of 0.15 mg/l and 0.20 mg/l, concentrations in liver and bile were markedly higher. By exclusion of other reasons for death a lethal sertraline intoxication was decided. Sertraline is suggested to possess a low inherent toxicity, however, a risk of side-effects which may occur in single cases even under moderate dosages should be considered.
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PMID:[Postmortem distribution of sertraline and desmethylsertraline in a fatality]. 1236 35

There have been no studies specifically examining the efficacy of selective serotonin reuptake inhibitor antidepressants for the symptoms of depression in schizophrenia. This study aimed to determine the efficacy and safety of sertraline as a treatment for depressive symptoms in patients with stable, chronic schizophrenia. The Beck Depression Inventory (BDI) was used as the principal outcome measure and other measures of depressive symptoms as secondary outcome measures. Twenty-six patients were entered into a double-blind, placebo-controlled, 8-week trial of sertraline and were included in the intent-to-treat (ITT) analysis (13 in each group). Eight patients in the sertraline group and 12 in the placebo group completed at least four weeks in the study and were considered to have had adequate treatment. On the ITT analysis, the mean score on the BDI fell 14.5% for the sertraline group and 5.6% for the placebo group (p > 0.05); the mean score on the Hamilton Depression Rating Scale (HDRS) fell 16.99% for the sertraline group and 8.3% for the placebo group (p > 0.05). When the analysis was repeated for those who had received adequate treatment, the mean BDI score fell by 28% for the sertraline group and 6% for the placebo group (p = 0.1); the mean HDRS score fell 31% for the sertraline group and 8.6% for the placebo group (p = 0.02). On the Clinical Global Impression-Improvement Scale, 10 of the 13 patients on sertraline improved against four of the 13 in the placebo group (p = 0.05). Sertraline-treated patients showed a significant improvement on the anxiety/ depression subscale of the BPRS on ITT analysis (F = 10.1, p = 0.004). There was no significant effect on negative or positive symptoms. Sertraline was well tolerated. The results suggest that sertraline is useful as a treatment for depressive symptoms in schizophrenia.
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PMID:A double-blind, placebo-controlled trial of sertraline for depressive symptoms in patients with stable, chronic schizophrenia. 1268 Jul 47

The acute treatment efficacy, tolerability, and effects on health-related quality of life of sertraline (50-200 mg/day) versus imipramine (75-225 mg/day) were compared in outpatients with non-melancholic depression. The study employed an open-label, parallel-group design. One hundred and sixteen patients were randomized to receive sertraline and 123 to receive imipramine for 8 weeks. In the intent-to-treat (ITT), last-observation-carried-forward (LOCF) analysis, sertraline produced statistically significantly greater improvements in depressive (21-item Hamilton Depression Rating Scale [HAM-D(21)] scores of 24.9 and 24.4 were reduced to 10.3 and 13.1 at endpoint, P<.005) and anxiety symptoms (Hamilton Anxiety Rating Scale [HAM-A] scores of 21.8 and 21.9 were reduced to 9.5 and 13.9, P<.01), as well as in response (69.0% versus 53.7% at endpoint, P=.016) and remission rates (51.3% versus 38.0% at endpoint, P=.041) from week 4 onwards compared with imipramine. The proportion of patients who were 'very much improved' or 'much improved' (Clinical Global Impressions Scale of Improvement [CGI-I] score of 1 or 2) was significantly higher at endpoint in the sertraline group (76.1%) than in the imipramine group (62.8%) (P=.028). At week 8, patients in both treatment groups showed clear improvements in quality of life, although nonstatistically significant differences were evident in the quality of life of sertraline- versus imipramine-treated patients. Sertraline was significantly superior in tolerability with less discontinuations due to adverse events (10.3%) compared with the imipramine group (24.4%) (P=.004). It was concluded that sertraline is more effective than imipramine in the acute treatment of depressive and anxiety symptoms in patients with non-melancholic depression.
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PMID:Sertraline is more effective than imipramine in the treatment of non-melancholic depression: results from a multicentre, randomized study. 1269 86

Comorbidity of mood and anxiety disorders is common in patients suffering from post-traumatic stress disorder (PTSD). The current study evaluated the efficacy and tolerability of sertraline in a subgroup of PTSD patients suffering from anxiety or depression comorbidity. Two multicenter, 12-week, double-blind, flexible-dose US studies of adult outpatients from the general population with a DSM-III-R diagnosis of PTSD evaluated the safety and efficacy of sertraline (50 to 200 mg/d) compared to placebo in the treatment of PTSD. The total severity score of the Clinician-Administered PTSD Scale (CAPS-2) and the Davidson Trauma Scale (DTS) were used to examine the effect of comorbidity on treatment outcome. Among the combined 395 subjects enrolled in the two trials, 32.9% had a comorbid depressive diagnosis (no anxiety diagnosis), 6.3% had a comorbid anxiety disorder diagnosis (no depression), 11.4% had both a depression and anxiety disorder diagnosis, and 49.4% had no comorbidity. The correlation, at baseline, between Hamilton Depression Rating Scale (HAM-D) total score and the three CAPS-2 clusters was 0.37 for the re-experiencing/intrusion cluster, 0.52 for the avoidance/numbing cluster, and 0.45 for the hyperarousal cluster. Patients suffering from PTSD complicated by a current diagnosis of both depression and an anxiety disorder showed the highest baseline CAPS-2 cluster score severity. Patients treated with sertraline improved significantly (P <.05) compared to placebo on both the CAPS-2 and DTS whether or not they had a comorbid depressive or anxiety disorder. Sertraline was well tolerated. The presence of comorbidity was associated with a modest and mostly nonspecific increase in the side effect burden of approximately 10% to 20% on both study treatments. Patients suffering from dual depression and anxiety disorder comorbidity benefited from somewhat higher doses (147 mg v 125 mg; P =.08). Similarly, the presence of dual comorbidity resulted in a modest but nonsignificant increase in the mean time to response from 4.5 weeks to 5.5 weeks. We conclude that sertraline (50 to 200 mg/d) is effective and well tolerated in the treatment of PTSD for patients suffering from a current, comorbid depressive or anxiety disorders.
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PMID:Affective and anxiety comorbidity in post-traumatic stress disorder treatment trials of sertraline. 1450 96

Alcoholism and depression are common disorders that frequently co-occur in the same individual. Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of depression and also had decreased drinking in some studies of heavy drinkers and alcoholics. The reported effect of serotonergic medications on alcohol intake in depressed alcoholics has not been consistent. Most previous studies have not investigated the use of an SSRI in the context of cognitive behavioral therapy (CBT), a known efficacious treatment of both alcoholism and depression. The study presented here was a randomized placebo-controlled 12-week trial of sertraline combined with individual CBT focused on both alcoholism relapse prevention and depressive symptoms. Subjects were 82 currently depressed, actively drinking alcohol-dependent individuals. Subjects had either primary (independent) major depression (70 subjects) or substance-induced mood disorder and at least 1 first-degree relative (parent, sibling, or child) with an affective disorder (12 subjects). Depression and alcohol consumption outcomes were measured weekly over 12 weeks. Sertraline was well tolerated and all subjects had decreases in both depression and alcohol use during the study compared with baseline. Subjects who received sertraline had fewer drinks per drinking day than subjects who received placebo, but other drinking outcomes were not different between the 2 treatment groups. Treatment with sertraline was associated with less depression at the end of treatment in female subjects compared with female subjects who received placebo. Less drinking during the study was associated with improved depression outcome. The findings in this study suggest that sertraline, compared with placebo, may provide some modest benefit in terms of drinking outcome and also may lead to improved depression in female alcohol-dependent subjects. Additionally, alcohol relapse prevention CBT, delivered according to manual guidelines with modifications that provide specific attention to depression, appeared to be of benefit to subjects, although this interpretation is limited by the design of the study.
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PMID:Sertraline and cognitive behavioral therapy for depressed alcoholics: results of a placebo-controlled trial. 1462 85


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