Antidepressants In Individuals Research Articles

Baseline benzodiazepine exposure is associated with greater risk of transition in clinical high-risk for psychosis (CHR-P): a meta-analysis.

Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics and to antidepressants in individuals at clinical high-risk for psychosis (CHR-P) have opposite prognostic effects as regards imminent transition to psychosis, with antipsychotics associated with higher risk and antidepressants associated with a lower risk in comparison to not-exposed individuals. Despite their common use, baseline exposure to benzodiazepines (BDZ) in CHR-P has surprisingly received poor attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap. Systematic scrutiny of Medline and Cochrane library, performed up to 31 December 2022, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on BDZ baseline exposure in relation to such outcome. Of 1893 identified records, five studies were included in the systematic review and meta-analysis. The proportion of participants with exposure to BDZ at baseline ranged from 5.5% (one study) to 46.2%, with an average of 16.8%. At the end of the period of observation, i.e., the follow-up as reported in the study, 28.4% [95% confidence interval (CI) 19.7-39.1%] participants developed psychosis among the BDZ-exposed against 9.3% (7.3 to 11.9%) among the controls. CHR-P participants who were already under BDZ treatment at baseline had more than double chance of transition to psychosis than CHR-P participants who were BDZ-naïve. The risk ratio (RR) was 2.42 (95% CI 1.38-4.23) in the common effects model (z = 3.09; p = 0.002), and 2.40 (1.53 to 3.77) in the random-effects model (z = 5.40; p = 0.006; tau-squared = 0.0). There was no relevant heterogeneity: Cochran's Q = 1.49; df = 4; p = 0.828; I2 = 0.0% (95% CI 0.0-79%). Quality was good in four studies. Ongoing BDZ exposure at inception in CHR-P is associated with a higher risk of transition to psychosis at follow up. This meta-analytic association, which echoes a similar effect of baseline antipsychotic exposure, plausibly indicates that the clinicians' prescription of pharmacological intervention captures some form of prognostically-relevant information (e.g. an anxiety permeated mental state requiring BDZ prescription) that are not adequately encompassed by current CHR-P categorical criteria.

Initiation of antidepressants in young adults after ischemic stroke: a registry-based follow-up study

ObjectiveData on post-stroke use of antidepressants in young individuals are scarce. We examined pattern and factors associated with initiating post-stroke antidepressants (PSAD) after ischemic stroke (IS) in young adults.MethodsHelsinki Young Stroke Registry includes patients aged 15–49 years with first-ever IS, 1994–2007. Data on prescriptions, hospitalizations and death came from nationwide registers. We defined time of initiating PSAD as time of the first filled prescription for antidepressants within 1 year from IS. We assessed factors associated with initiating PSAD with multivariable Cox regression models, allowing for time-varying effects when appropriate.ResultsWe followed 888 patients, of which 206 (23.2%) initiated PSAD. Higher hazard of starting PSAD within the first 100 days appeared among patients with mild versus no limb paresis 2.53 (95% confidence interval 1.48–4.31) and during later follow-up among those with silent infarcts (2.04; 1.27–3.28), prior use of antidepressants (2.09; 1.26–3.46) and moderate versus mild stroke (2.06; 1.18–3.58). The relative difference in the hazard rate for moderate–severe limb paresis persisted both within the first 100 days (3.84, 2.12–6.97) and during later follow-up (4.54; 2.51–8.23). The hazard rate was higher throughout the follow-up among smokers (1.48; 1.11–1.97) as well as lower (1.78; 1.25–2.54) and upper white-collar workers (2.00; 1.24–3.23) compared to blue-collar workers.ConclusionOne-fourth of young adults started PSADs within 1 year from IS. We identified several specific clinical characteristics associated with PSAD initiation, highlighting their utility in assessing the risk of post-stroke depression during follow-up.

Elevating the level of hypoxia inducible factor may be a new potential target for the treatment of depression

Hypoxia inducible factor-1 (HIF-1) is a transcriptional factor that regulates gene expressions in response to decreased oxygen levels in the tissue, or hypoxia. HIF-1 exerts protective effects against hypoxia by mediating mitochondrial metabolism and consequently reducing oxidative stress. Recently, increased levels of oxidative stress and abnormal energy metabolism in the brain have been suggested to play essential roles in the pathogenesis of depression. Given that HIF-1 activates creatine metabolism and increases phosphocreatine levels in the intestinal epithelial cells, we assume that HIF-1 may induce similar processes in the brain. Elevated phosphocreatine levels in the brain, as measured by magnetic resonance spectroscopy, were associated with better treatment response to the antidepressants in individuals with depression. In addition, oral creatine supplements, which led to increased phosphocreatine levels in the brain, also enhanced the effects of antidepressants in individuals with depression. As such, we hypothesized that increasing the HIF-1, which potentially facilitates creatine metabolism in the brain, might be a new therapeutic target in depression. With this regard, we suggested that interventions to elevate the HIF-1 levels in the brain, including the intermittent hypoxia conditioning and hyperbaric oxygen therapy, might be considered as new additional treatments for depression.

Associations of Clinically Relevant Levels of Depressive Symptoms and Antidepressant Use With Mortality in African American Health

BackgroundThe Institute of Medicine has highlighted unequal treatment for African American individuals in health care. We examined the association of underuse of antidepressants in African American individuals with increased mortality. MethodsWe conducted a longitudinal cohort study in Metropolitan St Louis, Missouri, in a population-based study of community-dwelling African American individuals, aged 52 to 68 years. Medication evaluations and clinically relevant levels of depressive symptoms (CRLDS) assessments occurred in 2000 and 2004. The analytic sample included 830 (of 853 total, 97%) participants with complete data. CRLDS was defined as ≥9 on the 11-item Center for Epidemiologic Studies Depression scale. Antidepressant use was determined by in-home medication recording and in-center coding. Participants were placed into 4 exposure categories: persistent CRLDS–no antidepressant (n = 69); intermittent CRLDS–no antidepressant (n = 123); antidepressant treatment (n = 110); and no CRLDS–no antidepressant (n = 528). Logistic regression with backwards elimination of the 9 identified potential confounders was used to examine associations of exposures with all-cause mortality over 6 years (2004–2010). Five sensitivity analyses investigated robustness of the primary findings. ResultsThe antidepressant group was independently associated with reduced mortality compared with the persistent–no antidepressant group (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.08–0.44). Sensitivity analyses showed no substantive differences from the primary model; one indicated that the persistent CRLDS–no antidepressant group experienced significantly increased mortality compared with the no CRLDS–no antidepressant group (OR 2.12, 95% CI 1.10–4.09), whereas the intermittent–no antidepressant group did not (OR 0.83, 95% CI 0.44–1.58). ConclusionsThese results highlight that underuse of antidepressants in African American individuals is associated with increased mortality.

Is the efficacy of antidepressants in panic disorder mediated by adverse events? A mediational analysis.

It has been hypothesised that the perception of adverse events in placebo-controlled antidepressant clinical trials may induce patients to conclude that they have been randomized to the active arm of the trial, leading to the breaking of blind. This may enhance the expectancies for improvement and the therapeutic response. The main objective of this study is to test the hypothesis that the efficacy of antidepressants in panic disorder is mediated by the perception of adverse events. The present analysis is based on a systematic review of published and unpublished randomised trials comparing antidepressants with placebo for panic disorder. The Baron and Kenny approach was applied to investigate the mediational role of adverse events in the relationship between antidepressants treatment and efficacy. Fourteen placebo-controlled antidepressants trials were included in the analysis. We found that: (a) antidepressants treatment was significantly associated with better treatment response (ß = 0.127, 95% CI 0.04 to 0.21, p = 0.003); (b) antidepressants treatment was not associated with adverse events (ß = 0.094, 95% CI -0.05 to 0.24, p = 0.221); (c) adverse events were negatively associated with treatment response (ß = 0.035, 95% CI -0.06 to -0.05, p = 0.022). Finally, after adjustment for adverse events, the relationship between antidepressants treatment and treatment response remained statistically significant (ß = 0.122, 95% CI 0.01 to 0.23, p = 0.039). These findings do not support the hypothesis that the perception of adverse events in placebo-controlled antidepressant clinical trials may lead to the breaking of blind and to an artificial inflation of the efficacy measures. Based on these results, we argue that the moderate therapeutic effect of antidepressants in individuals with panic disorder is not an artefact, therefore reflecting a genuine effect that doctors can expect to replicate under real-world conditions.

Depression and use of antidepressants in Swedish nursing homes: a 12-month follow-up study

The prescription of antidepressants in nursing homes has increased markedly since the introduction of SSRIs, while at the same time depressive symptoms often go unrecognized and untreated. The aim of this study was to examine whether depression among residents in nursing homes is treated adequately. A sample of 429 participants from 11 Swedish nursing homes was selected and was assessed with the Cornell Scale for Depression in Dementia (CSDD) and using medical records and drug prescription data. For 256 participants a follow-up assessment was performed after 12 months. The prevalence of depression, according to medical records, was 9.1%, and the prevalence of CSDD score of ≥8 was 7.5%. Depression persisted in more than 50% of cases at the 12-month follow-up. Antidepressants were prescribed to 33% of the participants without a depression diagnosis or with a CSDD score of <8. 46.2% of all participants were prescribed antidepressants. 14% of the participants without a depression diagnosis or with a CSDD score of <8 had psychotropic polypharmacy. 15.2% of all participants had psychotropic polypharmacy, which persisted at the 12-month follow-up in three-quarters of cases. The prescription of antidepressants in frail elderly individuals is extensive and may be without clear indication. The clinical implication is that there is a need for systematic drug reviews at nursing homes, paying special attention to the subjects which are on antidepressants.

National trends (2003–2009) and factors related to psychotropic medication use in community-dwelling elderly population

We aimed to analyze the prevalence of prescription anxiolytics and antidepressants in elderly individuals in Spain between the years 2003 and 2009, and to identify those factors associated with the likelihood of consumption of these drugs during the study period. We used individualized secondary data retrieved from the 2003 and 2006 Spanish National Health Surveys (SNHS) and the 2009 European Health Interview Survey (EHIS) for Spain to conduct a nationwide, descriptive, cross-sectional pharmacoepidemiology study on psychotropic medication in the population aged 65 years and over in Spain. A total of 12,228 interviews were analyzed (5,117 from 2003; 7,084 from 2006; and 5,144 from 2009). The dichotomous dependent variables chosen were the answers "yes" or "no" to the question "In the last two weeks have you taken the following medicines and were they prescribed for you by a doctor?" referring to intake of anxiolytics and antidepressants. Independent variables were sociodemographic, comorbidity, and healthcare resources. Multivariate analysis highlighted the association between increased psychoactive drug intake and female gender, depression, polypharmacy, and negative perception of health. We observed a significant increase in the consumption of prescription anxiolytics (AOR, 1.08 [95% CI, 1.06-1.10]) and antidepressants (AOR, 1.11 [95% CI, 1.08-1.14]) in individuals aged ≥65 years in Spain between the years 2003 and 2009. The prevalence of anxiolytics and antidepressants consumption is higher in elderly women than men, and increases with negative perception of health. The Spanish elderly individuals taking antidepressants reported having problems to manage these medicines in their own homes.

Serum Concentrations of Antidepressants in The Elderly

The elderly is the most rapidly growing subpopulation in many countries, and the use of antidepressant drugs among elderly patients may be increasing as depression is one of the most common comorbid conditions in age-related diseases. The aim of the present study was to compare serum concentrations of antidepressants in older versus younger individuals in a naturalistic setting. Serum concentrations from patients treated with antidepressant drugs were withdrawn from a routine therapeutic drug monitoring database and stratified into the age groups younger than 40 years, 40-65 years, and older than 65 years. Dose-adjusted serum concentrations (concentration to dose ratios; nanomoles per liter per milligram per day) and absolute serum concentrations were compared between the subgroups using patients younger than 40 years as control. Altogether, 32,126 serum concentration samples from 17,930 patients treated with selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, or tetracyclic antidepressant drugs were included. Only minor differences in mean concentration to dose ratios and absolute serum concentrations were observed between patients aged 40-65 years and controls. In contrast, for 12 of the 14 drugs included, approximately 1.5- to 2-fold higher mean concentration to dose ratios were observed in patients older than 65 years versus controls (P < 0.01). Significantly higher absolute serum concentrations were also observed in the former compared with the latter subgroup for 8 of these 12 agents (P < 0.01). Patients older than 65 years had a 1.5- to 2-fold higher exposure of most antidepressant drugs compared with those younger than 40 years when given equal doses. This may indicate an increased risk of concentration-dependent side effects in the elderly.

NIH State-of-the-Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults

NIH State-of-the-Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults

Antidepressants for neuroenhancement in healthy individuals: a systematic review

Neuroenhancement offers the prospect of improving the cognitive, emotional and motivational functions of healthy individuals. Of all the conceivable interventions, psychopharmacology provides the most readily available ones, such as antidepressants which are thought to make people “better than well”. However, up until now, whether they possess such an enhancing ability remains controversial and therefore in this systematic review we will evaluate the effect and safety of modern antidepressants in healthy individuals. A search of MEDLINE and EMBASE databases and cross-references was carried out and the pharmaceutical industry was contacted for suitable data. Trials published in any language through the third week of July 2007 were regarded. Included were single or double blind randomised or quasi-randomised controlled trials that compared a placebo to one or more of the following antidepressants: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, moclobemide, paroxetine, reboxetine, sertraline or venlafaxine in any dose or dosing schedule. Eligible studies were those involving healthy people of any age and either sex who showed no evidence of a psychiatric disorder, cognitive decline or other disease. One hundred thirty-five articles met our inclusion criteria reporting single dose trials and trials with repeated drug administration. Sixty-five of these articles were eligible for a statistical analysis. Based on a linear mixed model, a meta-analysis and a fixed effects meta-regression were performed. Pooling of results by meta-analysis was stratified by the outcome measures (a) mood, (b) emotional processing, (c) wakefulness, (d) attention, (e) memory, and (f) executive functions. On a significance level of p < 0.05 the following significant results emerged: After a single dose of an antidepressant, a significant effect was shown in two of the analysed outcomes. Firstly, there was a small yet significant negative effect on wakefulness. On memory, a positive effect after several measurements was found, but this result could be traced to the results of the one study out of all included studies, which had that many assessment points. The analysis of trials with repeated drug administration (mean duration 14 days, standard deviation 9) yielded the following effects: on mood, a non-significant positive effect was detected that was continuously increasing and reached significance at the last assessment point. Regarding attention, a fluctuating effect was found, while for memory, the fact that the two groups started with a group difference confounded the results. For wakefulness there was no significant effect in any particular assessment point, while for emotional processing and executive functions, the small number of studies did not allow for any effect to emerge. In summary, no consistent evidence for enhancing effects of antidepressants could be found. There is little evidence so far to support the popular opinion that antidepressants have a positive effect on the mood of healthy individuals after repeated administration. No evidence of a significant adverse event profile could be found. The studies included in this systematic review not only provide insufficient evidence for or against any effect in healthy people, but they are inapt to be used for answering this question. This may be explained by the fact that most of them were not designed to examine neuroenhancement effects. The growing public interest in neuroenhancement stands in stark contrast to the paucity of data on enhancement effects of available psychopharmacological agents.

Antidepressants and Violence: Problems at the Interface of Medicine and Law

Recent regulatory warnings about adverse behavioural effects of antidepressants in susceptible individuals have raised the profile of these issues with clinicians, patients, and the public. We review available clinical trial data on paroxetine and sertraline and pharmacovigilance studies of paroxetine and fluoxetine, and outline a series of medico-legal cases involving antidepressants and violence. Both clinical trial and pharmacovigilance data point to possible links between these drugs and violent behaviours. The legal cases outlined returned a variety of verdicts that may in part have stemmed from different judicial processes. Many jurisdictions appear not to have considered the possibility that a prescription drug may induce violence. The association of antidepressant treatment with aggression and violence reported here calls for more clinical trial and epidemiological data to be made available and for good clinical descriptions of the adverse outcomes of treatment. Legal systems are likely to continue to be faced with cases of violence associated with the use of psychotropic drugs, and it may fall to the courts to demand access to currently unavailable data. The problem is international and calls for an international response.

Antidepressants Augment Natural Killer Cell Activity: In vivo and in vitro

Depressed mood has been associated with reduced natural killer cell activity (NKCA). Further, amelioration of depressive symptoms by pharmacotherapy has resulted in augmented NKCA. Serotonin, an indoleamine implicated in the pathophysiology of affective disorders, enhances NKCA in vitro and lymphocytes possess serotonin transporters and receptors. The present study evaluated NKCA in depressed outpatients before and during treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac^®). Further, the SSRIs, fluoxetine and paroxetine (Paxil^®), were also incubated in vitro with lymphoid cells to evaluate possible direct effects of SSRIs on NKCA. Depressed outpatients were administered fluoxetine (20 mg/day) for 4 weeks. NKCA and severity of depression were evaluated at weeks 0, 1, 2, and 4. Serum concentrations of fluoxetine and norfluoxetine were obtained as well. Mononuclear cells obtained from nonpatient volunteers were incubated with pharmacologic concentrations of fluoxetine or paroxetine and NKCA measured with a standard chromium release assay. Fluoxetine treatment resulted in decreased symptoms of depression and increased serum concentrations of fluoxetine and norfluoxetine. Further, fluoxetine treatment was associated with augmented NKCA in a subgroup of depressed outpatients exhibiting low NKCA at baseline. Fluoxetine had no effect on NKCA in depressed individuals exhibiting high NKCA at baseline. Incubation of mononuclear cells with fluoxetine and paroxetine augmented NKCA in vitro. The enhancing effects of antidepressants on NKCA in vivo and in vitro indicate a possible direct drug interaction with lymphoid cells during pharmacotherapy, suggesting that pharmacologic treatment of depression may result in enhanced immune competence as indexed by enhanced NKCA and that NKCA could be pharmacologically augmented with antidepressants in individuals with compromised immune function.