Antidepressants for Major Depressive Disorder and Dysthymic Disorder in patients with co-morbid Alcohol Use Disorders: state of the art and a meta-analysis of placebo-controlled randomized trials.

Abstract Major depressive disorder (MDD) and dysthymic disorder (DD) are often complicated by the co-occurrence of alcohol use disorders (AUDs), each condition often aggravating the course and outcome of the other in terms of severity, functional impairment, risk of suicide, relapse of depression and drinking behaviors, and chronicity. Recently, there has been some evidence that antidepressants may improve depressive symptoms in patients with concurrent AUDs, even if they have only a limited effect in decreasing alcohol use in these subjects. To date, however, there is a paucity of randomized, double-blind, placebo-controlled trials that have been conducted to evaluate the efficacy, safety, and tolerability of antidepressants as monotherapy for patients with MDD/DD and co-occurring AUDs. Although previous meta-analyses have found antidepressants to be more effective than placebo in the treatment of this specific patient population, efficacy for newer agents (i.e. the SSRIs) was questionable. The aim of this study is to examine the efficacy of antidepressants in patients with unipolar depression (MDD and/or DD) with co-morbid AUDs, and to compare compare study design characteristics, patient characteristics, and drug-/placebo- outcomes between depressed patients with or without co-morbid AUDs. Method Medline/Pubmed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for the acute-phase treatment of MDD and/or DD in patients with or without AUDs. The search was limited to articles published between January 1980 and March 2010 (inclusive). We selected for studies which focused on the treatment of adult patients, were at least 4 weeks of duration, used antidepressants in their oral formulation, and used either the Hamilton Depression Rating Scale (HDRS), the Montgomery-Asperg Depression Rating Scale (MADRS), or the Clinical Global Impression-Improvement Scale (CGI) as one of their outcome measures. The primary outcome for our meta-analysis was clinical response, defined as a 50% or greater reduction in HDRS or MADRS scores, baseline to endpoint, or a CGI-I<3 at the final visit. Results A total of 195 manuscripts were found eligible for inclusion in our analysis (n=46,820 patients), 11 of which focused on the treatment of MDD/DD in patients with co-morbid AUDs. We found that antidepressant therapy was more effective than placebo in patients with co-morbid AUDs (RR=1.336; p=0.021), but not when SSRIs were examined alone (RR= 1.145; p=0.316). There was no difference in the relative efficacy of antidepressants (versus placebo) when comparing studies in MDD/DD patients with or without AUDs (p=0.973). Meta-regression analyses yielded no significant differences in the RR of responding to antidepressants versus placebo in trials with co-morbid AUDs whether antidepressants were used alone or adjunctively to psychotherapy, whether used in patients actively drinking or recently sober, or whether used in pure MDD or in combined MDD and DD populations. Moreover, the baseline severity of drinking (assessed as the number of heavy drinking days in the week before randomization) did not predict a significantly difference in the response rate to antidepressants (coefficient= -0.644, p=0.467). Finally, there was no statistically significant difference in the percentage of heavy drinking days at the end of the study between antidepressant- and placebo- treated patients (RR = 0.691, p=0.275) Conclusions Our results suggests that antidepressants are more effective than placebo in treating depression in patients with co-morbid AUDs, and lend further support to the argument that antidepressants should represent first-line therapy for targeting depressive symptoms in patients with alcohol use disorders, a condition which is highly prevalent and is associated with high rates of medical and psychiatric comorbidity, disability, and increased use of general medical health services as well as psychiatric hospitalizations. However, the use of SSRIs for treating depression in such patients is not convincingly supported by the evidence. More data on the use of newer antidepressants, including SNRIs and SSRIs, for this select patient population are needed. Moreover, our work showed that the efficacy of antidepressants was not influenced whether patients were actively drinking or recently sober, and we did not find any relationship between the severity of baseline drinking and treatment outcome. This suggests that the decision whether to recommend antidepressants in this patient population should not be determined by these variables, at least as far as the potential efficacy of treatment is concerned

Antidepressants and age

Antidepressants as a commodity have been remarkably little-studied by economists. This study shows in new data for 27 European countries that 8% of people (and 10% of those middle-aged) take antidepressants each year. The probability of antidepressant use is greatest among those who are middle-aged, female, unemployed, poorly educated, and divorced or separated. A hill-shaped age pattern is found. The adjusted probability of using antidepressants reaches a peak -- approximately doubling -- in people‟s late 40s. This finding is consistent with, and provides a new and independent form of corroboration of, recent claims in the research literature that human well-being follows a U-shape through life

Neural correlates of emotion processing comparing antidepressants and exogenous oxytocin in postpartum depressed women: An exploratory study

Despite common use of antidepressants to treat postpartum depression, little is known about the impact of antidepressant use on postpartum brain activity. Additionally, although oxytocin has been investigated as a potential treatment for postpartum depression, the interaction between antidepressants and exogenous oxytocin on brain activity is unknown. We explored postpartum depressed women’s neural activation in areas identified as important to emotion and reward processing and potentially, antidepressant response: the amygdala, nucleus accumbens and ventral tegmental area. We conducted a secondary analysis of a functional imaging study of response to sexual, crying infant and smiling infant images in 23 postpartum depressed women with infants under six months (11 women taking antidepressants, 12 unmedicated). Participants were randomized to receive a single dose of oxytocin or placebo nasal spray. There was significantly higher amygdala activation to sexual stimuli than either neutral or infant-related stimuli among women taking antidepressants or receiving oxytocin nasal spray. Among unmedicated women receiving placebo, amygdala activation was similar across stimuli types. There were no significant effects of antidepressants nor oxytocin nasal spray on reward area processing (i.e., in the nucleus accumbens or ventral tegmental area). Among postpartum women who remain depressed, there may be significant interactions between the effects of antidepressant use and exogenous oxytocin on neural activity associated with processing emotional information. Observed effect sizes were moderate to large, strongly suggesting the need for further replication with a larger sample

Medication used in intentional drug overdose in Flanders 2008-2013

Background : Intentional drug overdose is the most common method of self-harm. As psychiatric disorders are very common in self-harm patients, the medication used to treat these disorders can become the means for the self-harm act. The present study aimed at investigating an association between the use of prescribed medication (analgesics and antipyretics, anti-epileptics, antipsychotics, antidepressants and psychostimulants) as a method of self-harm and prescription rates of this medication in Flanders. We investigated the possible effect of gender, alcohol use during the self-harm act and a history of self-harm. Methods : Data from the multicenter study of self-harm in Flanders between 2008 and 2013 were used. The significance of differences in percentages was calculated by GEE and the strength by odds ratios (OR). Results : There was an increase in the odds of using antidepressants (0.8%) and antipsychotics (2%) among females when the rate of prescription increases. Analgesics and antipyretics (39.3/1,000) and antidepressants (124.9/1,000) were the most commonly prescribed drugs among females. Antidepressants (63.9/1,000) and antipsychotics (26.5/1,000) were the most commonly prescribed drugs among males. Antidepressants and analgesics and antipyretics were the most frequently used medications for self-harm. Analgesics and antipyretics during the self-harm act were more common among first-timers, while repeaters more commonly overdosed using antipsychotics and antidepressants. Conclusion : These findings suggest that the availability of medication via prescriptions plays an important role in the choice of the medication ingested during the self-harm act. Precautions are necessary when prescribing medication, including restrictions on the number of prescriptions and the return of unused medication to pharmacies after cessation of treatment. These issues should be a focus of attention in the education and training of physicians and pharmacists

Depression, antidepressants and driving safety.

BackgroundThe purpose of this study was to review to review the reported associations of depression and antidepressants with motor vehicle crashes.PurposeA literature search for material published in the English language between January, 1995, and October, 2015, in bibliographic databases was combined with a search for other relevant material referenced in the retrieved articles.MethodsRetrieved articles were systematically reviewed for inclusion criteria: 19 epidemiological studies (17 case-control and 2 cohort studies) fulfilled the inclusion criteria by estimating the crash risk associated with depression and/or psychotropic medications in naturalistic settings.ResultsThe estimates of the odds ratio (OR) of crash involvement associated with depression ranged from 1.78 to 3.99. All classes of antidepressants were reported to have side effects with the potential to affect driving safety. The majority of studies of antidepressant effects on driving reported an elevated crash risk, and ORs ranged from 1.19 to 2.03 for all crashes, and 3.19 for fatal crashes. In meta-analysis, depression was associated with approximately 2-fold increased crash risk (summary OR = 1.90; 95% CI, 1.06 to 3.39), and antidepressants were associated with approximately 40% increased crash risk (summary OR = 1.40; 95%CI, 1.18 to 1.66).ConclusionBased on the findings of the studies reviewed, depression, antidepressants or the combination of depression and antidepressants may pose a potential hazard to driving safety. More research is needed to understand the individual contributions of depression and the medications used to treat depression

Trends in long-term prescribing of dependence forming medicines

Using patient-level primary care data to estimate the extent to which antidepressant medicines are prescribed to people continuously for long periods of time. Aim This descriptive research used patient-level primary care data to estimate the extent to which antidepressant medicines are prescribed to people continuously for long periods of time. The study also drew on survey data and data on the number of prescriptions dispensed. Findings - The number of antidepressant prescriptions dispensed each year in England doubled between 2008 and 2018 - Survey data show that the proportion of adults reporting use of antidepressants in the past year increased in the 1990s, and again between 2007 and 2014 - The average length of time that antidepressants are continuously prescribed to people for has increased over time. - Some types of antidepressants (for example, tricyclics and other antidepressants) tend to be prescribed for longer periods than other types (such as SSRIs). - In 2014, one in twelve prescribing periods for tricyclics and other antidepressants lasted for three years or more Methods The analyses in this report are descriptive and show the overall prevalence of long-term prescribing in each year. We used a sample of around 50,000 patients prescribed at least one antidepressant medicine between 2000 and 2017. This was drawn from the Clinical Practice Research Datalink (CPRD). The CPRD contains data about prescriptions issued by GPs (including the length and size of prescription) and characteristics of the patients prescribed to (such as their age, sex, and area where they live). Medicines were grouped for analysis into: tricyclics, selective serotonin reuptake inhibitors (SSRIs), and other ADMs. The length of individual prescriptions and continuous prescribing periods were derived using information on consultation dates, the quantity of tablets prescribed, and the numeric daily dose

Antidepressants and Age

Antidepressants as a commodity have been remarkably little-studied by economists. This study shows in new data for 27 European countries that 8% of people (and 10% of those middle-aged) take antidepressants each year. The probability of antidepressant use is greatest among those who are middle-aged, female, unemployed, poorly educated, and divorced or separated. A hill-shaped age pattern is found. The adjusted probability of using antidepressants reaches a peak – approximately doubling – in people’s late 40s. This finding is consistent with, and provides a new and independent form of corroboration of, recent claims in the research literature that human well-being follows a U-shape through life.well-being, aging, mental health, depression, happiness, Easterlin paradox

Neurotrophins Role in Depression Neurobiology: A Review of Basic and Clinical Evidence

Depression is a neuropsychiatric disorder affecting a huge percentage of the active population especially in developed countries. Research has devoted much of its attention to this problematic and many drugs have been developed and are currently prescribed to treat this pathology. Yet, many patients are refractory to the available therapeutic drugs, which mainly act by increasing the levels of the monoamines serotonin and noradrenaline in the synaptic cleft. Even in the cases antidepressants are effective, it is usually observed a delay of a few weeks between the onset of treatment and remission of the clinical symptoms. Additionally, many of these patients who show remission with antidepressant therapy present a relapse of depression upon treatment cessation. Thus research has focused on other possible molecular targets, besides monoamines, underlying depression. Both basic and clinical evidence indicates that depression is associated with several structural and neurochemical changes where the levels of neurotrophins, particularly of brain-derived neurotrophic factor (BDNF), are altered. Antidepressants, as well as other therapeutic strategies, seem to restore these levels. Neuronal atrophy, mostly detected in limbic structures that regulate mood and cognition, like the hippocampus, is observed in depressed patients and in animal behavioural paradigms for depression. Moreover, chronic antidepressant treatment enhances adult hippocampal neurogenesis, supporting the notion that this event underlies antidepressants effects. Here we review some of the preclinical and clinical studies, aimed at disclosing the role of neurotrophins in the pathophysiological mechanisms of depression and the mode of action of antidepressants, which favour the neurotrophic/neurogenic hypothesis

Antidepressants and Age

Antidepressants as a commodity have been remarkably little-studied by economists. This study shows in new data for 27 European countries that 8% of people (and 10% of those middle-aged) take antidepressants each year. The probability of antidepressant use is greatest among those who are middle-aged, female, unemployed, poorly educated, and divorced or separated. A hill-shaped age pattern is found. The adjusted probability of using antidepressants reaches a peak -- approximately doubling -- in people?s late 40s. This finding is consistent with, and provides a new and independent form of corroboration of, recent claims in the research literature that human well-being follows a U-shape through lifeWell-being; aging; mental health; depression; happiness; Easterlin paradox