[Use of antidepressants in unipolar depression in the elderly]. / L'utilisation des antidépresseurs dans l'épisode dépressif caractérisé unipolaire du sujet âgé.

OBJECTIVE: To study the ageing-related pharmacological modifications about major depressive episodes in the elderly and their impact on the efficiency and tolerability of antidepressants. METHODS: Research through Pubmed and the Cochrane Database of Systematic Reviews, using the following keywords "antidepressant" ; "treatment"; "late life depression"; "elderly"; up until July 2021. RESULTS: Antidepressants were found to be more efficient than a placebo in the elderly's response to and remission from major depressive episodes. Some depressive episode subtypes seem to be less responsive to antidepressants, such as depressive episodes of vascular origin, for which treating cardiovascular risk factors by statins, angiotensin receptor blockers or calcium channel blockers seems relevant. Two other depressive episode subtypes were highlighted : post-stroke depressive episodes and those induced by major neurocognitive disorders. Antidepressants showed an efficient response in the first case but not in the second. Even though antidepressants are known to stimulate cognitive performances in animals, as yet there is not sufficient evidence to prove they indeed improve cognitive functions, or reduce the risk of developing a neurocognitive disorder, or decelerate the cognitive decline in major neurocognitive disorders in humans. Ageing creates pharmacodynamical changes that increase older people's vulnerability to the side effects of antidepressants. Moreover, age-related pharmacokinetic modifications can also change every step in a drug's transformation process in the body, which leads to a high probability of having adverse effects. Since most antidepressants are eliminated using the P450 cytochrome system, their dosage must be adapted to changes of the P450 system. Somatic comorbidities can, in themselves, influence the pharmacokinetics of antidepressants. Many antidepressants interact with the P450 cytochrome and the P-GP protein, which puts them at a high risk of drug interactions. There is no proven efficiency difference between antidepressant classes. Some antidepressant adverse effects can be of particular importance in the elderly, like the risk of bleeding, cardiovascular episodes, hyponatremia, falling and fractures, anticholinergic effects, extrapyramidal syndrome, epilepsy, liver disease and death. Selective serotonin reuptake inhibitors have an indication as the first line of treatment, avoiding paroxetine and fluoxetine. Serotonin and norepinephrine re-uptake inhibitors are relevant if the patient presents psychomotor retardation or pain, while keeping in mind to check blood pressure. Tricyclics and monoamine oxidase inhibitors should be avoided because of their anticholinergic effects. Bupropion can be prescribed if the patient has extreme fatigue. Mirtazapine is useful when the patient presents sleep or appetite disturbance. Several molecules can be used in the case of drug-resistant depression, such as associating aripiprazole with small-dosage antidepressants, or electroconvulsive therapy, or repetitive Transcranial Magnetic Stimulation (rTMS). Ketamine and psychostimulants seem to have antidepressant effects, but complementary studies are needed to conclude. CONCLUSIONS: Unipolar major depressive episodes in the elderly are frequent and their medicinal treatment has specific features. Knowing the specificities of antidepressant use in the elderly allows to optimize its efficiency and to limit the risk of inappropriate prescription leading to harmful adverse effects.

Interest of pharmacoepidemiology for the study of psychotropic drugs.

In psychiatry, drug evaluation using pharmacoepidemiological methods has been of growing interest in recent decades. Studies based on observational databases are particularly useful for psychotropic drugs due to their important prevalence in populations, and their use over long period. The authors discussed the specific interest of pharmacoepidemiological studies in the field of psychiatry through two examples: first, the use of antidepressants, and, second, the risks associated with antipsychotics.

Serious central nervous system side effects of cephalosporins: A national analysis of serious reports registered in the French Pharmacovigilance Database.

INTRODUCTION: Among antibiotics, Central Nervous System (CNS) adverse drug reactions (ADRs) are often under-suspected and overlooked. Cephalosporins are an important cause of drug-induced CNS ADRs but the characteristics of such ADR have not been fully explored. We aimed to characterize the profile of cephalosporins serious CNS ADRs. METHOD: We performed an analysis of serious reports recorded in the French Pharmacovigilance database from 1987 to 2017. RESULTS: A total of 511 serious ADRs reports was analyzed. Patients had a mean age of 67.1 years and were mainly men (52.5%), with a mean creatinine clearance of 32.9 ml/min. The most involved molecules were cefepime (33.1%), ceftriaxone (29.7%), ceftazidime (19.6%), cefotaxime (9%) and cefazoline (2.9%), mostly administered intravenously (87.3%). A CNS history was observed in 25% of the reports (n = 128). Patients exhibited encephalopathy (30.3%), confusional state (19.4%), convulsion (15.1%), myoclonia (9.4%), status epilepticus (9.2%), coma (6.3%) and hallucination (4.3%). The mean time of onset was 7.7 days and the mean duration was 6 days. Cephalosporin plasma levels were recorded for 153 patients (29.9%) and 107 were above the standards including 62 (57.9%) related to renal impairment. Electroencephalograms were performed in 38.2% (n = 195) of the patients and 81% (n = 158) were abnormal. CONCLUSION: This study characterizes an off-target CNS ADRs of several cephalosporins. Ceftriaxone represented a large part of our reports after cefepime and it would be relevant to warn healthcare professionals. Investigations (EEG, though plasma levels and renal function) can be precious tools for clinicians to make a prompt diagnosis and improve patients' outcomes.

Manic switches induced by antidepressants: an umbrella review comparing randomized controlled trials and observational studies.

OBJECTIVE: We aimed to explore whether the prevalence of manic switch was underestimated in randomized controlled trials (RCTs) compared to observational studies (OSs). METHOD: Meta-analyses and simple and systematic reviews were identified by two reviewers in a blinded, standardized manner. All relevant references were extracted to include RCTs and OSs that provided data about manic switch prevalence after antidepressant treatment for a major depressive episode. The primary outcome was manic switch prevalence in the different arms of each study. A meta-regression was conducted to quantify the impact of certain variables on manic switch prevalence. RESULTS: A total of 57 papers (35 RCTs and 22 OSs) were included in the main analysis. RCTs underestimated the rate of manic switch [0.53 (0.32-0.87)]. Overestimated prevalence was related to imipraminics [1.85 (1.22-2.79)]; to serotonin-norepinephrine reuptake inhibitors [1.74 (1.06-2.86)]; and to other classes of drugs [1.58 (1.08-2.31)], compared to placebo treatment. The prevalence of manic switch was lower among adults than among children [0.2 (0.07-0.59)]; and higher [20.58 (8.41-50.31)] in case of bipolar disorder. CONCLUSION: Our results highlight an underestimation of the rates of manic switch under antidepressants in RCTs compared to the rates observed in observational studies.

Analysis of patients' narratives posted on social media websites on benfluorex's (Mediator® ) withdrawal in France.

WHAT IS KNOWN AND OBJECTIVE: Websites and discussion lists on health issues are among the most popular resources on the Web. Use experience reported on social media websites may provide useful information on drugs and their adverse reactions (ADRs). Clear communication on the benefit/harm balance of drugs is important to inform proper use of drugs. Some data have shown that communication (advisories or warnings) is difficult. This study aimed to explore the Internet as a source of data on patients' perception of risk associated with benfluorex and the impact of wider media coverage. METHODS: Three French websites were selected: Doctissimo, Atoute.org considered the best-known and visited website in France for health questions and Vivelesrondes (Long live the Tubbies) for overweight people. Three periods were chosen: (1) before November 2009 (i.e. before benfluorex withdrawal), (2) between November 2009 and November 2010 (when the risk of valvulopathy with benfluorex appeared in social media) and (3) after November 2010. RESULTS AND DISCUSSION: Two hundred twenty initial postings were analysed. These lead to 660 secondary postings which were analysed separately. In period 1, 114 initial postings were analysed, mostly concerning efficacy of the drug (72%). In period 2, 42 initial postings were analysed involving mainly ADRs or warnings (73%). In period 3, 64 initial postings were analysed; most frequent expressing anger directed at the healthcare system (58%) and anxiety about cardiovascular ADRs (30%). Online consumer postings showed that there were drastic changes in consumers' perceptions following media coverage. WHAT IS NEW AND CONCLUSION: This study suggests that analysis of website data can inform on drug ADRs. Social media are important for communicating information on drug ADRs and for assessing consumer behaviour and their risk perception.