Clinical value of ACE genotyping in diagnosis of sarcoidosis

Forensic Science International, 2010

The British Journal of Psychiatry, 2010

Self-poisoning is a common method of suicide, especially in women. 1 Antidepressants are frequently used for self-poisoning, being involved in around 20% of all poisoning suicides in the UK 1 and in 20-30% of non-fatal overdoses. 2 This reflects the facts that depression is the most frequent psychiatric disorder in people dying by suicide, 3 the method used for suicidal acts is often determined by availability, 4 and self-poisoning in individuals with depression often involves antidepressants prescribed for them. 5 Relative toxicity is an important factor likely to determine the outcome of an antidepressant overdose. Studies using different approaches have shown wide variation in the relative toxicity of antidepressants, 6,7 with the older tricyclic antidepressants (TCAs) generally being more toxic than the newer selective serotonin reuptake inhibitors (SSRIs). We have used two approaches to assessing the relative toxicity of classes of antidepressants and individual antidepressants. The first approach was to relate drug-specific poisoning mortality rates to prescription ratestermed the 'fatal toxicity index'. 8 The second, and generally less used approach, is to compare the rate of death with the rate of non-fatal self-poisoning, 7,9 which generates a 'case fatality' index. The fatal toxicity index approach is probably less accurate because it is more heavily influenced by prescribing policies, including use of some antidepressants for conditions other than depression, 10 and selective prescribing, for example, based on the clinician's assessment of suicide risk i.e. 'confounding by indication'. The specific aims of the study were to provide up-to-date information on the relative toxicity of individual antidepressants that may assist clinicians in making decisions about prescribing and inform interventions by regulatory authorities.

Acta Psychiatrica Scandinavica, 1994

The objective of this study was a) to compare patterns of drug use in fatal and nonfatal overdoses and b) to find out if toxic drugs are overrepresented in overdoses with fatal outcome. A total of 179 cases of fatal overdoses in Switzerland (population 6.6 million) were compared with 269 medically treated self-poisoners from the agglomeration of Berne (population 30 1,630). Because of frequent multiple drug use, all the different compounds taken singly or in combination with other drugs were recorded and grouped according to drug types. The patterns of the frequencies of drugs used were remarkably similar in both groups. The majority of the drugs were psychotropics (8 1 % in fatal and 68 % in nonfatal overdose). Twenty-nine completed suicides were the result of drug combinations specifically recommended by EXIT. In the remaining cases benzodiazepines were used most frequently in both attempted and completed suicide, often in combination with other drugs or alcohol. Barbiturates were the only drugs recorded significantly more often in fatal overdoses (9% V,F 3%). No significant difference was found for tricyclic antidepressants (13 % vs lo%), or other types of drugs. The results are consistent with our assumption that drugs with higher toxicity would be overrepresented in overdoses with fatal outcome. Barbiturates, which are well known to be dangerous in overdose, were clearly associated with fatal overdoses, but not tricyclic antidepressants. This, in our view, suggests that the risk of prescribing tricyclic antidepressants should not be overestimated. The frequent use of benzodiazepines in completed suicide, however, indicates that there are no truly safe drugs in overdose.

Case Reports in Medicine, 2020

Sarcoidosis is a systemic disorder characterized by the presence of noncaseating granulomas that are most commonly observed in the lungs. Sarcoid-like reaction has been reported to develop in response to several immune modulator agents and antidepressants. In this report, a case of pulmonary sarcoidosis that was strongly related to the use of more than the average recommended dose of selective serotonin-reuptake inhibitor (SSRI) medications has been described. The patient, a 37-year-old, single, Caucasian woman, who suffered from severe depression and who presented to the emergency department with shortness of breath, low-grade fever, a dry cough, fatigue, and the loss of appetite, was diagnosed with this condition, and she failed to respond to the administered sarcoidosis treatment until the SSRI medications that she was using were discontinued; furthermore, she relapsed when one of these medications was reintroduced. Based on these observations, we were able to show a possible rel...

International journal of legal medicine, 2018

Depression is known to be a risk factor for suicide. Currently, the most used antidepressants are selective serotonin reuptake inhibitors (SSRIs). Not all users, however, benefit from them. In such cases, treatment failure can be explained in part by genetic differences. In this study, we investigated the role of pharmacogenetic factors in citalopram-positive completed suicides (n = 349). Since citalopram is metabolized by CYP2C19 and CYP2D6 enzymes, the study population was genotyped for clinically relevant CYP2C19 and CYP2D6 polymorphisms and CYP2D6 copy number variation. To assess genetic differences between suicide cases and Finns in general, Finnish population samples (n = 855) were used as controls. Also, the role of drug interactions among suicide cases was evaluated. We found enrichment of a combined group of genetically predicted poor and ultrarapid metabolizer phenotypes (gMPs) of CYP2C19 among suicide victims compared to controls 0.356 [0.31-0.41] vs. 0.265 [0.24-0.30] (p...

Journal of Affective Disorders, 2000

Background: Debate continues over the relative merits of tricyclics and selective serotonin re-uptake inhibitors (SSRIs) as first line antidepressant treatment for depression. SSRIs are safer in overdose but more expensive than tricyclics. This report compared the hospital costs of cases of overdose with both groups of drug. Methods: Records of all persons aged over thirteen years presenting to a general hospital in one year were analysed for demographic information and details of their attendance. Results: There were 1165 episodes of self-poisoning, 151 involving tricyclics as the sole antidepressant and 69 SSRIs as the sole antidepressant. Those taking SSRIs had a shorter (1.96 vs. 2.59 days) and less expensive (£330 vs. £567) stay. A large proportion of this difference in cost was due to a small number of admissions to the Intensive Care Unit. Limitations: This study used only hospital costs, so excluding costs associated with primary care. Conclusions and clinical relevance: If there were similar cost differences countrywide, the difference in hospital costs of self poisoning with SSRIs and tricyclics would represent an additional £3.87 million per year due to self poisoning with tricyclics across the whole of England and Wales. This is a small proportion of the estimated £100 million cost of switching to first-line prescribing of SSRIs for depression.

Selective Serotonin Reuptake Inhibitors, 1999

The selective serotonin reuptake inhibitors (SSRIs) have increased in popularity and extent of use since their introduction. At the same time, our knowledge concerning the relationship between suicide and depression has increased. The impact of this group of drugs on this knowledge has been considerable. An additional consideration is that, as with all drugs and particularly with antidepressants, they are liable to be taken in overdose. This chapter reviews some of the links between the SSRIs and depression, overdose and suicide.

To compare the clinical features of deliberate self- poisoning with venlafaxine and selective serotonin reuptake inhibitors (SSRIs) presenting to the emergency department of an Australian tertiary referral hospital. A retrospective cohort study comparing all 36 patients who presented with venlafaxine self-poisoning with 44 randomly selected patients with SSRI self-poisoning between 1997 and 2006. Patients who had overdosed on venlafaxine were older (mean age 37.4 versus 28.8 years (p ≤ 0.001) and generally exhibited a higher degree of suicidal intent (p≤0.017). Median venlafaxine dose taken was 35 defined daily doses (DDDs) compared with SSRIs 19.4 DDDs. Those who ingested venlafaxine were more likely to become confused (25% versus 0%; p = 0) and have mydriasis (19.4% versus 2%; p ≤ 0.02), than those who took SSRIs. One patient from the venlafaxine group died. Compared with SSRI self-poisoners, patients who deliberately ingested venlafaxine were more likely to exhibit serious suicide intent. They were also more likely to be older, take a higher DDD of the drug, and have confusion and mydriasis. This has implications for management of severely depressed and suicidal patients.

BMC Psychiatry, 2018

Background: Bipolar and other psychiatric disorders are associated with considerably increased risk of suicidal behaviour, which may include self-poisoning with medication used to treat the disorder. Therefore, choice of medication for treatment should include consideration of toxicity, especially for patients at risk. The aim of this study was to estimate the relative toxicity of specific drugs within two drug categories, antipsychotics and mood stabilizers, using large-scale databases to provide evidence that could assist clinicians in making decisions about prescribing, especially for patients at risk of suicidal behaviour. Method: Two indices were used to assess relative toxicity of mood stabilisers and antipsychotics: case fatality (the ratio between rates of fatal and non-fatal self-poisoning) and fatal toxicity (the ratio between rates of fatal self-poisoning and prescription). Mood stabilisers assessed included lithium [reference], sodium valproate, carbamazepine, and lamotrigine, while antipsychotics included chlorpromazine [reference], clozapine, olanzapine, quetiapine and risperidone. Fatal selfpoisoning (suicide) data were provided by the Office for National Statistics (ONS), non-fatal self-poisoning data by the Multicentre Study of Self-harm in England, and information on prescriptions by the Clinical Practice Research Datalink. The primary analysis focussed on deaths due to a single drug. Cases where the drug of interest was listed as the likely primary toxic agent in multiple drug overdoses were also analysed. The study period was 2005-2012. Results: There appeared to be little difference in toxicity between the mood stabilisers, except that based on case fatality where multiple drug poisonings were considered, carbamazepine was over twice as likely to result in death relative to lithium (OR 2.37 95% CI 1.16-4.85). Of the antipsychotics, clozapine was approximately18 times more likely to result in death when taken in overdose than chlorpromazine (single drug case fatality: OR 18.53 95% CI 8.69-39.52). Otherwise, only risperidone differed from chlorpromazine, being less toxic (OR 0.06 95% CI 0.01-0.47). Conclusions: There was little difference in toxicity of the individual mood stabilisers. Clozapine was far more toxic than the other antipsychotics. The findings are relevant to prescribing policy, especially for patients at particular risk of suicidal behaviour.

2016

Sudden, unexpected death may occur in apparently healthy individuals. Its occurrence in psychiatric patients has raised the concern that the use of psychotropics, especially antipsychotics, may be associated with an increased risk of sudden death. This concern is maintained even though not all psychiatric patients who have succumbed to sudden death have been on psychotropics. Early reports presented the concern that the use of chlorpromazine and thioridazine were associated with sudden death. More recently, the focus shifted to the more potent agents. Indeed, the FDA Advisory Committee discussed the possibility of a connection between sudden death and haloperidol. No decision could be reached by the FDA Committee because of the enormous complexity of the problem. Nonetheless, since sudden death continues to catastrophically complicate the course of some patients, the scope of this review is to further investigate the relationship between antipsychotic agents and sudden death.