Pharmacovigilance: A Review of Opioid-Induced Respiratory Depression in Chronic Pain Patients.

Pharmacovigilance: a review of opioid-induced respiratory depression in chronic pain patients.

Pain Physician. 2013 Mar; 16(2): E85-94
Dahan A, Overdyk F, Smith T, Aarts L, Niesters M

Opioids may induce life-threatening respiratory depression, but limited knowledge is available on factors that contribute to opioid-induced respiratory depression (OIRD). This is especially true for patients with chronic pain on prolonged opioid therapy. There are no good quality case control studies or randomized controlled trials available on this topic. Here we present and analyze all case series since 1980 on OIRD in chronic pain patients extracted from PubMed.To describe and understand clinically identified factors involved in life-threatening OIRD in patients receiving opioids for chronic pain relief.A literature search was performed for all relevant case reports on OIRD in chronic pain.We searched PubMed ( for all available case reports/series on OIRD in adolescent (12 years and older) and adult patients treated with opioids for chronic pain, from which we identified specific commonalities that contributed to OIRD (akin to closed claims analyses). The dataset was post-hoc divided into 2 distinct categories: cases published from 1980 to 1999 and those from 2000 to 2012.Thirty-four reports describing 42 chronic pain patients experiencing OIRD were retrieved. Cases published before the year 2000 (pre-2000) predominantly involved morphine in cancer patients, whereas cases since 2000 (post-2000) predominantly involved methadone or transdermal fentanyl in non-cancer pain patients. Specific factors that contributed to OIRD were elevated opioid plasma levels due to renal impairment and sensory deafferentiation in pre-2000 cases, and elevated plasma levels due to drug interactions on the cytochrome P450 in post-2000 cases.The case series analysis of published case reports imposes limitations in terms of the types of cases presented (only severe cases are published or cases with specific precipitating factors), the journal-related publication strategy, and changes in clinical practice.Our case review confirms that life-threatening OIRD in chronic pain patients involves a series of complex often-interacting factors. In spite of the factors identified in this cases series, OIRD remains unpredictable and safe opioid prescribing requires careful titration of opioid dosages and continuous monitoring to prevent life-threatening OIRD.  HubMed – depression


Transitions in Illicit Drug Use Status Over 3 Years: A Prospective Analysis of a General Population Sample.

Am J Psychiatry. 2013 Mar 20;
Compton WM, Dawson DA, Conway KP, Brodsky M, Grant BF

OBJECTIVE The authors examined 3-year transitions among nonuse, asymptomatic use, and problem use of illicit drugs for U.S. adults in the general household population. METHOD Data were from the nationally representative National Epidemiologic Survey on Alcohol and Related Conditions, a study of 34,653 adults interviewed twice, 3 years apart. Respondents were categorized on three mutually exclusive categories of baseline drug status: past-year nonusers (N=32,675), past-year asymptomatic drug users (N=861), and past-year symptomatic drug users (N=1,117). Symptomatic drug use, or problem use, was defined as presence of one or more symptoms that operationalize DSM-IV drug abuse and dependence criteria. The authors assessed sociodemographic, health, substance use, and psychiatric covariates for association with 3-year transitions to different status categories. RESULTS Among baseline nonusers, 95.4% continued to be nonusers at follow-up, 2.1% became asymptomatic users, and 2.5% developed problem use. Among baseline asymptomatic users, 66.6% had stopped using drugs at follow-up, 14.3% continued to be asymptomatic users, and 19.1% had developed problem use. Nearly half (49.0%) of those with problem use at baseline had stopped using drugs at follow-up, 10.9% had transitioned to asymptomatic use, and 40.1% continued to have problem use. Younger age, male sex, white race, and not being married were associated with progression from nonuse to use or problem use, as were alcohol and tobacco use and disorders, major depression, and schizotypal, borderline, and narcissistic personality disorders. Panic disorder and avoidant personality disorder were associated with less progression. CONCLUSIONS Transitions in drug use status are common. The finding that alcohol and tobacco variables and co-occurring psychopathology are important correlates of transitions suggests the value of addressing all co-occurring disorders and substance use in patient assessments and treatment planning, both to prevent adverse transitions and to promote positive transitions. HubMed – depression


Psychiatric pharmacogenomics predicts health resource utilization of outpatients with anxiety and depression.

Transl Psychiatry. 2013; 3: e242
Winner J, Allen JD, Anthony Altar C, Spahic-Mihajlovic A

Antidepressants are among the most widely prescribed medications, yet only 35-45% of patients achieve remission following an initial antidepressant trial. The financial burden of treatment failures in direct treatment costs, disability claims, decreased productivity, and missed work may, in part, derive from a mismatch between optimal and actual prescribed medications. The present 1 year blinded and retrospective study evaluated eight direct or indirect health care utilization measures for 96 patients with a DSM-IV-TR diagnosis of depressive or anxiety disorder. The eight measures were evaluated in relation to an interpretive pharmacogenomic test and reporting system, designed to predict antidepressant responses based on DNA variations in cytochrome P450 genes (CYP2D6, CYP2C19, CYP2C9 and CYP1A2), the serotonin transporter gene (SLC6A4) and the serotonin 2A receptor gene (5HTR2A). All subjects had been prescribed at least one of 26 commonly prescribed antidepressant or antipsychotic medications. Subjects whose medication regimen included a medication identified by the gene-based interpretive report as most problematic for that patient and are in the ‘red bin’ (medication status of ‘use with caution and frequent monitoring’), had 69% more total health care visits, 67% more general medical visits, greater than three-fold more medical absence days, and greater than four-fold more disability claims than subjects taking drugs categorized by the report as in the green bin (‘use as directed’) or yellow bin (‘use with caution’). There were no correlations between the number of medications taken and any of the eight healthcare utilization measures. These results demonstrate that retrospective psychiatric pharmacogenomic testing can identify past inappropriate medication selection, which led to increased healthcare utilization and cost. HubMed – depression



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