Intranasal or transdermal nicotine for the treatment of postoperative pain.

BACKGROUND: Acute pain frequently occurs after surgical procedures. Nicotine has been explored as an adjunctive medication for management of postoperative pain.   OBJECTIVES: To assess the effect of transdermal or intranasal nicotine administration on postoperative pain, opioid analgesic use, and opioid-related adverse events.   SEARCH METHODS: We searched MEDLINE (1966 to 20 March 2014), the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 3), EMBASE (1980 to 20 March 2014), and also databases of ongoing trials (www.controlled-trials.com/ and http://clinicaltrials.gov/). We re-ran the search on 28 April 2015. We will assess the one study of interest when we update the review. SELECTION CRITERIA: We included randomized, placebo-controlled clinical trials that evaluated the effects of perioperative (pre-, intra-, or postoperative) administration of nicotine on postoperative pain, opioid use, and opioid-related adverse events. We excluded all other studies. DATA COLLECTION AND ANALYSIS: Two authors independently screened all titles and abstracts for eligibility and documented reasons for exclusion. In case of disagreement, a third author decided on the inclusion or exclusion of a trial report. When additional information was needed in order to decide if a trial should be included, one of the authors contacted the corresponding author of the trial in question. MAIN RESULTS: Nine trials (666 participants) evaluated nicotine for postoperative pain. Nicotine may reduce postoperative pain scores at 24 hours by a small amount compared with placebo (eight trials, mean difference -0.88 on a 0 to 10 scale, 95% confidence interval (CI) -1.58 to -0.18; low quality evidence). The effect on pain at one hour and 12 hours postoperatively was less certain (very low quality evidence). Statistical heterogeneity was substantial and not adequately explained by stratification of trials according to type of surgical procedure, smoking status, mode of nicotine administration, timing of administration, or assessed risk of bias. Excluding one trial at high risk of bias resulted in similar findings. The effect of nicotine on postoperative opioid use was uncertain due to small number of participants in the studies. Nicotine probably increases the risk of postoperative nausea (seven trials, RR 1.24, 95% CI 1.03 to 1.50; moderate quality evidence). Three trials assessed sedation but the effect is very uncertain due to the very low quality of evidence. We found no evidence that nicotine increased the risk of vomiting (seven studies, risk difference (RD) 0.03, 95% CI -0.04 to 0.09; low quality evidence). The results from one single small trial were insufficient to establish whether nicotine led to an earlier hospital discharge (very low quality evidence). AUTHORS' CONCLUSIONS: Based on evidence of generally low quality, nicotine may reduce postoperative pain at 24 hours compared with placebo, but the effects were relatively small (less than 1 point on a 10 point pain scale) and there was substantial heterogeneity in the results of our analyses. Nicotine does not appear to reduce postoperative use of opioids or opioid-related adverse events but probably increases the risk of nausea. More research is needed to determine the effectiveness of nicotine for postoperative pain and to understand the optimal timing, dose, and method of delivery of nicotine.

The role of antipsychotics in smoking and smoking cessation.

Persons with severe and persistent mental illnesses, e.g. schizophrenia spectrum disorders and bipolar disorder, smoke at a much higher rate than the general population. Treatment options for schizophrenia spectrum disorders and bipolar disorder often include the first-generation (typical) and second-generation (atypical) antipsychotics, which have been shown to be effective in treating both psychotic and mood symptoms. This article reviews studies examining the relationship between antipsychotic medication and cigarette smoking. These studies suggest that in persons with schizophrenia and schizoaffective disorder, typical antipsychotics may increase basal smoking and decrease people's ability to stop smoking, whereas atypical antipsychotics decrease basal smoking and promote smoking cessation. However, we found that the data available were generally of moderate quality and from small studies, and that there were conflicting findings. The review also critically assesses a number of potential mechanisms for this effect: the use of smoking as a form of self-medication for the side effects of antipsychotics, the effect of antipsychotics on smoking-related cues and the effect of antipsychotics on the appreciation of the economic cost of smoking behaviour. Gaps in the research are noted and recommendations for further study are included. More study of this important issue is needed to clarify the effect of antipsychotics on smoking behaviours.

Depression comorbidity and antidepressant use in veterans with chronic hepatitis C: results from a retrospective chart review.

BACKGROUND: The 2002 National Institutes of Health Consensus Conference Statement recommended that both clinical and research efforts be made to increase the availability of hepatitis C virus (HCV) treatment to patients who were previously ineligible because of comorbid psychiatric illness and substance use disorders. However, little research on patients with HCV and comorbid depression has been conducted that can serve to inform and guide treatment of HCV. In this study we characterize the prevalence and severity of co-morbid depression, as well as antidepressant and other psychotropic prescribing patterns, in a sample of U.S. veterans with HCV. METHOD: Participants were recruited between November 2002 and July 2005 from the liver specialty clinic and from a 1-time HCV patient education class conducted through the Portland Department of Veterans Affairs Northwest Hepatitis C Resource Center. Patients who signed informed consent were asked to complete the Beck Depression Inventory, Second Edition (BDI-II), and their medical records were reviewed for information regarding active prescriptions for psychotropic medications and prior psychiatric diagnoses. RESULTS: Of the 881 veterans enrolled in the study, 783 (89%) completed the BDI-II. Approximately one third (34%, 264/783) of the veterans endorsed moderate to severe symptoms of depression (BDI-II score >or= 20), and 37% (290/783) were prescribed an antidepressant; however, 48% (140/290) of veterans prescribed an antidepressant continued to endorse moderate to severe depressive symptoms. Furthermore, of all veterans endorsing moderate to severe symptoms of depression (N = 264), only about half (56%, 148/264) were prescribed an antidepressant. CONCLUSION: On the basis of BDI-II scores, a significant proportion of veterans with HCV experience moderate to severe depressive symptoms. Although antidepressants were the most commonly prescribed psychotropic medication, many who were prescribed an antidepressant continued to experience high levels of depressive symptoms, an important consideration when deciding whether to initiate antiviral therapy to treat HCV.

Hepatitis C testing and infection rates in bipolar patients with and without comorbid substance use disorders.

OBJECTIVES: To determine and compare hepatitis C (HCV) screening and testing rates among four groups: those with (i) bipolar disorder [BD group (history of BD but no substance use disorder)]; (ii) substance use disorders [SUD group (history of SUD but no BD)]; (iii) co-occurring disorders [DD group (history of both BD and an SUD)]; and (iv) a control group (no history of either bipolar disorder or substance use disorder). Our hypothesis was that HCV antibody testing rates and HCV prevalence would be higher in the BD, SUD, and DD groups than the control group. METHODS: Data were retrospectively collected on 325,410 patients seen between 1998 and 2004 within facilities and clinics of the Veterans Integrated Service Network (VISN) 20 Northwest Veterans Health Care Administration from electronic medical records. HCV screening and prevalence rates were compared between the BD, SUD, DD, and control groups. Odds ratios and relative risks were determined and compared between groups. RESULTS: Patients in the BD, SUD, and DD groups had been tested at a higher rate than controls and were at increased risk for HCV infection compared with controls. These high-risk groups had a 1.31-fold, 4.86-fold, and 5.46-fold increase in the relative risk of HCV infection, respectively. Overall, compared to the control group, the relative risk of a patient having HCV if he or she had BD (with or without an SUD) was 3.6. CONCLUSIONS: Patients with BD and comorbid SUD had an over fourfold increase in relative risk for HCV than our control group and a similar risk as patients in our SUD group. Furthermore, even if bipolar patients did not have a comorbid SUD (the BD group), their relative risk of HCV was significantly higher than that of the control group. This suggests that patients with BD, particularly those with a comorbid SUD, should be screened and tested for HCV.

Selective publication of antidepressant trials and its influence on apparent efficacy.

BACKGROUND: Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials--and the outcomes within those trials--can lead to unrealistic estimates of drug effectiveness and alter the apparent risk-benefit ratio. METHODS: We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications. For trials that were reported in the literature, we compared the published outcomes with the FDA outcomes. We also compared the effect size derived from the published reports with the effect size derived from the entire FDA data set. RESULTS: Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall. CONCLUSIONS: We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients.

Psychiatric and substance use disorders in individuals with hepatitis C: epidemiology and management.

Hepatitis C virus (HCV) infection is a major health concern in the US as well as in other countries worldwide. Treatment issues and disease management strategies are complicated by the extremely high rate of psychiatric and substance use disorders in those who have HCV. The majority of new and existing cases of HCV are related to injection drug use and, in this population, the prevalence of psychiatric comorbidity is high. Optimally, all patients with HCV should be screened for psychiatric and substance use disorders before initiation of antiviral therapy. If a patient screens positive, he or she should be referred to a mental healthcare provider or addiction specialist, assessed for the presence of a psychiatric or substance use disorder, and appropriately treated prior to initiation of antiviral (i.e. interferon) therapy. Although interferon-based therapies can lead to severe neuropsychiatric adverse effects, including in rare instances suicide, evidence suggests that many patients with comorbid psychiatric and substance use diagnoses can be treated safely and effectively using comanagement strategies. However, most patients with HCV are not treated with antiviral therapy. Therefore, we must expand our definition of HCV 'treatment' to include treatment of the comorbid psychiatric and substance use disorders that accompany HCV infection and precede antiviral therapy. This paper reviews the epidemiology and management of psychiatric and substance use disorders in patients with HCV, the issue of psychiatric and substance use disorders as contraindications for antiviral therapy, and current treatment strategies for HCV patients with these comorbid conditions.