Psychosis Related to Nitrous Oxide Misuse: A Case Series and Systematic Review.

e20031 Background: Insufficient outpatient care among vulnerable patients, such as those with a history of alcohol or illicit substance use disorder (SUD), may contribute to poor outcomes in non-small cell lung cancer (NSCLC). We hypothesize that patients with newly diagnosed localized NSCLC and a history of SUD have a shorter time from diagnosis to last known contact, greater rates of depression, less family support, poorer follow-up, and increased emergency room and inpatient usage compared to those without a history of SUD. Methods: To investigate this, we conducted a retrospective review of all lung cancer patients with localized non-small cell carcinoma (N = 52) with visits between 9/2012 and 9/2018 at an academic county hospital with a dedication to the underserved in a major US city. Data were collected from electronic medical records manually and analyzed using ANOVA for continuous variables or Pearson's Chi-squared for categorical data. Results: Among patients with localized NSCLC (n = 52), 44% had a history of SUD. The mean time from diagnosis to last known contact and rate of loss-to-follow-up among those with a history of SUD vs no history of SUD was: 2.9 vs 4.4 years (p = 0.14) and 26.1% vs 20.7% (p = 0.64) respectively. Patients with history of SUD were more likely to live without family members and have a history of depression, anxiety or PTSD than those without a SUD history; 78.3% vs 44.8% (p = 0.023) and 60.9% vs 20.7% (p = 0.004). In the year following diagnosis the mean percentage of missed appointments, number of ER visits, number of inpatient stays, and total length of inpatient stay for patients with history of SUD vs no history of SUD were: 19% vs 8% (p = 0.01), 3.7 vs 1.4 (p = 0.08), 2.6 vs 0.9 (p = 0.10), and 17.7 vs 5.9 days (p = 0.06) respectively. Conclusions: In this retrospective analysis of patients with localized NSCLC, those with a history of SUD had shorter time from diagnosis to last known contact without increased rates of loss-to-follow-up. They also had greater rates of depression, less family support, increased rates of missed appointments, more emergency room visits, increased hospitalizations, and increased total duration of inpatient stay in the year following their diagnosis.

International audience

BackgroundAmong the psychological difficulties seen in children of parents with substance use problems, the anxiety disorders are among the most chronic conditions. Although children of alcoholic parents often struggle with the effects of parental substance use problems long into adulthood, empirical investigations of the influence of parental substance use disorders on the course of anxiety disorders in adult offspring are rare. The purpose of this study was to examine prospectively the relationship between parental substance use disorders and the course of anxiety disorders in adulthood over the course of 12 years.MethodsData on 618 subjects were derived from the Harvard/Brown Anxiety Research Project (HARP), a longitudinal naturalistic investigation of the clinical course of multiple anxiety disorders. Kaplan-Meier survival estimates were used to calculate probabilities of time to anxiety disorder remission and relapse. Proportional hazards regressions were conducted to determine whether the likelihood of remission and relapse for specific anxiety disorders was lower for those who had a history of parental substance use disorders than for individuals without this parental history.ResultsAdults with a history of parental substance use disorders were significantly more likely to be divorced and to have a high school level of education. History of parental substance use disorder was a significant predictor of relapse of social phobia and panic disorders.ConclusionThese findings provide compelling evidence that adult children of parents with substance use disorders are more likely to have relapses of social phobia and panic disorders. Clinicians who treat adults with anxiety disorders should assess parental substance use disorders and dependence histories. Such information may facilitate treatment planning with regards to their patients' level of vulnerability to perceive scrutiny by others in social situations, and ability to maintain a long-term panic-free state.

Back to table of contents Previous article Next article Communications and UpdatesFull AccessResponse to Lustman et al. LetterCarrie L. Dodrill, Ph.D., Drew A. Helmer, M.D., and Thomas R. Kosten, M.D.Carrie L. DodrillHoustonSearch for more papers by this author, Ph.D., Drew A. HelmerHoustonSearch for more papers by this author, M.D., and Thomas R. KostenHoustonSearch for more papers by this author, M.D.Published Online:1 Oct 2011https://doi.org/10.1176/appi.ajp.2011.11060869rAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Although we disagree with the extrapolation of the incidence rates presented by Lustman et al., we agree with the important advice they offer regarding the urgent need for greater vigilance to stop this growing problem. It is not logically possible to apply the 0.2% incidence rate found in Fishbain and colleagues' study (1) to estimate the percentage of new cases of opioid use disorder in people who have no history of substance use disorder. The populations in these studies are entirely different, which precludes using statistics from one to draw conclusions about the other.The question of what percentage of people who have no history of substance use disorder develop abuse or dependence on opioid painkillers is important. It is a hotly debated topic for which little data exists. The 0.2% rate we cited of opioid abuse or dependence among people with no previous history of substance use disorder was revealed by Fishbain et al. (1) after a meticulous and thorough review and compilation of data from previous studies. We believe this represents the best data available regarding this question. The authors themselves expressed some surprise at the low percentage. They noted that the studies reviewed did not report the opioid dosages to which the patients had been exposed to. They also noted that the lack of widely endorsed and consistently applied operational definitions of opioid abuse or dependence can also skew estimates. In addition, Fishbain and colleagues' analyses revealed that among the chronic pain patients exposed to chronic opioid analgesic therapy who had no history of substance use disorder, 11% displayed aberrant drug-related behavior. It was possible that the 11% of patients found to exhibit aberrant drug-related behaviors may ultimately qualify for a diagnosis of substance use disorder.We agree that a history of substance use disorder is not the only risk factor for opioid abuse or dependence. We agree with requiring prescribers to monitor patients who receive chronic opioid analgesic therapy with urine drug screens, and we agree with time-limited use of opioids and with efforts to vastly improve communication with patients about opioid risks.In sum, the treatment recommendations provided in our Treatment in Psychiatry article highlighted the importance of screening for an obvious risk factor (history of substance use disorder) but did not intend to imply that there are not other recognized risk factors. At the same time, we take the position that the data suggest that people with no history of substance use disorders or other current major risk factors may receive chronic opioid analgesic therapy with very little risk of addiction. Many important questions regarding definition and assessment of opioid dependence remain, and history has revealed ill effects of extreme positions regarding opioid use.HoustonThe authors' disclosures accompany the original article.Accepted for publication in July 2011.Reference1. Fishbain DA , Cole B , Lewis J , Rosomoff RS , Rosomoff HL: What percentage of chronic nonmalignant pain patients exposed to chronic opioid analgesic therapy develop abuse/addiction and/or aberrant drug-related behaviors? a structured evidence-based review. Pain Med 2008; 9:444–459Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 168Issue 10 October 2011Pages 1118-1119 Metrics PDF download History Accepted 1 July 2011 Published online 1 October 2011 Published in print 1 October 2011

Concurrent Use of Alcohol and Sedatives Among Persons Prescribed Chronic Opioid Therapy: Prevalence and Risk Factors

Objectives: Risk for substance use disorders is widely studied, but relatively less is known about risk of early substance use initiation. Childhood aggression has been identified as predictive of early substance use initiation, although it typically is measured as a heterogenous mix of behaviors that may underestimate the magnitude of this relationship. The purpose of this study was to extend prior research by investigating the relationship of distinct aggressive behaviors with early substance use initiation among youths with family histories of substance use disorders. Methods: Children (ages 10 to 12 years) with a family history of substance use disorder were tested on a variety of potential risk factors and monitored for substance use initiation prospectively at 6-month intervals. By age 14, 41 youth initiated substance use and 78 had not. Comparisons were made examining predictive relationships between specific aggressive behaviors, externalizing symptoms, internalizing symptoms, and social adjustment with early initiation of substance use (extending the approach of Ernst and colleagues). Results: Children who had assaulted people and had school discipline problems due to aggressive behavior were at increased odds of early substance use initiation. Even in the context of family history of substance use disorder, individual differences in childhood aggression confer increased risk for early substance use initiation. Discussion: Even in the context of family history of substance use disorder, individual differences in childhood aggression and thought problems confer increased risk for early substance use initiation.

Background Recreational use of nitrous oxide (N2O) is associated with many side effects, of which neurological complications are most common. Nitrous oxide abuse is also associated with psychiatric symptoms, but these have received less attention so far. Vitamin B12 deficiency may play a role in the development of these psychiatric symptoms. Aims To explore the relationship among the occurrence of recreational nitrous oxide-induced psychiatric symptoms, accompanying neurological symptoms, vitamin B12 status and choice of treatment. Methods A retrospective search for case reports was conducted across multiple databases (Pubmed, Embase, Web of Science, PsycINFO and CINAHL). Keywords included variants of “nitrous oxide”, “case report” and “abuse”. No restrictions to language or publication date were applied. Results The search retrieved 372 articles. A total of 25 case reports were included, representing 31 patients with psychiatric complications following nitrous oxide abuse. The most often reported symptoms were: hallucinations (n = 16), delusions (n = 11), and paranoia (n = 11). When neurological symptoms were present, patients were treated more frequently with vitamin B12 supplementation. Conclusions This review highlights the need to recognize that psychiatric symptoms may appear in association with nitrous oxide use. Approximately half of the cases that presented with nitrous oxide-induced psychiatric complaints did not show neurological symptoms, and their vitamin B12 concentration was often within the hospital's reference range. Psychiatrists and emergency physicians should be aware of isolated psychiatric symptoms caused by recreational nitrous oxide abuse. We suggest asking all patients with new psychiatric symptoms about nitrous oxide use and protocolizing the management of nitrous oxide-induced psychiatric symptoms.

Parental response to pediatric patients with somatic symptom and related disorders (SSRDs) can impact symptom presentation. However, little is known about the impact of parent psychiatric and substance use disorder (SUD) history on the functional status and medical healthcare utilization of patients with SSRDs. The current study explored the associations between parent psychiatric & SUD history and patient somatic symptoms, functional disability, and hospital course in a medically hospitalized sample of pediatric patients with SSRDs. The electronic medical records of 375 pediatric patients with SSRDs, ages 5 to 18, admitted at a tertiary pediatric hospital were retrospectively reviewed. Parent psychiatric histories were identified in 45.1% of the sample. Parent SUD history and maternal psychiatric history were associated with more patient reported somatization. Parent psychiatric and SUD history were not associated with pediatric patients' level of functional disability or healthcare utilization during admission, including admission length, number of tests, and number of consultations obtained. This study has implications regarding reduction of potential stigma towards parents with psychiatric or SUD histories whose children are hospitalized with SSRDs. While such histories may provide insights regarding somatization presentation of pediatric patients with these disorders, it may not necessarily impact level of functional disability or hospital course.

BackgroundIndividuals with substance use disorders (SUDs) are at increased risk for hepatitis C viral infection (HCV), and few studies have explored their treatment responses empirically. The objective of this study was to assess interferon alpha therapy (IFN) completion and response rates among patients with HCV who had a history of comorbid SUDs. More data is needed to inform treatment strategies and guidelines for these patients. Using a medical record database, information was retrospectively collected on 307,437 veterans seen in the Veterans Integrated Service Network 20 (VISN 20) of the Veterans Healthcare Administration (VHA) between 1998 and 2003. For patients treated with any type of IFN (including regular or pegylated IFN) or combination therapy (IFN and ribavirin) who had a known HCV genotype, IFN completion and response rates were compared among patients with a history of SUD (SUD+ Group) and patients without a history of SUD (SUD- Group).ResultsOdds ratio analyses revealed that compared with the SUD- Group, the SUD+ Group was equally likely to complete IFN therapy if they had genotypes 2 and 3 (73.1% vs. 68.0%), and if they had genotypes 1 and 4 (39.5% vs. 39.9%). Within the sample of all patients who began IFN therapy, the SUD- and SUD+ groups were similarly likely to achieve an end of treatment response (genotypes 2 and 3, 52.8% vs. 54.3%; genotypes 1 and 4, 24.5% vs. 24.8%) and a sustained viral response (genotypes 2 and 3, 42.6% vs. 41.1%; genotypes 1 and 4: 16.0% vs. 22.3%).ConclusionIndividuals with and without a history of SUD responded to antiviral therapy for HCV at similar rates. Collectively, these findings suggest that patients who have co-morbid SUD and HCV diagnoses can successfully complete a course of antiviral therapy.

Vitamin B12 deficiency can result in neurological, psychiatric, and hematological symptoms. The neurological symptoms, which may vary from person to person, depend on the degree and duration of the B12 deficiency and frequently occur in the absence of anemia. If early vitamin B12 deficiency is not recognized and promptly corrected, the neuropsychiatric conditions can progress and become irreversible in one to three years. The purpose of this commentary is twofold: first, to draw attention to the marginal vitamin B12 status of pregnant women around the world and especially in developing countries; and second, to encourage physicians, public health and governmental agencies, and international health organizations to incorporate vitamin B12 supplements into the antenatal and well-baby programs where undernutrition is common. Dietary sources of vitamin B12 are restricted to foods of animal origin. In many regions of the world where diets are largely vegetarian, low serum concentrations of vitamin B12 are common 1. Whether or not these are associated with clinically significant diseases in most cases remains uncertain and little studied. However, the presence of neurological symptoms has been observed in individuals with serum vitamin B12 concentrations at the low end of normal 2. Moreover, maternal vitamin B12 deficiency can also result in neuropathy in the newborn. Korenke and coworkers 3 recently described severe encephalopathy in a four-year-old infant that was caused by subclinical maternal pernicious anemia. A deficiency of either folate or vitamin B12 can result in increased serum concentrations of homocysteine, which is associated with birth defects (neural tube defects) and pregnancy complications (pre-eclampsia) 4. Whereas periconceptual use of folate supplements has greatly reduced the incidence of neural tube defects worldwide, the possible benefits of vitamin B12 supplements to fetal outcomes has received much less attention. As vitamin B12 deficiency is an independent risk factor for neural tube defects 6, folate supplements in the absence of vitamin B12 administration may offer minimal protection against birth defects. Our concerns regarding vitamin B12 deficiency in pregnant women derive from our nutritional assessment studies of pregnant women in northern Nigeria 5, 6. In a series of recent studies in northern Nigeria, we have observed that the vitamin B12 status of pregnant women and young girls of marrying age was generally inferior to that of folate 1. Furthermore, the finding of adequate folate status in 35% of the women, suggested that marginal vitamin B12 status may be contributing to the high serum concentrations of homocysteine. In another study conducted in Gombe, Nigeria 2, we found the mean serum folate level in healthy pregnant women to be 17.7 nmol/l, a value in the middle of the normal range, whereas the mean serum vitamin B12 level of these women was in the lowest quartile of the reference range. Thus, recent investigations in northern Nigeria paint a picture in which the nutrition of teenage girls and pregnant women attending antenatal clinics is adequate with respect to folate and iron, but suboptimal with regard to vitamin B12. Finally, while the authors were writing this piece, several research questions arose. First, how common are neurological deficits among pregnant women in northern Nigeria, including those attending the various antenatal clinics? This question could be answered by testing pregnant women for evidence of neurological problems. Furthermore, vitamin B12 status should be evaluated not by serum vitamin B12 concentrations alone, but by the serum or urine concentrations of homocysteine and methylmalonic acid. Concentrations of homocysteine and methylmalonic acid increase before other symptoms are evident. It might also be worth investigating the perinatal occurrence of deep venous thrombosis, a reasonably common event in pregnancy and possibly a reflection of the vasculotoxic effects of homocysteine. Second, what effect would vitamin B12 supplements have on the serum concentrations of homocysteine and methylmalonic acid in pregnant women in northern Nigeria? Third, would vitamin B12 supplementation of pregnant women decrease the incidence of neural tube defects in the region? Fourth, how might vitamin B12 supplementation programs for pregnant women and their fetuses be implemented in such poor regions of the world? The costs and benefits of such efforts would have to be weighed against those of the numerous other health problems confronting underdeveloped countries with small budgets. Fifth and last, though it is certainly not an easy question to answer, we wonder: how might vitamin B12 supplements impact on the quality of life of pregnant women in northern Nigeria where vitamin B12 nutrition appears to be suboptimal?

Individuals with a family history of substance use disorders (Family History Positive) are more likely to have early-onset substance use (i.e., prior to age 15), which may contribute to their higher rates of substance use disorders. One factor that may differentiate Family History Positive youth who engage in early-onset substance use from other Family History Positive youth is exposure to stressors. The aim of this study was to quantify how exposure to stressors from age 11-15 varies as a function of family history of substance use disorders and early-onset substance use. Self-reported stressors were prospectively compared in a sample of predominately (78.9%) Hispanic youth that included 68 Family History Positive youth (50% female) who initiated substance use by age 15 and demographically matched non-users with (n = 136; 52.9% female) and without (n = 75; 54.7% female) family histories of substance use disorders. Stressors were assessed at 6-month intervals for up to 4 years. Both the severity of stressors and the degree to which stressors were caused by an individual's own behavior were evaluated. All three groups differed from one another in overall exposure to stressors and rates of increase in stressors over time, with Family History Positive youth who engaged in early-onset substance use reporting the greatest exposure to stressors. Group differences were more pronounced for stressors caused by the participants' behavior. Family History Positive users had higher cumulative severity of stressors of this type, both overall and across time. These results indicate greater exposure to stressors among Family History Positive youth with early-onset substance use, and suggest that higher rates of behavior-dependent stressors may be particularly related to early-onset use.

We investigated the association between tramadol use, co-morbid substance use disorders and hepatitis in former adolescent psychiatric inpatients. The study sample consisted of 508 adolescents, admitted to psychiatric inpatient care between 13 and 17 years of age. Follow-up information of tramadol prescriptions, substance use disorders and hepatitis were obtained from the Finnish national health care registers. The users of prescription tramadol were categorized as follows: single users (one tramadol purchase), mild users (2–5 purchases) and heavy users (≥6 purchases). About one tenth (11.0%, n = 56) of study participants were tramadol users. Heavy users of tramadol had mothers with psychiatric problems (p = .039), and a diagnosis of substance use disorder (p < .001) in adolescence. Heavy use of tramadol was predicted with adolescent substance use disorder (OR = 8.31, 95%Cl 2.10–32.91, p = .003) and with mother´s psychiatric problems (OR = 5.85, p = .003). Hepatitis C (n = 54, 10.6%) associated with mild and heavy tramadol use (p < .001). Comorbid diagnosis of opioid dependence prevailed among heavy tramadol users (p <.001). Tramadol should only be prescribed to adolescents after careful evaluation. Particular caution is required in adolescents with a history of substance use disorders.

Problem substance use often begins in adolescence. This vulnerability likely stems, at least partially, from relatively rapid increases in sensation seeking occurring in early to mid-adolescence and more gradual improvements in impulse control occurring through later adolescence. Better understanding how these processes develop in high-risk youth may lead to enhanced substance use disorder treatment and prevention strategies. We characterized trajectories of self-reported impulsivity and sensation seeking in 305 FH+ youths who at minimum had a father with a history of alcohol or other drug use disorders and 81 youths with no family histories of substance use disorders (FH-). Assessments started at ages 10 to 12 and continued at 6-month intervals for up to 42months. In addition, a subset of 58 FH+ youths who began alcohol or other drug use before age 15 (FH+ Users) were compared to 58 FH+ propensity-matched adolescents who did not initiate substance use before age 15 (FH+ Non-Users). Compared to FH- youths at preadolescence, FH+ youths reported higher general impulsivity and higher impulsivity related to poor planning and attention. Over time, there were no differential effects of FH status on changes in impulsivity or sensation seeking across adolescence. FH+ Users had smaller decreases in general impulsivity and impulsivity related to restlessness and fidgeting across adolescence than FH+ Non-Users. FH+ Users also had greater increases in sensation seeking across adolescence than FH+ Non-Users. Increased impulsivity in FH+ youths may make them less able to regulate sensation seeking drives that peak in adolescence, which may contribute to their high risk for developing substance use disorders. Additionally, FH+ adolescents who initiate early use may be at increased risk in part due to increased impulsivity coupled with greater increases in sensation seeking.

We examined the prospective associations between nicotine dependence and the likelihood of psychiatric and substance use disorders in the general adult population. Participants came from a nationally representative sample of US adults aged 18 years or older, who were interviewed 3 years apart in the National Epidemiologic Survey on Alcohol and Related Conditions (Wave 1, 2001-2002; Wave 2, 2004-2005). The primary analyses were limited to 32,671 respondents (13,751 male (47.9% weighted); mean age of 45 years (SD = 0.18)) who were interviewed in both waves. We used multiple regression and propensity score matching (PSM) to estimate the strength of independent associations between nicotine dependence related to the use of tobacco products at Wave 1 and incident psychiatric disorders at Wave 2. Psychiatric disorders were measured with a structured interview (Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV). All analyses adjusted for multiple potential confounders, including childhood (family history of substance use disorders, parental loss, vulnerable family environment), early-adolescence (self-esteem, social deviance, conduct disorder), late-adolescence (education, personality and psychiatric disorders), adulthood (divorce, stressful life events, social deviance, quality of life, history of alcohol or other substance use disorder), and sociodemographic factors. Multiple regression analysis and PSM converged in indicating that nicotine dependence was associated with significantly increased incidence of any psychiatric disorder (OR = 1.39(95%CI:1.20;1.60)), including substance use disorders (OR = 1.91(95%CI:1.47;2.47)), and anxiety disorders (OR = 1.31(95%CI:1.06;1.62)). Population Attributable Risk Proportions were substantial, ranging from 12.5%(95%CI:8.10;17.0) for any psychiatric disorder to 33.3%(95%CI:18.7;48.0) for any other drug use disorder. Supplementary analyses also indicated significant associations between nicotine dependence and persistence of psychiatric and substance use disorders among patients having a disorder at Wave 1. In the general adult population, nicotine dependence is associated with an increased likelihood for several psychiatric and substance use disorders. Given its high prevalence, these findings have important public health implications.

To examine family functioning as a mediator of relations between having a family history of substance use disorder and impulsivity. Participants included a majority Hispanic sample of pre-adolescent boys and girls (mean age 10.99, SD = .84) recruited from the community who did (FH+) and did not (FH-) have a family history of substance use disorder. FH status and the quality of family functioning were compared at the initial visit with impulsiveness assessed a year later. Results showed FH+ children had worse family functioning; worse family functioning was related to higher levels of impulsivity, and higher levels of impulsivity among FH+ children were due to the influence of family functioning on levels of impulsivity. In other words, family functioning mediated relations between having a family history of substance use disorder and impulsivity. These results indicate that higher levels of impulsivity in FH+ children are due in part to worse family functioning.