Shannon C. Miller

Mental health impact of the Iraq and Afghanistan conflicts: A review of US research, service provision, and programmatic responses

Abstract Although documentation that war inflicts psychological casualties dates back to the American Civil War and earlier, most research began after the Vietnam conflict, when studies focused on post-traumatic stress disorder (PTSD). With ongoing conflicts in Iraq and Afghanistan, there has been significant research to illuminate the epidemiology of war-related psychological casualties. Significant findings include an appreciation for the role combat plays in the development of mental disorders, including PTSD and traumatic brain injury (TBI). Recent research has endeavoured to understand and improve psychological resilience to temper potentially adverse mental health effects of military service in the theatre of combat operations. Over 2 million US service members have now deployed and returned over 3 million times to the Iraq and Afghanistan conflicts. Mental health providers in the Departments of Defense and Veterans Affairs healthcare systems have consequently observed steep increases in mental health service use among these personnel. The Departments have responded aggressively to bolster staffing levels, increase capacity, improve available services, and anticipate future needs. Scientists and clinicians continue efforts to understand the determinants, prevention, recognition, and treatment of combat-related mental disorders.

Dextromethorphan psychosis, dependence and physical withdrawal

As part of a synthesis of evidence regarding the abuse and addiction liability of dextromethorphan (DM), an over‐the‐counter cough medicine available in over 140 preparations, an uncommonly published case of dextromethorphan dependence (addiction) is described, with specific, rarely published complications. The individual was interviewed and several medical databases were also reviewed (Medline, 1966–present; PubMed) for all content relating to the Keywords: dextromethorphan, abuse, dependence, cough medicine, addiction, withdrawal, psychosis. The patient evidenced history suggesting substance dependence, substance‐induced psychosis and substance withdrawal in relation to DM. A literature review revealed that DM has specific serotonergic and sigma‐1 opioidergic properties. Dextrorphan (DOR), the active metabolite of DM, has similar properties; however, DOR is a weaker sigma opioid receptor agonist, and a stronger NMDA receptor antagonist. DM and DOR display specific biological features of addiction, and are capable of inducing specific psychiatric sequelae. A specific, reproducible toxidrome with significant psychiatric effects occurred, when DM was abused at greater than indicated doses, with more profound and potentially life‐threatening effects at even higher doses. DM withdrawal appears evident. DMs active metabolite, DOR, has pharmacodynamic properties and intoxication effects similar to dissociatives, and may be more responsible for the dissociative effect that this DM abuser sought. However, it is this same metabolite that may be fraught with the potentially life‐threatening psychoses and dissociative‐induced accidents, as well as addiction. While DM has been hypothesized as the most commonly abused dissociative, health‐care providers seem largely unaware of its toxidrome and addiction liability.

Risk for addiction-related disorders following mild traumatic brain injury in a large cohort of active-duty U.S. airmen

OBJECTIVE Military personnel are at increased risk for traumatic brain injury (TBI) from combat and noncombat exposures. The sequelae of moderate to severe TBI are well described, but little is known regarding long-term performance decrements associated with mild TBI. Furthermore, while alcohol and drug use are well known to increase risk for TBI, little is known regarding the reverse pattern. The authors sought to assess possible associations between mild TBI and addiction-related disorders in active-duty U.S. military personnel. METHOD A historical prospective study was conducted using electronically recorded demographic, medical, and military data for more than a half million active-duty U.S. Air Force service members. Cases were identified by ICD-9-CM codes considered by an expert panel to be indicative of mild TBI. Outcomes included ICD-9-CM diagnoses of selected addiction-related disorders. Cox proportional hazards modeling was used to calculate hazard ratios while controlling for varying lengths of follow-up and potential confounding variables. RESULTS Airmen with mild TBI were at increased risk for certain addiction-related disorders compared with a similarly injured non-mild TBI comparison group. Hazards for alcohol dependence, nicotine dependence, and nondependent abuse of drugs or alcohol were significantly elevated, with a consistent decrease over time. CONCLUSIONS A novel finding of this study was the initial increased risk for addiction-related disorders that decreased with time, thus eroding war fighter performance in a military population. Moreover, these results suggest that mild TBI is distinguished from moderate to severe TBI in terms of timing of the risk, indicating that there is a need for screening and prevention of addiction-related disorders in mild TBI. Screening may be warranted in military troops as well as civilians at both short- and long-term milestones following mild TBI.

Smokeless tobacco use related to military deployment, cigarettes and mental health symptoms in a large, prospective cohort study among US service members.

AIMS To characterize smokeless tobacco initiation and persistence in relation to deployment, combat, occupation, smoking and mental health symptoms. DESIGN Prospective cohort, utilizing self-reported survey data from the Millennium Cohort Study. SETTING US military service members in all branches including active duty, reserve and National Guard. PARTICIPANTS Population-based sample of 45,272 participants completing both baseline (July 2001-June 2003; n = 77,047) and follow-up (June 2004-January 2006; n = 55,021) questionnaires (follow-up response rate = 71.4%). MEASUREMENTS Self-reported smokeless tobacco initiation and persistence. FINDINGS Over the study period, 72.4% did not deploy, 13.7% deployed without combat exposures and 13.9% deployed with combat exposures, while 1.9% were smokeless tobacco initiators and 8.9% were persistent users. The odds of initiation were greater for deployers with combat exposure [odds ratio (OR), 1.76; 95% confidence interval (CI), 1.49-2.09], deployers without combat exposure (OR, 1.31; 95% CI, 1.07-1.60) and those who deployed multiple times (OR, 1.67; 95% CI, 1.31-2.14), as well as in smoking recidivists/initiators (OR, 4.65; 95% CI, 3.82-5.66) and those reporting post-traumatic stress disorder symptoms (OR, 1.54; CI, 1.15-2.07). A similar pattern for higher odds of persistent use was observed for deployment and combat exposure, but not for smoking and mental health symptoms. Military occupation was not significantly associated with initiation or persistence. CONCLUSIONS Deployment and combat exposure in the US military are associated with increased risk of smokeless tobacco initiation and persistence while smoking and symptoms of post-traumatic stress disorder increase the odds for initiation. Research is needed on aspects of military service amenable to the reduction or prevention of tobacco consumption.

Longitudinal assessment of mental disorders, smoking, and hazardous drinking among a population-based cohort of US service members

Objectives: Combat exposure is known to increase the risk for mental disorders; however, less is known about the temporal relationship between mental disorders and alcohol misuse or smoking. To better understand these interrelationships, this study investigated mental disorders in association with hazardous drinking and cigarette smoking. Methods: Using data from a large population-based military cohort, standardized instruments were used to screen for posttraumatic stress disorder, depression, panic, and other anxiety syndromes. Self-reported use of cigarettes and hazardous drinking was also assessed. Subjects were classified as having “new-onset,” “persistent,” or “resolved” mental disorders and health risk behaviors on the basis of screening results from baseline to follow-up (n = 50,028). Multivariable logistic regression models were used to investigate temporal patterns between the development of mental disorders and the uptake of smoking or hazardous drinking. Results: The strongest associations of new-onset mental disorders were among those who newly reported smoking or hazardous drinking (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.28-2.59 and OR, 2.49; 95% CI, 2.15-2.89, respectively), even after adjustment for combat deployment experience. In addition, persistent smokers and hazardous drinkers had elevated odds for developing a mental disorder at follow-up. Conclusions: This study demonstrates a positive association between the onset of mental disorders with the uptake of smoking and hazardous drinking and the likelihood that multiple temporal sequence patterns exist to explain the relationship between mental disorders and hazardous drinking and smoking. Clinical approaches to mitigate deployment-related mental disorders should include alcohol and tobacco-related assessments and interventions.

Pathologic gambling disorder. How to help patients curb risky behavior when the future is at stake.

PREVIEW Pathologic gambling disorder and problem gambling are becoming increasingly common in the United States as more states legalize gambling. Although gambling-related disorders can cause devastating consequences, well-studied treatments are few. Fortunately, clinical experience suggests that pathologic gambling disorder is highly treatable. In this article, Drs Sumitra and Miller briefly summarize gambling-related disorders and discuss available, effective treatments.

Ketamine as a preferred substance of abuse.

etamine is a cyclohexane anesthetic agent legally manufactured in the United States. It is pharmacologically similar to the illicit substance phencyclidine, though with a much lower potency. 1 As such, ketamine carries with it a significant abuse potential; however, it is rarely identified as a patient’s substance of choice. We present such a case below, with a discussion concerning potential contributory factors that may have led to his preference for ketamine. CC is a 20-year-old male who selfreferred to an intensive addiction rehabilitation facility after an accidental lorazepam and ketamine overdose. The patient had an extensive substance use history, including abuse of cannabis, LSD, PCP, barbiturates, cocaine, opioids, and MDMA, and dependence upon alcohol and benzodiazepines; however,CCdefinedhissubstanceofchoice as ketamine. Ketamine was mostly used alone in its injectable form in order to achieve the desired effect of rapid onset dissociation. Even though agents such as cocaine, other stimulants, and benzodiazepines were sometimes used in order to augment this dissociative effect, CC insisted that his preference for ketamine was based largely upon his belief that it ``was not a bad drug’’ because of its FDA approval as being ``safe to use on humans.’’ He rationalized thatbecause ketaminecould be obtained in a sterile and unadulterated form, it was both ``clean and safe.’’ He was also aware that ketamine carried a lower potential for cardio-respiratory sequelae than PCP, another dissociative agent. The frequency of ketamine injections increased as greater amounts of the substance became required in order to achieve the target dissociative effect. While heat first exercised at leastsomemeasureofcautionin monitoring hisuseof thesubstance,CCdescribeda progressively intense yearning for the dissociative effects of ketamine as a means to ``escape’’ from a myriad of interpersonal problems, giving way to the misuse of the substance in greater amounts than at first intended during individual injections and repetition of this increasingly compulsive pattern of use over a longer period of time

Risk for broad-spectrum neuropsychiatric disorders after mild traumatic brain injury in a cohort of US Air Force personnel

Background Military personnel are at increased risk for traumatic brain injury (TBI) from combat and non-combat exposures. Sequelae of moderate-to-severe TBI are well described, but the literature remains conflicted regarding whether mild TBI (mTBI) results in lasting brain injury and functional impairments. This study assessed risk for a range of neuropsychiatric disorders presenting after mTBI while adjusting for the potential confounds of depression and post-traumatic stress disorder (PTSD). Methods A historical prospective association study was conducted utilising electronic demographic, medical and military-specific data for over 49 000 active duty US Air Force service members (Airmen). This study utilised diagnostic codes considered by an expert panel to be indicative of mTBI to identify cases. Cox proportional hazards modelling calculated HRs for neuropsychiatric outcomes while controlling for varying lengths of follow-up and potentially confounding variables. Results Airmen with mTBI were at increased risk for specific neuropsychiatric disorders compared with a similarly injured non-mTBI control group. HRs for memory loss/amnesia, cognitive disorders, schizophrenia, PTSD, and depression were significantly elevated and remained so for at least 6 months post-mTBI, even after eliminating those with previous neuropsychiatric diagnoses. Conclusions mTBI was positively associated with neuropsychiatric disorders in this population of primarily young adult males; with increased HRs 6 months post-mTBI. The results support that mTBI is distinguished from moderate-to-severe TBI in terms of risk for developing neuropsychiatric disorders. Further, these findings suggest the importance of screening for psychiatric and cognitive disorders post-mTBI in general medical practice.

The Abuse Liability of Dextromethorphan Among Adolescents: A Review

ABSTRACT Dextromethorphan (DM) is a popular over-the-counter antitussive medication. Although adverse effects from appropriate use are rare, a specific toxidrome with significant psychomimetic effects occurs with ingestions in excess of those recommended. Both DM and its active metabolite, dextrorphan (DOR), share pharmacologic and neurobehavioral properties similar to opiates and phencyclidine (PCP). As such, cases of recreational DM abuse and, rarely, dependence, have been reported, and some data suggest that such abuse is on the rise. DM may be considered by substance abusers, especially adolescents, to be a dissociative agent devoid of financial concerns, legal limitations, negative stigma, problems with access or adverse health consequences. However, DMs popularity among adolescent substance abusers is generally not matched by adequate health care provider awareness, pharmacological understanding or epidemiological characterization. In this review, we summarize the current understanding of DMs addiction medicine-based neuropharmacology and epidemiology, describe social characteristics more unique to DM as an agent of abuse, review treatment and prevention issues, and identify areas in need of further research.

Dextromethorphan to dextrorphan: a pathway towards abuse liability†

Human Psychopharmacology (Zawertailo et al., 2010) published a highly salient original study assessing the effect of quinidine, a cytochrome P450 2D6 enzyme inhibitor, on the catabolism of dextromethorphan (DM) to its psychoactive metabolite dextrorphan (DXO) and resultant pharmacodynamic effects on human subjects. This builds on the previous work by this group (Zawertailo et al., 1998). DXO is best classified as a dissociative as it shares pharmacodynamic effects with the well-known dissociatives phencyclidine and ketamine. DM is particularly attractive to youth. Youth consider DM a ‘‘SMART’’ drug to abuse: there is minimal stigma associated with its use (unlike heroin, cocaine, or ‘‘street’’ drugs), very little money is required to acquire it, it is readily accessible over the counter or in the home medicine cabinet, there are few medical risks perceived by users, and it is not routinely tested for on drug screen testing (Miller, 2005a). Since 2006, the Monitoring the Future Study has queried eighth, tenth, and twelfth graders in the U.S. regarding whether they have used DM to ‘‘get high.’’ Roughly 4–6% of these students respond affirmatively (Johnston et al., 2010). A 5-year study supports that DM/DXO is increasingly used by teens in the U.S. (Bryner et al., 2006); and a 6-year study of Wisconsin driver’s urine that screened positive for other drugs of abuse found alarmingly high DM levels present (a mean of 207 ng/ml of DM present, with expected levels from therapeutic ingestion being 0.5–5.9 ng/ml) (Cochems et al., 2007). Dose ranges for abuse range from 20 to over 200 times the recommended therapeutic dose (Miller, 2005b). Moreover, with over 140 over the counter versions of DM available in the U.S., several commonly added ingredients portend added risk of