Integrated Care Increases Treatment and Improves Outcomes of Patients With Chronic Hepatitis C Virus Infection and Psychiatric Illness or Substance Abuse.

BACKGROUND & AIMS: Patients with hepatitis C virus (HCV) infection with psychiatric disorders and/or substance abuse face significant barriers to antiviral treatment. New strategies are needed to improve treatment rates and outcomes. We investigated whether an integrated care (IC) protocol, which includes multidisciplinary care coordination and patient case management, could increase the proportion of patients with chronic HCV infection who receive antiviral treatment (a combination of interferon-based and direct-acting antiviral agents) and achieve a sustained virologic response (SVR). METHODS: We performed a prospective randomized trial at 3 medical centers in the United States. Participants (n = 363 patients attending HCV clinics) had been screened and tested positive for depression, post-traumatic stress disorder, and/or substance use; they were assigned randomly to groups that received IC or usual care (controls) from March 2009 through February 2011. A midlevel mental health practitioner was placed at each HCV clinic to provide IC with brief mental health interventions and case management, according to formal protocol. The primary end point was SVR. RESULTS: Of the study participants, 63% were non-white, 51% were homeless in the past 5 years, 64% had psychiatric illness, 65% were substance abusers within 1 year before enrollment, 57% were at risk for post-traumatic stress disorder, 71% had active depression, 80% were infected with HCV genotype 1, and 23% had advanced fibrosis. Over a mean follow-up period of 28 months, a greater proportion of patients in the IC group began receiving antiviral therapy (31.9% vs 18.8% for controls; P = .005) and achieved a SVR (15.9% vs 7.7% of controls; odds ratio, 2.26; 95% confidence interval, 1.15-4.44; P = .018). There were no differences in serious adverse events between groups. CONCLUSIONS: Integrated care increases the proportion of patients with HCV infection and psychiatric illness and/or substance abuse who begin antiviral therapy and achieve SVRs, without serious adverse events. ClinicalTrials.gov # NCT00722423.

Clinical practice guideline: tinnitus.

OBJECTIVE: Tinnitus is the perception of sound without an external source. More than 50 million people in the United States have reported experiencing tinnitus, resulting in an estimated prevalence of 10% to 15% in adults. Despite the high prevalence of tinnitus and its potential significant effect on quality of life, there are no evidence-based, multidisciplinary clinical practice guidelines to assist clinicians with management. The focus of this guideline is on tinnitus that is both bothersome and persistent (lasting 6 months or longer), which often negatively affects the patient's quality of life. The target audience for the guideline is any clinician, including nonphysicians, involved in managing patients with tinnitus. The target patient population is limited to adults (18 years and older) with primary tinnitus that is persistent and bothersome. PURPOSE: The purpose of this guideline is to provide evidence-based recommendations for clinicians managing patients with tinnitus. This guideline provides clinicians with a logical framework to improve patient care and mitigate the personal and social effects of persistent, bothersome tinnitus. It will discuss the evaluation of patients with tinnitus, including selection and timing of diagnostic testing and specialty referral to identify potential underlying treatable pathology. It will then focus on the evaluation and treatment of patients with persistent primary tinnitus, with recommendations to guide the evaluation and measurement of the effect of tinnitus and to determine the most appropriate interventions to improve symptoms and quality of life for tinnitus sufferers. ACTION STATEMENTS: The development group made a strong recommendation that clinicians distinguish patients with bothersome tinnitus from patients with nonbothersome tinnitus. The development group made a strong recommendation against obtaining imaging studies of the head and neck in patients with tinnitus, specifically to evaluate tinnitus that does not localize to 1 ear, is nonpulsatile, and is not associated with focal neurologic abnormalities or an asymmetric hearing loss. The panel made the following recommendations: Clinicians should (a) perform a targeted history and physical examination at the initial evaluation of a patient with presumed primary tinnitus to identify conditions that if promptly identified and managed may relieve tinnitus; (b) obtain a prompt, comprehensive audiologic examination in patients with tinnitus that is unilateral, persistent (≥ 6 months), or associated with hearing difficulties; (c) distinguish patients with bothersome tinnitus of recent onset from those with persistent symptoms (≥ 6 months) to prioritize intervention and facilitate discussions about natural history and follow-up care; (d) educate patients with persistent, bothersome tinnitus about management strategies; (e) recommend a hearing aid evaluation for patients who have persistent, bothersome tinnitus associated with documented hearing loss; and (f) recommend cognitive behavioral therapy to patients with persistent, bothersome tinnitus. The panel recommended against (a) antidepressants, anticonvulsants, anxiolytics, or intratympanic medications for the routine treatment of patients with persistent, bothersome tinnitus; (b) Ginkgo biloba, melatonin, zinc, or other dietary supplements for treating patients with persistent, bothersome tinnitus; and (c) transcranial magnetic stimulation for the routine treatment of patients with persistent, bothersome tinnitus. The development group provided the following options: Clinicians may (a) obtain an initial comprehensive audiologic examination in patients who present with tinnitus (regardless of laterality, duration, or perceived hearing status); and (b) recommend sound therapy to patients with persistent, bothersome tinnitus. The development group provided no recommendation regarding the effect of acupuncture in patients with persistent, bothersome tinnitus.

Clinical practice guideline: tinnitus executive summary.

The American Academy of Otolaryngology--Head and Neck Surgery Foundation (AAO-HNSF) has published a supplement to this issue featuring the new Clinical Practice Guideline: Tinnitus. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 13 recommendations developed address the evaluation of patients with tinnitus, including selection and timing of diagnostic testing and specialty referral to identify potential underlying treatable pathology. It will then focus on the evaluation and treatment of patients with persistent primary tinnitus, with recommendations to guide the evaluation and measurement of the impact of tinnitus and to determine the most appropriate interventions to improve symptoms and quality of life for tinnitus sufferers.

Review of biological mechanisms and pharmacological treatments of comorbid PTSD and substance use disorder.

Posttraumatic stress disorder (PTSD) and alcohol/substance use disorder (A/SUD) are frequently comorbid. Comorbidity is associated with poorer psychological, functional, and treatment outcomes than either disorder alone. This review outlines biological mechanisms that are potentially involved in the development and maintenance of comorbid PTSD and A/SUD including neurotransmitter and hypothalamic-pituitary-adrenal dysregulation, structural differences in the brain, and shared genetic risk factors. The literature regarding pharmacological treatments that have been investigated for comorbid PTSD and A/SUD is also reviewed. Empirical data for each proposed mechanism and pharmacological approach is reviewed with the goal of making recommendations for future research. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

Predictors of treatment retention for substance-dependent adults with co-occurring depression.

Low attendance in addiction treatment, particularly in cases of comorbidity, has been identified as a pervasive challenge. We examine predictors of treatment retention in a sample of veterans (N = 253) participating in a clinical trial comparing two types of psychotherapy for co-occurring depression and substance use disorders. The study protocol included 24 weeks of outpatient group psychotherapy in either a newly developed Integrated Cognitive Behavioral Therapy (ICBT) or Twelve-Step Facilitation Therapy (TSF). Using a model of treatment utilization developed by Aday and Anderson, we analyzed predictors categorized into predisposing factors, enabling resources, need for treatment, and type of treatment received. Outcome included total number of sessions attended (maximum of 36 sessions). Treatment retention did not differ between the two study interventions. Bivariate analyses indicated that predisposing factors were most predictive, with older participants, Caucasians, and those using only alcohol in the month before treatment attending more sessions, and individuals who had recently experienced a health event remained in treatment longer. Importantly, several factors were not related to treatment retention: marital status, education, neuropsychological functioning, financial stress, chronic health problems, treatment motivation, and psychiatric severity. In the combined model of predisposing, enabling and need factors, age and ethnicity were the only significant predictors.

Alcohol attenuates activation in the bilateral anterior insula during an emotional processing task: a pilot study.

AIMS: Alcohol acutely reduces agitation and is widely used in social situations, but the neural substrates of emotion processing during its intoxication are not well understood. We examine whether alcohol's social stress dampening effect may be via reduced activity in the cortical systems that subserve awareness of bodily sensations, and are associated with affective distress. METHODS: Blood oxygen level-dependent activation was measured through 24 functional magnetic resonance imaging sessions in 12 healthy volunteers during an emotional face-processing task following ingestion of a moderate dose of alcohol and a placebo beverage. RESULTS: Results revealed that bilateral anterior insula response to emotional faces was significantly attenuated following consumption of alcohol, when compared with placebo (clusters >1472 µl; corrected P < 0.05). CONCLUSION: Attenuated response in the anterior insula after alcohol intake may explain some of the decreased interoceptive awareness described during intoxication.

Acute ethanol effects on brain activation in low- and high-level responders to alcohol.

BACKGROUND: A low level of response (LR) to alcohol is an important endophenotype associated with an increased risk of alcoholism. However, little is known about how neural functioning may differ between individuals with low and high LRs to alcohol. This study examined whether LR group effects on neural activity varied as a function of acute alcohol consumption. METHODS: A total of 30 matched high- and low-LR pairs (N = 60 healthy young adults) were recruited from the University of California, San Diego, and administered a structured diagnostic interview and laboratory alcohol challenge followed by two functional magnetic resonance imaging (fMRI) sessions under placebo and alcohol conditions, in randomized order. Task performance and blood oxygen level-dependent response contrast to high relative to low working memory load in an event-related visual working memory (VWM) task were examined across 120 fMRI sessions. RESULTS: Both LR groups performed similarly on the VWM task across conditions. A significant LR group by condition interaction effect was observed in inferior frontal and cingulate regions, such that alcohol attenuated the LR group differences found under placebo (p < 0.05). The LR group by condition effect remained even after controlling for cerebral blood flow, age, and typical drinking quantity. CONCLUSIONS: Alcohol had differential effects on brain activation for low- and high-LR individuals within frontal and cingulate regions. These findings represent an additional step in the search for physiological correlates of a low LR and identify brain regions that may be associated with the low LR response.

A randomized controlled trial of cognitive-behavior therapy for tinnitus.

This study is a randomized, waitlist-controlled trial testing the effect of a brief, "manualized" cognitive-behavioral group therapy on distress associated with tinnitus, quality of well-being, psychological distress including depression, and internal focus. Cognitive-behavioral therapy (CBT) included training in activity planning, relaxation training and, primarily, cognitive restructuring. Sixty-five participants were recruited, and 41 completed treatment. Participants were randomly assigned to receive 8 weeks of manualized group CBT either immediately or after an 8-week waiting period. Participants completed outcome measures at the time of their random assignment and at 8, 16, and 52 weeks later. Repeated-measure analysis of covariance revealed significant group-by-time interactions on measures of tinnitus distress and depression, indicating that CBT led to greater improvement in those symptoms. The current results suggest that CBT, applied in a group format using a manual, can reduce the negative emotional distress, including depression, associated with tinnitus.

Antidepressant therapy in tinnitus.

OBJECTIVE: Review the literature on the co-morbidity of depression and anxiety with tinnitus. Briefly consider proposed mechanisms by which antidepressants might be helpful for tinnitus, including treatment of co-morbid depression and anxiety and a more direct serotonergic mechanism of tinnitus. Survey the literature on antidepressants and tinnitus including tinnitus reported as a side effect of antidepressants (phenelzine, amitriptyline, protriptyline, doxepin, imipramine, fluoxetine, trazadone, bupropion, venlafaxine), tinnitus associated with withdrawal of antidepressants (venlafaxine and sertraline) and antidepressants as a treatment for tinnitus (case reports--fluoxetine and paroxetine, retrospective reviews--imipramine and selective serotonin reuptake inhibitors, single blind trials of amitriptyline and double blind placebo controlled trials of trimipramine, nortriptyline, paroxetine and sertraline). Provide suggestions on future directions, specifically replication of prior studies and a dose finding study of paroxetine for the treatment of tinnitus.

Associations of variations in alcohol dehydrogenase genes with the level of response to alcohol in non-Asians.

BACKGROUND: Risk and protective factors for alcohol use disorders (AUDs) are complex and reflect both environmental and genetic factors. Genetic components account for about 50% of the variation and influence several phenotypes, including the level of response (LR) to alcohol as well as alcohol-metabolizing enzyme polymorphisms. Variations in the ADH1B and ADH1C genes may influence the LR to alcohol by increasing levels of acetaldehyde during alcohol metabolism, although most data on this question come from Asian populations. METHODS: This study evaluated associations of ADH1B and ADH1C genotypes in a non-Asian sample. Participants (N = 117, 69.2% female) were 18- to 29-year-old men and women, primarily Caucasian (70.1%) and black (26.5%), recruited in San Diego, California. The Semi-Structured Assessment for the Genetics of Alcoholism Interview was used to assess demographic, substance use, and psychiatric history information, and the Family History Assessment Module was used to determine first-degree family history of alcohol dependence. An alcohol challenge paradigm was used to gather data on the LR to alcohol over 210 minutes. RESULTS: Participants with the ADH1B*1/*2 genotype had a higher LR to alcohol early in the alcohol challenge (i.e., 30, 60, and 90 minutes after drinking) as measured by both alcohol-related changes in subjective feelings of intoxication and body sway, even when controlling for sex and Russian/Eastern European ancestry. A similar trend was seen for ADH1C*1/*1 genotype, although the results were not significant. CONCLUSIONS: These findings suggest that studies searching for genes relating to the LR to alcohol as a vulnerability factor for AUDs should consider controlling for ADH1B genotype, as the ADH1B*2 allele could obscure the impact of other genetic polymorphisms.

Randomized placebo-controlled trial of a selective serotonin reuptake inhibitor in the treatment of nondepressed tinnitus subjects.

OBJECTIVE: To assess the efficacy of a selective serotonin reuptake inhibitor (paroxetine) for relief of tinnitus. DESIGN: One hundred twenty tinnitus sufferers participated in a randomized double-blind placebo-controlled trial. Paroxetine or placebo was increased to a maximally tolerated dose (up to 50 mg/day), and patients were treated for a total of 31 days at the maximal dose. METHODS: Patients with chronic tinnitus were recruited from our university-based specialty clinic by referral from otolaryngologists and audiologists in the local community and by advertisement. Patients with psychotic or substance use disorders or suicidal ideation were excluded, as were those using psychoactive medications (this resulted in only 1 subject with major depression in the study) or any other medications that interact with paroxetine and those with inability to hear at one's tinnitus sensation level. Fifty-eight percent of patients were male, 92% were Caucasian, and the average age was 57. OUTCOMES MEASURES: Tinnitus matching, the Tinnitus Handicap Questionnaire, the question: How severe (bothered, aggravating) is your tinnitus? Quality of Well-Being and other psychological questionnaires. RESULTS: Paroxetine was not statistically superior to placebo on the following tinnitus measures (tinnitus matching, 5- or 10-db drop, Tinnitus Handicap Questionnaire, quality of well-being measures, how severe, how bothered, positive change). There was a significant improvement in the single item question, How aggravating is your tinnitus? for those in the paroxetine group compared with the placebo group. CONCLUSIONS: These results suggest that the majority of individuals in this study did not benefit from paroxetine in a consistent fashion. Further work remains to be done to determine if subgroups of patients (e.g., those who tolerate higher doses, those who are depressed) may benefit.

Rapid oral loading of extended release divalproex in patients with acute mania.

BACKGROUND: Oral loading with the delayed release formulation of divalproex sodium is widely used for the treatment of patients with acute mania and produces rapid attainment of therapeutic serum levels. Recently, an extended release formulation of divalproex sodium (divalproex ER) was approved for treatment of migraine headaches. This formulation may be a useful treatment option for patients with acute mania. METHOD: A retrospective review of medical records was conducted on 14 inpatients with acute mania whose treatment included initiation of divalproex ER at a dose of 30 mg kg(-1) day(-1) in a single dose. Doses, serum levels and side effects associated with this treatment were recorded from the medical records of these patients. RESULTS: The average dose of divalproex ER was 2034 mg day(-1) (range, 1500-3000 mg day(-1)). Two of the 14 patients (14%) had documented side effects, none of which were severe. The average level obtained on day 3 after initiation of divalproex ER treatment was 93.2 mug ml(-1) (range, 47-136 mug ml(-1)), and in all but three patients valproate levels at this time point were within the therapeutic range of 50-125 mug ml(-1). In no case was divalproex ER discontinued due to a perceived lack of efficacy. CONCLUSION: The results suggest that divalproex ER can be safely administered by oral loading in inpatients with acute mania and that using a standard loading protocol can result in therapeutic serum levels in most patients in 3 days or less.

Relationship of tinnitus questionnaires to depressive symptoms, quality of well-being, and internal focus.

Twenty percent of people endure tinnitus to a degree that their quality of well-being and productivity in life are impaired, and up to 60% report depression. Four measures are widely used to assess tinnitus-related distress, yet the relationship among all four measures or their relationship to relevant psychiatric variables has yet to be studied. This study assessed the association between the four commonly used measures of tinnitus and their relationship to depressive symptoms, quality of well-being, and internal focus. Sixty-five people with tinnitus completed the following measures: Iowa Tinnitus Handicap Questionnaire (THQ); Tinnitus Reaction Questionnaire (TRQ); Tinnitus Handicap Inventory (THI); Tinnitus Questionnaire (TQ); Hamilton Rating Scale for Depression (HRSD); Beck Depression Inventory (BDI); Quality of Well-Being Scale (QWBS); Modified Somatic Perception Questionnaire (MSPQ); and Private Self-Consciousness Scale (PSCS). All the tinnitus measures were highly intercorrelated (r = .76-.90; all p values < .001), and related to depressive symptoms (r = .48-.66; p < .001) and QWBS (r = .37-.48; all p values < 0.008). The tinnitus measures correlated with the MSPQ (r = .37-.52; all p values < .01) but not with the PSCS. When controlling for the shared variance between tinnitus measures, the THQ independently predicted the HRSD, whereas the TRQ independently predicted the BDI.