Arthur Watts

University Center Rochester, Rochester, Minnesota, United States

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Publications (12)56.43 Total impact

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    ABSTRACT: Objective: Major depressive episodes may be substance induced or occur independent of substance use. Studies of the roles of substance-induced depression (SID) and independent depression (IND) in suicidal behavior are limited to retrospective reports. The purpose of this study was to examine proximal (i.e., acute) risk for suicide attempts associated with SID and IND. Method: Individuals who had attempted suicide (n = 100) and nonsuicidal controls (n = 100) matched for site were recruited from residential substance use treatment programs. Participants were ages 18 and older and screened positive for potential alcohol use disorder. Validated semistructured interviews were used to assess SID, IND, and suicide attempts. Analyses of individual-level risk for attempts were based on multivariate logistic regression that adjusted for risk factors. Population-level attributable risk (PAR) fractions for suicide attempts were also calculated to provide estimates of the percentage of attempts in the study population attributable to SID and IND, respectively. Results: SID was identified in 60% of attempters and 35% of controls and IND in 13% of attempters and 3% of controls. Both variables conferred risk for suicide attempt (SID: odds ratio [OR] = 3.73, 95% CI [1.84, 7.58]; IND: OR = 10.38, 95% CI [2.48, 43.49]. PAR for suicide attempts associated with SID and IND was 0.44 and 0.12, respectively. Conclusions: Both SID and IND confer proximal risk for suicide attempts after adjusting for other risk factors. SID also contributes substantial risk in this population overall. Future research should test the hypothesis that IND confers greater risk than SID at the individual level. (J. Stud. Alcohol Drugs, 75, 567-572, 2014).
    Journal of studies on alcohol and drugs. 07/2014; 75(4):567-72.
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    ABSTRACT: IMPORTANCE Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. OBJECTIVE To examine whether CoQ10 could slow disease progression in early PD. DESIGN, SETTING, AND PARTICIPANTS A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. INTERVENTIONS The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. MAIN OUTCOMES AND MEASURES Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. RESULTS The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo). CONCLUSIONS AND RELEVANCE Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00740714.
    JAMA Neurology 03/2014; 71(5):543-552. · 7.58 Impact Factor
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    ABSTRACT: Stressful life events (SLEs) play a key role in suicidal behavior among adults with alcohol use disorders (AUD), yet there are meager data on the severity of SLEs preceding suicidal behavior or the timing of such events. Patients in residential substance use treatment who made a recent suicide attempt (cases, n=101) and non-suicidal controls matched for site (n=101) were recruited. SLEs that occurred within 30 days of the attempt and on the day of the attempt in cases were compared to SLEs that occurred in the corresponding periods in controls. SLEs were categorized by type (interpersonal, non-interpersonal) and severity (major, minor) and were dated to assess timing. Degree of planning of suicide attempts was also assessed. Major interpersonal SLEs conferred risk for a suicide attempt, odds ratio (95% CI)=5.50 (1.73, 17.53), p=0.005. Cases were also more likely to experience an SLE on the day of the attempt than on the corresponding day in controls, OR (95% CI)=6.05 (1.31, 28.02), p=0.021. However, cases that made an attempt on the day of a SLE did not make lower planned suicide attempts compared to other cases, suggesting that suicide attempts that are immediately preceded by SLEs cannot be assumed to be unplanned. Results suggest the central importance of major interpersonal SLEs in risk among adults with AUD, a novel finding, and documents that SLEs may lead to suicide attempts within a short window of time (i.e., same day), a daunting challenge to prevention efforts.
    Drug and alcohol dependence 08/2011; 120(1-3):155-61. · 3.60 Impact Factor
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    ABSTRACT: Finding effective and efficient options for training mental health professionals to assess and manage suicide risk is a high priority. To test whether an innovative, brief workshop can improve provider knowledge, confidence, and written risk assessment in a multidisciplinary sample of ambulatory and acute services professionals and trainees. We conducted a pre/post evaluation of a 3 h workshop designed to improve clinical competence in suicide risk assessment by using visual concept mapping, medical records documentation, and site-specific crisis response options. Participants (N = 338 diverse mental health professionals) completed pre- and postworkshop questionnaires measuring their knowledge and confidence. Before and after the workshop, participants completed documentation for a clinical vignette. Trained coders rated the quality of risk assessment formulation before and after training. Participants' knowledge, confidence, and objectively-rated documentation skills improved significantly (p < .001), with large effect sizes. Participants' expectation of their ability to transfer workshop content to their clinical practice was high (mean = 4.10 on 1-5 scale). Commitment to Living is a promising, innovative, and efficient curriculum for educating practicing clinicians to assess and respond to suicide risk. Well-designed, brief, suicide risk management programs can improve clinicians' knowledge, confidence, and skill.
    Crisis The Journal of Crisis Intervention and Suicide Prevention 07/2011; 33(1):30-8. · 1.09 Impact Factor
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    ABSTRACT: To estimate the efficacy of common treatments for vulvodynia: topical lidocaine monotherapy, oral desipramine monotherapy, and lidocaine-desipramine combined therapy. A 12-week randomized, double-blinded, placebo-controlled trial was conducted on 133 vulvodynia-afflicted women assigned to four treatment arms: placebo tablets-placebo cream, desipramine tablets-placebo cream, placebo tablets-lidocaine cream, and desipramine tablets-lidocaine cream. The tampon test was selected as primary end point using a modified intention-to-treat analysis. Twelve secondary end points were also examined. At completion of the 12-week randomized phase, women were examined "open label" through 52 weeks postrandomization. All treatment arms reported substantial tampon-test pain reduction: 33% reduction placebo cream-placebo tablet, 20% reduction lidocaine cream-placebo tablet, 24% reduction placebo cream-desipramine tablet, and 36% reduction lidocaine cream-desipramine tablet. Compared with placebo, we found no significant difference in tampon-test pain reduction with desipramine (t=0.90; P=.37) or lidocaine (t=1.27; P=.21). Of the remaining 12 outcome measures, only the Index of Sexual Satisfaction, improved with desipramine compared with placebo (t=-2.81; P=.006). During the open-label phase, women undergoing vestibulectomy surgery reported significantly improved pain as measured by cotton swab test and the McGill Pain Scale compared with nonsurgical alternatives. Oral desipramine and topical lidocaine, as monotherapy or in combination, failed to reduce vulvodynia pain more than placebo. Placebo or placebo-independent effects are behind the substantial pain improvement seen in all treatment allocations. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00276068. I.
    Obstetrics and Gynecology 09/2010; 116(3):583-93. · 4.80 Impact Factor
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    ABSTRACT: The risk of Parkinson disease (PD) and its rate of progression may decline with increasing concentration of blood urate, a major antioxidant. To determine whether serum and cerebrospinal fluid concentrations of urate predict clinical progression in patients with PD. Eight hundred subjects with early PD enrolled in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial. The pretreatment urate concentration was measured in serum for 774 subjects and in cerebrospinal fluid for 713 subjects. Treatment-, age-, and sex-adjusted hazard ratios (HRs) for clinical disability requiring levodopa therapy, the prespecified primary end point of the original DATATOP trial. The HR of progressing to the primary end point decreased with increasing serum urate concentrations (HR for highest vs lowest quintile = 0.64; 95% confidence interval [CI], 0.44-0.94; HR for a 1-SD increase = 0.82; 95% CI, 0.73-0.93). In analyses stratified by alpha-tocopherol treatment (2000 IU/d), a decrease in the HR for the primary end point was seen only among subjects not treated with alpha-tocopherol (HR for a 1-SD increase = 0.75; 95% CI, 0.62-0.89; vs HR for those treated = 0.90; 95% CI, 0.75-1.08). Results were similar for the rate of change in the Unified Parkinson's Disease Rating Scale score. Cerebrospinal fluid urate concentration was also inversely related to both the primary end point (HR for highest vs lowest quintile = 0.65; 95% CI, 0.44-0.96; HR for a 1-SD increase = 0.89; 95% CI, 0.79-1.02) and the rate of change in the Unified Parkinson's Disease Rating Scale score. As with serum urate concentration, these associations were present only among subjects not treated with alpha-tocopherol. Higher serum and cerebrospinal fluid urate concentrations at baseline were associated with slower rates of clinical decline. The findings strengthen the link between urate concentration and PD and the rationale for considering central nervous system urate concentration elevation as a potential strategy to slow PD progression.
    Archives of neurology 10/2009; 66(12):1460-8. · 7.58 Impact Factor
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    ABSTRACT: A standardized tampon insertion and removal test, the Tampon Test provides an alternative to sexual intercourse pain as an outcome measure for vulvodynia research. We report upon the reliability, validity, and responsiveness to change of the Tampon Test as an outcome measure for vulvodynia clinical trials. Outcome measures were assessed in women enrolled in the Vulvar Vestibulitis Clinical Trial, a randomized clinical trial of oral desipramine and topical lidocaine effectiveness. Reliability estimates of the Tampon Test using the Kappa statistic evaluated week-to-week measures at baseline. Tampon Test construct and discriminant validity were assessed through correlation with other outcome measures. Patients' ability to regularly perform the Tampon Test was compared with regularity of reporting intercourse pain. During the 2-week baseline phase, women with vulvodynia reported stable mean Tampon Test scores 4.6+/-2.6 (week -2); 4.6+/-2.7 (week -1); and 4.7+/-2.8 (week 0) with moderate week-to-week reliability (weighted Kappa 0.52). Over an 8-week phase of trial intervention, change in the Tampon Test measure significantly correlated to a number of outcome measures, including daily pain (r=0.42), intercourse pain (r=0.35), cotton swab vestibular pain (r=0.38), and the Brief Pain Inventory (r=0.49). Women with vulvodynia study participants performed the Tampon Test 96.3% of the requested time, which was twofold higher adherence than intercourse pain measurement (49.7%). The Tampon Test reflects a real life experience that is reliable, with good construct validity as shown by the breadth of correlated outcome measures. The Tampon Test is an appropriate outcome measure for vulvodynia research that can be considered for use as the primary efficacy endpoint in clinical trials of treatments for vulvodynia. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00276068 II.
    Obstetrics and Gynecology 05/2009; 113(4):825-32. · 4.80 Impact Factor
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    ABSTRACT: The prevalence and consequences of comorbid pain and depression in gynecology patients are understudied. The purpose of the study was to determine the prevalence of pain, depression, and their co-occurrence among gynecology patients, and to examine how pain and depression are associated with additional comorbid mental disorders. Self-reported pain, depressive symptoms, other mental-disorder symptoms, functional status, interpersonal distress, and abuse were assessed in 1,647 gynecology patients by use of the Patient Health Questionnaire and the Medical Outcomes Study (SF-20). Moderate-to-severe pain was reported by 29% of patients; depression, by 21%; with both present in 10.3%. Comorbid pain and depression was associated with anxiety, suicidal or death ideation, functional impairment, interpersonal distress, and physical or sexual abuse. Innovative approaches are needed to assess and treat gynecology patients with comorbid pain and depression, given the degree of overlap between them.
    Psychosomatics 01/2009; 50(3):270-6. · 1.73 Impact Factor
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    ABSTRACT: To determine whether concentration of serum urate, a purine metabolite and potent antioxidant that has been linked to a reduced risk of Parkinson disease (PD), predicts prognosis in PD. Prospective study. The Parkinson Research Examination of CEP-1347 Trial (PRECEPT) study, which investigated the effects of a potential neuroprotectant on rates of PD progression, was conducted between April 2002 and August 2005 (average follow-up time 21.4 months). Eight hundred four subjects with early PD enrolled in the PRECEPT study. The primary study end point was progression to clinical disability sufficient to warrant dopaminergic therapy. Cox proportional hazards models were used to estimate the hazard ratio (HR) of reaching end point according to quintiles of baseline serum urate concentration, adjusting for sex, age, and other potential covariates. Change in striatal uptake of iodine I 123-labeled 2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane ([(123)I]beta-CIT), a marker for the presynaptic dopamine transporter, was assessed with linear regression for a subset of 399 subjects. The adjusted HR of reaching end point declined with increasing baseline concentrations of urate; subjects in the top quintile reached the end point at only half the rate of subjects in the bottom quintile (HR, 0.51; 95% confidence interval [CI], 0.37-0.72; P for trend < .001). This association was markedly stronger in men (HR, 0.39; 95% CI, 0.26-0.60; P for trend < .001) than in women (HR, 0.77; 95% CI, 0.39-1.50; P for trend = .33). The percentage of loss in striatal [(123)I]beta-CIT uptake also improved with increasing serum urate concentrations (overall P for trend = .002; men, P = .001; women, P = .43). These findings identify serum urate as the first molecular factor directly linked to the progression of typical PD and suggest that targeting urate or its determinants could be an effective disease-modifying therapy in PD. Trial Registration clinicaltrials.gov Identifier: NCT00040404.
    Archives of neurology 07/2008; 65(6):716-23. · 7.58 Impact Factor
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    ABSTRACT: Depression among women with childhood sexual abuse histories has a chronic and treatment-refractory course, and is accompanied by high rates of comorbid illness and adult trauma exposures. Reducing the disproportionate burden of serious mental illness among depressed, traumatized women must be a priority in community mental health settings. Effective treatments are needed. The feasibility and effects of interpersonal psychotherapy (IPT) for women with major depression and childhood trauma histories were tested. Twenty-five women in a community mental health center were enrolled in a 16-session course of IPT. Symptoms, functioning, and feasibility (e.g., participation rates) were measured at baseline, 10 weeks, 24 weeks, and 36 weeks. Fifteen of the 25 participants completed eight or more sessions. Significant improvements in depression and psychological functioning, but not in social functioning, were observed. Although a 16-session course of IPT appears feasible and promising, modifications may be needed to reduce barriers to care and enhance treatment potency.
    Journal of Nervous & Mental Disease 01/2006; 193(12):847-50. · 1.84 Impact Factor
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    ABSTRACT: The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear. To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes. Multicenter, parallel-group, double-blind, randomized controlled trial. Academic movement disorders clinics at 22 sites in the United States and Canada. Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001. Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability. Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events. Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups. Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but they are associated with different efficacy and adverse-effect profiles.
    JAMA Neurology 08/2004; 61(7):1044-53. · 7.58 Impact Factor
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    ABSTRACT: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.
    Neurology 03/2001; 56(4):455-62. · 8.25 Impact Factor