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GME Research Review

GME Research Review is a monthly newsletter where internationally recognized experts select, summarize, and provide a clinical commentary on the latest published research in psychiatry.  Each summary has been derived from the relevant article’s abstract and the clinical commentary has been provided by our expert.

ISSUE 7, October 2012 — Guest Commentator: W. Vaughn McCall, MD, MS, Georgia Health Sciences University


A Randomized Controlled Trial of Telephone-Delivered Cognitive-Behavioral Therapy for Late-Life Anxiety Disorders

Brenes GA, Miller ME, Williamson JD, et al
Am J Geriatr Psychiatry. 2012;20(8):707-716.

Objectives: Older adults face a number of barriers to receiving psychotherapy, such as a lack of transportation and access to providers. One way to overcome such barriers is to provide treatment by telephone. The purpose of this study was to examine the effects of cognitive behavioral therapy delivered by telephone (CBT-T) to older adults diagnosed with an anxiety disorder.

Methods: This randomized controlled trial included 60 participants age 60 and older with a diagnosis of generalized anxiety disorder, panic disorder, or anxiety disorder not otherwise specified. CBT-T versus information-only comparison was utilized in the homes of the participants. Co-primary outcomes included worry (Penn State Worry Questionnaire) and general anxiety (State Trait Anxiety Inventory). Secondary outcomes included clinician-rated anxiety (Hamilton Anxiety Rating Scale), anxiety sensitivity (Anxiety Sensitivity Index), depressive symptoms (Beck Depression Inventory), quality of life (SF-36), and sleep (Insomnia Severity Index). Assessments were completed prior to randomization, immediately upon completion of treatment, and 6 months after completing treatment.

Results: CBT-T was superior to information-only in reducing general anxiety (ES = 0.71), worry (ES = 0.61), anxiety sensitivity (ES = 0.85), and insomnia (ES = 0.82) at the posttreatment assessment; however, only the reductions in worry were maintained by the 6-month follow-up assessment (ES = 0.80).

Conclusions: These results suggest that CBT-T may be efficacious in reducing anxiety and worry in older adults, but additional sessions may be needed to maintain these effects.

Clinical Commentary
Anxiety is a potentially disabling problem in older adults which, left unaddressed, could lead to premature loss of independence. Delivery of adequate treatment for geriatric anxiety disorders is beset by several challenges including (1) a lack of adequate numbers of mental health providers with geriatric expertise; (2) barriers for older people in attending appointments in doctor’s offices, and (3) dangers in prescribed anxiolytics, including risk for falls and amnestic disturbance. These challenges may be offset by bringing the treatment to the older person’s home. This could be accomplished by self-help books, the Internet, house calls, or in the case of this report, telephone-assisted psychotherapy. The positive findings of this report may surprise those who assume that older persons do not do well without a face-to-face treatment component. Further development of telephone-assisted psychotherapy will require definition of means of provider reimbursement, which for Medicare recipients usually requires face-to-face interaction. Replication of this study will challenge the status quo regarding how mental health care is delivered to older people.


Electroconvulsive Therapy in China: Clinical Practice and Research on Efficacy

Tang YL, Jiang W, Ren YP, et al
J ECT. 2012 Jul 13.

Objective: Electroconvulsive therapy (ECT) was first introduced in China in the early 1950s and has evolved into a significant psychiatric treatment. Research from Chinese psychiatrists provides important clinical data for ECT practitioners. However, most of the research has only been published in Chinese language journals. This article summarizes data from publications in the Chinese scientific community related to the clinical practice of ECT and research on efficacy in the treatment of psychiatric disorders.

Methods: Descriptive study primarily based on Chinese language literature identified from searches of the China National Knowledge Infrastructure and the Medline databases (1979-2012).

Results: More than 900 journal papers on ECT have been published in the Chinese language between 1979 and 2012. Currently, modified ECT has replaced unmodified ECT, and treatments were performed both in inpatient and outpatient settings. Electroconvulsive therapy is primarily used for the treatment of schizophrenia and mood disorders and has been shown to be very effective in both. The primary use of ECT in China is in the treatment of schizophrenia. The Chinese literature provides a rich database on the efficacy of modified and unmodified ECT, with and without adjunctive antipsychotics, in the treatment of schizophrenia.

Conclusion: The Chinese medical literature provides an important database that will help advance the practice of ECT in both China and the international community.

Clinical Commentary
Electroconvulsive therapy (ECT) is used principally in the treatment of severe mood disorders in the USA, Western Europe, Australia, and the remainder of the developed world. Therefore, the research conducted by Tang et al may surprise Western readers. It claims that in China, the main indication of ECT is for schizophrenia and other primary psychotic disorders. This report is entirely consistent with the use of ECT in India, parts of Africa, and other developing worlds. The reasons for these differences are complicated, but at the very least this report challenges the notion that ECT has limited application in psychotic disorders. Practitioners of ECT in the developed world should take note that ECT may help some otherwise intractable cases of schizophrenia, or may accelerate symptom relief in conjunction with standard antipsychotic treatment of schizophrenia.


Naltrexone Implant for the Treatment of Poly-Drug Dependence: a Randomized Controlled Trial

Tiihonen J, Krupitsky E, Verbitskaya E, et al
Am J Psychiatry. 2012;169(5):531-536.

Objective: The majority of drug addicts are polydrug dependent, and no effective pharmacological treatment is currently available for them. The authors studied the overall real-world effectiveness of the naltrexone implant in this patient population.

Methods: The authors assessed the effectiveness of a naltrexone implant in the treatment of coexisting heroin and amphetamine polydrug dependence in 100 heroin- and amphetamine-dependent outpatients in a 10-week randomized, double-blind, placebo-controlled trial. The main outcome measures were retention in the study, proportion of drug-free urine samples, and improvement score on the Clinical Global Impressions Scale (CGI). Analyses were conducted in an intent-to-treat model.

Results: At week 10, the retention rate was 52% for patients who received a naltrexone implant and 28% for those who received a placebo implant; the proportions of drug-free urine samples were 38% and 16%, respectively, for the two groups. On the CGI improvement item, 56% of the patients in the naltrexone group showed much or very much improvement, compared with 14% of those in the placebo group (number needed to treat=3).

Conclusions: Naltrexone implants resulted in higher retention in the study, decreased heroin and amphetamine use, and improved clinical condition for patients, thus providing the first evidence of an effective pharmacological treatment for this type of polydrug dependence.

Clinical Commentary
Substance abuse treatment requires a multi-modal approach that necessarily includes a psychosocial component. However, a period of abstinence is often required before psychosocial approaches can provide protection against relapse. Detoxification and abstinence may rely upon substitution approaches (benzodiazepines for alcohol; methadone for heroin) or relief of craving and/or blunting of the euphoria from the substance. All of the oral medications used in detoxification are liable to failure if the substance abuser fails to take the medication; thus, the study by Tiihonen et al. represents an encouraging, novel approach to non-adherence. While the rates of drug-free urine samples at week 10 were significantly twice as high in the those receiving the naltrexone implant as compared with the placebo implant, the overall low rate of drug-free urine tests underscores both the difficulty in treating this population and the need to combine medication therapy with a variety of psychosocial approaches.


Residual Sleep Disturbances in Patients Remitted From Major Depressive Disorder: A 4-Year Naturalistic Follow-up Study

Li SX, Lam SP, Chan JW, et al
Sleep. 2012;35(8):1153-1161.

Objective: To investigate the prevalence and clinical, psychosocial, and functional correlates of residual sleep disturbances in remitted depressed outpatients.

Methods: A 4-yr prospective observational study in a cohort of psychiatric outpatients with major depressive disorder was conducted with a standardized diagnostic psychiatric interview and a packet of questionnaires, including a sleep questionnaire, Hospital Anxiety and Depression Scale, NEO personality inventory, and Short Form-12 Health Survey.

Results: Four hundred twenty-one depressed outpatients were recruited at baseline, and 371 patients (mean age 44.6 ± 10.4 yr, female 81.8%; response rate 88.1%) completed the reassessments, in which 41% were classified as remitted cases. One-year prevalence of frequent insomnia at baseline and follow-up in remitted patients was 38.0% and 19.3%, respectively. One-year prevalence of frequent nightmares at baseline and follow-up was 24.0% and 9.3%, respectively. Remitted patients with residual insomnia were more likely to be divorced (P < 0.05) and scored higher on the anxiety subscale (P < 0.05). Remitted patients with residual nightmares were younger (P < 0.05) and scored higher on neuroticism (P < 0.05) and anxiety subscales (P < 0.01). Residual insomnia and nightmares were associated with various aspects of impaired quality of life. Residual nightmares was associated with suicidal ideation (odds ratio = 8.40; 95% confidence interval 1.79-39.33).

Conclusions: Residual sleep disturbances, including insomnia and nightmares, were commonly reported in remitted depressed patients with impaired quality of life and suicidal ideation. A constellation of psychosocial and personality factors, baseline sleep disturbances, and comorbid anxiety symptoms may account for the residual sleep disturbances. Routine assessment and management of sleep symptoms are indicated in the integrated management of depression.

Clinical Commentary
The psychiatric literature has a growing body of evidence that many depressed persons continue to experience residual symptoms despite meeting criteria for remission. Continuing symptoms of insomnia may be the most common residual symptom in otherwise successfully treated cases of depression, and this symptom puts these patients at risk for relapse. The paper by Li et al now adds the additional concern that residual symptoms of insomnia/nightmares identify otherwise-remitted patients who will have a risk for ongoing suicidal ideation. This finding was true principally in female patients. This paper provides the clinician with one more reason to aggressively pursue symptoms of insomnia in depressed patients.


Role of Referrals in Mental Health Service Disparities for Racial and Ethnic Minority Youth

Alegría M, Lin JY, Green JG, et al
J Am Acad Child Adolesc Psychiatry. 2012;51(7):703-711.e2.

Objective: To investigate racial/ethnic differences in teachers and other adults' identification and/or encouragement of parents to seek treatment for psychiatric problems in their children and to evaluate if and whether identification/encouragement is associated with service use.

Method: Data on identification/encouragement to seek treatment for externalizing disorders (i.e., attention-deficit/hyperactivity disorder, oppositional-defiant disorder, and/or conduct disorder) and internalizing disorders (i.e., major depressive episode/dysthymia and/or separation anxiety disorder) and services used were obtained for 6,112 adolescents (13-17 years of age) in the National Comorbidity Survey Adolescent Supplement. Racial/ethnic differences were examined for Latinos, non-Latino blacks, and non-Latino whites.

Results: There were few racial/ethnic differences in rates of youth identification/encouragement and how identification/encouragement related to service use. Only non-Latino black youth with low severity internalizing disorders were less likely to be identified/encouraged to seek services compared with non-Latino white youth with the same characteristics (odds ratio [OR] = 0.4, 95% confidence interval [CI] = [0.2-0.7]). Identification/encouragement increased the likelihood of seeking services for externalizing and internalizing disorders for all youth. However, compared with their non-Latino white counterparts, non-Latino black youth who met criteria for internalizing disorders appeared less likely to have used any services (OR = 0.4, 95%, CI = 0.2-0.7), after adjusting for identification/encouragement, clinical, and sociodemographic characteristics. Non-Latino black youth with internalizing disorders and without identification/encouragement were less likely to use the specialty care sector than their non-Latino white counterparts.

Conclusions: In this study of a nationally representative sample of adolescents, almost no ethnic/racial differences in identification/encouragement were found. However, identification/encouragement may increase service use for all youth.

Clinical Commentary
The history of mental health treatment in the USA is replete with stories of misdiagnoses, inequities in access to care, and variability in treatment as a function of racial and ethnic differences. For this reason, the report of Alegría et al is somewhat of a pleasant surprise in that, for the most part, ethnicity and race were not related to differences in identification and encouragement for treatment in youth. Does this mean that teachers, counselors, and mental health providers are doing a better job at providing unbiased assessment of youth? Perhaps. But as the paper notes, there are areas still needing improvement, especially in obtaining treatment for depressive and anxiety disorders in black youths.


Prediction of Incident Dementia: Impact of Impairment in Instrumental Activities of Daily Living and Mild Cognitive Impairment-Results From the German Study on Ageing, Cognition, and Dementia in Primary Care Patients

Luck T, Luppa M, Wiese B, et al
Am J Geriatr Psychiatry. 2012 Jun 14. [epub ahead of print]

Objectives: There is an increasing call for a stronger consideration of impairment in instrumental activities of daily living (IADL) in the diagnostic criteria of Mild Cognitive Impairment (MCI) to improve the prediction of dementia. Thus, the aim of the study was to determine the predictive capability of MCI and IADL impairment for incident dementia.

Methods: This longitudinal cohort study consisted of four assessments at 1.5-year intervals over a period of 4.5 years. A primary care medical record registry sample was utilized. As part of the German Study on Ageing, Cognition, and Dementia in Primary Care Patients, a sample of 3,327 patients from general practitioners, aged 75 years and older, was assessed. The predictive capability of MCI and IADL impairment for incident dementia was analyzed using receiver operating characteristics, Kaplan-Meier survival analyses, and Cox proportional hazards models were used.

Results: MCI and IADL impairment were found to be significantly associated with higher conversion to, shorter time to, and better predictive power for future dementia. Regarding IADL, a significant impact was particularly found for impairment in responsibility for one's own medication, shopping, and housekeeping, and in the ability to use public transport.

Conclusions: Combining MCI with IADL impairment significantly improves the prediction of future dementia. Even though information on a set of risk factors is required to achieve a predictive accuracy for dementia in subjects with MCI being clinically useful, IADL impairment should be a very important element of such a risk factor set.

Clinical Commentary
Mild cognitive impairment (MCI) is recognized as a prodrome for dementia, but its utility as a risk factor is limited by the finding that only a minority of older persons with MCI will progress to dementia. Luck et al now reports that the presence of limitations in instrumental activities of daily living (IADL) improves the predictive power of MCI in dementia risk assessment. Of course, mental health providers should routinely ask older persons about IADL function if for no other reason than to identify the proper level of care (outpatient versus inpatient, etc). Li et al further highlights the utility of IADL assessment in every older patient.


The Nature of Dopamine Dysfunction in Schizophrenia and What This Means for Treatment: Meta-analysis of Imaging Studies

Howes OD, Kambeitz J, Kim E, et al
Arch Gen Psychiatry. 2012 Apr 2. [epub ahead of print]

Objective: Current drug treatments for schizophrenia are inadequate for many patients, and despite five decades of drug discovery, all of the treatments rely on the same mechanism: dopamine D(2) receptor blockade. Understanding the pathophysiology of the disorder is thus likely to be critical to the rational development of new treatments for schizophrenia. This study sought to investigate the nature of the dopaminergic dysfunction in schizophrenia using meta-analysis of in vivo studies.

Methods: The MEDLINE, EMBASE, and PsycINFO databases were searched for studies from January 1, 1960, to July 1, 2011. A total of 44 studies were identified that compared 618 patients with schizophrenia with 606 controls, using positron emission tomography or single-photon emission computed tomography to measure in vivo striatal dopaminergic function. Demographic, clinical, and imaging variables were extracted from each study, and effect sizes were determined for the measures of dopaminergic function. Studies were grouped into those of presynaptic function and those of dopamine transporter and receptor availability. Sensitivity analyses were conducted to explore the consistency of effects and the effect of clinical and imaging variables.

Results: There was a highly significant elevation (P < .001) in presynaptic dopaminergic function in schizophrenia with a large effect size (Cohen d = 0.79). There was no evidence of alterations in dopamine transporter availability. There was a small elevation in D(2/3) receptor availability (Cohen d = 0.26), but this was not evident in drug-naive patients and was influenced by the imaging approach used.

Conclusions: The locus of the largest dopaminergic abnormality in schizophrenia is presynaptic, which affects dopamine synthesis capacity, baseline synaptic dopamine levels, and dopamine release. Current drug treatments, which primarily act at D(2/3) receptors, fail to target these abnormalities. Future drug development should focus on the control of presynaptic dopamine synthesis and release capacity.

Clinical Commentary
The CATIE study (along with other practical effectiveness studies such as STAR*D) have humbled psychiatrists. We now realize that our treatments for serious mental illness, while better than placebo, leave many patients with only minimal improvement. In the case of schizophrenia, the “road ahead” may be found by re-directing our attention to a new target for drug development. As noted by Howes et al, existing treatments of schizophrenia are focused on targets that are postsynaptic (downstream) from the dopamine neuron. This compelling meta-analysis makes the case that the real problem with dopamine function in persons with schizophrenia is presynaptic, not postsynaptic. For the clinician, this means that we should all anticipate new schizophrenia treatments that target pre-synaptic dopamine function.

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