Antipsychotic Drugs in Schizophrenia: Relative Effects in Patients With and Without Treatment Resistance.
J Clin Psychiatry. 2016 Dec;77(12):e1656-e1660
Authors: Andrade C
How antipsychotic drugs compare in schizophrenia, and especially in medication-refractory schizophrenia, is a subject of considerable interest. Two network meta-analyses and 1 direct comparison meta-analysis recently compared antipsychotics in schizophrenia patients with and without documented treatment resistance. One network meta-analysis of antipsychotic drugs in non-refractory patients found clear efficacy advantages for clozapine, amisulpride, olanzapine, and risperidone. One network meta-analysis of antipsychotic drugs in refractory patients found a clear efficacy advantage for olanzapine; surprisingly, in this meta-analysis, clozapine was superior to first-generation but not second-generation antipsychotics. One direct comparison meta-analysis found clozapine generally superior to first- and second-generation antipsychotics, with advantages more clearly apparent in studies that were 3 months in duration or less. Drug discontinuation and adverse effect data from these meta-analyses are presented, and issues arising from the results are briefly discussed. At the risk of oversimplification, it appears that clozapine retains its preeminence in medication-refractory schizophrenia and that clozapine and olanzapine are both associated with superior efficacy outcomes in non-refractory patients. Interestingly, haloperidol, generally considered a reference neuroleptic and a reference comparator drug, fared poorly in most comparisons.
PMID: 28086018 [PubMed - in process]
J Clin Psychiatry. 2016 Dec;77(12):e1655
PMID: 28086017 [PubMed - in process]
Dr Lurie and Colleagues Reply.
J Clin Psychiatry. 2016 Dec;77(12):e1654
Authors: Lurie I, Yang YX, Haynes K, Mamtani R, Boursi B
PMID: 28086016 [PubMed - in process]
Antibiotics or Infection Itself? The Possible Importance of Inflammatory Cytokines on Mental States.
J Clin Psychiatry. 2016 Dec;77(12):e1653
Authors: Ishii W, Komine-Aizawa S, Hayakawa S
PMID: 28086015 [PubMed - in process]
Considering the Complexity of Treatment Response in Psychiatric Clinical Trials.
J Clin Psychiatry. 2016 Dec;77(12):e1652
Authors: Diniz JB, Shavitt RG, Miguel EC, Costa DL
PMID: 28086014 [PubMed - in process]
Clinical Correlates of Oral Glucose Tolerance Test Performance in Olanzapine-Treated Patients with Schizophrenia or Schizoaffective Disorder.
J Clin Psychiatry. 2016 Dec;77(12):e1650-e1651
Authors: Guina J, Gupta A, Langleben DD, Elman I
PMID: 28086013 [PubMed - in process]
The Need to Assess Suicidal Risk in the Checklist for Prescribing Opioids.
J Clin Psychiatry. 2016 Dec;77(12):1719
Authors: Olié E, Courtet P
PMID: 28086012 [PubMed - in process]
Incident Psychosis in Subjects With Mild Cognitive Impairment or Alzheimer's Disease.
J Clin Psychiatry. 2016 Dec;77(12):e1564-e1569
Authors: Weamer EA, DeMichele-Sweet MA, Cloonan YK, Lopez OL, Sweet RA
OBJECTIVE: To estimate the incidence of psychotic symptoms in Alzheimer's disease.
METHODS: The study consists of 776 elderly subjects presenting to the Alzheimer Disease Research Center at the University of Pittsburgh (Pittsburgh, Pennsylvania) between May 9, 2000, and August 19, 2014. All participants were diagnosed with mild cognitive impairment (National Institute on Aging-Alzheimer's Association workgroup criteria) or possible or probable Alzheimer's disease (National Institute of Neurologic and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria) and were without psychosis at entry. Psychotic symptoms were evaluated using the Consortium to Establish a Registry for Alzheimer's Disease Behavioral Rating Scale every 6 months. One-, 3- and 5-year cumulative incidences of psychosis were calculated.
RESULTS: The 1-year psychosis incidence was 10% (95% CI, 8%-12%), and this annual rate remained remarkably consistent at 3 and 5 years. Psychosis incidence was related to cognitive status at all time points. However, the incidence rate reached a plateau during the disease course. Cumulative psychosis incidence at 5 years was 61% (95% CI, 52%-69%) in individuals with moderate to severe Alzheimer's disease, not statistically significantly different from the cumulative incidence at 3 years in this group, which was 48% (95% CI, 40%-55%) or from the 5-year incidence in individuals who entered the study with mild Alzheimer's disease, which was 48% (95% CI, 41%-56%).
CONCLUSIONS: Psychosis in Alzheimer's disease has been associated with a number of adverse clinical outcomes. We provide estimates of the risk of psychosis onset within clinically defined subgroups of individuals, a tool clinicians can use in treatment planning. Anticipating which subjects are at high risk for psychosis and the poor outcomes associated with it can help with family education and support decisions to implement nonpharmacologic strategies that may reduce or prevent symptoms.
PMID: 28086011 [PubMed - in process]
Threshold of Dopamine D2/3 Receptor Occupancy for Hyperprolactinemia in Older Patients With Schizophrenia.
J Clin Psychiatry. 2016 Dec;77(12):e1557-e1563
Authors: Iwata Y, Nakajima S, Caravaggio F, Suzuki T, Uchida H, Plitman E, Chung JK, Mar W, Gerretsen P, Pollock BG, Mulsant BH, Rajji TK, Mamo DC, Graff-Guerrero A
OBJECTIVE: Although hyperprolactinemia carries a long-term risk of morbidity, the threshold of dopamine D2/3 receptor (D2/3R) occupancy for hyperprolactinemia has not been investigated in older patients with schizophrenia. Data were taken from a positron emission tomography (PET) study conducted between August 2007 and August 2015. The present post hoc study included 42 clinically stable outpatients with schizophrenia (DSM-IV) (mean ± SD age = 60.2 ± 6.7 years) taking olanzapine or risperidone. Subjects underwent [¹¹C]-raclopride PET scans to measure D2/3R occupancy before and after reducing their dose of antipsychotic by up to 40%. Blood samples were collected before each PET scan to measure prolactin levels.
METHODS: The relationship between prolactin levels and D2/3R occupancy was examined using stepwise linear regression analyses. The D2/3R occupancy thresholds for hyperprolactinemia were explored using Fisher exact tests.
RESULTS: Prolactin levels decreased following dose reduction (mean ± SD = 24.1 ± 30.2 ng/mL to 17.2 ± 15.1 ng/mL; P < .001). Prolactin levels were associated with female gender (β = .32, P = .006, vs male), antipsychotics (β = .23, P = .02, risperidone vs olanzapine), and D2/3R occupancy (β = .23, P = .04). Those with D2/3R occupancy of 66% or higher were more likely to have hyperprolactinemia than those with D2/3R occupancy lower than 66% (P = .03). Sensitivity, specificity, positive predictive value, and negative predictive value of this threshold were 0.44, 0.81, 0.78, and 0.48, respectively. We identified a D2/3R occupancy threshold for hyperprolactinemia of 66% in older patients with schizophrenia, which is lower than that reported in younger patients (73%) by other researchers.
CONCLUSIONS: Our results suggest a higher sensitivity to antipsychotics in older patients. Prolactin levels could assist in the determination of appropriate antipsychotic dosing to minimize adverse effects.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00716755.
PMID: 28086010 [PubMed - in process]
Adherence to Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Prescriptions Affects Overall Medication Adherence in Older Persons: Evidence From the Italian Nationwide OsMed Health-DB Database.
J Clin Psychiatry. 2016 Dec;77(12):1712-1718
Authors: Marengoni A, Onder G, Esposti LD, Russo P, Sangiorgi D, Buda S, Fini M, Marchionni N, Bonassi S, Mammarella F, Marrocco W, Pozzi G, Palmer K, Monaco A, Pecorelli S, Pani L, Geriatrics Steering Committee of the Italian Medicines Agency on behalf of the OsMed Health-DB Network
OBJECTIVE: This study aimed to evaluate prevalence of prescription of and adherence to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and whether adherence to these classes of drugs affects overall medication adherence in older persons.
METHODS: In a cross-sectional analysis of administrative data comprehensive of all prescribed drugs reimbursed by the Italian national health care system, new prescriptions of SSRIs and SNRIs to persons aged 65 years or older were analyzed (n = 380,400 in 2011; 395,806 in 2012; 409,741 in 2013, from a total sample of 3,762,299 persons aged 65 years or older) as well as prescriptions of antihypertensives, statins, other psychiatric drugs, antidiabetics, antiplatelets, anticoagulants, drugs for chronic obstructive pulmonary disease, and antiosteoporotics. Adherence was estimated by calculating the proportion of days covered by drugs dispensed during a period of 365 days. Adherence was defined as a proportion of days covered of more than 80%.
RESULTS: Prevalence of SSRI and SNRI prescriptions varied from 11.4% in 2011 to 12.1% in 2013. Adherence to SSRI and SNRI prescriptions ranged from 31.2% in persons aged ≥ 95 years in 2011 to 41.8% in persons aged 75-84 years in 2013. Persons adherent to SSRI and SNRI prescriptions were more likely to be adherent to the other medications, after adjustment for age, gender, and number of drugs prescribed. The highest association was found for adherence to psychiatric drugs (OR = 1.9; 95% CI, 1.8-2.0).
CONCLUSIONS: Adherence to SSRI and SNRI prescriptions is poor in older persons. However, people adherent to these classes of antidepressants are more likely to be adherent to the other medications they are prescribed. Studies are needed to evaluate the reasons for and the potential benefits of increasing adherence to antidepressants on overall adherence.
PMID: 28086009 [PubMed - in process]
J Clin Psychiatry. 2016 Dec;77(12):1702-1703
Authors: Lavretsky H
PMID: 28086008 [PubMed - in process]
A Radical Proposal to Address the Problem of the Lack of Generalizability of Placebo-Controlled Studies of Antidepressants.
J Clin Psychiatry. 2016 Dec;77(12):e1647-e1649
Authors: Zimmerman M
PMID: 28086007 [PubMed - in process]
Generalizability of Neuroimaging Studies in 5 Common Psychiatric Disorders Based on the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).
J Clin Psychiatry. 2016 Dec;77(12):e1618-e1625
Authors: Blanco C, Wall MM, Lindquist MA, Rodríguez-Fernández JM, Franco S, Wang S, Olfson M
OBJECTIVE: Although neuroimaging studies have an important role in psychiatric nosology and treatment development, little is known about the representativeness of participants in neuroimaging research. We estimated the effects of commonly used study eligibility criteria on the representativeness of neuroimaging research participants in relation to the general population with the psychiatric disorders of interest.
METHODS: Common eligibility criteria were applied from 112 published neuroimaging studies of DSM-IV nicotine dependence (13 studies), alcohol dependence (12 studies), drug use disorders (13 studies), major depressive disorder (MDD) (37 studies), and posttraumatic stress disorder (PTSD) (36 studies) to representative US samples with these conditions from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (n = 43,093). The analyses were repeated with NESARC respondents with the disorders and substantial psychosocial impairment.
RESULTS: Most NESARC respondents with nicotine dependence (64.1%), alcohol dependence (57.7%), drug use disorders (86.6%), and PTSD (66.9%), though not with MDD (18.2%), would have been excluded by eligibility criteria used in at least half of the relevant neuroimaging studies. Across the diagnostic groups, comorbid psychiatric and general medical conditions resulted in the largest percentages of exclusions. Corresponding analyses limited to respondents with substantial impairment excluded larger percentages with nicotine dependence (77.6%), alcohol dependence (75.8%), drug use disorders (93.5%), and PTSD (76.8%), though not MDD (18.3%).
CONCLUSIONS: Neuroimaging studies tend to recruit highly selected samples with the psychiatric disorders of interest that markedly underrepresent individuals with common comorbid conditions. Larger studies with less restrictive eligibility criteria may promote translation of advances in neuroimaging research to populations commonly encountered in clinical practice.
PMID: 28086006 [PubMed - in process]
Reducing Dropout in Treatment for Depression: Translating Dropout Predictors Into Individualized Treatment Recommendations.
J Clin Psychiatry. 2016 Dec;77(12):e1584-e1590
Authors: Zilcha-Mano S, Keefe JR, Chui H, Rubin A, Barrett MS, Barber JP
OBJECTIVE: Premature discontinuation of therapy is a widespread problem that hampers the delivery of mental health treatment. A high degree of variability has been found among rates of premature treatment discontinuation, suggesting that rates may differ depending on potential moderators. In the current study, our aim was to identify demographic and interpersonal variables that moderate the association between treatment assignment and dropout.
METHODS: Data from a randomized controlled trial conducted from November 2001 through June 2007 (N = 156) comparing supportive-expressive therapy, antidepressant medication, and placebo for the treatment of depression (based on DSM-IV criteria) were used. Twenty prerandomization variables were chosen based on previous literature. These variables were subjected to exploratory bootstrapped variable selection and included in the logistic regression models if they passed variable selection.
RESULTS: Three variables were found to moderate the association between treatment assignment and dropout: age, pretreatment therapeutic alliance expectations, and the presence of vindictive tendencies in interpersonal relationships. When patients were divided into those randomly assigned to their optimal treatment and those assigned to their least optimal treatment, dropout rates in the optimal treatment group (24.4%) were significantly lower than those in the least optimal treatment group (47.4%; P = .03).
CONCLUSIONS: Present findings suggest that a patient's age and pretreatment interpersonal characteristics predict the association between common depression treatments and dropout rate. If validated by further studies, these characteristics can assist in reducing dropout through targeted treatment assignment.
TRIAL REGISTRATION: Secondary analysis of data from ClinicalTrials.gov identifier: NCT00043550.
PMID: 28086005 [PubMed - in process]
Evidence to Support Montgomery-Asberg Depression Rating Scale Administration Every 24 Hours to Assess Rapid Onset of Treatment Response.
J Clin Psychiatry. 2016 Dec;77(12):1681-1686
Authors: Johnson KM, Devine JM, Ho KF, Howard KA, Saretsky TL, Jamieson CA
OBJECTIVE: This study investigated the suitability of the Montgomery-Asberg Depression Rating Scale (MADRS), with a 24-hour recall period (MADRS-24hr), to assess the rapid onset of the antidepressant effect of a treatment in patients with treatment-resistant depression (TRD). Psychometric properties of the MADRS-24hr were assessed together with qualitative assessment of content validity.
METHODS: Content validity was assessed using semistructured interviews conducted from November 2013 to December 2013 in patients (18-64 years old) with TRD who met DSM-IV diagnostic criteria and health care professionals (HCPs) experienced in treating major depressive disorder and familiar with using the MADRS. The psychometric properties of MADRS-24hr were evaluated using data from 2 randomized clinical studies involving patients with TRD.
RESULTS: A total of 23 patients (15 [65%] women) with TRD (mean age = 45 years) and 11 HCPs were interviewed. With the exception of reduced sleep, the majority of patients and HCPs reported that the items captured in the MADRS can fluctuate in a 24-hour period. The majority of participants also reported that a meaningful change in depression symptoms could be assessed in a 24-hour recall period, except for reduced sleep and appetite. Assessment of the psychometric properties of the MADRS-24hr showed that this instrument had high internal consistency reliability (Cronbach α of 0.84 and 0.91) and test-retest reliability (intraclass correlation coefficients of 0.96 and 0.91), had construct validity, and was responsive to change following an intervention.
CONCLUSIONS: Overall, results suggest that MADRS-24hr can be used to assess the rapid onset of antidepressant efficacy of a treatment in patients with TRD.
TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT01627782 and NCT01640080.
PMID: 28086004 [PubMed - in process]