Robert H Howland

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (192)540.38 Total impact

  • Robert H Howland
    JAMA Pediatrics 07/2014; 168(7):683. · 4.28 Impact Factor
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    ABSTRACT: Recently, both the manufacturer of quetiapine and the US Food and Drug Administration warned healthcare providers and patients about quetiapine-induced QTc interval prolongation and torsade de pointes (TdP) when using this drug within the approved labeling. We reviewed the case-report literature and found 12 case reports of QTc interval prolongation in the setting of quetiapine administration. There were no cases of quetiapine-induced TdP or sudden cardiac death (SCD) among patients using quetiapine appropriately and free of additional risk factors for QTc interval prolongation and TdP. Among the 12 case reports risk factors included female sex (nine cases), coadministration of a drug associated with QTc interval prolongation (eight cases), hypokalemia or hypomagnesemia (six cases) quetiapine overdose (five cases), cardiac problems (four cases), and coadministration of cytochrome P450 3A4 inhibitors (two cases). There were four cases of TdP. As drug-induced TdP is a rare event, prospective studies to evaluate the risk factors associated with QTc prolongation and TdP are difficult to design, would be very costly, and would require very large samples to capture TdP rather than its surrogate markers. Furthermore, conventional statistical methods may not apply to studies of TdP, which is rare and an 'outlier' manifestation of QTc prolongation. We urge drug manufacturers and regulatory agencies to periodically publish full case reports of psychotropic drug-induced QTc interval prolongation, TdP, and SCD so that clinicians and investigators may better understand the clinical implications of prescribing such drugs as quetiapine.
    Therapeutic advances in psychopharmacology. 06/2014; 4(3):130-8.
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    Robert H. Howland
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    ABSTRACT: The vagus nerve is a major component of the autonomic nervous system, has an important role in the regulation of metabolic homeostasis, and plays a key role in the neuro-endocrine-immune axis to maintain homeostasis through its afferent and efferent pathways. Vagus nerve stimulation (VNS) refers to any technique that stimulates the vagus nerve, including manual or electrical stimulation. Left cervical VNS is an approved therapy for refractory epilepsy and for treatment-resistant depression. Right cervical VNS is effective for treating heart failure in preclinical studies and a phase II clinical trial. The effectiveness of various forms of non-invasive transcutaneous VNS for epilepsy, depression, primary headaches, and other conditions has not been investigated beyond small pilot studies. The relationship between depression, inflammation, metabolic syndrome, and heart disease might be mediated by the vagus nerve. VNS deserves further study for its potentially favorable effects on cardiovascular, cerebrovascular, metabolic, and other physiologic biomarkers associated with depression morbidity and mortality.
    Current Behavioral Neuroscience Reports. 06/2014; 1(2).
  • Robert H. Howland
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    ABSTRACT: A potential adverse effect of many non-cardiac drugs, including certain psychotropic medications, is an abnormally prolonged QTc interval and an increased risk of developing torsades de pointes. A relatively recent literature review suggested that haloperidol is more likely to cause QTc prolongation than other antipsychotic drugs. This letter critically evaluates their conclusions regarding haloperidol by examining the original source studies cited by the authors and additional studies in the literature. The authors’ interpretation and presentation of the findings from the studies they review results in a misleading characterization of the relative risks of haloperidol. The studies they cite and additional studies in the literature, especially randomized head-to-head comparisons, do not support their conclusions. Haloperidol is not necessarily riskier than other antipsychotic drugs.
    Psychosomatics 01/2014; · 1.73 Impact Factor
  • Journal of clinical psychopharmacology 12/2013; · 5.09 Impact Factor
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    ABSTRACT: We reviewed the literature and found 31 adult cases and 1 newborn case of methadone-associated QTc interval prolongation and/or torsade de pointes (TdP). Parametric statistics may not be useful in studying this issue because methadone-associated TdP is a very rare event and, hence, "an extreme outlier" consistent with scalable randomness. We may have to rely upon narrative medicine in the form of case reports with all its limitations and hazards to provide our best understanding. We report risk factors for methadone-associated QTc interval prolongation and TdP based on review of published case reports. We believe both drug manufacturers and the FDA would better serve our patients and inform clinicians if they more readily reported drug-induced outliers such as methadone-associated TdP using a case report format.
    Therapeutic advances in psychopharmacology. 08/2013; 3(4):219-32.
  • Robert H Howland
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    ABSTRACT: Clostridium difficile (C.difficile) infection (CDI) is a common and clinically significant cause of diarrhea associated with the use of antibiotic drugs. Two observational studies have suggested that antidepressant drug use is associated with an increased risk of developing CDI. Because of the potential public health significance of this finding, this article critically evaluates the methodology of these studies and provides evidence to question the plausibility and validity of this finding. The safety of antidepressant and other psychotropic drugs should not be taken for granted, but studies that receive media attention may cause harm if their findings are not valid and they result in a reluctance to use these drugs for treating serious mental disorders.
    Journal of Psychosocial Nursing and Mental Health Services 07/2013; 51(7):11-4. · 0.83 Impact Factor
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    Mehrul Hasnain, Robert H Howland, W Victor R Vieweg
    Journal of psychiatry & neuroscience: JPN 07/2013; 38(4):E11. · 6.24 Impact Factor
  • Robert H Howland
    Journal of Neurosurgery 06/2013; · 3.15 Impact Factor
  • Robert H Howland
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    ABSTRACT: The hypothalamic-pituitary-adrenal (HPA) axis is the body's main stress-response system, and cortisol is the major adrenal glucocorticoid hormone secreted in human beings. HPA axis activity and cortisol secretion is regulated by a negative feedback system involving glucocorticoid receptors. Dysregulation of the HPA axis and increased cortisol levels have been implicated in mood, psychotic, and other psychiatric disorders. Mifepristone, as a potent antagonist of glucocorticoid receptors, has been studied or is currently being investigated as a potential therapeutic agent for psychotic depression, posttraumatic stress disorder, and alcohol and cocaine dependence, as well as for mitigating the weight gain associated with the use of antipsychotic drugs and for improving cognitive dysfunction in schizophrenia and bipolar disorder. This article will review some of the work in these areas.
    Journal of Psychosocial Nursing and Mental Health Services 06/2013; 51(6):11-4. · 0.83 Impact Factor
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    Article: The Reply.
    W Victor R Vieweg, Mehrul Hasnain, Robert H Howland
    The American journal of medicine 06/2013; 126(6):e23. · 5.30 Impact Factor
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    ABSTRACT: BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability, morbidity, and mortality worldwide. The lifetime prevalence in the United States is estimated at 17%. Treatment-resistant depression (TRD) is generally defined as failure to achieve remissions despite adequate treatment. About 30% of patients do not achieve remission after 4 different antidepressant treatment trials. A few studies have examined the economic burden of TRD, but none has investigated the cost associated with more chronic and extensive forms of TRD characterized by nonresponse to ≥4 treatment trials. OBJECTIVE: The objective of this study was to compare the health care utilization (HCU) and direct medical expenditures of TRD patients with those of chronic MDD patients. METHODS: Patients with chronic MDD (defined as ≥2 years of continuous treatment) and patients with TRD (defined as undergoing at least 4 different qualifying antidepressant therapy trials) were identified in the PharMetrics Patient-centric Database. The association between TRD and medical expenditures was measured by using multivariate regression analysis. RESULTS: The classification of TRD had a clinically meaningful and statistically significant association with increased medical expenditures. Holding all else equal, the classification of TRD was associated with a 29.3% higher costs (P < 0.001) in medical expenditures compared with patients not meeting the study definition of TRD. CONCLUSIONS: These results demonstrate that TRD is associated with significantly higher per-patient medical costs due to higher HCU. The findings suggest that the development of treatment alternatives for TRD is warranted. Limitations related to the use of secondary administrative data are noted.
    Clinical Therapeutics 03/2013; · 2.23 Impact Factor
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    ABSTRACT: Clinical trials in major depressive disorder (MDD) commonly assess remission at a single endpoint. Complementary, clinically relevant metrics include the likelihood and speed of achieving sustained remission. A neurophysiologic measure, the Antidepressant Treatment Response (ATR) index, previously predicted 8-week outcomes of pharmacotherapy. We retrospectively examined data from the Biomarkers for Rapid Identification of Treatment Effectiveness in Major Depression (BRITE-MD) trial to evaluate this biomarker's properties in predicting sustained remission and time to achieve sustained remission. In the BRITE-MD trial, 67 adults with DSM-IV MDD received escitalopram continuously for 13 weeks. The 17-item Hamilton Depression Rating Scale (HDRS17) was used to define sustained remission as achieving remission (HDRS17 score ≤ 7) at a series of consecutive assessments, including week 13. The onset of sustained remission was defined as the earliest time from which all subsequent HDRS17 assessments were ≤ 7. The ATR was evaluated by using frontal quantitative electroencephalogram recordings at baseline and week 1. Subjects were stratified based on ATR status (ie, ATR+/ATR-). Kaplan-Meier survival analysis evaluated group differences in time to sustained remission. Higher ATR was hypothesized to predict sustained remission and time to sustained remission. Subjects participated between January 2006 and July 2007. Of 67 subjects, 36 achieved remission by week 13, and ATR predicted this single endpoint in receiver operating characteristic analyses (P = .016; sensitivity, 52.8%; positive predictive value, 76.0%). Remitters had a higher mean (SD) ATR value than those who did not remit (57.9 [10.0] vs 51.9 [8.7], P = .012). Sixteen of the 31 individuals with sustained remission had ATR+ status, while 28 of the 36 who were not sustained remitters had ATR- status (P = .012). The mean time to reach sustained remission was significantly shorter among ATR+ subjects than ATR- individuals (38 vs 53 days, P = .038). The ATR index predicted remission at 13 weeks as well as the speed of achieving sustained remission with antidepressant monotherapy. This finding suggests that the ATR biomarker may predict stable longer-term outcomes. identifier: NCT00289523.
    The Journal of Clinical Psychiatry 01/2013; 74(1):51-6. · 5.81 Impact Factor
  • Robert H Howland
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    ABSTRACT: Ketamine (Ketalar®) is an anesthetic agent derived from the hallucinogenic drug phencyclidine (PCP). It is a high-affinity antagonist at N-methyl-0-aspartate receptors and also binds to opioid mu and sigma receptors.Ketamine is being intensively investigated as an antidepressant therapy.To date, five short-term controlled studies and other open-label studies in patients with unipolar or bipolar depression have demonstrated that intravenous ketamine is safe and has a rapid and profound short-term effect on depressive symptoms, including suicidal thoughts, even among patients considered treatment-resistant to standard medications or electroconvulsive therapy. Before ketamine can be incorporated into clinical practice, however, its longterm safety and effectiveness need to be evaluated. Although the effectiveness of alternative routes of ketamine administration (i.e., oral, intranasal,or intramuscular) needs to be determined,intravenous ketamine could be conceptualized as a clinic-based procedural therapy for treatment resistant forms of depression.
    Journal of Psychosocial Nursing and Mental Health Services 01/2013; 51(1):11-4. · 0.83 Impact Factor
  • Robert H Howland
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    ABSTRACT: Understanding pharmacogenetic differences in drug response and tolerability has been an important area of research in personalized medicine, but the clinical utility of pharmacogenetics testing has not been established. Identification of genetic polymorphisms due to single nucleotide polymorphisms is the most common approach, but this does not take into account the potential relevance of copy number variants, noncoding RNA gene regulation, gene-gene and gene-interactions, and epigenetic modifications, which increase the complexity of pharmacogenomics research.
    Journal of Psychosocial Nursing and Mental Health Services 12/2012; 50(12):13-6. · 0.83 Impact Factor
  • Robert H Howland
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    ABSTRACT: Prescribing medications for off-label uses is not illegal. Off-label prescribing includes using medications for unapproved indications; using a drug outside of the recommended dosage range or duration of use; using a drug in certain unapproved patient populations, such as those defined by age, sex, or particular clinical parameters; or intentionally using a medication in a patient who has a known contraindication. Medications would be considered appropriate for off-label use based on their known clinical pharmacology, evidence from clinical studies, and sometimes from the personal experience of the prescriber. The decision to use a drug off label should be based on a careful assessment of the patient's treatment history and the drug's potential risks and benefits. Patients should be given adequate informed consent about how the drug is being used off label and why, along with appropriate information about known risks and side effects.
    Journal of Psychosocial Nursing and Mental Health Services 08/2012; 50(9):11-3. · 0.83 Impact Factor
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    ABSTRACT: Recently, both the manufacturer of citalopram and the US Food and Drug Administration have warned health care providers and patients about new information implicating drug-induced QTc interval prolongation and torsade de pointes when using citalopram in doses >40 mg/day. This warning is not placed in the context of either benefits or risks in real-world clinical practice, leaving clinicians with an untenable choice between depriving patients of high-dose citalopram or malpractice litigation. We reviewed the literature and found no cases of citalopram-induced sudden cardiac death among patients taking up to 60 mg/day of citalopram and free of risk factors for QTc interval prolongation and torsade de pointes. Because psychotropic drug-induced sudden cardiac death is an outlier in the absence of identified risk factors for QTc interval prolongation and torsade de pointes, we do not believe current Phase 3 and Phase 4 studies provide sufficient information to limit current prescribing practices for citalopram (20 mg to 60 mg/day). We urge drug manufacturers and regulatory agencies to periodically publish full case reports of psychotropic drug-induced QTc interval prolongation, torsade de pointes, and sudden cardiac death so that clinicians and investigators may better understand the clinical implications of prescribing such drugs as citalopram.
    The American journal of medicine 06/2012; 125(9):859-68. · 5.30 Impact Factor
  • Robert H Howland
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    ABSTRACT: Given the availability of a large and diverse number of medications for the treatment of various mental disorders, how should a clinician decide which medication(s) to try for any particular patient? This article explores eight questions that should be considered when selecting medication for a patient. Medication selection should be individually tailored by the answers to these questions, which take into account factors such as the diagnosis and associated symptoms, the expected efficacy/tolerability profile, medical and psychiatric comorbidity, concurrent drug use, past treatment history, family history, patient/family preferences, and cost considerations.
    Journal of Psychosocial Nursing and Mental Health Services 06/2012; 50(7):13-5. · 0.83 Impact Factor
  • Robert H Howland
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    ABSTRACT: Many dietary supplements are readily accessible and commonly used for the treatment of depression. A dietary supplement is a product intended to supplement the diet but is not intended to treat, diagnose, prevent, or cure disease. The U.S. Food and Drug Administration can take action against dietary supplement manufacturers for products only after they are marketed, mainly if the product is found to be unsafe or if false or misleading claims are made about the product. Few dietary supplement products have been adequately studied for their safety and efficacy. Of the five products reviewed in this article (L-methylfolate, S-adenosyl-L-methionine [SAM-e], omega-3 fatty acids, L-tryptophan, and inositol), only omega-3 fatty acids and SAM-e have sufficient supporting evidence for their efficacy to warrant safe use.
    Journal of Psychosocial Nursing and Mental Health Services 05/2012; 50(6):13-6. · 0.83 Impact Factor
  • Robert H Howland
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    ABSTRACT: Collaboration among health care providers in the treatment of mental health patients with comorbid medical and neurological conditions can be very challenging, especially with pharmacotherapy management where medications are prescribed by multiple providers. An individual example of a patient with a number of comorbid conditions taking multiple concurrent medical and psychotropic medications is described to highlight how challenging such situations can be. Medical conditions or medical medications might trigger or exacerbate symptoms of mental disorders. Psychotropic drugs may cause adverse effects that come to the attention of medical providers. Accurate communication among providers-and between the patient and providers-is important to avoid misinformation or misunderstandings in the care of patients with complicated problems.
    Journal of Psychosocial Nursing and Mental Health Services 04/2012; 50(5):17-20. · 0.83 Impact Factor

Publication Stats

3k Citations
540.38 Total Impact Points


  • 1990–2014
    • University of Pittsburgh
      • • Department of Psychiatry
      • • School of Medicine
      Pittsburgh, Pennsylvania, United States
    • Western Psychiatric Institute and Clinic
      Pittsburgh, Pennsylvania, United States
  • 2013
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 2012–2013
    • Virginia Commonwealth University
      • Department of Psychiatry
      Richmond, VA, United States
  • 2009–2012
    • Overton Brooks VA Medical Center
      Shreveport, Louisiana, United States
  • 2008
    • Cornell University
      • Department of Psychiatry
      Ithaca, NY, United States
  • 2007–2008
    • University of Texas Southwestern Medical Center
      • Department of Psychiatry
      Dallas, TX, United States
  • 2003
    • Free University of Brussels
      Bruxelles, Brussels Capital Region, Belgium
  • 2001
    • Stanford University
      • Department of Psychiatry and Behavioral Sciences
      Palo Alto, California, United States
  • 1999
    • Stony Brook University
      • Department of Psychology
      Stony Brook, NY, United States
  • 1998
    • Singapore-MIT Alliance
      Cambridge, Massachusetts, United States