Robert H Howland

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (212)604.23 Total impact

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    ABSTRACT: Transcranial Magnetic Stimulation (TMS) customarily uses high-field electromagnets to achieve therapeutic efficacy in Major Depressive Disorder (MDD). Low-field magnetic stimulation also may be useful for treatment of MDD, with fewer treatment-emergent adverse events. To examine efficacy, safety, and tolerability of low-field magnetic stimulation synchronized to an individual's alpha frequency (IAF) (synchronized TMS, or sTMS) for treatment of MDD. Six-week double-blind sham-controlled treatment trial of a novel device that used three rotating neodymium magnets to deliver sTMS treatment. IAF was determined from a single-channel EEG prior to first treatment. Subjects had baseline 17-item Hamilton Depression Rating Scale (HamD17) ≥ 17. 202 subjects comprised the intent-to-treat (ITT) sample, and 120 subjects completed treatment per-protocol (PP). There was no difference in efficacy between active and sham in the ITT sample. Subjects in the PP sample (N = 59), however, had significantly greater mean decrease in HamD17 than sham (N = 60) (-9.00 vs. -6.56, P = 0.033). PP subjects with a history of poor response or intolerance to medication showed greater improvement with sTMS than did treatment-naïve subjects (-8.58 vs. -4.25, P = 0.017). Efficacy in the PP sample reflects exclusion of subjects who received fewer than 80% of scheduled treatments or were inadvertently treated at the incorrect IAF; these subgroups failed to separate from sham. There was no difference in adverse events between sTMS and sham, and no serious adverse events attributable to sTMS. Results suggest that sTMS may be effective, safe, and well tolerated for treating MDD when administered as intended. Copyright © 2015 Elsevier Inc. All rights reserved.
    Brain Stimulation 05/2015; 8(4). DOI:10.1016/j.brs.2015.05.005 · 5.43 Impact Factor
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    Brain Stimulation 03/2015; 8(2):408. DOI:10.1016/j.brs.2015.01.301 · 5.43 Impact Factor
  • Brain Stimulation 03/2015; 8(2):404. DOI:10.1016/j.brs.2015.01.287 · 5.43 Impact Factor
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    ABSTRACT: Multiple open-label trials of deep brain stimulation (DBS) for treatment-resistant depression (TRD), including those targeting the ventral capsule/ventral striatum target, have shown encouraging response rates. However, no randomized controlled trials of DBS for TRD have been published. Thirty patients with TRD participated in a sham-controlled trial of DBS at the ventral capsule/ventral striatum target for TRD. Patients were randomized to active versus sham DBS treatment in a blinded fashion for 16 weeks, followed by an open-label continuation phase. The primary outcome measure was response, defined as a 50% or greater improvement on the Montgomery-Åsberg Depression Rating Scale from baseline. There was no significant difference in response rates between the active (3 of 15 subjects; 20%) and control (2 of 14 subjects; 14.3%) treatment arms and no significant difference between change in Montgomery-Åsberg Depression Rating Scale scores as a continuous measure upon completion of the 16-week controlled phase of the trial. The response rates at 12, 18, and 24 months during the open-label continuation phase were 20%, 26.7%, and 23.3%, respectively. The results of this first randomized controlled study of DBS for the treatment of TRD did not demonstrate a significant difference in response rates between the active and control groups at the end of the 16-week controlled phase. However, a range of 20% to 26.7% of patients did achieve response at any time during the open-label continuation phase. Future studies, perhaps utilizing alternative study designs and stimulation parameters, are needed. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
    Biological Psychiatry 12/2014; DOI:10.1016/j.biopsych.2014.11.023 · 10.25 Impact Factor
  • Robert H Howland
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    ABSTRACT: Most drugs used in psychiatry are classified according to their initial or main therapeutic indications rather than by their pharmacological profiles. A proposed multi-axial, pharmacologically driven nomenclature system that would reclassify existing psychotropic drugs and provide a framework for classifying new drug compounds is described. The five axes of this system would describe a drug's primary pharmacological target and relevant mechanism; relevant neurotransmitter and mechanism; neurobiological activities; efficacy and side effects; and approved indications. The proposed multi-axial system is a common sense but scientifically informed approach for classifying psychotropic drugs that would be practically useful for prescribers, clinicians, and patients. [Journal of Psychosocial Nursing and Mental Health Services, 52(12), 13-15.]. Copyright 2014, SLACK Incorporated.
    Journal of Psychosocial Nursing and Mental Health Services 12/2014; 52(12):13-5. DOI:10.3928/02793695-20141118-05 · 0.72 Impact Factor
  • Robert H Howland
    JAMA Psychiatry 10/2014; 71(10):1195. DOI:10.1001/jamapsychiatry.2014.483 · 12.01 Impact Factor
  • Robert H Howland
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    ABSTRACT: Suvorexant is a pharmacologically novel dual antagonist of orexin receptors OX1R and OX2R, which has an effect that promotes sleep by reducing arousal and wakefulness. Its approval for the treatment of insomnia was based on three clinical trials that found it to be efficacious and relatively well tolerated. Somnolence, headache, and dry mouth are the most common side effects. Because suvorexant has unique effects on arousal systems and rapid eye movement (REM) sleep, it is contraindicated in patients with narcolepsy, and its use should be avoided or closely monitored in patients at risk for REM sleep behavior disorder, depression, or delirium. [Journal of Psychosocial Nursing and Mental Health Services, 52(10), 23-26.].
    Journal of Psychosocial Nursing and Mental Health Services 10/2014; 52(10):23-26. DOI:10.3928/02793695-20140924-01 · 0.72 Impact Factor
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    ABSTRACT: Background: At least 10-20% of the patients suffering from depression meet criteria for treatment-resistant depression (TRD). In the last decades, an important role of glutamate in mood modulation has been hypothesized and ketamine, a non noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, has been demonstrated to be effective in both MDD and TRD. However, concerns emerged about the optimal dosage, and frequency of administration of this treatment. Methods: aiming to systematically review the current literature focusing on the main pharmacological properties and impact of ketamine in TRD, a detailed literature search in PubMed/Medline and ScienceDirect databases was conducted. Twenty-four manuscripts including a total of 416 patients fulfilled inclusion criteria. Results: Most studies demonstrated that the NMDA antagonist ketamine has rapid antidepressant effects in TRD patients, confirming the active role of glutamate in the pathophysiology of this complex condition. Ketamine has been demonstrated to be rapidly effective and was associated with a significant clinical improvement in depressive symptoms within hours after administration. Also, ketamine was also found to be effective in reducing suicidality in TRD samples. Limitations: The long-term efficacy of ketamine has not been investigated by most studies. The psychotomimetic properties may complicate the application of this pharmacological agent. Conclusions: Ketamine may be considered a valid and intriguing antidepressant option for the treatment of TRD. Further studies are needed to evaluate its long-term antidepressant efficacy in patients with TRD.
    Journal of Applied Statistics 09/2014; 12(5). DOI:10.2174/1570159X12666140619204251 · 0.45 Impact Factor
  • 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 07/2014; 55(6). DOI:10.1016/j.psym.2014.07.004 · 1.67 Impact Factor
  • Robert H Howland
    JAMA Pediatrics 07/2014; 168(7):683. DOI:10.1001/jamapediatrics.2014.175 · 4.25 Impact Factor
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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.
    06/2014; 1(2). DOI:10.1007/s40473-014-0010-5
  • 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 corrected QT (QTc) interval and an increased risk of developing torsade de pointes, a type of tachyarrhythmia associated with sudden death. A relatively recent literature review suggested that haloperidol (Haldol(®)) is more likely to cause QTc prolongation than quetiapine (Seroquel(®)). The current article critically evaluates this literature review by examining the original source studies cited by the authors to support their conclusion. The authors' interpretation and presentation of the findings from the studies they review results in a misleading characterization of the relative risks of haloperidol and quetiapine. Looking at individual study methodologies closely and critically evaluating the findings from each study should be done before drawing generalized conclusions about the actual and comparative risks of various drugs. [Journal of Psychosocial Nursing and Mental Health Services, 52(6), 23-26.].
    Journal of Psychosocial Nursing and Mental Health Services 06/2014; 52(6):23-26. DOI:10.3928/02793695-20140515-01 · 0.72 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. DOI:10.1177/2045125313510194 · 1.53 Impact Factor
  • Robert H Howland
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    ABSTRACT: Delirium is a complex neurobehavioral syndrome caused by dysregulation of brain activity, characterized by an alteration in the level of attention and awareness, which develops over a short period of time and is seen as a change from the patient's baseline. Dysregulation of 24-hour circadian cycles, including melatonin secretion or activity, has suggested the potential therapeutic use of melatonergic drugs for delirium. Melatonin and the melatonin analog drug ramelteon have been shown to be effective in the prevention of delirium in three controlled studies. Additional studies using these drugs are warranted. [Journal of Psychosocial Nursing and Mental Health Services, 52(5), 13-16.].
    Journal of Psychosocial Nursing and Mental Health Services 05/2014; 52(5):13-6. DOI:10.3928/02793695-20140423-02 · 0.72 Impact Factor
  • Robert H Howland
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    ABSTRACT: Deep brain stimulation (DBS) is a commonly used neurosurgical form of therapeutic brain stimulation that has been demonstrated to be safe, well tolerated, and effective for the treatment of essential tremor, Parkinson's disease, and primary dystonia. These particular uses have been approved by the U.S. Food and Drug Administration (FDA). Investigational studies using DBS have been conducted for refractory epilepsy, obesity, chronic pain, tardive dyskinesia, Tourette syndrome, and other movement disorders, but none of these studies has led to FDA approval for these indications. Although the use of DBS has been approved by the FDA under a Humanitarian Device Exemption for the treatment of treatment-resistant obsessive-compulsive disorder, studies systematically investigating the potential use of DBS for various severe chronic psychiatric disorders are in their earliest stages, and further studies are warranted. [Journal of Psychosocial Nursing and Mental Health Services, 52(4), 23-26.].
    Journal of Psychosocial Nursing and Mental Health Services 04/2014; 52(4):23-6. DOI:10.3928/02793695-20140324-01 · 0.72 Impact Factor
  • Robert H Howland
    [Show abstract] [Hide abstract]
    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. Vagus nerve stimulation (VNS) refers to any technique that stimulates the vagus nerve. Left cervical VNS is an approved therapy for refractory epilepsy and treatment-resistant depression. Right cervical VNS has proven effective for treating heart failure in preclinical studies and a Phase II clinical trial. The effectiveness of noninvasive transcutaneous VNS for epilepsy, depression, and other conditions has not been investigated beyond small pilot studies. The relationship between depression, inflammation, and cardiovascular, cerebrovascular, and metabolic syndromes might be mediated by the vagus nerve. Transcutaneous VNS deserves further study as an antidepressant therapy and for its potential effect on physiological biomarkers associated with depression morbidity and mortality.
    Journal of Psychosocial Nursing and Mental Health Services 03/2014; 52(3):11-4. DOI:10.3928/02793695-20140218-01 · 0.72 Impact Factor
  • Robert H Howland
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    ABSTRACT: Gabapentin, a gamma-aminobutyric acid analog drug, appears to be safe and efficacious for the treatment of alcohol dependence. Gabapentin is not a controlled drug, but there are anecdotal reports of its misuse and abuse as well as reports of withdrawal symptoms associated with abrupt discontinuation. The risk of gabapentin misuse is inconsistent, the magnitude of the risk is small, and the risk is not comparable to the much higher risks associated with alcohol use; benzodiazepine, opioid, and stimulant drug use; or illicit drug use. Reports of gabapentin misuse are not unique to this drug, as misuse of prescription medications not typically considered "drugs of abuse" can also occur.
    Journal of Psychosocial Nursing and Mental Health Services 01/2014; 52(1):12-5. DOI:10.3928/02793695-20131213-01 · 0.72 Impact Factor
  • Source
    Journal of clinical psychopharmacology 12/2013; 34(1). DOI:10.1097/JCP.0000000000000075 · 3.76 Impact Factor
  • Robert H Howland
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    ABSTRACT: The amino acid gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. Four placebo-controlled studies found the GABA analog drug gabapentin effective for treating alcohol dependence. Gabapentin may also be effective for treating alcohol withdrawal syndromes. One placebo-controlled pilot study found gabapentin beneficial for cannabis dependence, but several controlled studies found no benefit for cocaine or methamphetamine dependence. Whether gabapentin is effective for other substance use disorders is unknown.
    Journal of Psychosocial Nursing and Mental Health Services 12/2013; 51(12):11-4. DOI:10.3928/02793695-20131120-01 · 0.72 Impact Factor
  • Robert H Howland
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    ABSTRACT: The newly approved drug Diclegis(®), indicated for the treatment of nausea and vomiting associated with pregnancy, has a very interesting background story going back more than 50 years, in which science, celebrity individuals, the media, and the courts crossed paths. The story illustrates how concepts of truth, evidence, objectivity, and disinterested inquiry can become distorted in various ways, and this is especially relevant and prevalent in today's media environment of cable television, talk radio, and especially the Internet.
    Journal of Psychosocial Nursing and Mental Health Services 10/2013; 51(11):1-4. DOI:10.3928/02793695-20131010-02 · 0.72 Impact Factor

Publication Stats

5k Citations
604.23 Total Impact Points

Institutions

  • 1998–2015
    • University of Pittsburgh
      • • Department of Psychiatry
      • • Department of Medicine
      Pittsburgh, Pennsylvania, United States
  • 1990–2015
    • Western Psychiatric Institute and Clinic
      Pittsburgh, Pennsylvania, United States
  • 2013
    • Virginia Commonwealth University
      • Department of Psychiatry
      Richmond, VA, United States
  • 2010
    • Massachusetts General Hospital
      • Department of Psychiatry
      Boston, Massachusetts, United States
  • 2008
    • Northwestern University
      • Asher Center – Study & Treatment of Mood Disorders
      Evanston, Illinois, United States
  • 2007
    • University of Texas at Dallas
      Richardson, Texas, United States