Amer M. Burhan

Trends in Psychotropic Dispensing Among Older Adults with Dementia Living in Long-Term Care Facilities: 2004-2013.

OBJECTIVE Guidelines worldwide have cautioned against the use of antipsychotics as first-line agents to treat neuropsychiatric symptoms of dementia. We aimed to investigate the changes over time in the dispensing of antipsychotics and other psychotropics among older adults with dementia living in long-term care facilities. METHODS We used drug claims data from Ontario, Canada, to calculate quarterly rates of prescription dispensing of six psychotropic drug classes among all elderly (≥65 years of age) long-term care residents with dementia from January 1, 2004, to March 31, 2013. Psychotropic drugs were classified into the following categories: atypical and conventional antipsychotics, non-sedative and sedative antidepressants, anti-epileptics, and benzodiazepines. We used time-series analysis to assess trends over time. RESULTS The study sample increased by 21% over the 10-year study period, from 49,251 patients to 59,785 patients. The majority of patients (within the range of 75%-79%) were dispensed at least one psychotropic medication. At the beginning of the study period atypical antipsychotics (38%) were the most frequently dispensed psychotropic, followed by benzodiazepines (28%), non-sedative antidepressants (27%), sedative antidepressants (17%), anti-epileptics (7%), and conventional antipsychotics (3%). Dispensing of anti-epileptics (2% increase) and conventional antipsychotics (1% decrease) displayed modest changes over time, but we observed more pronounced changes in dispensing of benzodiazepines (11% decrease) and atypical antipsychotics (4% decrease). Concurrently, we observed a substantial growth in the dispensing of both sedative (15% increase) and non-sedative (9% increase) antidepressants. The proportion of patients dispensed two or more psychotropic drug classes increased from 42% in 2004 to 50% in 2013. CONCLUSIONS Utilization patterns of psychotropic drugs in institutionalized patients with dementia have changed over the past decade. Although their use declined slightly over the study period, atypical antipsychotics continue to be used at a high rate. A decline in the use of benzodiazepines along with an increased use of sedative and non-sedative antidepressants suggests that the latter class of drugs is being substituted for the former in the management of neuropsychiatric symptoms. Psychotropic polypharmacy continues to be highly prevalent in these patient samples.

Clinical applications of neuroimaging in patients with Alzheimer's disease: a review from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012

In May 2012, the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia brought together in Montreal experts from around Canada to update Canadian recommendations for the diagnosis and management of patients with neurodegenerative conditions associated with deterioration of cognition. Multiple topics were discussed. The present paper is a highly condensed version of those recommendations that were produced to support discussions in the field of neuroimaging for clinical diagnosis of those conditions.

Role of emerging neuroimaging modalities in patients with cognitive impairment: a review from the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012.

The Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4) was held 3 to 4 May 2012 in Montreal, Quebec, Canada. A group of neuroimaging experts were assigned the task of reviewing and summarizing the literature on clinical and research applications of different neuroimaging modalities in cognitive disorders. This paper summarizes the literature and recommendations made to the conference regarding the role of several emerging neuroimaging modalities in cognitive disorders. Functional magnetic resonance imaging (MRI), magnetic resonance spectroscopy, and diffusion tensor imaging are discussed in detail within this paper. Other emergent neuroimaging modalities such as positron emission tomography with novel ligands, high-field MRI, arterial spin labeling MRI and noncerebral blood flow single-photon emission computerized tomography are only discussed briefly. Neuroimaging modalities that were recommended at the CCCDTD4 for both clinical and research applications such as amyloid and flurodeoxyglucose positron emission tomography, computerized tomography and structural MRI are discussed in a separate paper by the same authors. A literature search was conducted using the PubMed database including articles in English that involved human subjects and covered the period from the last CCCDTD publication (CCCDTD3; January 2006) until April 2012. Search terms included the name of the specific modality, dementia, Alzheimers disease, and mild cognitive impairment. A separate search used the same parameters but was restricted to review articles to identify recent evidence-based reviews. Case studies and small case series were not included. Papers representing current evidence were selected, reviewed, and summarized, and the results were presented at the CCCDTD4 meeting with recommendations regarding the utility of various neuroimaging modalities in cognitive disorders. The evidence was graded according to the Oxford Centre for Evidence Based Medicine guidelines. Due to the limitations of current evidence, the neuroimaging modalities discussed in this paper were not recommended for clinical investigation of patients presenting with cognitive impairment. However, in the research setting, each modality provides a unique contribution to the understanding of basic mechanisms and neuropathological markers of cognitive disorders, to the identification of markers for early detection and for the risk of conversion to dementia in the at-risk populations, to the differentiation between different types of cognitive disorders, and to the identification of treatment targets and indicators of treatment response. In conclusion, for all of the neuroimaging modalities discussed in this paper, further studies are needed to establish diagnostic utility such as validity, reliability, and predictive and prognostic value. More multicenter studies are therefore needed with standardized image acquisition, experimental protocols, definition of the clinical population studied, larger numbers of participants, and longer duration of follow-up to allow generalizability of the results to the individual patient.

Modulation of the Left Prefrontal Cortex with High Frequency Repetitive Transcranial Magnetic Stimulation Facilitates Gait in Multiple Sclerosis.

Multiple Sclerosis (MS) is a chronic central nervous system (CNS) demyelinating disease. Gait abnormalities are common and disabling in patients with MS with limited treatment options available. Emerging evidence suggests a role of prefrontal attention networks in modulating gait. High-frequency repetitive transcranial magnetic stimulation (rTMS) is known to enhance cortical excitability in stimulated cortex and its correlates. We investigated the effect of high-frequency left prefrontal rTMS on gait parameters in a 51-year-old Caucasian male with chronic relapsing/remitting MS with residual disabling attention and gait symptoms. Patient received 6 Hz, rTMS at 90% motor threshold using figure of eight coil centered on F 3 location (using 10-20 electroencephalography (EEG) lead localization system). GAITRite gait analysis system was used to collect objective gait measures before and after one session and in another occasion three consecutive daily sessions of rTMS. Two-tailed within subject repeated measure t-test showed significant enhancement in ambulation time, gait velocity, and cadence after three consecutive daily sessions of rTMS. Modulating left prefrontal cortex excitability using rTMS resulted in significant change in gait parameters after three sessions. To our knowledge, this is the first report that demonstrates the effect of rTMS applied to the prefrontal cortex on gait in MS patients.

Non-invasive brain stimulation for food cravings, consumption, and disorders of eating: A review of methods, findings and controversies

OBJECTIVE To describe the state of the human research literature pertaining to the use of non-invasive brain stimulation (NIBS) procedures for modulating food cravings, food consumption, and treating disorders of eating (i.e., obesity, bulimia nervosa, and anorexia nervosa). METHODS A narrative review of methods, empirical findings, and current areas of controversy. Both single-session experimental and multi-session therapeutic modalities are considered, separately for repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) technologies. RESULTS Single-session studies involving NIBS report more consistent effects of rTMS than tDCS, but this advantage is more clear in relation to food cravings than actual food consumption. Multisession therapeutic approaches have been applied to both obesity and eating disorders. With respect to obesity, the three published (tDCS) and one ongoing trial (rTMS) have yielded promising though very preliminary findings. Application of multi-session NIBS (predominantly rTMS) to eating disorders has also yielded promising but ultimately inconclusive results, both in relation to bulimia nervosa and binge eating disorder. Findings regarding excitatory NIBS in the context of anorexia are more controversial, with evidence of improvement in affective functioning, but a trend of iatrogenic weight loss. CONCLUSIONS Excitatory NIBS-particularly rTMS-can reliably reduce food cravings in single and multi-session format. For multi-session treatment of clinical conditions, more studies are needed for both rTMS and tDCS, particularly in relation to obesity, bulimia, and binge eating disorder. Application of NIBS for anorexia is less clear at this point, and excitatory NIBS may be contraindicated on theoretical and empirical grounds.

Role of Hybrid Brain Imaging in Neuropsychiatric Disorders.

This is a focused review of imaging literature to scope the utility of hybrid brain imaging in neuropsychiatric disorders. The review focuses on brain imaging modalities that utilize hybrid (fusion) techniques to characterize abnormal brain molecular signals in combination with structural and functional changes that have been observed in neuropsychiatric disorders. An overview of clinical hybrid brain imaging technologies for human use is followed by a selective review of the literature that conceptualizes the use of these technologies in understanding basic mechanisms of major neuropsychiatric disorders and their therapeutics. Neuronal network abnormalities are highlighted throughout this review to scope the utility of hybrid imaging as a potential biomarker for each disorder.

Worsening of "passivity" symptoms with low-frequency bilateral temporo-parietal repetitive transcranial magnetic stimulation used to treat refractory auditory hallucinations: a case report.

Recent meta-analysis evidence supports the use of low frequency Repetitive Trans-cranial Magnetic Stimulation (rTMS) applied to left temporo-parietal cortex (TPC) for the treatment of anti-psychotic refractory auditory hallucinations (AH) (Freitas et al., 2009). We report here the unusual adverse effect of worsening “passivity” symptoms or delusions of control in a young woman with a primary diagnosis of treatment-refractory schizophrenia that was treated with rTMS for AH at our center. This 24 year old woman had her first psychotic episode four years previously. Since then, she had been treated with typical and atypical antipsychotic medication with limited success. She reported experiencing continuous imperative, derogatory and occasionally, inspirational auditory hallucinations mainly in the form of three male voices. She reported feelings of helplessness in regards to the hallucinations and stated it was nearly impossible to resist many of the commands related to self-hygiene. She also attached emotional significance to the experiences. For example, she stated one of the voices “did not like (her) having a shower”. She reported experiencing passivity of impulse 3–4 times per week and volition 2–3 times per week but not somatic or affect passivity. She had a history of one grand-mal seizure thought to have been related to illicit substance use at the time but no history of epilepsy, and had co-morbid PTSD. At the time she was on Flupenthixol injection, the dose of which was unchanged throughout rTMS treatment. Clozapine was offered but declined. She was offered a course of rTMS for AH as the risk of seizures is small with low-frequency rTMS, which has been used in epilepsy patients safely (Bae et al., 2007). Low frequency rTMS (1 Hz.) at 100% resting motor threshold was applied to the left TPC initially (3 treatments) and later, due to limited response to this, bilaterally to TPC identified as determined by the 10-20-20 EEG lead placement system and as per practice in published reports (Hoffman et al., 2003; Vercammen et al., 2009). Treatment was administered 5 days/week for 4 weeks after which it was stopped for 1 week to review clinical response. She reported an average of 4.4 cm improvement in auditory hallucinations on self-rated visual analogue scale

Effects of left dlPFC modulation on social cognitive processes following food sampling

BACKGROUND The dorsolateral prefrontal cortex (dlPFC) plays a central role in the inhibition of eating, but also the modulation of conscious thought processes that might precede, accompany or follow initial food tasting. The latter might be particularly important to the extent that post-tasting cognitions may drive prolonged eating beyond the satiety point. However, we know very little about the effect of the dlPFC on conation following initial food sampling. This investigation compared the effects of dlPFC attenuation using repetitive transcranial magnetic stimulation (rTMS) on social cognition following (Study 1) and prior to (Study 2) a food consumption opportunity. METHODS In Study 1, participants (N = 21; Mage = 21 years) were randomized to active or sham continuous theta-burst stimulation (cTBS; an inhibitory variant of rTMS) targeting the left dlPFC followed by an interference task. Participants subsequently completed measures of attitudes, norms and perceived control following a mock taste test. In Study 2, a second sample of right handed participants (N = 37; Mage = 21 years) were assigned to active or sham cTBS, followed by an interference task and two measures of attitudes (implicit and explicit), both assessed prior to the same taste test paradigm. RESULTS In Study 1, findings revealed a reliable effect of cTBS on post-tasting attitudes (t(1,19) = 3.055, p = .007; d = 1.34), such that attitudes towards calorie dense snack foods were significantly more positive following active stimulation than following sham stimulation. Similar effects were found for social norms (t(1,19) = 3.024, p = .007, d = 1.31) and perceived control (t(1,20) = 19.247, p < .001, d = 0.50). In Study 2, no effects of cTBS were observed on pre-consumption attitudes, despite reliable effects on interference scores and subsequent consumption. CONCLUSIONS The left dlPFC may selectively modulate facilitative social cognition following initial food sampling (but not pre-consumption).

Repetitive Transcranial Magnetic Stimulation for Depression Due to Cerebrovascular Disease: A Systematic Review

OBJECTIVE This study aims to perform a systematic review evaluating the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in improving depression resulting from cerebrovascular disease including vascular depression (VD) and poststroke depression (PSD). METHODS A literature search of multiple scientific databases was conducted for English studies published from January 1980 to June 2016. Studies were included if the sample consisted of 50% or more adult humans with VD or PSD and had 3 or more subjects, the intervention applied was rTMS, and depression was assessed pre- and post intervention using a formal outcome measure. Randomized controlled trials (RCTs) were assessed for methodological quality using the Physiotherapy Evidence Database (PEDro) tool. A level of evidence was assigned to each study according to the modified Sackett Scale. RESULTS Five studies met the inclusion criteria including 3 RCTs (level 1b; PEDro range: 6-8) and 2 uncontrolled pre-post studies (level 4). There were 186 participants with either PSD (n = 40) or VD (n = 146); the majority of the participants were female (52.7%) and had a mean age ranging from 51.9 to 67.9 years. There were no adverse effects reported by any of the studies. Using clinically accepted criteria for the response rate, all studies reported a benefit from rTMS for the treatment of depression. Three studies also demonstrated a benefit on remission rates as well. CONCLUSIONS rTMS was reported to be beneficial in treating depression among individuals with cerebrovascular disease over the short term. However, heterogeneous populations and variability in study design and protocol, as well as a limited number of studies to review, challenge the ability to form conclusions as to the effectiveness of rTMS.

The Experience of Patients with Schizophrenia Treated with Repetitive Transcranial Magnetic Stimulation for Auditory Hallucinations

Introduction. Auditory hallucinations are a common symptom experience of individuals with psychotic disorders and are often experienced as persistent, distressing, and disruptive. This case series examined the lived experiences of four individuals treated (successfully or unsuccessfully) with low-frequency (1 Hz) rTMS for auditory hallucinations. Methods. A phenomenological approach was used and modified to involve some predetermined data structuring to accommodate for expected cognitive impairments of participants and the impact of rTMS on auditory hallucinations. Data on thoughts and feelings in relation to the helpful, unhelpful, and other effects of rTMS on auditory hallucinations, on well-being, functioning, and the immediate environment were collected using semistructured interviews. Results. All four participants noted some improvements in their well-being following treatment and none reported a worsening of their symptoms. Only two participants noted an improvement in the auditory hallucinations and only one of them reported an improvement that was sustained after treatment completion. Conclusion. We suggest that there are useful findings in the study worth further exploration, specifically in relation to the role of an individuals acceptance and ownership of the illness process in relation to this biomedical intervention. More mixed methods research is required to examine rTMS for auditory hallucinations.