Use of heroin in self-management of Restless Leg Syndrome (RLS) has not heretofore been described. Such a case is presented.

Case study: This 29 years old right handed male presented with a long history of major depressive disorder, generalized anxiety disorder and opioid dependence. The Patient felt compelled to take quetiapine since was the only drug found to be effective in controlling racing thoughts, Major Depressive Disorder with psychotic features. Prior to use of quetiapine the patient never experienced RLS. Quetiapine in doses ranging from 25mg to 300mg a day precipitated severe RLS whereby he was forced to move his leg all night long leading to poor sleep quality. The RLS was unresponsive to Gabapentin and Benztropine, however it was eliminated with a variety of opioids including hydrocodone, buprenorphine, buprenorphine/naloxone. Particularly sensitive to heroin, 1/2 twenty dollar bag, self-administered IV prior to sleep eliminated the RLS immediately, but when injected more than four hours before sleep it had no effect. RLS acted only when induced with quetiapine, since he wished to continue quetiapine to control his mood, he felt compelled to self-medicate with heroin to stop RLS side effects. He showed no other signs of extrapyramidal symptomatology or evidence of any other movement disorder.

Abnormalities in physical examination: General: Abundance of tattoos on body and face. Cranial Nerve (CN): CN I: Alcohol Sniff Test: 7cm (anosmia). CN II: Anisocoria OD 5mm OS 2mm. Motor Examination: drift testing: right pronator drift. Cerebellar: Finger to Nose: end point dysmetria bilaterally. Low amplitude high frequency tremor in both upper extremities on extension. Sensory Examination: decreased graphesthesia in both upper extremities. Reflexes: 3+ knee jerks, absent ankle jerks, positive jaw jerk, bilateral palmomental reflex is present.

This patient has a long history of quetiapine use due to his major depressive disorder with psychotic features and subsequent self-administration of IV heroin reportedly to reduce the symptoms of quetiapine-induced RLS. Heroin elevates dopamine levels in forebrain by blocking inhibitory GABA interneurons near the ventral tegmental area, leading to activation of mesocorticolimbic dopaminergic neurons (Nakagawa 2008, Steidl 2011). The time frame of opioid administration has a critical impact on its efficacy in improving RLS symptoms. However, the drug’s effects only up to 3 to 6hours (Buchfuhrer 2012). In this case administration of heroin more than 4hours before sleep would not alleviate the RLS symptoms. Patient chose the time of injection, not for hedonic pleasure of heroin, but rather to prevent RLS symptoms. In those with heroin dependence, the possibility that is a result of self-medication of underlying movement disorder warrants additional investigation. In those with RLS who are unresponsive to other treatment modalities, a trial of opioids maybe worthwhile.

Tardive dyskinesia (TD) is typically caused by exposure to antipsychotics, is often irreversible, and can be debilitating. TD symptoms can increase the social stigma of patients with comorbid psychiatric disorders, negatively impact quality of life, and potentially increase medical morbidity and mortality. An increased risk of developing TD has been associated with factors such as older age, female sex, underlying mental illness, and long-term use and higher doses of antipsychotics. The association of TD with the use of typical versus atypical antipsychotics has also been evaluated, with mixed results. To date, predictive models assessing the joint effect of clinical characteristics on TD risk have not been developed and validated in the US population.

To develop a prediction model to identify patient and treatment characteristics associated with the occurrence of TD among patients with psychiatric disorders taking antipsychotic medications, using a retrospective database analysis.

Adult patients with schizophrenia, major depressive disorder, or bipolar disorder who were taking oral antipsychotics, and who had 6months of data prior to the index date were identified from Medicaid claims from six US states. The index date was defined as the date of the first claim for an antipsychotic drug after a claim for the underlying disorder but before TD diagnosis. A multivariate Cox prediction model was developed using a cross-validated version of the least absolute shrinkage and selection operator (LASSO) regression method to improve prediction accuracy and interpretability of the model. The predictive performance was assessed in a separate validation set via model discrimination (concordance) and calibration.

A total of 189,415 patients were identified: 66,723 with bipolar disorder, 68,573 with depressive disorder, and 54,119 with schizophrenia. The selected prediction model had a clinically meaningful concordance of 70% and was well calibrated (P=0.46 for Hosmer–Leme show goodness-of-fit test). Patient’s age at index date (hazard ratio [HR]: 1.03), diagnosis of schizophrenia (HR: 1.73), dosage of antipsychotic at index date (up to 100mg/day chlorpromazine equivalent; HR: 1.40), and presence of bipolar and related disorders (HR: 1.16) were significantly associated with an increased risk of TD diagnosis. Use of atypical antipsychotics at index date was associated with a modest reduction in the risk of TD (HR=0.94).

This study identified a group of factors associated with the development of TD among patients with psychiatric disorders treated with antipsychotics. This may allow physicians to better monitor their patients receiving antipsychotics, allowing for the prompt identification and treatment of TD to help maintain quality of life.

Presented at: American Psychiatric Association Annual Meeting; May 5–9, 2018, New York, New York, USA

Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.

One of the challenges in schizophrenia long-term trials is that clinical outcomes are often confounded by covert nonadherence to prescribed oral antipsychotics. This is a post hoc analysis (>2 years) of the symptoms and illness trajectory of patients treated with the long-acting injectable (LAI) antipsychotic aripiprazole lauroxil (AL). As adherence to LAIs can be monitored, these data could assess outcome trajectories unaffected by medication discontinuations that may occur with oral antipsychotics.

The efficacy and safety of once-monthly AL (441 or 882mg) for the treatment of schizophrenia were previously demonstrated in a phase 3 trial, followed by a 52-week, long-term safety study of two AL doses (441 or 882mg once monthly; patients continuing from the phase 3 study remained on their fixed AL dose [NCT01626456]), after which patients could enroll in a second long-term extension study. Patients entering the second long-term study continued on their fixed AL dose, with a variable follow-up period of up to 128 additional weeks (NCT01895452). In this post hoc analysis, the extension studies were combined to provide continuous outcome data over 2 years’ follow-up. The 12-week assessment visit (rather than the first visit) in the first extension study was chosen as the baseline to account for patients entering this study with variable AL exposure histories (with/without prior AL exposure). We report on the trajectory of symptoms and illness severity for >2 years (up to 112weeks) after the 12-week visit using the Positive and Negative Syndrome Scale (PANSS) total and Clinical Global Impression–Severity (CGI-S) scale scores. Course of illness was measured as the difference in PANSS and CGI-S scale scores within dose groups from baseline to end of follow-up, analyzed using MMRM.

Overall, 432/478 patients entering the initial 52-week study were included in the post hoc analysis. For the AL 441 and 882mg groups, respectively, baseline scores (mean±SD) were 59.91±16.25 and 56.27±12.89 (PANSS), and 2.99±0.97 and 2.79±0.79 (CGI-S scale). Approximately 49% of patients (211/432) remained for the entire 112-week follow-up. Over this period, the trajectory of PANSS scores improved significantly compared with baseline for both the 441 and 882mg groups, with changes from baseline (least squares mean±SE) of −5.46±0.92 (P<.0001) and −4.99±0.53 (P<.0001), respectively. CGI-S scale scores had similar improvement: changes from baseline of −0.32±0.07 (P<.0001) and −0.28±0.04 (P<.0001) for the AL 441 and 882mg groups, respectively. Overall, AL was well tolerated, with a safety profile over a 2-year follow-up that was consistent with the initial 52-week safety results.

This post hoc analysis demonstrates the safety and continued therapeutic efficacy of long-term treatment with AL in patients with schizophrenia. There were no apparent dose differences in the trajectory of symptom changes over the course of a 2-year follow-up.

Funding Acknowledgements: This study was funded by Alkermes, Inc.

1. To assess the effectiveness, functionality and tolerability of Aripiprazole long-acting injectable (ALAI) in patients with stable schizophrenia

2. Compare hospitalizations and emergency assists during 18-month period before (retrospective period) and after (prospective period) switch to ALAI

The study sample involved 18 patients with stable schizophrenia (DSM 5 criteria) who started treatment with ALAI between January-December 2016.

Variables: age, gender, psychopharmacological treatment.

- Follow-up study: Prospective assessments were performed at baseline and at 3, 6, 9, 12, 15 and 18 months:

∙ Brief Psychiatric rating Scale (BPRS)

∙ Global Clinical Impression Scale (ICG-SI)

∙ Personal and social Performance (PSP)

∙ Side effects reported

- Mirror-image study: 18-month before and afters witch

∙ Number of hospitalizations and emergency assists

The study was performed in accordance with the Declaration of Helsinki and all the participants provided written consent for participation.

Student’s t-test and Chi-square test were used to assess differences between baseline evaluation and subsequent visits. For mirror-image analysis test Z and MacNemar was used.

a) Efficacy and functionality: At the end of the study we observed:

∙ A statistically significant: reduction in the total score of ICG-SI, and increase in the total score of PSP

∙ A reduction in the total score of BPRS.

There is an indirect correlation between age and changes in the score on: BPRS and ICG-SI (p<0.05) and PSP scale (p<0.05)

b) Tolerability: The most frequent side effect with an incidence of 22% was transient mild insomnia

c) Psychopharmacological treatment: The percentage of patients on monotherapy increased from 39.6% baseline to 66.6%, and treatment with Biperidene decreased from 27.5% to 5.5% at the end of the study

d) Number of hospitalizations and emergency assist:

∙ 12 hospital admission during 18-month period before switch to ALI, and 3 hospital admission 18-month after switch

∙ 24 emergency assist during 18-month period before switch to ALI, and 7 emergency assist 18-month afterswitch

e) Treatment compliance: shown in Table 1.

ALAI can be effective therapy for the treatment of patients with schizophrenia: improves psychopathological symptoms, functionality and can prevent hospitalizations and emergency visits. In addition, ALAI is well tolerated, achieving a high percentage of patients in monotherapy.

Antipsychotic drug treatment is a key component of multiple psychiatric treatment algorithms. Second-generation long-acting injectable antipsychotics (LAIs) have been shown to improve adherence in numerous clinical trials. Patients who can benefit from LAIs therapy can be treated with aripiprazole long acting once-monthly (AOM). However the nature of the introduction patterns of AOM is not well characterized in clinical practice.

A retrospective observational study of AOM introduction was conducted on 157 patients aged 18–75 years-old (95 males, 62 females) who were initiated on AOM treatment between January 2017 – December 2017 in two independent Mental Health Units in the autonomous region of Galicia (Spain). An analysis of the different trends in switching strategies and its adaptation to the prescribing information was carried out. Results were compared between different dose treatment plans and a comparison between inpatients and outpatients’ outcomes was also undertaken. Additional data regarding off-label use was obtained from the sample.

The sample was composed of 157 patients: 31% diagnosed of Schizophrenia (n=48), 14% Schizoaffective Disorder (n=22), 21% Delusional Disorder (n=33), 17% Bipolar Disorder (n=27), 10% Brief Psychotic Disorder (n=15), 4% Psychotic Disorder Not Specified (n=6), 2% Obsessive-Compulsive Disorder (n=3), 2% Paranoid Personality Disorder (n=3). Regarding the location of the first dose administration: 44% (n=69) were administered in an Acute Psychiatric Inpatient Unit, 44% (n=65) were administered in Mental Health Outpatient Clinics, 11% (n=18) in Psychiatric Day Hospitals and 3% (n=5), in Assertive Community Treatment Programs. 74% (n=116) of patients received an initial dose of 400mg of AOM whereas 26% (n=41) were given 300mg of AOM. The previous antipsychotic was aripiprazole orale (OA) in 61% (n=96) of the cases. The most frequent switch between LAIs was “immediate switch” and in the switch between orale antipsychotics and AOM “tapering and overlap” was found to be the most common pattern. The average dose was 20mg/day in all groups except for patients diagnosed with Delusional Disorder (15mg/day). The average duration of treatment with OA after the first dose was: 32days for patients with Schizophrenia, 23days for Delusional Disorder, 30days for Bipolar Disorder and 19days in Schizoaffective Disorder.

Our analysis identified two main patterns of drug switching, the most frequent being “tapering and overlap” in oral treatment, followed by “immediate switch” in patients treated with LAIs.

Although our patients are unlike many of those enrolled in clinical trials, the present study indicates that the predominant switching strategies conforms with the Safety Data Sheet.

Valbenazine is approved for tardive dyskinesia (TD) in adults based on clinical trials that included patients with mood disorders (e.g., bipolar disorder, major depressive disorder). In two long-termphase 3 trials, KINECT 3 (NCT02274558) and KINECT 4 (NCT02405091), sustained TD improvements were found in participants who received once-daily treatment with valbenazine (40 or 80mg). Data from these studies were analyzed post hoc to evaluate changes in psychiatric status of patients with a primary mood disorder.

Data were pooled from participants with mood disorders in KINECT 3 (6-week double-blind, placebo-controlled period; 42-week double-blind extension period; 4-week drug-free washout) and KINECT 4 (48week open-label treatment; 4-week drug-free washout). At screening, patients must have had a Brief Psychiatric Rating Scale total score <50. Mood changes were evaluated after long-term treatment (Week 48) and washout (Week 52) using the Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS). For each scale, mean changes from baseline in the total score and individual item scores were analyzed descriptively.

Of the 95 participants with a primary mood disorder (40mg , n=32; 80mg , n=63), 59 (62.1%) were diagnosed with bipolar disorder, 32 (33.7%) with major depressive disorder, and 4 (4.2%) with another mood disorder. A majority of all mood participants received concomitant antidepressants (84.2%) and/or antipsychotics (76.8%) during treatment; other common concomitant medications included antiepileptics (47.4%), anxiolytics (38.9%), and anticholinergics (22.1%). Mean YMRS and MADRS total scores in all mood participants indicated mood symptom stability at baseline (YMRS, 2.7; MADRS, 5.9). This stability was maintained during the studies, as indicated by minimal changes from baseline in mean total scores (YMRS: Week 48, 1.0; Week 52, –1.0; MADRS: Week 48, 0.3; Week52,0.9). Changes in individual items on both scales were also small (<±0.3), indicating no clinically significant changes or worsening in specific mood symptoms or domains.

Mood symptom stability was maintained in patients with TD and a primary mood disorder who received up to 48 weeks of treatment with once-daily valbenazine in addition to their psychiatric medication(s).

Funding Acknowledgements: Neurocrine Biosciences, Inc.

To assess differences in cognitive impairment in a group of patients with schizophrenia receiving first-generation long-acting antipsychotics (FG-LAI) versus Aripiprazole long-actinginjectable (ALAI).

A descriptive, cross-sectional, multi-centerstudy.

Study sample: 28 outpatients with stable schizophrenia (18 men and 10 women) with ages ranging from 22 to 64years.

Inclusion criteria were: Clinically stable patients with a diagnosis of schizophrenia (according to DSM-5 criteria) and without any changes to their antipsychotic or antidepressant therapy in the last six months.

Simple stratified sampling was performed to collect data from patients with schizophrenia receiving FG-LAI (n=14) versus patients with schizophrenia receiving Aripiprazole long-acting injectable (ALAI) (n=14)

Groups were matched by age, gender, years of evolution of the disease, and years on formal education.

Functionality in the different cognitive domains was evaluated based on the Brief Assessment of cognition in Schizophrenia (BACS.), a hetero-applied instrument, which Spanish version has been validated. BACS evaluates the following cognitive domains:

Verbal memory (V.M): Word list test

Working memory (W.M): Digit sequencing task

Motor speed (M.S): Token motor task

Verbal fluency (V.F): Semantic or category fluency

Attention (A): Symbol coding

Executive function (E.F): Tower of London

The data obtained were analyzed using the SPSS 22.0 statistical package Differences between the means of quantitative variables were assessed using the independent-sample Student-t test. Individual test scores were converted into standardized (T and Z) scores and composite scores that were corrected for age and gender.

Informed consent was obtained from all patients according to the Declaration of Helsinki (World Medical Association).

In the group receiving ALAI, the most severely impaired cognitive domain was attention, whereas motor speed was barely affected. In contrast, verbal memory was most impaired, whereas motor speed was the least impaired cognitive domain in the group receiving FG-LAI.

Patients with schizophrenia taking ALAI showed a better cognitive function in all domains (except for motor speed and attention) than patients receiving FG-LAI.

Summarized results in Table1.

In our study, patients with schizophrenia receiving Aripiprazole long-acting injectable have better cognitive function than patients receiving first-generation long-acting antipsychotics.

While learning is at the core of any education (e.g., primary or high school, college, or continuing medical education, to name a few), evidence-based methods of effective memorization are lacking from most forms of education. If attempts are made to teach memorization techniques, they are often without a sound scientific backing. The classical form of memorization (popularly known as “cramming”, or “rote learning”) is tedious, time consuming, and - we know from personal experience - can be so boring that students avoid memorizing at all. A “new” technique of memorization, which is usually referred to as “mnemonics” or “memory techniques” (first reported as being used by the Greeks and the Romans to learn speeches by heart) has received rave reviews from enthusiastic users. A quick search of the scientific databases shows the technique has been studied quite extensively in a number of areas, including education, the medical world, and in the field of learning disabilities, but as far as we know no systematic reviews have assessed the effectivity of using the mnemonics technique versus classical memorization in education.

We hypothesize that memorization using mnemonics is a more effective strategy than classical memorization(cramming). To study this hypothesis we have performed a systematic review as described below. In this poster we will describe our study and show preliminary findings.

Design: We have performed a systematic review using the Rapid Evidence Assessment procedure described by the Center for Evidence Based Management.

Setting and participants: Studies included limited to those that tested the use of mnemonics in education (primary school, high school, university).

Interventions and main outcome measure of the primary studies: We included studies that compared memorization using mnemonics with “regular” memorization (cramming).

Using 4 databases (Academic Search Premier, PubMed, ERIC and PsycInfo) we found 803 articles. After one round of filtering 589 articles were excluded from the study. The major reasons for exclusion were: learning disabilities, non-educational setting, and no study. In this poster we present the results of the first 10 papers that were included after the second, more stringent, round of filtering. In all 10 papers the mnemonics group performed significantly better on at least a number of the memorization tasks, but in no instance worse than the control group. In some cases where the control groups performed worse, the results were not significant.

This poster describes the analysis of the first 10 papers of our full set of mnemonics studies. They all show a significant advantage of using mnemonics in memorization. If these results are confirmed in our full systematic review, we expect this to have a significant impact on the way “learning how to learn” is taught.

Improvement in hypergeusia in response to alpha lipoic acid treatment has not heretofore been described. Such a case is presented.

Case Study: A 64 year old right handed nasute female noted the sudden onset of salty hypergeusia, about 200% saltier than foods should be. Concurrently she experienced a constant phantogeusia of salt involving the front half of her tongue, lips, and inside her mouth. She denied any smell problems, cacogeusia, or palinageusia. This persisted for five months until treatment with 1800mg/day of alpha lipoic acid, whereupon, over a one month duration, the salty hypergeusia gradually resolved. Suppression of the salty hypergeusia continued until she developed an upper respiratory infection, whereupon, despite the continuation of alpha lipoic acid, the salty hypergeusia returned to 250% of normal. During the cold, her ability to taste dropped down from 100% to 80%, and ability to smell dropped from 100% to 50% and upon resolution of the cold, the senses returned to normal and the salty hypergeusia remitted.

Abnormalities in Neurologic Examination: Reflexes: 3+ bilateral quadriceps femoris and pendular. Chemosensory testing: Olfaction: Alcohol Sniff Test: 12 (hyposmia), Phenylethyl Alcohol Threshold: greater than –2 (anosmia). Suprathreshold Amyl Acetate Odor Intensity Testing: parallel pattern (normosmia). Pocket Smell Test: 4(normosmia). Retronasal Olfactory Testing: Retronasal Smell Index: 8(normosmia). Gustatory testing: Propylthiouracil Disc Taste Test: 5(normogeusia). Taste Super threshold Testing: normogeusia to sodium chloride, sucrose, and phenylthiocarbamol: hypogeusia(10–30%) to urea; ageusia(0%) to hydrochloric acid. Taste Quadrant Testing: taste weakness to sodium chloride for the entire mouth.

The alpha lipoic acid may have acted to improve smell and associated enhanced retro nasal smell, inhibiting savory gustatory discharge, and thus, effectively reducing salt perception. Such a mechanism would also explain the recurrence of hypergeusia with the upper respiratory infection; the infection presumably transiently reducing the olfactory ability, overcoming any olfactory enhancing effects of alpha lipoic acid. On the other hand, this agent could have acted to improve smell as well as taste. With such enhanced chemosensory capacity, the normal olfactory and gustatory components of food would have inhibited competing pathologically discharging gustatory receptors for salt, reducing dysgeusia and hypergeusia. Moreover, the alpha lipoic acidmay have acted to focus the patient’s attention on the gustatory stimulation which may have caused her to perceive not just the predominant salt sensation but enhanced perception of the other gustatory sensations which acted to competitively inhibit the perception of salt. Further investigation of alpha lipoic acid in the management of dysgeusia and hypergeusia is warranted.

Patients treated with antipsychotics, regardless of psychiatric diagnosis, are at risk for developing tardive dyskinesia (TD), a potentially debilitating drug-induced movement disorder. Valbenazine (INGREZZA; VBZ) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved to treat TD in adults. Data from KINECT 4 (NCT02405091) were analyzed to evaluate the long-term effects of VBZ in adults with schizophrenia/schizoaffective disorder (SZD) or mood disorder (MD) and moderate or severe TD.

KINECT 4 included open-label treatment (48weeks) followed by washout (4weeks). Entry requirements included: moderate or severe TD, qualitatively assessed at screening by a blinded, external reviewer; DSM diagnosis of SZD or MD; psychiatric stability (Brief Psychiatric Rating Scale score <50). Stable concomitant psychiatric medications were allowed. Dosing was initiated at 40mg, with escalation to 80mg at Wk4 if participants had a Clinical Global Impression of Change-TD score of ≥3 (minimally improved to very much worse) and tolerated 40mg. A reduction to 40mg was allowed if 80mg was not tolerated (80/40mg); participants unable to tolerate 40mg were discontinued. Safety was the primary focus, but the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1–7) was used to evaluate changes in TD. Mean changes from baseline (BL) in AIMS total score (rated by on-site investigators) were analyzed descriptively. Safety assessments included treatment-emergent adverse events (TEAEs) and psychiatric scales (Positive and Negative Syndrome Scale [PANSS], Calgary Depression Scale for Schizophrenia [CDSS], Montgomery-Åsberg Depression Rating Scale [MADRS], Young Mania Rating Scale [YMRS], and Columbia-Suicide Severity Rating Scale [C SSRS]).

Of 163 participants in the analyses, 103 completed the study. Adverse events (n=26) was the most common reason for discontinuation. Analyses included 119 participants with SZD (40mg=37; 80mg=76; 80/40mg=6) and 44 with MD (40mg=8; 80mg=31; 80/40mg=5). At Wk48, mean improvements from BL in AIMS total score were: SZD (40mg, –10.1; 80mg,–10.7); MD (40mg, 10.2; 80mg: –11.6). AIMS total scores at Wk52 (end of washout) indicated a return toward BL levels. Compared to SZD, the MD subgroup had a higher incidence of any TEAE (84% vs 61% [all doses]) but fewer TEAEs leading to discontinuation (7% vs 18%). Urinary tract infection was the most common TEAE in the MD subgroup (18%); somnolence and headache were most common in the SZD subgroup (7% each). Psychiatric status remained stable from BL to Wk48: SZD (PANSS positive, –0.7, PANSS negative, –0.6; CDSS, –0.7); MD (MADRS, –0.3; YMRS, –0.3). Most participants (95%) had no change in C-SSRS score during the study.

Sustained and clinically meaningful TD improvements were observed with VBZ, regardless of primary psychiatric diagnosis. VBZ was generally well tolerated and no notable changes in psychiatric status were observed.

Funding Acknowledgements: Supported by Neurocrine Biosciences, Inc.

The purpose of this case report is to provide information regarding the importance and effectiveness of monthly maintenance therapy (if required) after completing full course of 36 TMS (Transcranial magnetic stimulation) sessions. (Most patients do not require the maintenance after full course of treatment.)

This is the first study to evaluate the cause of relapse of depression after TMS treatment can be due to failure to do maintenance therapy, no related studies are found in the literature.

The participant is a 57-year-old female with chronic history of treatment resistant MDD since her teenage years. She has been treated 3 times with full course of TMS treatment in 2 years with excellent results, and she went in remission from depression after every treatment. However, due to lack of her attendance for maintenance therapy, despite suggestions by the psychiatrist, her depression relapsed each time within 2–3 months. She was unable to follow-up with maintenance therapy due to her financial situation and lack of coverage of maintenance therapy cost through insurance.

Patient was monitored from initiation of therapy each day until end with clinical rating scale PHQ9& GAD7 for depression & anxiety (in all 3 therapies in 2 years). Marked improvement was observed in her symptoms as shown with range during 3 therapies in the chart below. During each therapy, her remission started anytime from10th-14th treatment and after completion of treatment, she was in remission, fully functional & back to normal life.

Clinical rating    Baseline score in 3    Outcome score in

                           therapies (Before       3 therapies (End

                           TMS treatment of      36 TMS)

PHQ-9                Range: 18-26             Range: 5-9

GAD-7               Range: 14-21             Range: 6-7

Regardless of the limitations of the study (such as case study on one patient), our findings highly suggest that lack of maintenance therapy when needed after completing TMS treatment with full remission may be a cause of relapse of depression in MDD patients. Following through with proper maintenance therapy will prevent relapse of MDD and may have lead to more successful outcomes in subsequent patients. Randomized clinical trial is warranted on large patient population for further evaluation.

Research suggests that repetitive Transcranial Magnetic Stimulation (rTMS) is effective, safe, and proven treatment option for patients with treatment resistant major depressive disorder (MDD). Success rate is high, around 65–70% nationwide. Around 30% patients are still not responding to the treatment. Objective of this study is to evaluate the cause of treatment failure or non-responsiveness of TMS treatment despite high efficacy of the therapy. This is the first study to evaluate the cause of treatment failure of TMS therapy.

Retrospective, 16months, post- TMS treatment, Clinical rating scales PHQ-9 and GAD-7.

68 patients who got treatment over 16months were included in the study, inclusion criteria for thisstudy

includes patients with primary diagnosis of MDD, have previously received at least 20 TMS treatments

and must be evaluated with at least two clinical rating scales that were entered each day during treatment.

Number of treated patients:68

Patients responded to treatment: 50 (73.5%)

Patients not responded: 18 (26.4%)

Mean # of treatments received:37

Mean Baseline PHQ-9 Score:19

Mean Outcome PHQ-9 Score:7

To evaluate the cause of treatment failure in 18 non-responsive patients, patient charts were reviewed in detail. Patients were interviewed near the end of treatment, during follow-ups, and over the phone. It was established that they were either misdiagnosed, have symptoms of other psychiatric disorders such as bipolar depression, have dual diagnoses (e.g: MDD with anxiety, OCD, PTSD) or unclear diagnoses and in need of further psychiatric evaluations. The variety of these diagnostic scenarios mentioned are not typically treated with TMS therapy or treated differently with TMS as compared to MDD, hence the explanation of therapy failure.

Number one cause of TMS treatment failure is misdiagnosis due to various reasons. That includes failure to be accurately diagnosed by a primary psychiatrist, as those patients did not have primary psychiatrist and were referred by primary care physicians and were getting treated for MDD without a proper psychiatric evaluation and diagnosis. However, due to the limitations of the study due to small sample size, we propose that further investigations are needed to be replicated in larger patient population.

We compared the bioavailability of racemic amphetamine (d-amphetamine and l-amphetamine) from a manipulation-resistant immediate-release (IR) amphetamine sulfate capsule (AR19) versus amphetamine sulfate IR tablets (reference).

In this open-label, randomized, two-period, two-treatment, two-sequence, crossover study, 36 healthy volunteers aged 18–45 received a single dose (20-mg capsule) of AR19 in one period and a single dose (2 x 10-mg tablets) of reference in another period, after a 10-hour overnight fast. Each drug administration was separated by a washout period of at least 6days. Bioequivalence for d- and l-amphetamine was assessed using time to peak concentration (Tmax), peak concentration in plasma (Cmax), and area under the plasma concentration–time curve from time-zero to the time of the last quantifiable concentration (AUClast) and extrapolated to infinity (AUCinf).

All 36 volunteers completed both treatment sequences. Mean (standard deviation; SD) Tmax for d- and l-amphetamine was similar for AR19 (2.84[1.05]; 3.05[1.22], respectively) and reference (2.52[0.75]; 2.75[1.00], respectively). The geometric least-squares mean ratios and 90% confidence intervals were within the boundary of 80%–125% for bioequivalence for Cmax (d-amphetamine, 98.35% [96.12–100.64]; l-amphetamine, 98.82% [96.42–101.28]), AUClast (d-amphetamine, 99.45% [96.92–102.05]; l-amphetamine, 99.29% [96.55–102.10]), and AUCinf (d-amphetamine, 99.50%[96.77–102.30]; l-amphetamine, 99.23% [96.06–102.50]). A total of 13 mild adverse events were reported by 7 volunteers (AEs; AR19, n=5; reference, n=8). No serious AEs were reported.

AR19 was well tolerated and was bioequivalent to reference when administered as a 20-mg dose in healthy volunteers.

Funding Acknowledgements: This study was funded by Arbor Pharmaceuticals, LLC.

Relief of phantogeusia through ice cube stimulation has not heretofore been noted.

This 70-year-old left handed (familial) female noted the onset, three and a half years ago, of reduced taste 80 percent of normal, distorted taste, hallucinated metallic taste, and BMS. Upon application of an ice cube to the tongue, both the metallic taste and the BMS resolved for a few seconds, without impairing her true taste ability. With repeat application, the alleviation effect persists.

Abnormalities in Neurologic Examination: Sensory Examination: Decreased pinprick and temperature bilateral lower extremities. Reflexes: 3+ throughout. Bilateral positive Hoffman’s reflexes. Chemosensory testing: Olfaction: Brief Smell Identification Test: 9 (normosmia). Retronasal Smell Index: 10 (normosmia). Gustation: Propylthiouracil Disc Taste Test: 5 (normogeusia).

Transient Receptor Potential 5, is expressed in tongue taste buds, facilitating sweet perception, and is temperature dependent (Fujiyama, 2010). Ice may act to reduce such sweet taste receptor discharge, causing an imbalance in taste fiber discharge thus inhibiting the perceived metallic taste. In those who suffer from intractable phantogeusia, a trial of ice cubes or mechanisms to reduce temperature of the tongue is warranted.

Catatonia is not only present in adults; children & adolescents can suffer from catatonia but are often misdiagnosed. A study by Ghaziuddin, Dhossche and Marcotte (2012) found that 18 of the 101 child and adolescent patients had symptoms of catatonia, but only 2 actually had been given a diagnosis by their providers.

17-year-old male who was recently discharged from the inpatient psychiatric unit with the diagnosis of Major Depressive Disorder. His discharge medication was bupropion XL 150mg daily. Within 10 days of his discharge, he was back to the emergency room with worsening anxiety and manic symptoms. At the emergency room, patient’s sister reported that he was acting differently within the last 3–4 days, and making statements that he can save the world that everyone was talking about him. He was also speaking faster than usual, having decreased need for sleep. He reported hearing voices, seeing things. Patient was admitted again, and was given diagnosis of Bipolar Mood Disorder, type I, manic phase, with psychosis. He was started on divalproex 500mg bid for mood stabilization. His Bupropion was discontinued. Gradually his Divalproex was increased to 750mg bid. During his hospital stay he developed lack of spontaneous speech, sluggish responses to questions with automatic answers such as “I don’t know”. He also developed very sluggish motor movements. There was negativism. He needed one on one support for his daily activities of living, needed step by step instructions for all ADLs.

All the test results were negative including EEG, MRI and CT scan of the brain. Bush Francis catatonia rating scale was done and he scored 15. Lorazepam Challenge Test was performed, and the scale was repeated after the patient was given an IM dose of 2mg of Lorazepam, and he scored 2. At this point catatonia diagnosis was confirmed. He was started on scheduled doses of Lorazepam, gradually his Lorazepam dose was increased up to 9mg per day. His catatonia responded to Lorazepam treatment.

17 year old male who initially hospitalized for symptoms of MDD and discharged with antidepressant, came back to the ER within 10 day with symptoms of mania with psychosis. During in-patient’s 2nd in-patient stay he developed catatonia, which was promptly diagnosed and appropriately treated with Lorazepam.

Catatonia can happen in children & adolescents with mood disorders, or with other psychiatric or medical conditions. Timely diagnosis and treatment is very crucial to avoid poor outcome, especially because treatment options for catatonia are well understood; Benzodiazepines, electroconvulsive therapy and reduction or discontinuation of antipsychotics are successful in the treatment of catatonia (Ghaziuddin, Dhossche and Marcotte, 2012).

Among adults in the US, bipolar disorder affects 2.6% or 5.7 million individuals; 83% of cases are considered to be severe. Even when an accurate diagnosis of bipolar disorder is established, its treatment remains suboptimal, and those with the disorder often fail to receive any care or evidence‐based care.

A continuing medical education (CME)-certified 25-item, multiple choice clinical practice assessment survey was developed to assess recognition and treatment of bipolar disorder, specifically, the use of LAIs in these patients.

The survey included knowledge- and case-based multiple-choice questions completed confidentially online. The survey was launched on December 20, 2017 and hosted on the Medscape Education website. Participant responses were collected through January 31, 2018. Confidentiality was maintained, and responses were de-identified and aggregated before analyses.

(n=1123 psychiatrists; 305 primary care physicians [PCPs]):

- When asked about assessment tools in bipolar disorder, only 43% of psychiatrists and 36% of PCPs could identify the correct use of the MDQ screening instrument, while only 64% of psychiatrists and 51% of PCPs knew that the use of the MDQ can improve recognition of bipolar disorder in patients with depression;

- Psychiatrists were more likely to correctly identify the symptoms that most strongly support a diagnosis of bipolar disorder compared to PCPs (76% vs 43%, respectively);

- When asked about laboratory testing in mood disorders, 52% of psychiatrists and 46% of PCPs knew that laboratory testing can help exclude alternative causes for mood symptoms;

- The majority of both healthcare professionals (73%–75%) did not know that diagnosis of bipolar I disorder relies heavily on changes in activity, energy, and mood;

- 87% of psychiatrists and 76% of PCPs did not identify oral aripiprazole as the only SGA not approved by the FDA for the maintenance treatment of bipolar I disorder;

- 49% of PCPs did not recognize lithium as the first choice for maintenance monotherapy for bipolar I disorder according to the guidelines;

- Only 19% of psychiatrists and 20% of PCPs correctly chose aripiprazole monohydrate and risperidone microspheres as the LAI SGAs indicated for use as monotherapy for patients with bipolar I disorder;

- When asked what is the most common barrier to prescribing LAI antipsychotics in patients with bipolar disorder, 34% of psychiatrists selected “Patients fear of injectables”

This educational research identified psychiatrists and PCPs’ current real-world clinical practices and gaps in the knowledge and competence in the diagnosis and assessment of bipolar disorder, and the treatment options for this condition. Further educational efforts tailored to address identified gaps for each audience are warranted.

Funding Acknowledgements:Otsuka

“I know everybody here”

Hyperfamiliarity for unknown faces, a delusion of misidentification, is a rare disorder.

We present a 67-year-old female admitted with worsening cognitive impairment and poor self-care associated with parkinsonian symptoms of one-year duration. During evaluation, she was noted to relate to strangers with familiar gestures like people she already knew causing distress for family and care givers.

Workup revealed significant cognitive impairment, MOCA of 9/30 and neuroimaging showing diffuse temporal lobe volume loss predominantly on the left.

Assessment was Lewy body dementia with hyperfamiliarity for unknown faces.

This rare presentation reflects the need for detailed examination and workup during evaluation.

Report the efficacy of open-label amphetamine extended-release oral suspension (AMPH EROS) for the treatment of children with ADHD.

AMPH EROS has a 1-hr onset of effect and a duration of action of 13hours and was approved by FDA for treatment of ADHD in children aged 6–17 years based on a double-blind, placebo-controlled efficacy and safety study in children aged 6–12 years with ADHD. A significant treatment difference in change from pre-dose SKAMP-combined score was observed at the primary endpoint of 4hours post-dose (p<0.0001) and each post-dose time point assessed (1, 2, 4, 6, 8, 10, 12, 13hours).

Data reported here are from the 5-week, open-label dose optimization period. These efficacy data support the primary endpoint result.

Males and females aged 6 to 12 years with ADHD enrolled and began open-label treatment with 2.5 mg or 5mg/day of AMPH EROS titrated in 2.5–10mg/day increments until optimal dose (maximum 20mg/day). Doses could be decreased for tolerability. Subjects took morning AMPH EROS for 5weeks. Other efficacy outcomes during the open-label dose optimization phase: ADHD-RS (ADHD-Rating Scale), CGI-S (Clinical Global Impression of Severity), CGI-I (CGI-of Improvement) and CPRS (Conners’ Parent Rating Scale). All subjects were assessed for safety.

For the ITT population (n=99): treatment with AMPH EROS was associated with a mean change in ADHD-RS-IV (baseline to end of the open-label dose optimization; week 6) of 28.2 (±9.03) (Baseline score = 41.3±7.95). 90.9% of subjects had a change from baseline to open-label week 6 of ≥50% in the ADHD-RS-IV total score and were defined as responders. The CGI-S scores decreased continuously from baseline, with a high 4.8 at baseline to a low of 2.0 at open-label week 6. The percentage of subjects classified as moderately ill or greater correspondingly decreased from 97% at Baseline to 1% at open-label week 6. The decrease in the CGI-I over the study was similar to the change in CGI-S scores. CPRS for most categories decreased continuously from Baseline to open-label week 6. Mean change from baseline to open-label week 6 on the CPRS inattention T-score subscale was –25.3 (±14.38) and –24.4 (±13.87).

Adverse events (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings and headache.

AMPH EROS was effective in reducing symptoms of ADHD in this open-label dose optimization. The AE profile of AMPH EROS was consistent with those of other amphetamine products.

Funding Acknowledgements: This work was funded by Tris Pharma, Inc.

To determine the efficacy and safety of amphetamine extended-release oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity disorder (ADHD) compared with placebo in a dose-optimized, randomized, double-blind study.

The efficacy of AMPH EROS was evaluated in a laboratory classroom study conducted in 108 pediatric patients (aged 6–12 years) with ADHD. The study began with an open-label dose optimization (5weeks) with an initial AMPH EROS dose of 2.5 or 5mg once daily in the morning. The dose could be titrated every 4–7 days in increments of 2.5–10mg until an optimal dose or the maximum dose of 20mg/day was reached. Subjects were required to tolerate a minimal dose of 10mg/day. Subjects then entered a 1-week randomized, double-blind treatment phase with the individually optimized dose or placebo. At the end of the week, raters evaluated the attention and behavior of the subjects in a laboratory classroom using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP-C) rating scale. SKAMP-C is a 13-item teacher-rated scale that assesses manifestations of ADHD in a classroom setting.

The primary efficacy endpoint was change from pre-dose in the SKAMP-C score at 4hours post dose. The key secondary endpoint efficacy parameters were onset and duration of clinical effect. The change scores from pre-dose SKAMP-C scores at post dose time points (1, 2, 6, 8, 10, 12 and 13hours) were used to evaluate the key secondary efficacy endpoints.

More boys (68.7%) than girls participated in the study. The study population was 55.6% white, most patients had inattentive or combined type ADHD presentations. The primary efficacy endpoint, the change from pre-dose SKAMP-C score at 4hours post dose was statistically significantly improved (p<0.0001) compared with placebo. Each of the secondary efficacy endpoints were also significantly improved (p<0.0001 at each time point) compared with placebo. Adverse events reported (frequency >5%) reported during the dose optimization phase were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache.

AMPH EROS was effective in reducing symptoms or ADHD from 1 to 13hours after dosing. Adverse events reported were consistent with those of other amphetamine products.

Funding Acknowledgements: This study was supported by Tris Pharma, Inc.