Tardive dyskinesia (TD) is an involuntary movement disorder that is more prevalent in older patients. However, there is limited information on TD treatment for this population. In two 12-week pivotal trials (ARM-TD and AIM-TD), TD patients demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) score with deutetrabenazine versus placebo.

Patients who completed ARM-TD or AIM-TD enrolled in an open-label extension (OLE) study. This post hoc analysis assessed change and percent change from baseline in AIMS score, response rates for ≥50% AIMS improvement, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and safety in younger (<55 years) and older (≥55 years) patients.

This analysis included 119 younger and 218 older patients enrolled in the OLE. Data presented at Week 145 (mean±SE): total deutetrabenazine dose was 39.4±1.39mg/day and 39.5±1.04mg/day in younger and older patients, respectively. Changes from baseline in AIMS score were –6.7±0.62 and –6.5±0.47, respectively (percent changes of –61.4%±4.10% and –54.6%±3.01%). The majority of younger and older patients achieved treatment success per CGIC (67% and 76%) and PGIC (64% and 63%) and achieved ≥50% AIMS response (76% and 62%). Deutetrabenazine was generally well tolerated in both groups. Exposure-adjusted incidence rates (incidence/patient-years) were <0.01 and 0.02 for akathisia, 0.07 (both) for somnolence and sedation, 0.04 and 0.11 for parkinson-like events, and 0.06 and 0.09 for depression in younger and older patients, respectively.

Deutetrabenazine treatment was associated with sustained improvements in AIMS score and was well tolerated in both younger and older TD patients.

Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel

To evaluate the risk of relapse for patients with schizophrenia (SZ), bipolar disorder (BP), and major depressive disorder (MDD) who switched antipsychotics compared with those who did not switch.

Antipsychotics are commonly used for maintenance treatment of SZ, BP, and MDD but can have significant side effects, such as extrapyramidal symptoms (EPS). Adherence to treatment is important for reducing the risk of relapse, but fear of side effects may prompt medication switching.

Medicaid claims from 6 US states spanning 6 years were retrospectively analyzed for antipsychotic switching versus non-switching. For all patients with SZ, BD or MDD and for the subset of patients who also had ≥1 EPS diagnosis during the baseline period, times to the following outcomes, during a 2-year study period were analyzed: underlying disease relapse, psychiatric relapse, all-cause emergency room (ER) visit, all-cause inpatient (IP) admission and EPS diagnosis.

Switchers (N=10,548) had a shorter time to disease relapse, other psychiatric relapse, IP admissions, ER visits, and EPS diagnosis (all, log-rank P<0.001) than non-switchers (N=31,644). Switchers reached the median for IP admission (21.50 months) vs non-switchers (not reached) and for ER visits (switchers, 9.07 months; non-switchers, 13.35 months). For disease relapse, other psychiatric relapse, and EPS diagnosis, <50% of patients had an event during the 2-year study period. Comparisons in a subgroup of patients with ≥1 EPS diagnosis revealed similar outcomes.

These results show that disease and other psychiatric relapse, all-cause ER visits, IP admissions, and EPS diagnosis occurred earlier for switchers than for non-switchers, suggesting that switching is associated with an increased risk of relapse in patients with SZ, BP and MDD.

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

Prior research suggests that religiosity may be associated with healthier levels of mental health in certain domains (eg, higher self-esteem and lower rates of substance use problems). However, very little is known about religiosity and impulsive plus compulsive tendencies. This study examined associations between religiosity and impulsive and compulsive behaviors and traits among university students.

Nine thousand, four hundred and forty-nine students received a 156-item anonymous online survey which assessed religiosity, alcohol and drug use, mental health issues, and impulsive and compulsive traits. Two groups of interest were defined: those with high religiosity, and those with low religiosity, based on z-scores. The two groups were compared on the measures of interest.

Three thousand, five hundred and seventy-two university students (57.1% female) responded to the survey. Those with high levels of organizational religious activity, as well as those with high levels of intrinsic or subjective religiosity, differed from their fellow students in having better self-esteem, being less likely to have alcohol or drug problems, and generally being less impulsive in terms of attention and planning. Compulsivity did not differ between groups. Associations were of small effect size except for the link between religiosity and lower impulsivity, which was of medium effect size.

This study shows a link between higher religiosity and lower impulsivity, as well as higher levels of mental health across several domains. Whether these associations are causal—and if so, the direction of such causality—requires rigorous longitudinal research.

Buprenorphine/Naloxone combination drugs such as Suboxone and Bunavail have not been reported to induce glycolimia. Two such cases are presented.

CASE STUDY: Case 1: A 30-year-old, right-handed, white female with a history of opioid abuse was started on 4.2 mg buprenorphine/0.7 mg naloxone (Bunavail) BID and began sweet cravings and consumption of sweet foods. In a typical day she would eat 16 strawberry pop-tarts and 2 boxes of Little Debbie cookies. This may have provoked the 10 pound weight augmentation in the first two weeks of treatment. She denied any craving for opioids and no evidence of opioid withdrawal was present. Her Clinical Opiate Withdrawal Scale (COWS) score =4 (normal).

Case 2: A 51-year-old, right-handed, male with opiate dependence, four days following the initiation of Suboxone (8 mg buprenorphine/2 mg naloxone) BID, developed strong cravings for sugary foods including donuts and ice cream, of which he was previously never inclined to eat and gained 10 pounds in one month. His COWS score= 7 (mild symptoms).

There are myriad mechanisms that may be acting to induce sugar cravings with buprenorphine/naloxone. Humans and rats acutely withdrawing from opiates, such as heroin, develop strong urges for consumption of sugary substances (Lieblich et al., 1991; Sapira, 1968; Weiss, 1982). Glycolimia in the above cases may reflect early or subclinical withdrawal, which if becoming more severe, would manifest as opioid craving. If the value of the reward system induced by sweets doesn’t meet the threshold invoked by the opioid stimulation, this “withdrawal” may lead to further sugar cravings in an attempt to reach the same reward level. In animals, certain foods and drugs share the same neurological pathway involved in the “reward system” potentially explaining why opioids influence food palatability in humans (Pelchat, 2002).

Alternatively, it is possible that buprenorphine induces hypoglycemia at high doses (Bullingham et al., 1981) such that hypoglycemia may paradoxically act to enhance sugar craving similar to the Somogyi effect in insulin dependent diabetics. Another possible mechanism of action is that since buprenorphine acts to decrease glucose metabolism in the brain (Walsh et al., 1994), this may lead to a neural compensatory response by increasing sugar access to the brain behaviorally via glycolimiaand somatically reducing insulin release, thus explaining the high hemoglobin A1c observed in opioid addicts (Giugliano, 1984). Given the above presentation, complaints of sugar craving may indicate consideration to increase buprenorphine dosing and trial of this in those with glycolimia without opioid dependence may be warranted.

No funding.

Eye’ve Seen Enough: Oculogyric Crisis in a 13 year old Male Treated for Comorbid ADHD and Psychosis After Stopping Lisdexamphetamine

Oculogyric crisis is a dystonic movement disorder caused by sustained contractions of ocular muscles that may last minutes to hours. It is known to occur during hypodopaminergic states. Combined use of stimulants and antipsychotics increase the risk for developing a hypodopaminergic state in the brain leading to various dystonic reactions described as a stimulant-antipsychotic syndrome (SAS).

A unique example of SAS occurred in a 13 year-old male with comorbid ADHD and schizoaffective disorder hospitalized for acute psychotic decompensation who had been treated for several months with risperidone and lisdexamphetamine. On admission, the patient had received olanzapine 5mg ODT for acute agitation and lisdexamphetamine was discontinued. He started to cross-taper from risperidone to quetiapine. In this setting he developed dystonia including an oculogyric crisis that resolved with diphenhydramine.

In this case the use of lisdexamphetamine and risperidone may have set up an environment where there was decreased endogenously made dopamine and up-regulation of postsynaptic dopamine receptors. Upon discontinuation of the lisdexamphetamine and acute use of additional atypical antipsychotics (olanzapine and quetiapine), the body experienced a hypodopaminergic state resulting in dystonic reactions that included an oculogyric crisis. This case is unique from previously reported cases by occurring with the use and discontinuation of lisdexamphetamine while most reported cases involved a derivative of methylphenidate as the stimulant. This report adds to the literature showing the importance of monitoring and being aware of potential medication interactions especially when treating for comorbid conditions. This is even more important to recognize after adding or removing either of these medications.

Funding: no funding.

Understand the mechanism and pharmacokinetics involved in an unintentional overdose of injectableantipsychotic medication; identify how to transition between long acting injectable antipsychotics; formulate steps to ensure patient safety in an event of an unintentional overdose of injectable antipsychotic

Review of a case study involving a 47-year-old male, with history of schizoaffective disorder and previous episodes of loss of consciousness of unknown etiology, who was admitted to the inpatient psychiatry unit at UConn Health John Dempsey Hospital for stabilization of psychotic symptoms and monitoring of unintentional overdose after initially being admitted to the ICU. He was found unconscious at home following a period of days where he self-injected four of 37.5mg Risperidone injections (estimated 150mg) along with limited adherence to prescribed oral clozapine, doxepin and lorazepam. He reported self-injecting additional medication to treat paranoia, auditory, visual and olfactory hallucinations. In the ICU, he was evaluated by Toxicology and Neurology for loss of consciousness thought to be from seizures, with no clear outcome. He was awake and alert within 24 hours of medical admission but became agitated, hostile, and psychotic prompting psychiatric admission. When his worsening paranoia had resulted in termination of his visiting nurse services that administered injections and in home assessments, his outpatient psychiatrist allowed him to self-administer bi-monthly injections. Over three weeks in the hospital, he was evaluated for signs and symptoms of antipsychotic overdose.

Initial literature review did not reveal information involving an overdose of injectable Risperidone. Thus, the time frame and symptoms to monitor were uncertain. As the injectable medication was expected to peak in 2-3 weeks and persist for 4-6 weeks, there was a concern about delayed potential side effects such as EPS, sedation, QTC prolongation and electrolytes imbalances. He was treated with oral antipsychotic medication. Clozapine and doxepin were discontinued due to patient non-adherence, side effects, and drug interactions. He exhibited signs of EPS and was started on benztropine. To simplify his regimen, he was switched to another long acting injectable, Paliperidone Palmitate, prior to his discharge.

Given the nature of the presentation, he was advised not to self-administer injectable medication and was referred for visiting nurse services. He was educated on the potential side effects of injectable antipsychotic medication. As there was a change in antipsychotic medications, follow up was recommended in an intensive outpatient program for psychotic symptoms and prolonged side effects. Due to the patient’s concordant episode of loss of consciousness, he was advised to follow up with an outpatient long term EEG monitoring and complete Neurology evaluation.

No funding.