On June 14, 2018, the FDA approved generic buprenorphine/naloxone, as an alternative to the brand Suboxone (FDA,2018). A patient who developed acute withdrawal symptoms when switched from Suboxone to generic buprenorphine/naloxone at the same dosage, with resolution with replacement with brand name Suboxone, is presented. Induction of withdrawal with generic buprenorphine/naloxone has not heretofore been described.

Case Study: A 39-year-old right handed single male presented with a past medical history of intravenous heroin dependence. He was relapse free for 5 years and without change on Suboxone film 8mg/2mg twice daily, and was provided with prescriptions for the same, which was substituted to generic brand Dr. Reddy’s Lab SA buprenorphine HCl/naloxone HCl 8mg/2mg film. After two days on this, one hour after taking generic buprenorphine/naloxone film, symptoms of withdrawal began as manifest by hot flashes, diaphoresis, cold chills, leg cramping, and nausea without vomiting. These were the same symptoms he experienced during his past inpatient withdrawal from opioids. These symptoms recurred every day for an entire week until switching back to brand name Suboxone, whereupon his withdrawal symptoms resolved.

The mechanism whereby the generic buprenorphine/naloxone combination induced withdrawal symptoms is unclear. It appears that this generic version was either not effectively blocking the mu receptors or the naloxone was inducing a withdrawal state. Possibly the porous nature of the film was such that less of the buprenorphine was absorbed through the mucosa. As a result, less was transferred into the bloodstream, across the blood brain barrier, to the nucleus accumbens, and ultimately on kappa opioid/mu receptor (Centerwatch, 2002). Alternatively, a greater amount of naloxone may have been absorbed transmucosally, thus inducing withdrawal. The absorption may have been normal, but the exact milligram dosage may not be accurate with either too little buprenorphine or too much naloxone. On the other hand, this buprenorphine compound may have been pH sensitive, such that it became inactivated upon exposure to the mildly acidic salivary pH. He could have been malingering this response. Again this is unlikely since he was not given a higher dose of buprenorphine/naloxone, rather the same dose of Suboxone as previously prescribed. It is important that physicians be aware of the possibility for acute withdrawal and increased cravings, which can lead to relapse while using this agent. Further investigation of the efficacy of the generic variant and Suboxone as replacement therapy is warranted.

Evidence is clear that the nation is experiencing an increasing number of incompetent to stand trial (IST) admissions to state hospitals. As a result, defendants in need of treatment can wait in jail for weeks for admission for restoration. This study was conducted to better understand this growing population and to inform hospital administration about the characteristics of IST admissions.

The study was conducted at the Department of State Hospitals (DSH) facility in Napa (DSH-Napa), a 1200-bed primarily forensic inpatient psychiatric facility located in northern California. The records of patients found IST and admitted to DSH-Napa for restoration of competence between the dates of 1/1/2009 and 12/31/2016 were eligible for inclusion in the study.

There were a total of 3158 unduplicated IST admissions available during the specified time period. Our data indicate that the number of admissions with more than 15 prior arrests increased significantly, from 17.7% in 2009 to 46.4% in 2016. In contrast, the percent of patients reporting prior inpatient psychiatric hospitalization evidenced a consistent decrease over time from over 76% in 2009 to less than 50% in 2016.

Our data add to the body of literature on the potential causes of the nationwide increase in competency referrals. The literature is clear that jails and prisons are now the primary provider of the nation’s mental health care. Our data suggest that another system has assumed this role: state hospitals and other providers charged with restoring individuals to competence.

While monoballismus has been reported to be associated with hemorrhagic lesions in the subthalamic nucleus (Ohnishi, 2009) and multiple sclerosis (MS) (Rosa, 2011), the duration has been reported to be at least six days (Soysal, 2012). A patient with epochs of monoballismus lasting for 45 minutes is presented.

Case Study: A 57 year old right handed female with attention deficit hereditary disorder predominantly inattentive on amphetamine sulphate, presented with two years of memory loss. For instance, after ordering food in restaurants, by the time the food arrives, she could not recall what she ordered. At the onset of this symptom, she noted three epochs of her left arm jerking for 45 minutes. The jerking would begin with low amplitude and low frequency and rapidly progress to the forearm and arm of greater magnitude and low frequency. With her right hand she would try to hold down her left arm without success. There was no associated paresis, sensory phenomena, headaches, dizziness, presyncope, loss of consciousness, or strong emotions. She admitted to frequent jamais vu.

Abnormalities: Neurological Examination: Mental Status Examination: Memory: Immediate Recall: 5 digits forward and 2 digits backwards. Cranial Nerve (CN) Examination: CN I: Alcohol Sniff Test 8 (hyposmia). CN XII: tongue tremor on protrusion. Motor Examination: Drift Test: positive right pronator drift. Gait Examination: Tandem Gait: unstable. Reflexes: 0-1 throughout. Neuropsychiatric Examination: Go-No-Go Test: 6/6 (normal). Animal Fluency Test: 15 (normal). Clock Drawing Test: 3 (abnormal). Center for Neurologic Study Lability Scale: 16 (pseudobulbar affect). Other: MRI with and without infusion: normal.

Transient tonic-clonic movements of one limb have been described with focal epilepsy associated with diabetic non-ketotic hyperglycemia (Grant, 1985). A metabolic abnormality such as transient hypoglycemia or hyperkalemia can cause a focal dystonia (Soysal, 2012), which theoretically could manifest with monoballismus. This could be a somatic manifestation of underlying conflict, conversion disorder, or as a result of a physical manifestation of panic attack with hyperventilation and tetany (Mihai, 2008). This may be the first manifestation of a generalized cerebral disorder associated with chorea or ballismus such as Wilson’s disease, or Huntington’s Chorea (Mihai, 2008). It is possible that this is a variant of Alien Hand Syndrome with parietal lobe involvement (Shrestha, 2015). But this is unlikely given the absence of hemineglect or hemiagnosia. It is possible that amphetamines may have induced a monochorea. Chronic amphetamine use has been demonstrated to cause chorea (Klawans, 1974) and it theoretically could have caused ballismus movements in this case. In patients who present with short duration monoballismus, evaluation for subthalamic nuclei function, seizure disorders and other origins of ballismus are warranted.

Smell & Taste Treatment and Research Foundation

Glycolimia is observed in a plethora of medical conditions including burning mouth syndrome, opioid withdrawal, as well as from a variety of medications including vortioxetine, l-methylfolate, lisdexamfetamine, and gabapentin. While vilazodone, an antidepressant with agonist like effects on 5-HT1A receptors, has been found to induce hyperglycemia, it has not heretofore been reported to induce glycolimia. Such a case is described.

Case study: A 60-year-old, left-handed (pathological) male presented with a past history of depression, minimally responsive to a variety of antidepressant medications, was begun on vilazodone, initially 20 mg and gradually increased to 60 mg a day. On 60 mg a day he noticed severe cravings for sweets, which he had never experienced prior to starting vilazodone. He found he had increased consumption, craving sweet foods including cookies and candy. For instance, in a typical day, he would eat eight Oreos, chocolate-covered graham crackers, one pint of ice cream a day, and he would crave sweets even after feeling satiated after consuming a meal. Along with this increased eating, he gained 20 pounds over the 3 months while on the vilazodone. Upon discontinuing the vilazodone, although the weight didn’t change, the sweet cravings resolved.

Abnormalities on: Neurological examination: Mental status examination: Immediate recall: able to remember 6 digits forwards and 3 digits backwards. Motor examination: Drift testing: right inward drift. Gait examination: unstable tandem gait. Neuropsychiatric examination: Go-No-Go test: 6/6 (normal). Animal Fluency Test: 22 (normal).

There are myriad mechanisms whereby vilazodone may have induced glycolimia. Possibly due to its antidepressant effects, it increased hedonics, generating appetitive behaviors, including enhanced socialization, sexual, and other consumptive behaviors, including eating. Peradventure it may have enhanced motivation and socialization. Along with socialization, there is escalation in social intercourse, with accompanying commensalism. Along with such consumptive behaviors, we could anticipate glycolimia. As a 5-HT1A receptor agonist, possibly vilazodone may have acted on the arcuate pro-opiomelanocortin neurons associated with hyperphagia, with modulation of energy homeostasis in the serotonin pathway. Alternatively, vilazodone may have triggered an enhanced insulin response with secondary reduction in blood sugar, leading to a homeostatic behavioral response of increased glucose intake. In those who are treated with vilazodone, query as to glycolimia is warranted and warning as to potential manifestations of hyperglycemia should be entertained.

No Funding

The value of early functional improvement at week 2 for predicting subsequent functional outcomes at week 8 was assessed in a pooled analysis of patients with major depressive disorder (MDD) treated with desvenlafaxine (50 or 100 mg/d) or placebo.

Data were pooled from eight double-blind, placebo-controlled studies of desvenlafaxine 50 mg/d or 100 mg/d for the treatment of MDD. Optimal week-2 improvement thresholds in Sheehan Disability Scale (SDS) score, which best predicted week-8 treatment success, were determined using receiver operating characteristic (ROC) analysis. Four definitions of treatment success were established: (1) functional response, (2) functional/depression response, (3) functional remission, and (4) functional/depression remission. Odds ratios (ORs) of early improvement for prediction (based on thresholds determined in the ROC analysis) of week-8 treatment success were computed using logistic regression models.

Functional early improvement thresholds of 17%–32% were predictive of week-8 treatment success across treatment groups and definitions of treatment success. Optimal thresholds were higher for more stringent definitions. Negative predictive value exceeded positive predictive value, indicating that failure to achieve early functional improvement was more informative about later treatment success than was the achievement of early functional improvement. Early change in SDS was a highly significant predictor of functional response/remission (ORs, 4.981–8.737; all p < 0.0001); the interaction between treatment and early functional improvement was not significant.

Early improvement in SDS total score was predictive of functional outcomes for patients treated with desvenlafaxine 50 mg, desvenlafaxine 100 mg, or placebo.

To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.

In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.

Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).

343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.

These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.

Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA

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

The association of sleep disorders and post-traumatic stress disorder (PTSD) is almost universal. Nightmares are not only one of the most commonly associated but also featured as a diagnostic criterion for PTSD. PTSD-related nightmares are particularly distressing, may impair functioning and increase risk of suicide. No specific pharmacologic agent has been demonstrated to impair dreaming. Inhibition of PTSD-related nightmares with pramipexole has not heretofore been described. Such a case is presented.

Case study - This 60 year-old male with PTSD and trauma-related nightmares upon introduction of pramipexole 0.5mg PO qHS for Restless Leg Syndrome (RLS) had total elimination of dreams, which recurred upon discontinuation of this agent as a result of insomnia and increased anxiety. A lower dose of 0.375mg qHS provided optimal RLS-symptom control and overall improved tolerance despite nightmare recurrence.

Abnormalities on Neurological examination: Recent recall: 2 of 4 objects without improvement with reinforcement. Able to spell the word “world” forwards but not backwards. Abstract thought impaired. Chemosensory testing: Anosmia and normogeusia. Motor: Drift: mild right pronator drift with right cerebellar spooning and right abductor digiti minimi sign. Reflexes: 3+ brachioradialis and biceps bilaterally, absent ankle jerks. Other: CT scan with and without contrast: normal.

Nightmares related to PTSD may occur during Rapid Eye Movement (REM) sleep and non-REM sleep. Underlying sympathetic activation may lead to disruptive motor behavior similar to that seen in REM sleep behavior disorder. The exact mechanism of action by which inhibition of dreams occurred with use of pramipexole is unclear. Such a response is consistent with prior documented evidence of REM sleep suppression with low-dose pramipexole such as it‘s efficacy in reducing the intensity and frequency of nightmares and dream enactment related to REM sleep behavior disorder. Further research on therapeutic interventions that target nightmares directly may be beneficial for the management of patients with PTSD.

To describe the effect of supplemental psychotropic medications, specifically anxiolytics with sedative/hypnotics (ASH) combined with lamotrigine (LTG) on stabilization of symptoms in patients with bipolar I disorder.

Symptomatic patients participating in two LTG maintenance trials were classified post-hoc as those initiating LTG as monotherapy (n=313) or as adjunctive therapy (n=814) and further characterized by supplemental add-on therapies received during an open-label treatment phase. Patients were considered stabilized if they reached a stable dose of LTG monotherapy (100–200 mg/day) and had a Clinical Global Impressions-Severity scale score ≤3 for at least 4 weeks. Stabilization rates were compared across initial- and supplemental-treatment groups.

Patients who initiated and were maintained on LTG monotherapy were stabilized at a slightly higher rate compared with those taking LTG adjunctive therapy (55% vs 48%; P=.080). Stabilization rates were numerically higher for LTG monotherapy patients who later received only ASH as supplemental medication compared with LTG monotherapy throughout, but this difference was not significant (66% vs 55%; P=.271). Stabilization rates were significantly higher for monotherapy patients who later received ASH alone versus other psychotropic medications (66% vs 28%; P=.001). For patients initiating LTG as adjunctive therapy, adding ASH alone resulted in significantly higher stabilization rates than adding another psychotropic medication (62% vs 33%; P<.001).

LTG and adjunctive treatment with ASH may be useful in the treatment of acute mood symptoms in patients with bipolar I disorder.