Clinical Neuropharmacology

Factors Associated With Delirium in Surgical Intensive Care Unit Patients Treated With Supplemental Melatonin: A Case-Cohort Study Objectives Intensive care unit (ICU) delirium is a common neuropsychiatric syndrome that confers significant morbidity and mortality. Melatonin is an endogenous neurohormone involved with regulating sleep-wake cycles and has been found to be disturbed in ICU delirium. We hypothesized that there are independent factors that predict delirium in a cohort of patients on melatonin in the surgical ICU (SICU). Methods A retrospective, observational case-cohort analysis of adult SICU patients was conducted. Cases were defined by testing positive on the Confusion Assessment Method for the ICU (CAM-ICU). Delirioprotective and deliriogenic factors were assessed prior to the studied melatonin administration. Results Forty-one CAM-ICU–positive cases and 59 CAM-ICU–negative controls were included. Higher mean Acute Physiology and Chronic Health Evaluation II scores were associated with delirium in univariable analysis. Stratified analysis found a higher incidence of delirium in baseline CAM-ICU–positive patients who experienced emergency surgery within 24 hours of admission compared with baseline CAM-ICU–negative patients after melatonin administration. Conclusions This study describes the use of melatonin in the SICU and characterizes the patients who receive it. Further research is needed to determine the role of melatonin in deliriogenesis and to clarify its utility as a delirioprotectant for postsurgical, critical care patients.

Effect of Duloxetine for the Treatment of Chronic Central Poststroke Pain Objectives Central poststroke pain (CPSP) is the neuropathic pain in areas of the body corresponding to stroke lesions. It is often refractory to treatment, reduces quality of life, and impedes rehabilitation. The pharmacological treatment of CPSP is challenging. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is known to be effective against neuropathic pain. The current study describes the efficacy of duloxetine in reducing pain severity in CPSP patients. Subjects and Methods For the purpose of this study, CPSP was defined as spontaneous pain within an area of the body corresponding to the brain lesion that emerged at or after stroke onset. Any previously prescribed medical therapy for the patients was not changed or stopped; duloxetine 30 mg was added to their ongoing treatment. Pain was assessed at baseline and thereafter at 1 and 3 weeks using Numeric Rating Scale (NRS) and Short-form MC Gill Pain Questionnaire scores. At the first follow-up, scores were reviewed and dose was doubled if no improvement or adverse effects were observed. Results From a total of 37 patients, 4 were withdrawn because of adverse effects including nausea, agitation, and somnolence. The mean elapsed time of observed symptoms since stroke onset was 3.1 ± 4.1 years. There was a significant difference between the mean values of Short-form MC Gill Pain Questionnaire and NRS scores at baseline and those at the follow-up assessment. Twenty-six (70.3%) of the patients showed at least 30% reduction of NRS compared with baseline at the third week. Conclusions Our findings suggest that duloxetine can be effective for managing CPSP.

The Dopamine Receptor Antagonism of Opipramol: Relevance to Parkinsonism? Drug-induced Parkinsonism (DIP) represents the second most-frequent etiology of Parkinson syndromes after neurodegenerative disorders. It has been described mainly for antipsychotics, Ca++-channel blockers, antiemetics, and gastrointestinal prokinetics. In this article, we present a clinical case series of 10 patients, retrieved within our movement disorders hospital, with DIP under intake of opipramol. Symptoms completely resolved after drug withdrawal, and associated risk factors were old age, high doses, and presence of cortical atrophy. This frequently prescribed anxiolytic drug has so far not been associated with DIP. Our objective is to raise awareness of DIP as an adverse effect of opipramol.

Chronotherapeutics: Recognizing the Importance of Timing Factors in the Treatment of Disease and Sleep Disorders This review describes the characteristics of a number of pathologies, which are considered from the point of view of chronobiology, that is, the way in which biological processes are expressed throughout the 24-hour day. This perspective is a relatively new way of thinking about disease and additionally about how to treat diseases. It has called attention to the importance of not only the quantity of a drug that is administered but also when it is administered. In addition, the review presents an overview of the emerging clinical strategies known as chronotherapeutics, that is, the effects of the daily scheduling of drug administration and the consequences of the activity and efficacy of therapies that are applied in this manner. This article also reviews innovative ways in which physicians are applying time-specified drug treatment (chronopharmacology) for sleep disorders. Here, we present a systematic description of chronopharmacology as well as definitions of key terms that, we believe, will be helpful for newcomers to the field. It is hoped that greater awareness of this new perspective on pharmacology will promote its adoption by researchers and clinicians.

An Option to Consider for Alternating Hemiplegia of Childhood: Aripiprazole Alternating hemiplegia of childhood (AHC) is an infrequent neurological disorder characterized by recurrent transient attacks of hemiplegia that last minutes to days and impress either side of the body, dystonic or tonic attacks, and nystagmus. Cognitive or neurological deficits with progressive course are another findings. Epileptic seizures may occur in some patients. We report the medical treatment in a case of AHC in a-12-year-old male patient with convulsions. The patient did not respond to available therapies for AHC, except for aripiprazole. After the initiation of aripiprazole therapy, duration and frequency of hemiplegia episodes were decreased. Also, he is currently seizure-free with topiramate treatment for 3 months. On follow-up, a compound heterozygous ATP1A3 mutation c.868C > T (p.R290C)/c.684 + 1G > A was determined. Aripiprazole may reduce the attacks of AHC, which are resistant to other available therapies.

Gabapentin-Associated Urinary Incontinence: A Case Verified by Rechallenge Introduction Gabapentin (GBP) is an analog of γ-aminobutyric acid and was originally designed as an anticonvulsant. Because its mechanism of action is unclear, assumed to have no abuse potential, and apparent lack of toxicity, GBP is used widely off-label to treat an array of disorders, including essential tremor. Case Report We present a case of an elderly woman diagnosed with essential tremor, in which GBP was initiated. In the following day, she complained of urinary incontinence with the absence of dysuria and urgency. It was not worse with movement, coughing, sneezing, or laughing. The vaginal parity of the patient was one. Laboratory tests and urinalysis were within normal limits. Assuming that the urinary symptom was an adverse drug reaction, the GBP was withdrawn and the patient's incontinence completely resolved within 2 days. Several weeks later, a rechallenge with GBP was tried. In the day 1 of GBP use, the subject reported intermittent urinary incontinence. Medication was discontinued and her continence returned. One year later, in the follow-up, the subject remained continent. Conclusions Only a few cases with GBP-associated urinary incontinence have been reported in the literature. To the authors' knowledge, these cases described individuals with only 1 attempt of the use of GBP. In this way, the present case was the first to describe a subject with the recurrence of urinary incontinence with the GBP rechallenge. This adverse effect, although not potentially fatal, can be very embarrassing to patients and lead to poor compliance with therapy.

Drug-Induced Parkinsonism Manifesting as Gait Freezing in a Patient With Traumatic Brain Injury: A Case Report Background Among the neuropsychiatric complications commonly induced by traumatic brain injury (TBI), behavioral disorders, such as agitation and aggression, can hinder neurological recovery and deteriorate rehabilitation outcomes. Pharmacological treatment for behavioral disorders might be beneficial but could lead to drug-induced parkinsonism. We report a case of a patient with drug-induced parkinsonism manifested as freezing of gait after TBI, which improved with the cessation of the offending drugs and comprehensive rehabilitation. Case Presentation A 35-year-old male patient left with a TBI after a car accident was referred to our hospital. He had been on many neuropsychiatric medications, including atypical antipsychotics, for his agitated behaviors. He could walk independently but showed freezing of gait at the initiation of his gait, when turning to the side, when reaching his destination, and passing through narrow corridors. Under the impression of drug-induced parkinsonism, we gradually tapered the patient off his neuropsychiatric medications. He also underwent comprehensive rehabilitation, including gait training under visual and auditory cues and balance training. Five weeks after admission to the hospital, the patient's freezing of gait improved, with disappearance of his hesitation at gait initiation and a decreased freezing duration while turning around. Conclusions This is a rare report of drug-induced parkinsonism manifested as freezing of gait, which showed improvement after discontinuation of the causative drugs and subsequent rehabilitation.

Levetiracetam-Related Mania-Like Symptoms: An Adolescent Case Levetiracetam is an antiepileptic agent that is used for partial and generalized epilepsy. Although it is well tolerated in most cases, behavioral and nonbehavioral adverse effects may be observed. Among behavioral symptoms, depression, hostility, and agitation have been frequently reported. However, mania or mania-like symptoms are relatively rare, especially in children and adolescents. Hereby, we report mania-like symptoms with levetiracetam use in a 15-year-old boy. Mania-like symptoms emerged 3 weeks after starting levetiracetam and disappeared after adding risperidone to ongoing levetiracetam treatment.

Sertraline-Related Amenorrhea in an Adolescent Amenorrhea is one of the clinical consequences of hyperprolactinemia. Although symptomatic hyperprolactinemia is among the well-described adverse reactions of antipsychotic agents, it may also be reported with the use of selective serotonin reuptake inhibitors. Hereby, we present a case of sertraline-related hyperprolactinemic amenorrhea in an adolescent. Amenorrhea occurred 2 months after starting sertraline, and menstrual cycle restored after stopping the treatment.

Two Cases of De Novo Pathological Gambling Associated With Aripiprazole Objectives Pathological gambling can be potentiated by treatment with dopamine agonists. Aripiprazole, bearing a partial agonist activity at dopamine D2 and D3 receptors, has also been linked to such a behavioral aberration, usually on subjects predisposed with tendency of impulsive or addictive behaviors. Methods Review of patient's medical records and literature review. Results Two young patients' pathological gambling emerged simply due to exposure to aripiprazole, neither related to manic or psychotic symptoms nor with history of addictive or impulsive behaviors. Their pathological gambling disappeared soon after switching aripiprazole to other antipsychotics. One patient has tested such a relationship by reexposure to aripiprazole while his compulsion to gamble recurred. Conclusions In addition to previously recognized risk factors, pathological gambling might occur in young patients whose history did not reveal an addictive tendency while they were sensitive to the pharmacological effect, as well as adverse effects, of psychotropic agents.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com