pregabalin and Psychomotor-Agitation

Behavioral disturbances and pain are common in nursing home (NH) patients with dementia. An association between pain and increased agitation has been suggested, and recently a significant reduction of agitation has been demonstrated by pain treatment in patients with moderate to severe dementia. We now examined which specific agitated behaviors respond to individualized pain treatment.. Cluster randomized clinical trial.. 60 clusters (i.e., clusters defined as single independent NH units) in 18 NHs within five municipalities of Western Norway.. 352 patients with moderate to severe dementia and clinically significant behavioral disturbances.. The control group received usual treatment and care. According to a predefined scheme for 8 weeks, all patients in the intervention group received individual daily pain treatment with acetaminophen, extended release morphine, buprenorphine transdermal patch, and/or pregabaline.. Cohen-Mansfield Agitation Inventory subscales and items.. Analyses demonstrated that Factor 3 (Verbally agitated behaviors) showed the largest significant difference (DF = 1204.0, t = -4.308, p <0.001), followed by Factor 2 (Physically non-aggressive behaviors) (DF = 1198.0, t = -2.672, p = 0.008), and Factor 1 (Aggressive behaviors) (DF = 1196.0, t = -2.093, p = 0.037) after 8 weeks, by a linear random intercept mixed model in two-way repeated-measures configuration with adjustment for heteroscedasticity.. We found that verbal agitation behaviors such as complaining, negativism, repetitious sentences and questions, constant request for attention, and cursing or verbal aggression responded to pain treatment. In addition, restlessness and pacing were sensible to analgesics. Such behaviors should therefore lead to an assessment of pain, and pain treatment. Further studies comparing how pain treatment should be balanced against other strategies including psychotropic drugs are needed.

Topics: Acetaminophen; Aged, 80 and over; Analgesics; Buprenorphine; Delayed-Action Preparations; Dementia; Female; gamma-Aminobutyric Acid; Humans; Male; Morphine; Norway; Nursing Homes; Pain; Pain Management; Pregabalin; Psychomotor Agitation; Transdermal Patch

Pregabalin (PGB) is an analog of the inhibitory neurotransmitter gamma-aminobutyric acid. The currently available evidence favors the misuse and abuse potential of PGB. However, its neurotoxicity remains unclear. Therefore, this study assessed the toxic effects of chronic pregabalin dependence as well as withdrawal on the cortical neurons of the frontal lobe. This study included eighty adult male albino rats which were divided into three groups. Group I (Control) included 40 rats and was further subdivided into two equal subgroups (IA and IB) as negative and positive controls. Group II (PGB-dependent) included 20 rats which received PGB starting with the therapeutic dose (300 mg/day), then the doses were gradually increased until they reached the dependent dose (3400 mg/day) by the end of the first month. Further, the dependent dose was given daily for another 2 months. Group III (PGB withdrawal) included 20 rats which received PGB as described in group II. After that, administration of PGB was stopped and the rats were kept for another one month. By the end of the experiment, all animals were sacrificed by cervical decapitation. The specimens were taken from the frontal cortex for histologic and immunohistochemical staining as well as morphometric analysis. Sections of the frontal cortex of group II showed changes in the form of disturbed architectural pattern of cortical layers, apoptotic cells, weak immunoexpression of Bcl-2 and VEGF as well as moderate-strong immunoexpression of iNOS and nestin. These expressions were significantly different from the control groups, but they were non-significant in comparison with group III. These findings indicate that chronic PGB dependence induces neurotoxic effects mainly in the form of neuronal apoptosis, gliosis, and oxidative stress injury of the frontal cortex. The PGB- induced neurotoxic effects persisted after withdrawal. The influence of these neurotoxic effects and their relevance to the cognitive or neurologic disorders in PGB-dependent individuals warrants further research. Furthermore, it is recommended to quantify the behavioral changes related to PGB dependence as well as withdrawal in future studies.

Topics: Aggression; Animals; Behavior, Animal; Frontal Lobe; Irritable Mood; Male; Nestin; Neuroglia; Neurons; Nitric Oxide Synthase Type II; Pregabalin; Proto-Oncogene Proteins c-bcl-2; Psychomotor Agitation; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders; Vascular Endothelial Growth Factor A

Oxaliplatin, a platinum derivative used in the treatment of gastrointestinal cancers, has been associated with sensory neuropathies and, more infrequently, a neuromyotonia-like hyperexcitability syndrome. We present a case of hyperexcitability syndrome that developed during the treatment of pancreatic cancer with oxaliplatin and gemcitabine (GEMOX) that was successfully treated with pregabalin.. A 54-year-old woman was undergoing chemotherapy with gemcitabine and oxaliplatin (GEMOX) for stage II-B pancreatic adenocarcinoma. On the third day of her fourth cycle, she presented with twitching of eyelids and tremors of hands. This twitching started bilaterally on the eyelids, followed by teeth jittering, hand shaking, and slurring of speech. A thorough neurological exam revealed no abnormalities except increased tone of both hands-she had difficulty opening her hand after closing it for a hand-grip. She was given a dose of 1 g of IV magnesium sulfate and 1 g of IV calcium gluconate, and 50 mg of IV diphenhydramine. In addition to reassurance, pregabalin was prescribed for these myotonic symptoms at a dosage of 50 mg by mouth three times daily. Improvement occurred in these symptoms within 12 h and she was almost asymptomatic within 72 h.. Oxaliplatin causes a unique spectrum of acute neurological toxicities that have not been observed in patients receiving either cisplatin or carboplatin. Clinically, sensory alterations are most prominent, particularly cold-induced and perioral paresthesias. Other symptoms, such as cramps, jaw stiffness, voice changes, ptosis, and visual field changes suggest that motor nerves or muscles may also be involved (hyperexcitability). Hyperexcitability syndrome, distinct from cold-induced paresthesias and sensory neuropathy, is a rare complication of oxaliplatin chemotherapy; and up to date no pharmacotherapy has been successful in treating these symptoms. This is the first report of the successful amelioration of this syndrome with the antiepileptic pregabalin.

Topics: Adenocarcinoma; Adult; Anticonvulsants; Antimetabolites, Antineoplastic; Antineoplastic Agents; Calcium Gluconate; Deoxycytidine; Diphenhydramine; Female; gamma-Aminobutyric Acid; Gemcitabine; Histamine H1 Antagonists; Humans; Magnesium Sulfate; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Pregabalin; Psychomotor Agitation