topiramate and Psychomotor-Agitation

Dementia, besides the dominant cognitive disorders that define it, is associated with behavioral disturbances, the consequences of which are, on various levels, a determining factor for the handling of these patients. The treatment of behavioral and psychological symptoms is essential and although, to date, no therapeutic solution is satisfactory, it is necessary to look for an alternative to the neuroleptics usually employed, which raise real problems of tolerance in this geriatric population.. For several years, anticonvulsants, among which some have shown mood stabilizing activity, have been the object of research in this indication. The purpose of this review of the literature is to assess the interest and the limits of anticonvulsant mood stabilizers (carbamazepine, valproic acid, gabapentin, lamotrigine, topiramate, oxcarbazepine) in the treatment of the so-called "noncognitive" symptoms of dementia. Their mechanism of action in mood disorders is not well known, but it would appear to be via the modulation of glutamate-mediated excitatory synaptic transmission and gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission that anticonvulsants might reduce behavioral symptoms in demented patients.. The method employed in this work was a systematic bibliographic review, in which only the double-blind placebo-controlled studies or the clinically detailed enough open-labelled studies using validated scales were retained.. Among these medications, only carbamazepine demonstrated its efficacy in behavioral and psychological symptoms of dementia (BPSD) in controlled studies, notably that of Tariot et al. [J Am Geriatr Soc 42 (1994) 1160-1166 and Am J Psychiatry 155 (1998) 54-61] and Olin et al. [Am J Geriatr Psychiatry 9 (2001) 400-405], but with significant adverse events (sedation, hyponatremia, cardiac toxicity), particularly in the elderly and, being a strong enzymatic inducer, with a high likelihood of drug-drug interactions. Valproic acid showed some interesting results in BPSD within a large number of open studies and case reports. However, among the five controlled studies that have been published [Curr Ther Res 62 (2001) 51-67; Am J Geriatr Psychiatry 9 (2001) 58-66; Int J Geriatr Psychiatry 17 (2002) 579-585; Curr Alzheimer Res 2 (2005) 553-558 and Am J Geraitr Psychiatry 13 (2005) 942-945], none confirmed its efficacy on these symptoms. Regarding its tolerability in the geriatric population, no notable major side effect was reported (haematologic and hepatic effects are not more frequent than in the general population), except possible excessive sedation. Moreover, it appears that valproic acid could have neuroprotective effects, even if the contrary has been observed in a recent study. More studies need to be (and are being) conducted, notably on the interest of valproic acid in prophylaxis of BPSD. Gabapentin seems to be worthwhile and well tolerated in this indication, but no controlled study has been conducted to prove its efficacy, even if a quite important number of case reports and open studies have shown encouraging results. Concerning lamotrigine, which may potentially induce severe cutaneous side effects when administered with valproic acid, this drug has shown its efficacy in bipolar disorders and two recent case reports seem to indicate some interest in BPSD. Furthermore, lamotrigine appears to have neuroprotective effects. Although topiramate has shown interesting results in one open study in BPSD, its use in demented patients cannot be recommended because of its deleterious effect on cognitive functions. Oxcarbazepine, theoretically, could be an alternative to carbamazepine, which is, as aforesaid, the only anticonvulsant that proved its interest in BPSD. However, no clinical study has yet been published to support this hypothesis. This drug is better tolerated than carbamazepine, but induces severe and more frequent hyponatremia.. Finally, although we all know that antipsychotics should no longer be prescribed in the elderly, the treatment of behavioral and psychological symptoms of dementia remains a difficult problem, considering the lack of a real alternative to these medications. Anticonvulsant mood stabilizers are an interesting solution but none of them, other than carbamazepine, which did, but which is not better tolerated than the usual drugs in this population - was able to prove its efficacy in this indication. Among these medications, valproic acid, gabapentin and lamotrigine should be studied further, and the neuroprotective effect of some of them is an interesting route for research.

Topics: Aged; Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Dementia; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Oxcarbazepine; Psychomotor Agitation; Topiramate; Treatment Outcome; Triazines; Valproic Acid

Behavioral disturbances are determining factors in handling patients with Alzheimer dementia. The current pharmacotherapy for behavioral symptoms associated with dementia is not satisfactory. Our goal was to compare a new anticonvulsant, topiramate, with a usually used medication, risperidone, for controlling behavioral disturbances of patients with Alzheimer dementia.. Elderly patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of Alzheimer disease and significant behavioral disturbances were randomized to receive, for a period of 8 weeks, a flexible dose of either topiramate (25-50 mg/d) or risperidone (0.5-2 mg/d). Outcome measures were the Cohen-Mansfield Agitation Inventory, Neuropsychiatry Inventory parts 1 and 2, and the Clinical Global Impression.. Forty-eight patients were randomized to treatment with either topiramate or risperidone, and 41 patients (21 of 25 in topiramate group and 20 of 23 in risperidone group) completed the trial. Both groups showed significant improvement in all outcome measures without important difference (Neuropsychiatry Inventory total score P < 0.531, Z = 0.62; Cohen-Mansfield Agitation Inventory P < 0.927, Z = 0.09; Clinical Global Impression, P < 0.654, Z = 0.48). There were no significant changes in the cognitive status of patients (assessed by Mini-Mental Status Examination) taking topiramate or risperidone during the trial.. Treatment with a low dose of topiramate (25-50 mg/d) demonstrated a comparable efficacy with risperidone in controlling behavioral disturbances of patients with Alzheimer dementia.

Topics: Aged; Alzheimer Disease; Anticonvulsants; Antipsychotic Agents; Behavioral Symptoms; Caregivers; Double-Blind Method; Female; Fructose; Humans; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Risperidone; Topiramate; Treatment Outcome

Many patients with Lewy body dementia develop visual hallucinations and other psychiatric symptoms. These patients are hypersensitive to antipsychotic drugs. Although patients tolerate atypical better than typical antipsychotics, both types can cause major extrapyramidal side effects. The anticonvulsant mood stabilizer topiramate, which does not cause parkinsonism, has been used as adjuvant therapy for both the positive and negative symptoms of schizophrenia; these symptoms can resemble those of Lewy body dementia. This report documents a 65-year-old woman with a 3-year history of progressive dementia that over the past 2 years had become complicated by severe extrapyramidal symptoms and agitated hallucinations. Her hallucinations became daily and were disrupting to her family. She was given a clinical diagnosis of Lewy body dementia after imaging and laboratory studies ruled out other etiologies. Treatment with olanzapine relieved her psychotic symptoms but caused severe dystonias, daily myoclonic jerks, and tremors. Stopping the olanzapine and starting topiramate 25 mg daily eliminated the hallucinations and agitation without worsening her extrapyramidal side effects. However, the topiramate was stopped because the patient reportedly developed anorexia and significant weight loss. Her hallucinations returned. When topiramate was reinstated at 12.5 mg a day, her agitation resolved, although her hallucinations continued. After 6 months on this dose, her agitation was still fairly well controlled without serious side effects or worsening of her parkinsonian symptoms.

Topics: Aged; Anticonvulsants; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Female; Fructose; Hallucinations; Humans; Lewy Body Disease; Neuroprotective Agents; Olanzapine; Psychomotor Agitation; Schizophrenia; Topiramate; Treatment Outcome

The use of topiramate therapy to control the neuropsychiatric and behavioral disturbances in individuals with mental and/or developmental disabilities with co-occurring psychiatric disturbances has become a standard of practice in many long-term care assisted living facilities. With increased utilization of this anticonvulsant, there has been a rise in the number documented cases of agitation and/or aggressive behavior associated with topiramate therapy. It is the purpose of this article to explore the current literature documenting the connection between topiramate utilization and the development of aggressive and/or agitated behavior.

Topics: Adult; Aggression; Anticonvulsants; Epilepsy; Fructose; Humans; Male; Mental Disorders; Psychomotor Agitation; Topiramate

Topiramate is an antiepileptic drug, recently also used in the treatment of psychiatric diseases. Inasmuch as topiramate and valproate, which are currently used for aggressive behavior, share several pharmacological mechanisms (positive modulatory effect on the GABA activity and negative modulatory effect on glutamatergic neurotransmission), the objective of the present study was to compare the pharmacological effects of topiramate with those of valproate and their combination in patients with psychiatric disorders showing marked aggression and agitation. A retrospective, case-controlled, mirror-image study was carried out in a sample of 45 inpatients affected by schizophrenia, schizoaffective and bipolar disorder, and hospitalized in a maximum-security Canadian psychiatry hospital. Overt Aggression Scale, Agitation-Calmness Evaluation Scale, number and intensity of psychotic episodes, number of episodes of withdrawal from group activities per week, and number of therapeutic isolation per week and of strict surveillance intervention per week were evaluated before and after the treatments. Results indicate that patients treated with topiramate show a decrease in the average score of the Overt Aggression Scale, a decrease of episodes of agitation and of strict surveillance interventions. This effect was similar to the group treated with valproate or with the combination of valproate-topiramate. However, valproate therapy, but not topiramate therapy, decreased the intensity of agitation episodes measured by the Agitation-Calmness Evaluation Scale; valproate and the combination topiramate-valproate decreased the number of psychotic disorganization episodes as well. These results suggest that topiramate could be a valid medicine in the control of aggression in psychosis. Double-blind, randomized, placebo-controlled studies need to further assess this pharmacological indication.

Topics: Adult; Aggression; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Case-Control Studies; Drug Therapy, Combination; Female; Fructose; Humans; Male; Patient Dropouts; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Topiramate; Treatment Outcome; Valproic Acid

Published literature on the toxicity of a topiramate overdose is limited to case reports. This retrospective study of poison center data was performed to examine the severity of topiramate overdoses. Data on single substance exposures to topiramate reported to the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS) in 2000 and 2001 were retrospectively analysed. A total of 567 cases met the inclusion criteria, of which 39% occurred in adults over 19 years of age and 30.2% in children < or = 4 years old. The majority of patients (62.1%) experienced no toxicity. The most common clinical effects reported were drowsiness/lethargy (15.5%), dizziness/vertigo (4.9%), agitation (4.9%), confusion (3.9%), nausea (2.6%) and vomiting (2.5%). Symptomatic patients were older than asymptomatic patients and adults were more likely to be managed in a healthcare facility (P <0.0001). Patients who received gastrointestinal decontamination experienced less serious outcomes than those without decontamination (P <0.02). It is concluded that clinicians should expect relatively mild mental status changes in adults or children with toxicity from topiramate overdose. Serious toxic effects, such as CNS depression with respiratory depression or persistent non-anion gap metabolic acidosis, are infrequent.

Topics: Adolescent; Adult; Age Factors; Anticonvulsants; Child; Child, Preschool; Cohort Studies; Dizziness; Drug Overdose; Female; Fructose; Humans; Male; Poison Control Centers; Psychomotor Agitation; Retrospective Studies; Sleep Stages; Topiramate; United States