RESUMEN
The authors review the literature from the last year examining the benefits of cholinesterase inhibitors in the treatment of behavioral disturbance in Alzheimer's disease (AD) and other dementias. Previous review has indicated that cholinesterase inhibitors have psychotropic properties. We found more evidence to support both the benefits of cholinesterase inhibitors in behavioral disturbance, and that specific behaviors may be selectively responsive to treatment.
Asunto(s)
Inhibidores de la Colinesterasa/uso terapéutico , Demencia/psicología , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/etiología , Anciano , Anciano de 80 o más Años , Inhibidores de la Colinesterasa/efectos adversos , Demencia/clasificación , HumanosRESUMEN
BACKGROUND: The efficacy of extended-release physostigmine salicylate, an acetylcholinesterase inhibitor, was evaluated in 850 subjects with mild-to-moderate Alzheimer disease (AD) in a multicenter trial. METHODS: Subjects initially entered a dose-enrichment phase in which they received 1 week each of physostigmine salicylate, 24 mg/d and 30 mg/d, and daily placebo. Among the subjects who completed this phase, 35.9% responded to physostigmine treatment, whereas 62.4% were considered nonresponders, and 1.6% could not be evaluated because of missing data. After a 4-week placebo-washout phase, 176 responder subjects were randomized to receive their best dose of physostigmine or placebo in a 12-week double-blind phase. Primary efficacy measures included the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), the Clinician's Interview-Based Impression of Change With Caregiver Input (CIBIC+), and the Clinical Global Impression of Change (CGIC). RESULTS: In the intent-to-treat analysis of the double-blind phase, physostigmine-treated subjects scored -2.02 points better than placebo-treated subjects on the ADAS-Cog (F1,167 = 6.42 [P = .01]) and 0.33 points higher on the CIBIC+ (F1,150 = 5.68 [P = .02]). No significant improvement was observed on the CGIC or the secondary outcome measures. Nausea and vomiting were experienced by 47.0% of all physostigmine-treated subjects during the double-blind phase. CONCLUSIONS: Physostigmine demonstrated a statistically significant benefit compared with placebo on a clinical global rating of change and an objective test of cognitive function. Given the frequency of gastrointestinal side effects, the role of this agent in clinical use remains to be determined.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/uso terapéutico , Fisostigmina/uso terapéutico , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Inhibidores de la Colinesterasa/administración & dosificación , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/psicología , Preparaciones de Acción Retardada , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Pruebas Neuropsicológicas , Fisostigmina/administración & dosificación , Fisostigmina/efectos adversos , Placebos , Resultado del Tratamiento , Vómitos/inducido químicamenteRESUMEN
OBJECTIVE: Glutamatergic neurotransmission is important for memory and cognition and is severely affected in Alzheimer's disease. D-Cycloserine exhibits partial agonist activity at the glycine site of N-methyl-D-aspartate subtype glutamate receptor, facilitating activation of the receptor and improving cognition and memory. METHOD: Seventeen patients with Alzheimer's disease received a three-phase, double-blind, placebo-controlled trial of 50 mg and 100 mg/day of D-cycloserine. RESULTS: D-Cycloserine was associated with significant improvement in scores on the cognitive subscale of the Alzheimer's Disease Assessment Scale (improvement of 3.0 points) when given at a dose of 100 mg/day. CONCLUSIONS: D-Cycloserine has cognitive benefits for patients with Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Trastornos del Conocimiento/tratamiento farmacológico , Cicloserina/administración & dosificación , Anciano , Enfermedad de Alzheimer/psicología , Cognición/efectos de los fármacos , Trastornos del Conocimiento/psicología , Cicloserina/farmacología , Cicloserina/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Glicina/metabolismo , Humanos , Masculino , Memoria/efectos de los fármacos , Persona de Mediana Edad , Placebos , Escalas de Valoración Psiquiátrica , Receptores de N-Metil-D-Aspartato/efectos de los fármacosRESUMEN
D-cycloserine is a partial agonist on the glycine site of the N-methyl-D-aspartate glutamate receptor. This double-blind crossover study of 15 mg D-cycloserine in Alzheimer's disease patients did not demonstrate clinical benefit. Higher medication dosage or long-term treatment may be required.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Cicloserina/uso terapéutico , Agonistas de Aminoácidos Excitadores/uso terapéutico , Anciano , Análisis de Varianza , Cognición/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Proyectos Piloto , Resultado del TratamientoRESUMEN
OBJECTIVE: Tardive dystonia, historically combined with tardive dyskinesia, is now viewed as probably having a different pathophysiology, course, outcome, and treatment response than tardive dyskinesia. In addition, patients with tardive dystonia are reported to be younger, and most are men. This study evaluates characteristics of 32 patients with tardive dystonia and compares results to other reports. METHOD: Twenty-four patients had been referred for research purposes and were videotaped, while eight had been followed clinically. Two of the authors reviewed all available videotapes and clinical reports to assess the course of symptoms over time. For global ratings and ratings of affected body parts, two scales were used: the Abnormal Involuntary Movement Scale (AIMS) for tardive dyskinesia and a similar scale for tardive dystonia. The method of case finding does not provide incidence or prevalence data for tardive dystonia. RESULTS: Fifty-nine percent of the patients experienced onset of tardive dystonia symptoms within 6 years of antipsychotic drug exposure; women had a shorter exposure time. No patient had complete remission of tardive dystonia symptoms, and 22 were moderately or severely impaired when their movements were most prominent. CONCLUSIONS: While epidemiological studies of tardive dystonia have yet to be performed, these results support the observations of others that most patients with tardive dystonia are men, have a short history of exposure to antipsychotic drugs, and may initially present with blepharospasm. Tardive dystonia rarely remits completely, can cause notable disability, and may partially respond to anticholinergic agents.
Asunto(s)
Antipsicóticos/efectos adversos , Discinesia Inducida por Medicamentos/diagnóstico , Distonía/inducido químicamente , Adulto , Factores de Edad , Anciano , Antipsicóticos/administración & dosificación , Diagnóstico Diferencial , Discinesia Inducida por Medicamentos/etiología , Discinesia Inducida por Medicamentos/fisiopatología , Distonía/diagnóstico , Distonía/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Humor/tratamiento farmacológico , Examen Neurológico , Trastornos Psicóticos/tratamiento farmacológico , Factores Sexuales , Factores de TiempoRESUMEN
In a double-blind, random-assignment, parallel-group trial, outpatients with major depression received either the new antidepressant clovoxamine, the tricyclic amitriptyline, or placebo for 6 weeks. By an "improvement" criterion of 50% or greater improvement in the Hamilton Depression Scale (HAM-D) total score, 88% of clovoxamine completers improved versus 75% with amitriptyline and 43% with placebo; however, due to small numbers, the differences failed to reach statistical significance. Diminished salivary flow was significantly greater with amitriptyline, as were complaints of dry mouth, somnolence, dizziness, and headache. Nausea and vomiting were more common in the clovoxamine-treated group. With amitriptyline, but not with clovoxamine, memory performance declined over a month. However, psychomotor performance was not affected.
Asunto(s)
Amitriptilina/uso terapéutico , Antidepresivos , Trastorno Depresivo/tratamiento farmacológico , Oximas/uso terapéutico , Adulto , Amitriptilina/efectos adversos , Trastorno Depresivo/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oximas/efectos adversos , Escalas de Valoración Psiquiátrica , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
We treated 65 outpatients with RDC major depression in a randomized, prospective, double-blind comparison of oral L-tyrosine, 100 mg/kg/day, imipramine, 2.5 mg/kg/day, or placebo for 4 weeks. Tyrosine increased and imipramine decreased 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion significantly, but there was no evidence that tyrosine had antidepressant activity. The only side effect to achieve statistical significance was greater dry mouth with imipramine. MHPG excretion and plasma amino acid concentrations failed to predict or correlate with clinical improvement.
Asunto(s)
Trastorno Depresivo/tratamiento farmacológico , Tirosina/uso terapéutico , Adulto , Trastorno Depresivo/psicología , Método Doble Ciego , Femenino , Humanos , Imipramina/uso terapéutico , Masculino , Metoxihidroxifenilglicol/orina , Persona de Mediana Edad , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
S-adenosyl-l-methionine (SAMe), a naturally occurring brain metabolite, has previously been found to be effective and tolerated well in parenteral form as a treatment of major depression. To explore the antidepressant potential of oral SAMe, we conducted an open trial in 20 outpatients with major depression, including those with (n = 9) and without (n = 11) prior history of antidepressant nonresponse. The group as a whole significantly improved with oral SAMe: 7 of 11 non-treatment-resistant and 2 of 9 treatment-resistant patients experienced full antidepressant response. Side effects were mild and transient.
Asunto(s)
Trastorno Depresivo/terapia , S-Adenosilmetionina/administración & dosificación , Administración Oral , Adulto , Ensayos Clínicos como Asunto , Trastorno Depresivo/sangre , Trastorno Depresivo/psicología , Dexametasona , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Método Simple Ciego , Tirotropina/sangre , Hormona Liberadora de TirotropinaRESUMEN
The authors enrolled 21 patients in a random-order, crossover, double-blind trial of phosphatidylcholine (lecithin) 20 g/day and placebo. Fourteen patients completed at least 6 weeks of the second 8-week trial and were used for efficacy analyses. Side effects were minimal. The lecithin treatment effect--about one half of an Abnormal Involuntary Movement Scale point--was seen as a statistical effect of treatment order, based on differences between patients who took the active compound before or after they took the placebo. Clinically, however, the lecithin effect was negligible.
Asunto(s)
Discinesia Inducida por Medicamentos/tratamiento farmacológico , Fosfatidilcolinas/uso terapéutico , Adolescente , Adulto , Anciano , Actitud Frente a la Salud , Colina/sangre , Método Doble Ciego , Discinesia Inducida por Medicamentos/fisiopatología , Discinesia Inducida por Medicamentos/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Examen Físico , Placebos , Escalas de Valoración Psiquiátrica , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y CuestionariosRESUMEN
S-adenosyl-L-methionine (SAMe), a putative antidepressant, is a naturally occurring substance whose mechanism of action is still a matter of speculation. It has been recently postulated that SAMe may increase the dopaminergic tone in depressed patients. Since dopamine inhibits both thyrotropin (TSH) and prolactin secretion, we investigated the effects of treatment with SAMe on the TSH and prolactin response to thyrotropin-releasing-hormone (TRH) stimulation in 7 depressed outpatient women (mean age: 46.1 +/- 7.2 years) and 10 depressed outpatient men (mean age: 38.0 +/- 10.0 years) participating in a six-week open study of oral SAMe in the treatment of major depression. At the end of the study, there was a significant reduction after treatment with SAMe in the response of both prolactin and TSH to TRH stimulation in the group of depressed men compared to pre-treatment values. On the other hand, in the group of depressed women, the posttreatment prolactin response to TRH did not appear to change when compared to pre-treatment and the TSH response to TRH challenge tended even to augment slightly after treatment with SAMe. Our results, at least in depressed men, seem to support the hypothesis of a stimulating effect of SAMe on the dopaminergic system.
Asunto(s)
Antidepresivos , Trastorno Depresivo/tratamiento farmacológico , Prolactina/sangre , Receptores Dopaminérgicos/efectos de los fármacos , S-Adenosilmetionina/administración & dosificación , Tirotropina/sangre , Administración Oral , Adulto , Encéfalo/efectos de los fármacos , Trastorno Depresivo/sangre , Trastorno Depresivo/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Método Simple Ciego , Hormona Liberadora de TirotropinaRESUMEN
Of the first 60 patients treated at our clinic with the antidepressant fluoxetine, 5 (8.3%) developed treatment-emergent sexual dysfunction (anorgasmia and/or delayed orgasm). Three of those 5 patients had a history of treatment-emergent sexual dysfunction while receiving other antidepressant agents. Clinicians should be aware of this side effect of fluoxetine.
Asunto(s)
Fluoxetina/efectos adversos , Orgasmo/efectos de los fármacos , Disfunciones Sexuales Psicológicas/inducido químicamente , Adulto , Atención Ambulatoria , Trastornos de Ansiedad/tratamiento farmacológico , Trastorno Depresivo/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A total of 27 subjects began active treatment in this double-blind study comparing the efficacy and safety of trazodone and fluoxetine in geriatric depressed patients, but only 13 completed 6 weeks on study medication. Both agents were effective according to weekly and endpoint analyses, and there was no evidence of significant effects on blood pressure, pulse, or weight. Separate analysis of patients who had received an adequate trial of medication indicated a trend toward relatively more fluoxetine-treated patients meeting clinical criteria for resolved depression.
Asunto(s)
Trastorno Depresivo/tratamiento farmacológico , Fluoxetina/uso terapéutico , Trazodona/uso terapéutico , Trastorno Depresivo/psicología , Método Doble Ciego , Femenino , Fluoxetina/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Personalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Trazodona/efectos adversosRESUMEN
To evaluate anticholinergic effects on cognition and other functions, we studied 60 healthy volunteers in a double-blind crossover trial of two antiparkinsonian agents, benztropine and amantadine. Benztropine 4 mg/day, but not amantadine 200 mg/day, impaired free recall and perception of time, and subjects' perception of their own memory impairment was significantly greater with benztropine. Side effects in general were worse with benztropine, particularly such anticholinergic effects as dry mouth and blurred vision, and benztropine decreased measured salivary flow to a significantly greater degree than amantadine. Our findings support the hypothesis that drugs that decrease cholinergic transmission impair storage of new information into long-term memory, but have little effect on retrieval from memory or on tasks involving only immediate memory. Clinically, anticholinergic agents can levy a considerable burden on memory and time perception.
Asunto(s)
Amantadina/toxicidad , Benzotropina/toxicidad , Encéfalo/efectos de los fármacos , Memoria/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Receptores Colinérgicos/efectos de los fármacos , Tropanos/toxicidad , Adolescente , Adulto , Afecto/efectos de los fármacos , Nivel de Alerta/efectos de los fármacos , Atención/efectos de los fármacos , Ensayos Clínicos como Asunto , Método Doble Ciego , Humanos , Masculino , Persona de Mediana Edad , Distribución Aleatoria , Retención en Psicología/efectos de los fármacos , Salivación/efectos de los fármacos , Aprendizaje Seriado/efectos de los fármacosRESUMEN
Among approximately 1450 patients treated with neuroleptics in a short-term psychiatric hospital, there were no cases of the neuroleptic malignant syndrome (NMS). Six patients with histories of NMS were treated, either with nonneuroleptic therapies or with low doses of low-potency antipsychotic agents. No case of NMS developed, but one patient suffered transient subsyndromal signs while treated briefly with loxapine. Staff education, screening for patients with history of NMS, and detection of early signs can lower the incidence of this serious drug toxicity.
Asunto(s)
Trastornos Mentales/tratamiento farmacológico , Síndrome Neuroléptico Maligno/prevención & control , Readmisión del Paciente , Adulto , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Femenino , Educación en Salud , Humanos , Masculino , Anamnesis , Persona de Mediana Edad , Síndrome Neuroléptico Maligno/diagnóstico , Personal de Hospital/educaciónRESUMEN
Amnesia is the most common adverse effect among patients receiving electroconvulsive therapy. In a double-blind pilot study, patients receiving bilateral ECT were pretreated with ergoloid mesylates (N = 5) or placebo (N = 5). Consistent with the hypothesis that ergoloid mesylates might protect against ECT-associated amnesia, nonsignificant trends on some memory tests showed better performance for patients receiving active treatment. Unexpectedly, patients treated with ergoloid mesylates had a significantly better antidepressant response.
Asunto(s)
Amnesia/prevención & control , Trastorno Depresivo/terapia , Dihidroergotoxina/uso terapéutico , Terapia Electroconvulsiva , Amnesia/etiología , Ensayos Clínicos como Asunto , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/psicología , Dihidroergotoxina/farmacología , Método Doble Ciego , Terapia Electroconvulsiva/efectos adversos , Humanos , Memoria/efectos de los fármacos , Inventario de Personalidad , Proyectos Piloto , Escalas de Valoración PsiquiátricaRESUMEN
Based on the cholinergic-deficiency hypothesis of tardive dyskinesia (TD), we administered cytidine diphosphoryl choline (CDP-Choline) (a naturally occurring biochemical intermediary in the synthesis of phosphatidylcholine), 500 mg twice a day orally, to four women and one man with TD for 2 to 8 weeks in a double-blind, placebo-controlled crossover trial. Although the small sample size provides only limited power to detect a treatment effect, there was no evidence of efficacy, adverse effects, or changes in psychopathology.
Asunto(s)
Colina/análogos & derivados , Citidina Difosfato Colina/uso terapéutico , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Adulto , Ensayos Clínicos como Asunto , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Of 1,470 patients treated with neuroleptics during 1 year at a private psychiatric hospital, only one patient developed neuroleptic malignant syndrome--an annual frequency of 0.07%. Use of low doses of neuroleptics may account for this frequency, which is below recent estimates.