Asunto(s)
Benzodiazepinas/efectos adversos , Antagonistas de Dopamina/efectos adversos , Hipotálamo/efectos de los fármacos , Antagonistas de la Serotonina/efectos adversos , Aumento de Peso/efectos de los fármacos , Administración Oral , Proteína Relacionada con Agouti/metabolismo , Animales , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Expresión Génica/efectos de los fármacos , Hipotálamo/metabolismo , Leptina/sangre , Masculino , Proteínas del Tejido Nervioso/metabolismo , Neuropéptido Y/metabolismo , Olanzapina , Proopiomelanocortina/metabolismo , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas Wistar , Aumento de Peso/fisiologíaAsunto(s)
Ensayos Clínicos como Asunto/ética , Evaluación Preclínica de Medicamentos/ética , Fluorobencenos/uso terapéutico , Médicos Generales/ética , Piperidinas/uso terapéutico , Mala Conducta Científica/legislación & jurisprudencia , Antagonistas de la Serotonina/uso terapéutico , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Fluorobencenos/efectos adversos , Médicos Generales/legislación & jurisprudencia , Humanos , Masculino , Irlanda del Norte , Piperidinas/efectos adversos , Antagonistas de la Serotonina/efectos adversos , Resultado del TratamientoRESUMEN
The prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) continues to pose a challenge for clinicians. The development of 5-hydroxytryptamine (serotonin) antagonists and neurokinin-1 receptor antagonists (NK1 -RAs) have demonstrated significant improvements in acute and delayed CINV for highly and moderately emetogenic chemotherapy. Delayed and breakthrough CINV, however, continue to be difficult to manage despite available treatment agents. Randomized clinical trial data suggest that olanzapine, a second-generation thienobenzodiazepine, traditionally used in the treatment of manifestations of psychotic disorders, is an effective agent in these clinical settings. The short-term use of olanzapine has a favorable adverse event profile and was not associated with grade 3 or 4 toxicity in a phase III study. Olanzapine is recommended as an option within first-line prophylaxis for CINV in the National Comprehensive Cancer Network (NCCN) guidelines and is an option for treatment of refractory CINV in the Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology and NCCN guidelines.
Asunto(s)
Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Benzodiazepinas/uso terapéutico , Medicina Basada en la Evidencia , Náusea/prevención & control , Antagonistas de la Serotonina/uso terapéutico , Vómitos/prevención & control , Antieméticos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Benzodiazepinas/efectos adversos , Instituciones Oncológicas , Humanos , Agencias Internacionales , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Olanzapina , Guías de Práctica Clínica como Asunto , Antagonistas de la Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Sociedades Hospitalarias , Sociedades Médicas , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológicoRESUMEN
(E)-methyl isoeugenol (MIE) is a natural food flavour that constitutes 93.7% of an essential oil from Pimenta pseudocaryophyllus leaf. The leaf extracts of this species are used as a calming agent. As a ubiquitous food additive, the application of MIE for treating mood disorders appears to be globally attractive. Hence, we sought to evaluate general pharmacological activities, anticonvulsant, anxiolytic and antidepressant effects and the possible mechanisms of MIE actions. Administration of MIE was carried out prior to the exposure of a male Swiss mice to general behavioural tests, barbiturate sleep, PTZ-induced convulsion, light dark box (LDB), elevated plus maze (EPM), wire hanging, open field (OF) and forced swimming test (FST). The involvement of monoamine system was studied by mice pretreatment with WAY100635 (antagonist of 5-HT1A), α-methyl-p-tyrosine (AMPT; depletor of catecholamine) or p-chlorophenylalanine (PCPA; depletor of serotonin storage). There was no record of neurotoxic effect or animal's death during the course of general pharmacological tests. MIE at 250 and 500 mg kg(-1) potentiated the hypnotic effect of sodium pentobarbital. However, MIE did not protect against PTZ-induced convulsion. Except for MIE at 500 mg kg(-1), parameters evaluated in the LDB, EPM and OF demonstrated an anxiolytic like property of MIE. This effect was blocked by WAY100635 pretreatment. MIE at 500 mg kg(-1) elicited a reduction in locomotor activity of the mice in the OF. Anti-immobility effect of MIE 250 mg kg(-1) in the FST suggested an antidepressive like property. Unlike AMPT, pretreatment with PCPA reversed the antidepressant like effect of MIE. Our findings demonstrated anxiolytic and antidepressant like properties of (E)-methyl isoeugenol and suggested the participation of serotonergic pathways.
Asunto(s)
Anisoles/farmacología , Ansiolíticos/farmacología , Antidepresivos/farmacología , Aromatizantes/farmacología , Extractos Vegetales/farmacología , Animales , Relación Dosis-Respuesta a Droga , Fenclonina/efectos adversos , Masculino , Ratones , Condicionamiento Físico Animal , Piperazinas/efectos adversos , Piridinas/efectos adversos , Serotonina/sangre , Antagonistas de la Serotonina/efectos adversos , alfa-Metiltirosina/efectos adversosRESUMEN
Aspartame is one of the most widely used artificial sweeteners globally. Data concerning acute neurotoxicity of aspartame is controversial, and knowledge on its chronic effect is limited. In the current study, we investigated the chronic effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter concentrations in the brain. Our results showed that aspartame at high dose caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We also investigated the effects of aspartame on brain regional monoamine synthesis, and the results revealed that there was a significant decrease of dopamine in corpus striatum and cerebral cortex and of serotonin in corpus striatum. Moreover, aspartame treatment significantly alters the tyrosine hydroxylase activity and amino acids levels in the brain. Our data suggest that chronic use of aspartame may affect electrolyte homeostasis and monoamine neurotransmitter synthesis dose dependently, and this might have a possible effect on cognitive functions.
Asunto(s)
Apoptosis , Aspartame/efectos adversos , Corteza Cerebral/metabolismo , Cuerpo Estriado/metabolismo , Antagonistas de Dopamina/efectos adversos , Edulcorantes no Nutritivos/efectos adversos , Antagonistas de la Serotonina/efectos adversos , Animales , Aspartame/administración & dosificación , Corteza Cerebral/enzimología , Cuerpo Estriado/enzimología , Antagonistas de Dopamina/administración & dosificación , Masculino , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/metabolismo , Neuronas/enzimología , Neuronas/metabolismo , Síndromes de Neurotoxicidad/enzimología , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/metabolismo , Edulcorantes no Nutritivos/administración & dosificación , Fenilalanina/agonistas , Fenilalanina/metabolismo , Distribución Aleatoria , Ratas Wistar , Antagonistas de la Serotonina/administración & dosificación , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Pruebas de Toxicidad Crónica , Triptófano/antagonistas & inhibidores , Triptófano/metabolismo , Tirosina/agonistas , Tirosina/metabolismo , Tirosina 3-Monooxigenasa/antagonistas & inhibidores , Tirosina 3-Monooxigenasa/metabolismo , Desequilibrio Hidroelectrolítico/enzimología , Desequilibrio Hidroelectrolítico/etiología , Desequilibrio Hidroelectrolítico/metabolismoRESUMEN
Psychostimulant abuse is a serious social and health problem, for which no effective treatments currently exist. A number of review articles have described predominantly 'clinic'-based pharmacotherapies for the treatment of psychostimulant addiction, but none have yet been shown to be definitively effective for use in humans. In the present article, we review various 'hypothesis'- or 'mechanism'-based pharmacological agents that have been studied at the preclinical level and evaluate their potential use in the treatment of psychostimulant addiction in humans. These compounds target brain neurotransmitter or neuromodulator systems, including dopamine (DA), gamma-aminobutyric acid (GABA), endocannabinoid, glutamate, opioid and serotonin, which have been shown to be critically involved in drug reward and addiction. For drugs in each category, we first briefly review the role of each neurotransmitter system in psychostimulant actions, and then discuss the mechanistic rationale for each drug's potential anti-addiction efficacy, major findings with each drug in animal models of psychostimulant addiction, abuse liability and potential problems, and future research directions. We conclude that hypothesis-based medication development strategies could significantly promote medication discovery for the effective treatment of psychostimulant addiction.
Asunto(s)
Estimulantes del Sistema Nervioso Central , Trastornos Relacionados con Sustancias/rehabilitación , Animales , Encéfalo/efectos de los fármacos , Moduladores de Receptores de Cannabinoides/metabolismo , Trastornos Relacionados con Cocaína/diagnóstico , Trastornos Relacionados con Cocaína/psicología , Trastornos Relacionados con Cocaína/rehabilitación , Dopamina/metabolismo , Agonistas de Dopamina/efectos adversos , Agonistas de Dopamina/uso terapéutico , Antagonistas de Dopamina/efectos adversos , Antagonistas de Dopamina/uso terapéutico , Evaluación Preclínica de Medicamentos , Agonistas de Aminoácidos Excitadores/efectos adversos , Agonistas de Aminoácidos Excitadores/uso terapéutico , Agonistas del GABA/efectos adversos , Agonistas del GABA/uso terapéutico , Inhibidores de Recaptación de GABA , Ácido Glutámico/metabolismo , Humanos , Antagonistas de Narcóticos/efectos adversos , Antagonistas de Narcóticos/uso terapéutico , Receptores AMPA/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Antagonistas de la Serotonina/efectos adversos , Antagonistas de la Serotonina/uso terapéutico , Agonistas de Receptores de Serotonina , Trastornos Relacionados con Sustancias/diagnóstico , Trastornos Relacionados con Sustancias/psicología , Resultado del Tratamiento , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Ácido gamma-Aminobutírico/metabolismoRESUMEN
The cardiac safety of renzapride, a novel benzamide currently under clinical development for the treatment of irritable bowel syndrome, was investigated in a four-way randomized crossover electrocardiographic clinical study in healthy human subjects and also in an in vitro cardiac conductivity study in sheep isolated Purkinje fibres. The primary endpoint in the clinical study was prolongation of the individually corrected QT interval (QTci). No clinically or statistically significant prolongation of QTci after 4 or 20 mg renzapride compared with placebo was observed. The relative effects of renzapride and cisapride in the in vitro study showed that the cardiac action potential duration was unaltered by 0.2 and 2 microM renzapride, shortened by 20 microM renzapride, and prolonged by 1 microM cisapride. Cisparide was also a 1000-fold more potent inhibitor of human ether-a-go-go related gene (hERG) channels in HEK293 cells than renzapride. These studies indicate that therapeutic doses of renzapride are unlikely to prolong cardiac action potentials and, therefore, are also unlikely to cause cardiac arrhythmias in clinical use.
Asunto(s)
Benzamidas , Compuestos Bicíclicos Heterocíclicos con Puentes , Síndrome del Colon Irritable/tratamiento farmacológico , Antagonistas de la Serotonina , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Adolescente , Adulto , Animales , Antiinfecciosos/farmacología , Arritmias Cardíacas/inducido químicamente , Compuestos Aza/farmacología , Benzamidas/efectos adversos , Benzamidas/farmacología , Benzamidas/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Línea Celular , Cisaprida/efectos adversos , Cisaprida/farmacología , Cisaprida/uso terapéutico , Estudios Cruzados , Electrocardiografía , Canales de Potasio Éter-A-Go-Go/antagonistas & inhibidores , Canales de Potasio Éter-A-Go-Go/metabolismo , Femenino , Fluoroquinolonas , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/farmacología , Fármacos Gastrointestinales/uso terapéutico , Corazón/efectos de los fármacos , Corazón/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Moxifloxacino , Placebos , Ramos Subendocárdicos/efectos de los fármacos , Ramos Subendocárdicos/metabolismo , Quinolinas/farmacología , Antagonistas de la Serotonina/efectos adversos , Antagonistas de la Serotonina/farmacología , Antagonistas de la Serotonina/uso terapéutico , Agonistas de Receptores de Serotonina/efectos adversos , Agonistas de Receptores de Serotonina/farmacología , Agonistas de Receptores de Serotonina/uso terapéutico , OvinosRESUMEN
The 5-HT(3)-receptor antagonists, considered as 'gold standard' therapy for cancer patients, are generally perceived to have similar efficacy and safety profiles, andmost antiemetic guidelines do not distinguish between agents. However, important pharmacological differences exist between agents, which may translate into potential benefits for some patients. In particular, 5-HT(3)-receptor antagonists vary in the nature of their receptor antagonism and plasma half-lives, possibly leading to differences in duration of action. Agents with a longer duration of action provide antiemetic protection throughout the acute emetic period (24 h) with a single daily dose, whereas shorter-acting agents, e.g. ondansetron, may require multiple dosing for full efficacy. Differences also exist between agents in their hepatic metabolism and cardiovascular safety, which may present particular problems for elderly patients who often receive additional medications for comorbid conditions, increasing the risk of drug-drug interaction. Recent antiemetic guidelines from the National Comprehensive Cancer Network recommend preferential use of palonosetron for moderately emetogenic chemotherapy; however, this agent is newly approved and key clinical questions remain unanswered by clinical trial data. Selection of an appropriate 5-HT(3)-receptor antagonist should be based on proven efficacy and safety, as well as on the individual characteristics of the patient.
Asunto(s)
Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Receptores de Serotonina 5-HT3/fisiología , Antagonistas del Receptor de Serotonina 5-HT3 , Antagonistas de la Serotonina/farmacología , Antagonistas de la Serotonina/uso terapéutico , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Interacciones Farmacológicas , Humanos , Neoplasias/tratamiento farmacológico , Antagonistas de la Serotonina/efectos adversos , Antagonistas de la Serotonina/farmacocinéticaRESUMEN
Although still controversial, iron deficiency has been indicated as one of the risk factors for developing neuroleptic-induced extrapyramidal symptoms (EPSs), including akathisia, dystonia, and neuroleptic malignant syndrome. Here we report our experience of iron supplementation and alternating neuroleptics for treating Parkinsonism in a schizophrenic female patient having severe iron deficient anemia.
Asunto(s)
Antipsicóticos/efectos adversos , Deficiencias de Hierro , Enfermedad de Parkinson Secundaria/etiología , Esquizofrenia/complicaciones , Antagonistas de la Serotonina/efectos adversos , Adolescente , Antipsicóticos/administración & dosificación , Dibenzotiazepinas/administración & dosificación , Femenino , Humanos , Hierro/uso terapéutico , Enfermedad de Parkinson Secundaria/tratamiento farmacológico , Fumarato de Quetiapina , Índice de Severidad de la EnfermedadRESUMEN
A role for serotonin in season affective disorder (SAD) has been explored with a variety of serotonergic pharmacologic agents. The authors initially hypothesized that metergoline, a nonspecific serotonin antagonist, would exacerbate depressive symptoms. In a small, open-label pilot study, the authors observed the opposite effect. They decided to follow up on this finding with this formal study. The study followed a double-blind, randomized cross-over design. Sixteen untreated, depressed patients with SAD received single oral doses of metergoline 8 mg and of placebo, spaced 1 week apart. Fourteen patients were restudied after 2 weeks of light treatment. Depression ratings using the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version were performed at baseline and at 3 and 6 days after each intervention. These data were analyzed by baseline-corrected repeated measures with analysis of variance. In the off-lights condition, severity of depression was diminished after metergoline compared with placebo administration (p = 0.001). Patient daily self-ratings suggested that the peak effect occurred 2 to 4 days after study drug administration. In contrast, after 2 weeks of treatment with bright artificial light, metergoline did not demonstrate a significant effect on mood. These data suggest that single doses of metergoline may have antidepressant effects that last several days. Possible mechanisms include 5-hydroxytryptamine(2) receptor downregulation and dopamine agonism.
Asunto(s)
Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Metergolina/administración & dosificación , Trastorno Afectivo Estacional/tratamiento farmacológico , Antagonistas de la Serotonina/administración & dosificación , Adulto , Antidepresivos/efectos adversos , Terapia Combinada , Estudios Cruzados , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Agonistas de Dopamina/administración & dosificación , Agonistas de Dopamina/efectos adversos , Método Doble Ciego , Regulación hacia Abajo/efectos de los fármacos , Femenino , Humanos , Masculino , Metergolina/efectos adversos , Persona de Mediana Edad , Fototerapia , Receptores de Serotonina/efectos de los fármacos , Trastorno Afectivo Estacional/diagnóstico , Trastorno Afectivo Estacional/psicología , Antagonistas de la Serotonina/efectos adversosRESUMEN
The inhibitory effect of ramosetron hydrochloride (Ram), a 5-HT3 receptor antagonist, on nausea and vomiting occurring in CMF or CEF therapy as a pre- or postoperative adjuvant chemotherapy or chemotherapy for recurrent cancer was evaluated in 34 patients with breast cancer. On days 1 and 8, the patients received Ram (0.3 mg) concomitantly with these agents intravenously and were observed for nausea and vomiting to evaluate the inhibitory effect. Food intake was observed at the same time. On day 1, there was moderate to severe nausea in one patient and vomiting in two patients, while results for 32 of 34 patients (94.1%) were classified as "excellent". On day 8, no moderate or severe nausea was seen, but vomiting occurred in one patient; the results of 33 patients (97.1%) were classified as "excellent". Even when considering only 12 patients who had experienced nausea or vomiting on chemotherapy, 11 showed an "excellent" response on day 1. Moreover, no patient received any additional dose of an anti-emetic drug within 24 hours of Ram administration. Food intake decreased to less than 50% of the baseline in three patients on day 1 and four patients on day 8. Administration of Ram to breast cancer patients on CMF or CEF therapy is thus concluded to be useful in the inhibition of nausea and vomiting.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bencimidazoles/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Náusea/prevención & control , Antagonistas de la Serotonina/uso terapéutico , Vómitos/prevención & control , Adulto , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Apetito/efectos de los fármacos , Bencimidazoles/administración & dosificación , Bencimidazoles/efectos adversos , Neoplasias de la Mama Masculina/tratamiento farmacológico , Cisplatino/efectos adversos , Ciclofosfamida/administración & dosificación , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Masculino , Metotrexato/efectos adversos , Persona de Mediana Edad , Náusea/inducido químicamente , Seguridad , Antagonistas de la Serotonina/administración & dosificación , Antagonistas de la Serotonina/efectos adversos , Resultado del Tratamiento , Vómitos/inducido químicamenteAsunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Demencia por Múltiples Infartos/tratamiento farmacológico , Depuradores de Radicales Libres/administración & dosificación , Extractos Vegetales/administración & dosificación , Antagonistas de la Serotonina/administración & dosificación , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Depuradores de Radicales Libres/efectos adversos , Ginkgo biloba , Humanos , Masculino , Escala del Estado Mental , Extractos Vegetales/efectos adversos , Antagonistas de la Serotonina/efectos adversosRESUMEN
Migraine is a primary headache disorder characterized by recurring attacks of pain and associated symptoms. Migraine sufferers require a continuum of clinical care that depends on their disability and response to treatment. Treatment consists of: (1) prevention of attacks by avoidance of triggers; (2) the use of nonpharmacologic treatments; (3) treatment of the acute attack; and (4) long-term prophylactic therapy. Migraine is comorbid for affective disorders, epilepsy, stroke, and mitral valve prolapse. The therapy selected depends on the headache severity and frequency, the pattern of associated symptoms, comorbid illnesses, and the patient's treatment response profile. Acute treatment can be symptomatic or specific, using drugs such as dihydroergotamine (DHE) or sumatriptan. Preventive treatment can be episodic, subacute, or chronic. The major drug groups include beta-adrenergic blockers, anti-depressants, calcium channel blockers, serotonin antagonists, anticonvulsants, and nonsteroidal anti-inflammatory drugs (NSAIDs). These can be divided into two major categories and second-line choices.
Asunto(s)
Trastornos Migrañosos/terapia , Analgésicos/efectos adversos , Analgésicos/uso terapéutico , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Biorretroalimentación Psicológica , Terapia Combinada , Humanos , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/prevención & control , Bloqueo Nervioso , Antagonistas de la Serotonina/efectos adversos , Antagonistas de la Serotonina/uso terapéuticoAsunto(s)
Trastorno Depresivo/terapia , Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Antidepresivos Tricíclicos/efectos adversos , Antidepresivos Tricíclicos/uso terapéutico , Terapia Conductista , Terapia Cognitivo-Conductual , Contraindicaciones , Trastorno Depresivo/inducido químicamente , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/etiología , Terapia Electroconvulsiva , Femenino , Humanos , Masculino , Inhibidores de la Monoaminooxidasa/efectos adversos , Inhibidores de la Monoaminooxidasa/uso terapéutico , Norepinefrina/antagonistas & inhibidores , Fototerapia , Atención Primaria de Salud , Terapia Psicoanalítica , Psicoterapia , Antagonistas de la Serotonina/efectos adversos , Antagonistas de la Serotonina/uso terapéuticoRESUMEN
The authors review preclinical data; clinical pharmacology data; and efficacy data of sertraline, a novel serotonin uptake inhibitor. Both in vitro and in vivo, sertraline is a potent and specific serotonin uptake inhibitor (possessing up to 10 times the activity of similar agents). Chronic dosing produces down-regulation of beta-adrenergic receptors. In man, sertraline inhibits platelet serotonin uptake and is devoid of obvious cardiac effects. The plasma half-life of sertraline is 25 hours. Studies on psychomotor performance show little or no effect at doses up to 100 mg, whereas 200 and 400 mg appear to possess some sedating action. Sertraline exhibits acute antidepressant effects in the dose range 50 to 200 mg/day; in addition, in the same dose range it prevents recurrence of depression. Its side-effect profile is similar to that of drugs of the same class (dry mouth, nausea, and diarrhea being the most prominent); it lacks the obvious anticholinergic and sedating effects of amitriptyline.