RESUMEN
BACKGROUND: Physicians have prescribed anticholinergic agents such as benztropine, procyclidine, biperiden and trihexyphenidyl for treatment and prophylaxis of antipsychotic-induced extrapyramidal symptoms (EPS) for decades. Anticholinergic agents can however worsen tardive dyskinesia and cause many adverse effects, including cognitive impairment. Previous studies of anticholinergic discontinuation in patients with schizophrenia receiving antipsychotics have yielded a wide range of EPS relapse rates. Improvement in cognition after anticholinergic withdrawal was observed in some studies. OBJECTIVE: This study evaluated the effect of anticholinergic discontinuation on movement disorders, cognition and general psychopathology after a 4-week taper in 20 outpatients with schizophrenia or schizoaffective disorder treated with antipsychotics. RESULTS: Eighteen of twenty patients successfully discontinued their anticholinergic medication; two did not because of akathisia. Repeated measures analysis of variance did not show a significant effect of anticholinergic discontinuation on total Extrapyramidal Symptoms Rating Scale score or on the Parkinsonism, Akathisia, Dystonia or Tardive Dyskinesia subscales. However, significant improvement was found on the Brief Assessment of Cognition in Schizophrenia composite z score at weeks 6, 8 and 12 compared with baseline. Significant improvements were seen on the motor and the symbol-coding tasks. No significant effects were observed on the Positive and Negative Syndrome Scale, Clinical Global Impression - Severity and Clinical Global Impression - Improvement scales. CONCLUSION: In this 12-week study of anticholinergic discontinuation in 20 outpatients with schizophrenia or schizoaffective disorder, gradual decrease and discontinuation of anticholinergics led to a positive effect on cognition. There were no adverse consequences on general psychopathology and no significant differences for 18 of 20 subjects on movement disorders.
RESUMEN
Anticholinergic agents are usually prescribed to prevent or treat antipsychotic-induced extrapyramidal symptoms. Their long-term benefits are questionable and they carry diverse adverse effects, including cognitive impairment and worsening of tardive dyskinesia. This literature review explores the impact of anticholinergic medication discontinuation on movement disorders, cognition and psychopathology in patients receiving antipsychotics. Medline, Embase and PsycInfo were searched from 1950 to July 2011 using "cessation /withdrawal /discontinuation /stopping" with "anticholinergic*" or "antiparkinson*" and "neuroleptic*" or "antipsychotic*". Additional articles were obtained by searching the bibliographies of relevant references. Earlier studies of anticholinergic agent discontinuation in patients receiving first-generation antipsychotics reported relapse rates of extrapyramidal symptoms between 4% and 80%, reflecting the heterogeneity of the studies. Two recent studies of patients prescribed second-generation antipsychotics obtained relapse rates of 4% and 33%. Some studies suggest improvement in tardive dyskinesia with cessation of anticholinergics. Four studies examined the effects of anticholinergic agent discontinuation on cognition and all observed an improvement post-discontinuation. Changes in symptoms of schizophrenia with anticholinergic discontinuation are conflicting, with more recent studies suggesting an improvement. Given their questionable benefit with continued use, clinicians should consider a gradual withdrawal of anticholinergic agents in stable patients receiving antipsychotics.
Asunto(s)
Antipsicóticos/efectos adversos , Antagonistas Colinérgicos/uso terapéutico , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Mantención/efectos adversos , Síndromes de Neurotoxicidad/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Acatisia Inducida por Medicamentos/tratamiento farmacológico , Acatisia Inducida por Medicamentos/fisiopatología , Acatisia Inducida por Medicamentos/prevención & control , Antipsicóticos/administración & dosificación , Antipsicóticos/uso terapéutico , Antagonistas Colinérgicos/administración & dosificación , Antagonistas Colinérgicos/efectos adversos , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/fisiopatología , Trastornos del Conocimiento/prevención & control , Interacciones Farmacológicas , Monitoreo de Drogas , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Discinesia Inducida por Medicamentos/fisiopatología , Discinesia Inducida por Medicamentos/prevención & control , Humanos , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/fisiopatología , Trastornos Mentales/prevención & control , Síndromes de Neurotoxicidad/fisiopatología , Síndromes de Neurotoxicidad/prevención & control , Esquizofrenia/fisiopatología , Esquizofrenia/prevención & control , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Cholinesterase inhibitors (ChEIs) represent the mainstay of symptomatic treatment in Alzheimer's disease. Three medications belonging to this class are presently widely available. These agents differ in their individual mechanisms of action and pharmacokinetic properties. Switching ChEIs can be a reasonable option in cases of intolerance or lack of clinical benefit. METHODS: A systematic literature search of switching ChEIs was conducted, and all studies specifically evaluating this issue were identified. Published consensus guidelines were also searched for recommendations on ChEI switching. RESULTS: Eight clinical studies are summarized and discussed. All of these studies are open-label or retrospective and they cannot be readily compared because of heterogeneity in design, number of patients, agents used, and endpoints. Switching in most of these studies was done for both "lack of benefit" or "loss of response" after up to 29 months of treatment. Nevertheless, the majority of studies did not include individuals switched for lack of response after several years of treatment. Lack of satisfactory response or intolerance with the initial agent was not predictive of similar results with the second agent. CONCLUSIONS: In light of these findings, we propose the following practical approach to switching ChEIs: (1) in the case of intolerance, switching to a second agent should be done only after the complete resolution of side-effects following discontinuation of the initial agent; (2) in the case of lack of efficacy, switching can be done overnight, with a quicker titration scheme thereafter; (3) switching ChEIs is not recommended in individuals who show loss of benefit several years after initiation of treatment.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/uso terapéutico , Anciano , Inhibidores de la Colinesterasa/efectos adversos , Donepezilo , Galantamina/efectos adversos , Galantamina/uso terapéutico , Humanos , Indanos/efectos adversos , Indanos/uso terapéutico , Fenilcarbamatos/efectos adversos , Fenilcarbamatos/uso terapéutico , Piperidinas/efectos adversos , Piperidinas/uso terapéutico , Guías de Práctica Clínica como Asunto , Rivastigmina , Resultado del TratamientoRESUMEN
Generic medications do not undergo the rigorous approval process required of original medications. Their effectiveness and safety is expected to be equal to that of their more expensive counterparts. However, several case reports and studies describe clinical deterioration and decreased tolerability with generic substitution. Pubmed was searched from January 1, 1974 to March 1, 2010. The MeSH term "generic, drugs" was combined with "anticonvulsants," "mood stabilizers," "lithium," "antidepressants," "antipsychotics," "anxiolytics," and "benzodiazepines." Additional articles were obtained by searching the bibliographies of relevant references. Articles in English, French, or Spanish were considered if they discussed clinical equivalence of generic and brand-name medications, generic substitution, or issues about effectiveness, tolerability, compliance, or economics encountered with generics. Clinical deterioration, adverse effects, and changes in pharmacokinetics are described with generic substitution of several anticonvulsants/mood stabilizers (carbamazepine, valproate, lamotrigine, gabapentin, topiramate, lithium), antidepressants (amitriptyline, nortriptyline, desipramine, fluoxetine, paroxetine, citalopram, sertraline, venlafaxine, mirtazapine, bupropion), antipsychotics (risperidone, clozapine), and anxiolytics (clonazepam, alprazolam). Generics do not always lead to the anticipated monetary savings and also raise compliance issues. Although the review is limited by publication bias and heterogeneity of the studies in the literature, we believe there is enough concern to advise generic switching on an individual basis with close monitoring throughout the transition. Health professionals should be aware of the stakes around generic substitution especially when health economics promote universal use of generics.
Asunto(s)
Medicamentos Genéricos/uso terapéutico , Psicotrópicos/uso terapéutico , Equivalencia Terapéutica , Ansiolíticos/farmacología , Ansiolíticos/uso terapéutico , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antimaníacos/farmacología , Antimaníacos/uso terapéutico , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Canadá , Medicamentos Genéricos/economía , Humanos , Trastornos Mentales/tratamiento farmacológico , Trastornos del Humor/tratamiento farmacológico , Psicotrópicos/economíaRESUMEN
OBJECTIVE: Tamoxifen, a medication used in the treatment of breast cancer, often induces menopausal symptoms. Certain medications and natural supplements taken or prescribed to alleviate tamoxifen-induced hot flashes and depressive states in women with breast cancer interact with tamoxifen. This paper reviews potentially problematic interactions and offers treatment recommendations. METHODS: Medline (1950-June 1, 2010), Embase Classic+Embase (1947-June 1, 2010) and PsycINFO (1967-June 1, 2010) were searched through Ovid. The word "tamoxifen" was searched with "depression" and then with "menopaus*" and "symptoms", with "treatment" as a limit. "Tamoxifen" was later searched with the MeSH terms "drug interaction" or "drug incompatibility". RESULTS: Venlafaxine is efficacious for the treatment of hot flashes and depression and safe to use in combination with tamoxifen. Gabapentin is also efficacious in treating tamoxifen-induced hot flashes and, since it does not interact with cytochrome P450 system, is likely safe to use in patients using tamoxifen. Desvenlafaxine and pregabalin may be alternatives to venlafaxine and gabapentin, respectively, although desvenlafaxine has not yet been studied in this population. Paroxetine, fluoxetine and bupropion are strong CYP2D6 inhibitors which should be avoided in tamoxifen users. Fluvoxamine and nefazodone both inhibit CYP3A, which could potentially affect the metabolism of tamoxifen. Clonidine can be an alternative agent but may carry significant side effects. Evidence of medicinal products for the treatment of tamoxifen-induced hot flashes is equivocal at best. CONCLUSIONS: Clinicians should remain cautious about using strong inhibitors and/or inducers of cytochrome 2D6 and 3A4 concomitantly with tamoxifen. Use of natural menopausal supplements and diets rich in isoflavones should not be encouraged in tamoxifen users until more data is available. There are however safe treatments for hot flashes and depression in tamoxifen users.
Asunto(s)
Antidepresivos/uso terapéutico , Antineoplásicos Hormonales/efectos adversos , Depresión/tratamiento farmacológico , Sofocos/tratamiento farmacológico , Menopausia , Tamoxifeno/efectos adversos , Hidrocarburo de Aril Hidroxilasas/antagonistas & inhibidores , Depresión/inducido químicamente , Interacciones Farmacológicas , Femenino , Sofocos/inducido químicamente , Humanos , Menopausia/psicologíaRESUMEN
Drugs acting on the cholinergic system can improve or worsen cognitive abilities, and their effects are particularly pronounced in frail elderly individuals and patients with alzheimer disease. Guidelines are urgently needed on the judicious use of cholinergic drugs.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Colinérgicos/uso terapéutico , Humanos , Pautas de la Práctica en MedicinaRESUMEN
Generic formulations of medications are marketed as therapeutically equivalent and less expensive than branded ones. Multiple studies and case reports have described relapses and worsening clinical outcome in patients after a switch from a brand name to a generic medication. Recent studies have shown that generics do not always lead to the expected costs savings, reducing the impetus to proceed with compulsory generic switching. We report on three patients who experienced clinical deterioration after commencing the generic formulation of their previous brand name psychotropic medication. We discuss key clinical differences between original and generic formulations of the same medication. The use of bioequivalence as an indicator of therapeutic and clinical equivalence, the lack of appropriate studies comparing generic and brand name medications and differences in excipients are some of the factors that could explain variation in clinical response between generic and brand name medications. Generic switching should be decided on a case-by-case basis with disclosure of potential consequences to the patient.
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Medicamentos Genéricos/uso terapéutico , Equivalencia Terapéutica , Femenino , Fluoxetina/uso terapéutico , Humanos , Masculino , Mianserina/análogos & derivados , Mianserina/uso terapéutico , Persona de Mediana Edad , Mirtazapina , Prevención Secundaria , Ácido Valproico/uso terapéuticoRESUMEN
OBJECTIVE: Women taking tamoxifen for the treatment or prevention of recurrence of breast cancer are likely to take antidepressants either for a psychiatric disorder or for hot flashes. Recent evidence suggested that some antidepressants inhibit the metabolism of tamoxifen to its more active metabolites by the cytochrome P450 2D6 (CYP2D6) enzyme, thereby decreasing the anticancer effect. This article reviews the literature on the interactions between newer antidepressants and tamoxifen via CYP2D6 and offers treatment recommendations. DATA SOURCES: A literature search of clinical and nonclinical studies published prior to September 2008 was conducted on PubMed. We performed 3 different searches combining the terms tamoxifen and SSRIs; tamoxifen and CYP2D6 inhibitors; and antidepressant and breast cancer recurrence. A fourth search with CYP2D6 inhibition and the generic names of individual antidepressants was carried out. STUDY SELECTION: Seven clinical research articles were selected. Nonclinical research articles about antidepressants were included if they mentioned in vitro or in vivo inhibition of CYP2D6. DATA SYNTHESIS: There is consistent evidence that paroxetine and fluoxetine have a large effect on the metabolism of tamoxifen and should not be used. Indirect evidence indicates that bupropion may also have a large effect on the metabolism of tamoxifen. Venlafaxine has little or no effect on the metabolism of tamoxifen and may be considered the safest choice of antidepressants. Desvenlafaxine is not metabolized by the P450 system and may consequently be another option. Mirtazapine has not been extensively studied, but existing research suggests minimal effect on CYP2D6. The remaining commonly prescribed antidepressants have mild to moderate degrees of CYP2D6 inhibition. CONCLUSIONS: Clinicians treating patients with breast cancer should review the prescription profiles of their patients to evaluate the need for treatment modification. There are safe options for the treatment of depression and clinicians and patients should bear in mind the health risks of untreated depressive states.
Asunto(s)
Antidepresivos/farmacocinética , Citocromo P-450 CYP2D6/metabolismo , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/metabolismo , Tamoxifeno/farmacocinética , Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Bupropión/efectos adversos , Bupropión/farmacocinética , Bupropión/uso terapéutico , Ciclohexanoles/efectos adversos , Ciclohexanoles/farmacocinética , Ciclohexanoles/uso terapéutico , Citocromo P-450 CYP2D6/efectos de los fármacos , Inhibidores del Citocromo P-450 CYP2D6 , Sistema Enzimático del Citocromo P-450/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/metabolismo , Interacciones Farmacológicas , Femenino , Fluoxetina/efectos adversos , Fluoxetina/farmacocinética , Fluoxetina/uso terapéutico , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacocinética , Tamoxifeno/efectos adversos , Tamoxifeno/uso terapéutico , Clorhidrato de VenlafaxinaRESUMEN
This study prospectively assessed the preferences and satisfaction of 98 psychiatric inpatients and 40 of their relatives with family involvement in discharge planning. Preferences questionnaires were administered during hospitalization. Satisfaction questionnaires were completed 3 months later. Preferences noted by most participants included information concerning patient health status, ways to prevent further hospitalizations, services for relatives, and signs of patient decompensation. More relatives than patients felt that post-discharge residence and activities were important areas to be involved in. Most participants were satisfied if relatives were involved in discharge planning. However, up to 89% of patients, and 84% of relatives, reported no communication between clinical staff and relatives regarding discharge. When this was the case, satisfaction rates dropped sharply, especially for relatives. The need for increased communication between clinicians and relatives regarding discharge planning remains a problem.