BACKGROUND: Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. This review, one in a series examining the treatment of TD, covers miscellaneous treatments not covered elsewhere.
OBJECTIVES: To determine whether drugs, hormone-, dietary-, or herb-supplements not covered in other Cochrane reviews on TD treatments, surgical interventions, electroconvulsive therapy, and mind-body therapies were effective and safe for people with antipsychotic-induced TD.
SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including trial registers (16 July 2015 and 26 April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information.
SELECTION CRITERIA: We included reports if they were randomised controlled trials (RCTs) dealing with people with antipsychotic-induced TD and schizophrenia or other chronic mental illnesses who remained on their antipsychotic medication and had been randomly allocated to the interventions listed above versus placebo, no intervention, or any other intervention.
DATA COLLECTION AND ANALYSIS: We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CIs). We assumed that people who left early had no improvement. We assessed risk of bias and created 'Summary of findings' tables using GRADE.
MAIN RESULTS: We included 31 RCTs of 24 interventions with 1278 participants; 22 of these trials were newly included in this 2017 update. Five trials are awaiting classification and seven trials are ongoing. All participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. Studies were primarily of short (three to six6 weeks) duration with small samples size (10 to 157 participants), and most (61%) were published more than 20 years ago. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment, generation of the sequence, and blinding.Nineteen of the 31 included studies reported on the primary outcome 'No clinically important improvement in TD symptoms'. Two studies found moderate-quality evidence of a benefit of the intervention compared with placebo: valbenazine (RR 0.63, 95% CI 0.46 to 0.86, 1 RCT, n = 92) and extract of Ginkgo biloba (RR 0.88, 95% CI 0.81 to 0.96, 1 RCT, n = 157), respectively. However, due to small sample sizes we cannot be certain of these effects.We consider the results for the remaining interventions to be inconclusive: Low- to very low-quality evidence of a benefit was found for buspirone (RR 0.53, 95% CI 0.33 to 0.84, 1 RCT, n = 42), dihydrogenated ergot alkaloids (RR 0.45, 95% CI 0.21 to 0.97, 1 RCT, n = 28), hypnosis or relaxation, (RR 0.45, 95% CI 0.21 to 0.94, 1 study, n = 15), pemoline (RR 0.48, 95% CI 0.29 to 0.77, 1 RCT, n = 46), promethazine (RR 0.24, 95% CI 0.11 to 0.55, 1 RCT, n = 34), insulin (RR 0.52, 95% CI 0.29 to 0.96, 1 RCT, n = 20), branched chain amino acids (RR 0.79, 95% CI 0.63 to 1.00, 1 RCT, n = 52), and isocarboxazid (RR 0.24, 95% CI 0.08 to 0.71, 1 RCT, n = 20). There was low- to very low-certainty evidence of no difference between intervention and placebo or no treatment for the following interventions: melatonin (RR 0.89, 95% CI 0.71 to 1.12, 2 RCTs, n = 32), lithium (RR 1.59, 95% CI 0.79 to 3.23, 1 RCT, n = 11), ritanserin (RR 1.00, 95% CI 0.70 to 1.43, 1 RCT, n = 10), selegiline (RR 1.37, 95% CI 0.96 to 1.94, 1 RCT, n = 33), oestrogen (RR 1.18, 95% CI 0.76 to 1.83, 1 RCT, n = 12), and gamma-linolenic acid (RR 1.00, 95% CI 0.69 to 1.45, 1 RCT, n = 16).None of the included studies reported on the other primary outcome, 'no clinically significant extrapyramidal adverse effects'.
AUTHORS' CONCLUSIONS: This review has found that the use of valbenazine or extract of Ginkgo biloba may be effective in relieving the symptoms of tardive dyskinesia. However, since only one RCT has investigated each one of these compounds, we are awaiting results from ongoing trials to confirm these results. Results for the remaining interventions covered in this review must be considered inconclusive and these compounds probably should only be used within the context of a well-designed evaluative study.
AIM: The effects of nutrient-based treatments, including adjunctive vitamin or antioxidant supplementation, have been explored extensively in long-term schizophrenia. However, no systematic evaluation of trials in "first-episode psychosis" (FEP) has been conducted, despite the potential benefits of using these treatments during the early stages of illness. Therefore, we aimed to review all studies examining efficacy, tolerability and the biological mechanisms of action, of nutrient supplementation in FEP.
METHODS: A systematic review of electronic databases was conducted from inception to July 2017. All information on feasibility, clinical outcomes and mechanistic findings from nutrient supplementation clinical trials was extracted and systematically synthesized.
RESULTS: Eleven studies with a total of 451 patients with FEP (from 8 independent randomized controlled trials) were eligible for inclusion. Six studies examined omega-3 fatty acids, with inconsistent effects on psychiatric symptoms. However, mechanistic studies found significant improvements in hippocampal neuronal health and brain glutathione. Antioxidants "n-acetyl cysteine" (n = 1) and vitamin C (n = 2) also improved oxidative status in FEP, which was associated with reduced psychiatric symptoms. No benefits were found for vitamin E (n = 1). Finally, one study trialling the amino acid taurine, showed significant improvements in positive symptoms and psychosocial functioning.
CONCLUSION: There is preliminary evidence that taurine improves outcomes in FEP, whereas effects of omega-3 and antioxidant vitamins/amino-acids are inconsistent; perhaps mainly benefitting patients with high levels of oxidative stress. Future studies should evaluate multifaceted dietary and supplementation interventions in FEP; targeting-specific nutritional deficits and the range of aberrant biological processes implicated in the disorder.
Neuroinflammation has been implicated in the neurobiological pathways of schizophrenia. This meta-analysis evaluated the efficacy and tolerability of adjunctive celecoxib as a noncompetitive anti-inflammation drug in treating schizophrenia. Data were searched, extracted, checked and entered into the RevMan (version 5.3) software by two independent investigators. Standardized/weighted mean differences (SMDs/WMDs), risk ratio (RR) and their 95% confidence intervals (CIs) were calculated, as appropriate. Included were 8 randomized controlled trials (RCTs) with a total of 626 patients with schizophrenia including 316 (50.5%) treated on celecoxib (400 mg/day) and 310 (49.5%) on placebo over 8.3 ± 2.3 weeks of treatment. Adjunctive celecoxib outperformed placebo with respect to total psychopathology [3 RCTs, n = 180; SMD: -0.47; 95%CI: -0.81, -0.14; P = 0.005; I2 = 18%; 'moderate quality'], symptoms positive [3 RCTs, n = 180; SMD: -0.50; 95%CI: -0.79, -0.20; P = 0.001; I2 = 0%; 'moderate quality'], negative symptoms [3 RCTs, n = 180; SMD: -0.32; 95%CI: -0.66, 0.02; P = 0.06; I2 = 22%; 'moderate quality'], and general psychopathology scores [3 RCTs, n = 180; SMD: -0.35; 95%CI: -0.65, -0.06; P = 0.02; I2 = 0%; 'moderate quality'] in first-episode, but not chronic patients. Additionally, superiority of celecoxib for the Positive and Negative Syndrome Scale (PANSS) total scores was moderated by higher PANSS positive scores and lower PANSS negative scores at baseline. All-cause discontinuation [RR: 1.02; (95%CI: 0.56, 1.86); P = 0.94; I2 = 0%] and adverse drug reactions were similar between the two groups. Adjunctive celecoxib appears to be an efficacious and safe treatment in improving psychotic symptoms, particularly in first-episode schizophrenia.
REVIEW REGISTRATION: CRD42016054233 (http://www.crd.york.ac.uk/prospero/).
In this systematic review, we will consider and debate studies that have explored the effects of ω-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow related, developmental psychiatric disorders: Autism, Attention Deficit and Hyperactivity disorder and Psychosis. The impact of ω-3 PUFAs on clinical symptoms and, if possible, brain trajectory in children and adolescents suffering from these illnesses will be reviewed and discussed, considering the biological plausibility of the effects of omega-3 fatty acids, together with their potential perspectives in the field. Heterogeneity in study designs will be discussed in the light of differences in results and interpretation of studies carried out so far.
Cognitive function deficit is a constant phenomenon described in the population of patients with schizophrenia – in the premorbid period, during exacerbations and between the successive episodes. Cognitive dysfunction is an independent prognostic factor in schizophrenia. Studies indicate that this pathology dimension affects patient-functioning indicators, such as: treatment and rehabilitation outcomes, cooperation during treatment, professional, family and social functioning, the ability to live independently as well as the quality of life. Current methods for the treatment of schizophrenia fail to ensure sufficient improvement in this dimension of the disease. The usefulness of omega-3 polyunsaturated fatty acids, both as a monotherapy and an augmentation of antipsychotic treatment in schizophrenia, has been investigated during the last 25 years. The obtained results are inconclusive, however, a positive tendency in the outcomes related to symptomatic improvement have been observed. The effects of omega-3 polyunsaturated fatty acid supplementation on the cognitive functioning of patients diagnosed with schizophrenia has been relatively rarely evaluated. However, there is a theoretical rationale for the beneficial effect of omega-3 polyunsaturated fatty acid supplementation on cognitive function. The known effects of these substances that could contribute to the improvement in cognitive function include: immunomodulatory effects in the CNS, improvement of oxidative stress parameters, changes in neurotransmission as well as effects on neuroplasticity. The aim of this paper is to present a systematic review of research findings on the changes in cognitive performance in patients diagnosed with schizophrenia who receive omega-3 polyunsaturated fatty acid supplementation.
ANTECEDENTES: Hay pruebas de que los cambios progresivos en la estructura y función del cerebro se llevan a cabo como la esquizofrenia se desarrolla. Entre muchos candidatos posibles, el estrés oxidativo puede ser uno de los mediadores de la neuroprogression, pérdida de materia gris y el deterioro cognitivo y funcional subsiguiente. Los antioxidantes son moléculas endógenas o exógenas que mitiguen cualquier forma de estrés oxidativo o sus consecuencias. Pueden actuar de barrido de radicales libres directamente a aumentar las defensas antioxidantes. Hay evidencia de que los tratamientos actuales impactan vías oxidativas y pueden, en cierta medida inversa estados pro-oxidantes en la esquizofrenia. La literatura existente, sin embargo, indica que estos tratamientos no restablecen plenamente los déficit en los niveles de antioxidantes o restauran los niveles de oxidantes en la esquizofrenia. Como tal, ha habido interés en el desarrollo de intervenciones destinadas a restablecer este equilibrio oxidativo más allá de los beneficios de los antipsicóticos en esta dirección. Si los antioxidantes han de tener un lugar en el tratamiento de esta grave enfermedad, la información pertinente y actualizada información debe estar disponible para los clínicos e investigadores.
Objetivos: Evaluar el efecto de los antioxidantes como complemento a los tratamientos de la medicación antipsicótica estándar para la mejora de episodios psicóticos agudos y síntomas de la base, y la prevención de recaídas en personas con esquizofrenia.
ESTRATEGIA DE BÚSQUEDA: Se realizaron búsquedas registro basado en estudios del Grupo Cochrane de Esquizofrenia de los ensayos que se basa en búsquedas regulares en CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, y los registros de ensayos clínicos. No hay idioma, hora, tipo de documento, o las limitaciones del estado de publicación para la inclusión de los registros en el registro. Nos encontramos con esta búsqueda en noviembre de 2010, y de nuevo el 8 de enero de 2015. También se revisaron las referencias de todos los estudios identificados para obtener ensayos y se estableció contacto con autores de ensayos para obtener información adicional.
Criterios de selección: Se incluyeron informes si eran ensayos controlados aleatorios (ECA) que implican las personas con esquizofrenia que habían sido asignados a cualquiera de una sustancia con potencial antioxidante o con un placebo como un complemento al tratamiento antipsicótico estándar.
Recopilación y análisis de datos: Se extrajeron de forma independiente los datos de estos ensayos y se calcularon los cocientes de riesgo (RR) o las diferencias de medias (DM), con intervalos de confianza del 95% (IC). Se evaluó el riesgo de sesgo de los estudios incluidos y creamos un "Resumen de los hallazgos" tabla usando GRADO.
Resultados principales: La revisión incluye 22 ECA de diversa calidad y tamaño de la muestra a estudiar Ginkgo biloba, N-acetilcisteína (NAC), alopurinol, la dehidroepiandrosterona (DHEA), vitamina C, vitamina E o selegilina. La mediana de seguimiento fue de ocho semanas. Sólo tres estudios que incluyeron una minoría de los participantes informaron de nuestra priori resultado primario seleccionado de respuesta clínicamente importante. Los datos a corto plazo para este resultado (medidos como la mejora de al menos el 20% en las puntuaciones de la Escala de Síndrome Positivo y Negativo (PANSS)) fueron similares (3 ECA, n = 229, RR 0,77, IC del 95%: 0,53 a 1,12, pruebas de baja calidad ). Los estudios generalmente se informan sólo puntuaciones de la escala de psicopatología calificación de punto final. Los síntomas psicóticos fueron más bajos en los que el uso de un antioxidante adyuvante de acuerdo con la escala PANSS (7 ECA, n = 584, MD -6,00; IC del 95% -10.35 a -1,65 a pruebas de calidad muy baja) y la Escala de Valoración Psiquiátrica Breve (BPRS) ( 8 ECA, n = 843, MD -3,20, IC del 95% -5,63 a -0,78, pruebas de baja calidad). No hubo diferencias en general a corto plazo en abandono temprano del estudio (16 ECA, n = 1584, RR 0,73, IC 95% 0,48 a la 1,11; pruebas de calidad moderada), o en general de funcionar (2 ECA, n = 52, MD - 1.11, 95% IC -8,07 a 5,86, pruebas de baja calidad). Los eventos adversos se informaron de manera deficiente en general. Tres estudios informaron datos utilizables para 'ningún efecto adverso grave', los resultados fueron equívocos (3 ECA, n = 234, RR 0,65; IC del 95%: 0,19 a 2,27; pruebas de baja calidad). No se dispone de pruebas de recaída, calidad de vida o el uso del servicio.
Conclusiones de los revisores: Aunque 22 ensayos podrían ser incluidos en esta revisión, la evidencia proporcionada es limitado y generalmente no es relevante para los médicos o los consumidores. En general, aunque hubo un bajo riesgo de desgaste y sesgo de informe dentro de los ensayos selectivos de datos, los mismos ensayos fueron no poder estadístico adecuado y necesitan períodos de seguimiento más sustanciales. Hay una necesidad de ensayos más grandes con períodos de seguimiento más largos para ser llevado a cabo. Los resultados deben ser significativos para las personas con esquizofrenia, e incluir medidas de mejora y la recaída (no sólo rating puntuaciones de la escala), el funcionamiento y la calidad de vida y la aceptabilidad y, sobre todo, los datos de seguridad.
Schizophrenia is a severe, chronic and debilitating mental disorder. Past literature has reported various hypotheses about the psychopathology of schizophrenia. Recently, a growing literature has been trying to explain the role of inflammation in the etiopathogenesis of schizophrenia. In the past, numerous immune modulation and anti-inflammatory treatment options have been proposed for schizophrenia, but sometimes the results were inconsistent. Electronic search was carried out in November 2015. PubMed and Scopus databases have been used to find studies to introduce in this review. Only randomized-placebo-controlled add-on trials were taken into account. In this way, six articles were obtained for the discussion. Celecoxib showed beneficial effects mostly in early stages of schizophrenia. In chronic schizophrenia, the data are controversial, possibly in part for methodological reasons.
Los ácidos grasos omega-3 han demostrado ser prometedores como un tratamiento adyuvante para la esquizofrenia. Sin embargo, la eficacia entre los estudios ha sido inconsistente. Se realizó un metanálisis de estudios controlados publicados con el objetivo de detectar diferentes perfiles de eficacia en diferentes estadios de la esquizofrenia. MÉTODOS: Se realizó una búsqueda en línea para ensayos clínicos aleatorios, doble ciego, controlados con placebo y se realizó un metanálisis. RESULTADOS: Diez estudios cumplieron con los criterios de inclusión. Entre los pacientes en la fase prodrómica de la esquizofrenia, los suplementos de omega-3 redujeron la gravedad de los síntomas psicóticos y redujeron las tasas de conversión al primer episodio de psicosis. En pacientes con esquizofrenia de primer episodio, los omega-3 disminuyeron los síntomas no psicóticos, requirieron dosis más bajas de medicamentos antipsicóticos y mejoraron las tasas de respuesta temprana al tratamiento. Omega-3 tuvo resultados mixtos en pacientes con esquizofrenia crónica estable, con sólo algunos pacientes experimentando beneficios significativos. Entre los pacientes con esquizofrenia crónica, el uso de ácidos grasos omega-3, tanto por los que experimentan exacerbaciones agudas como por los que suspendieron los medicamentos antipsicóticos, dio como resultado un empeoramiento de los síntomas psicóticos. Los datos sugieren que los ácidos grasos omega-3 pueden ser eficaces para reducir los síntomas clínicos de los pacientes en las primeras etapas de la esquizofrenia (pródromo y primer episodio), produciendo resultados mixtos para los pacientes en estadios crónicos. Sobre la base de estos resultados, los ácidos grasos omega-3 no se recomiendan para las exacerbaciones agudas en pacientes con esquizofrenia crónica ni para la prevención de la recaída después de la interrupción de los antipsicóticos.
OBJETIVOS: Los tratamientos existentes para la esquizofrenia pueden mejorar los síntomas positivos, pero no está claro si tienen algún impacto en los síntomas negativos. Este metanálisis se realizó para evaluar la eficacia de los tratamientos disponibles para los síntomas negativos en la esquizofrenia. Métodos: Se recuperaron todos los ensayos controlados aleatorios de intervenciones para síntomas negativos en la esquizofrenia hasta diciembre de 2013; Se utilizaron 168 ensayos únicos e independientes controlados con placebo. Se extrajeron las puntuaciones de los síntomas negativos en la línea de base y el seguimiento, la duración de la enfermedad, las dosis de medicación, el tipo de intervenciones y la demografía de la muestra. La heterogeneidad se trató con la estadística I (2) y Q. La diferencia de medias estandarizada en los valores de la escala de calificación de síntomas negativos utilizada en cada estudio se calculó como la principal medida de resultado. RESULTADOS: Se incluyeron 6503 pacientes en el brazo de tratamiento y 5815 pacientes en el grupo placebo. No hay evidencia de sesgos de publicación encontrados. La mayoría de los tratamientos redujeron los síntomas negativos en el seguimiento en relación con el placebo: antipsicóticos de segunda generación: -0.579 (-0.755 a -0.404); Antidepresivos: -0.349 (-0.551 a -0.146); Combinaciones de agentes farmacológicos: -0,518 (-0,757 a -0,279); Medicamentos glutamatérgicos: -0,289 (-0,478 a -0,1); Intervenciones psicológicas: -0.396 (-0.563 a -0.229). No se encontraron efectos significativos para los antipsicóticos de primera generación: -0,531 (-1,104 a 0,041) y estimulación cerebral: -0,228 (-0,775 a 0,319). Los efectos de la mayoría de los tratamientos no fueron clínicamente significativos, como se midió en la Escala de Severidad de la Impresión Clínica Global. CONCLUSIONES Y RELEVANCIA: Aunque algunos efectos estadísticamente significativos sobre los síntomas negativos fueron evidentes, ninguno alcanzó el umbral para una mejoría clínicamente significativa.
enfoques psicofarmacológicos actuales para reducir la fenomenología psicótica en la esquizofrenia se asocian con efectos adversos incluyendo extrapiramidales y efectos secundarios metabólicos. A la vista de los datos que se desprenden de las intervenciones administración de suplementos nutricionales en la esquizofrenia que no son del todo coherente, que tuvo como objetivo revisar los estudios existentes se centran en intervenciones de ácidos grasos y vitaminas y resumir la evidencia actual sobre dichos administración de suplementos nutricionales en la esquizofrenia. Se realizaron búsquedas en las bases de datos digitales (ScienceDirect, Scopus, SpringerLink, PubMed / Medline) para los estudios pertinentes relacionados con las intervenciones de ácidos grasos y vitamina en el tratamiento de los síntomas psicóticos en la esquizofrenia hasta febrero del año 2015. En general, hubo más estudios realizados sobre los ácidos grasos sobre administración de suplementos de vitaminas en pacientes con esquizofrenia. Hubo resultados más positivos en apoyo de la administración de suplementos de ácidos grasos en comparación con la administración de suplementos vitamínicos en el contexto de las características específicas de intervención (dosis de suplementación de nutrientes, único versus la combinación de intervenciones nutricionales, antipsicóticos específicos), las funciones están sujetos (edad avanzada, larga duración de la enfermedad, la línea de base los niveles de ácidos grasos poliinsaturados) y los resultados clínicos (mejoras de los síntomas psicóticos y / o efectos secundarios extrapiramidales de los antipsicóticos). Sin embargo, las investigaciones de ambas modalidades de administración de suplementos eran limitadas por un número relativamente pequeño tamaño muestral del estudio, corta duración del estudio, lo que impidió una mayor segmentación del impacto en más diversos subtipos de pacientes y perfiles de los síntomas. Los estudios futuros podrían considerar el examen de muestras de mayor tamaño en un período de tiempo más largo, el reclutamiento de los sujetos más jóvenes con menor duración de la enfermedad, el examen de diferentes características clínicas incluyendo dominios cognitivos específicos, y el uso de una sola versus intervenciones nutricionales de combinación.
Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. This review, one in a series examining the treatment of TD, covers miscellaneous treatments not covered elsewhere.
OBJECTIVES:
To determine whether drugs, hormone-, dietary-, or herb-supplements not covered in other Cochrane reviews on TD treatments, surgical interventions, electroconvulsive therapy, and mind-body therapies were effective and safe for people with antipsychotic-induced TD.
SEARCH METHODS:
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including trial registers (16 July 2015 and 26 April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information.
SELECTION CRITERIA:
We included reports if they were randomised controlled trials (RCTs) dealing with people with antipsychotic-induced TD and schizophrenia or other chronic mental illnesses who remained on their antipsychotic medication and had been randomly allocated to the interventions listed above versus placebo, no intervention, or any other intervention.
DATA COLLECTION AND ANALYSIS:
We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CIs). We assumed that people who left early had no improvement. We assessed risk of bias and created 'Summary of findings' tables using GRADE.
MAIN RESULTS:
We included 31 RCTs of 24 interventions with 1278 participants; 22 of these trials were newly included in this 2017 update. Five trials are awaiting classification and seven trials are ongoing. All participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. Studies were primarily of short (three to six6 weeks) duration with small samples size (10 to 157 participants), and most (61%) were published more than 20 years ago. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment, generation of the sequence, and blinding.Nineteen of the 31 included studies reported on the primary outcome 'No clinically important improvement in TD symptoms'. Two studies found moderate-quality evidence of a benefit of the intervention compared with placebo: valbenazine (RR 0.63, 95% CI 0.46 to 0.86, 1 RCT, n = 92) and extract of Ginkgo biloba (RR 0.88, 95% CI 0.81 to 0.96, 1 RCT, n = 157), respectively. However, due to small sample sizes we cannot be certain of these effects.We consider the results for the remaining interventions to be inconclusive: Low- to very low-quality evidence of a benefit was found for buspirone (RR 0.53, 95% CI 0.33 to 0.84, 1 RCT, n = 42), dihydrogenated ergot alkaloids (RR 0.45, 95% CI 0.21 to 0.97, 1 RCT, n = 28), hypnosis or relaxation, (RR 0.45, 95% CI 0.21 to 0.94, 1 study, n = 15), pemoline (RR 0.48, 95% CI 0.29 to 0.77, 1 RCT, n = 46), promethazine (RR 0.24, 95% CI 0.11 to 0.55, 1 RCT, n = 34), insulin (RR 0.52, 95% CI 0.29 to 0.96, 1 RCT, n = 20), branched chain amino acids (RR 0.79, 95% CI 0.63 to 1.00, 1 RCT, n = 52), and isocarboxazid (RR 0.24, 95% CI 0.08 to 0.71, 1 RCT, n = 20). There was low- to very low-certainty evidence of no difference between intervention and placebo or no treatment for the following interventions: melatonin (RR 0.89, 95% CI 0.71 to 1.12, 2 RCTs, n = 32), lithium (RR 1.59, 95% CI 0.79 to 3.23, 1 RCT, n = 11), ritanserin (RR 1.00, 95% CI 0.70 to 1.43, 1 RCT, n = 10), selegiline (RR 1.37, 95% CI 0.96 to 1.94, 1 RCT, n = 33), oestrogen (RR 1.18, 95% CI 0.76 to 1.83, 1 RCT, n = 12), and gamma-linolenic acid (RR 1.00, 95% CI 0.69 to 1.45, 1 RCT, n = 16).None of the included studies reported on the other primary outcome, 'no clinically significant extrapyramidal adverse effects'.
AUTHORS' CONCLUSIONS:
This review has found that the use of valbenazine or extract of Ginkgo biloba may be effective in relieving the symptoms of tardive dyskinesia. However, since only one RCT has investigated each one of these compounds, we are awaiting results from ongoing trials to confirm these results. Results for the remaining interventions covered in this review must be considered inconclusive and these compounds probably should only be used within the context of a well-designed evaluative study.
