RESUMEN
There is no established treatment for patients with clozapine-resistant schizophrenia (CRS). Clozapine augmentation strategies with antipsychotics or others substances are effective in comparison with placebo while and Electroconvulsive therapy (ECT) showed to be effective in comparison with treatment as usual (TAU) but not with placebo (sham-ECT). In the present double- blind randomized controlled trial, we compared 40 outpatients who received 20 sessions of ECT (n = 21) or sham-ECT (n = 19) (age = 37.40 ± 9.62, males = 77.5 %, illness duration = 14.95 ± 8.32 years, mean total Positive and Negative Syndrome Scale (PANSS) = 101.10 ± 24.91) who fulfilled well-defined CRS criteria including baseline clozapine plasma levels ≥350 ng/mL. The primary outcome was the ≥50 % PANSS Total Score reduction; secondary outcomes were the scores of the PANSS subscales, PANSS five-factor dimensions, PANSS-6 and the Calgary Depression Rating Scale (CDRS). Treatment response was analyzed by percentage reduction, Linear Mixed Models and effect sizes. At baseline both groups showed no differences except for years of school education (included as a covariate). At endpoint, only 1/19 of the completers (5.26 %) in the ECT group and 0/17 in the sham-ECT group showed a ≥50 % total PANSS score reduction. Both groups showed no significant differences of the total PANSS score (F = 0.12; p = 0.73), Positive (F = 0.27, p = 0.61), Negative (F = 0.25, p = 0.62), and General Psychopathology scores (F = 0.01, p = 0.94) as well for all PANSS five factors, the PANSS-6 and CDRS. Thus, the present study found no evidence that ECT is better than Sham-ECT in patients with CRS. Future sham-ECT controlled studies with larger sample sizes are warranted to test the efficacy of ECT for patients with CRS.
Asunto(s)
Antipsicóticos , Clozapina , Terapia Electroconvulsiva , Esquizofrenia Resistente al Tratamiento , Humanos , Masculino , Femenino , Terapia Electroconvulsiva/efectos adversos , Adulto , Clozapina/uso terapéutico , Clozapina/efectos adversos , Método Doble Ciego , Antipsicóticos/uso terapéutico , Persona de Mediana Edad , Esquizofrenia Resistente al Tratamiento/terapia , Esquizofrenia Resistente al Tratamiento/tratamiento farmacológico , Escalas de Valoración Psiquiátrica , Resultado del Tratamiento , Esquizofrenia/terapia , Esquizofrenia/tratamiento farmacológico , Evaluación de Resultado en la Atención de SaludRESUMEN
Treatment-resistant schizophrenia (TRS) will affect about one in three patients with schizophrenia. Clozapine is the only treatment approved for TRS, and patients should be treated as soon as possible to improve their chances of achieving remission. Despite its effectiveness, concern over side effects, monitoring requirements, and inexperience with prescribing often result in long delays that can expose patients to unnecessary risks and compromise their chances of achieving favorable long-term outcomes. We critically reviewed the literature on clozapine use in TRS, focusing on guidelines, systematic reviews, and algorithms to identify strategies for improving clozapine safety and tolerability. Based on this, we have provided an overview of strategies to support early initiation of clozapine in patients with TRS based on the latest evidence and our clinical experience, and have summarized the key elements in a practical, evidence-based checklist for identifying and managing patients with TRS, with the aim of increasing confidence in prescribing and monitoring clozapine therapy.
Asunto(s)
Antipsicóticos , Clozapina , Esquizofrenia , Antipsicóticos/efectos adversos , Lista de Verificación , Clozapina/efectos adversos , Humanos , Esquizofrenia/tratamiento farmacológico , Esquizofrenia Resistente al TratamientoRESUMEN
PURPOSE: Childhood abuse is associated with an increased risk of developing eating disorders (EDs) as well as personality disorders (PDs). However, their interaction is still uncertain, particularly in adolescents. This study investigates the correlations between childhood emotional neglect (CEN), childhood emotional abuse (CEA), and obsessive-compulsive and borderline personality styles in female adolescent inpatients with eating disorders (EDs). METHODS: One hundred and twenty-eight inpatients (ages 14-18) were assessed, 54 were diagnosed with restricting-type anorexia nervosa (AN-R) and 33 with a binge-purging ED [BP-ED; comprising patients with binge-purging type anorexia nervosa (AN-BP), n = 15, and bulimia nervosa (BN), n = 18]. Fifty healthy participants made up the control group (CG). CEN and CEA were assessed with the Childhood Trauma Questionnaire, while the Personality Style and Disorder Inventory was implemented to determine personality styles. RESULTS: A MANOVA revealed a significant main effect of CEA on spontaneous-borderline personality style [F(8,119) = 17.1, p < 0.001, η2 = 0.126], as well as a main effect of ED group on spontaneous-borderline [F(2,119) = 3.1, p = 0.048, η2 = 0.050]. A significant interaction between ED group, CEA, and spontaneous-borderline was found [F(2,119) = 3.5, p = 0.034, η2 = 0.055] with BP-ED showing significantly higher scores in CEA (9.3 ± 4.0) and in spontaneous-borderline (14.2 ± 6.2). CONCLUSIONS: Considering CEA and borderline personality style in adolescent inpatients with BN or AN-BP may help improve the understanding of the etiology and maintenance of BP-ED and provide more effective treatment targets. LEVEL OF EVIDENCE: Level III, case-control analytic study.
Asunto(s)
Anorexia Nerviosa , Bulimia Nerviosa , Trastornos de Alimentación y de la Ingestión de Alimentos , Adolescente , Anorexia Nerviosa/psicología , Bulimia Nerviosa/psicología , Niño , Abuso Emocional , Trastornos de Alimentación y de la Ingestión de Alimentos/complicaciones , Femenino , Humanos , Pacientes Internos , PersonalidadRESUMEN
AIMS: Antipsychotics are primarily labelled for the treatment of severe mental illness and have documented clinical utility in certain neurological disorders or palliative care. However, off-label use of antipsychotics is common and increasing, and prior studies on antipsychotic utilisation have not specifically assessed users in neurology, palliative care or general practice. We aimed to explore diagnoses associated with antipsychotic use, treatment patterns and characteristics of users without diagnoses relevant to antipsychotic treatment. METHODS: Population-based study identifiying all users of antipsychotics in Denmark (pop 5.7 mio.) 1997-2018 in the Danish National Prescription Register (DNPR). Possible indications for antipsychotic therapy were evaluated using in- and outpatient contacts from the DNPR. Users were divided hierarchically into six groups: severe mental disorders (schizophrenia, bipolar-spectrum disorders), chronic mental disorders (dementias, mental retardation, autism), other mental disorders (depression-spectrum, anxiety and personality disorders, etc.), selected neurological diseases, cancer and antipsychotic users without any of these diagnoses. This last group was characterised regarding demographics, antipsychotic use, health care utilisation and likely antipsychotic treatment initiator in 2018. RESULTS: Altogether, 630 307 antipsychotic users were identified, of whom 127 649 had filled prescriptions during 2018. Users without diagnoses relevant to antipsychotic treatment comprised of the largest group (37%), followed by schizophrenia and bipolar-spectrum disorders (34%), other mental disorders (15%), dementia, autism and mental retardation (11%), cancer (2.2%) and neurological diagnoses (2.0%). Of 37 478 incident users in 2018, 39% had no diagnosis relevant to antipsychotic treatment, 7.9% had major depression, 7.7% neurotic/stress-related disorders and 7.5% dementia. Quetiapine was most commonly used, both overall (51%) and among users without diagnoses relevant to antipsychotic treatment (58%). Of 14 474 incident users in 2018 without diagnoses relevant to antipsychotic treatment, treatment was most likely initiated by a general practitioner (65%), with only 17% seeing a psychiatrist during the following year. As many as 18% of patients with adjustment disorders and 14% of those without relevant diagnoses for antipsychotic use, remained on antipsychotic treatment 5 years after their first prescription. CONCLUSIONS: Over one-third of antipsychotic users in Denmark did not have psychiatric, neurological or cancer diagnoses as possible indications for antipsychotic therapy. Many antipsychotics are initiated or prescribed in general practice, and a concerningly large subgroup without documented diagnoses relevant for antipsychotics continued to receive them. Rational prescribing, adequate side effect monitoring and further research into reasons for the observed antipsychotic use patterns and their risk-benefit ratio are needed.
Asunto(s)
Antipsicóticos , Utilización de Medicamentos , Trastornos Mentales , Uso Fuera de lo Indicado , Antipsicóticos/uso terapéutico , Dinamarca/epidemiología , Utilización de Medicamentos/estadística & datos numéricos , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/epidemiología , Uso Fuera de lo Indicado/estadística & datos numéricosRESUMEN
Since the first publication of the guideline in 2012, which included critically reviewed evidence up to 2010, several hundred articles with new evidence were published and some topics of the clinical consensus needed to be reconsidered. Therefore, it was urgently necessary to revise the guideline to bring them up to date. In this article important revisions and updates are presented and the chances and limitations of the development of the guidelines and their implementation are discussed.
Asunto(s)
Trastorno Bipolar , Guías como Asunto , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/terapia , Alemania , Guías como Asunto/normas , HumanosRESUMEN
BACKGROUND: Schizophrenia is a severe psychiatric disorder with variable therapeutic responses, the etiology and pathophysiology of which require further elucidation. OBJECTIVE: To review which pharmacological options are effective and safe and for which treatment goals in schizophrenia. MATERIAL AND METHODS: Narrative review of the pharmacological therapy of adults diagnosed with schizophrenia. RESULTS: Despite heterogeneous therapeutic responses, to date only dopamine antagonists or partial agonists are approved for the treatment of schizophrenia. The efficacy of antipsychotic agents differs only gradually, with the exception of clozapine for treatment-resistant schizophrenia, whereas undesired adverse effects are more variable. Those antipsychotic agents that show gradual efficacy advantages in meta-analyses of acute and maintenance treatment (clozapine, amisulpride, olanzapine, risperidone) are also those where at least one undesired adverse effect is most severely expressed. Antipsychotic adverse effects occur in subgroups of patients and are generally tolerable or treatable, whereas the "side effect" of untreated schizophrenia affects almost all patients, including relapses, psychosocial deterioration, secondary treatment resistance and increased mortality. Therefore, in patients with a confirmed diagnosis of schizophrenia, a lifelong continuous therapy is currently most likely indicated, ideally with antipsychotic agents for which adherence is directly measurable and improved. In the case of treatment resistant clozapine is the agent of choice, followed by electroconvulsive therapy, which also has the best evidence as augmentation treatment in cases of clozapine resistance. CONCLUSION: New therapeutic agents with improved efficacy and tolerability as well as effectiveness for negative symptoms and cognitive disturbance are needed.
Asunto(s)
Antipsicóticos , Esquizofrenia , Adulto , Antipsicóticos/uso terapéutico , Clozapina/uso terapéutico , Humanos , Olanzapina/uso terapéutico , Risperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológicoRESUMEN
OBJECTIVE: To compare cost-effectiveness of integrated care with therapeutic assertive community treatment (IC-TACT) versus standard care (SC) in multiple-episode psychosis. METHOD: Twelve-month IC-TACT in patients with schizophrenia-spectrum and bipolar I disorders were compared with a historical control group. Primary outcomes were entropy-balanced cost-effectiveness based on mental healthcare costs from a payers' perspective and quality-adjusted life years (QALYs) as a measure of health effects during 12-month follow-up. RESULTS: At baseline, patients in IC-TACT (n = 214) had significantly higher illness severity and lower functioning than SC (n = 56). Over 12 months, IC-TACT had significantly lower days in inpatient (10.3 ± 20.5 vs. 28.2 ± 44.9; P = 0.005) and day-clinic care (2.6 ± 16.7 vs. 16.4 ± 33.7; P = 0.004) and correspondingly lower costs (-55 084). Within outpatient care, IC-TACT displayed a higher number of treatment contacts (116.3 ± 45.3 vs. 15.6 ± 6.3) and higher related costs (+1417). Both resulted in lower total costs in IC-TACT (mean difference = -13 248 ± 2975, P < 0.001). Adjusted incremental QALYs were significantly higher for IC-TACT versus SC (+0.10 ± 0.37, P = 0.05). The probability of cost-effectiveness of IC-TACT was constantly higher than 99%. CONCLUSION: IC-TACT was cost-effective compared with SC. The use of prima facies 'costly' TACT teams is highly recommended to improve outcomes and save total cost for patients with severe psychotic disorders.
Asunto(s)
Servicios Comunitarios de Salud Mental/economía , Análisis Costo-Beneficio/estadística & datos numéricos , Prestación Integrada de Atención de Salud/estadística & datos numéricos , Trastornos Psicóticos/terapia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To quantify the risk of hip fracture, thromboembolism, stroke, myocardial infarction, pneumonia and sudden cardiac death associated with exposure to antipsychotics. METHODS: Systematic searches were conducted in Medline, Embase and PsycINFO from inception until 30/07/2018 for systematic reviews of observational studies. AMSTAR-2 was used for the quality assessment of systematic reviews, while the strength of associations was measured using GRADE and quantitative umbrella review criteria (URC). RESULTS: Sixty-eight observational studies from six systematic reviews were included. The association between antipsychotic exposure and pneumonia was the strongest [URC = class I; GRADE = low quality; odds ratio (OR) = 1.84, 95% confidence interval (CI) = 1.62-2.09; participants = 28 726; age = 76.2 ± 12.3 years], followed by the association with hip fracture (URC = class II; GRADE = low quality; OR = 1.57, 95% CI = 1.42-1.74; participants = 5 288 118; age = 55.4 ± 12.5 years), and thromboembolism (URC = class II; GRADE = very low quality; OR = 1.55, 95% CI = 1.31-1.83; participants = 31 417 175; age = 55.5 ± 3.2 years). The association was weak for stroke (URC = class III; GRADE = very low quality; OR = 1.45, 95% CI = 1.24-1.70; participants = 65 700; age = 68.7 ± 13.8 years), sudden cardiac death (URC = class III; GRADE = very low quality; OR = 2.24, 95% CI = 1.45-3.46; participants = 77 488; age = 52.2 ± 6.2 years) and myocardial infarction (URC = class III; GRADE = very low quality; OR = 2.21, 95% CI = 1.41-3.46; participants = 399 868; age = 74.1 ± 9.3 years). CONCLUSION: The most robust results were found for the risk of pneumonia, followed by the risk of hip fracture and thromboembolism. For stroke, sudden cardiac death and myocardial infarction, the strength of association was weak. The observational nature of the primary studies may represent a source of bias.
Asunto(s)
Antipsicóticos/efectos adversos , Muerte Súbita Cardíaca/etiología , Fracturas de Cadera/etiología , Infarto del Miocardio/etiología , Estudios Observacionales como Asunto , Neumonía/etiología , Accidente Cerebrovascular/etiología , Tromboembolia/etiología , Muerte Súbita Cardíaca/epidemiología , Fracturas de Cadera/epidemiología , Humanos , Infarto del Miocardio/epidemiología , Neumonía/epidemiología , Accidente Cerebrovascular/epidemiología , Tromboembolia/epidemiologíaRESUMEN
OBJECTIVE: Treatment with most antipsychotics is associated with an increased risk of weight gain and metabolic disturbances. In a randomized trial, we previously demonstrated that 16 weeks of glucagon-like peptide-1 receptor agonist liraglutide treatment vs. placebo significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. The aim of this study was to investigate whether the beneficial effects of the 16-week intervention were sustained beyond the intervention period. METHOD: One year after completion of the intervention, we investigated changes in body weight, fasting glucose, glycated hemoglobin, C-peptide, and lipids comparing 1-year follow-up levels to end of treatment (week 16) and baseline (week 0) levels. RESULTS: From end of treatment to the 1-year follow-up, body weight had increased in the liraglutide-treated group. However, compared to baseline levels, the placebo-subtracted body weight loss remained significantly reduced (-3.8 kg, 95% CI: -7.3 to -0.2, P = 0.04). Fasting glucose, glycated hemoglobin, C-peptide, and lipids had each returned to baseline levels 1 year after stopping liraglutide. CONCLUSION: The body weight reduction during 16 weeks of liraglutide treatment was partially sustained 1 year after the intervention was completed. However, the improvements in other metabolic parameters returned to baseline levels.
Asunto(s)
Hipoglucemiantes/farmacología , Liraglutida/farmacología , Obesidad/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Estado Prediabético/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Glucemia/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Péptido C/efectos de los fármacos , Clozapina/efectos adversos , Clozapina/uso terapéutico , Dinamarca/epidemiología , Ayuno , Femenino , Estudios de Seguimiento , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hemoglobina Glucada/efectos de los fármacos , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Metabolismo de los Lípidos/efectos de los fármacos , Liraglutida/administración & dosificación , Liraglutida/uso terapéutico , Masculino , Persona de Mediana Edad , Obesidad/inducido químicamente , Obesidad/epidemiología , Olanzapina/efectos adversos , Olanzapina/uso terapéutico , Sobrepeso/inducido químicamente , Sobrepeso/epidemiología , Placebos/administración & dosificación , Estado Prediabético/inducido químicamente , Estado Prediabético/epidemiología , Esquizofrenia/sangre , Esquizofrenia/diagnóstico , Esquizofrenia/tratamiento farmacológico , Adulto JovenRESUMEN
OBJECTIVE: To test the validity and sensitivity of the six-item version (PANSS-6) of the 30-item Positive and Negative Syndrome Scale (PANSS-30) in treatment-resistant schizophrenia (TRS). METHOD: Using data from the clozapine phase (2E) of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, we investigated the following: (i) The scalability of PANSS-6 and PANSS-30; (ii) The correlation between PANSS-6 and PANSS-30 total scores; (iii) Whether PANSS-6 could identify cross-sectional symptom remission; and (iv) The efficacy of clozapine, olanzapine, risperidone and quetiapine in TRS using the 'speed of change' on PANSS-6 and PANSS-30 (change in total score per week) as outcome measures. RESULTS: We found that (i) only PANSS-6 and not PANSS-30 was scalable; (ii) The correlation between PANSS-6 and PANSS-30 total scores was high (Spearman coefficient: 0.85), (iii) PANSS-6 accurately identified cross-sectional symptom remission as defined by the Andreasen et al. criteria; and (iv) The only antipsychotic that caused improvement (speed of change significantly lower than 0 during the first three months of treatment) was clozapine, both when using PANSS-6 (speed of change: -0.50 points/week; 95%CI: -0.84, -0.17) and PANSS-30 (speed of change: -1.41 points/week; 95%CI: -2.80, -0.02) as outcome measures. CONCLUSION: PANSS-6 validly measures severity, remission and antipsychotic efficacy in TRS.
Asunto(s)
Antipsicóticos/farmacología , Clozapina/farmacología , Evaluación de Resultado en la Atención de Salud/normas , Escalas de Valoración Psiquiátrica/normas , Estudios Transversales , Humanos , Olanzapina/farmacología , Fumarato de Quetiapina/farmacología , Reproducibilidad de los Resultados , Risperidona/farmacología , Esquizofrenia , Sensibilidad y EspecificidadRESUMEN
á½ φελÎειν, á¼¢ µá½´ ßλάπτειν (Primum non nocere) - Hιppocrates' principle should still guide daily medical prescribing. Therefore, assessing evidence of psychopharmacologic agents' safety and harms is essential. Randomised controlled trials (RCTs) and observational studies may provide complementary information about harms of psychopharmacologic medications from both experimental and real-world settings. It is considered that RCTs provide a better control of confounding variables, while observational studies provide evidence from larger samples, longer follow-ups, in more representative samples, which may be more reflective of real-life clinical scenarios. However, this may not always hold true. Moreover, in observational studies, safety data are poorly or inconsistently reported, precluding reliable quantitative synthesis in meta-analyses. Beyond individual studies, meta-analyses, which represent the highest level of 'evidence', can be misleading, redundant and of low methodological quality. Overlapping meta-analyses sometimes even reach different conclusions on the same topic. Meta-analyses should be assessed systematically. Descriptive reviews of reviews can be poorly informative. Conversely, 'umbrella reviews' can use a quantitative approach to grade evidence. In this editorial, we present the main factors involved in the assessment of psychopharmacologic agents' harms from individual studies, meta-analyses and umbrella reviews. Study design features, sample size, number of the events of interest, summary effect sizes, p-values, heterogeneity, 95% prediction intervals, confounding factor adjustment and tests of bias (e.g., small-study effects and excess significance) can be combined with other assessment tools, such as AMSTAR and GRADE to create a framework for assessing the credibility of evidence.
Asunto(s)
Metaanálisis como Asunto , Psicofarmacología , Psicotrópicos/efectos adversos , Humanos , Psicotrópicos/uso terapéutico , Proyectos de InvestigaciónRESUMEN
OBJECTIVE: Evidence-based guidance of clinical decision-making for the management of Autism Spectrum Disorder (ASD) is lacking, particularly for co-occurring psychiatric symptoms. This review evaluates treatment evidence for six common symptom targets in children/adolescents with ASD and provides a resource to facilitate application of the evidence to clinical practice. METHOD: A systematic search identified randomized controlled trials (RCTs) and high-quality systematic reviews published between 2007 and 2016, focused on: social interaction/communication impairment, stereotypic/repetitive behaviours, irritability/agitation, attention-deficit/hyperactivity disorder symptoms, mood or anxiety symptoms, and sleep difficulties. We then completed qualitative evaluation of high-quality systematic reviews/meta-analyses and quantitative evaluation of recently published RCTs not covered by prior comprehensive systematic reviews. RESULTS: Recently published RCTs focused on social interaction and communication impairment (trials = 32) using psychosocial interventions. Interventions for irritability/agitation (trials = 16) were mainly pharmacological. Few RCTs focused on other symptom targets (trials = 2-5/target). Integration of these results with our qualitative review indicated that few established treatment modalities exist, and available evidence is limited by small studies with high risk of bias. CONCLUSION: Given the current evidence-base, treatment targets must be clearly defined, and a systematic approach to intervention trials in children/adolescents with ASD must be undertaken with careful consideration of the limitations of safety/efficacy data.
Asunto(s)
Trastornos de Ansiedad/terapia , Trastorno por Déficit de Atención con Hiperactividad/terapia , Trastorno del Espectro Autista/terapia , Trastornos de la Comunicación/terapia , Trastornos del Humor/terapia , Guías de Práctica Clínica como Asunto , Agitación Psicomotora/terapia , Trastornos del Sueño-Vigilia/terapia , Conducta Estereotipada , Adolescente , Trastornos de Ansiedad/etiología , Trastorno por Déficit de Atención con Hiperactividad/etiología , Trastorno del Espectro Autista/complicaciones , Niño , Trastornos de la Comunicación/etiología , Humanos , Trastornos del Humor/etiología , Agitación Psicomotora/etiología , Trastornos del Sueño-Vigilia/etiologíaRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of antidepressant augmentation of antipsychotics in schizophrenia. METHODS: Systematic literature search (PubMed/MEDLINE/PsycINFO/Cochrane Library) from database inception until 10/10/2017 for randomized, double-blind, efficacy-focused trials comparing adjunctive antidepressants vs. placebo in schizophrenia. RESULTS: In a random-effects meta-analysis (studies = 42, n = 1934, duration = 10.1 ± 8.1 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction [standardized mean difference (SMD) = -0.37, 95% confidence interval (CI) = -0.57 to -0.17, P < 0.001], driven by negative (SMD = -0.25, 95% CI = -0.44-0.06, P = 0.010), but not positive (P = 0.190) or general (P = 0.089) symptom reduction. Superiority regarding negative symptoms was confirmed in studies augmenting first-generation antipsychotics (FGAs) (SMD = -0.42, 95% CI = -0.77, -0.07, P = 0.019), but not second-generation antipsychotics (P = 0.144). Uniquely, superiority in total symptom reduction by NaSSAs (SMD = -0.71, 95% CI = -1.21, -0.20, P = 0.006) was not driven by negative (P = 0.438), but by positive symptom reduction (SMD = -0.43, 95% CI = -0.77, -0.09, P = 0.012). Antidepressants did not improve depressive symptoms more than placebo (P = 0.185). Except for more dry mouth [risk ratio (RR) = 1.57, 95% CI = 1.04-2.36, P = 0.03], antidepressant augmentation was not associated with more adverse events or all-cause/specific-cause discontinuation. CONCLUSIONS: For schizophrenia patients on stable antipsychotic treatment, adjunctive antidepressants are effective for total and particularly negative symptom reduction. However, effects are small-to-medium, differ across antidepressants, and negative symptom improvement seems restricted to the augmentation of FGAs.
Asunto(s)
Antidepresivos/farmacología , Antipsicóticos/farmacología , Evaluación de Resultado en la Atención de Salud , Esquizofrenia/tratamiento farmacológico , Antidepresivos/efectos adversos , Antipsicóticos/efectos adversos , Sinergismo Farmacológico , Quimioterapia Combinada , HumanosRESUMEN
OBJECTIVE: The objective of the study was to investigate whether a combined intervention composed of early detection plus integrated care (EDIC) enhances outcomes in patients with early psychosis compared to standard care (SC). METHODS: ACCESS III is a prospective non-randomized historical control design 1-year study examining the efficacy of EDIC (n = 120) vs. SC (n = 105) in patients aged 12-29 years. Primary outcome was the rate of ≥6 months combined symptomatic and functional remission. Additional outcomes comprised the reduction of DUP and course of psychopathology, functioning, quality of life, and satisfaction with care. RESULTS: In observed cases, 48.9% in the EDIC and 15.2% in the SC group reached the primary endpoint. Remission was predicted by EDIC (OR = 6.8, CI: 3.15-14.53, P < 0.001); younger age predicted non-remission (OR = 1.1, CI: 1.01-1.19, P = 0.038). Linear regressions indicated a reduction of DUP in EDIC (P < 0.001), but not in SC (P = 0.41). MMRMs showed significantly larger improvements in PANSS positive (P < 0.001) and GAF (P < 0.01) scores in EDIC vs. SC, and in EDIC over time in CGI-Severity (P < 0.001) and numerically in Q-LES-Q-18 (P = 0.052). CONCLUSIONS: EDIC lead to significantly higher proportions of patients achieving combined remission. Moderating variables included a reduction of DUP and EDIC, offering psychotherapeutic interventions.
Asunto(s)
Intervención Médica Temprana/estadística & datos numéricos , Atención al Paciente/estadística & datos numéricos , Trastornos Psicóticos/dietoterapia , Adolescente , Adulto , Diagnóstico Precoz , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Estudios Prospectivos , Trastornos Psicóticos/epidemiología , Adulto JovenRESUMEN
Anticholinergic medications are used to treat extrapyramidal adverse effects induced by antipsychotics. Anticholinergics are associated with adverse effects: constipation, dry mouth and worsening of cognitive function. Anticholinergics have potential for abuse and are not recommended for long term-treatment. We aimed to investigate the use of anticholinergics in patients with schizophrenia. The national health registers in Denmark were used to examine: The prevalence of anticholinergics in 1996-2012 using a cross-sectional design; geographic variations in the prescription of anticholinergics in 2012; correlates of treatment with anticholinergics. The proportion of patients using anticholinergics decreased significantly from 11.7% in 1996 to 5.7% in 2012. The prescription pattern varied considerably between national regions in 2012, ranging from 4.0% in the Capital Region to 8.1% in the Northern Denmark Region. Long-term use of anticholinergics was predicted by older age, age at debut of schizophrenia, receiving early retirement pension, typical antipsychotic use, antipsychotic polypharmacy, typical + atypical antipsychotics, antidepressant treatment, high doses of antipsychotics measured in defined-daily-dose, physical comorbidity and psychiatrists` greater caseload. Use of anticholinergics declined during the study period, and showed substantial variation across the regions in 2012. Long-term use was linked to typical antipsychotic use and variables that are associated with greater illness severity.
Asunto(s)
Antagonistas Colinérgicos/uso terapéutico , Farmacoepidemiología/tendencias , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/epidemiología , Adulto , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Antagonistas Colinérgicos/efectos adversos , Cognición/efectos de los fármacos , Cognición/fisiología , Estudios Transversales , Dinamarca/epidemiología , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Farmacoepidemiología/métodos , Polifarmacia , Esquizofrenia/diagnósticoRESUMEN
Antipsychotic polypharmacy (APP) is commonplace despite lacking evidence of its effectiveness. We aimed to identify psychiatrists' rationale for and attitudes towards APP and to determine if attitudes influence antipsychotic polypharmacy prescription rates in a survey of a nationally representative sample of Nigerian psychiatrists (of which a majority were senior trainees: 74.2%). Prescriber characteristics, practices and attitudes were compared in 'high' (>30%) vs. 'low' (≤30%) antipsychotic polypharmacy prescribers and results were adjusted for multiple comparisons. Altogether, prescribers reported utilizing antipsychotic polypharmacy in 36.2% of their patients. Compared to 'low' antipsychotic polypharmacy prescribers, 'high' prescribers were significantly more likely using first-generation antipsychotics (FGA) combination, to have attempted a switch to monotherapy in less patients, or been successful in doing so. 'High' and 'low' antipsychotic polypharmacy prescribers were equally moderately concerned about the effects of antipsychotic polypharmacy and also did not differ regarding reasons not justifying antipsychotic polypharmacy. In a multivariable, backward elimination logistic regression model, 'low' antipsychotic polypharmacy was associated with having successfully switched patients to monotherapy, whereas the 'high' antipsychotic polypharmacy was associated with preferring FGA+FGA combinations and aiming for a reduction of non-antipsychotic medications. Antipsychotic polypharmacy is common among psychiatrists in Nigeria, with 'high' and 'low' antipsychotic polypharmacy prescribers sharing similar concerns/attitudes, but differing regarding their primary aim for antipsychotic polypharmacy and in their specific antipsychotic polypharmacy use characteristics.
Asunto(s)
Antipsicóticos/uso terapéutico , Actitud del Personal de Salud , Polifarmacia , Psiquiatría , Esquizofrenia/tratamiento farmacológico , Femenino , Humanos , Modelos Logísticos , Masculino , Nigeria , Pautas de la Práctica en Medicina , Psicología del Esquizofrénico , Encuestas y CuestionariosRESUMEN
This review aims to describe the importance of i) detecting individuals at clinical high-risk for psychosis (schizophrenia) or bipolar disorder, especially in children and adolescents, in order to enable early intervention, and ii) evaluating different intervention strategies, especially pharmacotherapy, during the subsyndromal or "prodromal" stages of these severe and often debilitating disorders. The different approaches regarding the psychotic and bipolar clinical high-risk state are discussed, including reasons and evidence for early (pharmacological) intervention and risks of treatment vs. non-treatment. Only 10 prospective studies of antipsychotics (randomized=4) and 6 prospective studies of non-antipsychotic pharmacologic agents (randomized=3, i. e., omega-3 fatty acids=2, glycine=1) for the psychotic clinical high-risk state and only 4 prospective studies of mood stabilizing medications for the bipolar clinical high-risk state (randomized=2, i. e., lithium=1, valproate=1) were detected. Based on the minimal efficacy data, adverse effect risks, especially in pediatric populations, nonspecific psychopathology, and unknown true risk for the development of either psychosis or bipolar disorder or of chronically disabling symptoms and disability, medication treatment currently remains second choice after psychosocial intervention. Additional research in this area is clearly needed in order to shed more light on the relevance and predictive value of potentially prodromal symptoms, their identification and most appropriate management options.
Asunto(s)
Antipsicóticos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Trastornos Psicóticos/tratamiento farmacológico , Adolescente , Trastorno Bipolar/dietoterapia , Niño , Ensayos Clínicos como Asunto , HumanosRESUMEN
OBJECTIVE: To systematically examine the randomized controlled trial (RCT) evidence regarding efficacy and tolerability of topiramate cotreatment with antipsychotics in schizophrenia-spectrum disorders. METHODS: Random-effects meta-analysis of RCTs of topiramate cotreatment with antipsychotics vs. placebo/ongoing antipsychotic treatment in schizophrenia-spectrum disorders. Standardized or weighted mean difference (SMD/WMD), risk ratio (RR) ±95% confidence intervals (CIs), and number needed to harm (NNH) were calculated. RESULTS: Across 16 RCTs (n = 934, duration = 11.8 ± 5.6 weeks), topiramate outperformed the comparator regarding change/endpoint of total (SMD: -0.58, 95% CI: -0.82, -0.35, P < 0.00001), positive (SMD: -0.37, 95% CI: -0.61, -0.14, P = 0.002), negative (SMD: -0.58, 95% CI: -0.87, -0.29, P < 0.0001), and general symptoms (SMD: -0.68, 95% CI: -0.95, -0.40, P < 0.00001). Furthermore, topiramate was superior regarding body weight (WMD: -2.75 kg, 95% CI: -4.03, -1.47, P < 0.0001), body mass index (BMI) (WMD: -1.77, 95% CI: -2.38, -1.15, P < 0.00001), triglycerides (P = 0.006), and insulin levels (P < 0.00001). Superiority regarding psychopathology and body weight/BMI was consistent across Chinese/Asian and Western RCTs, double-blind and open designs, clozapine and non-clozapine cotreatment, augmentation and co-initiation RCTs, and higher and lower quality RCTs. In meta-regression analyses, topiramate's efficacy for total symptoms was moderated by shorter illness duration (P = 0.047), while weight loss was greater in prevention/co-initiation vs. intervention/augmentation RCTs (-4.11 kg, 95% CI: -6.70, -1.52 vs. -1.41 kg, 95% CI: -2.23, -0.59, P < 0.001). All-cause discontinuation was similar between topiramate and comparators (RR: 1.28, 95% CI: 0.91, 1.81, P = 0.16). While topiramate led to more concentration/attention difficulties (P = 0.03, NNH = 8, 95% CI=4-25), psychomotor slowing (P = 0.02, NNH = 7, 95% CI = 4-25), and paresthesia (P = 0.05, NNH = 2, 95% CI = 4-33), it led to less ≥7% weight gain (P = 0.0001, NNH = 2, 95% CI = 2-3) and constipation (P = 0.04, NNH = 9, 95% CI = 5-100) than the comparator. CONCLUSIONS: These results indicate that adjunctive topiramate to antipsychotics is an effective and safe treatment choice for symptomatic improvement and weight reduction in patients with schizophrenia-spectrum disorders.