مقاله انگلیسی رایگان در مورد درمان علائم منفی در اسکیزوفرنی – اسپرینگر 2017

Negative symptoms (such as amotivation and diminished expression) associated with schizophrenia are a major health concern. Adequate treatment would mean important progress with respect to quality of life and participation in society. Distinguishing primary from secondary negative symptoms may inform treatment options. Primary negative symptoms are part of schizophrenia. Well-known sources of secondary negative symptoms are psychotic symptoms, disorganisation, anxiety, depression, chronic abuse of illicit drugs and alcohol, an overly high dosage of antipsychotic medication, social deprivation, lack of stimulation and hospitalisation. We present an overview of reviews and meta-analyses of double-blind, controlled randomised trials, in which the efficacy of pharmacological and non-pharmacological interventions for negative symptoms was assessed. Unfortunately, there have been very few clinical trials focusing on primary negative symptoms and selecting chronically ill patients with predominant persistent negative symptoms. An important limitation in many of these studies is the failure to adequately control for potential sources of secondary negative symptoms. At present, there is no convincing evidence regarding efficacy for any treatment of predominant persistent primary negative symptoms. However, for several interventions there is short-term evidence of efficacy for negative symptoms. This evidence has mainly been obtained from studies in chronically ill patients with residual symptoms and studies with a heterogeneous study population of patients in both the acute and chronic phase. Unfortunately, reliable information regarding the distinction between primary and secondary negative symptoms is lacking. Currently, early treatment of psychosis, add-on therapy with aripiprazole, antidepressants or topiramate, music therapy and exercise have been found to be useful for unspecified negative symptoms. These interventions can be considered carefully in a shared decision-making process with patients, and are promising enough to be examined in large, well-designed long-term studies focusing on primary negative symptoms. Future research should be aimed at potential therapeutic interventions for primary negative symptoms since there is a lack of research in this field.

Introduction

The lifetime prevalence estimate for schizophrenia is 0.4% [1]. Schizophrenia is a heterogeneous disorder presenting with positive and negative symptoms, emotional dysregulation and cognitive disturbances. Antipsychotic drugs have a moderate beneficial effect on positive symptoms [2, 3]. Unfortunately, negative symptoms respond poorly to medication [4], while these symptoms mainly account for functional and social outcome in schizophrenia [5]. Primary negative symptoms are thought to be intrinsic to schizophrenia. By definition, negative symptoms mean the absence of normal behaviour. Two subdomains can be distinguished: (1) avolition, apathy, lack of energy, anhedonia and social withdrawal, and (2) expressive deficits, which include blunted affect and poverty of speech [6]. Negative symptoms are associated with neurocognitive impairments [7] involving olfaction, social cognition, global cognition and language [8]. Patients with prominent negative symptoms fail to respond to both internal and external stimuli. Apathy does not seem to be associated with reduced attention to novel stimuli, but with slowed information processing [9]. Avolition may result from aberrant reinforcement learning. Patients with prominent negative symptoms fail to recognize the relative value of different rewards [10]. Impaired reward processing results in a limited behavioural repertoire and failure to activate behaviour to accomplish goals. In addition to disruptions in anticipatory pleasure and reward learning, impaired effort-based decision-making and social motivation also contribute to negative symptoms [11]. Psychomotor poverty with a flattened affect and decrease in spontaneous movements contribute to the loss of expression of emotions [12]. It is possible that psychomotor slowing with a decreased processing speed underlies verbal working memory impairment, which may mediate the association between working memory span deficit and negative symptoms [13]. A correlation has been found between working memory and awareness of illness, which explains the association between negative symptoms and poorer insight [14]. In the first 5 years of schizophrenia, negative symptoms decrease or remain stable [15]. Evidence indicating that negative symptoms persist in the long term is inconsistent [15, 16], which may suggest that more improvement of negative symptoms can be achieved than previously assumed [16].