Treatment for Negative Symptoms in Schizophrenia: A Comprehensive Review

Abstract

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.

Alterations of Astrocytes in the Context of Schizophrenic Dementia

“…Traditional pharmacotherapy, based on the dopamine theory of schizophrenia, has several significant limitations. The use of antipsychotics improves predominantly positive symptoms, although there is evidence of improvement of negative symptoms with the use of clozapine (Kane, 1988) and aripiprazole (Veerman et al, 2017). Approximately 25% of patients are resistant to therapy (Remington et al, 2017), in addition, the rate of metabolic syndrome among patients was 32.5% (Mitchell et al, 2013), which worsens life quality and predisposes to cardiovascular diseases.…”

Early-Onset Schizophrenia With Predominantly Negative Symptoms: A Case Study of a Drug-Naive Female Patient Treated With Cariprazine

“…These studies were mainly conducted in patients with general symptoms of schizophrenia, therefore a secondary effect on negative symptoms could not be ruled out. Therefore negative symptom improvement cannot be considered a core component of atypicality (Veerman et al, 2017). Previous studies have demonstrated that no drug had a beneficial effect on negative symptoms when compared to another drug (Arango et al, 2013;Millan et al, 2014;Fusar-Poli et al, 2015), meaning that head to head comparisons of different agents among each other did not result in superiority of one drug to another.…”

Outcomes and safety of concomitant topiramate or metformin for antipsychotics-induced obesity: A randomized controlled trial

“…Topiramate, a new antiepileptic drug, which is increasingly being used as a mood stabilizer in bipolar disorder, and does not cause parkinsonism, has also been used as adjuvant therapy for both the positive and negative symptoms of schizophrenia. [15][16][17] And it holds some promise as an adjunctive therapy for both overweight and treatment of psychotic symptoms. 5 Topiramate has the strongest mean weight loss compared with placebo, metformin, H2 receptor antagonists, and norepinephrine reuptake inhibitors in some reviews 5,8,18,19 although it has some adverse events which are possibly uncommon.…”