Management of the Negative Symptoms of Schizophrenia: New Treatment Options

This article presents a systematic review of pharmacological treatment for negative symptoms of schizophrenia, based on MEDLINE searches from 1995 to September 2002 to identify pertinent clinical trials. The pharmacotherapy of negative symptoms in schizophrenia includes novel/atypical antipsychotics and classical antipsychotics, as well as antidepressants, glutamatergic compounds, antiepileptic drugs and estrogens. In the assessment of therapy for negative symptoms of schizophrenia, it is imperative that better studies of sound methodology are performed. In such studies, some important aspects to be considered include an accurate definition and assessment of negative symptoms (including well designed, valid and reliable rating scales), the differentiation between primary and secondary negative symptoms, an appropriate selection of standard comparators, adequate dosages of comparators (e.g. haloperidol dosages) and an overall optimal study design. Most of the available studies on treating negative symptoms in schizophrenia have focused on the atypical antipsychotics, while other potential candidates, mostly in the context of add-on therapy, have not been so intensively investigated. Atypical antipsychotics have been proven in placebo-controlled trials to be effective in treating negative symptoms of acute schizophrenic episodes. In many of the comparator studies, they showed efficacy in treating negative symptoms that was superior to that of typical antipsychotics. Data on stable, predominant negative symptoms in subchronic or chronic cases of schizophrenia, although limited, have demonstrated the efficacy of atypical antipsychotics. If the beneficial tolerability profile with respect to extrapyramidal symptoms is also taken into account during clinical decision making, the atypical antipsychotics should be preferred for the treatment of negative symptoms. It is also worth noting that the traditional antipsychotics have the risk of inducing negative symptoms in the context of akinesia. The benefits of add-on therapy with SSRIs or a glutamatergic compound are well documented. Estrogen add-on therapy seems promising. Other traditionally suggested approaches, such as comedication with an antiepileptic drug, lithium or beta-adrenoceptor antagonist, cannot generally be recommended on the basis of the available data.