However, several instruments have been developed to measure negative symptoms. The Table presents the domains of negative symptoms from the Negative Symptom Assessment (NSA)24 and describes the behaviors that might be observed in each domain. In addition to observation, it is important to ask questions regarding the person's daily activities and engagement with others. A very good question derived from the NSA asks, "Starting from the time you get up, could you tell me how you have spent a typical day in the past week?" From this one question, many different levels of clinical information can be gathered. Does the person generate a multifaceted answer without prompting, or as in the interview above, does the psychiatrist have to pull out every detail? Is the individual enthusiastic about specific activities? Is the individual actively engaged with hobbies, friends, and productive activity during the day? How does this individual compare with a person without schizophrenia of the same age and sex?

Options for treatment of negative symptoms

If negative symptoms are secondary to antipsychotic treatment, the symptoms can be decreased by prescribing an antipsychotic with a low likelihood of producing parkinsonian adverse effects or by reducing the dosage of the current antipsychotic to a level that does not produce extrapyramidal adverse effects. Similarly, if negative symptoms are related to depressed affect, treatments for depression could be considered. While there is no clear evidence that depression in schizophrenia responds to SSRIs, there is some evidence that SSRIs can have a positive impact on negative symptoms.25

Alternatively, if negative symptoms, such as social withdrawal, are caused by immersion in positive symptoms, increasing the dosage of antipsychotic medication or switching to a different antipsychotic may be warranted. If options for treating secondary causes of negative symptoms have failed, the options for pharmacological treatment are limited at present. Current antipsychotic treatments appear to have a modest impact at best on negative symptoms.20,26

The perceived benefits of the atypical antipsychotics on negative symptoms may result primarily from decreasing the burden of extrapyramidal adverse effects rather than better efficacy for core negative symptoms.20 However, there is some evidence that patients treated with atypical antipsychotics are more likely to participate in psychosocial treatments.27 The negative symptom benefits often attributed to atypical antipsychotics may reflect improvements because of the psychosocial interventions and not the medications per se.26 Novel compounds to specifically address negative symptoms are actively being developed,15 and there is a great deal of discussion in the literature about the best study designs to test these compounds for treatment effectiveness.28,29 Although a few studies with ampakines and more traditional broad-spectrum atypical antipsychotics are under way in patients with predominant and/or persistent negative symptoms, results for many of these trials are not yet available. Recently reported results of a trial of an ampakine were negative.30

Combining atypical antipsychotics with psychosocial interventions may have more potential to improve negative symptom outcomes than pharmacotherapy alone.31 In several randomized, rater-blind trials, we have found that environmental supports to prompt and cue adaptive behaviors led to improvement on the motivation factor of the NSA.32,33 Improvements on this factor suggest that individuals are more involved in activities, more engaged in the world around them, are performing grooming and hygiene tasks more regularly, and are more likely to pursue goals. It may be that some of this improvement has to do with decreasing the environmental impoverishment that contributes to secondary negative symptoms rather than improving primary negative signs of schizophrenia. Environmental supports may also prompt individuals to take part in activities they would otherwise not initiate, bypassing some of the apathy associated with negative symptoms. Moreover, social skills training has been found to improve social adjustment for individuals with schizophrenia.34,35 The teaching of skills needed to interact with others makes more successful attempts at initiation of conversations and maintenance of relationships likely. While more work on psychosocial treatments that specifically target negative symptoms is necessary, referral to psychosocial treatment is an important option for physicians to consider in dealing with enduring negative symptoms.

In addition, it is important to educate families about the nature of schizophrenia and negative symptoms. When the family is more aware that poor motivation, flat affect, and decreased involvement and activity reflect symptoms of schizophrenia rather than problems with the character of the individual, this can reduce the likelihood that the family will be overly critical of these behaviors.

Negative symptoms represent an important treatment target in schizophrenia. It is essential to assess for negative symptoms, treat the secondary causes of these symptoms and refer patients and families to psychosocial therapy in an attempt to improve outcomes and quality of life for these individuals. New pharmacological treatments to address negative symptoms should also be actively pursued.

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