Negative Symptoms in Schizophrenia: The Importance of Identification and Treatment
By Dawn I. Velligan, PhD and Larry D. Alphs, PhD |
March 1, 2008
Dr Velligan is professor and codirector of the Division of Schizophrenia and Related Disorders in the department of psychiatry at the University of Texas Health Science Center at San Antonio. Dr Alphs is therapeutic area leader in psychiatry, Medical and Scientific Affairs, for Janssen, LP, Ortho-McNeil Janssen Scientific Affairs, LLC, Titusville, NJ. Dr Velligan reports that she has the following relationships: AstraZeneca: consultant, travel expenses, honoraria, research grant, Speakers' Bureau, and advisory board; Bristol-Myers Squibb: consultant, honoraria, and research grant; Janssen: consultant, honoraria, research grant, Speakers' Bureau, and advisory board; Pfizer: consultant, honoraria, research grant, and Speakers' Bureau; and Organon: consultant, advisory board, and research grant. Dr Alphs reports that he is employed by Ortho-McNeil Janssen.
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.
- Goff DC, Lamberti JS, Leon AC, et al. A placebo-controlled add-on trial of the ampakine, CX516, for cognitive deficits in schizophrenia. Neuropsychopharmacology. 2007 May 9; [Epub ahead of print].
- Velligan DI, Prihoda TJ, Ritch JL, et al. A randomized single-blind pilot study of compensatory strategies in schizophrenia outpatients. Schizophr Bull. 2002;28: 283-292.
1. Jaeger J, Berns SM, Czobor P. The multidimensional scale of independent functioning: a new instrument for measuring functional disability in psychiatric populations. Schizophr Bull. 2003;29:153-168.
2. Wu EQ, Birnbaum HG, Shi L, et al. The economic burden of schizophrenia in the United States in 2002. J Clin Psychiatry. 2005;66:1122-1129.
3. Wyatt RJ, Hentler I, Leary MC, Taylor E. An economic evaluation of schizophrenia 1991. Soc Psychiatr Psychiatr Epidemiol. 1995;30:196-205.
4. Souetre E. Economic evaluation in schizophrenia. Neuropsychobiology. 1997;35:67-69.
5. Trauer T, Duckmanton RA, Chiu E. Estimation of costs of public psychiatric treatment. Psychiatr Serv. 1998;49:440-442.
6. Sharma T, Antonova L. Cognitive function in schizophrenia. Deficits, functional consequences, and future treatment. Psychiatr Clin North Am. 2003;26:25-40.
7. Anthony WA, Blanch A. Supported employment for persons who are psychiatrically disabled: an historical and conceptual perspective. Psychosoc Rehabil J. 1987;11:5-23.
8. Mueser KT, Becker DR, Wolfe R. Supported employment, job preferences, and job tenure and satisfaction. J Ment Health. 2001;10:411-417.
9. McGurk SR, Mueser KT. Cognitive functioning, symptoms, and work in supported employment: a review and heuristic model. Schizophr Res. 2004;70: 147-173.
10. Velligan DI, Mahurin RK, Diamond PL, et al. The functional significance of symptomatology and cognitive function in schizophrenia. Schizophr Res. 1997; 25:21-31.
11. Lysaker PH, Lancaster RS, Nees MA, Davis LW. Attributional style and symptoms as predictors of social function in schizophrenia. J Rehabil Res Dev. 2004; 41:225-232.
12. Lysaker PH, Davis LW. Social function in schizophrenia and schizoaffective disorder: associations with personality, symptoms, and neurocognition. Health Qual Life Outcomes. 2005;2:15.
13. Norman RM, Malla AK, McLean T, et al. The relationship of symptoms and level of functioning in schizophrenia to general well-being and the Quality of Life Scale. Acta Psychiatr Scand. 2000;102:303-309.
14. Milev P, Ho BC, Arndt S, Andreasen NC. Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: a longitudinal first-episode study with 7-year follow-up. Am J Psychiatry. 2005;162:495-506.
15. Kirkpatrick B, Fischer B. Subdomains within the negative symptoms of schizophrenia: commentary. Schizoph Bull. 2006;32:246-249.
16. Kurtz MM. Symptoms versus neurocognitive skills as correlates of everyday functioning in severe mental illness. Expert Rev Neurother. 2005;6:47-56.
17. Provencher HL, Mueser KT. Positive and negative symptom behaviors and caregiver burden in the relatives of persons with schizophrenia. Schizophr Res. 1997;26:71-80.
18. Alphs L. An industry perspective on the NIMH consensus statement on negative symptoms. Schizophr Bull. 2006;32:225-230.
19. Leeuwenkamp O, Velligan DI, Wang M, et al. Association between changes on the negative symptom assessment scale and measures of functional outcome in schizophrenia. Schizophr Bull. 2007;33:594-595.
20. Erhart SM, Marder SR, Carpenter WT. Treatment of schizophrenia negative symptoms: future prospects. Schizophr Bull. 2006;32:234-237.
21. Tarrier N. Negative symptoms in schizophrenia: comments from a clinical psychology perspective. Schizophr Bull. 2006;32:231-233.
22. Carpenter WT, Arango C, Buchanan RW, Kirkpatrick B. Deficit psychopathology and a paradigm shift in schizophrenia research. Biol Psychiatry. 1999; 46:352-360.
23. Selten JP, Wiersma D, van den Bosch RJ. Discrepancy between subjective and objective ratings for negative symptoms. J Psychiatr Res. 2000;34:11-13.
24. Alphs L, Summerfelt A, Lann H, Muller RJ. The Negative Symptom Assessment: a new instrument to assess negative symptoms of schizophrenia. Psychopharmacol Bull. 1989;25:159-163.
25. Jockers-Scherubl MC, Bauer A, Godemann F, et al. Negative symptoms of schizophrenia are improved by the addition of paroxetine to neuroleptics: a double-blind placebo-controlled study. Int Clin Psycho- pharmacol. 2005;20:27-31.
26. Buckley PF, Stahl SM. Pharmacological treatment of negative symptoms of schizophrenia: therapeutic opportunity or cul-de-sac? Acta Psychiatr Scand. 2007;115:93-100.
27. Marder SR. Lessons from each drug trial. Am J Psychiatry. 2007;164:375-376.
28. Alphs L, Panagides J, Lancaster S. Asenapine in the treatment of negative symptoms of schizophrenia: clinical trial design and rationale. Psychopharmacol Bull. 2007;40:41-53.
29. Laughren T, Levin R. Food and Drug Administration perspective on negative symptoms in schizophrenia as a target for a drug treatment claim. Schizophr Bull. 2006;32:220-222.
30. Goff DC, Lamberti JS, Leon AC, et al. A placebo-controlled add-on trial of the ampakine, CX516, for cognitive deficits in schizophrenia. Neuropsychopharmacology. 2007 May 9; [Epub ahead of print].
31. Marder SR. Integrating pharmacological and psychosocial treatments for schizophrenia. Acta Psychiatr Scand. 2000;102:87-90.
32. Velligan DI, Bow-Thomas CC, Huntzinger CD, et al. Randomized controlled trial of the use of compensatory strategies to enhance adaptive functioning in outpatients with schizophrenia. Am J Psychiatry. 2000; 157:1317-1323.
33. Velligan DI, Prihoda TJ, Ritch JL, et al. A randomized single-blind pilot study of compensatory strategies in schizophrenia outpatients. Schizophr Bull. 2002;28:283-292.
34. Glynn SM, Marder SR, Liberman RP, et al. Supplementing clinic-based skills training with manual-based community support sessions: effects on social adjustment of patients with schizophrenia. Am J Psychiatry. 2002;159:829-837.
35. Granholm E, McQuaid JR, McClure FS, et al. Randomized controlled trial of cognitive behavioral social skills training for older people with schizophrenia: 12-month follow-up. J Clin Psychiatry. 2007;68:730-737.
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