Comorbid depression may require adding an antidepressant, or it may respond directly to an antipsychotic. Lack of stimulation is best handled by placing the patient in a more appropriately stimulating (but not overstimulating) and supportive environment. Nonenduring primary or psychotic-phase negative symptoms respond to effective antipsychotic treatment of the positive symptoms.
Atypical antipsychotics. Conventional antipsychotics (e.g., haloperidol, chlorpromazine) clearly offer some benefit in treating negative symptoms, but they have a much greater effect on positive symptoms.15 Using higher-than-appropriate doses diminishes their effect on negative symptoms and may result in severe EPS.
Two-thirds of the approximately 35 studies comparing conventional and atypical antipsychotics in treating negative symptoms have found atypicals to be significantly more effective (regardless of which atypical was used). In general, atypical antipsychotics improve negative symptoms by about 25%, compared with 10 to 15% improvement with conventional agents.16,17
Much of the greater benefit with atypicals appears to be related to their at least equivalent ability to improve positive symptoms without causing EPS. Consequently, the key to improved patient outcomes is appropriate dosing of atypical antipsychotics that reduces positive symptoms optimally without EPS and without the need for an anticholinergic (Figure).
Whether the greater improvement with atypical agents implies an improvement in primary versus secondary negative symptoms is academic.18 From the patient’s perspective, the greater reduction in negative symptoms is meaningful, regardless of why it occurs.
Other medications. Secondary negative symptoms are most effectively treated with medications directed at the primary etiology. For EPS, change the antipsychotic, reduce the dosage, or add an anticholinergic. For depression, try an antidepressant (preferably a selective serotonin reuptake inhibitor). If a likely contributing factor can be identified, then initiate specific treatment.
Figure
ANTIPSYCHOTICS IMPROVE NEGATIVE SYMPTOMS THROUGH THEIR EFFECT ON PSYCHOSIS
Source: Adapted from Tandon et al. J Psychiatric Res. 1993;27:341-347.
Antipsychotics improve negative symptoms through their effect on positive (psychotic) symptoms, but they do not affect secondary components—such as environmental deprivation and depression—or the primary components of deterioration and premorbid symptoms. Typical and atypical antipsychotics have similar effects on positive symptoms, but atypical antipsychotics carry a lower risk of extrapyramidal side effects.
Empiric therapy—trying one agent and then another in an effort to reduce negative symptoms—is appropriate if done systematically and sequentially. Medications that are found not to be helpful should be discontinued. Electroconvulsive therapy is not effective in treating negative symptoms.
Related resources
- Greden JF, Tandon R (eds). Negative schizophrenic symptoms: pathophysiology and clinical implications. Washington, DC: American Psychiatric Press, 1991.
- Keefe RSE, McEvoy JP (eds). Negative symptom and cognitive deficit treatment response in schizophrenia. Washington, DC: American Psychiatric Press, 2001.
Drug brand names
- Chlorpromazine • Thorazine
- Clozapine • Clozaril
- Haloperidol • Haldol
- Olanzapine • Zyprexa
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Ziprasidone • Geodon