Schizophrenia treatment with antipsychotics

Since early detection and intervention in schizophrenia is important for maximizing outcomes, treatment with antipsychotic medications should begin as soon as psychotic symptoms are recognized. Antipsychotic medications are the cornerstone of therapy for people with schizophrenia, and most patients are on lifelong therapy since non-adherence and discontinuation of antipsychotics are associated with high relapse rates. If other symptoms are present such as depression and anxiety, these symptoms should also be aggressively treated. Additionally, psychosocial treatments should be used concomitantly to improve patient outcomes. 

Younger patients with schizophrenia may be less responsive to pharmacotherapy than adult patients ( 164, 165). Nonresponse to typical antipsychotics is as high as 40% to 50% in some reports. Thought disorder is the most drug-refractory of the classic psychotic symptoms in children and adolescents with schizophrenia. Thus, even when the more florid symptoms (e.g., hallucinations and delusions) abate following treatment with antipsychotics, these patients frequently continue to have substantial impairment in social functioning and scholastic performance. 

Antipsychotic drugs are also indicated for schizoaffective disorders, which share characteristics of both schizophrenia and affective disorders. No fundamental difference between these two diagnoses has been reliably demonstrated. They are part of a continuum with bipolar psychotic disorder. The psychotic aspects of the illness require treatment with antipsychotic drugs, which may be used with other drugs such as antidepressants, lithium, or valproic acid. The manic phase in bipolar affective disorder often requires treatment with antipsychotic agents, although lithium or valproic acid supplemented with high-potency benzodiazepines (eg, lorazepam or clonazepam) may suffice in milder cases. Recent controlled trials support the efficacy of monotherapy with atypical antipsychotics in the acute phase (up to 4 weeks) of mania, and olanzapine and quetiapine has been approved for this indication. 

McClure RK, Phillips I, Jazayerli R, Barnett A, Coppola R, et al. 2006. Regional change in brain morphometry in schizophrenia associated with antipsychotic treatment. Psychiatry Res 148(2-3) 121-132. 

Bertolino A, Callicott JH, Mattay VS, Weidenhammer KM, Rakow R, et al. 2001. The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia. Biol Psychiatry 49 39-46. 

Bustillo JR, Rowland LM, Jung R, Brooks WM, Qualls C, et al. 2007. Proton magnetic resonance spectroscopy during initial treatment with antipsychotic medication in schizophrenia. Neuropsychopharmacology 33 2456-2466. 

Schroeter ML, Abdul-Khaliq H, Fruhauf S, Hohne R, Schick G, Diefenhacher A, Blasig IE (2003) Serum SIOOB is increased dnring early treatment with antipsychotics and in deficit schizophrenia. Schizophr Res 62 231-236. 

In summary, existing drug treatments for schizophrenia are of limited efficacy and have substantial side effects. New treatment can arise only on the basis of a new hypothesis. The phospholipid hypothesis of schizophrenia provides the theoretical basis for treatment with PUPA supplementation. Pre vlous studies using n-6 supplementation have had mixed results. We now have evidence from a double-blind, placebo-controlled trial that EPA, but not DHA, is effective in reducing the symptoms of schizophrenia. It is possible that the response to EPA is impaired by concomitant treatment with antipsychotic drugs that damage membrane phospholipids. The best treatment effects of EPA have been seen in patients who are otherwise unmedicated or who are currently taking clozapine. This remains to be explored further. 

The cornerstone of treatment is antipsychotic medications. Because most patients with schizophrenia relapse when not medicated, long-term treatment is usually necessary. 

For approximately 20% to 30% of people with schizophrenia, drug treatment is ineffective. A standard definition of treatment resistance includes patients who have persistent positive symptoms despite treatment with at least two different antipsychotics given at adequate doses (at least 600 chlorpro-mazine equivalents) for an adequate duration (4 to 6 weeks). In addition, patients must have a moderately severe illness as defined by rating instruments, and have a persistence of illness for at least 5 years.40 These patients are often highly symptomatic and require extensive periods of hospital care. 

Lee, C. et al. (2006). Treatment with olanzapine, risperidone or typical antipsychotic drugs in Asian patients with schizophrenia. Aust. N. Z. J. Psychiatry, 40, 437-45. 

Fortunately, new treatments have greatly improved the plight of the patient with schizophrenia. Thanks in large part to the introduction of newer antipsychotic medications, few patients with this disease spend their lives in long-term psychiatric hospitals anymore. However, we have a long way to go. Individuals with schizophrenia are currently a sizeable proportion of both the homeless population and the prison population in the United States. Even with the great advances in schizophrenia treatment in the last 50 years, this illness still takes a tremendous toll on the lives of its sufferers and their families. 

One of the more methodologically rigorous studies on the utility of TCA/antipsychotic combinations in treating PMD was completed by Spiker et al. [1985). In this study, 54 patients who met criteria for depression with psychotic features on the Schedule for Affective Disorders and Schizophrenia [Endicott and Spitzer 1978) and by Research Diagnostic Criteria [Spitzer et al. 1985) were randomly selected to treatment with amitriptyline alone, perphenazine alone, or the combination of two drugs. After a 7-day placebo washout, patients were treated for 35 days with doses averaging approximately 50 mg/day of perphenazine and approximately 200 mg/day of ami-... 

Evidence indicates that the long-term outcome for a patient with schizophrenia is better when treatment of the acute episode is initiated rapidly. After a patient s first psychotic episode, treatment with the antipsychotic medication should be continued for at least 1 year after a full remission of psychotic symptoms. A trial period without medication may then be considered, except for patients with a history of serious suicide attempts or violent aggressive behavior... 

Muller and Schoneich (1992) also reported on favorable experience with intensive outpatient psychotherapy combined with antipsychotic drug treatment. On the basis of a before-and-after comparison over 2x5 years in a university outpatient clinic, they were able to show that the duration of rehospitalizations required by 89 patients could be reduced from a mean of 10 weeks to 2 weeks per year when a special schizophrenia outpatient service offering individualized psychotherapy and psychosocial treatment was available to the patients instead of the routine psychiatric outpatient service. A beneficial effect of psychotherapy was demonstrated both in those patients taking antipsvchotics continuously for long-term prophylaxis and in those taking the drugs intermittently when prodromal symptoms appeared in order to prevent relapse. 

Harvey, P.D., Keefe, R.S.E. Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am. J. Psychiatry 158, 176-184, 2001. 

About 30% of patients with schizophrenia show no, or very poor response, to the drugs described above or may have unacceptabie adverse effects. Around haif of these wiii achieve better response on ciozapine. Ciozapine carries a 5-10% risk of neutropenia and 1% risk of agranuiocytosis, hence its use is restricted to patients resistant to treatment with other antipsychotics. Reguiar monitoring of the neutrophii count is mandatory. 

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