Schizophrenia treatment has significantly evolved since Nobel Laureate John Nash was initially treated with electro-convulsive therapy (ECT) and insulin coma “therapies” in the 50-60’s — as portrayed in the movie, A Beautiful Mind. Now, the ultimate goals of schizophrenia clinical management are to reduce or eliminate all associated symptoms, improve socio-behavioral functioning, foster reintegration into society, prevent the relapse of psychotic episodes, and treat or prevent (further) co-morbidity. Clinicians employ a combination of pharmacological (neuroleptic) and psychosocial interventions according to the vulnerability-stress-coping model. The first line of coping is usually medicinal options for the suppression of symptoms and control of disturbed behavior. Psychosocial modalities contribute to improve patient insight and compliance, while promoting the development and implementation of personal goals.

Psychopharmacology

Until recently and since the 1950’s, first-generation antipsychotic medications have been the staple of schizophrenia treatment, including chlorpromazine and haloperidol. The neuroleptic mode of action is presumably dopamine (DA) blockade — for excessive DA activity is shown to cause schizophrenia-like symptoms. The drug affects the mesolimbic-mesocortical system — particular areas of the brain associated with emotions and behavioral control and patterns (Hurd, Pristupa, Herman, Niznik, & Kleinman, 1994). However, if the antipsychotic action and the antischizophrenic action where one and the same, schizophrenic symptoms would cease just hours after administration. This is not the case; rather, gradual improvement is observed over a period of weeks. The antischizophrenic properties of neuroleptics may be attributed to a tolerance mechanism caused by long-term therapy. Essentially, DA neurotransmission returns to more normal state significantly improving positive symptoms.

Most patients taking first-generation antipsychotic agents have some response, whereas 20% have complete remission (Hogarty & Goldberg, 1973; Hogarty, Goldberg, & Schooler, 1974; Hogarty, Goldberg, Schooler, & Ulrich, 1974). However, neuroleptic induced DA blockage in the basal ganglia and more generally the nigrostriatial system contribute to extrapyramidal reactionary movement disorders.

Over the past 15 years, clozapine has served as the progenitor of second-generation (atypical) antipsychotic drugs. All second-generation drugs share the DA blockade mechanism of first-generations; however, they have selective affinity for DA and like receptors and also implicate additional neurotransmission systems (e.g. serotonin). Clinically, their efficacy is established by reducing extrapyramidal therefore improving medication compliance, treating refractory schizophrenia, and reducing negative symptoms and cognitive impairments. However, clozapine is never prescribed as the first antipsychotic for it presents with an increased incidence of seizures and agranulocytosis — an immune system disorder marked by a decrease of granulocytes and thus patients are prone to chronic bacterial infections (Miller, 2000).

Newer second-generation drugs, such as risperdone, olanzapine, quetiapine, and ziprasidone, have an equal or greater clinical efficacy and better adverse effect profile than first generations, and a lower incidence of agranulocytosis than clozapine.

Adverse Effects: Antipsychotics have there share of adverse affects, first-generations more so than newer drugs. The side effects may significantly impact tolerated dosage, anticipated benefits, and patient compliance.

Sedation: The most common adverse effect is sedation especially with low-potency drugs. Long-term administration will gradually ease this effect, while prescribing a single bedtime dose can minimize the effect. Patients with notable agitation and/or insomnia may require more sedating drugs.

Weight gain: Antipsychotic agents are known to significantly increase weight. However, two second-generation agents have little or no weight gain: ziprasidone and aripiprazole. This should serve as a medication selection factor if the body-mass index (BMI) is 25 or greater (Marder et al., 2004).

Extrapyramidal reactions: Generally, acute dystonia (e.g. usually muscle spasms of the head and neck) and akathisia (intense motor restlessness) present early in drug treatment, whereas Parkinson-like effects (e.g. tremor, rigidity, slow motor response) are encountered weeks later. Transient use of anti-muscarinic agents such as benztropine may help to alleviate such effects.

A common reaction especially with first-generation medication, tardive dyskinesia is a late onset extrapyramidal syndrome with increasing risk with prolonged neuroleptic use. The patient has abnormal and involuntary movements of the face and tongue (e.g. smacking lips). Usually, the benefit of antischizophrenic therapy supercedes tardive dyskinesia treatment — terminating neuroleptic administration.

Early Intervention for Psychosis: Pharmacological treatment for schizophrenia is warranted when the patient presents positive symptoms and especially in a first psychotic response — often accompanied by angry outbursts and suicidal thoughts. Early interventions correlate with better prognosis and do not affect differential diagnosis (DeQuardo, 1998). After stabilization, continued pharmacological treatment with psychosocial interventions is warranted.

Psychosocial

Patients with schizophrenia have social, occupational, and self-care difficulties owing to their illness (e.g. anhedonia and apathy), clinical management (e.g. adverse effects), and societal conceptions (i.e. stigmatization and discrimination). Psychosocial interventions aim to improve these troubles by enhancing functioning and aiding pharmacological interventions. Mental health professionals collaboratively design treatment plans that include psychoeducation and cognitive behavior therapy.

Psychoeducation: Patients, family members, caregivers, and close friends are informed about the disorder symptoms, interventions, adherence protocols, and multidimensional plan of therapy. Furthermore, they are specifically instructed on the impact of stress on health and active coping mechanisms than can place the locus of control back to the family unit and patient. Long term psychoeducation programs have significantly improved relapse and rehospitalization rates — 60% to 30% over a period of 2 years (Pitschel-Walz, Leucht, Bauml, Kissling, & Engel, 2001).

Cognitive behavior therapy: Schizophrenic patients on psychopharmacology agents may continue to experience psychotic symptoms. Cognitive behavior therapy for psychosis recognizes the misrepresentations of events in patients and directs alternative portrayals that are both rationale and healthy or adaptive in nature (i.e. less stressful for the body and mind). There is modest evidence of speeded recovery in acute schizophrenia and strong data for relapse prevention and early intervention (see Tarrier & Wykes, 2004 for a review).

Health Monitoring

Schizophrenia is associated with greater co-morbidity and lowered life expectancy than the general population. The disease process, antipsychotic interventions, and socioeconomics foster very unhealthy habits (e.g. poor diet, smoking, drug abuse) and disease (e.g. obesity, diabetes, hyperlipidemia, cardiovascular disease, cataracts). These factors contribute to the overall decline is health, interfere with clinical management, and place a strain on the medical infrastructures. Clinicians should be aware of the likelihood of co-morbidity and how to detect and prevent medical complications. BMI measurements, lipid lab tests, and ocular examinations should be done at regular intervals (Marder et al., 2004). Moreover, making available nutrition counseling, smoking cessation programs, and substance-abuse counseling may reduce co-morbidity and improve health.

Final Note

Schizophrenia still remains a disabling condition, but advancements in collaborative mental health care, more efficacious pharmacology for negative symptom and cognitive dysfunction, and greater societal awareness of mental health issues may help alleviate this problem.

References

DeQuardo, J. R. (1998). Pharmacologic treatment of first-episode schizophrenia: early intervention is key to outcome. J Clin Psychiatry, 59 Suppl 19, 9-17.

Hogarty, G. E., & Goldberg, S. C. (1973). Drug and sociotherapy in the aftercare of schizophrenic patients. One-year relapse rates. Arch Gen Psychiatry, 28(1), 54-64.

Hogarty, G. E., Goldberg, S. C., & Schooler, N. R. (1974). Drug and sociotherapy in the aftercare of schizophrenic patients. III. Adjustment of nonrelapsed patients. Arch Gen Psychiatry, 31(5), 609-618.

Hogarty, G. E., Goldberg, S. C., Schooler, N. R., & Ulrich, R. F. (1974). Drug and sociotherapy in the aftercare of schizophrenic patients. II. Two-year relapse rates. Arch Gen Psychiatry, 31(5), 603-608.

Hurd, Y. L., Pristupa, Z. B., Herman, M. M., Niznik, H. B., & Kleinman, J. E. (1994). The dopamine transporter and dopamine D2 receptor messenger RNAs are differentially expressed in limbic- and motor-related subpopulations of human mesencephalic neurons. Neuroscience, 63(2), 357-362.

Marder, S. R., Essock, S. M., Miller, A. L., Buchanan, R. W., Casey, D. E., Davis, J. M., et al. (2004). Physical health monitoring of patients with schizophrenia. Am J Psychiatry, 161(8), 1334-1349.

Miller, D. D. (2000). Review and management of clozapine side effects. J Clin Psychiatry, 61 Suppl 8, 14-17; discussion 18-19.

Pitschel-Walz, G., Leucht, S., Bauml, J., Kissling, W., & Engel, R. R. (2001). The effect of family interventions on relapse and rehospitalization in schizophrenia–a meta-analysis. Schizophr Bull, 27(1), 73-92.

Tarrier, N., & Wykes, T. (2004). Is there evidence that cognitive behaviour therapy is an effective treatment for schizophrenia? A cautious or cautionary tale? Behav Res Ther, 42(12), 1377-1401.

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