Schizophrenia

Schizophrenia is generally a lifelong disorder that can present as acute or chronic psychosis. This condition is commonly associated with a constellation of symptoms described as negative and positive symptoms. Patients with schizophrenia may also experience mood and anxiety symptoms or cognitive decline.

Prominent negative symptoms include:

• alogia (poverty of speech)

• flat affect

• anhedonia (inability to feel pleasure)

• apathy

Prominent positive symptoms include:

• hallucinations

• delusions

• disorganized thoughts and behaviors

Characteristics of schizophrenia can also be viewed based on the neuropsychological performance of patients as compared with healthy subjects. In a case-control study that assessed a variety of cognitive processes, the most significant difference between schizophrenic patients and controls was a deficit in the performance of tasks involving verbal memory and processing speed.

Diagnosis

The diagnosis of schizophrenia involves identification of characteristic negative or positive symptoms (described above) that cause significant disturbance to daily functioning.

Treatment

Antipsychotics

Antipsychotics are the first-line treatment for schizophrenia in both the acute and chronic states, and specifically address positive symptoms of this condition.

• First-generation antipsychotics (typical antipsychotics) include haloperidol, fluphenazine, and chlorpromazine.

• Second-generation antipsychotics (atypical antipsychotics) are newer agents and include risperidone, olanzapine, and clozapine.

The choice of agent depends on a variety of factors including previous positive response, route of administration, and side-effect and toxicity profiles. The following table lists some commonly prescribed antipsychotic medications for schizophrenia.

(Source: Schizophrenia. N Engl J Med 2019.)

Management of Poor Treatment Response

When assessment after the start of treatment reveals little or no response, it is important to evaluate for and address underlying causes, including poor medication adherence or concurrent substance use. Adherence can be improved with the use of long-acting injectable forms of medication.

Clozapine is the most effective antipsychotic in patients with poor or partial response to current medication. Clozapine may also reduce suicidality in patients with schizophrenia.

Cognitive behavioral therapy may be effective in reducing persistent psychotic symptoms in patients who have a partial response to clozapine or other antipsychotic medications. Psychosocial interventions can help patients improve functioning in areas of work education, relationships, and skills for independent living. Evidence-based psychosocial interventions for patients with schizophrenia are shown in the table below.

(Source: Schizophrenia. N Engl J Med 2019.)

Adverse Effects of Antipsychotics

Management of drug treatment in patients with schizophrenia includes monitoring and addressing side effects, particularly because these adverse effects can affect patient adherence.

The primary toxicities associated with antipsychotic medications are as follows:

• Extrapyramidal effects are due to decreased dopamine or dopamine-receptor antagonism and can be managed by reducing the dose of antipsychotic medication, changing to an alternative antipsychotic, or adding an anticholinergic agent.

  • akathisia (restlessness)

  • dystonia (muscular spasms, oculogyric crisis, and torticollis)

  • parkinsonism (a movement disorder more commonly seen with first-generation antipsychotic agents)

• tardive dyskinesia: abnormal involuntary movement, often of the mouth, face, jaw, tongue, hands, or feet)

• weight gain

• sexual side effects (e.g., menstrual disturbances in women and sexual dysfunction in men)

• elevated lipid and glucose levels

(Source: Schizophrenia. N Engl J Med 2019.)

Olanzapine: The Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) study compared the effectiveness of second-generation antipsychotics (olanzapine, risperidone, quetiapine, and ziprasidone) to the first-generation antipsychotic perphenazine. Olanzapine was associated with a longer time to discontinuation for any cause (the primary outcome). However, olanzapine was associated with greater weight gain, hyperlipidemia, and hyperglycemia.

Clozapine: Although clozapine is effective, it is more likely than other antipsychotics to be myelosuppressive and cause agranulocytosis, a rare but potentially fatal side effect. Therefore, it is important to assess absolute neutrophil count when patients start treatment.

Neuroleptic malignant syndrome (NMS): NMS is considered a life-threatening emergency associated with the use of antipsychotic drugs, especially high-potency first-generation antipsychotics. Symptoms of NMS include:

• muscle rigidity (described as lead pipe rigidity; correlates with elevated creatine kinase)

• hyperthermia (may require fluid resuscitation)

• delirium or mental status changes

• autonomic instability (must be addressed promptly)

Treatment of NMS may include dantrolene, bromocriptine, or amantadine. Patients may need to be re-challenged with antipsychotic medication therapy after experiencing NMS. Rechallenge should be attempted in collaboration with the guidance of a specialist and only when the symptoms and biochemical abnormalities related to NMS have fully resolved.