A 65-Year-Old Man Brought to the ED by Military Police

Jeffrey S. Forrest, MD; Alexander B. Shortridge


August 06, 2019

Schizophrenia affects approximately 1 in 100 individuals, with roughly equal incidence between the sexes.[2] The age of onset varies between men and women, however. In men, the typical onset is age 15-25 years. In women, most cases present at age 25-35, but 3%-10% of cases in women present after age 40. Schizophrenia rarely presents before age 15 or after age 55. Monozygotic twin studies suggest a rate of about 50% concordance for development of schizophrenia syndrome.[2] This suggests a strong, but not exclusive, genetic component, with environmental factors also significant in the pathogenesis of the disease process. Thus, an epigenetic mechanism is in play; both hereditary and environmental factors are involved. Numerous studies have demonstrated the role of stress in activating a schizophrenic episode, such as the stress of living in highly populated urban environments.[5]

As with the evaluation of most psychiatric conditions, the timely obtainment of collateral and supplemental history is essential in formulating an appropriate diagnosis. In the case presented, essential history from relatives provided critical information in the chronicity of the patient's symptoms and prior psychiatric history.

Psychotic symptoms may also arise from medical conditions, medications, or substance abuse. A careful metabolic workup, including a metabolic panel, is appropriate to rule out possible alternative causes. Certain infections and blood conditions may also contribute to psychiatric symptoms, making a complete blood count an appropriate test as well. A CT scan of the head is important to rule out organic or structural precipitants for psychotic symptoms. A urine toxicology screen is also essential to exclude contribution from the effects of illicit substances.

In evaluating mental health conditions, a careful evaluation of patient risk to personal safety and that of others is imperative. Should such an evaluation reveal the presence of dangerous delusions, hallucinations, suicidal thoughts, or other severe symptoms that might cause harm (or the inability to avoid harm) to the patient or others, the patient may be temporarily committed on an involuntary basis for a brief period while further evaluation can be conducted. A patient who is suicidal and/or homicidal must not be left unattended. Requirements and durations vary and are based on regional laws.

The first-line treatments for schizophrenia symptoms are antipsychotic agents. The primary mechanism of action for the therapeutic effect of antipsychotic agents is blockade at the dopamine receptor D2 in the mesolimbic pathway of the brain.[3] Unfortunately, such agents also may block dopamine receptors in the substantia nigra, resulting in the common side effect of extrapyramidal symptoms (EPS). These include akathisia, dyskinesia, dystonia, and akinesia. The most concerning of these is the syndrome of tardive dyskinesia (TD), wherein a patient may develop chronic and intractable repetitive movements of the face, tongue, or body.[3]

The balance of dopaminergic and cholinergic activity is central to the pathogenesis of EPS, including TD. Dopamine typically inhibits acetylcholine release. Blocking D2 receptors reduces dopamine's ability to inhibit acetylcholine release, leading to increased cholinergic activity. For this reason, anticholinergic agents such as benztropine are often administered with antipsychotics to reduce EPS such as TD.[3,6]

First-generation antipsychotic agents, such as haloperidol or perphenazine, have a greater risk of inducing EPS because of their overall greater level of D2 receptor blockade (approximately 80%). By contrast, second-generation antipsychotic agents (eg, quetiapine, ziprasidone) have lower rates of TD induction, as D2 blockade varies from 60% to 80%; however, the risk for metabolic side effects is increased.[3,7]

Two common tools for assessing TD in patients with schizophrenia are the Abnormal Involuntary Movement Scale (AIMS) and the Extrapyramidal Symptom Rating Scale (ESRS). AIMS categorizes abnormal movements by anatomic location and overall severity. ESRS rates symptoms on the basis of severity and frequency. Subjective and objective measures of parkinsonism, dystonia, akathisia, and dyskinesia are included. A cross-scale comparison found high concordance between AIMS and ESRS.[8]

Medication noncompliance is a major challenge to relapse prevention in the treatment of schizophrenia. By nature of the condition, symptoms may impede treatment. Patients with schizophrenia may come to believe that they no longer require medication, may experience hallucinations commanding them to stop taking medication, or may simply become apathetic and avolitional in regard to all activities. One pharmacologic strategy for preventing medication noncompliance includes use of long-acting injectable antipsychotic agents. Depot preparations of antipsychotic medications require administration much less frequently than daily oral antipsychotic medications and have been demonstrated to reduce rehospitalizations.[9] Patients with schizophrenia may stop their medication because of the aforementioned adverse effects of their drugs.

In addition to pharmacologic management, psychosocial interventions may be used to improve outcomes in schizophrenia. One example is Assertive Community Treatment, in which a team-based approach to care helps to assure access, delivery, and administration of medications. Such a team may include a psychiatrist, nurse, case manager, social worker, and primary care physician, working in tandem to monitor and provide services to chronic mental health patients. Cognitive-behavioral therapy has also been demonstrated to reduce positive symptoms in schizophrenia.[10] Social skills training for patients with schizophrenia encourages the development and maintenance of social networks, which is correlated with a reduction in negative symptoms.[4]


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