Schizophrenia

Mr. Q

Mr. Q is a 23-year-old, single male who presented with paranoid delusions and auditory hallucinations. He had three previous episodes of psychosis beginning at age 19 when he was first hospitalized. Mr. Q describes that others are out to get him but does not know why. He also reports that when he leaves home, people are paying special attention to him and following him. He hears a voice warning of danger and the need
to protect himself. Mr. Q has been unable to finish college and spends most of his time in the basement of the family home. He reports enjoying watching television but has no friends or social contacts. The family tends to leave him alone but brings dinner in the evenings. The family also reports that he is not compliant with medications and in the last few weeks has become increasingly agitated, paranoid, and withdrawn.

Schizophrenia is a severe, chronic, psychotic disorder. The lifetime prevalence worldwide is often quoted as 1%, but may vary slightly based on demographics such as economic class and gender. Although there is an equal distribution between men and women, men develop clinical symptoms approximately 6 years earlier. Onset is usually during adolescence and early adulthood. This disorder is characterized by various symptom complexes, which include the following:

Positive (e.g., hallucinations, delusions)
Negative or deficit (e.g., isolation, amotivation)
Cognitive (e.g., verbal and nonverbal working memory, executive functioning, verbal and visual learning)
Mood (e.g., dysphoric, suicidal ideation)

These symptoms may vary over time with most individuals experiencing a gradual deterioration in their ability to function. Negative and cognitive symptoms are the most disabling and less amenable to treatment. In addition, these patients are plagued by high rates of suicide and comorbidity with other psychiatric and medical disorders. As a result, their life expectancies are substantially shortened compared to the general population.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of schizophrenia includes a variety of conditions that may present with psychotic symptoms. Some of the more common considerations are:

Schizoaffective disorder
Delusional disorder
Mood disorders with psychosis (e.g., acute mania with delusions)
Drug-induced psychotic episodes (e.g., phencyclidine intoxication)
Psychosis secondary to a nonpsychiatric medical condition (e.g., dementia with psychosis)

NEUROBIOLOGY

The development of clinical symptoms involves a complex interaction between biological predisposition (e.g., genetics) and environmental stressors (e.g., viral infection) occurring during critical developmental periods (e.g., fetal, neonatal, puberty). These abnormal neurodevelopmental events are further exacerbated by subsequent neurodegenerative processes as evidenced by imaging studies, which demonstrate:

Structural brain volume changes
Changes in functional activity in relevant neurocircuits
Altered central nervous system (CNS) blood flow and glucose metabolism
Biochemical alterations in related CNS regions

For example, progressive reductions in frontal lobe gray and white matter correlate with functional impairment in schizophrenia. Further, lower hippocampal volumes are found in both patients and their nonpsychotic first-degree relatives. In addition, functional deficits in cortical and subcortical areas are observed in those patients who are medication-free, first-episode schizophrenia and may also appear in unaffected siblings. Clinical issues
often associated with reduced cortical volume and enlarged ventricles include:

Soft neurologic signsw
Poorer response to treatment
Worse prognosis

TREATMENT OF SCHIZOPHRENIA

Ideally, early detection and prevention represent the optimal strategy for schizophrenia and other psychotic disorders. In this context, certain factors may improve prediction in younger individuals, ¹ including:

Genetic risk with recent functional deterioration
Higher levels of unusual thought content
Higher levels of suspicion/paranoia
Greater social impairment
History of substance abuse

Although work continues on earlier interventions to preclude a full episode, most patients are first treated after they meet full criteria for schizophrenia.

Pharmacotherapy for Schizophrenia

The use of antipsychotics is the primary mode of treatment to control acute exacerbations, reduce relapse rates, and prevent recurrence.² Although both first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) are effective for positive symptoms, SGAs arguably produce additional benefit in negative, cognitive, and mood symptoms compared to their first-generation counterparts. For example, clozapine is the only antipsychotic approved by the U.S. Food and Drug Administration (FDA) for management of suicidal symptoms in patients with schizophrenia or schizoaffective disorder. The SGAs have also demonstrated a more robust effect then placebo or FGAs in reducing relapse rates. These results, however, were derived from randomized, placebo, or active comparator-controlled trials
and may not readily translate into more real-world conditions as evidenced by the results of the National Institute ofMental Health (NIMH)-sponsored Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Study.³

Therefore, the choice of antipsychotic often depends on the safety and tolerability profile of a specific agent matched to an individual’s proclivity for developing certain complications (e.g., a personal or family history of diabetes). Tables 7-1 and 7-2 list the various classes of antipsychotics and their common adverse effect profiles.

Device-Based Therapies for Schizophrenia

Electroconvulsive Therapy.

Although medication remains the primary treatment strategy for schizophrenia, electroconvulsive therapy (ECT), usually in combination with an antipsychotic, has demonstrated acute benefit, particularly in patients with severe mood symptoms, suicidal behavior, or catatonia.⁴ Examples of other situations where ECT may be considered include patients refractory to clozapine (using ECT for augmentation) and patients who have recently experienced an episode of neuroleptic malignant syndrome (NMS) secondary to their antipsychotic medication (using ECT as an alternative).⁵,⁶

Transcranial Magnetic Stimulation.

Preliminary evidence demonstrates the potential efficacy of transcranial magnetic stimulation (TMS) for positive symptoms such as auditory hallucinations.⁷ The evidence that TMS benefits negative symptoms is less compelling. Presently, there is a need to clarify and optimize TMS‘ delivery for specific psychotic symptoms to determine its utility in schizophrenia.⁸

Psychotherapy for Schizophrenia

Unfortunately, the complexity of symptoms manifested in schizophrenia makes the psychotherapy of choice unclear. Numerous studies have examined various approaches, always as adjuncts to medication. Many of these adjunctive therapies reduced relapse, increased functioning, increased social skills, and reduced family stress. The decision as to which patient is best suited for a specific treatment, however, depends on the presenting symptoms, course of illness, and social situation. Several therapeutic approaches are reported to be efficacious, including: