Psychotic Disorders Including Schizophrenia

Schizophrenia is a neurodevelopmental disorder that is associated with deficits in cognition, affect, and social functioning. Onset of the illness occurs rarely before the age of 13 years, but then increases steadily during adolescence. 

Psychiatric Assessment

Physical Assessment: Potential organic conditions that need to be considered include acute intoxication, delirium, CNS lesions, tumors or infections, metabolic disorders, and seizure disorders. A thorough physical examination is needed. Other tests and procedures, such as neuroimaging, electroencephalographs, laboratory tests, and toxicology screens, should be ordered as indicated based on the history and physical examination. In addition, some laboratory testing, such as assessing renal or hepatic functioning, may also be indicated for monitoring potential adverse effects of psychopharmacological agents. Finally, some cases may require consultation with other medical specialties.

Psychological Assessment: An intellectual assessment may be indicated when there is clinical evidence of developmental delays, since these deficits may influence the presentation and/or interpretation of symptoms [CG]. Cognitive testing also may be useful for assessing the degree of impairment associated with the illness and to help guide treatment planning.

Phases of Schizophrenia:

Prodrome. Prior to developing overt psychotic symptoms, most individuals will experience some period of deteriorating function, which may include social isolation, idiosyncratic or bizarre preoccupations, unusual behaviors, academic problems, and/or deteriorating self-care skills. However, while the presence of these problems should raise concerns, psychotic symptoms must be present before a diagnosis of schizophrenia can be made.

Acute Phase: This is the phase in which patients often present, and it is dominated by positive psychotic symptoms (i.e., hallucinations, delusions, formal thought disorder, bizarre psychotic behavior) and functional deterioration.

Recovery Phase: This follows the acute phase, as the active psychosis begins to remit. This phase often has some ongoing psychotic symptoms and may also be associated with confusion, disorganization, and/or dysphoria.

Residual Phase: During this phase, positive psychotic symptoms are minimal. However, patients will still generally have ongoing problems with “negative symptoms,” i.e., social withdrawal, apathy, amotivation, and/or flat affect.

Chronic Impairment: Some patients remain chronically impaired by persistent symptoms that have not responded adequately to treatment.

Treatment

Psychopharmacology: Traditional neuroleptic medications (block dopamine receptors) and the atypical antipsychotic agents (that have a variety of effects, including antagonism of serotonergic receptors). Compared with traditional agents, the atypical antipsychotics are at least as effective for positive symptoms, and they may be more helpful for negative symptoms. Clozapine has documented efficacy for treatment-resistant schizophrenia in adults. However, clozapine is usually not considered a first-line agent because of its significant potential adverse effects, and it is generally used only after therapeutic trials of at least two other antipsychotic medications (one or both of which should be an atypical agent).

Side Effects:

Typicals:

1. Neurological

a. Acute Extrapyramidal Side Effects: Acute extrapyramidal side effects often occur during the initial phases of treatment. Children and adolescents may be at higher risk for extrapyramidal side effects than adults. Types of extrapyramidal side effects include:

i. Dystonia: A dystonic reaction involves the sudden spastic contraction of distinct muscle groups, often in the neck, eyes (oculogyric crisis), or torso. Risk factors include young age, male gender, and the use of high-potency agents. Dystonias are often quite distressing and, in the case of laryngospasm, can be life-threatening. They usually respond well to anticholinergic or antihistaminic medications.

ii. Parkinsonism: Antidopaminergic agents can induce symptoms of Parkinson’s disease, including bradykinesia, tremors, and rigidity. Anticholinergic or mild dopaminergic agents (amantadine) are used to treat these symptoms. At times differentiating between Parkinson side effects and symptoms of the illness, i.e., negative symptoms, or in severe cases, catatonia, may be difficult.

iii. Akathisia: Akathisia, a sense of severe restlessness frequently manifest as pacing or physical agitation, is commonly seen in patients treated with antipsychotics. It is often misinterpreted as psychotic agitation or anxiety and is a common reason for medication noncompliance. It is, unfortunately, also at times difficult to treat. If clinically feasible, lowering the antipsychotic dose should be attempted. Antiparkinsonian agents are not consistently helpful, although relief has been reported with β-blockers and benzodiazepines. 

To avoid acute extrapyramidal symptoms, the use of prophylactic antiparkinsonian agents may be considered, especially in those at risk for acute dystonias or who have a history of dystonic reactions. This is particularly true in patients whose compliance may be an issue (e.g., those who are paranoid or otherwise distrust medication treatments). The need for antiparkinsonian agents should be reevaluated after the acute phase of treatment or if doses are lowered, as many patients no longer need them during long-term therapy.

Late-Appearing Extrapyramidal Side Effects. 

i. Tardive Dyskinesia: Tardive dyskinesia (TD) is an involuntary movement disorder usually consisting of athetoid or choreic movements in the orofacial region, but it may affect any part of the body. TD is a major public health concern in the treatment of schizophrenia, with both clinical and medicolegal implications. TD is typically associated with the long-term use of neuroleptics. Withdrawal dyskinesia may occur with either gradual or sudden cessation of neuroleptic agents. As many as 50% of youth receiving neuroleptics may experience some form of tardive or withdrawal dyskinesia. Withdrawal dyskinesias almost always resolve over time, whereas TD may persist even if the antipsychotic agent is discontinued.

Because there is no specific treatment for TD other than discontinuing the medication, strategies for prevention and early detection need to be followed. The concern over TD should not outweigh the potential benefits provided by antipsychotics for patients with schizophrenia. However, adequate informed consent is necessary, and baseline measures of abnormal movements should be recorded.

Once neuroleptic therapy has been started, assessment for dyskinesias should occur at least every 3 to 6 months. The Abnormal Involuntary Movement Scale is a useful measure for monitoring this problem. If TD occurs, the medication should be continued at the current dose only if the patient is in full remission and there is reason to believe that any change in dosage or agent will precipitate a relapse. Otherwise, attempts should be made to either lower the dose or switch to another medication, most likely an atypical antipsychotic.

Neuroleptic malignant syndrome (NMS): It is characterized by severe rigidity, hyperthermia, confusion, markedly elevated creatinine phosphokinase, and unstable vital signs. If untreated, mortality rates of 5% to 20% are reported in adults. When NMS is suspected, the antipsychotic agent should be discontinued and supportive medical care sought. Dopamine agonists (e.g., bromocriptine) and antispasticity agents (e.g., dantrolene) also have been used to treat adult patients with NMS.

Atypicals:

  1. Weight Gain: The weight gain associated with atypical antipsychotic agents may be extreme
  2. Neurological: Extrapyramidal side effects and neuroleptic malignant syndrome can theoretically occur with any of the atypical agents; however, the risk for these problems is less than that for traditional neuroleptics. Of the atypical agents, risperidone appears to be the most likely to produce extrapyramidal side effects.
  3. Cardiac: Orthostatic hypotension can be a problem. In adults, minor electrocardiogram changes, specifically QT prolongation, have been associated with atypical antipsychotics. While this has generally not been a clinically significant issue, it raises concerns because youth may be more susceptible to the cardiac effects of medications.
  4. Hematological: Although primarily associated with clozapine, agranulocytosis can occur with any antipsychotic agent.
  5. Hepatic: Atypical agents may produce elevations in hepatic transaminase levels. These elevations are often transient and generally resolve with cessation of the drug. There are two reported cases of liver enzyme abnormalities and fatty infiltrates, associated with obesity, developing in adolescent males during risperidone therapy. Thus it may be prudent to check baseline liver functions prior to initiating treatment, with periodic monitoring during ongoing therapy.
  6. Ocular: Quetiapine therapy was associated with the development of cataracts in studies of dogs. This adverse effect has not been reported in humans, but the Food and Drug Administration still recommends obtaining baseline and 6-month follow-up eye examinations when prescribing quetiapine.
  7. Other Side Effects: Other common side effects include sedation, activation, and dizziness.

Psychosocial Interventions: 

  1. Psychoeducational therapy for the patient, including ongoing education about the illness, treatment options, social skills training, relapse prevention, basic life skills training, and problem-solving skills and strategies.
  2. Psychoeducational therapy for the family to increase their understanding of the illness, treatment options, and prognosis and for developing strategies to cope with the patient’s symptoms.

Specialized educational programs and/or vocational training programs may be indicated for some children or adolescents to address the cognitive and functional deficits associated with the illness [CG]. Some individuals will require more intensive community support services, including day programs. Furthermore, there are some cases in which the severity and chronicity of symptoms warrants long-term placement in a residential facility. However, efforts should always be made to maintain the child or adolescent in the least restrictive setting possible.

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