Cases That Test Your Skills

Afraid to leave home

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Clozapine alleviates Mr. B’s schizophrenia symptoms, but he develops anxieties that leave him virtually homebound. Is the antipsychotic to blame?



CASE: Disabling anxiety

Mr. B, age 35, has a history of schizophrenia, chronic paranoid type and has been hospitalized more than 12 times since its onset 10 years ago. He received clozapine during his most recent hospitalization approximately 5 years ago and experienced full symptom response without the motor side effects he developed in response to other medications. He visits a psychiatrist monthly for medications and supportive psychotherapy, and he receives intensive case management and housing from a community mental health center.

When Mr. B is assigned to my (CK) care, his psychotic symptoms are in remission, but he complains of anxiety that leaves him almost homebound. He has intense fear of bridges, upper-floor windows, express buses, subways, riding in speeding vehicles, and having a seizure.

If Mr. B faces any of these triggers, he experiences harmful thoughts—such as jumping out a window or off a bridge—even though he does not endorse suicidality. These thoughts are intrusive, ego-dystonic, and ruminative. He avoids these triggers at all costs, which compromises his housing and employment opportunities. He experienced a single panic attack in the subway 1 year earlier. Mr. B firmly believes that any intense anxiety he experiences will trigger a psychotic episode. When faced with sudden urges, he believes his illness would interfere with his ability to control his impulses.

He reports that these symptoms started when he began clozapine and have worsened. Mr. B says he experiences a feeling of “uneasiness” approximately 2 hours after taking clozapine that is exacerbated if he faces a trigger. He describes the uneasiness as “the feeling of being about to have a seizure” during which he would “lose control” of his body.

When I begin treating Mr. B, he is receiving clozapine, 125 mg bid. In an effort to combat Mr. B’s anxiety, a previous psychiatrist had titrated clonazepam up to 5 mg/d as needed. Mr. B is compliant with his medications and appointments but refuses to change his psychotropic or psychotherapy regimen.

The authors’ observations

Approximately 50% of patients with schizophrenia have at least 1 anxiety disorder, and close to 30% meet criteria for >1 anxiety disorder.1 Social anxiety disorder (SAD), generalized anxiety disorder, panic disorder, posttraumatic stress disorder, and obsessive-compulsive disorder (OCD) have been found comorbid with schizophrenia, with rates as high as 30% for each.1

Possible causes of unusually high rates of anxiety disorders in schizophrenia include trauma history, delusional conviction and inflexibility of abstract thought,2 and passive coping mechanisms.

Schizophrenic illnesses may be linked to anxiety antecedents such as panic or social phobia that:

  • develop into more profound psychopathology
  • or bring about anxiety symptoms, given the severity of the subjective psychotic experience.
In a twin pairs study, the schizophrenic twin had an almost threefold increase in rates of comorbid psychiatric disorders compared with their non-schizophrenic twins; social or environmental factors may not account for this.3

Comorbid OCD, panic disorder, and SAD frequently persist after remission of psychotic symptoms. Comorbid anxiety disorders may play a role in the psychotic symptoms themselves (such as panic and social anxiety related to paranoia, OCD, and bizarre behavior) and negatively impact quality of life.4

In patients with schizophrenia, higher anxiety levels are associated with:
  • increased hallucinations
  • poor psychosocial function
  • hopelessness.5
Accurately assessing and diagnosing anxiety disorders in patients with schizophrenia is challenging because there is inconsistency among clinical interviewers (poor reliability scores), and anxiety scales are not as accurate as we would like them to be (poor construct validity).6 Treatment options for comorbid anxiety and schizophrenia include psychopharmacology and psychotherapy (Table 1).

Table 1

Treatment options for comorbid schizophrenia and anxiety

  • Increase antipsychotic dose
  • Change antipsychotic
  • Add an atypical with serotonergic action (ziprasidone, aripiprazole)
Favor monotherapy at full dose for full trial period before considering adjunct therapy with a second antipsychotic, for which evidence is still equivocal
  • SSRI
  • SNRI
Avoid bupropion because of possible dopamine agonism
BenzodiazepinesWeigh risks of sedation and potential for addiction vs benefits of immediate relief
GabapentinUse high doses to obtain symptomatic response
PsychotherapyCBT (for psychosis and anxiety)
Supportive (for decompensating psychosis)
Activity and vocational
CBT: cognitive-behavioral therapy; SSRI: selective serotonin reuptake inhibitor; SNRI: serotonin-norepinephrine reuptake inhibitor

HISTORY: Propensity for violence

Mr. B was born in a large city and raised by his single mother. He denies childhood physical or sexual abuse. Mr. B reports engaging in violent activity since he was an adolescent, but this activity is undocumented because he has never been arrested. Mr. B still belongs to a gang he joined after being assaulted at age 16.

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