Cases That Test Your Skills

Treating schizophrenia in the ‘real world’

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Mr. F—with a history of severe motor effects and noncompliance—seems ‘damned’ to a life of delusional, violent behavior. After 17 years of treatment failures, can a more tolerable therapy be found?


 

References

HISTORY: Jesus’ ‘cousin’

Mr. F, age 60, was hospitalized in May 1995 after expressing fear he would hurt—or kill—himself or someone else. He cooperated with admission procedures but refused to participate in ward activities or meetings. His hygiene was poor, he made little eye contact, and reportedly heard voices. Two days after admission, he emphatically denied suicidal or homicidal ideation and was discharged against medical advice.

Two weeks later, Mr. F was readmitted after his symptoms worsened. He said voices told him that he was a cousin to Jesus Christ and that he had telepathic abilities. He also reported visual hallucinations.

Twice divorced, Mr. F has three uncles who have been diagnosed with schizophrenia. His late father had a history of alcohol abuse, and his late mother suffered from Alzheimer’s disease.

Mr. F lived a normal life until 1975, when he began drinking heavily. Three years later, he quit his job of 11 years at the local airport. At that time, he told a psychiatrist that “people are out to get me. I feel nervous a lot.” He was diagnosed as having generalized anxiety disorder and treated with diazepam, 20 mg/d.

Four months later he complained of severe insomnia, was diagnosed with depression, and was prescribed amitriptyline, 100 mg at bedtime. He was hospitalized 1 week later after he complained of chest pain and expressed paranoid thoughts. During the 3-week hospitalization, he experienced persecutory delusions and heard voices telling him he was “damned.” He was diagnosed with paranoid schizophrenia and alcohol dependence. The amitriptyline was stopped, and Mr. F was discharged on chlorpromazine, 300 mg/d.

From 1978 to 1995, Mr. F was hospitalized 35 times, often at his family’s urging after he made threats or became violent at home. He once kicked his elderly father and another time was jailed after a domestic violence incident. Religious delusions characterized his thought content. Thought blocking, flight of ideas, and somatic and sexual delusions were also apparent.

Was Mr. F’s diagnosis accurate, or do his frequent psychotic episodes meet criteria for a type of mania?

Dr. Canive’s observations

Diagnoses of mania or mood disorder with psychotic features were not considered because Mr. F never experienced a distinct period of persistently expansive or depressed mood.

Mr. F’s initial complaints of increased anxiety and depression were considered prodromal symptoms of schizophrenia and may have reflected his inability to discuss or cope with his delusions and hallucinations during the initial evaluation. What’s more, his occupational functioning gradually deteriorated months before his initial mental health assessment.

TREATMENT: Many medications, no progress

At different times from 1978 to 1995, Mr. F had taken chlorpromazine, 100 to 300 mg/d; thioridazine, 50 to 200 mg/d; loxapine, 25 mg/d; fluphenazine, 5 to 10 mg/d; haloperidol, 2 to 4 mg/d, and fluphenazine decanoate, 3.125 to 6.25 mg biweekly, as well as concomitant anticholinergics, benzodiazepines, or other hypnotics.

A closer look at Mr. F’s chart revealed that medication noncompliance often preceded hospitalization. He was extremely prone to antipsychotic-related extrapyramidal symptoms (EPS), even at low dosages. Whenever motor symptoms surfaced, he would stop taking his antipsychotics.

Buccolingual tardive dyskinesia (TD) was first noticed in 1987. Four years later, an Abnormal Involuntary Movement Scale (AIMS) exam revealed mild TD that was managed with vitamin E, 400 IU/d.

While hospitalized, Mr. F many times received injectable antipsychotics and benzodiazepines, mostly to control violence. Depot antipsychotics also were tried in an effort to promote compliance, but recurrent alcohol abuse often triggered a relapse.

How would you confront Mr. F’s history of noncompliance? Can his delusions be controlled without prompting severe motor effects?

Dr. Canive’s observations

For Mr. F, poor tolerability, incomplete efficacy, and variable compliance have repeatedly led to symptom exacerbation and hospitalization. Low dosing because of sensitivity to EPS may partially explain his insufficient response to antipsychotics.

In 1995, after numerous unsuccessful drug treatments, we considered entering Mr. F into a phase II clinical trial of the atypical antipsychotic aripiprazole.

Now FDA-approved for treatment of schizophrenia, aripiprazole decreases dopaminergic transmission in the nigrostriatal and tuberoinfundibular pathways, thus reducing the likelihood of EPS.1,2 Also, aripiprazole’s dopamine-serotonin stabilization effects have been reported in clinical trials to improve tolerability, compliance, and overall effectiveness in patients with schizophrenia.3

Common side effects of aripiprazole are mild nausea, insomnia, and restlessness, although data indicate that these effects have a low prevalence and disappear within 2 weeks. If insomnia and restlessness are prominent, a low-dose, short-acting benzodiazepine may be added, tapered after 1 week, and discontinued at week 2.

Table

Mr. F’s progress while taking aripiprazole, 1995-2003

Pages

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