Cases That Test Your Skills

When clozapine is not an option

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After 30 years, Mr. S’ catatonic schizophrenia finally responds to medication, but the drug causes a precipitous WBC decrease. The challenge: find a tolerable yet effective regimen.


 

References

History: ‘leaving town’

Mr. S, age 58, escaped repeatedly from his group home over 4 weeks. During one episode, he removed mail from neighbors’ mailboxes and tried to direct midday traffic. He would disappear for a few hours, sometimes overnight, before returning or being brought back by police.

The patient—who has had schizophrenia with catatonic features for 30 years—offered assorted explanations for escaping, most of them based on delusional beliefs, such as “I’m leaving town to get married” or “I’m late for engineering class.”

Since his last escape 3 weeks ago, Mr. S has remained in the group home without incident but has not been reporting for his usual outpatient psychiatric care. One day, he finally presents to us at the group home sponsor’s urging.

On evaluation, Mr. S shows stereotyped speech, staring, posturing, speech-prompt mutism, and odd mannerisms such as saluting. He has not been bathing or sleeping and smiles inappropriately. He speaks only when spoken to and answers with short phrases punctuated with ”By the grace of the good Lord.”

The authors’ observations

DSM-IV-TR requires at least two features to diagnose catatonic schizophrenia:

  • peculiar voluntary movements
  • extreme negativism
  • excessive motor activity
  • echolalia or echopraxia
  • motoric immobility.1
Mr. S has the first three features.

Catatonia is common among the chronic mentally ill,2 yet it often goes undiagnosed.3 As a form of psychosis, catatonia might lead to greater functional impairment if not treated.

Treatment: time to try clozapine?


Over 10 years, numerous antipsychotic regimens plus adjunctive valproic acid, 500 mg tid, or lorazepam, up to 2 mg tid, have not lessened Mr. S’ psychosis and impulsivity. We start clozapine, 400 mg/d, and order twice-monthly blood tests to check for clozapine-induced agranulocytosis.

After nearly 6 months, some catatonic features improve gradually based on clinical interview. Serum clozapine is 363 ng/mL.

poll here

The authors’ observations

Second-generation antipsychotics (SGAs) are favored over first-generation antipsychotics to treat schizophrenia with catatonic features (Table),4,5 but no drug in either class has worked for Mr. S.

ECT can alleviate catatonic schizophrenia,4,6 but this option often is not available because the clinician fears a negative outcome would prompt legal action, or the guardian or next of kin do not consent to the procedure.3 We considered referring Mr. S to an ECT provider, but he has no legal guardian to provide consent. The group home sponsor also objected to ECT because Mr. S would have been sent out of town for treatment.

Catatonia patients who are immobile, physically compromised, and refuse food and drink typically are considered ECT candidates. Mr. S eats and drinks regularly and is physically able.

Lorazepam can produce rapid response, but it can be addictive.2 Also, an adjunctive 2 mg/d dosage showed no effect.

Clozapine monotherapy has shown effectiveness in catatonic schizophrenia7 and might be an option after other antipsychotics have failed.

Table 1

Treatments for catatonia: risks and benefits

MedicationUseRationaleBenefitsRisks
First-generation antipsychotics (FGAs)Often used for schizophreniaControl positive symptomsWell-establishedCatatonia might be difficult to distinguish from NMS
Less expensive than other medications
Second-generation antipsychotics (SGAs)Beneficial in catatoniaLess likely than FGAs to worsen catatonia because of low D2 blockadeSome studies suggest greater efficacy than with FGAsMetabolic syndrome, agranulocytosis with clozapine
BenzodiazepinesLorazepam helpful in acute catatoniaCan be added to any antipsychoticSafe, first-line treatment for catatoniaRespiratory compromise, incoordination, sedation, potential for abuse
Electroconvulsive therapy
Electroconvulsive therapyBeneficial in malignant catatoniaEffective in catatonia, NMSUseful for treatment-refractory catatoniaConcerns with anesthesia, informed consent, availability
Rapid onset of action
NMS: Neuroleptic malignant syndrome

Complication: agranulocytosis, then nms

Six months after starting clozapine, Mr. S starts having diaphoresis and night sweats, suggesting neutropenia. Blood testing shows a white blood cell count (WBC) of 3.6/μL, down from 4.6/μL 2 weeks before (normal range, 4.6 to 11/μL).

One week later, Mr. S’ WBC is 1.6/μL with a 46% relative neutrophil value (normal range, 50% to 70%) and an absolute neutrophil count of 736 (normal range, 2,500 to 7,000).

We diagnose agranulocytosis and stop clozapine, but Mr. S’ WBC continues to fall over 2 weeks to 0.8/μL with a 16% relative and 128 absolute neutrophil count. After 1 more week, his WBC increases to 2.6/μL and returns to normal 1 week later—4 weeks after stopping clozapine

We then target Mr. S’ catatonia with intramuscular haloperidol, 100 mg/d for 4 weeks, and ziprasidone, 80 mg bid with food. He tolerates this combination but gradually develops tremor and rigidity. Six weeks later, we add levodopa/carbidopa, 25/250 mg bid for his movement problems.

Two weeks later, Mr. S is sweating profusely, disoriented, rigid, and febrile (104.6°F). We diagnose neuroleptic malignant syndrome (NMS), stop both antipsychotics, and admit him for treatment. We start lorazepam, 1 mg tid for catatonia; bromocriptine, 250 mg bid for rigidity; and continue levodopa/carbidopa at the same dosage. We also add dantrolene, 25 mg tid for 5 days for fever and rigidity, and provide a cooling blanket for hyperthermia.

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