Cases That Test Your Skills

Unexpected improvement

Author and Disclosure Information

For 30 years, Ms. U, age 53, has experienced treatment-resistant schizophrenia. After she is treated for a neurologic disorder, her psychotic symptoms improve markedly. What could be the cause?


 

References

Discuss this article at www.facebook.com/CurrentPsychiatry
CASE: Relapsing psychosis

Ms. U, age 53, was diagnosed with paranoid schizophrenia at age 21 and has a continuous pattern of frequent relapses and inpatient admissions. She has received therapeutic doses of trifluoperazine, sertindole, haloperidol, loxapine, thioridazine, olanzapine, risperidone, clozapine, and several other antipsychotics not available in the United States. Clozapine had been prescribed at 600 mg/d (average blood level was 350 ng/mL), at times in combination with other antipsychotics or lithium.

Despite treatment, Ms. U has never achieved clinical stability. She has fluctuating yet persistent auditory hallucinations (eg, voices threatening to “announce disasters” or songs of a religious nature), associated disorganized behavior (eg, covering her ears or asking third parties “to turn off the radio”), severe hyponatremia secondary to potomania, paranoid ideation (eg, being followed by a “hidden camera”), and a strong tendency toward negativism, mutism, and emotional lability secondary to her psychotic symptoms. Her affect is predominantly poor and flattened, with very poor insight. Her symptoms are associated with progressive social isolation and poor grooming. Because of her worsening status, Ms. U was admitted to a residential facility 3 years ago.

Ms. U is single and the eldest of 2 siblings. Her parents are deceased; one parent may have committed suicide. She reports a family history of psychosis in her first cousins, but no history of hereditary neurologic disorders. Ms. U is a heavy smoker, did not complete college, and has a job in a family business.

The authors’ observations

Historically, the prevailing theory to explain the pathophysiology of schizophrenia has been the dopamine hypothesis, which links a hyperdopaminergic state in the mesolimbic system with acute psychosis. This theory could explain positive symptoms of schizophrenia but not other core domains, such as negative symptoms and cognitive dysfunction.1-3 The glutamate hypothesis postulates a hypoglutamatergic state can be the cause, at least in part, of various symptoms of psychosis, similar to those induced by phencyclidine and ketamine. Antagonists at the glycine modulatory site of the N-methyl-d-aspartate (NMDA) receptor are being studied as a way to influence this pathway,1 which is believed to be influenced by genetic factors.4

Glutamate, an amino acid, is the primary excitatory neurotransmitter in the brain. Its action is exerted in 2 types of receptors on the postsynaptic neuron: ionotropic and metabotropic.

The activation of NMDA receptors generated by glutamate and glycine coagonist can stimulate an uncontrolled release of calcium and subsequent cell death known as excitotoxicity. This phenomenon has been described in amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and Huntington’s disease. Although overstimulation of NMDA receptors induces neurodegeneration, NMDA hypoactivity has been observed in psychotic states.5

EVALUATION: Neurologic symptoms

A few months after arriving at the residential facility, Ms. U develops dysarthria and drooling, which the treatment team initially interprets as secondary to high doses of clozapine. In the absence of clinical response after clozapine dose reduction and with the subsequent appearance of dysphagia with solid foods and liquids, Ms. U is evaluated by a ear, nose, and throat physician, and later by a neurologist. Both clinicians describe frontal release signs, anarthria, facial hypomimia, bilateral mild central paresis, absence of soft palate elevation with symmetrical phonation, decreased gag reflex and palatal atrophy, fasciculations, and bilateral lingual mandibular reflex and diagnose Ms. U with progressive bulbar palsy, a variant of ALS.

The authors’ observations

ALS is a progressive, degenerative neuromuscular condition of unknown etiology affecting the corticospinal tracts and the anterior horn of the spinal cord, leading to dysfunction of the upper and lower motor neurons.6 It is more common in men, persons with diets rich in glutamate, and smokers.7,8

Riluzole is the only FDA-approved medication for ALS.9 It interferes with the responses mediated by the NMDA receptor, stabilizes inactive sodium voltage-dependent channels, inhibits glutamate release from synaptic endings, and activates extracellular reuptake of glutamate, all of which are thought to confer a neuroprotective effect.10

TREATMENT: Psychosis improves

As suggested by the neurology team, we begin riluzole, 50 mg every 12 hours. At this time Ms. U also is taking clozapine, 600 mg/d; lithium, 1200 mg/d; and haloperidol, 6 mg/d; her psychiatric symptoms have not changed since the initial evaluation at the residential facility.

Seven months after initiating riluzole Ms. U is more receptive, less querulant, and no longer experiences delusions or hallucinations. At the same time, she develops an interest in her clinical status regarding her ALS diagnosis, which reflects improved insight. One year after starting riluzole, she is more cooperative and adherent with treatment. Ms. U is able to reestablish relationships with her family. Clozapine and haloperidol are tapered and discontinued. Ms. U’s medication regimen includes risperidone, 1 mg/d; methotrimeprazine, 10 mg/d; venlafaxine, 75 mg/d; trazodone, 100 mg/d; and lithium, 600 mg/d, in addition to riluzole, 50 mg every 12 hours.

Pages

Recommended Reading

DSM-5 Might Get Fewer Personality Disorders
MDedge Psychiatry
FDA, Company Announce Risperidone Recall
MDedge Psychiatry
Treatment-resistant schizophrenia: What can we do about it?
MDedge Psychiatry
The ABCs of estimating adherence to antipsychotics
MDedge Psychiatry
Evaluating medication outcomes: 3 key questions
MDedge Psychiatry
Opiates and psychotropics: Pharmacokinetics for practitioners
MDedge Psychiatry
Comments & Controversies
MDedge Psychiatry
A dangerous GI complication
MDedge Psychiatry
How to best help patients with residual schizophrenia symptoms
MDedge Psychiatry
How to assess for possible drug-drug interactions
MDedge Psychiatry