Management of the Refractory Psychotic

Vernon M Neppe MD, PhD

Educational Objectives

  1. To educate in the area of refractory, atypical and nonresponsive psychosis, particularly the clinical psychopharmacologic management.
  2. To create a workable outline with regard to management options and problems.


The patient with refractory psychosis is particularly difficult to treat. These patients have invariably failed trials of several neuroleptics. Their treatments of necessity go beyond FDA approved indications and are still being researched.

A specific treatment approach is outlined in my book Innovative Psychopharmacotherapy.

  1. First ensure compliance, if necessary with short-acting intramuscular injection or with depot neuroleptics.
  2. Second, evaluate toleration of antipsychotic doses on the basis of extrapyramidal, hypnogenic, and autonomic side-effects. Non-toleration implies organic disease, often hyperthyroidism.
  3. Third, test the limits of appropriate neuroleptic: low doses in some instances are suitable, high doses in others particularly chronic hallucinosis.
  4. Fourth, recognize that not all neuroleptics are equal. Clozapine is especially topical and difficult to use. Unmarketed drugs such as sulpiride and pipothiazine are especially interesting. Each drug has special effects at several different receptors.

The major approach, however, is to seek out target features. Add medication usually as adjunct to neuroleptic to treat these target elements.

  1. Carbamazepine may be useful in hostility, lability, temporal lobe pathology and previous hallucinogens. Other anticonvulsants may at times have roles.
  2. Lithium and antidepressants have applications in affectively linked conditions.
  3. Anticholinergics have special roles in possible akathisia and extrapyramidal side-effects.
  4. Propranolol and other beta 2 active drugs such as nadolol have roles in significant anxiety.
  5. Benzodiazepines can be used in mania, catatonia, for nonspecific sedation and in epileptics.
  6. Nutrition elements are important as is the special role of caffeine, cigarettes and drugs of abuse.
  7. Levodopa is particularly interesting in the catatonic patient and has special implications for dopamine research.
  8. Buspirone may have a special role in tardive dyskinesia, tardive psychosis, possible tardive prophylaxis, irritability and obsessionality. The doses may be critical. There may be a link of serotonin 1A and dopamine.

Using this framework, a fascinating and apparently successful intervention plan can be developed.


© Copyright 1997 Pacific Neuropsychiatric Institute.