Tardive dysphrenia

The medical expression Tardive Dysphrenia, was proposed by the American neurologist Stanley Fahn, the head of the Division of Movements Disorders of the Neurological Institute of New York, in collaboration with the psychiatrist David V Forrest in the 1970s. It originally was linked to a unique, rare, behavioral/mental neuroleptic drug-induced tardive syndrome observed in psychiatric patients (Schizophrenia in particular) treated with the typical antipsychotic drugs or neuroleptics. Tardive dysphrenia is one of many neuroleptic-induced tardive syndromes, including tardive dyskinesia and the other already recognized tardive dystonia, tardive akathisia.

More recently, the Brazilian psychiatrist Leopoldo Hugo Frota, Adjunct Professor of Psychiatry at Federal University of Rio de Janeiro, extended the original Fahn's construct to enclose the -independently described but etiologically related concepts of- rebound psychosis, supersensitivity psychosis (Guy Chouinard) and the Schizophrenia pseudo-Refractoriness (Heinz Lehmann & Thomas Ban) or Secondary Acquired Refractoriness.

There is some disagreement in the psychiatric community regarding the diagnosis of tardive dysphrenia. Therefore the following description should be considered general and tentative.

Description
Tardive dysphrenia is characterized by a worsening of psychiatric symptoms that can be directly traced to the administration of antipsychotic medication.

Etiology
The etiology of all these syndromes was ascribed by Frota to an adaptative, but extreme and long-lasting up-regulation of the dopaminergic mesolimbic pathway D2-like receptor. He also emphasized the outstanding role of modern second generation atypical antipsychotic drugs with predominant actions on the dopaminergic mesolimbic pathway differently from the typical ones, that acts chiefly on the nigrostriatal pathway.

Symptoms and diagnosis
Six symptoms are considered when diagnosing tardive dysphrenia:

A) The patient shows:
 * New or exacerbated previous psychotic symptomatology with unprecedented or unjustifiable severity.
 * Upon dose lowering, withdrawal or soon after long sustaining fixed doses of antipsychotic typical or atypical drugs,
 * Then improves, at least for a while, after reinstitution or increasing daily doses.

B) The symptoms are present for a full four weeks (full two weeks if successfully treated by immediate reinstitution or augmentation with a more potent drug and/or the rising of the previous drug) and contain any of these patterns:
 * Psychotic symptoms: hallucinations, delusions, behavior or thought disorganization;
 * Manic/hypomanic, cyclothymic, cycloid, polymorphic and/or severe dysphoric symptoms;
 * Obsessive-Compulsive/Tic-like symptoms.

C) Criteria A & B signs and symptoms emerge progressively with the administration of an oral antipsychotic drug or during the four weeks that follows its withdrawal (8 weeks for dépôt formulations).

D) There has been any exposure to a typical and/or atypical antipsychotic drug for at least three full months (full 12 weeks), or 1 full month (full 4 weeks) if the patient is sixty years old or over.

E) The clinical signs and symptoms can not be attributed to another psychiatric condition, neurological condition, somatic illness or severe stress. Also, exposure to other psychosis inducing medicines must be excluded.

F) The signs and symptoms could not be better explained by an eventual previous psychiatric/neurological condition unfavorable natural evolution (i.e., Primary Refractory or poor prognosis Schizophrenia; severe Acute Mania; Dementia with Psychotic Symptoms) nor by Neuroleptic Dysphoria.

Treatment
Like other neuroleptic-induced tardive syndromes there is no definite treatment for tardive dysphrenia. The continuing to take the drug or changing the dosage of the atypical antipsychotic drug in use, or augmenting it with a typical antipsychotic can alleviate symptoms temporarily. However, these solutions carry the risk of worsening or perpetuating the iatrogenesis in the long term.

Some patients could gradually benefit from changing to a dopamine D2 receptor partial agonist agent like clozapine. These drugs do not induce up-regulation, instead acting as a prophylaxis.