Tardive dysphrenia
Encyclopedia
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
, and 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 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.
medication.
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, which act chiefly on the nigrostriatal pathway
.
A) The patient shows:
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:
C) Criteria A & B signs and symptoms emerge progressively with the administration of an oral antipsychotic drug or during the four-weeks period 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 older.
E) The clinical signs and symptoms cannot 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) or by Neuroleptic Dysphoria.
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 prophylactic.
Dysphrenia
The term dysphrenia was coined by the German medical specialist Karl Kahlbaum to designate a clinical picture in 19th century psychiatry. Today the concept is still used in the western world as a lay generic synonym for mental disorder in adults, and as a term to describe different...
, was proposed by the American neurologist Stanley Fahn, the head of the Division of Movements Disorders of the Neurological Institute of New York
Neurological Institute of New York
The Neurological Institute of New York is located at 710 West 168th Street in New York City in the United States of America. Its current building was constructed in the 1950s...
, 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
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
observed in psychiatric patients (schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
in particular) treated with the typical antipsychotic
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
drugs or neuroleptics. Tardive dysphrenia is one of many neuroleptic-induced tardive syndromes, including tardive dyskinesia
Tardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
and the other already-recognized tardive dystonia
Dystonia
Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
, and tardive akathisia
Akathisia
Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
.
More recently, the Brazilian psychiatrist Leopoldo Hugo Frota, Adjunct Professor of Psychiatry
Psychiatry
Psychiatry is the medical specialty devoted to the study and treatment of mental disorders. These mental disorders include various affective, behavioural, cognitive and perceptual abnormalities...
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
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
, supersensitivity psychosis (Guy Chouinard) and schizophrenia pseudo-refractoriness (Heinz Lehmann
Heinz Lehmann
Heinz Edgar Lehmann, OC, FRSC was a German born Canadian psychiatrist best known for his use of chlorpromazine for the treatment of schizophrenia in 1950s....
& 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 antipsychoticAntipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
medication.
Etiology
The etiologyEtiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
of all these syndromes was ascribed by Frota to an adaptative, but extreme and long-lasting up-regulation of the dopaminergic mesolimbic pathway
Mesolimbic pathway
The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex...
D2-like receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
. He also emphasized the outstanding role of modern second-generation atypical antipsychotic drugs with predominant actions on the dopaminergic mesolimbic pathway
Mesolimbic pathway
The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex...
differently from the typical ones, which act chiefly on the nigrostriatal pathway
Nigrostriatal pathway
The nigrostriatal pathway is a neural pathway that connects the substantia nigra with the striatum. It is one of the four major dopamine pathways in the brain, and is particularly involved in the production of movement, as part of a system called the basal ganglia motor loop.Loss of dopamine...
.
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 period 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 older.
E) The clinical signs and symptoms cannot 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) or by Neuroleptic Dysphoria.
Treatment
As with 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 antipsychoticAntipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
drug in use, or augmenting
Augmentation (psychiatry)
Augmentation is the combination of two or more drugs to achieve better treatment results....
it with a typical antipsychotic, can alleviate symptoms temporarily. However, these solutions carry the risk of worsening or perpetuating the iatrogenesis
Iatrogenesis
Iatrogenesis, or an iatrogenic artifact is an inadvertent adverse effect or complication resulting from medical treatment or advice, including that of psychologists, therapists, pharmacists, nurses, physicians and dentists...
in the long term.
Some patients could gradually benefit from changing to a dopamine D2 receptor
Dopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....
partial agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
agent like clozapine
Clozapine
Clozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew...
. These drugs do not induce up-regulation, instead acting as a prophylactic.