TARDIVE DYSKINESIA

CHAIRPERSON Dr.DENZIL A PINTO PRESENTER Dr.D.ARCHANAA O

Neuroleptic-Induced Tardive Dyskinesia

Definition Neuroleptic-induced tardive dyskinesia (TD) is a syndrome consisting of abnormal, involuntary movements caused by long-term treatment with antipsychotic medication. Dyskinesia can occur spontaneously in old age (non drug induced)

Medication-Induced Movement Disorders

Neuroleptic-Induced Acute Dystonia Neuroleptic-Induced Parkinsonism Neuroleptic-Induced Acute Akathisia Neuroleptic-Induced Tardive Dyskinesia Neuroleptic Malignant Syndrome Medication-Induced Postural Tremor

 bucco-linguo-masticatory syndrome, orofacial dyskinesia, terminal extra pyramidal insufficiency syndrome The term tardive dyskinesia (TD) was introduced by Faurbye and Rasch to emphasise the delayed or tardive onset of the syndrome secondary to neuroleptic drug Tardive late onset atleast after 4 weeks (DSM IV)

Neuroleptic-induced tardive sub syndromes

Movement disorders Tardive dyskinesia Oro-buccal-lingual-facial syndrome Limb-truncal syndrome Mixed Tardive akathisia Tardive dystonia Tardive tics and Tourettes syndrome Tardive myoclonus Tardive tremor Tardive parkinsonism *Behavioural syndrome Supersensitivity psychosis Tardive dysmentia Tardive dysbehaviour

Time of Emergence of Neuroleptic-Induced Movement Disorders

Condition Acute dystonia Neuroleptic malignant Akathisia Parkinsonism Tardive dyskinesia Highest Risk of Emergence Days 07 Days 07 (continues at lesser degree syndrome until end of first mo) Days 714 (continues at lesser degree until 2.5 mo) Days 1430 (continues at lesser degree until 2.5 mo) Month 3* onward (risk increases with increasing time on neuroleptic)

EPIDEMIOLOGY
Preliminary 1-year incidence rates of TD with atypical antipsychotics- 0.4 to 2.6% (35% with typical agents) (Nasrallah06). Gender (female) was thought to be a risk factor Indian study Doongaji et al (1982) : 9.6% Prevalence Dutta et al (1994) : 25.5% Bhatia et al (2004) : 28.7%

ETIOLOGY & PATHOPHYSIOLOGY

Striatal dopamine receptor supersensitivity confirmed by PET among TD patients (Margolese et al. 2005 ) GABA; chronic neuroleptic treatment decreases GABA turnover and increases GABA receptors, which can be explained on the basis of reduced GABA release or a loss of GABA terminals

Gunne and Andren proposed that the degeneration occurred in the GABAergic neurons projecting from the globus pallidum to the thalamus..

Basal Ganglia (Microcircuitary) Connections

Motor Cortex

glutamate

Striatum

+
glutamate ?

glutamate

+
VA-VL complex

GABA

GP, SNr
GABA

Contd..
Degeneration of striatal cholinergic interneuron's and the resulting dopamine acetylcholine imbalance play a role in TD pathogenesis (Jeste et al. 1992 , Margolese et al. 2005 ). Lohr and Jeste ( 1988b ) suggested that long-term antipsychotic use may produce toxic free radicals that damage striatal neurons

Contd..
Antipsychotics may increase dopamine turnover, elevating levels of hydrogen peroxide and consequently free radicals, and antipsychotics may also generate free radicals via inhibition of the mitochondrial respiratory chain (Margolese et al. 2005) Neuroleptics accumulation of iron in the basal ganglia neurotoxic through free radical mechanisms

Contd..
EXCITOTOXICITY Dopamine has an inhibitory effect on the release of excitatory neurotransmitters, and dopamine D2 blockade leads to an increase of glutamate (Glu) and aspartate release in the striatum

Higher concentrations of N-acetylaspartate, N-aspartylglutamate and aspartate in the cerebrospinal fluid of TD patients

Contd..
reduced levels of brain-derived neurotrophic factor (BDNF) and elevated serum homocysteine (Lerner et al. 2005 , Tan et al. 2005 ). several candidate genes Related to neurobiology of schizophrenia itself

DSM IV TR (333.82)
A. Involuntary movements of the tongue, jaw, trunk, or extremities have developed in association with the use of neuroleptic medication. B. The involuntary movements are present over a period of at least 4 weeks and occur in any of the following patterns: (1) choreiform movements (i.e., rapid, jerky, nonrepetitive) (2) athetoid movements (i.e., slow, sinuous, continual) (3) rhythmic movements (i.e., stereotypies) C. The signs or symptoms in criteria A and B develop during exposure to a neuroleptic medication or within 4 weeks of withdrawal from an oral (or within 8 weeks of withdrawal from depot) neuroleptic medication. D. There has been exposure to neuroleptic medication for at least 3 months (1 month if age 60 years or older)

ICD 10
Diseases of the nervous system G00-G99 Extrapyramidal and movement disorders G20-G26 Dystonia G24 ICD-10-CM Diagnosis Code G24.01 Drug induced subacute dyskinesia Applicable To Drug induced blepharospasm Drug induced orofacial dyskinesia Neuroleptic induced tardive dyskinesia Tardive dyskinesia

Clinical features
Fine vermicular movements of the tongue while it is sitting at the base of the oral cavity is a common and early feature Dyskinetic blinking may be another early sign of TD. Lip smacking, puckering or pouting, chewing, jaw clenching or mouth opening, facial grimacing, blowing, blepharospasm and frowning are also common features Extremities & trunk movement is common in young patients, orofacial movements is common in older individuals

Associated features
Some neurological, behavioural and cognitive features have been described as associated with TD. These include saccadic eye movement abnormalities neurological soft signs and ventricular enlargement Tardive dyskinesia, when it occurs in patients with schizophrenia, is more likely to be associated with negative symptoms and cognitive impairment

RISK FACTORS
Old age Diabetes Depression Parkinsonism Akathisia Negative symptoms, Cognitive impairments, Premorbid substance abuse ( Sachdev 2005) Traumatic head injury encephalitis

Assessment
Involuntary movements of the tongue, face, and neck muscles upper and lower extremities trunk. Most rare of all are involuntary movements of the muscle groups involved with breathing and swallowing. earliest symptoms typically involve buccolingualmasticatory movements

SCALES
AIMS (Guy 1976) SMITH TD SCALE (Smith et al. 1977) SIMPSON TD RATING SCALE (Simpson et al 1979) TD VIDEOTAPE RATING TECHNIQUE (Barnes & Trauer 1982)

AIMS
1. Muscles of Facial Expression 2. Lips and Perioral Area 3. Jaw 4. Tongue 5. Upper (arms, wrists, hands, fingers) 6. Lower (legs, knees, ankles, toes) 7. Neck, shoulders, hips 8. Severity of Abnormal Movements 9. Incapacitation Due to Abnormal Movements 10. Patient's Awareness of Abnormal Movements 11. Current Problems with Teeth and/or Dentures 12. Does Patient Usually Wear Dentures?

 Ask patient to remove shoes and socks if there is anything in his/her mouth (eg, gum, candy); if there is, to remove it. Ask patient about the current condition of his/her teeth. Ask patient if he/she wears dentures. Do teeth or dentures bother the patient now? Ask patient whether he/she notices any movements in mouth, face, hands, or feet. If yes, ask to describe and to what extent they currently bother patient or interfere with his/her activities.

How to assess T D

 Have patient sit in chair with hands on knees, legs slightly apart and feet flat on floor. (Look at entire body for movements while in this position.) Ask patient to sit with hands hanging unsupported. If male, between legs, if female and wearing a dress, hanging over knees. (Observe hands and other body areas.) Ask patient to open mouth. (Observe tongue at rest in mouth.) Do this twice Ask patient to protrude tongue. (Observe abnormalities of tongue movement.) Do this twice. Ask patient to tap thumb, with each finger, as rapidly as possible for 10 to 15 seconds; separately with right hand, then with left hand. (Observe facial and leg movements.)

 Flex and extend patient's left and right arms (one at a time). (Note any rigidity) Ask patient to stand up. (Observe in profile. Observe all body areas again, hips included.) Ask patient to extend both arms outstretched in front with palms down. (Observe trunk, legs, and mouth.) Have patient walk a few paces, turn and walk back to chair. (Observe hands and gait.) Do this twice.

Worsening
psychostimulants, short-term withdrawal of antipsychotic medication, anticholinergic medication, emotional arousal, stress, voluntary movements of other parts of the body.

Improved
relaxation, Voluntary movements of the involved parts of the body sleep increased dose of antipsychotics (temporarily)

D/D
neuroleptic-induced parkinsonism, rabbit syndrome, Wilsons disease cerebellar disease anxiety states, alcoholism, hyperthyroidism

Acute dystonias, myoclonus, tics, mannerisms, compulsions, akathisia Withdrawal dyskinesia

metoclopramide, antiemetics, amoxapine levodopa,amantadine, bromocriptine Sydenhams chorea Conversion disorder Malingering Huntingtons disease

 Course
TD seems to stabilize in 50%, worsen in 25%, and improve in 25% Onset of the disorder may be gradual, occurring over a period of months to years.

Treatment
Patients with nonpsychotic mood or other disorders who need antipsychotics should receive the minimal necessary amounts of antipsychotic treatment and should have the medication tapered and then stopped once the clinical need is no longer present Atypical antipsychotics appear to offer some advantage compared to older agents in terms of TD risk increase in dosage of a conventional agent usually (in approximately 66% of patients) results in a clinically significant but temporary reduction in TD symptoms (Jeste et al. 1988 ).

TREATMENT
Clozapine may be effective in reducing TD in patients with existing TD (Lieberman et al. 1991 , Small et al. 1987 ); however, side effects such as agranulocytosis, seizures, and anticholinergic symptoms limit its use studies have noted a beneficial effect of other atypical agents (i.e., risperidone and olanzapine) on preexisting TD (Jeste et al. 1997 , Littrellet al. 1998 ) Zhang et al. ( 2004 ) showed an improvement in TD with vitamin E compared to placebo,

TREATMENT
Neuroleptic to be used only for appropriate indications Education and informed consent of patients before initiation of neuroleptic Prevention of TD by 1. Lowest dose of medication 2. Shortest possible time of treatment 3. Routine assessment TD is suspected or diagnosed Medical workup to rule out other cases of dyskinesia

TREATMENT
Perform riskbenefit analysis to decide whether to continue neuroleptic or attempt taper Taper any anticholinergic medications, if possible Consider switch from neuroleptic to another neuroleptic, especially to an atypical antipsychotic. Also consider vitamin E as adjunctive therapy

TREATMENT
VITAMIN B6 ( Am J Psy, Sep 2001) TETRABENZINE (Am J Psy 1999) MELATONIN Damier and coworkers ( 2007 ) recently reported promising benefits of deep brain stimulation of the globus pallidus for recalcitrant TD Ca Channel Blockers Beta blockers

Results: Incidence of TD was: Atypicals: 19% Nave: 5 % Typicals for <5 years :19% Typicals for >5 years : 42% When TD cases were classified according to duration of exposure, most were associated with typical exposure (82%) When severe TD was examined, those with atypicals did not appear to have a better profile. (de Leon,2006)

IMPORTANCE
Common and disabling side-effect At times life-threatening Potentially irreversible May be increased or decreased by stopping the offending drug Legal issues

Complication
TD may lead to numerous physical complications and psychosocial problems Ulcerations of the tongue, cheeks, and lips Hyperkinetic dysarthria and swallowing disorders shortness of breath at rest, irregularities in respiration, and various grunts, snorts, and gasps vomiting and dysphagia Emotional distress may accompany severe dyskinesia.

Complications
Social embarrassment Suicidal ideation mild dyskinesia may lead to anxiety, guilt,shame,and anger. TD is largely an aesthetic problem, but may impair social relationships and be an impediment to employment. About 510% of TD patients suffer impairment from the dyskinesia. Orofacial movements may lead to difficulty in eating or retaining dentures, and weight loss or cachexia may develop.

COMPLICATIONS
Pharyngeal involvement may rarely cause aspiration pneumonia. Involvement of the limbs and trunk may interfere with ambulation. Diaphragmatic involvement may lead to respiratory dysfunction and even failure. These occurrences of potentially life threatening complications have placed medicolegal spotlight for justification of use of neuroleptics (Psychopharmacology 1993)

APA TASK FORCE RECOMMENDATIONS (1997, 2004)

Establish objective evidence that antipsychotics are effective for an individual Using the lowest effective dose Cautious use in children, the elderly and in mood disorders Regular examination of patients for TD Consider alternatives, obtain informed consent, and consider dosage reduction if TD present If worsening, consider (a) stopping the drug, (b) change to another drug, (c) clozapine

 Is dyskinesia a feature of schizophrenia?

The occurrence of peculiar, sprawling, irregular, choreiform, outspreading movements in schizophrenic patients were noted by Kraepelin Many studies have investigated neuroleptic-naive schizophrenic patients and reported rates of dyskinesia that vary from nil to as high as 53% These findings have raised the argument that dyskinesias may be intrinsic to the pathophysiology of schizophrenia, and that neuroleptics serve to enhance the process

CONCLUSIONS
The need for continued antipsychotic therapy needs to be evaluated
Emphasis on prevention; as treatment is difficult Switching to atypical antipsychotics may be considered

CONCLUSIONS
Clozapine is the gold standard of treatment.
Periodic evaluation with a standard movement Atypical Antipsychotics havent been around long enough.

Thank u