Extrapyramidal Symptoms

Acute Dystonia
  • "Long-lasting contraction or spasm of musculature develops secondary to the use of antipsychotic medication.
  • Acute dystonia typically subsides spontaneously within hours after onset.
Common Dystonias
  • Torticollis (lateral neck rotation)
  • Retrocollis (neck extension)
  • Limb torsion
  • Forced jaw closing (trismus) or opening
  • Tongue protrusion
  • Opisthotonus (extension of head, neck, and paraspinal muscles in an arch)
  • Oculogyric crisis (forceful eye deviation).
  • Usually emerge within 0–7 days
  • Pathophysiology
    • Abnormalities in dopamine–acetylcholine balance - (cholinergic antagonists and dopaminergic agonists improve the dystonia in many patients)
  • Epidemiology
    • 2 to 12% of patients - conventional antipsychotic medication
  • Risk factors include
    • high-potency conventional antipsychotics, e.g. haloperidol
    • Young age, male sex, and a prior dystonic reaction.
  • Clinical features
    • Abnormal positioning of the head and neck in relation to the body (e.g., retrocollis, torticollis)
    • Spasms of the jaw muscles (trismus, gaping, grimacing)
    • Impaired swallowing (dysphagia), speaking, or breathing (laryngeal–pharyngeal spasm, dysphonia)
    • Thickened or slurred speech due to hypertonic or enlarged tongue (dysarthria, macroglossia) tongue protrusion or tongue dysfunction
    • Eyes deviated up, down, or sideward (oculogyric crisis)
    • Abnormal positioning of the distal limbs or trunk
  • Treatment
    • Standard treatment is anticholinergic agent- equivalent of 2 mg of benztropine or 50 mg of diphenhydramine/promethazine.
    • In case of laryngeal or pharyngeal dystonias with airway compromise, repeated dosing of medication should occur at shorter intervals until resolution is achieved.
Parkinsonism
  • A condition characterized by Parkinsonian signs or symptoms (resting tremor, muscle rigidity, and bradykinesia/akinesia) that develop in association with the use of an antipsychotic medication.
  • Most commonly associated with use of Dopamine Receptor Antagonists.
  • Pathophysiology
    • Blockade of postsynaptic dopamine (D2 ) receptors in the corpus striatum.
  • Epidemiology
    • 5 to 90%, depending on the use of first-generation antipsychotics, high-potency FGAs and associated medical and neurological disorders.
  • Clinical features include:
    • Parkinsonian tremor (i.e., a coarse, rhythmic, resting tremor with a frequency between 3 and 6 cycles per second, affecting the limbs,
      head, mouth, or tongue)
    • Parkinsonian muscular rigidity (i.e., cogwheel rigidity or continuous “lead-pipe” rigidity)
    • Akinesia (i.e., a decrease in spontaneous facial expressions, gestures, speech, or body movements)
  • Differential diagnosis include:
    • Major depressive disorder
    • Catatonia
    • Negative symptoms of schizophrenia
  • Treatment
    • Milder cases do not require treatment, reassurance that condition will improve as patient will tolerate the drug over time.
    • Decrease the dose of antipsychotic to the lowest effective
      dose for the patient.
    • Low dose anticholinergic - benztropine/trihexyphenidyl
    • Treat with atypical antipsychotics.
Akathisia (“inability to sit”)
  • Definition : “A subjective feeling of restlessness and an intensely unpleasant need to move occurring secondary to antipsychotic treatment”.
  • Usually emerge with in 7–14 days of starting antipsychotics therapy.
  • Pathophysiology
    • Excessive noradrenergic activity (the efficacy of beta-adrenergic blockers in improving some cases of akathisia)
    • Mesocortical dopaminergic neurons that innervate the prefrontal cortex seem to be resistant to depolarization induced by long-term antipsychotic treatment.
  • Epidemiology
    • Occur in 20–75% of patients treated with conventional agents.
  • Clinical features
    • Subjective complaints of restlessness
    • Fidgety movements or swinging of the legs
    •  Rocking from foot to foot while standing
    •  Pacing to relieve restlessness
    •  Inability to sit or stand for at least several minutes
  • Differential Diagnosis
    • Primary psychiatric disorders presenting with agitation, such as depression, mania, anxiety, schizophrenia, dementia, delirium, substance intoxication/withdrawal, and attention-defi cit/hyperactivity disorder.
    • Restless legs syndrome (RLS)
  • Treatment
    • Beta-blocker propranolol - often considered first-line treatment
    • Benzodiazepines - clonazepam and Lorazepam
    • Anticholinergic agents – benztropine
Tardive Dyskinesia
  • Definition:
    • "A syndrome consisting of abnormal, involuntary, choreoathetoid movements typically involve the mouth, face, limbs, and trunk caused by long-term treatment with antipsychotic medication.
  • Pathophysiology - hypotheses
    1. Striatal dopamine receptor supersensitivity as a compensatory reaction to prolonged dopamine receptor blockade.
    2. Damage to gamma-aminobutyric acid (GABA)-containing striatal neurons.
    3. Long-term antipsychotic use may produce toxic free radicals that damage striatal neurons and result in persistent TD.
    4. Reduced levels of brain-derived neurotrophic factor (BDNF) and elevated serum homocysteine.
  • Epidemiology - (after starting antipsychotics)
    • 5% after 1 year
    • 18.5% after 4 years
    • 40% after 8 years
  • Clinical Features
    • Involuntary movements of the tongue, jaw, trunk, or extremities have developed in association with the use of neuroleptic medication.
    • Choreiform movements (i.e., rapid, jerky, nonrepetitive)
    • Athetoid movements (i.e., slow, sinuous, continual)
    • Rhythmic movements (i.e., stereotypies)
  • Differential Diagnosis
    • Sydenham’s chorea
    • Huntington’s disease
    • Conversion disorder and malingering
    • Hyperthyroidism
  • Complications
    • Emotional distress
    • Dental problems
    • Respiratory alkalosis
  • Treatment
    • Atypical antipsychotics may improve the condition
    • Clozapine may be effective in reducing TD in patients with existing TD
    • Vitamin E (alpha-tocopherol) has some efficiency
    • Abnormal Involuntary Movement Scale (AIMS) may be used to monitor progress of the treatment.
Scales & Instruments
Simpson-Angus Rating Scale for Extrapyramidal Side Effects
  • The Simpson-Angus scale was developed to monitor the effects of antipsychotic drugs.
  • It has 10 items, each of which is rated on an item-specific, five-point severity scale ranging from 0 to 4.
  • Scores are reported as the mean on all 10 items, with 0.3 considered the upper limit of normal.
  • It is focused on parkinsonian symptoms, -rigidity,includes one akathisia item.
  • It can be administered by trained lay raters.
  • Good psychometric properties have been reported.
Abnormal Involuntary Movement Scale (AIMS)
  • developed to measure dyskinetic symptoms in patients taking antipsychotic drugs.
  • 12 items, on five-point severity scale ranging from 0 to 4.
  • Total scores are not generally reported. Instead, changes in global severity and individual areas can be monitored over time.
  • Ten items cover the movements themselves, divided into sections rating global severity and those related to specific body regions; two items concern dental factors that can complicate the diagnosis of dyskinesia.
  • In the presence of extended neuroleptic exposure and the absence of other conditions causing dyskinesia, mild dyskinetic movements in two areas or moderate movements in one area suggest a diagnosis of tardive dyskinesia.
  • The scale can be administered by trained raters.
  • It can be completed in under 10 minutes.
  • Good psychometric properties have been reported.
References
  1. Miyamoto S, Merrill DB, Lieberman JA, Fleischacker WW, Marder SR. Antipsychotic Drugs. In Psychiatry, Third Edition. Edrs. Allan Tasman, Jerald Kay, Jeffrey A. Lieberman, Michael B. First and Mario Maj.John Wiley & Sons, Ltd, 2008.
  2. Daniel DG, Igan MF, Wolf SS. Neuropsychiatric Aspects of Movement Disorders. In Comprehensive Textbook of Psychiatry , Vol 7 , Kaplan HI and Saddock BJ (eds). Williams & Wilkins , Baltimore, MD, USA .

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