Neuroleptic Malignant Syndrome (NMS)

• NMS is more likely to develop following initiation of neuroleptic therapy or an increase in the dose.

• The onset can be within hours, but on average, it is 4-14 days after initiation of therapy. However, NMS can occur at any time during neuroleptic use, even years after initiating therapy.

• Of those patients who develop NMS, 90% of them will do so within 10 days.

• NMS is a heterogenous syndrome that spans a broad severity continuum. The diagnosis is made on clinical grounds based on the presence of certain historical, physical, and laboratory findings. The diagnosis is confirmed, but not necessarily excluded, by the presence of the following 5 criteria:

• Recent treatment with neuroleptics within past 1-4 weeks

• Hyperthermia (above 38°C)

• Muscular rigidity

• At least 5 of the following:
• Change in mental status
• Tachycardia
• Hypertension or hypotension
• Diaphoresis or sialorrhea
• Tremor
• Incontinence
• Increased creatinine phosphokinase (CPK) or urinary myoglobin
• Leukocytosis
• Metabolic acidosis
• Exclusion of other drug-induced, systemic, or neuropsychiatric illness

Tardive Dyskinesia

• The pathophysiology of TD is not well understood
• Striatal dopamine receptor supersensitivity may be responsible.
• Central dopamine blockade is hypothesized to play a role in the pathogenesis of TD.
• Chronic dopamine blockade may result in up-regulation of dopamine receptor responsiveness.
• TD is hypothesized to result from compensatory supersensitivity of dopamine receptors following chronic blockade. Long-term blockade of dopamine D2 receptors in the basal ganglia by dopamine D2 antagonists (eg, neuroleptics) may produce TD.
• When dopamine receptor blockade is reduced (even slightly), an exaggerated response of the postsynaptic dopamine receptor (even to low concentrations of dopamine) may result.
• Striatal disinhibition of the thalamocortical pathway from imbalance of D1 and D2 receptors may be involved.
• Neurodegeneration secondary to lipid peroxidation or excitotoxic mechanisms may be responsible.
• Mounting evidence exists that for some individuals, the dopamine D3, D4, and D5 receptors are involved.

Symptoms of Tardive Dyskinesia (TD)

Involuntary movements, which develop with antipsychotic exposure, are present for at least 4 weeks and may be:

1. Choreiform movements (rapid, jerky, nonrepetitive, purposeless)
2. Athetoid movements (slow, sinuous, continual)
3. Rhythmic movements (stereotypes)

Perioral Movements (most common)

Darting, twisting, protruding movements of the tongue (lip-licking, sucking, smacking, “fly-catching tongue”)

Chewing and lateral jaw movements

Lip puckering

Puffing cheeks

Face and Eyes

Facial grimacing

Tics

Blinking

Brow arching

Upward deviation of the eyes

Extremities

Finger, wrist, arm movements—athetoid (wormlike and twisting) or myokymic (jerking and twisting)

Hand clenching

Toe bending or jerking

Flexing of ankles

Foot tapping

Trunk

Torticollis—neck muscles contracting, pulling the head to that side   

Retrocollis—neck muscles contracting, pulling the head backwards

Trunk twisting

Pelvic thrusting

Rocking/Swaying