Dopaminomimetic psychosis in Parkinson’s Disease

05 November 2004

Parkinson’s disease

            >60% loss in striatal area of dopamine function

            eventual hypersensitivity of D receptors with (un)predictable motor response

fluctuations

            loss of dopamine in ventral tegmental area (projects to frontal & limbic)

            abnormal mentation, anxiety disorders, sexual disorders, sleep disorders,

            depression

Drug induced dopaminomimetic psychosis

20% PD patients on treatment

Strong risk factor for nursing home placement

Risk factors:     elderly

                        Pre-existing cognitive disturbance

                        Sleep disruption

                        Vivid dreams

Hallucinations: visual > acoustic

Delusions: usually paranoid (persecution, infidelity, jealousy)

Psychosis needs to be differentiated from toxic confusional state

Theories:          overstimulation of mesocorticolimbic D receptors

                        Interaction between dopamine & serotonin

THERAPY

STANDARD

Exclude psychotogenic factors

Avoid sensory overload / deprivation

Active day program

Night time orientation

Withdraw anticholinergics, amantadine

Withdraw dopaminomimetic agents if tolerable

Atypical neuroleptics:    antagonism 5HT2A > D2

                                    Selective binding: mesocorticolimbic (D4, D1) > D2

                                    Risperidone profile closer to typical antipsychotic

CLOZAPINE

Antagonist: 5HT2A, D2, muscarinic, cholinergic, adrenergic, histaminergic

Responds to low dose 25-50 mg

Improves sleep quality, relieves anxiety, depression, hypersexuality

SE: 1-2% agranulocytosis, sedation, toxic confusional state, drooling, cardiomyopathy, tachycardia

RISPERIDONE

Antagonist: 5HT2A, D2, adrenergic but not cholinergic

Dose: 0.5 – 2.5 mg

QUETIAPINE

Antagonist: 5HT2A > D2, histaminergic

Replaced clozapine in New Jersey as Medicaid does not reimburse for FBE

Efficacy: visual hallucinations > paranoia, delusions

SE:       42%     dizziness

            42%     daytime drowsiness

            17%     lethargy

            17%     headache

            17%     irritability

Common side effects often abate

OLANZAPINE

Antagonist: 5HT2A > D2, cholinergic, adrenergic, histaminergic

Dose: 2.5 –5 mg

Improves sleep

ONDANSETRON

Antagonist: 5HT3

1 study not reproducible

No head to head comparison