|
| |
Algorithm for initiating treatment in
early Parkinson's disease |
| Age |
Strategy |
| >60 yo |
 | Maintain Cognitive status, avoid Selegiline, Amantadine, anticholinergic. |
| Use Sinemet CR |
| If inadequate response, switch to regular Sinemet |
| If inadequate response, add dopamine agonist |
|
| 50-59 |
| Selegiline or dopamine agonist or both |
| if inadequate response, add Sinemet CR |
| Add Amantadine, anticholinergic |
|
| < 50 |
| Selegiline, Amantadine or anticholinergic
|
|
| adapted from Silver DE, Ruggieri S.
Initiating Therapy for Parkinson's disease. Neurology 1998; 50(suppl 6):S18-S22. |
| Parkinson medications |
| Dopaminergic Agents |
Sinemet
(Carbidopa/ levodopa) |
| Tab: 25/100, 25/250 |
| dose: 25/100 tid, titrate up, maximum dose around 1500 - 2000 mg of
Levodopa per day |
|
| Sinemet CR (Carbidopa/ levodopa) |
| Tab: 25/100, 50/200 |
| Dose: 50/200 bid, titrate up |
| May split tablet, but do not crush. Max around 800 mg/day. |
| Need 20 - 40% more dose than Sinemet |
|
Lodosyn
(Carbidopa) |
| Tab: 25 mg, bottles of 100
|
| Need 75 to 100 mg/day to inhibit peripheral decarboxylase |
| Take 1/2 to 1 tablet 30 to 60 min before Sinemet.
|
| Available from: DuPont Pharmaceutical. DuPont Merck Plaza, Hickory
Run, PO Box 80723, Wilmington DE 19880-0723. Attention: Sample Accountability
Manager |
| Phone # is (302) 992-5000. |
|
Eldepryl
(Selegiline) |
| Tab: 5 mg |
| Take 1 am, 1 noon |
| Monoamine oxidase B (MAO-B) inhibitor that reduces dopamine metabolism |
|
| Dopamine agonists: act
directly on the dopamine receptors, not requiring a conversion step and storage, as with
levodopa |
| Advantages
 | Antiparkinsonian effects when used as monotherapy or as an adjunct to levodopa |
| Reduced risk for developing levodopa-related motor complications |
| Do not generate oxidative metabolites |
| Levodopa-sparing effect |
| Potential neuroprotective benefits |
|
| Disadvantages
| Neuropsychiatric side effects (especially hallucinations and psychosis) |
| Agonist-specific side effects (erythromelalgia, ankle edema) |
| Sedative side effect |
| Do not completely prevent development of levodopa-related motor complications |
| Do not treat all features of PD, such as freezing, postural instability, autonomic
dysfunction, dementia |
| Do not stop disease progression |
|
|
| Permax (Pergolide)
| D2 agonist, weak D1, long half life |
| Tab: 0.05, 0.25,1.0 mg |
| Usual dose: 0.05 mg bid, increase by 0.1 mg/day every 2 days. Max 4mg/day |
|
|
| Parlodel (Bromocriptin)
| D2 agonist, half life 3-6 hours |
| Tab 2.5 mg, Cap 5 mg |
| Dose: 1.25 mg bid, up to 5 mg q4 |
|
|
| Mirapex (Pramipexole)
| Selective nonergot D2 agonist |
| Renal excretion |
| Tab 0.125, 0.25, 0.5, 1, 1.5 mg |
| Dose: 0.125 mg tid, increase weekly. Max around 4.5 mg/day. |
| May help depression in a small study when added to a variety of standard antidepressants in 6 patients. |
|
|
| Requip (Ropinirole)
| Selective nonergot D2 agonist |
| Tab 0.25, 0.5, 1 mg |
| Dose: 0.25 mg tid, increase weekly to 1 mg tid. Max around 6-24 mg/day |
|
|
| COMT inhibitor: increase
the availability and transfer of levodopa into the brain |
| Advantages
| No titration; easy to administer |
| Decreased "off" time, increased "on" time, and enhanced motor responses in patients with levodopa motor fluctuations |
| Improved motor and ADL scores in stable levodopa responders |
| May reduce risk for motor complications if used from onset of levodopa therapy |
|
| Disadvantages
| Dopaminergic side effects, especially dyskinesia |
| Discoloration of urine |
| Tolcapone:
 | explosive diarrhea in 5-10% of cases |
| Tolcapone associated with liver toxicity |
|
|
|
| Comtan
(entacapone)
| Approved in Oct 99 |
| 200 mg tab, given with each dose of L dopa, up
to 8 tab per day. |
| Placebo-controlled study:
| 4 week courses of entacapone or placebo as an
adjunct to levodopa/carbidopa |
| entacapone-treated patients
had a 34-minute increase in the mean duration of "on"
time after a single dose of levodopa and a 2.5-hour increase in
daily "on" time. |
| 16% reduction in the mean daily dose of
levodopa |
|
| Treatment with entacapone may cause 10% of
patients to have a brownish orange discoloration of urine. |
|
|
| Anticholinergic |
| Advantages: Some antiparkinson efficacy |
| Disadvantages: Limited clinical efficacy, cognitive side effects
|
|
| Cogentin (Benztropine)
| Tab 0.5, 1, 2 mg |
| Usual dose: 0.5 - 2 mg bid |
|
| Artane (Trihexyphenidyl)
| Tab 2, 5 mg, SR Cap 5 mg, Elixir 2 mg/ml |
| Usual dose: 2 mg tid |
|
| Akineton (Biperiden)
| Tab 2 mg, IM/IV: 5 mg/ml |
| Usual dose: 2 mg tid po, 2 mg iv or im up to 8 mg/day |
|
|
| Antipsychotic for Parkinson
patient |
| Clozaril (Clozapine)
| Selective for D4 receptors, may cause hypotension, drowsiness |
| Tab: 25, 100 |
| 12.5 hs, rarely need to go to a maximum of 50 bid. |
| Need weekly WBC, 2% chance
of agranulocytosis, non dose dependent. |
| Does not worsen PD symptoms |
|
|
| Risperdal (Risperidone)
| D2 and Serotonin blocker |
| Tab: 1, 2, 3, 4 mg |
| Dose: 0.5 hs, to 2 mg bid |
|
|
| Olanzapine (Zyprexa)
| Tab: 2.5, 5, 7.5, 10 mg |
| Dose: 5 mg qd, up to 10 mg qd |
| Less orthostasis, drowsiness. |
| does not worsen PD symptoms |
|
|
| Seroquel
| New antipsychotic agent. |
| Dose: begins at 25 mg bid and can be increased up to 100 mg bid.
|
| Main side effect is sedation. |
|
|
| Affective disorder in Parkinson
patients |
| Depression:
| 40% of PD patients & may be underdiagnosed. |
| In 25% of PD patients who are depressed, the depression precedes the
onset of motor symptoms. |
| Endogenous depression: feelings of guilt, helplessness, remorse, and
sadness occurs independent of age, disease duration, disease severity, or cognitive
impairment. The depression may cause apathy or agitation.
|
| Exogenous depression may be caused by job loss, retirement, midlife
crisis, or knowledge of a relative with advanced PD and fear of becoming like their
relative. |
|
| Treatment of depression:
| SSRI:
| One study raised concern that PD can worsen during SSRI treatment. This
occurs but is unusual. |
| Likewise, concern has been raised about adverse interaction between SSRIs
and selegiline, selegiline should be stopped if possible. |
|
| Tricyclic antidepressants:
| nortriptyline and desipramine have less anticholinergic activity and are
cleared more rapidly than their parent compounds. |
| Nortriptyline and desipramine can be given in an initial nighttime dose
of 25 to 50 mg. |
| In agitated patients the sedative properties of the tricyclics may be
desirable, but in apathetic, anergic, passive, and withdrawn patients, the sedative
properties may be undesirable. |
|
|
|
| Anxiety:
| About 40% of PD patients are anxious, and many of them have panic
attacks. Anxiety and panic attacks may be a reaction to PD or may conceivably be part of
PD. |
| If the anxiety and the panic attacks do not respond to anxiolytics,
buspirone or low doses of tricyclic antidepressants can be used. |
|
|
| Confusion & Dementia in
Parkinson patients |
| 18-37% of Parkinson patients are demented. More likely in the older
patients. |
| Cognitive impairment without dementia is common, about 19%. May present
with apathy, anergy, abulia, and passivity, difficult to distinguish from
depression. Patients report that they are not depressed, do not have guilt feelings, and
may not respond to antidepressants. The term Bradyphrenia is sometimes used to describe
slowness of thinking. |
| They are prone to development of delirium when they take antiparkinsonian
drugs |
| Agitation or delirium may be related to antiparkinsonian drugs or to
other conditions such as dehydration, electrolyte imbalance, or infection.
|
| The order in which antiparkinsonian drugs causing delirium are:
anticholinergics, amantadine, selegiline, dopamine agonists, and levodopa. |
| For dementia, a trial of the cholinomimetic donepezil, 5
to 10 mg/day, or Exelon (not available in US), 6 to 12 mg/day, may be helpful. |
|
| For Hypotension |
| Fludrocortisone (Florinef)
| Tab 0.1 mg |
| Dose: 0.1 to 0.5 mg/d |
|
| Midodrine (Proamatine)
| Recently approved |
| Dose: start at 5 mg 1/2 tab qAM and noon, to a maximum of 10 mg tid (give
the last dose before 6PM). |
| Main side effects: tingling, itching, change in urination, and supine
hypertension. |
|
|
| Surgical Treatment: unresponsive to
medical treatment |
| Ventrolateral Thalamotomy |
| Placing a lesion or stimulator in the ventral intermediate nucleus of the
thalamus to control tremor is quite effective and now FDA approved.
|
| Little effect on other parkinsonian symptoms, and do not help with
dyskinesias. |
| Should be reserved for patients with tremor predominant PD, and can only
be done unilaterally, to control the contralateral tremor, since dysarthria is a serious
complication of bilateral thalamic procedures. |
| Doing subthalamotomy or subthalamic nucleus stimulation may prove to be
the best surgical procedure. The arguments for doing a stimulator and not lesion is that
any adverse events would be reversible. |
|
| Pallidotomy |
| Placing a lesion in the internal globus pallidus, or placing a stimulator
there, has gained acceptance as a beneficial treatment for patients with advanced PD |
| Patients with predominantly unilateral PD are the best candidates, and
the younger the patient the better. |
| Benefits contralateral bradykinesia, tremor, and dyskinesias. Little
effect on postural instability and gait. |
| Dementia is a contraindication. |
|
| References & Further
reading |
|
|
Parkinsonism review
Staging of Parkinson's disease
Return to movement disorder info center
 |
