Add-on therapy to treat the adverse effects of primary therapy
Dopaminergic therapies come at the price of the development of off-time motor symptoms and dyskinesia.1,20 In general, these complications are managed by the addition of a dopamine agonist, MAO-B inhibitor, or a catechol-O-methyltransferase (COMT) inhibitor (entacapone).1
Rasagiline and entacapone are a good place to start and should be offered to patients to reduce off-time symptoms, according to the AAN (a Level A recommendation based on multiple high-level studies; see here for an explanation of Strength of Recommendation).20 As noted above, entacapone is a COMT inhibitor; it increases the plasma half-life of levodopa and decreases variations in peak-trough levels. Rasagiline is an MAO-B inhibitor and works to block dopamine metabolism.
The newest medication, safinamide, has been shown to increase “on” time by one hour per day when compared with placebo; however, it has not yet been tested against existing therapies.21 Other medications that can be considered to reduce drug-induced motor complications include pergolide, pramipexole, ropinirole, and tolcapone.20 Carbidopa/levodopa and bromocriptine are not recommended for the treatment of dopaminergic motor complications.20 Both sustained-release carbidopa/levodopa and bromocriptine are no longer recommended to decrease off time due to ineffectiveness.20
The only medication that has evidence for reducing dyskinesias in patients with PD is amantadine;20 however, it has no effect on other motor symptoms and should not be considered first line.16 Additionally, as an antiviral agent active against some strains of influenza, it should not be taken 2 weeks before or after receiving the influenza vaccine.
When tremor dominates …
For many patients with PD, tremor is more difficult to treat than is bradykinesia, rigidity, and gait disturbance.16 For patients with tremor-predominant PD (characterized by prominent tremor of one or more limbs and a relative lack of significant rigidity and bradykinesia), first-line treatment choices are dopamine agonists (ropinirole, pramipexole), carbidopa/levodopa, and anticholinergic medications, including benztropine and trihexyphenidyl.22 Second-line choices include clozapine, amantadine, clonazepam, and propranolol.22
Treating nonmotor symptoms
Treatment of hypersalivation should start with an evaluation by a speech pathologist. If it doesn’t improve, then adjuvant treatment with glycopyrrolate may be considered.16 Carbidopa/levodopa has the best evidence for treating periodic limb movements of sleep,14 although dopamine agonists may also be considered.16 More research is needed to find an effective therapy to improve insomnia in patients with PD, but for now consider a nighttime dose of carbidopa/levodopa or melatonin.14
Treating cognitive disorders associated with PD
Depression. Treatment of depression in patients with PD is difficult. Multiple systematic reviews have been unable to find a difference in those treated with antidepressants and those not.23 In practice, the use of tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and a combination of an SSRI and a norepinephrine reuptake inhibitor are commonly used. Additionally, some evidence suggests that pramipexole improves depressive symptoms, but additional research is needed.1
Dementia. Dementia occurs in up to 83% of those who have had PD for more than 20 years.1 Treatment includes the use of rivastigmine (a cholinesterase inhibitor).1 Further research is needed to determine whether donepezil improves dementia symptoms in patients with PD.1
Psychotic symptoms. Query patients and their families periodically about hallucinations and delusions.16 If such symptoms are present and not well tolerated by the patient and/or family, treatment options include quetiapine and clozapine.1 While clozapine is more effective, it requires frequent hematologic monitoring due to the risk of agranulocytosis.1 And quetiapine carries a black box warning about early death. Exercise caution when prescribing these medications, particularly if a patient is cognitively impaired, and always start with low doses.1
A newer medication, pimavanserin (a second-generation antipsychotic), was recently approved by the FDA to treat hallucinations and delusions of PD psychosis, although any improvement this agent provides may not be clinically significant.24 Unlike clozapine, no additional monitoring is needed and there are no significant safety concerns with the use of pimavanserin, which makes it a reasonable first choice for hallucinations and delusions. Other neuroleptic medications should not be used as they tend to worsen Parkinson symptoms.1